Note: Descriptions are shown in the official language in which they were submitted.
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JUMBO APPLICATIONS / PATENTS
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THAN ONE VOLUME.
THIS IS VOLUME 1 OF 2
NOTE: For additional volumes please contact the Canadian Patent Office.
CA 02761872 2011-11-14
WO 2010/132591
PCT/US2010/034586
PECVD COATING USING AN ORGANOSILICON PRECURSOR
FIELD OF THE INVENTION
[01] The present invention relates to the technical field of fabrication of
coated
vessels for storing biologically active compounds or blood. In particular, the
invention
relates to a vessel processing system for coating of a vessel, vessel
processing system
for coating and inspection of a vessel, to a portable vessel holder for a
vessel
processing system, to a plasma enhanced chemical vapour deposition apparatus
for
coating an interior surface of a vessel, to a method for coating an interior
surface of a
vessel, to a method for coating an inspection of a vessel, to a method of
processing a
vessel, to the use of a vessel processing system, to a computer-readable
medium and
to a program element.
[02] A method for coating a substrate surface by PECVD is provided, the
method
comprising generating a plasma from a gaseous reactant comprising an
organosilicon
precursor and optionally 02. The lubricity, hydrophobicity and/or barrier
properties of the
coating are set by setting the ratio of the 02 to the organosilicon precursor
in the
gaseous reactant, and/or by setting the electric power used for generating the
plasma.
In particular, a lubricity coating made by said method is provided. Vessels
coated by
said method and the use of such vessels protecting a compound or composition
contained or received in said coated vessel against mechanical and/or chemical
effects
of the surface of the uncoated vessel material are also provided.
[03] The present disclosure also relates to improved methods for processing
vessels, for example multiple identical vessels used for venipuncture and
other medical
sample collection, pharmaceutical preparation storage and delivery, and other
purposes. Such vessels are used in large numbers for these purposes, and must
be
relatively economical to manufacture and yet highly reliable in storage and
use.
1
CA 02761872 2011-11-14
WO 2010/132591
PCT/US2010/034586
BACKGROUND OF THE INVENTION
[04] For example, evacuated blood collection tubes are used for drawing
blood
from a patient for medical analysis. The tubes are sold evacuated. The
patient's blood
is communicated to the interior of a tube by inserting one end of a double-
ended
hypodermic needle into the patient's blood vessel and impaling the closure of
the
evacuated blood collection tube on the other end of the double-ended needle.
The
vacuum in the evacuated blood collection tube draws the blood (or more
precisely, the
blood pressure of the patient pushes the blood) through the needle into the
evacuated
blood collection tube, increasing the pressure within the tube and thus
decreasing the
pressure difference causing the blood to flow. The blood flow typically
continues until
the tube is removed from the needle or the pressure difference is too small to
support
flow.
[05] Evacuated blood collection tubes should have a substantial shelf life
to
facilitate efficient and convenient distribution and storage of the tubes
prior to use. For
example, a one-year shelf life is desirable, and progressively longer shelf
lives, such as
18 months, 24 months, or 36 months, are also desired in some instances. The
tube
desirably remains essentially fully evacuated, at least to the degree
necessary to draw
enough blood for analysis (a common standard is that the tube retains at least
90% of
the original draw volume), for the full shelf life, with very few (optimally
no) defective
tubes being provided.
[06] A defective tube is likely to cause the phlebotomist using the tube to
fail to
draw sufficient blood. The phlebotomist might then need to obtain and use one
or more
additional tubes to obtain an adequate blood sample.
[07] For another example, prefilled syringes are commonly prepared and sold
so
the syringe does not need to be filled before use. The syringe can be
prefilled with
saline solution, a dye for injection, or a pharmaceutically active
preparation, for some
examples.
[08] Commonly, the prefilled syringe is capped at the distal end, as with a
cap,
and is closed at the proximal end by its drawn plunger. The prefilled syringe
can be
2
CA 02761872 2011-11-14
WO 2010/132591
PCT/US2010/034586
wrapped in a sterile package before use. To use the prefilled syringe, the
packaging
and cap are removed, optionally a hypodermic needle or another delivery
conduit is
attached to the distal end of the barrel, the delivery conduit or syringe is
moved to a use
position (such as by inserting the hypodermic needle into a patient's blood
vessel or into
apparatus to be rinsed with the contents of the syringe), and the plunger is
advanced in
the barrel to inject the contents of the barrel.
[09] One important consideration in manufacturing pre-filled syringes is
that the
contents of the syringe desirably will have a substantial shelf life, during
which it is
important to isolate the material filling the syringe from the barrel wall
containing it, to
avoid leaching material from tne barrel into the pretilled contents or vice
versa.
[10] Since many of these vessels are inexpensive and used in large
quantities, for
certain applications it will be useful to reliably obtain the necessary shelf
life without
increasing the manufacturing cost to a prohibitive level. It is also desirable
for certain
applications to move away from glass vessels, which can break and are
expensive to
manufacture, in favor of plastic vessels which are rarely broken in normal use
(and if
broken do not form sharp shards from remnants of the vessel, like a glass tube
would).
Glass vessels have been favored because glass is more gas tight and inert to
pre-filled
contents than untreated plastics. Also, due to its traditional use, glass is
well accepted,
as it is known to be relatively innocuous when contacted with medical samples
or
pharmaceutical preparations and the like.
[11] A further consideration when regarding syringes is to ensure that the
plunger
can move at a constant speed and with a constant force when it is pressed into
the
barrel. For this purpose, a lubricity coating, either on one or on both of the
barrel and
the plunger, is desirable.
[12] A non-exhaustive list of patents of possible relevance includes US
Patents
6,068,884 and 4,844,986 and U.S. Published Applications 20060046006 and
200402671 94.
3
SUMMARY OF THE INVENTION
[13] It is an intended object of the invention to provide for an improved
fabrication of
coated vessels.
[14] In the following, methods and devices which are fabricated according to
the
methods are described, wherein the methods can be carried out by the vessel
processing system described further below and the devices can be fabricated by
this
system.
[14a] According to one aspect of the invention, there is provided a polymer
syringe
which comprises a syringe barrel and a plunger and which is coated on at least
part
of its interior surface with a lubricity coating which requires a lower force
to maintain
movement of the plunger in the syringe barrel than the uncoated surface,
wherein
the lubricity coating has the atomic ratio SiwOxCyHz wherein w is 1, x is from
about
0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2 to
about 9 and
wherein the lubricity coating has been prepared on the substrate surface by a
method
comprising the steps (a) providing a gaseous reactant comprising an
organosilicon
precursor which is octamethylcyclotetrasiloxane (OMCTS) in the vicinity of the
substrate surface; and (b) generating a plasma from the gaseous reactant, thus
forming a coating on the substrate surface by plasma enhanced chemical vapor
deposition (PECVD).
[14b] According to a second aspect of the invention, there is provided a
vessel
comprising an interior surface and a hydrophobic coating on at least a portion
of the
interior surface, the hydrophobic coating having a lower wetting tension than
the
uncoated surface, wherein the hydrophobic coating has the atomic ratio
SiwOxCyHz
wherein w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 to about
3, and z
is from about 2 to about 9, and wherein the hydrophobic coating has been
prepared
on at least a portion of the interior surface by a method comprising the
steps: (a)
providing a gaseous reactant comprising an organosilicon precursor which is
octamethylcyclotetrasiloxane (OMCTS) in the vicinity of at least a portion of
the
interior surface; and (b) generating a plasma from the gaseous reactant, thus
forming
a coating on at least a portion of the interior surface by plasma enhanced
chemical
vapor deposition.
[14c] According to a third aspect of the invention, there is provided a method
for
preparing the vessel according to the second broad aspect above, the method
comprising the steps of: (a) providing a gaseous reactant comprising an
4
Date Recue/Date Received 2021-02-23
organosilicon precursor which is octamethylcyclotetrasiloxane (OMCTS) in the
vicinity of at least a portion of the interior surface; and (b) generating a
plasma from
the gaseous reactant, thus forming a coating on at least a portion of the
interior
surface by plasma enhanced chemical vapor deposition.
[15] The present invention according to its embodiments provides a method
of
coating a surface, for example the interior surface of a vessel, with a
coating made
by PECVD from an organosilicon precursor. Furthermore, the present invention
according to its embodiments provides the resulting coating, a vessel coated
with
such coating, and the use of the coating, e.g. as lubricity coating,
hydrophobic
coating, or barrier coating. Moreover, apparatus and several devices for
performing
the invention are provided. The embodiments of the invention also provides
inspection methods for the coating, in particular a method utilizing the
outgassing of
volatile species by the coated surface for said inspection.
PECVD Coating Method
[16] The present invention according to its embodiments pertains to a method
of
preparing a coating by plasma enhanced chemical vapor deposition treatment
(PECVD), and for example a method of coating the interior surface of a vessel.
[17] A surface, for example an interior vessel surface, is provided, as is a
reaction
mixture comprising an organosilicon compound gas, optionally an oxidizing gas,
and
optionally a hydrocarbon gas.
[18] The surface is contacted with the reaction mixture. Plasma is formed in
the
reaction mixture. Illustratively, said plasma is non-hollow cathode plasma or,
in
another expression for the same condition, said plasma is substantially free
of hollow
cathode plasma. The coating is deposited on at least a portion of the surface,
e.g. a
portion of the vessel interior wall.
[19] The method is carried out as follows.
4a
Date Recue/Date Received 2021-02-23
[20] A precursor is provided. Illustratively, said precursor is an
organosilicon compound
(in the following also designated as "organosilicon precursor"), more
illustratively an
organosilicon compound selected from the group consisting of a linear
siloxane, a
monocyclic siloxane, a bolycyclic siloxane, a bolysilsesquioxane, an alkyl
trimethoxysilane, an aza analogue of any of these precursors (i.e. a linear
siloxazane, a
monocyclic siloxazane, a polycyclic siloxazane, a polysilsesquioxazane), and a
combination of any two or more of these precursors. The precursor is applied
to a
substrate under conditions effective to form a coating by PECVD. The precursor
is thus
polymerized, crosslinked, partially or fully oxidized, or any combination of
these.
[21] In embodiment of the invention, the coating is a lubricity coating, i.e.
it forms a
surface haying a lower frictional resistance than the uncoated substrate.
[22] In embodiment of the invention, the coating is a passivating coating, for
example a
hydrophobic coating resulting, e.g., in a lower precipitation of components of
a
composition in contact with the coated surface Such hydrophobic coating is
characterized by a lower wetting tension than its uncoated counterpart.
[23] A lubricity coating of the present invention according to its embodiments
may also
be a passivating coating and vice versa.
[24] In embodiment of the invention, the coating is a barrier coating, for
example an SiOx
coating. Typically, the barrier is against a gas or liquid, illustratively
against water vapor,
oxygen and/or air. The barrier may also be used for establishing and/or
maintaining a
vauuuiii iiisid d vsl uodLd with LIIC bdIIiI wdtiliy, y. iiisid a
blood uollutivii
tube.
[25] In addition, the method of the invention according to its embodiments
may
comprise the application of one or more additional coatings made by PECVD from
an
organosilicon precursor. An optional additional step is post-treating the SiOx
coating with
a process gas consisting essentially of oxygen and essentially free of a
volatile silicon
compound.
Lubricity Coating
[26] In a specific aspect, present invention according to its embodiments
provides a
lubricity coating.
Date Recue/Date Received 2020-08-17
[27] This coating is made by the PECVD method and using the precursors as
described
above.
[28] For example, the present invention according to its embodiments provides
a method
for setting the lubricity properties of a coating on a substrate surface, the
method
comprising the steps:
[29] (a) providing a gaseous reactant comprising an organosilicon precursor
and
optionally 02 in the vicinity of the substrate surface; and
[30] (b) generating
a plasma from the gaseous reactant, thus forming a coating on
the substrate surface by plasma enhanced chemical vapor deposition (PECVD),
wherein
the lubricity characteristics of the coating are set by setting the ratio of
the 02 to the
organosilicon precursor in the gaseous reactant, and/or by setting the
electric power
used for generating the plasma.
[31] An illustrative precursor for the lubricating coating is a monocyclic
siloxane, for
example octamethylcyclotetrasiloxane (OMCTS).
[32] The resulting coated surface has a lower frictional resistance than the
untreated
substrate. For example, when the coated surface is the inside of a syringe
barrel and/or
a syringe plunger, the lubricity coating is effective to provide a breakout
force or plunger
sliding force, or both that is less than the corresponding force required in
the absence of
the lubricating coating.
[33] The article coated with the lubricity coating may be a vessel having the
lubricating
coating on a wall, illustratively on the interior wall, e.g. a syringe barrel,
or a vessel part
or vessel cap having said coating on the vessel contacting surface, e.g. a
syringe plunger
or a vessel cap.
[34] The lubricity coating may in one aspect have the formula SiwOxCyHz, for
example
where vv is 1, x is w is 1, x is from about 0.5 to about 2.4, y is from about
0.6 to about 3,
and z is from about 2 to about 9, illustratively where w is 1, x is from about
0.5 to 1, y is
from about 2 to about 3, and z is from 6 to about 9.
6
Date Recue/Date Received 2020-08-17
Passivating, for example Hydrophobic Coating
[35] The passivating coating according to the embodiments of the present
invention is
for example a hydrophobic coating.
[36] An illustrative precursor for the passivating, for example the
hydrophobic coating
is a linear siloxane, for example hexamethyldisiloxane (HM DSO).
[37] A passivating coating according to the embodiments of the present
invention
prevents or reduces mechanical and/or chemical effects of the uncoated surface
on a
compound or composition contained in the vessel. For example, precipitation
and/or
clotting or platelet activation of a compound or component of a composition in
contact
with the surface are prevented or reduced, e9. blood clotting or platelet
activation or
precipitation of insulin, or wetting of the uncoated surface by an aqueous
fluid is
prevented.
[38] A particular aspect of the invention according to its embodiments is a
surface
having a hydrophobic coating with the formula SiwOxCyHz, for example where w
is 1, x is
from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from
about 2 to about
9, illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and Z
i3 from 0 to about 0.
[39] The article coated with the passivating coating may be a vessel having
the coating
on a wall, illustratively on the interior wall, e.g. a tube, or a vessel part
or vessel cap
having said coating on the vessel contacting surface, e.g. a vessel cap.
Coating of a Vessel
[40] When a vessel is coated by the above coating method using PECVD, the
coating
method comprises several steps. A vessel is provided having an open end, a
closed end,
and an interior surface. At least one gaseous reactant is introduced within
the vessel.
Plasma is formed within the vessel under conditions effective to form a
reaction product
of the reactant, i.e. a coating, on the interior surface of the vessel.
[41] Illustratively,
the method is performed by seating the open end of the vessel on
a vessel holder as described herein, establishing a sealed communication
between the
vessel holder and the interior of the vessel. In this illustrative aspect, the
gaseous
7
Date Recue/Date Received 2020-08-17
reactant is introduced into the vessel through the vessel holder. In a
particularly
illustrative aspect of the invention according to its embodiments, a plasma
enhanced
chemical vapor deposition (PECVD) apparatus comprising a vessel holder, an
inner
electrode, an outer electrode, and a power supply is used for the coating
method
according to the embodiments of the present invention.
[42] The vessel holder has a port to receive a vessel in a seated position for
processing.
The inner electrode is positioned to be received within a vessel seated on a
vessel
holder. The outer electrode has an interior portion positioned to receive a
vessel seated
on the vessel holder. The power supply feeds alternating current to the inner
and/or outer
electrodes to form a plasma within the vessel seated on the vessel holder.
Typically, the
power supply feeds alternating current to the outer electrode while Me inner
electrode is
grounded. In this embodiment, the vessel defines the plasma reaction chamber.
[43] In a particular aspect of the invention according to its embodiments,
the PECVD
apparatus as described in the preceding paragraphs comprises a as drain, not
necessarily including a source of vacuum, to transfer gas to or from the
interior of a
vessel seated on the port to define a closed chamber.
[44] In a further particular aspect of the invention according to its
embodiments, the
PECVD apparatus includes a vessel holder, a first gripper, a seat on the
vessel holder,
a reactant supply, a plasma generator, and a vessel release.
[45] The vessel holder is configured for seating to the open end of a vessel.
The first
yiippei is UUlifiguied rot seleutively holdif iy dud ieleesii iy tile CAUSed
end old Vessel di id,
while gripping the closed end of the vessel, transporting the vessel to the
vicinity of the
vessel holder. The vessel holder has a seat configured for establishing sealed
communication between the vessel holder and the interior space of the first
vessel.
[46] The reactant supply is operatively connected for introducing at least one
gaseous
reactant within the first vessel through the vessel holder. The plasma
generator is
configured for forming plasma within the first vessel under conditions
effective to form a
reaction product of the reactant on the interior surface of Me first vessel.
8
Date Recue/Date Received 2020-08-17
[47] The vessel release is provided for unseating the first vessel from the
vessel holder.
A gripper which is the first gripper or another gripper is configured for
axially transporting
the first vessel away from the vessel holder and then releasing the first
vessel.
[48] In a particular aspect of the invention according to its embodiments, the
method is
for coating an inner surface of a restricted opening of a vessel, for example
a generally
tubular vessel, by PECVD. The vessel includes an outer surface, an inner
surface
defining a lumen, a larger opening having an inner diameter, and a restricted
opening
that is defined by an inner surface and has an inner diameter smaller than the
larger
opening inner diameter. A processing vessel is provided having a lumen and a
processing vessel opening. The processing vessel opening is connected with the
restricted opening of the vessel to establish communication between the lumen
of the
vessel to be processed and the processing vessel lumen via the restricted
opening. At
least a partial vacuum is drawn within the lumen of the vessel to be processed
and the
processing vessel lumen. A PECVD reactant is flowed through the first opening,
then
through the lumen of the vessel to be processed, then through the restricted
opening,
then into the processing vessel lumen. Plasma is generated adjacent to the
restricted
opening under conditions effective to deposit a coating of a PECVD reaction
product on
thp innpr slit-far-AP nf thp rpstrintpri nppning
Coated Vessel And Vessel Parts
[49] The present invention according to its embodiments further provides
the coating
resulting from the method as described above, a surface coated with said
coating, and
for example a vessel coated with said coating.
[50] The surface coated with the coating, e.g. the vessel wall or a part
thereof, may
be glass or a polymer, illustratively a thermoplastic polymer, more
illustratively a polymer
selected from the group consisting of a polycarbonate, an olefin polymer, a
cyclic olefin
copolymer and a polyester. For example, it is a cyclic olefin copolymer, a
polyethylene
terephthalate or a polypropylene_
9
Date Recue/Date Received 2020-08-17
[51] In a particular embodiment of the invention, the vessel wall has an
interior polymer
layer enclosed by at least one exterior polymer layer. The polymers may be
same or
different. E.g., one of the polymer layers of a cyclic olefin copolymer (COC)
resin (e.g.,
defining a water vapor barrier), another polymer layer is a layer of a
polyester resin. Such
vessel may be made by a process including introducing COC and polyester resin
layers
into an injection mold through concentric injection nozzles.
[52] The coated vessel of the embodiments of the invention may be empty,
evacuated
or (pre)filled with a compound or composition.
[53] A particular embodiment of the invention is a vessel having a passivating
coating,
for example a hydrophobic coating as defined above.
[54] A further particular aspect of the invention is a surface having a
lubricity coating as
defined above. It may be a vessel having the lubricity coating on a wall,
illustratively on
the interior wall, e.g. a syringe barrel, or a vessel part or vessel cap
having said coating
on the vessel contacting surface, e.g. a syringe plunger or a vessel cap.
[55] A particular embodiment of the invention is a syringe including a
plunger, a syringe
barrel, and a lubricity coating as defined above on either one or both of
these syringe
parts. illustratively on the inside wall of the syringe barrel. The syringe
barrel includes a
barrel having an interior surface slidably receiving the plunger. The
lubricity coating may
be disposed on the interior surface of the syringe barrel, or on the plunger
surface
contacting the barrel, or on both said surfaces. The lubricity coating is
effective to reduce
tile uiudKout roiue ut tile plunget sliding futue I leUebb1 y to move Me
plunget within the
barrel.
[56] A further particular embodiment of the invention is a syringe barrel
coated with the
lubricity coating as defined in the preceding paragraph.
[57] In a specific
aspect of said coated syringe barrel, the syringe barrel comprises
a barrel defining a lumen and having an interior surface slidably receiving a
plunger. The
syringe barrel is made of thermoplastic material. A lubricity coating is
applied to the barrel
interior surface, the plunger, or both, by plasma-enhanced
Date Recue/Date Received 2020-08-17
chemical vapor deposition (PECVD). A solute retainer is applied over the
lubricity coating
by surface treatment, e.g. in an amount effective to reduce a leaching of the
lubricity
coating, the thermoplastic material, or both into the lumen. The lubricity
coating and
solute retainer are composed, and present in relative amounts, effective to
provide a
breakout force, plunger sliding force, or both that is less than the
corresponding force
required in the absence of the lubricity coating and solute retainer.
[58] Still another embodiment of the invention is a syringe including a
plunger, syringe
barrel, and interior and exterior coatings. The barrel has an interior surface
slidably
receiving the plunger and an exterior surface. A lubricity coating is on the
interior surface,
and an additional barrier coating of SiOx, in which x is from about 1.5 to
about 2.9, may
be provided on the interior surface of the barrel. A barrier coating, e.g. of
a resin or of a
further SiOx coating, is provided on the exterior surface of the barrel.
[59] Another embodiment of the invention is a syringe including a plunger, a
syringe
barrel, and a Luer fitting_ The syringe barrel has an interior surface
slidably receiving the
plunger. The Luer fitting includes a Luer taper having an internal passage
defined by an
internal surface. The Luer fitting is formed as a separate piece from the
syringe barrel
and joined to the syringe barrel by a coupling. The internal passage of the
Luer taper has
a barrier coating ot SiOx, in which x is trom about 1.b to about 2.9.
[60] Another embodiment of the invention is a plunger for a syringe, including
a piston
and a push rod. The piston has a front face, a generally cylindrical side
face, and a back
portion, the side face heing configured to movably seat within a syringe
barrel The
plunger has a lubricity coating according to the present embodiment invention
on its side
face. The push rod engages the back portion of the piston and is configured
for
advancing the piston in a syringe barrel. The plunger may additionally
comprise a SiOx
coating.
[61] A further embodiment of the invention is a vessel with just one opening,
Le. a vessel
for collecting or storing a compound or composition. Such vessel is in a
specific aspect
a tube, e_g_ a sample collecting tube, e_g_, a blood collecting tube_ Said
tube may be
closed with a closure, e.g. a cap or stopper. Such cap or stopper may comprise
a lubricity
coating according to the present embodiment invention on its surface which is
in contact
with the tube, and/or it may contain a passivating coating according to the
embodiment
present invention
11
Date Recue/Date Received 2020-08-17
on its surface facing the lumen of the tube. In a specific aspect, such
stopper or a part
thereof may be made from an elastomeric material.
[62] Such a stopper may be made as follows: The stopper is located in a
substantially
evacuated chamber. A reaction mixture is provided including an organosilicon
compound
gas, optionally an oxidizing gas, and optionally a hydrocarbon gas. Plasma is
formed in
the reaction mixture, which is contacted with the stopper. A coating is
deposited on at
least a portion of the stopper_
[63] A further
embodiment of the invention is a vessel having a barrier coating
according to the embodiment of the present invention. The vessel is generally
tubular
and may be made of thermoplastic material. The vessel has a mouth and a lumen
bounded at least in part by a wall. The wall has an inner surface interfacing
with the
lumen. In an illustrative aspect, an at least essentially continuous barrier
coating made
of SiOx as defined above is applied on the inner surface of the wall. The
barrier coating
is effective to maintain within the vessel at least 90% of its initial vacuum
level, optionally
95% of its initial vacuum level, for a shelf life of at least 24 months. A
closure is provided
covering the mouth of the vessel and isolating the lumen of the vessel from
ambient air.
[64] The PECVD made coatings and PECVD coating methods using an organosilicon
precursor described in this specification are also useful for coating
catheters or cuvettes
to form a barrier coating, a hydrophobic coating, a lubricity coating, or more
than one of
these. A cuvette is a small tube of circular or square cross section, sealed
at one end,
made of a polymer, glass, or fused quartz (for UV light) and designed to hold
samples
for spectroscopic experiments. The best cuvettes are as clear as possible,
without
impurities that might affect a spectroscopic reading. Like a test tube, a
cuvette may be
open to the atmosphere or have a cap to seal it shut. The PECVD-applied
coatings of
Me present embodiments of the invention can be very thin, transparent, and
optically flat,
thus not interfering with optical testing of the cuvette or its contents.
(Pre)filled Coated Vessel
[65] A specific embodiment of the invention is a coated vessel as described
above which
is prefilled or used for being filled with a compound or composition in its
lumen.
12
Date Recue/Date Received 2020-08-17
Said compound or composition may be
(i) a biologically active compound or composition, illustratively a
medicament, more
illustratively insulin or a composition comprising insulin; or
(ii) a biological fluid, illustratively a bodily fluid, more illustratively
blood or a blood
fraction (e.g. blood cells); or
(iii) a compound or composition for combination with another compound or
composition
directly in the vessel, e.g. a compound for the prevention of blood clotting
or platelet
activation in a blood collection tube, like citrate or a citrate containing
composition.
[66] Generally, the coated vessel of the present invention according to its
embodiments
is particularly useful for collecting or storing a compound or composition
which is
sensitive to mechanical and/or chemical effects of the surface of the uncoated
vessel
material, illustratively for preventing or reducing precipitation and/or
clotting or platelet
activation of a compound or a component of the composition in contact with the
interior
surface of the vessel.
[67] E.g., a cell preparation tube having a wall provided with a hydrophobic
coating
of the present invention according to its embodiments and containing an
aqueous sodium
citrate reagent is suitable for collecting blood and preventing or reducing
blood
coagulation. I ne aqueous sodium citrate reagent is disposed in tne lumen or
tne tube in
an amount effective to inhibit coagulation of blood introduced into the tube.
[68] A specific embodiment of the invention is a vessel for
collecting/receiving blood or
a hInnd hnntainino VPRSPI Thp VPSSPI has a wall: thp wall has an innpr SI
irfar.p dpfinino
a lumen. The inner surface of the wall has an at least partial hydrophobic
coating of the
embodiment of the present invention. The coating can be as thin as
monomolecular
thickness or as thick as about 1000 nm. The blood collected or stored in the
vessel is
illustratively viable for return to the vascular system of a patient disposed
witnin tne lumen
in contact with the coating. The coating is effective to reduce the clotting
or platelet
activation of blood exposed to the inner surface, compared to the same type of
wall
uncoated.
[69] Another embodiment of the invention is an insulin containing vessel
including a wall
having an inner surface defining a lumen. The inner surface has an at least
partial
hydrophobic coating of the embodiment of the present invention. The coating
can be
from monomolecular thickness to about 1000 nm thick on the inner surface.
Insulin or
a composition
13
Date Recue/Date Received 2020-08-17
comprising insulin is disposed within the lumen in contact with the coating.
Optionally,
the coating is effective to reduce the formation of a precipitate from insulin
contacting the
inner surface, compared to the same surface absent the coating.
[70] The present invention according to its embodiments thus provides the
following
embodiments with regard to coating methods, coated products and use of said
products:
[71] (1) A method for setting the lubricity properties of a coating on a
substrate surface,
the method comprising the steps
[72] (a) providing a gaseous reactant comprising an organosilicon precursor
and
optionally 02 in the vicinity of the substrate surface; and
[73] (b) generating a plasma from the gaseous reactant, thus forming a
coating on
the substrate surface by plasma enhanced chemical vapor deposition (PECVD),
[74] wherein the lubricity characteristics of the coating are set by
setting the ratio of
the 02 to the organosilicon precursor in the gaseous reactant, and/or by
setting the
electric power used for generating the plasma.
[75] (2) A method for preparing a hydrophobic coating on a substrate, the
method
comprising the steps
[76] (a) providing a gaseous reactant comprising an organosilicon precursor
and
optionally 02 in the vicinity of the substrate surface; and
[77] (b) generating a plasma from the gaseous reactant, thus forming a
coating on
the substrate surface by plasma enhanced chemical vapor deposition (PECVD),
[78] wherein the hydrophobic characteristics of the coating are set by setting
the ratio
of the 02 to the organosilicon precursor in the gaseous reactant, and/or by
setting the
electric power used for generating the plasma.
[79] (3)The method of (1) or (2), which results in a coating which is
characterized by
a sum formula wherein the atomic ratio C : 0 is increased and/or the atomic
ratio Si : 0
is decreased in comparison to the sum formula of the organosilicon precursor.
[80] (4) The method according to any of (1) to (3), wherein the 02 is present
in a volume-
volume ratio to the gaseous reactant of from 0:1 to 5:1, optionally from 0:1
to
14
Date Recue/Date Received 2020-08-17
1:1, optionally from 0:1 to 0.5:1, optionally from 0:1 to 0.1:1,
illustratively wherein at least
essentially no oxygen is present in the gaseous reactant.
[81] (5) The method according to any of (1) to (4), wherein the gaseous
reactant
comprises less than 1 vol% 02, more particularly less than 0.5 vol% 02, and
most
illustratively is 02-free.
[82] (6) The method according to any of (1) to (5), wherein the plasma is a
non- hollow-
cathode plasma.
[83] (7) The method according to any of (1) to (6), wherein the substrate is
the inside
wall of a vessel having a lumen, the lumen having a void volume of from 0.5 to
50 mL,
illustratively from 1 to 10 mL, more illustratively from 0.5 to 5 mL, most
illustratively from
1 to 3 mL.
[84] (8) The method according to any of (1) to (7)
[85] (i) wherein the plasma is generated with electrodes powered with
sufficient power
to form a coating on the substrate surface, illustratively with electrodes
supplied with an
electric power of from 0.1 to 25 W, illustratively from 1 to 22 W, more
illustratively from 3
to 17 W, even more illustratively of from 5 to 14 W, most illustratively of
from 7 to 11 W,
in particular of 0 W; and/or
[86] (ii) wherein the ratio of the electrode power to the plasma volume is
less than 10
W/ml, illustratively is from 5 W/ml to 0.1 W/ml, more illustratively is from 4
W/ml to 0.1
W/ml, most illustratively from 2 W/ml to 0.2 W/ml.
[87] (9)A method for preparing a coating on a substrate surface, the method
comprising
the steps
[88] (a) providing a gaseous reactant comprising an organosilicon precursor
and
optionally 02 in the vicinity of the substrate surface; and
[89] (b) generating a non-hollow-cathode plasma from the gaseous reactant at
reduced
pressure, thus forming a coating on the substrate surface by plasma enhanced
chemical
vapor deposition (PECVD),
Date Recue/Date Received 2020-08-17
[90] wherein the physical and chemical properties of the coating are set by
setting the
ratio of the 02 to the organosilicon precursor in the gaseous reactant, and/or
by setting
the electric power used for generating the plasma.
[91] (10) A method for preparing a barrier coating on a substrate, the method
comprising
the steps
[92] (a) providing a gaseous reactant comprising an organosilicon precursor
and 02
in the vicinity of the substrate surface; and
[93] (b) generating a non-hollow-cathode plasma from the gaseous reactant at
reduced
pressure, thus forming a coating on the substrate surface by plasma enhanced
chemical
vapor deposition (PECVD),
[94] wherein the barrier characteristics of the coating are set by setting
the ratio of
the 02 to the organosilicon precursor in the gaseous reactant, and/or by
setting the
electric power used for generating the plasma.
[95] (11) The method according to (10)
[96] (i) wherein the plasma is generated with electrodes powered with
sufficient power
to form a coating on the substrate surface, illustratively with electrodes
supplied with an
electric power of from 8 to 500 W, illustratively from 20 to 400 W, more
illustratively from
35 to 350 W, even more illustratively of from 44 to 300 W, most illustratively
of from 44 to
70 W; and/or
[07] thc ratio of thc cicotrodc powcr to thc plaorna volumc i 3 cqual or
morc than 5
W/ml, illustratively is from 6 W/ml to 150 W/ml, more illustratively is from 7
W/ml to 100
W/ml, most illustratively from 7 W/ml to 20 W/ml.
[98] (12) The method according to (10) or (11), wherein the 02 is present in a
volume:volume ratio to the gaseous reactant of from 1 : 1 to 100 : 1 in
relation to the
silicon containing precursor, illustratively in a ratio of from 5: 1 to 30: 1,
more illustratively
in a ratio of from 10 : 1 to 20 : 1, even more illustratively in a ratio of 15
: 1.
[99] (13) The method of any of (1) to (12), wherein the organosilicon
precursor is selected
from the group consisting of a linear siloxane, a monocyclic siloxane, a
16
Date Recue/Date Received 2020-08-17
polycyclic siloxane, a polysesquioxane, a linear silazane, a monocyclic
silazane, a
polycyclic silazane, a polysilsesquiazane, an alkyl trimethoxysiloxane, and a
combination
of any two or more of these
compounds, illustratively is a linear or
monocyclic siloxane.
[100] (14) The method of (1) or (2) wherein the organosilicon precursor is a
monocyclic
siloxane, illustratively OMCTS.
[101] (15) The method of (2) or (10), wherein the organosilicon precursor is a
linear
siloxane, illustratively HM DSO.
[102] (16) The method according to any of (1) to (15), wherein the PECVD is
performed
at a flow of the organosilicon precursor of equal or less than 6 sccm,
illustratively of equal
or less than 2.5 seem, more illustratively of equal or less than 1.5 scorn,
most illustratively
of equal or less than 1.25 seem.
[103] (17) The method according to any of (1) to (16), wherein the substrate
is a polymer
selected from the group consisting of a polycarbonate, an olefin polymer, a
cyclic olefin
copolymer and a polyester, and illustratively is a cyclic olefin copolymer, a
polyethylene
terephthalate or a polypropylene.
[104] (10) The method according to any of (1) to (17), wherein the
substrate surface
is part or all of the inner surface of a vessel having at least one opening
and an inner
surface, and wherein the gaseous reactant tills the interior lumen of the
vessel and the
plasma is generated in part or all of the interior lumen of the vessel.
[105] (19) The method according to any of (1) to (18), wherein the plasma is
generated
with electrodes powered at a radiofrequency, illustratively at a frequency of
from 10 kHz
to less than 300 MHz, more illustratively of from 1 to 50 MHz, even more
illustratively of
from 10 to 15 MHz, most illustratively at 13.56 MHz.
[106] (20) The method according to any of (1) to (19), wherein the plasma is
generated
at reduced pressure and the reduced pressure is less than 300 mTorr,
illustratively less
than 200 mTorr, even more illustratively less than 100 mTorr.
17
Date Recue/Date Received 2020-08-17
[107] (21) The method according to any of (1) to (20), wherein the PECVD
deposition
time is from 1 to 30 sec, illustratively from 2 to 10 sec, more illustratively
from 3 to 9 sec.
[108] (22) The method according to any of (1) to (21), wherein the resulting
coating
has a thickness of in the range of from 1 to 100 nm, illustratively in the
range of from 20
to 50 nm.
[109] (23) A coating which is obtainable by the method according to any of the
preceding
claims.
[110] (24) The coating of (23), which is a lubricity and/or hydrophobic
coating.
[111] (25) The coating of (24), wherein the atomic ratio of carbon to oxygen
is increased
in comparison to the organosilicon precursor, and/or wherein the atomic ratio
of oxygen
to silicon is decreased in comparison to the organosilicon precursor.
[112] (26) The coating of any of (23) to (25), wherein the precursor is
octamethylcyclotetrasiloxane and wherein the coating has a density which is
higher than
the density of a coating made from HMDSO under the same PECVD reaction
conditions.
[113] (27) The coating according to any of (24) to (26), wherein the
coating
(i) has a lower frictional resistance than the uncoated surface, wherein
illustratively the
frictional resistance is reduced by at least 25 %, more illustratively by at
least 45%, even
more illustratively by at least 60% in comparison to the uncoated surface.
[114] (28) The coating according to any of (24) to (27), which
[115] (i) has a lower wetting tension than the uncoated surface,
illustratively a wetting
tension of from 20 to 72 dyne/cm, more illustratively a wetting tension of
from 30 to 60
dynes/cm, more illustratively a wetting tension of from 30 to 40 dynes/cm,
illustratively
34 dyne/cm; and/or
[116] (iv) is more hydrophobic than the uncoated surface.
[117] (29) A vessel coated on at least part of its interior surface with the
coating according
to any of (23) to (28), illustratively a vessel which is
18
Date Recue/Date Received 2020-08-17
[118] (i) a sample collection tube, in particular a blood collection tube;
or
[119] (ii) a vial; or
[120] Op a syringe or a syringe part, in particular a syringe barrel or a
syringe plunger:
or
[121] (iv) a pipe; or
[122] (v) a cuvette.
[123] (30) The coated vessel according to (29), additionally comprising at
least one layer
of SiOx, wherein x is from 1.5 to 2.9, wherein
[124] (i) the coating is situated between the SiOx layer and the substrate
surface or
vice versa, or wherein
[125] (ii) the coating is situated between two SiOx layers or vice versa,
or wherein
[126] (iii) the layers of SiOx and the coating are a graded composite of
SiwOxCyHz to
SiOx or vice versa.
[127] (31) The coated vessel according to any of (29) to (30), which contains
at least
one further layer on its exterior surface, illustratively a further barrier
layer consisting of
plastic or SiOx, wherein x is from 1.5 to 2.9.
[128] (32) The coated vessel according to any of (29) to (31) which contains a
compound
or composition in its lumen, illustratively a biologically active compound or
composition
nr ci hinIngirtal fluid,rnnrp ilhistrativply (i) nitratp nr ci rtitratp
rtnntaining nnmpnsitinn, (ii) ci
medicament, in particular insulin or an insulin containing composition, or
(iii) blood or
blood cells.
[129] (33) The coated vessel according to any of (29) to (32), which is a
syringe barrel
made according to the method of claim 1 wherein the precursor is a siloxane,
more
illustratively is a monocyclic siloxane, even more illustratively is
octamethylcyclotetrasiloxane, and wherein in step (a) substantially no 02 gas
is provided
in the gaseous reactant, wherein the force for moving the plunger through said
coated
barrel is reduced by at least 25 %, more illustratively by at least 45%, even
more
illustratively by at least 60% in comparison to the uncoated syringe barrel.
19
Date Recue/Date Received 2020-08-17
[130] (34) Use of a coating having the sum formula SiwOxCyHz, wherein w is
1, x is
0.5 to 2.4, y is 0.6 to 3, and z is from 2 to 9 as
[131] (i) a lubricity coating having a lower frictional resistance than the
uncoated surface;
and/or
[132] (ii) a hydrophobic coating being more hydrophobic than the uncoated
surface.
[133] (35) The use of (34), wherein the coating is a coating as defined in
any of (24)
to (28).
[134] (36) The use of (34) or (35), wherein the coating prevents or reduces
the
precipitation of a compound or component of a composition in contact with the
coating,
in particular prevents or reduces insulin precipitation or blood clotting, in
comparison to
the uncoated surface and/or to a surface coated according to the method of (1)
using
HMDSO as precursor.
[135] (37) Use of the coated vessel according to any of (29) to (33) for
protecting a
compound or composition contained or received in said coated vessel against
mechanical and/or chemical effects of the surface of the uncoated vessel
material,
illustratively for preventing or reducing precipitation and/or clotting of a
compound or a
component of the compooition in contact with the interior ourface of the
VC55CI.
[136] (38) The use of (37), wherein the compound or composition is
[137] (i) a biologically active compound or composition, illustratively a
medicament, more
illuotratively inoulin or a compooition comprioing inoulin whet-6n inoulin
precipitation io
reduced or prevented; or
[138] (ii) a biological fluid, illustratively a bodily fluid, more
illustratively blood or a blood
fraction wherein blood clotting and/or platelet activation is reduced or
prevented.
[139] (39) a medical or diagnostic kit comprising a coated vessel according to
present
invention which may additionally comprise: a medicament or diagnostic agent
which is
contained in said coated vessel; and/or a hypodermic needle, double-ended
needle, or
other delivery conduit; and/or an instruction sheet.
[140] The present invention further provides the following embodiments:
Date Recue/Date Received 2020-08-17
I. VESSEL PROCESSING SYSTEM HAVING MULTIPLE PROCESSING
STATIONS AND MULTIPLE VESSEL HOLDERS
[141] According to an
aspect of the embodiments of the present invention, a vessel
processing system for coating of a vessel is provided, the system comprising a
first
processing station, a second processing station, a vessel holder and a
conveyor
arrangement. The first processing station is configured for performing a first
processing,
for example an inspection or a coating, of an interior surface of the vessel.
The second
processing station is based from the first processing station and configured
for
performing a second processing, for example an inspection or a coating, of the
interior
surface of the vessel. The vessel holder comprises a vessel port configured to
receive
and seat an opening of the vessel for processing (inspecting and/or coating
and/or
inspecting) the interior surface of the seated vessel via the vessel port at
the first
processing station and at the second processing station. The conveyor
arrangement is
adapted for transporting the vessel holder and the seated vessel after the
first processing
from the first processing station to the second processing station for the
second
processing of the interior surface of the seated vessel at the second
processing station.
[142] Vessels are broadly defined in this specification as including any type
of vessel,
Muludilly but nut limited to Jai i ipl LLILJCJ ful uolleuLiny ul bLuliny
blood, thine, ul otlii
samples, syringes for storing or delivering a biologically active compound or
composition,
vials for storing biological materials or biologically active compounds or
compositions,
catheters for transporting biological materials or biologically active
compounds or
compositions, and cuvettes for holding biological materials or biologically
active
compounds or compositions.
[143] The vessels described in the following are all processed with one of the
below
described processing systems or apparatus. In other words, features which are
in the
following described with respect to an apparatus or processing system may also
be
implemented as method steps and may affect the thus processed vessel.
[144] A cuvette is a small tube of circular or square cross section, sealed at
one end,
made of plastic, glass, or fused quartz (for UV light) and designed to hold
samples for
spectroscopic experiments. The best cuvettes are as clear as possible, without
21
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impurities that might affect a spectroscopic reading. Like a test tube, a
cuvette may be
open to the atmosphere on top or have a Gap to seal it shut.
[145] The term 'interior of the vessel" refers to the hollow space inside
the vessel
which can be used for storing blood or, according to another exemplary
embodiment, a
biologically active compound or composition.
[146] The term processing may comprise a coating step and/or an inspection
step
or a series of coating and inspection steps, for example an initial inspection
step,
followed by a coating step which is then followed by a second or even third or
fourth
inspection. The second, third and fourth inspection may be carried out
simultaneously.
[147] According to an exemplary embodiment of the present invention, the
vessel
holder comprises a vacuum duct for withdrawing a gas from an interior space of
the
seated vessel, wherein the vessel holder is adapted for maintaining a vacuum
in the
interior of the seated vessel, such that no additional vacuum chamber is
necessary for
processing the vessel. In other words, the vessel holder forms, together with
the seated
vessel, a vacuum chamber which is adapted for providing a vacuum in the
interior
space of the vessel. This vacuum is important for certain processing steps,
such as
plasma enhanced chemical vapour deposition (PECVD) or other chemical vapour
deposition steps. Furthermore, the vacuum inside the vessel may be important
for
performing a certain inspection of the vessel wall, in particular the coating
of the interior
surface of the vessel wall, for example by measuring an outgas rate of the
wall or an
electric conductivity of the wall.
[148] According to another exemplary embodiment of the present invention,
the first
processing is carried out during 30 seconds or less. Also, the second
processing is
carried out during 30 seconds or less.
[149] Thus, a vessel processing system for coating of vessels is provided
which
allows a fast fabrication of the vessels.
[150] According to another exemplary embodiment of the present invention,
the first
processing and/or second processing comprises an inspection of the interior
surface of
the vessel followed by a coating of the interior surface.
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[151] According to another exemplary embodiment of the present invention,
the
vessel holder comprises a gas inlet port for conveying a gas into the interior
of the
vessel.
[152] According to another exemplary embodiment of the present invention,
the
system is adapted for automatically re-processing of the vessel in case a
coating defect
is detected. For example, the vessel processing system and in particular the
vessel
holder may comprise an arrangement of different detectors, for example optical
detectors, pressure probes, gas detectors, electrodes for electric
measurements, etc.
[153] Furthermore, according to another exemplary embodiment of the present
invention, the vessel processing system, for example one or more of the
processing
stations, comprises one or more grippers for transporting the vessel to the
vessel holder
and/or for removing the vessel from the vessel holder.
[154] According to another exemplary embodiment of the present invention,
the
vessel holder comprises a gas inlet port for conveying a gas into the interior
of the
vessel.
[155] According to another exemplary embodiment of the present invention,
the
vessel processing system is adapted for automatically re-processing of the
vessel in
case a coating defect is detected.
[156] The gas conveyed into the interior space of the vessel can be used
for
PECVD coating of the interior surface of the vessel.
[157] According to another exemplary embodiment of the present invention,
the first
processing and/or the second processing comprises a coating of the interior
surface of
the vessel.
[158] According to another exemplary embodiment of the present invention,
the first
processing station and/or second processing station comprises a PECVD
apparatus for
coating of the interior surface of the vessel.
[159] According to another exemplary embodiment of the present invention,
the
system further comprises an outer electrode surrounding at least an upper part
of the
seated vessel.
23
[160] According to another exemplary embodiment of the present invention, the
vessel
holder comprises an electrically conductive probe to provide a counter-
electrode within
the vessel.
[161] According to another exemplary embodiment of the present invention, the
first
processing and/or second processing comprises an inspection of the interior
surface of
the vessel for defects.
[162] According to another exemplary embodiment of the present invention, the
system
further comprises a first detector adapted for being inserted into the vessel
via the vessel
port of the first processing station and/or the second processing station for
inspection of
the interior surface of the vessel for defects.
[163] According to another exemplary embodiment of the present invention, the
vessel
processing system further comprises a second detector located outside the
vessel for
inspection of the interior surface of the vessel for defects.
[164] According to another exemplary embodiment of the present invention, the
first
detector and/or the second detector is mounted to the vessel holder.
[165] According to another exemplary embodiment of the present invention, the
vessel
home! -- L,umpi ises a mould for for the vessel.
[166] According to another aspect of the embodiments of the present invention,
the
use of an above and below described vessel processing system is stated, for
fabricating
a blood tube for storing blood, a syringe for storing a biologically active
compound or
composition, a vial for storing a biologically active compound or composition,
a catheter
for transporting biologically active compounds or compositions, or a pipette
for pipetting
a biologically active compound or composition.
[167] The vessel processing system may also be adapted for inspection of a
vessel and
may in particular be adapted for performing a first inspection of the vessel
for defects,
application of a first coating to the interior surface of the vessel, followed
by second
inspection of the interior surface of the coated vessel for defects_
Furthermore, the
system may be adapted for evaluation of the data acquired during the different
24
Date Recue/Date Received 2020-08-17
inspections, wherein the second inspection and the data evaluation takes less
than 30
seconds.
[168] According to another aspect of the embodiments of the invention a vessel
processing system for coating and inspection of a vessel is provided, the
system
comprising a processing station arrangement which is configured for performing
a first
inspection of the vessel for defects, application of a first coating to the
interior surface of
the vessel, performing a second inspection of the interior surface of the
coated vessel
for defects and evaluating the data acquired during inspection, wherein the
second
inspection and the data evaluation takes less than 30 seconds.
[169] The application of the first coating may also be referred to as first or
second
processing and the performing of the second inspection of the interior surface
of the
coated vessel may be referred to as second processing.
[170] According to another exemplary embodiment of the present invention, the
processing station arrangement comprises a first processing station for
performing the
first inspection, application of the first coating to the interior surface of
the seated vessel
and performing the second inspection. Furthermore, the processing station
arrangement
comprises a vessel holder which comprises a vessel port configured to receive
and seat
an opening of the vessel for inspecting and applying the first coating of the
interior
surface of the seated vessel via the vessel port at the first processing
station.
[171] According to another exemplary embodiment of the present invention, the
piouessiny station ailanyeirient fuithei uoiripiises d second piuuessiny
station spaced
from the first processing station and configured for performing the second
inspection,
applying a second coating and performing a third inspection after the second
coating.
Furthermore, the vessel processing system comprises a conveyor arrangement for
transporting the vessel holder and the seated vessel after application of the
first coating
from the first processing station to the second processing station for
application of the
second coating to the interior surface of the seated vessel at the second
processing
station. The vessel port of the vessel holder is configured to receive and
seat the opening
of the vessel for coating and inspecting the interior surface of the seated
vessel via the
vessel port at the first processing station and at the second processing
station.
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[172] According to another exemplary embodiment of the present invention,
the
vessel holder comprises a vacuum duct for withdrawing a gas from an interior
of the
seated vessel, wherein the vessel holder is adapted for maintaining a vacuum
in the
interior of the seated vessel, such that no additional vacuum chamber is
necessary for
coating and inspecting the vessel.
[173] According to another exemplary embodiment of the present invention,
each
inspection is carried out during 30 seconds or less.
[174] According to another exemplary embodiment of the present invention,
the
vessel processing system is adapted for automatically re-processing of the
vessel in
case a coating defect is detected.
[175] According to another exemplary embodiment of the present invention,
the
first processing station and/or the second processing station comprises a
PECVD
apparatus for application of the coating of the interior surface of the
vessel.
[176] According to another exemplary embodiment of the present invention,
the
first coating is a barrier coating, wherein the system is adapted for
confirming whether a
barrier layer is present or absent.
[177] According to another exemplary embodiment of the present invention,
the
second coating is a lubricity coating, wherein the system is adapted for
confirming
whether the lubricity coating (i.e. the lubricity layer) is present or absent.
[178] According to another exemplary embodiment of the present invention,
the
first coating is a barrier coating, wherein the second coating is a lubricity
coating, and
wherein the system is adapted for confirming whether the barrier and the
lubricity layer
are present or absent.
[179] According to another exemplary embodiment of the present invention,
the
system is adapted for confirming whether the barrier layer and the lubricity
layer are
present or absent to at least a six sigma level of certainty.
[180] According to another exemplary embodiment of the present invention,
the
first inspection and/or the second inspection comprises at least one of
measuring of an
outgas rate of a gas from the coated vessel, performing an optical monitoring
of the
26
application of the coating, measuring optical parameters of the interior
surface of the
coated vessel, and measuring electrical properties of the coated vessel.
[181] The corresponding
measurement data can then be analyzed by a processor.
[182] According to another exemplary embodiment of the present invention, the
processing system further comprises a first detector for measuring the outgas
rate and/or
a second detector for measuring the diffusion rate and/or a third detector for
measuring
the optical parameters and/or a fourth detector for measuring the electrical
parameters.
[183] According to another exemplary embodiment of the present invention, the
first
coating and/or the second coating is less than 100 nm thick.
[184] According to another exemplary embodiment of the present invention, the
vessel
processing system further comprises a processor for evaluating data acquired
during
inspection.
[185] An aspect of the invention according to its embodiments is a vessel
processing
system comprising a first processing station, a second processing station, a
multiplicity
of vessel holders, and a conveyor. The first processing station is configured
for
processing a vessel having an opening and a wall defining an interior surface.
The
second processing station is spaced from the first proc,essing station and
configured for
processing a vessel having an opening and a wall defining an interior surface.
[186] At least some, optionally all, of the vessel holders include a vessel
port configured
to receive and seat the opening of a vessel for processing the interior
surface of a seated
vessel via the vessel port at the first processing station. The conveyor is
configured for
transporting a series of the vessel holders and seated vessels from the first
processing
station to the second processing station for processing the interior surface
of a seated
vessel via the vessel port at the second processing station.
27
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II. VESSEL HOLDERS
II.A. Vessel Holder Not Reciting Specific Sealing Arrangement
[187] The portable vessel holder of the vessel processing system may be
adapted
for holding a vessel while an interior surface of the vessel is coated and
inspected for
defects and while the vessel is transported from a first processing station to
a second
processing station of the vessel processing system, the vessel holder
comprising a
vessel port configured to seat an opening of the vessel and for processing the
interior
surface of the seated vessel via the vessel port at the first processing
station and at the
second processing station.
[188] The portable vessel holder further comprises, according to another
exemplary embodiment of the present invention, a second port for receiving an
outside
gas supply or vent and a duct for passing a gas between the opening of the
vessel
seated on the vessel port and the second port.
[189] According to another exemplary embodiment of the present invention,
the
portable vessel holder weights less than 2.25 kg.
[190] According to another exemplary embodiment of the present invention,
the
portable vessel holder further comprises a vacuum duct and an outside vacuum
port for
withdrawing a gas via the vessel port from an interior of the seated vessel,
wherein the
vessel holder is adapted for maintaining a vacuum in the interior of the
seated vessel,
such that no additional vacuum chamber is necessary for processing the vessel.
[191] According to another exemplary embodiment of the present invention,
the
portable vessel holder further comprises a vacuum duct and an outside vacuum
port for
withdrawing a gas via the vessel port from an interior of the seated vessel,
wherein the
vessel holder is adapted for maintaining a vacuum in the interior of the
seated vessel,
such that no additional vacuum chamber is necessary for processing the vessel.
[192] According to another exemplary embodiment of the present invention,
the
outside vacuum port also incorporates a gas inlet port, contained within the
vacuum port
for conveying gas into the interior of the seated vessel.
28
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[193] According to another exemplary embodiment of the present invention,
the
processing of the vessel comprises a coating of the interior surface of the
seated
vessel.
[194] According to another exemplary embodiment of the present invention,
the
vessel holder is essentially made of thermoplastic material.
[195] According to another exemplary embodiment of the present invention,
the
portable vessel holder further comprises a cylindrical inner surface for
receiving a
cylindrical wall of the vessel, a first annular groove in and coaxial with the
cylindrical
inner surface, and a first 0-ring disposed in the first annular groove for
providing a seal
between the seated vessel in the vessel holder.
[196] According to another exemplary embodiment of the present invention,
the
portable vessel holder further comprises a radially extending abutment
adjacent to the
round cylindrical inner surface against which the open end of the seated
vessel can be
butted.
[197] According to another exemplary embodiment of the present invention,
the
portable vessel holder further comprises a second annular groove in and
coaxial with
the cylindrical inner surface and axially spaced from the first annular
groove.
Furthermore, the vessel holder comprises a second 0-ring disposed in the
second
annular groove for providing a seal between the seated vessel in the vessel
holder.
[198] According to another exemplary embodiment of the present invention,
the
portable vessel holder furrier comprises a first detector for interrogating me
interior
space of the vessel via the vessel port for inspection of the interior surface
of the seated
vessel for defects.
[199] According to another exemplary embodiment of the present invention,
the
portable vessel holder comprises a mould for forming the vessel.
[200] According to another exemplary embodiment of the present invention,
the
vessel processing system for coating of a vessel comprises the above and below
described vessel holder.
29
[201] According to another aspect of the embodiments of the present invention
the
portable vessel holder includes a vessel port, a second port, a duct, and a
conveyable
housing. The vessel port is configured to seat a vessel opening in a mutually
communicating relation. The second port is configured to receive an outside
gas supply
or vent. The duct is configured for passing one or more gases between a vessel
opening
seated on the vessel port and the second port. The vessel port, second port,
and duct
are attached in substantially rigid relation to the conveyable housing.
Optionally, the
portable vessel holder weighs less than five pounds.
[202] Another aspect of the invention according to its embodiments is a
portable vessel
holder including a vessel port, a vacuum duct, a vacuum port, and a conveyable
housing.
The vessel port is configured to receive a vessel opening in a sealed,
mutually
communicating relation. The vacuum duct is configured for withdrawing a gas
via the
vessel port from a vessel seated on the vessel port. The vacuum port is
configured for
communicating between the vacuum duct and an outside source of vacuum. The
source
of vacuum can be a pump or a reservoir or ballast tank of lower pressure than
the vacuum
duct. The vessel port, vacuum duct, and vacuum port are attached in
substantially rigid
relation the conveyable housing. Optionally, the portable vessel holder weighs
less than
fivp pound
II.B. Vessel Holder Including Sealing Arrangement.
[203] Still another aspect of the invention according to its embodiments is a
vessel
holder for receiving an open end of a vessel having a substantially
cylindrical wall
adjacent to its open end. The vessel holder can have a generally cylindrical
inner surface
(for example a round cylindrical inner surface), an annular groove, and an 0-
ring. It will
be understood throughout this specification that vessels specified as having
round or
circular openings or cross-sections are merely exemplary, and do not limit the
scope of
the disclosure or claims. If the vessel has a non-round opening or cross-
section, which
for example is common where the vessel is a cuvette, the "round" cylindrical
surface of
the vessel holder can be non-round, and can be sealed using a non-round
sealing
element, such as a gasket or a seal shaped to seal to the non-round cross-
section,
except as
Date Recue/Date Received 2020-08-17
otherwise specifically required. Additionally, "cylindrical" does not require
a round-
section cylinder, and encompasses other cross-sectional shapes, for example
square
with rounded corners.
[204] The generally cylindrical inner surface is sized for receiving the
vessel cylindrical
wall.
[205] The annular groove is disposed in and coaxial with the generally
cylindrical inner
surface. The first annular groove has an opening at the generally cylindrical
inner surface
and a bottom wall radially spaced from the generally cylindrical inner
surface.
[206] The 0-ring is disposed in the first annular groove. The 0-ring is sized,
in relation
to the first annular groove, to normally extend radially through the opening
and to be
pressed radially outward by a vessel received by the generally cylindrical
inner surface.
This arrangement forms a seal between the vessel and the first annular groove.
[207] According to another aspect of the embodiments of the present invention,
a
method for coating and inspection of a vessel is provided, in which a first
inspection of
an interior surface of the vessel for defects is performed after which a
coating to the
interior surface of the vessel is applied. Then, a second inspection of the
interior surface
of the coated vessel for defects is performed. followed by an evaluation of
the data
acquired during the first and second inspection, wherein the second inspection
and the
data evaluation takes less than 30 seconds.
[208] According to another aspect of the embodiments of the invention a method
for
processing a vessel is provided, in which an opening of the vessel is seated
on a vessel
port of a vessel holder, after which an interior surface of the vessel is
coated via the
vessel port. Then, the coating is inspected for defects via the vessel port.
After that, the
vessel is transported from the first processing station to a second processing
station,
wherein the seated vessel is held during coating, inspection and transport by
the vessel
holder.
31
Date Recue/Date Received 2020-08-17
METHODS FOR TRANSPORTING VESSELS ¨ PROCESSING VESSELS
SEATED ON VESSEL HOLDERS
Transporting Vessel Holders To Processing Stations
[209] Another aspect of the invention according to its embodiments is a method
for
processing a vessel. A first processing station and a second processing
station spaced
from the first processing station are provided for processing vessels_ A
vessel is provided
having an opening and a wall defining an interior surface. A vessel holder is
provided
comprising a vessel port. The opening of the vessel is seated on the vessel
port. The
interior surface of the seated vessel is processed via the vessel port at the
first
processing station. The vessel holder and seated vessel are transported from
the first
processing station to the second processing station. The interior surface of
the seated
vessel is then processed via the vessel port at the second processing station.
Transporting Processing Devices To Vessel Holders or vice versa.
[210] Another aspect of the invention according to its embodiments is a method
for
processing a vessel including several parts. A first processing device and a
second
processing device are provided for processing vessels. A vessel is provided
having an
opening and a wall defining an interior surface. A vessel holder is provided
comprising a
vessel port. The opening of the vessel is seated on the vessel port.
[211] The firet proceseing device is moved into operative engagement with the
veeeel
holder, or vice versa. The interior surface of the seated vessel is processed
via the vessel
port using the first processing device.
[212] The second processing device is then moved into operative engagement
with the
vessel holder, or vice versa. The interior surface of the seated vessel via
the vessel port
using the second processing device.
32
Date Recue/Date Received 2020-08-17
I II. C. Using Gripper For Transporting Tube To and From Processing Station
[213] Yet another aspect of the invention according to its embodiments is a
method of
plasma-enhanced chemical vapor deposition (PECVD) treatment of a first vessel,
including several steps. A first vessel is provided having an open end, a
closed end, and
an interior surface. At least a first gripper is configured for selectively
holding and
releasing the closed end of the first vessel. The closed end of the first
vessel is gripped
with the first gripper and, using the first gripper, transported to the
vicinity of a vessel
holder configured for seating to the open end of the first vessel. The first
gripper is then
used to axially advance the first vessel and seat its open end on the vessel
holder,
establishing sealed communication between the vessel holder and the interior
of the first
vessel.
[214] At least one gaseous reactant is introduced within the first vessel
through the
vessel holder. Plasma is formed within the first vessel under conditions
effective to form
a reaction product of the reactant on the interior surface of the first
vessel.
[215] The first vessel is then unseated from the vessel holder and, using the
first gripper
or, another gripper, the first vessel is axially transported away from the
vessel holder. The
first vessel is then released from the gripper used to axially transport it
away from the
vessel holder.
IV. PECVD APPARATUS FOR MAKING VESSELS
!V.A. PECVD Apparatus Including Vessel Holder, Internal Electrode, Vessel
As Reaction Chamber
(21] According to another aspect of the embodiments of the invention a Plasma
Enhanced Chemical Vapour Deposition (PECVD) apparatus for coating an interior
surface of a vessel is provided. The PECVD apparatus may be part of the vessel
processing system and comprises a vessel holder, such as the holder described
above
and below, which comprises a vessel port configured to receive and seat a
first opening
of the vessel for processing the interior surface of the seated vessel via the
vessel port.
Furthermore, the PECVD apparatus comprises an inner electrode for being
arranged
within an interior space of the seated vessel and an outer electrode having an
interior portion for
33
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receiving the seated vessel. Furthermore, a power supply is provided to create
a
plasma within the vessel, wherein the seated vessel and the vessel holder are
adapted
for defining a plasma reaction chamber.
[217] According to another exemplary embodiment of the present invention,
the
PECVD apparatus further comprises a source of vacuum for evacuating the
interior
space of the seated vessel, wherein the vessel port and the seated vessel are
adapted
for defining a vacuum chamber.
[218] According to another exemplary embodiment of the present invention,
the
PECVD apparatus further comprises a gas feed for feeding a reactant gas from a
reactant gas source into the interior space of the vessel.
[219] According to another exemplary embodiment of the present invention,
the gas
feed is positioned at a distal portion of the inner electrode.
[220] According to another exemplary embodiment of the present invention,
the
inner electrode is a probe having a distal portion positioned to extend
concentrically into
the seated vessel.
[221] According to another exemplary embodiment of the present invention,
the
outer electrode has a cylindrical section and extends concentrically about the
seated
vessel.
[222] According to another exemplary embodiment of the present invention,
the
PECVD apparatus further comprises a gripper for selectively holding and
releasing a
closed end of the vessel and, while gripping the close end of the vessel, for
transporting
the vessel to a vicinity of the vessel holder.
[223] According to another exemplary embodiment of the present invention,
the
PECVD apparatus is adapted for forming a plasma in the interior space of the
vessel
that is substantially free of hollow cathode plasma.
[224] According to another exemplary embodiment of the present invention,
the
PECVD apparatus further comprises a detector for interrogating the interior
space of the
vessel via the vessel port for inspection of the interior surface of the
vessel for defects.
34
[225] According to another exemplary embodiment of the present invention, the
PECVD
apparatus further comprises a processing vessel having a processing vessel
opening for
connection with a second, restricted opening of the vessel to allow a reactant
gas to flow
from the interior space of the vessel into the processing vessel.
[226] According to another exemplary embodiment of the present invention, a
distal end
of the inner electrode is positioned less than half the distance to the
second, restricted
opening from the first, larger opening of the seated vessel.
[227] According to another exemplary embodiment of the present invention, the
distal
end of the inner electrode is positioned outside the first, larger opening of
the seated
vessel.
[228] Furthermore, a
method for coating an interior surface of a vessel is provided,
in which an opening of the vessel is received and seated on a vessel port of a
vessel
holder for processing the interior surface of the seated vessel. Then, an
inner electrode
is arranged within an interior space of the seated vessel after which a gas
feed is
positioned at the distal portion of the inner electrode. Furthermore, the
seated vessel is
received in an interior portion of an outer electrode. The seated vessel in
the vessel
holder is adapted for defining a plasma reaction chamber.
[229] In particular, a vacuum chamber may be defined by the vessel port and
the seated
vessel and gas is drawn from the interior space of the seated vessel, such
that no
external vacuum chamber is necessary for coating.
[230] In a further step a plasma is formed in the interior space of the vessel
and a coating
material is deposited on the interior surface of the seated vessel.
[231] According to another exemplary embodiment of the present invention, a
processing
vessel opening is connected with a restricted opening of the vessel to allow a
reactant
gas to flow from the interior space of the vessel into the processing vessel.
[232] According to another aspect of the embodiments of the invention the use
of an
above and below described PECVD apparatus for fabricating a blood tube for
storing
blood, a syringe for storing a biologically active compound or composition, a
vial for
storing a biologically active compound or composition, a catheter for
transporting
biologically active
Date Recue/Date Received 2020-08-17
compounds or compositions or a cuvette for holding a biologically active
compound or
composition.
[233] Another aspect of the invention according to its embodiments is a PECVD
apparatus comprising including a vessel holder, an inner electrode, an outer
electrode,
and a power supply.
[234] The vessel holder has a port to receive a vessel in a seated position
for processing.
The inner electrode is positioned to be received within a vessel seated on a
vessel
holder. The outer electrode has an interior portion positioned to receive a
vessel seated
on the vessel holder. The power supply feeds alternating current to the inner
and outer
electrodes to form plasma within a vessel seated on the vessel holder. The
vessel
defines a plasma reaction chamber.
[235] Even another aspect of the invention according to its embodiments is a
PECVD
apparatus as described in the preceding paragraphs, in which a gas drain, not
necessarily including a source of vacuum, is provided to transfer gas to or
from the
interior of a vessel seated on the port to define a closed chamber.
IV.B. PECVD Apparatus Using Gripper For Transporting Tube To and From
Coating Ctation
[236] Another aspect of the invention according to its embodiments is an
apparatus for
PECVD treatment of a first vessel having an open end, a closed end, and an
interior
spacp_ Thp apparatus inelndps a vp_s_spl holdpr, a first gripppr, a _spat on
thp vp_s_spl
holder, a reactant supply, a plasma generator, and a vessel release.
[237] The vessel holder is configured for seating to the open end of a vessel.
The first
gripper is configured for selectively holding and releasing the closed end of
a vessel and,
while gripping the closed end of the vessel, transporting the vessel to the
vicinity of the
vessel holder. The vessel holder has a seat configured for establishing sealed
communication between the vessel holder and the interior space of the first
vessel.
[238] The reactant supply is operatively connected for introducing at least
one gaseous
reactant within the first vessel through the vessel holder. The plasma
generator is
configured for forming plasma within the first vessel under conditions
36
Date Recue/Date Received 2020-08-17
effective to form a reaction product of the reactant on the interior surface
of the first
vessel.
[239] The vessel release is provided for unseating the first vessel from the
vessel holder.
A gripper which is the first gripper or another gripper is configured for
axially transporting
the first vessel away from the vessel holder and then releasing the first
vessel.
V. PECVD METHODS
[240] According to another aspect of the embodiments of the present invention
a method
for coating (and/or inspecting) an interior surface of a vessel is provided,
in which an
opening of the vessel is received and seated on a vessel holder for processing
the interior
surface of the seated vessel. It should be noted that the term processing may
refer to a
coating step or several coating steps or even to a series of coating and
inspection steps.
[241] Furthermore, a first processing of the interior surface of the seated
vessel is
performed via a vessel port of the vessel holder at a first processing
station. Then, the
vessel holder and the seated vessel are transported to a second processing
station after
the first processing at the first processing station. Then, at the second
processing station,
a erind pr ring of the interior i_ii-face of the pated I/PcgPi i performed
via the
vessel port of the vessel holder.
V.A. PECVD to apply SiOx barrier coating, using plasma that is
substantially
free of hollow cathode plasma
[242] Another aspect of the invention according to its embodiments is a method
of
applying a barrier coating of SiOx, in which x in this formula is from about
1.5 to about
2.9, alternatively frorn about
1.5 to about 2.6, alternatively about 2, on a surface, illustratively on the
interior of a
vessel. The method includes several steps.
[243] A surface, e_g_ a vessel wall is provided, as is a reaction mixture
comprising plasma
forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas,
and
optionally a hydrocarbon gas.
37
Date Recue/Date Received 2020-08-17
[244] Plasma is formed in the reaction mixture that is substantially free of
hollow cathode
plasma The vessel wall is contacted with the reaction mixture, and the coating
of SiOx
is deposited on at least a portion of the vessel wall.
V.B. PECVD Coating Restricted Opening of Vessel (Syringe Capillary)
[245] Another aspect of the invention according to its embodiments is a method
for
coating an inner surface of a restricted opening of a generally tubular vessel
to be
processed by PECVD. The method includes these steps.
[246] A generally tubular vessel is provided to be processed. The vessel
includes an
outer surface, an inner surface defining a lumen, a larger opening having an
inner
diameter, and a restricted opening that is defined by an inner surface and has
an inner
diameter smaller than the larger opening inner diameter.
[247] A processing vessel is provided having a lumen and a processing vessel
opening.
The processing vessel opening is connected with tne restricted opening of tne
vessel to
establish communication between the lumen of the vessel to be processed and
the
processing vessel lumen via the restricted opening.
[94.R] At IPASt a partial vaniiiim isrlrawn within thp Iiimpn nf thp vpsspl tn
hp prnnpsspri
and the processing vessel lumen. A PECVD reactant is flowed through the first
opening,
then through the lumen of the vessel to be processed, then through the
restricted
opening, then into the processing vessel lumen. Plasma is generated adjacent
to the
restricted opening under conditions enective to deposit a coating ot a 1-'LUVU
reaction
product on the inner surface of the restricted opening.
V.C. Method of Applying a Lubricity Coating
[249] Still another aspect of the invention according to its embodiments is a
method
of applying a lubricity coating on a substrate. The method is carried out as
follows.
[250] A precursor is provided. The precursor illustratively is an
organosilicon compound,
more illustratively a linear siloxane, a monocyclic siloxane, a polycyclic
siloxane, a
polysilsesquioxane, or a combination of any two or more of these
38
Date Recue/Date Received 2020-08-17
precursors. Other precursors, e.g., organometallic precursors containing
metals of
Group III and IV of the periodic system, are also contemplated. The precursor
is applied
to a substrate under conditions effective to form a coating. The coating is
polymerized or
crosslinked, or both, to form a lubricated surface having a lower "plunger
sliding force"
or "breakout force," as defined in this specification, than the untreated
substrate.
VI. VESSEL INSPECTION
VI.A. Vessel Processing Including Pre-Coating and Post-Coating Inspection
[251] Even another aspect of the invention according to its embodiments is a
vessel
processing method for processing a plastic vessel having an opening and a wall
defining
an interior surface. The method is carried out by inspecting the interior
surface of the
vessel as provided for defects; applying a coating to the interior surface of
the vessel
after inspecting the vessel as provided; and inspecting the coating for
defects.
[252] Another aspect of the invention according to its embodiments is a vessel
processing method in which a barrier coating is applied to the vessel after
inspecting the
vessel as molded, and the interior surface of the vessel is inspected for
defects after
applying the barrier coating.
VI.B. Vessel Inspection By Detecting Outgassing Of Container Wall, e.g.
Through
Barrier Layer
[253] Another aspect of the invention according to its embodiments is a method
for
inspecting a coating by measuring a volatile species outgassed by the coated
article
("Outgassing method"). Said method can be used for inspecting the product of a
coating
process wherein a coating has been applied to the surface of a substrate to
form a coated
surface. In particular, the method can be used as an inline process control
for a coating
process in order to identify and eliminate coated products not meeting a
predetermined
standard or damaged coating products_
[254] Generally, the "volatile species" is a gas or vapor at test
conditions, illustratively
is selected from the group consisting of air, nitrogen, oxygen, water vapor,
volatile
coating components, volatile substrate components, and a combination thereof,
more
39
Date Recue/Date Received 2020-08-17
illustratively is air, nitrogen, oxygen, water vapor, or a combination
thereof. The method
may be used to measure just one or a few volatile species, bur illustratively
a plurality of
different volatile species is measured in step (c), and more illustratively
substantially all
the volatile species released from the inspection object are measured in step
(c).
[255] The outgassing method comprises the steps:
(a) providing the product as inspection object;
(c) measuring the release of at least one volatile species from the inspection
object into
the gas space adjacent to the coated surface; and
(d) comparing the result of step (c) with the result of step (c) for at least
one reference
object measured under the same test conditions, thus determining the presence
or
absence of the coating, and/or a physical and/or chemical property of the
coating.
[256] In said outgassing method, the physical and/or chemical property of the
coating to
be determined may be selected from the group consisting of its barrier effect,
its wetting
tension, and its composition, and illustratively is its barrier effect.
[257] Step (c) is performed by measuring the mass flow rate or volume flow
rate of the
at least one volatile species in the gas space adjacent to the coated surface.
[258] Illustratively, the reference object (i) is an uncoated substrate: or
(ii) is a substrate
coated with a reference coating. This depends on, e.g., whether the outgassing
method
is used to determine the presence or absence of a coating (then the reference
object
may be an uncoated substrate) or to determine the properties of the coating,
e.g. in
compalison to a coaling with known properties. For determining tile coating's
identity
with a specific coating, a reference coating will also be a typical choice.
[259] The outgassing method may also comprise as an additional step between
steps
(a) and (c) the step of (b) changing the atmospheric pressure in the gas space
adjacent
to the coated surface such that a pressure differential through the coated
surface is
provided and a higher mass flow rate or volume flow rate of the volatile
species may be
realized than without the pressure differential. In this case, the volatile
species will
migrate into the direction of the lower side of the pressure differential. If
the
Date Recue/Date Received 2020-08-17
coated object is a vessel, the pressure differential is established between
the vessel
lumen and the exterior in order to measure the outgassing of the volatile
species from
the coated vessel wall. The pressure differential may e.g. be provided by at
least partially
evacuating the gas space in the vessel. In this case, the volatile species may
be
measured which is outgassed into the lumen of the vessel.
[260] If a vacuum is applied to create a pressure differential, the
measurement may
be performed by using a measurement cell interposed between the coated surface
of
the substrate and a source of vacuum.
[261] In one aspect, the inspection object may be contacted with a volatile
species
in step (a), illustratively a volatile species selected from the group
consisting of air,
nitrogen, oxygen, water vapor, and a combination thereof, illustratively in
order to allow
the adsorption or absorption of said volatile species onto or into the
material of the
inspection object. Then, the subsequent release of said volatile species from
the
inspection object is measured in step (c). As different materials (like, e.g.,
the coating
and the substrate) have different adsorption and absorption characteristics,
this can
simplify the determination of the presence and characteristics of a coating.
[262] The substrate may be a polymeric compound, illustratively is a
polyester, a
polyolefin, a cyclic olefin copolymer, a polycarbonate, or a combination of
these.
[263] In the context of present invention according to its embodiments, the
coating
characterized by the outgassing method is typically a coating prepared by
PECVD from,
aii oiyanosilicon piecuisoi s deutibed helein. lii paaioulat embodiments of
the
invention (i) the coating is a barrier coating, illustratively is a SiOx layer
wherein x is from
about 1.5 to about 2.9; and/or (ii) the coating is a coating modifying the
lubricity and/or
surface tension of the coated substrate, illustratively is a layer Of
SiwOxCyHz, where w is
1, x is from about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2
to about 9.
[264] When the coating process whose product is inspected by the outgassing
method
is a PECVD coating performed under vacuum conditions, the subsequent
outgassing
measurement may even be conducted without breaking the vacuum used for PECVD.
41
Date Recue/Date Received 2020-08-17
[265] The volatile species measured may be a volatile species released from
the coating,
a volatile species release form the substrate, or a combination of both. In
one aspect,
the volatile species is a volatile species released from the coating,
illustratively is a
volatile coating component, and the inspection is performed to determine the
presence,
the properties and/or the composition of the coating. In another aspect, the
volatile
species is a volatile species released from the substrate and the inspection
is performed
to determine the presence of the coating and/or the barrier effect of the
coating.
[266] The outgassing method of the present invention according to its
embodiments is
particularly suitable to determine the presence and characteristics of a
coating on a
vessel wall. Thus, the coated substrate may be a vessel having a wall which is
at least
partially coated on its inner or outer surface during the coating process. For
example,
the coating is disposed on the inner surface of the vessel wall.
[267] The conditions effective to distinguish the presence or absence of the
coating,
and/or to determine a physical and/or chemical property of the coating may
include a test
duration of less than one hour, or less than one minute, or less than 50
seconds, or less
than 40 seconds, or less than 30 seconds, or less than 20 seconds, or less
than 15
seconds, or less than 10 seconds, or less than 8 seconds, or less than 6
seconds, or
less tnan 4 seconas, or less tnan 3 seconas, or less tnan 2 seconas, or less
tnan 1
second.
[268] In order to increase the difference between the reference object and the
inspection
object with regard to the release rate and/or kind of the measured volatile
species, the
release rate of the volatile species may be modified by modifying the ambient
pressure
and/or temperature, and/or humidity.
[269] In a specific aspect, the outgassing is measured using a microcantilever
measurement technique. E.g., the measuring may be carried out by
(i) (a) providing at least one microcantilever which has the property, when
in the
presence of an outgassed material, of moving or changing to a different shape;
(b) exposing the microcanti lever to the outgassed material under conditions
effective to cause the microcantilever to move or change to a different shape;
42
Date Recue/Date Received 2020-08-17
and
(c) detecting the movement or different shape, illustratively by reflecting an
energetic incident beam, e.g. a laser beam, from a portion of the
microcantilever
that changes shape, before and after exposing the microcantilever to
outgassing,
and measuring the resulting deflection of the reflected beam at a point spaced
from the cantilever; or by
(ii) (a) providing at least one microcantilever which resonates at a
different
frequency when in the presence of an outgassed material;
(b) exposing the microcantilever to the outgassed material under conditions
effective to cause the microcantilever to resonate at a different frequency;
and
(c) detecting the different resonant frequency, e.g. using a harmonic
vibration
sensor.
[270] An apparatus for performing the outgassing method is also considered,
for
example an apparatus comprising a microcantilever as described above.
[271] Using the outgassing method of the present invention according to its
embodiments, for example a barrier layer on a material that outgasses a vapor
can be
inspected, wherein the inspection method has several steps. A sample of
material that
outgasses a gas and has at least a partial barrier layer is provided. In a
specific aspect
of the invention according to its embodiments, a pressure differential is
provided across
the barrier layer, such that at least some of the material that outgasses is
on the higher-
pressure side of the barrier layer. The outgassed gas passing through the
barrier layer
is measured. If a pressure differential is present, the measurement optionally
is
performed on the lower-pressure side of the barrier layer.
VII. PECVD TREATED VESSELS
VII.A.1.a.i. Hydrophobic Coating Deposited from an Organosilicon Precursor
[272] Another aspect of the invention according to its embodiments is a
hydrophobic
coating deposited from an organosilicon precursor, e.g. in a vessel having a
hydrophobic
coating on the inside wall. The coating is of the type made by the following
steps.
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Date Recue/Date Received 2020-08-17
[273] A precursor is provided, which is an organometallic compound,
illustratively an
organosilicon compound, more illustratively a compound selected from the group
consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane,
a
polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic
silazane,
a polycyclic silazane, a polysilsesquiazane, or a combination of any two or
more of these
precursors. Alternatively, organometallic compounds containing a metal of
Group III or
IV may be considered as precursors.
[274] The precursor is applied to a substrate under conditions effective to
form a coating.
The coating is polymerized or crosslinked, or both, to form a hydrophobic
surface having
a higher contact angle than the untreated substrate.
[275] The resulting coating may have the sum formula: SiwOxCyHz, where w is
1, x is
from about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from
about 2 to about
9, illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and z
is from 6 to about 9.
[276] The values of w, x, y, and z used throughout this specification should
be
understood as ratios in an empirical formula (e.g. for a coating), rather than
as a limit on
the number of atoms in a molecule. For example, octamethylcyclotetrasiloxane,
which
has the molecular formula Si404C81-124, may be described by the following
[Wording
changed by us.] empirical formula, arrived at by dividing each of w, x, y, and
z in the
molecular formula by 4, the largest common factor: Si101C2H6. The values of w,
x, y, and
z are also not limited to integers. For example, (acyclic)
octamethyltrisiloxane, molecular
formula Si302C81-124, is reducible to Si100.67C2.67H8.
VII.A.1.b. Citrate Blood Tube Having Wall Coated With Hydrophobic Coating
Deposited from an Organosilicon Precursor
[277] Another aspect of the invention according to its embodiments is a cell
preparation
tube having a wall provided with a hydrophobic coating and containing an
aqueous
sodium citrate reagent.
[278] The wall is made of thermoplastic material having an internal surface
defining
a lumen.
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Date Recue/Date Received 2020-08-17
[279] The hydrophobic coating is provided on the internal surface of the tube.
The
hydrophobic coating is made by providing an organometallic compound,
illustratively an
organosilicon compound, more illustratively a compound selected from the group
consisting of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane,
a
polysilsesquioxane, an alkyl trimethoxysilane, a linear silazane, a monocyclic
silazane,
a polycyclic silazane, a polysilsesquiazane, or a combination of any two or
more of these
precursors. PECVD is used to form a coating on the internal surface. The
resulting
coating may have the structure: SiwOxCyHz, where w is 1, x is from about 0.5
to about
2.4, y is from about 0.6 to about 3, and z is from about 2 to about 9,
illustratively where
w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from
6 to about 9.
[280] The aqueous sodium citrate reagent is disposed in the lumen of the tube
in an
amount effective to inhibit coagulation of blood introduced into the tube.
VII.A.1.c. SiOx Barrier Coated Double Wall Plastic Vessel - COC, PET, SiOx
layers
[281] Another aspect of the invention according to its embodiments is a vessel
having a
wall at least partially enclosing a lumen. The wall has an interior polymer
layer enclosed
by an exterior polymer layer. One of the polymer layers is a layer at least
0.1 mm thick
of a cyclic olefin copolymer (COC) resin defining a water vapor barrier.
Another of the
polymer layers is a layer at least 0.1 mm thick of a polyester resin.
[282] The wall includes an oxygen barrier layer of SiOx, in which x in this
formula is from
about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6,
alternatively about 2,
having a thickness of from about 10 to about 500 angstroms.
VII.A.1.d. Method of Making Double Wall Plastic Vessel - COC, PET, SiO.
layers
[283] Another aspect of the invention according to its embodiments is a method
of
making a vessel having a wall having an interior polymer layer enclosed by an
exterior
polymer layer, one layer made of COC and the other made of polyester. The
vessel is
made by a process including
Date Recue/Date Received 2020-08-17
introducing COC and polyester resin layers into an injection mold through
concentric
injection nozzles.
[284] An optional additional step is applying an amorphous carbon coating to
the vessel
by PECVD, as an inside coating, and outside coating, or as an interlayer
coating located
between the layers.
[285] An optional additional step is applying an SiOx barrier layer to the
inside of the
vessel wall, where SiOx is defined as before. Another optional additional step
is post-
treating the SiOx layer with a process gas consisting essentially of oxygen
and essentially
free of a volatile silicon compound.
[286] Optionally, the SiOx coating can be formed at least partially from a
silazane feed
gas.
VII.A.1.e. Barrier Coating Made Of Glass
[287] Another aspect of the invention according to its embodiments is a vessel
including
a vessel, a barrier coating, and a closure. The vessel is generally tubular
and made of
thermoplastic material. The vessel has a mouth and a lumen bounded at least in
part by
a wall having an inner surface interfacing with the lumen. There is an at
least essentially
continuous barrier coating made of glass on the inner surface of the wall. A
closure
covers the mouth and isolates the lumen of the vessel from ambient air.
[288] A related aspect of the invention according to its embodiments is a
vessel as
described in the previous paragraph, in which the barrier coating is made of
soda lime
glass or borosilicate glass, or another type of glass.
VII.A.2. Stoppers
VII.A.2.a. Method of Applying Lubricity Coating to a Stopper In Vacuum
Chamber
[289] Another aspect of the invention according to its embodiments is a
method of
applying a coating, for example a lubricity coating as defined above, on an
elastomeric
stopper. For example, a stopper
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Date Recue/Date Received 2020-08-17
is located in a substantially evacuated chamber. A reaction mixture is
provided including
plasma forming gas, i.e. an organosilicon compound gas, optionally an
oxidizing gas,
and optionally a hydrocarbon gas. Plasma is formed in the reaction mixture,
which is
contacted with the stopper. A lubricity coating, e.g. a coating of SiwOxCyHz,
illustratively
where vv is 1, x in this formula is from about 0.5 to 2.4, y is from about 0.6
to about 3,
and z is from 2 to about 9, illustratively where w is 1, x is from about 0.5
to 1, y is from
about 2 to about 3, and z is from 6 to about 9, is deposited on at least a
portion of the
stopper.
VII.A.2.b. Applying by PECVD a Coating of Group III or IV Element and
Carbon
on a Stopper
[290] Another aspect of the invention according to its embodiments is a method
of
applying a coating of a composition including carbon and one or more elements
of
Groups III or IV on an elastomeric stopper. To carry out the method, a stopper
is located
in a deposition chamber.
[291] A reaction mixture is provided in the deposition chamber, including a
plasma
forming gas with a gaseous source of a Group III element (e.g. Al), a Group IV
element
(e.g. Si, Sn), or a combination of two or more of these. The reaction mixture
optionally
contains an oxidizing gas and optionally contains a gaseous compound having
one or
more C-H bonds. Plasma is formed in the reaction mixture, and the stopper is
contacted
with the reaction mixture. A coating of a Group III element or compound, a
Group IV
element or compound, or a combination of two or more of these is deposited on
at least
a portion of the stopper.
VII.A.3. Stoppered Plastic Vessel Having Barrier Coating Effective To
Provide 95% Vacuum Retention for 24 Months
[292] Another aspect of the invention according to its embodiments is a vessel
including
a vessel, a barrier coating, and a closure. The vessel is generally tubular
and made of
thermoplastic material. The vessel has a mouth and a lumen bounded at least in
part by
a wall. The wall has an inner surface interfacing with the lumen. An at least
essentially
continuous barrier coating is applied on the inner surface of the wall. The
barrier coating
is
47
Date Recue/Date Received 2020-08-17
effective to maintain within the vessel at least 90% of its initial vacuum
level, optionally
95% of its initial vacuum level, for a shelf life of at least 24 months. A
closure is provided
covering the mouth of the vessel and isolating the lumen of the vessel from
ambient air.
VII.B.1.a. Syringe Having Barrel Coated With Lubricity Coating Deposited
from an Organometallic Precursor
Still another aspect of the invention according to its embodiments is a vessel
having a
lubricity coating made from an organosilicon precursor. A different
organometallic
precursor as defined herein may also be contemplated.
[293] The coating can be of the type made by the following process.
[294] A precursor is provided which is an organometallic precursor,
illustratively an
organosilicon precursor, more illustratively a linear siloxane, a monocyclic
siloxane, a
polycyclic siloxane, a polysilsesquioxane, a linear silazane, a monocyclic
silazane, a
polycyclic silazane, a polysilsesquiazane, or a combination of any two or more
of these
precursors.
[295] The precursor is applied to a substrate under conditions effective to
form a coating.
The coating is polymerized or crosslinked, or both, to form a lubricated
surface having a
lower plunger sliding force or breakout force than the untreated substrate.
[296] Another aspect of the invention according to its embodiments is a
syringe including
a plunger, a syringe barrel, and a lubricity layer. The syringe barrel has an
interior surface
slidably receiving the plunger_ The lubricity layer is disposed nn the
interior curfaceof
the syringe barrel and includes a coating of an SiwOxCyHz lubricity layer made
from an
organosilicon precursor as defined in this specification. The lubricity layer
is less than
1000 nm thick and effective to reduce the breakout force or the plunger
sliding force
necessary to move the plunger within the barrel.
[297] Another aspect of the invention according to its embodiments is a
lubricity coating
on the inner wall of a syringe barrel. The coating is produced from a PECVD
process
using the following materials and conditions_ A cyclic precursor is employed,
selected
from a monocyclic siloxane, a polycyclic siloxane, or a combination of two or
more of
these. At least
48
Date Recue/Date Received 2020-08-17
essentially no oxygen is added to the process. A sufficient plasma generation
power
input is provided to induce coating formation. The materials and conditions
employed are
effective to reduce the syringe plunger sliding force or breakout force moving
through
the syringe barrel by at least 25 percent relative to an uncoated syringe
barrel.
[298] The resulting coating may have the formula: SiwOxCyHz, where w is 1, x
is from
about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2
to about 9,
illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and z is
from 6 to about 9.
VII.B.1.a.i. Lubricity Coating: SiOx Barrier, Lubricity Layer, Surface
treatment.
[299] Another aspect of the invention according to its embodiments is a
syringe
comprising a barrel defining a lumen and having an interior surface slidably
receiving a
plunger. The syringe barrel may be made of thermoplastic base material. A
lubricity
coating is applied to, e.g., the barrel interior surface, the plunger, or both
by PECVD. The
lubricity coating may be made from an organosilicon precursor, and may be less
than
1000 nm thick. A surface treatment is carried out on the lubricity coating in
an amount
effective to reduce leaching of the lubricity coating, the thermoplastic base
material, or
both into the lumen, i.e. effective to form a solute retainer on the surface.
The lubricity
coating and solute retainer are composed, and present in relative amounts,
effective to
provide a breakout force, plunger sliding force, or both that is less than the
corresponding
force required in the absence of the lubricity coating and solute retainer.
VII.B.1.b Syringe Having
Barrel With SiOx Coated Interior and Barrier Coated
Exterior
[300] Still another aspect of the invention according to its embodiments is a
syringe
barrel including a plunger, a barrel, and interior and exterior barrier
coatings. The barrel
is made of thermoplastic base material defining a lumen. The barrel has an
interior
surface slidably receiving the plunger and an exterior surface. A barrier
coating of SiOx,
in which x in this formula is from about 1.5 to about 2.9, alternatively from
about 1.5 to
about 2.6, alternatively about 2, is provided on the interior surface of the
barrel. A barrier
coating of a resin is provided on the exterior surface of the barrel.
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Date Recue/Date Received 2020-08-17
VII.B.1.c Method of Making Syringe Having Barrel With SiOx Coated Interior
and Barrier Coated Exterior
[301] Even another aspect of the invention according to its embodiments is a
method
of making a syringe including a plunger, a barrel, and interior and exterior
barrier
coatings. A barrel is provided having an interior surface for slidably
receiving the plunger
and an exterior surface. A barrier coating of SiOx, in which x in this formula
is from about
1.5 to about 2.9, alternatively from about 1.5 to about 2.6, alternatively
about 2, is
provided on the interior surface of the barrel by PECVD. A barrier coating of
a resin is
provided on the exterior surface of the barrel. The plunger and barrel are
assembled to
provide a syringe.
VII.B.2. Plungers
VII.B.2.a. With Barrier Coated Piston Front Face
[302] Another aspect of the invention according to its embodiments is a
plunger for a
syringe, including a piston and a push rod. The piston has a front face, a
generally
cylindrical side face, and a back portion, the side face being configured to
movably seat
within a syringe barrel. The front face has a barrier coating. The push rod
engages the
back portion and is configured for advancing the piston in a syringe barrel.
VII.B.2.b. With Lubricity Coating Interfacing With Side Face
[303] Yet another aspect of the invention according to its embodiments is a
plunger for
a syringe, including a piston, a lubricity coating, and a push rod. The piston
has a front
face, a generally cylindrical side face, and a back portion. The side face is
configured to
movably seat within a syringe barrel. The lubricity coating interfaces with
the side face.
The push rod engages the back portion of the piston and is configured for
advancing the
piston in a syringe barrel.
Date Recue/Date Received 2020-08-17
VII.B.3. Two Piece Syringe and Luer Fitting
[304] Another aspect of the invention according to its embodiments is a
syringe including
a plunger, a syringe barrel, and a Luer fitting. The syringe barrel includes
an interior
surface slidably receiving the plunger. The Luer fitting includes a Luer taper
having an
internal passage defined by an internal surface. The Luer fitting is formed as
a separate
piece from the syringe barrel and joined to the syringe barrel by a coupling.
The internal
passage of the Luer taper has a barrier coating of SiO., in which x in this
formula is from
about 1.5 to about 2.9, alternatively from about 1.5 to about 2.6,
alternatively about 2.
VII.B.4. Lubricity Coating Made By In Situ Polymerizing Organosilicon
Precursor
VII.B.4.a. Product by Process and Lubricity
pos] Still another aspect of the invention according to its embodiments is a
lubricity
coating made from an organosilicon precursor. This coating is of the type made
by the
following process.
[306] A precursor is provided selected from an organometallic precursor,
illustratively
an organosilicon precursor, illustratively a linear siloxane, a monocyclic
siloxane, a
polycyclic siloxane, a polysilsesquioxane, a linear silazane, a monocyclic
silazane, a
polycyclic silazane, a polysilsesquiazane, or a combination of any two or more
of these
precursors. The precursor is applied to a substrate under conditions effective
to form a
coating. The coating is polymerized or crosslinked, or both, to form a
lubricated surface
having a lower plunger sliding force or breakout force than the untreated
substrate.
[307] The resulting coating may have the structure: SiwOxCyHz, where w is 1, x
is from
about 0.5 to about 2.4, y is from about 0.6 to about 3, and z is from about 2
to about 9,
illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and z is
from 6 to about 9.
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Date Recue/Date Received 2020-08-17
VII.B.4.b. Product by Process and Analytical Properties
[308] Even another aspect of the invention according to its embodiments is
a
lubricity coating deposited by PECVD from an organometallic precursor,
illustratively
from an organosilicon precursor, more illustratively from a linear siloxane, a
monocyclic
siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear silazane, a
monocyclic
silazane, a polycyclic silazane, a polysilsesquiazane, or a combination of any
two or
more of these precursors. The coating has a density between 1.25 and 1.65
g/cm3 as
determined by X-ray reflectivity (XRR).
[309] The use of an organometallic precursor containing a metal of Group III,
i.e. Boron,
Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, or Lanthanum, or Group
IV,
i.e. Silicon, Germanium, Tin, Lead, Titanium, Zirconium, Hafnium, Thorium, or
combinations of any two or more of these, may also be contemplated. Other
volatile
organic compounds may also be contemplated. However, organosilicon compounds
are
illustrative for perforrning present invention according to its embodiments.
[310] Still another aspect of the invention according to its embodiments is
a
lubricity coating deposited by PECVD from a feed gas comprising an
organometallic
precursor, illustratively an organosilicon precursor, more illustratively a
linear siloxane, a
monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear
silazane, a
monocyclic silazane, a polycyclic silazane, a polysilsesquiazane, or a
combination of any
two or more of these precursors. The use of a precursor containing a metal of
groups III
or IV may also be contemplated.
[311] The coating has as an outgas component one or more oligomers containing
repeating -(Me)25i0- moieties, as determined by gas chromatography / mass
spectrometry. Optionally, the coating meets the limitations of any of
embodiments
VII.B.4.a or VII.B.4.b.
[312] Yet another aspect of the invention according to its embodiments is a
lubricity
coating deposited by PECVD from a feed gas comprising an organometallic
precursor,
illustratively an organosilicon precursor, more illustratively a linear
siloxane, a monocyclic
siloxane, a polycyclic siloxane, a polysilsesquioxane, a linear silazane, a
monocyclic
silazane, a polycyclic
52
Date Recue/Date Received 2020-08-17
silazane, a polysilsesquiazane, or a combination of any two or more of these
precursors.
The coating has atomic concentrations normalized to 100% carbon, oxygen, and
silicon,
as determined by X-ray photoelectron spectroscopy (XPS), of less than 50%
carbon and
more than 25% silicon. Optionally, the coating meets the limitations of any of
embodiments VII.B.4.a or VII.B.4.b.
[313] The use of an organometallic precursor containing a metal of groups ill
or IV may
also be contemplated.
[314] Another aspect of the invention according to its embodiments is a
lubricity coating
deposited by PECVD from a feed gas comprising an organosilicon precursor,
illustratively a monocyclic siloxane, a monocyclic silazane, a polycyclic
siloxane, a
polycyclic silazane, or any combination of two or more of these. The coating
has an
atomic concentration of carbon, normalized to 100% of carbon, oxygen, and
silicon, as
determined by X-ray photoelectron spectroscopy (XPS), greater than the atomic
concentration of carbon in the atomic formula for the feed as Optionally, the
coating
meets the limitations of embodiments VII.B.4.a or VII.B.4.b.
[315] An additional aspect of the invention according to its embodiments is a
lubricity
coating deposited by PECVD from a feed gas comprising an organosilicon
precursor,
illustratively a monocyclic siloxane, a monocyclic silazane, a polycyclic
siloxane, a
polycyclic silazane, or any combination of two or more of these. The coating
has an
atomic concentration of silicon, normalized to 100% of carbon, oxygen, and
silicon, as
determined by X-ray photoelectron spectroscopy (XPS), less than the atomic
concentration of silicon in the atomic formula for the feed gas. Optionally,
the coating
meets the limitations of embodiments VII.B.4.a or VII.B.4.b.
vii.c.i. Vessel Containing Viable Blood, Having a Coating Deposited from
an Organosilicon Precursor
[316] Even another aspect of the invention according to its embodiments is a
blood
containing vessel. The vessel has a wall; the wall has an inner surface
defining a lumen.
The inner surface of the wall has an at least partial hydrophobic coating as
defined
above, illustratively a hydrophobic coating of SiwOxCyHz, illustratively where
w is 1, x in
this formula is from about 0.5 to 2A,
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Date Recue/Date Received 2020-08-17
y is from about 0.6 to about 3, and z is from 2 to about 9, more
illustratively where w is
1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from 6 to
about 9. The
coating can be as thin as monomolecular thickness or as thick as about 1000
nm. The
vessel contains blood viable for return to the vascular system of a patient
disposed within
the lumen in contact with the SiwOxCyHz coating.
VII.C.2. Coating Deposited from an Organosilicon Precursor Reduces
Clotting or Platelet Activation on Vessel Wall
[317] Another aspect of the invention according to its embodiments is a vessel
having
a wall. The wall has an inner surface defining a lumen and has an at least
partial
passivating, e_g_ hydrophobic coating made from an organosilicon precursor by
PECVD,
illustratively a coating of SiwOxCyHz, illustratively where w is 1, x in this
formula is from
about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2 to about 9,
more
illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and z is
from 6 to about 9. The thickness of the coating is from monomolecular
thickness to about
1000 nm thick on the inner surface. The coating is effective to reduce the
platelet
activation of blood plasma treated with a sodium citrate additive and exposed
to the inner
surface, compared to the same type of wall uncoated. The coating is effective
to reduce
the clotting of blood exposed to the inner surface, compared to the same type
of wall
uncoated.
VII.C.3. Vessel Containing Viable Blood. Having a Coating of Group III or
IV
Metal Element
[318] Another aspect of the invention according to its embodiments is a blood
containing
vessel having a wall having an inner surface defining a lumen. The inner
surface has an
at least partial coating of a composition including carbon, one or more metals
of Group
Ill, one or more metals of Group IV, or a combination of two or more of these.
The
thickness of the coating is between monomolecular thickness and about 1000 nm
thick,
inclusive, on the inner surface_ The vessel contains blood viable for return
to the vascular
system of a patient disposed within the lumen in contact with the coating.
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Date Recue/Date Received 2020-08-17
VII.C.4. Coating of Group III or IV Element Reduces Clotting Or Platelet
Activation of Blood in the Vessel
[319] Optionally, in the vessel of the preceding paragraph, the coating of the
Group III
or IV Element is effective to reduce the clotting or platelet activation of
blood exposed to
the inner surface of the vessel wall.
VII.D.1. Vessel Containing Insulin, Having a Coating Deposited from an
Organosilicon Precursor
[320] Another aspect of the invention according to its embodiments is an
insulin
containing vessel including a wall having an inner surface defining a lumen.
The inner
surface has an at least partial passivating coating made from an organosilicon
precursor
by PECVD, illustratively a coating of SiwOxCyHz, illustratively where w is 1,
x in this
formula is from about 0.5 to 2.4, y is from about 0.6 to about 3, and z is
from 2 to about
9, more illustratively where w is 1, x is from about 0.5 to 1, y is from about
2 to about 3,
and z is from 6 to about 9. The coating can be from monomolecular thickness to
about
1000 nm thick on the inner surface. Insulin is disposed within the lumen in
contact with
the SiwOxCyHz coating.
VII.D.2. Coating Deposited from an Organosilicon Precursor Reduces
Precipitation of Insulin in the Vessel
[321] Optionally, in the vessel of the preceding paragraph, the coating of
SiwOxCyHz, is
effective to reauce tne formation or a precipitate from insulin contacting tne
inner surface,
compared to the same surface absent the coating of SiwOxCyHz.
VII.D.3. Vessel Containing Insulin, Having a Coating of Group III or IV
Element
[322] Another aspect of the invention according to its embodiments is an
insulin
containing vessel including a wall having an inner surface defining a lumen.
The inner
surface has an at least partial coating of a composition comprising carbon,
one or more
elements of Group III, one or more elements of Group IV, or a combination of
two or
more of these. The coating can be from monomolecular thickness to about 1000
nm thick
on the inner surface. Insulin is disposed within the lumen in contact with the
coating.
Date Recue/Date Received 2020-08-17
VII.D.4. Coating of Group III or IV Element Reduces Precipitation of
Insulin
in the Vessel
[323] Optionally, in the vessel of the preceding paragraph, the coating of a
composition
comprising carbon, one or more elements of Group III, one or more elements of
Group
IV, or a combination of two or more of these, is effective to reduce the
formation of a
precipitate from insulin contacting the inner surface, compared to the same
surface
absent the coating.
VII.E. Cuvettes
[324] The PECVD coating methods, etc., described in this specification are
also useful
for coating cuvettes to form a barrier coating, a hydrophobic coating, a
lubricity coating,
or more than one of these. A cuvette is a small tube of circular or square
cross section,
sealed at one end, made of plastic, glass, or fused quartz (for UV light) and
designed to
hold samples for spectroscopic experiments_ The best cuvettes are as clear as
possible,
without impurities that might affect a spectroscopic reading. Like a test tube
or sample
collection tube, a cuvette may be open to the atmosphere or have a cap to seal
it shut.
The PECVD-applied coatings of the present invention according to its
embodiments can
be very tnin, transparent, and optically tiat, tnus not interrenng witn
optical testing ot the
cuvette or its contents.
VII.F. Vials
[325] The PECVD coating methods, etc., described in this specification are
also useful
for coating vials to form a coating, for example a barrier coating or a
hydrophobic coating,
or a combination of these coatings. A vial is a small vessel or bottle,
especially used to
store medication as liquids, powders or lyophilized powders. They can also be
sample
vessels e.g. for use in autosampler devices in analytical chromatography. A
vial can have
a tubular shape or a bottle-like shape with a neck. The bottom is usually flat
unlike test
tubes or sample collection tubes which usually have a rounded bottom. Vials
can be
made, for example, of plastic (e.g. polypropylene, COC, COP).
56
Date Recue/Date Received 2020-08-17
Computer-Readable Medium and Program Element
[326] Furthermore, a computer-readable medium is provided, in which a computer
program for coating and/or inspection of a vessel is stored which, when being
executed
by a processor of a vessel processing system, causes the processor to perform
the
above or below mentioned method steps.
[327] Furthermore, a program element for coating and/or inspection of a vessel
is
provided which, when being executed by a processor of a vessel processing
system,
causes the processor to carry out the above or below mentioned method steps.
[328] Other aspects of the invention according to its embodiments will be
apparent from
this disclosure and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[329] FIG. 1 is a schematic diagram showing a vessel processing system
according
to an embodiment of the disclosure.
[330] FIG. 2 is a schematic sectional view of a vessel holder in a coating
station
ar.r.nrrling In an P m hrvi m pnt nf thp disrinsiirp
[331] FIG. 3 is a view similar to FIG. 2 of an alternative embodiment of the
disclosure.
[332] FIG. 4 is a diagrammatic plan view of an alternative embodiment of the
vessel
holder.
[333] FIG. 5 is a diagrammatic plan view of another alternative embodiment of
the vessel
holder.
[334] FIG. 6 is a view similar to FIG. 2 of vessel inspection apparatus.
[335] FIG. 7 is a view similar to FIG. 2 of alternative vessel inspection
apparatus.
[336] FIG. 8 is a section taken along section lines A¨A of FIG. 2.
[337] FIG. 9 is an alternative embodiment of the structure shown in FIG. 8.
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[338] FIG. 10 is a view similar to FIG. 2 of a vessel holder in a coating
station
according to another embodiment of the disclosure, employing a COD detector.
[339] FIG. 11 is a detail view similar to FIG. 1D of a light source and
detector that
are reversed compared to the corresponding parts of FIG. 6.
[340] FIG. 12 is a view similar to FIG. 2 of a vessel holder in a coating
station
according to still another embodiment of the disclosure, employing microwave
energy to
generate the plasma.
[341] FIG. 13 is a view similar to FIG. 2 of a vessel holder in a coating
station
according to yet another embodiment of the disclosure, in which the vessel can
be
seated on the vessel holder at the process station.
[342] FIG. 14 is a view similar to FIG. 2 of a vessel holder in a coating
station
according to even another embodiment of the disclosure, in which the electrode
can be
configured as a coil.
[343] FIG. 15 is a view similar to FIG. 2 of a vessel holder in a coating
station
according to another embodiment of the disclosure, employing a tube transport
to move
a vessel to and from the coating station.
[344] FIG. 16 is a diagrammatic view of the operation of a vessel transport
system,
such as the one shown in FIG. 15, to place and hold a vessel in a process
station.
[345] FIG. 17 is a diagrammatic view of a mold and mold cavity for forming
a vessel
according to an aspect of the present disclosure.
[346] FIG. 18 is a diagrammatic view of the mold cavity of FIG. 17 provided
with a
vessel coating device according to an aspect of the present disclosure.
[347] FIG. 19 is a view similar to FIG. 17 provided with an alternative
vessel coating
device according to an aspect of the present disclosure.
[348] FIG. 20 is an exploded longitudinal sectional view of a syringe and
cap
adapted for use as a prefilled syringe.
[349] FIG. 21 is a view generally similar to FIG. 2 showing a capped
syringe barrel
and vessel holder in a coating station according to an embodiment of the
disclosure.
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[350] FIG. 22 is a view generally similar to FIG. 21 showing an uncapped
syringe
barrel and vessel holder in a coating station according to yet another
embodiment of the
invention.
[351] FIG. 23 is a perspective view of a blood collection tube assembly
having a
closure according to still another embodiment of the invention.
[352] FIG. 24 is a fragmentary section of the blood collection tube and
closure
assembly of FIG. 23.
[353] FIG. 25 is an isolated section of an elastomeric insert of the
closure of FIGS.
23 and 24.
[354] FIG. 26 is a view similar to FIG. 22 of another embodiment of the
invention for
processing syringe barrels and other vessels.
[355] FIG. 27 is an enlarged detail view of the processing vessel of FIG.
26.
[356] FIG. 28 is a schematic view of an alternative processing vessel.
[357] FIG. 29 is a schematic view showing outgassing of a material through
a
coating.
[358] FIG. 30 is a schematic sectional view of a test set-up for causing
outgassing
of the wall of a vessel to the interior of the vessel and measurement of the
outgassing
using a measurement cell interposed between the vessel and a source of vacuum.
[359] FIG. 31 is a plot of outgassing mass flow rate measured on the test-
set-up of
FIG. 30 for multiple vessels.
[360] FIG. 32 is a bar graph showing a statistical analysis of the endpoint
data
shown in FIG. 31.
[361] FIG. 39 is a longitudinal section of a combined syringe barrel and
gas
receiving volume according to another embodiment of the invention.
[362] FIG. 34 is a view similar to FIG 34 of another embodiment of the
invention
including an electrode extension.
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[363] FIG. 35 is a view taken from section lines 35 - 35 of FIG. 34,
showing the
distal gas supply openings and extension electrode of FIG. 34.
[364] FIG. 36 is a perspective view of a double-walled blood collection
tube
assembly according to still another embodiment of the invention.
[365] FIG. 37 is a view similar to FIG. 22 showing another embodiment.
[366] FIG. 38 is a view similar to FIG. 22 showing still another
embodiment.
[367] FIG. 39 is a view similar to FIG. 22 showing yet another embodiment.
[368] FIG. 40 is a view similar to FIG. 22 showing even another embodiment.
[369] FIG. 41 is a plan view of the embodiment of FIG. 40.
[370] FIG. 42 is a fragmentary detail longitudinal section of an
alternative sealing
arrangement, usable for example, with the embodiments of FIGS. 1, 2, 3, 6-10,
12- 16,
18,19,22, and 27-41 for seating a vessel on a vessel holder. FIG. 42 also
shows an
alternative syringe barrel construction usable, for example, with the
embodiments of
FIGS. 2, 3, 6-10, 12-22, 26-28, 33- 34, and 37-41.
[371] FIG. 43 is a further enlarged detail view of the sealing arrangement
shown in
FIG. 42.
[372] FIG. 44 is a view similar to FIG. 2 of an alternative gas delivery
tube/Inner
electrode usable, for example with the embodiments of FIGS. 1,2, 3, 8, 9, 12-
16, 18-19,
21-22, 33, 37-43,46-49, and 52-54.
[373] FIG. 45 is an alternative construction for a vessel holder usable,
for example,
with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16, 18, 19, 21, 22, 26, 28, 33-
35. and
37-44.
[374] FIG. 46 is a schematic sectional view of an array of gas delivery
tubes and a
mechanism for inserting and removing the gas delivery tubes from a vessel
holder,
showing a gas delivery tube in its fully advanced position.
[375] FIG. 47 is a view similar to FIG. 46, showing a gas delivery tube in
an
interm eciiate position.
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[376] FIG. 48 is a view similar to FIG. 46, showing a gas delivery tube in
a retracted
position. The array of gas delivery tubes of FIGS. 46-48 are usable, for
example, with
the embodiments of FIGS. 1, 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-
45, 49,
and 52-54. The mechanism of FIGS. 46-48 is usable, for example, with the gas
delivery
tube embodiments of FIGS. 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-
45, 49, and
52-54, as well as with the probes of the vessel inspection apparatus of FIGS.
6 and 7.
[377] FIG. 49 is a view similar to FIG. 16 showing a mechanism for
delivering
vessels to be treated and a cleaning reactor to a PECVD coating apparatus. The
mechanism of FIG. 49 is usable with the vessel inspection apparatus of FIGS.
1, 9, 15,
and 16, for example.
[378] FIG. 50 is an exploded view of a two-piece syringe barrel and Luer
lock fitting.
The syringe barrel is usable with the vessel treatment and inspection
apparatus of
FIGS. 1-22, 26-28, 33-35, 37-39,44, and 53-54.
[379] FIG. 51 is an assembled view of the two-piece syringe barrel and Luer
lock
f Ming of FIG. 50.
[380] FIG. 52 is a view simllar to FIG. 42 showing a syringe barrel being
treated
that has no flange or finger stops 440. The syringe barrel is usable with the
vessel
treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-51, and 53-
54.
[381] FIG. 53 is a schematic view of an assembly for treating vessels. The
assembly is usable with the apparatus of FIGS. 1-3, 8-9, 12-16, 18-22, 26-28,
33-35,
and 3 /-49.
[382] FIG. 54 is a diagrammatic view of the embodiment of FIG. 53.
[383] FIG. 55 is a diagrammatic view similar to FIG. 2 of an embodiment of
the
invention Including a plasma screen.
[384] FIG. 56 is a schematic sectional view of an array of gas delivery
tubes, having
independent gas supplies and a mechanism for inserting and removing the gas
delivery
tubes from a vessel holder.
[385] FIG. 57 is a plot of outgassing mass flow rate measured in Example
19.
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[386] FIG. 58 shows a linear rack, otherwise similar to FIG. 4.
[387] FIG. 59 shows a schematic representation of a vessel processing
system
according to an exemplary embodiment of the present invention.
[388] FIG. 60 shows a schematic representation of a vessel processing
system
according to another exemplary embodiment of the present invention.
[389] FIG. 61 shows a processing station of a vessel processing system
according
to an exemplary embodiment of the present invention.
[390] FIG. 62 shows a portable vessel holder according to an exemplary
embodiment of the present invention.
[391] The following reference characters are used in the drawing figures:
20 Vessel processing system 58 Vessel holder
22 Injection molding machine 60 Vessel holder
24 Visual inspection station 62 Vessel holder
26 Inspection station (pre- 64 Vessel holder
coating) 66 Vessel holder
28 Coating station 68 Vessel holder
Inspection station (post-
30 coating) 70 Conveyor
32 Optical source transmission 72 Transfer mechanism (on)
station (thickness) 74 Transfer mechanism (off)
Optical source transmission 80 Vessel
24 station (detects) 82 Opening
36 Output 84 Closed end
38 Vessel holder
86 Wall
40 Vessel holder
88 Interior surface
42 Vessel holder
90 Barrier coating
44 Vessel holder
92 Vessel port
46 Vessel holder 94 Vacuum duct
48 Vessel holder
96 Vacuum port
50 Vessel holder
98 Vacuum source
52 Vessel holder
100 0-ring (of 92)
54 Vessel holder
102 0-ring (of 96)
56 Vessel holder
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104 Gas inlet port 194 Microwave cavity
106 0-ring (of 100) 196 Gap
108 Probe (counter electrode) 198 Top end (of 194)
110 Gas delivery port (of 108) 200 Electrode
112 Vessel holder (Fig. 3) 202 Tube transport
114 Housing (of 50 or 112) 204 Suction cup
116 Collar 208 Mold Gore
118 Exterior surface (of 80) 210 Mold cavity
120 Vessel holder (array) 212 Mold cavity liner
122 Vessel port (Fig. 4, 58) 220 Bearing surface (Fig. 2)
130 Frame (Fig. 5) 222 Bearing surface (Fig. 2)
132 Light source 224 Bearing surface (Fig. 2)
134 Side channel 226 Bearing surface (Fig. 2)
136 Shut-off valve 228 Bearing surface (Fig. 2)
138 Probe port 230 Bearing surface (Fig. 2)
140 Vacuum port 232 Bearing surface (Fig. 2)
142 PECVD gas inlet port 234 Bearing surface (Fig. 2)
144 PECVD gas source 236 Bearing surface (Fig. 2)
146 Vacuum line (to 98) 238 Bearing surface (Fig. 2)
148 Shut-off valve 240 Bearing surface (Fig. 2)
150 Flexible line (of 134) 250 Syringe barrel
152 Hressure gauge 252 Syringe
154 Interior of vessel 80 254 Interior surface (of 250)
160 Electrode 256 Back end (of 250)
162 Power supply 258 Plunger (of 252)
164 Sidewall (of 160) 260 Front end (of 250)
166 Sidewall (of 160) 262 Cap
168 Closed end (of 160) 264 Interior surface (of 262)
170 Light source (Fig. 10) 266 Fitting
172 Detector 268 Vessel
174 Pixel (of 172) 270 Closure
176 Interior surface (of 172) 272 Interior facing surface
182 Aperture (of 186) 274 Lumen
184 Wall (of 186) 276 Wall-contacting surface
186 Integrating sphere 278 Inner surface (of 280)
190 Microwave power supply 280 Vessel wall
192 Waveguide 282 Stopper
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284 Shield 352 Vacuum
286 Lubricity layer 354 Gas molecule
288 Barrier layer 355 Gas molecule
290
Apparatus for coating, for Interface (between 346 and example, 250
356348)
292 Inner surface (of 294) 357 Gas molecule
294 Restricted opening (of 250) 358 PET vessel
296 Processing vessel 359 Gas molecule
298 Outer surface (of 250) 360 Seal
300 Lumen (of 250) 362 Measurement cell
302 Larger opening (of 250) 364 Vacuum pump
304 Processing vessel lumen 366 Arrows
306 Processing vessel opening 368 Conical passage
308 Inner electrode 370 Bore
310 Interior passage (of 308) 372 Bore
312 Proximal end (of 308) 374 Chamber
214 Distal end (of 308) 376 Chamber
316 Distal opening (of 308) 378 Diaphragm
318 Plasma 380 Diaphragm
320 Vessel support 382 Conductive surface
322 Port (of 320) 384 Conductive surface
324 Processing vessel (conduit 388 Bypass
type) 390 Plot (glass tube)
326 Vessel opening (of 324) 392 Plot (PET uncoated)
328 Second opening (of 324) 394 Main plot (SiO2 coated)
Vacuum port (receiving
330 396 Outliers (SiO2 coated)
328)
First fluting (male Luer 398 Inner electrode and gas
332 taper) supply tube
Second fitting (female Luer 400 Distal opening
334
taper) 402 Extension counter electrode
336 Locking collar (of 332) 404 Vent (Fig. 7)
338 First abutment (of 332) 406 Valve
340 Second abutment (of 332) 408 Inner wall (Fig. 36)
342 0-ring 410 Outer wall (Fig. 36)
344 Dog 412 Interior surface (Fig. 36)
346 Wall 414 Plate electrode (Fig. 37)
348 Coating (on 346) 416 Plate electrode (Fig. 37)
350 Permeation path 41B Vacuum conduit
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420 Vessel holder Radially extending
494
422 Vacuum chamber abutment surface
496 Radially extending wall
424 Vessel holder
498 Screw
426 Counter electrode
500 Screw
428 Vessel holder (Fig. 39)
502 Vessel port
430 Electrode assembly
504 Second 0-ring
432 Volume enclosed by 430
506 Inner diameter (of 490)
Pressure proportioning
434 valve 508 Vacuum duct (of 482)
436 Vacuum chamber conduit 510 Inner electrode
438 Syringe barrel (Fig. 42) 512 Inner electrode
440 Flange (of 438) Insertion and removal
514
442 Back opening (of 438) mechanism
516 Flexible hose
444 Barrel wall (of 438)
518 Flexible hose
450 Vessel holder (Fig 42)
520 Flexible hose
452 Annular lip
Generally cylindrical 522 Valve
454 sidewall (of 438) 524 Valve
Generally cylindrical inner 526 Valve
456 surface (of 450) 528 Electrode cleaning station
458 Abutment 530 Inner electrode drive
460 Pocket 532 Cleaning reactor
4b2 0-ring 534 Vent valve
464 Outside wall (of 460) 536 Second gripper
466 Bottom wall (of 460) 538 Conveyer
468 Top wall (of 460) 539 Solute retainer
470 Inner electrode (Fig. 44) 540 Open end (of 532)
4/2 Distal portion (ot 4'0) 542 Interior space (of 532)
474 Porous side wall (of 472) 544 Syringe
476 Internal passage (of 472) 546 Plunger
478 Proximal portion (of 470) 548 Body
480 Distal end (of 470) 550 Barrel
482 Vessel holder body 552 Interior surface (of 550)
484 Upper portion (of 482) 554 Coating
486 Base portion (of 482) 556 Luer fitting
Joint (between 484 and
488 558 Luer taper
486)
560 Internal passage (of 558)
490 0-ring
562 Internal surface
492 Annular pocket
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564 Coupling 5505 Processor
566 Male part (of 564) 5506 User interface
568 Female part (of 564) 5507 Bus
570 Barrier coating 5701 PECVD apparatus
572 Locking collar 5702 First detector
574 Main vacuum valve 5703 Second detector
576 Vacuum line 5704 Detector
578 Manual bypass valve 5705 Detector
580 Bypass line 5706 Detector
582 Vent valve 5707 Detector
584 Main reactant gas valve 7001 Conveyor exit branch
506 Main reactant feed line 7002 Conveyor exit branch
Organosilicon liquid 7003 Conveyor exit branch
588 reservoir 7004 Conveyor exit branch
590 Organosil icon feed line
(capillary)
592 Organosil icon shut-off valve
594 Oxygen lank
596 Oxygen feed line
598 Mass flow controller
600 Oxygen shut-off valve
602 Syringe exterior barrier
coating
604 Lumen
606 Barrel exterior surface
610 Plasma screen
612 Plasma screen cavity
614 Headspace
616 Pressure source
618 Pressure line
620 Capillary connection
630 Plots for uncoated COC
632 Plots for SiOx coated COC
634 Plots for glass
5501 First processing station
5502 Second processing station
5503 Third processing station
5504 Fourth processing station
66
DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS
[392] The present invention will now be described more fully with reference to
the
accompanying drawings, in which several embodiments are shown. This invention
may,
however, be embodied in many different forms and should not be construed as
limited
to the embodiments set forth here. Rather, these embodiments are examples of
the
invention, which has the full scope indicated by the language of the claims.
Like numbers
refer to like or corresponding elements throughout.
[393] In the context of the present invention according to its embodiments,
the following
definitions and abbreviations are used:
[394] RF is radio frequency; sccm is standard cubic centimeters per minute.
[395] The term "at least" in the context of the present invention according to
its
embodiments means "equal or more" than the integer tonowing said term. The
word
"comprising" does not exclude other elements or steps, and the indefinite
article "a" or
"an" does not exclude a plurality unless indicated otherwise.
[396] "First" and "second" or similar references to, ea, processing stations
or processing
devices refer to the rninimum number of processing stations or devices that
are present,
but do not necessarily represent the order or total number of processing
stations and
devices. These terms do not limit the number of processing stations or the
particular
processing cameo out at tne respective stations.
[397] For purposes of the present invention according to its embodiments, an
"organosilicon precursor" is a compound having at least one of the linkage:
¨0¨Si¨C¨H
which is a tetravalent silicon atom connected to an oxygen atom and an organic
carbon
atom (an organic carbon atom being a carbon atom bonded to at least one
hydrogen
atom). A volatile organosilicon precursor, defined as such a precursor that
can be
67
Date Recue/Date Received 2020-08-17
supplied as a vapor in a PECVD apparatus, is an illustrative organosilicon
precursor.
Illustratively, the organosilicon precursor is selected from the group
consisting of a linear
siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane,
an alkyl
trimethoxysilane, a linear silazane, a monocyclic silazane, a polycyclic
silazane, a
polysilsesquiazane, and a combination of any two or more of these precursors.
[398] In the context of the present invention according to its embodiments,
"essentially
no oxygen" or (synonymously) "substantially no oxygen" is added to the gaseous
reactant in some embodiments. This means that some residual atmospheric oxygen
can
be present in the reaction space, and residual oxygen fed in a previous step
and not fully
exhausted can be present in the reaction space, which are defined here as
essentially
no oxygen present. Essentially no oxygen is present in the gaseous reactant in
particular
if the gaseous reactant comprises less than 1 vol% 02, more particularly less
than 0.5
vol% 02, and even more particularly if it is 02-free, If no oxygen is added to
the gaseous
reactant, or if no oxygen at all is present during PECVD, this is also within
the scope of
"essentially no oxygen."
[399] A "vessel" in the context of the present invention according to its
embodiments
may be any type of vessel with at least one opening and a wall defining an
interior
sui faue. The Let iii "di ledbr in the uotiLexl. ol Me piesetit invention
auuoidiny to its
embodiments means "equal or more" than the integer following said term. Thus,
a vessel
in the context of the present invention according to its embodiments has one
or more
openings. One or two openings, like the openings of a sample tube (one
opening) or a
syringe barrel (two openings) are illustrative. If the vessel has two
openings, they may
be of same or different size. If there is more than one opening, one opening
may be used
for the gas inlet for a PECVD coating method according to the embodiments of
the
present invention, while the other openings are either capped or open. A
vessel
according to the embodiments of the present invention may be a sample tube,
e.g. for
collecting or storing biological fluids like blood or urine, a syringe (or a
part thereof, for
example a syringe barrel) for storing or delivering a biologically active
compound or
composition, e.g. a medicament or pharmaceutical composition, a vial for
storing
biological materials or biologically active compounds or compositions, a pipe,
e.g. a
catheter for transporting biological materials or biologically active
compounds or
compositions, or a cuvette for holding fluids, e.g. for holding biological
materials or
biologically active compounds or compositions.
68
Date Recue/Date Received 2020-08-17
[400] A vessel may be of any shape, a vessel having a substantially
cylindrical wall
adjacent to at least one of its open ends being illustrative. Generally, the
interior wall of
the vessel is cylindrically shaped, like, e.g. in a sample tube or a syringe
barrel. Sample
tubes and syringes or their parts (for example syringe barrels) are
particularly illustrative.
[401] A "hydrophobic coating" in the context of the present invention
according to its
embodiments means that the coating lowers the wetting tension of a surface
coated with
said coating, compared to the corresponding uncoated surface. Hydrophobicity
is thus a
function of both the uncoated substrate and the coating. The same applies with
appropriate alterations for other contexts wherein the term "hydrophobic" is
used. The
term "hydrophilic" means the opposite, i.e. that the wetting tension is
increased
compared to reference sample. A particular hydrophobic coating in the context
of present
invention according to its embodiments may be a coating having the empirical
or sum
formula SiwOxCyHz, where w is 1, x is from about 0.5 to about 2.4, y is from
about 0.6 to
about 3, and z is frorn 2 to about 9.
[402] "Wetting tension" is a specific measure for the hydrophobicity or
hydrophilicity
of a surface. The illustrative wetting tension measurement method in the
context of the
present invention according to its embodiments is ASTM D 2578 or a
modification of the
method described in ASTM D 2576. This method uses standard wetting tension
solutions
(called dyne solutions) to determine the solution that comes nearest to
wetting a plastic
film surface for exactly two seconds. This is the film's wetting tension. The
procedure
utilized is varied herein from ASTM D 2578 in that the substrates are not flat
plastic films,
but are tubes made according to the Protocol for Forming PET Tube and (except
for
controls) coated according to the Protocol for Coating Tube Interior with
Hydrophobic
Coating (see Example 9).
[403] A "lubricity coating" according to the present invention according to
its
embodiments is a coating which has a lower frictional resistance than the
uncoated
surface. In other words, it reduces the frictional resistance of the coated
surface in
comparison to the a reference surface which is uncoated. "Frictional
resistance" can be
static frictional resistance and/or kinetic frictional resistance. One of the
illustrative
embodiments of the present invention is a syringe part, e.g. a syringe barrel
or plunger,
coated with a lubricity coating. In this illustrative embodiment, the relevant
static frictional
resistance in the context of the
69
Date Recue/Date Received 2020-08-17
present invention is the breakout force as defined herein, and the relevant
kinetic
frictional resistance in the context of the present invention is the plunger
sliding force as
defined herein. For example, the plunger sliding force as defined and
determined herein
is suitable to determine the presence or absence and the lubricity
characteristics of a
lubricity coating in the context of the present invention according to its
embodiments
whenever the coating is applied to any syringe or syringe part, for example to
the inner
wall of a syringe barrel. The breakout force is of particular relevance for
evaluation of the
coating effect on a prefilled syringe, i.e. a syringe which is filled after
coating and may be
stored for some time, e.g. several months or even years, before the plunger is
moved
again (has to be "broken out").
[404] The "plunger sliding force" in the context of the present invention
according to its
embodiments is the force required to maintain movement of a plunger in a
syringe barrel,
e.g. during aspiration or dispense. It may be determined using the ISO 7886-
1:1993 test
described herein and known in the art. A synonym for "plunger sliding force"
often used
in the art is "plunger force" or "pushing force".
[405] The "breakout force" in the context of the present invention according
to its
embodiments is the initial force required to move the plunger in a syringe,
for example in
a preniiea syringe.
[406] Both "plunger sliding force" and "breakout force" and methods for their
measurement are described in more detail in subsequent parts of this
description.
[407] "Slidably" 11-1411-15 that the plunger is per to slide in a
syringe barrel.
[408] In the context of this invention according to its embodiments,
"substantially rigid"
means that the assembled components (ports, duct, and housing, explained
further
below) can be moved as a unit by handling the housing, without significant
displacement
of any of the assembled components respecting the others. Specifically, none
of the
components are connected by hoses or the like that allow substantial relative
movement
among the parts in normal use. The provision of a substantially rigid relation
of these
parts allows the location of the vessel seated on the vessel holder to be
neatly as well
known and precise as the locations of these parts secured to the housing.
Date Recue/Date Received 2020-08-17
[409] In the following, the apparatus for performing the present invention
according to its
embodiments will be described first, followed by the coating methods, coatings
and
coated vessels, and the uses according to the embodiments of the present
invention.
I. VESSEL PROCESSING SYSTEM HAVING MULTIPLE PROCESSING
STATIONS AND MULTIPLE VESSEL HOLDERS
[410] I. A vessel processing system is contemplated comprising a first
processing
station, a second processing station, a multiplicity of vessel holders, and a
conveyor. The
first processing station is configured for processing a vessel having an
opening and a
wall defining an interior surface. The second processing station is spaced
from the first
processing station and configured for processing a vessel having an opening
and a wall
defining an interior surface.
[411] I. At least some, optionally all, of the vessel holders include a vessel
port configured
to receive and at the opening of a vessel for processing the interior surface
of a seated
vessel via the vessel port at the first processing station. The conveyor is
configured for
transporting a series of the vessel holders and seated vessels from the first
processing
station to the second processing station for processing the interior surface
of a seated
vessel via the vessel port at the second processing station.
[412] I. Referring
first to FIG. 1, a vessel processing system generally indicated as
20 is shown. The vessel processing system can include processing stations
which more
broadly arp contpmplatpd to hp prorpgging dpviepg_ ThP I/PggPi proepgging
gygtpm 20 of
the illustrated embodiment can include an injection molding machine 22 (which
can be
regarded as a processing station or device), additional processing stations or
devices
24, 26, 28, 30, 32, and 34, and an output 36 (which can be regarded as a
processing
station or device). At a minimum, the system 20 has at least a first
processing station,
for example station 28, and a second processing station, for example 30, 32,
or 34.
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[413] I. Any of the processing stations 22-36 in the illustrated embodiment
can be a
first processing station, any other processing station can be a second
processing
station, and so forth.
[414] I. The embodiment illustrated in FIG. 1 can include eight processing
stations
or devices: 22, 24, 26, 28, 30, 32, 34, and 36. The exemplary vessel
processing system
20 includes an injection molding machine 22, a post-molding inspection station
24, a
pre-coating inspection station 26, a coating station 28, a post-coating
inspection station
30, an optical source transmission station 32 to determine the thickness of
the coating,
an optical source transmission station 34 to examine the coating for defects,
and an
output station 36.
[415] I. The system 20 can include a transfer mechanism 72 for moving
vessels
from the injection molding machine 22 to a vessel holder 38. The transfer
mechanism
72 can be configured, for example, as a robotic arm that locates, moves to,
grips,
transfers, orients, seats, and releases the vessels 80 to remove them from the
vessel
forming machine 22 and install them on the vessel holders such as 38.
[416] I. The system 20 also can include a transfer mechanism at a
processing
station 74 for removing the vessel from one or more vessel holders such as 66,
following processing the interior surface of the seated vessel such as 80
(FIG. 1). The
vessels 80 are thus movable from the vessel holder 66 to packaging, storage,
or
another appropriate area or process step, generally indicated as 36. The
transfer
mechanism 74 can be configured, for example, as a robotic arm that locates,
moves to,
grips, transfers, orients, places, and releases the vessels 80 to remove them
from the
vessel holders such as 38 and place them on other equipment at the station 36.
[417] I. The processing stations or devices 32, 34, and 36 shown in FIG. 1
optionally carry out one or more appropriate steps downstream of the coating
and
inspection system 20, after the individual vessels 80 are removed from the
vessel
holders such as 64. Some non-limiting examples of functions of the stations or
devices
32, 34, and 36 include:
= placing the treated and inspected vessels 80 on a conveyor to further
processing apparatus;
72
= adding chemicals to the vessels;
= capping the vessels;
= placing the vessels in suitable processing racks;
= packaging the vessels; and
= sterilizing the packaged vessels.
[418] I. The vessel processing system 20 as illustrated in FIG. 1 also can
include a
multiplicity of vessel holders (or "pucks," as they can in some embodiments
resemble a
hockey puck) respectively 38 through 68, and a conveyor generally indicated as
an
endless band 70 for transporting one or more of the vessel holders 38-68, and
thus
vessels such as 80, to or from the processing stations 22, 24, 26, 28, 30, 32,
34, and
36.
[419] I. The processing station or device 22 can be a device for forming the
vessels 80.
One contemplated device 22 can be an injection molding machine. Another
contemplated device 22 can be a blow molding machine. Vacuum molding machines,
draw molding machines, cutting or milling machines, glass drawing machines for
glass
or other draw-formable materials, or other types of vessel forming machines
are also
contemplated. Optionally, the vessel forming station 22 can be omitted, as
vessels can
be obtained already formed.
VESSEL HOLDERS
[420] RA. The portable vessel holders 38-68 are provided for holding and
conveying
a vessel having an opening while the vessel is processed. The vessel holder
includes a
vessel port, a second port, a duct, and a conveyable housing.
[421] ILA. The vessel port is configured to seat a vessel opening in a
mutually
communicating relation. The second port is configured to receive an outside
gas supply
or vent. The duct is configured for passing one or more gases between a vessel
opening
seated on the vessel port and the second port. The vessel port, second port,
and duct
are attached in substantially rigid relation to the conveyable housing.
Optionally, the
portable vessel holder weighs less than five pounds. An intended advantage of
a
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lightweight vessel holder is that it can more readily be transported from one
processing
elation to another.
[422] II.A. In certain embodiments of the vessel holder the duct more
specifically is
a vacuum duct and the second port more specifically is a vacuum port. The
vacuum
duct is configured for withdrawing a gas via the vessel port from a vessel
seated on the
vessel port. The vacuum port is configured for communicating between the
vacuum
duct and an outside source of vacuum. The vessel port, vacuum duct, and vacuum
port
can be attached in substantially rigid relation to the conveyable housing.
[423] II.A. The vessel holders of embodiments II.A. and II.A.1. are shown,
for
example, in FIG. 2. The vessel holder 50 has a vessel port 82 configured to
receive
and seat the opening of a vessel 80. The interior surface of a seated vessel
80 can be
processed via the vessel port 82. The vessel holder 50 can include a duct, for
example
a vacuum duct 94, for withdrawing a gas from a vessel 80 seated on the vessel
port 92.
The vessel holder can include a second port, for example a vacuum port 96
communicating between the vacuum duct 94 and an outside source of vacuum, such
as
the vacuum pump 98. The vessel port 92 and vacuum port 96 can have sealing
elements, for example 0-ring butt seals, respectively 100 and 102, or side
seals
between an inner or outer cylindrical wall of the vessel port 82 and an inner
or outer
cylindrical wall of the vessel 80 to receive and form a seal with the vessel
80 or outside
source of vacuum 98 while allowing communication through the port. Gaskets or
other
sealing arrangements can or also be used.
[424] II.A. The vessel holder such as 50 can be made of any material, for
example
thermoplastic material and/or electrically nonconductive material. Or, the
vessel holder
such as 50 can be made partially, or even primarily, of electrically
conductive material
and faced with electrically nonconductive material, particularly in the
passages defined
by the vessel port 92, vacuum duct 94, and vacuum port 96. Examples of
suitable
materials for the vessel holder 50 are: a polyacetal, for example Delrin
acetal material
sold by E. I. du Pont De Nemours and Company, Wilmington Delaware;
polytetrafluoroethylene (PTFE), for example Teflon PTFE sold by E. I. du Pont
De
Nemours and Company, Wilmington Delaware; Ultra-High-Molecular-Weight
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Polyethylene (UHMVVPE); High density Polyethylene (HDPE); or other materials
known
in the art or newly discovered.
[425] II.A. FIG. 2 also illustrates that the vessel holder, for example 50,
can have a
collar 116 for centering the vessel 80 when it is approaching or seated on the
port 92.
Array of Vessel Holders
[426] II.A. Yet another approach to treat, inspect, and/or move parts
through a
production system can be to use an array of vessel holders. The array can be
comprised of individual pucks or be a solid array into which the devices are
loaded. An
array can allow more than one device, optionally many devices, to be tested,
conveyed
or treated/coated simultaneously. The array can be one-dimensional, for
example
grouped together to form a linear rack, or two-dimensional, similar to a tub
or tray.
[427] II.A. FIGS. 4, 5, and 58 show three array approaches. FIG. 4 shows a
solid
array 120 into (or onto) which the devices or vessels 80 are loaded. In this
case, the
devices or vessels 80 can move through the production process as a solid
array,
although they can be removed during the production process and transferred to
individual vessel holders. A single vessel holder 120 has multiple vessel
ports such as
122 for conveying an array of seated vessels such as 80, moving as a unit. In
this
embodiment, multiple individual vacuum ports such as 96 can be provided to
receive an
array of vacuum sources 98. Or, a single vacuum port connected to all the
vessel ports
such as 96 can be provided. Multiple gas inlet probes such as 108 can also be
provided in an array. The arrays of gas inlet probes or vacuum sources can be
mounted to move as a unit to process many vessels such as 80 simultaneously.
Or, the
multiple vessel ports such as 122 can be addressed one or more rows at a time,
or
individually, in a processing station. The number of devices in the array can
be related
to the number of devices that are molded in a single step or to other tests or
steps that
can allow for efficiency during the operation. In the case of treating/coating
an array,
the electrodes can either be coupled together (to form one large electrode),
or can be
individual electrodes each with its own power supply. All of the above
approaches can
still be applicable (from the standpoint of the electrode geometry, frequency
etc.).
[428] II.A. In FIG. 5, individual pucks or vessel holders (as discussed above)
are brought
together into an array, as by surrounding them with an external frame 130.
This
arrangement provides the intended advantages of the solid array of FIG. 4,
when that is
desired, and also allows the array to be disassembled for other processing
steps in which
the vessels 80 are addressed in different arrays or singly.
[429] H.A. FIG. 58 shows a linear rack, otherwise similar to FIG. 4. If a
linear rack
is used, another option, in addition to those explained above, is to transport
the rack in
single file fashion through a processing station, processing the vessels
serially.
II.B. Vessel Holder Including 0-ring Arrangement
[430] II.B. FIGS. 42 and 43 are respectively a fragmentary detail longitudinal
section and
a detail view of a vessel holder 450 provided with an alternative sealing
arrangement,
usable for example, with the vessel holder embodiments of FIGS. 2, 3, 6, 7,
19, 12, 13,
16, 18, 19, 30, and 43 for seating a vessel on a vessel holder_ Referring to
FIG_ 42, the
vessel, for example a syringe barrel 438, seated on the vessel holder 450 has
a back
opening 442 defined by a generally annular (and commonly chamfered or rounded)
lip
452, as well as a generally cylindrical sidewall 454. A medical fluid
collection tube
commonly has the same type of lip 452, but without a flange 440, and thus can
be seated
on the vessel holder 450 instead.
[431] II.B. The vessel holder 450 in the embodiment as illustrated includes a
generally
cylindrical inner surface 456 that in the illustrated embodiment serves as a
guide surface
to receive the generally cylindrical sidewall 454 of the syringe barrel 438.
The well is
further defined by a generally annular abutment 458 against which the annular
lip 452
abuts when the syringe barrel 438 is seated on the vessel holder 450. A
generally annular
pocket or groove 460 formed in the inner surface 456 is provided for retaining
the sealing
element, for example an 0-ring 462. The radial depth of the pocket 460 is less
than the
radial cross-section of the sealing element, for example an 0-ring 462 (as
illustrated in
FIG. 42), and the inner diameter of the 0-ring 462 is illustratively slightly
smaller than the
outer diameter of the annular lip 452.
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[432] II.B. These relative dimensions cause the radial cross-section of the
0-ring
462 to compress horizontally between at least the outside wall 464 of the
pocket 460
and the generally cylindrical sidewall 454 of the syringe barrel 438, as shown
in FIG. 42,
when a vessel such as 438 is seated as shown in FIG. 42. This compression
flattens
the bearing surfaces of the 0-ring 462, forming a seal between at least the
outside wall
464 of the pocket 460 and the generally cylindrical sidewall 454 of the
syringe barrel
438.
[433] II.B. The pocket 460 optionally can be constructed, in relation to
the
dimensions of the 0-ring 462, to form two more seals between the bottom and
top walls
466 and 468 an the sidewall 454, by spacing toe top and bottom walls 468 and
466
about as far apart as the corresponding radial cross-section diameter of the 0-
ring 462.
When the 0-ring 462 is squeezed between the outside wall 464 and the generally
cylindrical sidewall 454 of the pocket 460, its resilience will cause it to
expand upward
and downward as shown in FIG. 43, thus also engaging the top and bottom walls
466
and 464 and flattening against them. The 0-ring 462 optionally will thus be
deformed
both vertically and horizontally, tending to square its normally round cross-
section.
Additionally, the annular lip 452 seated on the abutment 458 will limit the
flow of PECVD
procesa reactants arid other gases and materials introduced through ur
adjacent to the
back opening 442.
[434] II.B. As a result of this optional construction, only the gap at the
lower right
corner of the 0-ring 462, as shown in FIG. 43, is outside the 0-rings and thus
exposed
to process gases, plasma, etc. introduced to or generated in the interior of
the vessel
438. This construction protects the 0-ring 462 and the adjacent surfaces (as
of the
outside surface of the sidewall 438) from unwanted build-up of PECVD deposits
and
attack by the activated chemical species in the plasma. Additionally, the
vessel 438 is
more positively located by the hard surface of the abutment 458, as opposed to
the
resilient surface that would be presented by a butt seat of the annular lip
452 directly
against the 0-ring as illustrated in some of the other Figures. Further, the
forces on the
respective portions around the major circumference of the 0-ring 462 are more
evenly
distributed, as the vessel 438 is constrained against any substantial rocking.
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[435] II.B. Cr, the pocket 460 can be formed with its bottom wall 466 above
the
abutment 458 shown in FIG. 43. In another embodiment, more than one axially
spaced
pocket 460 can be provided to provide a double or higher-level seal and to
further
restrain the vessel 438 against rocking when seated against the abutment 458.
[436] II.B. FIG. 45 is an alternative construction for a vessel holder 482
usable, for
example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16, 18, 19, 21, 22,
26, 28, 33-
35, and 37-44. The vessel holder 482 comprises an upper portion 484 and a base
486
joined together at a joint 488. A sealing element, for example an 0-ring 490
(the right
side of which is cut away to allow the pocket retaining it to be described) is
captured
between the upper portion 484 and the base 486 at the joint 488. In the
illustrated
embodiment, the 0-ring 490 is received in an annular pocket 492 to locate the
0-ring
when the upper portion 484 is joined to the base 486.
[437] II.B. In this embodiment, the 0-ring 490 is captured and bears
against a
radially extending abutment surface 494 and the radially extending wall 496
partially
defining the pocket 492 when the upper portion 484 and the base 486 are
joined, in this
case by the screws 498 and 500. The 0-ring 490 thus seats between the upper
portion
484 and base 486. The 0-ring 490 captured between the upper portion 484 and
the
base 486 also receives the vessel 80 (removed in this figure for clarity of
illustration of
other features) and forms a first 0-ring seal of the vessel port 502 about the
vessel 80
opening, analogous to the 0-ring seal arrangement about the vessel back
opening 442
in FIG. 42.
[438] II.B. In this embodiment, though not a requirement, the vessel port
502 has
both the first 0-ring 490 seal and a second axially spaced 0-ring 504 seal,
each having
an inner diameter such as 506 sized to receive the outer diameter (analogous
to the
sldewall 454 in FIG. 43) of a vessel such as 80 for sealing between the vessel
port 502
and a vessel such as 80. The spacing between the 0-rings 490 and 504 provides
support for a vessel such as 80 at two axially spaced points, preventing the
vessel such
as 80 from being skewed with respect to the 0-rings 490 and 504 or the vessel
port
502. In this embodiment, though not a requirement, the radially extending
abutment
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surface 494 is located proximal of the 0-ring 490 and 506 seals and
surrounding the
vacuum duct 508.
III. METHODS FOR TRANSPORTING VESSELS ¨ PROCESSING VESSELS
SEATED ON VESSEL HOLDERS
Transporting Vessel Holders To Processing Stations
[439] III.A. FIGS. 1,2, and 10 show a method for processing a vessel 80.
The
method can be carried out as follows.
[440] III.A. A vessel 80 can be provided having an opening 82 and a wall 86
defining an interior surface 88. As one embodiment, the vessel 80 can be
formed in
and then removed from a mold such as 22. Optionally within 60 seconds, or
within 30
seconds, or within 25 seconds, or within 20 seconds, or within 15 seconds, or
within 10
seconds, or within 5 seconds, or within 3 seconds, or within 1 second after
removing the
vessel from the mold, or as soon as the vessel 80 can be moved without
distorting it
during processing (assuming that it is made at an elevated temperature, from
which it
progressively cools), the vessel opening 82 can be seated on the vessel port
92.
Quickly moving the vessel 80 from the mold 22 to the vessel port 92 reduces
the dust or
other impurities that can reach the surface 88 and occlude or prevent adhesion
of the
barrier or other type of coating 90. Also, the sooner a vacuum is drawn on the
vessel
80 after it is made, the less chance any particulate impurities have of
adhering to the
interior surface 88.
[441] III.A. A vessel holder such as 50 comprising a vessel port 92 can be
provided. The opening 82 of the vessel 80 can be seated on the vessel port 92.
Before, during, or after seating the opening 82 of the vessel 80 on the vessel
port 92,
the vessel holder such as 40 (for example in FIG. 6) can be transported into
engagement with one or more of the bearing surfaces 220-240 to position the
vessel
holder 40 with respect to the processing device or station such as 24.
[442] III.A. One, more than one, or all of the processing stations such as
24-34, as
illustrated by the station 24 shown in FIG. 6, can include a bearing surface,
such as one
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or more of the bearing surfaces 220, 222, 224, 226, 228, 230, 232, 234, 236,
238, or
240, for supporting one or more vessel holders such as 40 in a predetermined
position
while processing the interior surface 88 of the seated vessel 80 at the
processing
station or device such as 24. These bearing surfaces can be part of stationary
or
roving structure, for example tracks or guides that guide and position the
vessel holder
such as 40 while the vessel is being processed. For example, the downward-
facing
bearing surfaces 222 and 224 locate the vessel holder 40 and act as a reaction
surface
to prevent the vessel holder 40 from moving upward when the probe 108 is being
inserted into the vessel holder 40. The reaction surface 236 locates the
vessel holder
and prevents the vessel holder 40 from moving to the left while a vacuum
source 98
(per FIG. 2) is seated on the vacuum port 96. The bearing surfaces 220, 226,
228, 232,
238, and 240 similarly locate the vessel holder 40 and prevent horizontal
movement
during processing. The bearing surfaces 230 and 234 similarly locate the
vessel holder
such as 40 and prevent it from moving vertically out of position. Thus, a
first bearing
surface, a second bearing surface, a third bearing surface, or more can be
provided at
each of the processing stations such as 24-34.
[443] III.A. The interior surface 88 of the seated vessel 80 can be then
processed
via the vessel out 92 at the first processing station], which can be, as one
example, the
barrier application or other type of coating station 28 shown in FIG. 2. The
vessel
holder 50 and seated vessel 80 are transported from the first processing
station 28 to
the second processing station, for example the processing station 32. The
interior
surface 00 of the seated vessel 00 can be processed via the vessel port 92 at
the
second processing station such as 32.
[444] III.A. Any of the above methods can include the further step of
removing the
vessel 80 from the vessel holder such as 66 following processing the interior
surface 88
of the seated vessel 80 at the second processing station or device.
[445] III.A. Any of the above methods can include the further step, after
the
removing step, of providing a second vessel 80 having an opening 82 and a wall
86
defining an interior surface 88. The opening 82 of the second vessel such as
80 can be
seated on the vessel port 92 of another vessel holder such as 38. The interior
surface
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of the seated second vessel 80 can be processed via the vessel port 92 at the
first
processing station or device such as 24. The vessel holder such as 38 and
seated
second vessel 80 can be transported from the first processing station or
device 24 to
the second processing station or device such as 26. The seated second vessel
80 can
be processed via the vessel port 92 by the second processing station or device
26.
Transporting Processing Devices To Vessel Holders or vice versa.
[446] III.B. Or, the processing stations can more broadly be processing
devices,
and either the vessel holders can be conveyed relative to the processing
devices, the
processing devices can be conveyed relative to the vessel holders, or some of
each
arrangement can be provided in a given system. In still another arrangement,
the
vessel holders can be conveyed to one or more stations, and more than one
processing
device can be deployed at or near at least one of the stations. Thus, there is
not
necessarily a one-to-one correspondence between the processing devices and
processing stations.
[447] III.B. A method including several parts is contemplated for
processing a
vessel. A first processing device such as the probe 108 (FIG. 2) and a second
processing device such as a light source 170 (FIG. 10) are provided for
processing
vessels such as 80. A vessel 80 is provided having an opening 82 and a wall 86
defining an interior surface 88. A vessel holder 50 is provided comprising a
vessel port
92. The opening 82 of the vessel 80 is seated on the vessel port 92.
[448] III.B. The first processing device such as the probe 108 is moved
into
operative engagement with the vessel holder 50, or vice versa. The interior
surface 88
of the sealed vessel 80 is processed via the vessel port 92 using the first
processing
device or probe 108.
[449] III.B. The second processing device such as 170 (FIG. 10) is then
moved into
operative engagement with the vessel holder 50, or vice versa. The interior
surface 88
of the seated vessel 80 is processed via the vessel port 92 using the second
processing
device such as the light source 170.
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[450] III.B. Optionally, any number of additional processing steps can be
provided.
For example, a third processing device 34 can be provided for processing
vessels so.
The third processing device 34 can be moved into operative engagement with the
vessel holder 50, or vice versa. The interior surface of the seated vessel 80
can be
processed via the vessel port 92 using the third processing device 34.
[451] III.B. In another method for processing a vessel, the vessel 80 can
be
provided having an opening 82 and a wall 86 defining an interior surface 88. A
vessel
holder such as 50 comprising a vessel port 92 can be provided. The opening 82
of the
vessel 80 can be seated on the vessel port 92. The interior surface 88 of the
seated
vessel 80 can be processed via me vessel port 92 at by toe first processing
device,
which can be, as one example, the barrier or other type of coating device 28
shown in
FIG. 2. The vessel holder 50 and seated vessel 80 are transported from the
first
processing device 28 to the second processing device, for example the
processing
device 34 snown in FIGS. 1 and to. Tne interior surface 88 Of the seated
vessel 80 can
be then processed via the vessel port 92 by the second processing device such
as 34.
Using Gripper For Transporting Tube To and From Coating Station
[452] 111Ø Yet another embodiment is a method of PECVD treatment of a
first
vessel, including several steps. A first vessel is provided having an open
end, a closed
end, and an interior surface. At least a first gripper is configured for
selectively holding
and releasing the closed end of the first vessel. The closed end of the first
vessel is
gripped with the first gripper and, using the first gripper, transported to
the vicinity of a
vessel holder configured for sealing to the open end of the first vessel. The
first gripper
is then used to axially advance the first vessel and seat its open end on the
vessel
holder, establishing sealed communication between the vessel holder and the
interior of
the first vessel.
[453] 111Ø At least one gaseous reactant is introduced within the first
vessel
through the vessel holder. Plasma is formed within the first vessel under
conditions
effective to form a reaction product of the reactant on the interior surface
of the first
vessel.
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[454] 111Ø The first vessel is then unseated from the vessel holder and,
using the
first gripper or another gripper, the first vessel is axially transported away
from the
vessel holder. The first vessel is then released from the gripper used to
axially transport
it away from the vessel holder.
[455] III.C. Referring again to FIGS. 16 and 49, a series conveyor 538 can
be used
to support and transport multiple grippers such as 204 through the apparatus
and
process as described here. The grippers 204 are operatively connected to the
series
conveyor 538 and configured for successively transporting a series of at least
two
vessels 80 to the vicinity of the vessel holder 48 and carrying out the other
steps of the
cleaning method as described here.
IV. PECVD APPARATUS FOR MAKING VESSELS
!V.A. PECVD Apparatus
Including Vessel Holder, Internal Electrode, Vessel
As Reaction Chamber
[456] IV.A. Another embodiment is a PECVD apparatus including a vessel
holder,
an inner electrode, an outer electrode, and a power supply. A vessel seated on
the
vessel holder defines a plasma reaction chamber: which optionally can be a
vacuum
chamber. Optionally, a source of vacuum, a reactant gas source, a gas feed or
a
combination of two or more of these can be supplied. Optionally, a gas drain,
not
necessarily including a source of vacuum, is provided to transfer gas to or
from the
interior of a vessel seated on the port to define a closed chamber.
[457] IV.A. The PECVD
apparatus can be used for atmospheric-pressure
PECVD, in which case the plasma reaction chamber does not need to function as
a
vacuum chamber.
[458] IV.A. In the embodiment illustrated in FIG. 2, the vessel holder 50
comprises
a gas inlet port 104 for conveying a gas into a vessel seated on the vessel
port. The gas
inlet port 104 has a sliding seal provided by at least one 0-ring 106, or two
0-rings in
series, or three 0-rings in series, which can seat against a cylindrical probe
108 when
the probe 108 is inserted through the gas inlet port 104. The probe 108 can be
a gas
83
inlet conduit that extends to a gas delivery port at its distal end 110. The
distal end 110
of the illustrated embodiment can be inserted deep into the vessel 80 for
providing one
or more PECVD reactants and other process gases.
[459] IV.A. Optionally in the embodiment illustrated in FIG. 2, or more
generally in any
embodiment disclosed, such as the embodiments of FIGS. 1-5, 8, 9, 12-16, 18,
19,
21, 22,26-28, 33-35, 37-49, or 52-55, and as specifically disclosed in FIG.
55, a plasma
screen 610 can be provided to confine the plasma formed within the vessel 80
generally
to the volume above the plasma screen 610. The plasma screen 610 is a
conductive,
porous material, several examples of which are steel wool, porous sintered
metal or
ceramic material coated with conductive material, or a foraminous plate or
disk made of
metal (for example brass) or other conductive material. An example is a pair
of metal
disks having central holes sized to pass the gas inlet 108 and having 0.02-
inch (0.5 mm)
diameter holes spaced 0.04 inches (1 mm) apart, center-to-center, the holes
providing
22% open area as a proportion of the surface area of the disk.
[460] IV.A. The plasma screen 610, particularly for embodiments in which the
probe
108 also functions as an counter electrode, can make intimate electrical
contact with the
gas inlet 108 at or near the opening 82 of the tube, syringe barrel, or other
vessel 80
being processed. Alternatively, the plasma screen 61U can be grounded,
illustratively
having a common potential with the gas inlet 108. The plasma screen 610
reduces or
eliminates the plasma in the vessel holder 50 and its internal passages and
connections,
for example the vacuum duct 94, the gas inlet port 104, the vicinity of the 0-
ring 106, the
vacuum port 96, the 0-ring 102, and other apparatus adjacent to the gas inlet
108. At
the same time, the porosity of the plasma screen allows process gases, air,
and the like
to flow out of the vessel 80 into the vacuum port 96 and downstream apparatus.
[461] !V.A. in the coating station 26 illustrated in FIG. 3, the vessel holder
112 comprises
a composite gas inlet port and vacuum port 96 communicating with the vessel
port 92,
respectively for conveying a gas into a vessel 80 seated on the vessel port 92
(via the
probe 108) and withdrawing a gas from a vessel seated on the vessel port 92
(via the
vacuum source 98). In this embodiment, the gas inlet probe 108 and
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vacuum source 98 can be provided as a composite probe. The two probes can be
advanced as a unit or separately, as desired. This arrangement eliminates the
need for
a third seal 106 and allows the use of butt seals throughout. A butt seal
allows the
application of an axial force, for example by drawing a vacuum within the
vessel 80, to
positively seat the vessel 80 and vacuum source 98 by deforming the 0-rings,
tending
to close any gap left by the presence of any irregularities in the sealing
surface on either
side of the 0-ring. In the embodiment of FIG. 3, the axial forces applied by
the vessel
80 and vacuum source 98 on the vessel holder 112 are in opposition, tending to
hold
the vessel 80 and the vessel holder 112 together and maintain the respective
butt seals.
[462] !V.A. FIG. 13 is a view similar to FIG. 2 of a vessel holder 48 in a
coating
station according to yet another embodiment of the disclosure, in which the
vessel 80
can be seated on the vessel holder 48 at the process station. This can be used
to
process a vessel 80 that does not travel with a vessel holder such as 48, or
it can be
used in a barrier or other type of coating station 28 that first seats the
vessel 80 in a
vessel holder such as 48 before the seated vessel 80 is conveyed to other
apparatus by
the system 20.
[463] IV.A. FIG. 13 shows a cylindrical electrode 160 suited for
frequencies from
50 Hz to 1 GHz, as an alternative to the U-shaped electrode of FIGS. 2 and 9.
The
vessel holder (or the electrode) can be moved into place prior to activation
by either
moving the electrode down or the vessel holder up. Or, the movement of the
vessel
holder and electrode in the vertical plane can be circumvented by creating an
electrode
160 constructed like a clamshell (two half cylinders that can come together
from
opposite sides when the vessel holder is in position and ready for
treatment/coating).
IV.A. Optionally, at the coating station 28 the vacuum source 98 makes a seal
with the
puck or vessel holder 50 that can be maintained during movement of the vessel
holder,
if the process is a continuous process in which the tube is moved through the
coating
station such as 28 while a vacuum is drawn and gas is introduced through the
probe
108. Or, a stationary process can be employed in which the puck or vessel
holder 50 is
moved into a stationary position, at which time the probe 108 is pushed up
into the
device and then the pump or vacuum source 98 is coupled at the vacuum port 96
and
activated to create a vacuum. Once the probe 108 is in place and the vacuum
created,
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plasma can be established inside of the tube or vessel 80 with an external
fixed
electrode 160 that is independent of the puck or vessel holder 50 and the tube
or other
vessel 80.
[464] IV.A. FIG. 53 shows additional optional details of the coating
station 28 that
are usable, for example, with the embodiments of FIGS. 1, 2, 3, 6-10, 12-16,
18: 19, 21,
22, 26-28, 30, 33-35, 37-44, and 52. The coating station 28 can also have a
main
vacuum valve 574 in its vacuum line 576 leading to the pressure sensor 152. A
manual
bypass valve 578 is provided in the bypass line 580. A vent valve 582 controls
flow at
the vent 404.
[465] IV.A. Flow out of the PECVD gas source 144 is controlled by a main
reactant
gas valve 584 regulating flow through the main reactant feed line 586. One
component
of the gas source 144 is the organosilicon liquid reservoir 588. The contents
of the
reservoir 588 are drawn through the organosilicon capillary line 590, which is
provided
at a suitable length to provide the desired flow rate. Flow of organosilicon
vapor is
controlled by the organosilicon shut-off valve 592. Pressure is applied to the
headspace
614 of the liquid reservoir 588, for example a pressure in the range of 0-15
psi (0 to 78
cm. Hg), from a pressure source 616 such as pressurized air connected to the
headspace 614 by a pressure line 618 to establish repeatable organosilicon
liquid
delivery that is not dependent on atmospheric pressure (and the fluctuations
therein).
The reservoir 588 is sealed and the capillary connection 620 is at the bottom
of the
reservoir 588 to ensure that only neat organosilicon liquid (not the
pressurized gas from
the headspace 614) flows through the capillary tube 590. The organosilicon
liquid
optionally can be heated above ambient temperature, if necessary or desirable
to cause
the organosilicon liquid to evaporate, forming an organosilicon vapor. Oxygen
is
provided from the oxygen tank 594 via an oxygen feed line 596 controlled by a
mass
flow controller 598 and provided with an oxygen shut-off valve 600.
[466] IV.A. In the embodiment of FIG. 7, the station or device 26 can
include a
vacuum source 98 adapted for seating on the vacuum port 96, a side channel 134
connected to the probe 108, or both (as illustrated). In the illustrated
embodiment, the
side channel 134 includes a shut-off valve 136 that regulates flow between a
probe port
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138 and a vacuum port 140. In the illustrated embodiment, the selection valve
136 has
at least two states: an evacuation state in which the ports 138 and 140 are
connected,
providing two parallel paths for gas flow (thus increasing the rate of pumping
or
decreasing the pumping effort) and a disconnection state in which the ports
138 and
140 are isolated. Optionally, the selectIon valve 136 can have a third port,
such as a
PECVD gas inlet port 142, for introducing PECVD reactive and process gases
from a
gas source 144. This expedient allows the same vacuum supply and probe 108 to
be
used both for leak or permeation testing and for applying the barrier or other
type of
coating.
[467] !V.A. In tne illustrated embodiments, the vacuum line such as 146 to
the
vacuum source 98 can also include a shut-off valve 148. The shut-off valves
136 and
148 can be closed when the probe 108 and vacuum source 98 are not connected to
a
vessel holder such as 44 so the side channel 134 and the vacuum line 146 do
not need
to be evacuated on the side ot me valves 136 and 148 away from toe vessel 80
when
moved from one vessel holder 44 to another. To facilitate removing the probe
108
axially from the gas inlet port 104, a flexible line 150 can be provided to
allow axial
movement of the probe 108 independent of the position of the vacuum line 146
relative
to the putt 96.
[468] IV.A. FIG. 7 also shows another optional feature usable with any
embodiment ¨ a vent 404 to ambient air controlled by a valve 406. The valve
406 can
be opened to break the vacuum quickly after processing the vessel 80, whether
to
release the vessel 80 from the vessel holder 44, to release the vessel holder
44 at the
vacuum port 96 from the source of vacuum 98, or optionally both.
[469] IV.A. In the illustrated embodiment (still referring to FIG. 7), the
probe 108
can also be connected to a pressure gauge 152 and can communicate with the
interior
154 of the vessel 80, allowing the pressure within the vessel 80 to be
measured.
[470] IV.A. In the apparatus of FIG. 1, the vessel coating station 28 can
be, for
example, a PECVD apparatus as further described below, operated under suitable
conditions to deposit a SiOx barrier or other type of coating 90 on the
interior surface 88
of a vessel 80, as shown in FIG. 2.
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[471] IV.A. Referring especially to FIGS. 1 and 2, the processing station
28 can
include an electrode 160 fed by a radio frequency power supply 162 for
providing an
electric field for generating plasma within the vessel 80 during processing.
In this
embodiment, the probe 108 is also electrically conductive and is grounded,
thus
providing a counter-electrode within the vessel 80. Alternatively, in any
embodiment the
outer electrode 160 can be grounded and the probe 108 directly connected to
the power
supply 162.
[472] IV.A. In the embodiment of FIG. 2, the outer electrode 160 can either
be
generally cylindrical as illustrated in FIGS 2 and 8 or a generally U-shaped
elongated
channel as illustrated in FIGS. 2 and 9 (FIGS. 8 and 9 being alternative
embodiments of
the section taken along section line A¨A of FIG. 2). Each illustrated
embodiment has
one or more sidewalls, such as 164 and 166, and optionally a top end 168, all
disposed
about the vessel 80 in close proximity.
[473] IV.A., IV.B. FIGS. 12 to 19 show other variants of the vessel coating
station
or device 28 as previously described. Any one or more of these variants can be
substituted for the vessel coating station or device 28 shown in FIG. 1-5.
[474] IV.A. FIG. 12 shows an alternative electrode system that can be used
(in the
same manner as discussed above using the same vessel holder and gas inlet) at
frequencies above 1 GHz. At these frequencies the electrical energy from the
power
supply can be transferred to the interior of the tube through one or more
waveguides
that are connected to a cavity that either absorbs the energy or resonates the
energy.
Resonating the energy allows it to couple to the gas. Different cavities can
be provided
for use with different frequencies and vessels such as 80, since the vessel 80
will
interact with the cavity altering its resonation pont, creating plasma for
coating and/or
treatment.
[475] IV.A. FIG. 12 shows that the coating station 28 can include a
microwave
power supply 190 directing microwaves via a waveguide 192 to a microwave
cavity 194
at least partially surrounding the vessel 80 within which plasma can be to be
generated.
The microwave cavity 194 can be tuned, in relation to the frequency of the
microwaves
and the partial pressures and selection of gases, to absorb microwaves and
couple to
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the plasma-generating gas. In FIG. 13, as well as any of the illustrated
embodiments a
small gap 196 can be left between the vessel 80 and the cavity 194 (or
electrode,
detector, or other surrounding structure) to avoid scratching or otherwise
damaging the
vessel 80. Also in FIG. 13, the microwave cavity 194 has a flat end wall 198,
so the gap
196 is not uniform in width, particularly opposite the circular edge of the
end wall 198.
Optionally, the end 198 can be curved to provide a substantially uniform gap
196.IV.A.
FIG. 44 is a view similar to FIG. 2 of an alternative gas delivery tube/inner
electrode 470
usable, for example with the embodiments of FIGS. 1, 2, 3, 8,9, 12-16, 18-19,
21-22,
33, 37-43, 46-49, and 52-54. As shown in FIG. 44, the distal portion 472 of
the inner
electrode 470 comprises an elongated porous side wall 474 enclosing an
internal
passage 476 within the inner electrode. The internal passage 476 is connected
to the
gas feed 144 by the proximal portion 478 of the inner electrode 470 extending
outside
the vessel 80. The distal end 480 of the inner electrode 470 can also
optionally be
porous. The porosity of the porous side wall 474 and, if present, the porous
distal end
480 allow at least a portion of the reactant gas fed from the gas feed 144 to
escape
laterally from the passage 476 to supply reactant gas to the adjacent portion
of the
interior surface 88 of the vessel 80. In this embodiment, the porous portion
of the
porous side well 474 extends the entire length of the inner plAntrode 470
within the
vessel 80, although the porous portion could be less extensive, running only a
portion of
the length of the inner electrode 470. As indicated elsewhere in this
specification, the
inner electrode 470 could also be longer or shorter, relative to the length of
the vessel
80, than is shown in FIG. 44, and the porous portion can be continuous or
discontinuous.
[476] IV.A. The outer diameter of the inner electrode 470 can be at least
50% as
great, or at least 60% as great, or at least 70% as great, or at least 80% as
great, or at
least 90% as great, or at least 95% as great as the laterally adjacent inner
diameter of
the vessel. Employing a larger-diameter inner electrode 470, in relation to
the inner
diameter of the vessel 80, particularly if the electrode 470 is concentric
with the vessel
80, reduces the distance between the exterior of the inner electrode 470 and
the
adjacent interior surface 88 of the vessel 80, confining the plasma to a
smaller region
within which it can be more uniform. Employing a larger-diameter inner
electrode 470
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also provides more uniform distribution of the reactant gas and/or carrier gas
along the
interior surface 80, as fresh gases are introduced to the plasma at closely
spaced points
along the length of the interior surface 88, very close to the site of initial
reaction, as
opposed to flowing from a single point relative to the interior surface 88 to
form.
[477] IV.A. In one contemplated arrangement, shown in full lines, the power
supply
162 has one power connection to the electrode 200, which can be at any point
along the
electrode 200, and the probe 108 can be grounded. In this configuration a
capacitive
load can be used to generate the plasma within the vessel 80. In another
contemplated
arrangement, shown in phantom lines (and eliminating the connections shown in
full
lines), the respective leads of Me power supply 162 are connected to tine
respective
ends of the coil 200, which for convenience can be again referred to as an
"electrode" in
this specification. In this configuration, an inductive load can be used to
generate the
plasma within the vessel 80. A combination of inductive and capacitive loads
can also
be used, in an alternative embodiment.
[478] IV.A. FIGS. 46-48 show an array of two or more gas delivery tubes
such as
108 (also shown in FIG. 2), 510, and 512, which are also inner electrodes. The
array
can be linear or a carousel. A carousel array allows the electrodes to be
reused
periodically.
[479] IV.A. FIGS. 46-48 also show an inner electrode extender and retractor
514
for inserting and removing the gas delivery tubes / inner electrodes 108, 510,
and 512
into and from one or more vessel holders such as 50 or 48. These features are
optional
expedients for using the gas delivery tubes.
[480] IV.A. In the illustrated embodiment, referring to FIGS. 46-48 as well
as 53,
the inner electrodes 108, 510, and 512 are respectively connected by flexible
hoses
516,518, and 520 to a common gas supply 144, via shut-off valves 522,524, and
526.
(The flexible hoses are foreshortened in FIGS. 46-48 by omitting the slack
portions).
Referring briefly to FIG. 56, the flexible hoses 516, 518, and 520
alternatively can be
connected to independent gas sources 144. A mechanism 514 is provided to
extend
and retract an inner electrode such as 108. The inner electrode extender and
retractor
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is configured for moving an inner electrode among a fully advanced position,
an
intermediate position, and a retracted position with respect to the vessel
holder.
[481] IV.A. In FIGS. 46 and 56, the inner electrode 108 is extended to its
operative
position within the vessel holder 50 and vessel 80, and its shut-off valve 522
is open.
Also in FIG. 46, the idle inner electrodes 510 and 512 are retracted and their
shut-off
valves 524 and 526 are closed. In the illustrated embodiment, one or more of
the idle
inner electrodes 510 and 512 are disposed within an electrode cleaning device
or
station 528. One or more electrodes can be cleaned and others replaced within
the
station 528, optionally. The cleaning operations can involve chemical reaction
or
solvent treatment to remove deposits, milling to physically remove deposits,
or plasma
treatment to essentially burn away accumulated deposits, as non-limiting
examples.
[482] IV.A. In FIG. 47, the idle inner electrodes 510 and 512 are as
before, while
the working inner electrode 108 has been retracted out of the vessel 80, with
its distal
end remaining within the vessel holder 50, and its valve 522 has been closed.
In this
condition, the vessel 80 can be removed and a new vessel seated on the vessel
holder
50 without any danger of touching the electrode 108 with the vessels 80 being
removed
and replaced. After the vessel 80 is replaced, the inner electrode 108 can be
advanced
to the position of FIGS. 46 AND 56 and the shut-off valve 522 can be reopened
to
commence coating the new vessel 80 using the same inner electrode 108 as
before.
Thus, in an arrangement in which a series of the vessels 80 are seated on and
removed
from the vessel holder 50, the inner electrode 108 can be extended and
partially
retracted numerous times, as the vessel 80 is installed or removed from the
vessel
holder 50 at the station where the inner electrode 108 is in use
[483] IV.A. In FIG. 48, the vessel holder 50 and its vessel 80 have been
replaced
with a new vessel holder 48 and another vessel 80. Referring to FIG. 1, in
this type of
embodiment each vessel 80 remains on its vessel holder such as 50 or 48 and an
inner
electrode such as 108 is inserted into each vessel as its vessel holder
reaches the
coating station.
[484] IV.A. Additionally in FIG. 48, the inner electrodes 108, 510, and 512
are all
fully retracted, and the array of inner electrodes 108, 510, and 512 has been
moved to
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the right relative to the vessel holder 48 and electrode cleaning station 528,
compared
to the positions of each in FIG. 47, so the inner electrode 108 has been moved
out of
position and the inner electrode 510 has been moved into position with respect
to the
vessel holder 48.
[485] IV.A. It should be understood that the movement of the array of inner
electrodes can be independent of the movement of the vessel holders. They can
be
roved together or independently, to simultaneously or independently switch to
a new
vessel holder and/or a new inner electrode.
[486] IV.A. FIGS. 46-48 show an array of two or more gas delivery tubes
such as
108 (also shown in FIG. 2), 510, and 512, which are also inner electrodes. The
array
can be linear or a carousel. A carousel array allows the electrodes to be
reused
periodically.
[487] IV.A. FIGS. 46-48 also show an inner electrode extender and retractor
514
for inserting and removing the gas delivery tubes / inner electrodes 108, 510,
and 512
into and from one or more vessel holders such as 50 or 48. These features are
optional
expedients for using the gas delivery tubes.
[488] !V.A. In the illustrated embodiment, referring to FIGS. 46-48 as well
as 53,
the inner electrodes 108, 510, and 512 are respectively connected by flexible
hoses
516, 518, and 520 to a common gas supply 144, via shut-off valves 522, 524,
and 526.
(The flexible hoses are foreshortened in FIGS. 46-48 by omitting the slack
portions). A
mechanism 514 is provided to extend and retract an inner electrode such as
108. The
inner electrode extender and retractor is configured for moving an inner
electrode
among a fully advanced position, an intermediate position, and a retracted
position with
respect to the vessel holder.
[489] !V.A. In FIGS. 46 AND 55, the inner electrode 108 is extended to its
operative position within the vessel holder 50 and vessel 80, and its shut-off
valve 522
is open. Also in FIGS. 46 AND 56, the Idle inner electrodes 510 and 512 are
retracted
and their shut-off valves 524 and 526 are closed. In the illustrated
embodiment, the idle
inner electrodes 510 and 512 are disposed within an electrode cleaning or
station 528.
Some electrodes can be cleaned and others replaced within the station 528,
optionally.
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The cleaning operations can involve chemical reaction or solvent treatment to
remove
deposits, milling to physically remove deposits, or plasma treatment to
essentially burn
away accumulated deposits, as non-limiting examples.
[490] IV.A. In FIG. 47, the idle inner electrodes 510 and 512 are as
before, while
the working inner electrode 108 has been retracted out of the vessel 80, with
its distal
end remaining within the vessel holder 50, and its valve 522 has been closed.
In this
condition, the vessel 80 can be removed and a new vessel seated on the vessel
holder
50 without any danger of touching the electrode 108 with the vessels 80 being
removed
and replaced. After the vessel 80 is replaced, the inner electrode 108 can be
advanced
to the position of FIGS. 46 AND 56 and me snut-off valve 522 can be reopened
to
commence coating the new vessel 80 using the same inner electrode 108 as
before.
Thus, in an arrangement in which a series of the vessels 80 are seated on and
removed
from the vessel holder 50, the inner electrode 108 can be extended and
partially
retracted numerous times, as the vessel 80 is installed or removed from toe
vessel
holder 50 at the station where the inner electrode 108 is in use
[491] IV.A. In FIG. 48, the vessel holder 50 and its vessel 80 have been
replaced
with a new vessel holder 48 and another vessel 80. Referring to FIG. 1, in
this type of
embodiment each vessel 80 remains on its vessel holder such as 50 or 48 and an
inner
electrode such as 108 is inserted into each vessel as its vessel holder
reaches the
coating station.
[492] IV.A. Additionally in FIG. 48, the inner electrodes 108, 510, and 512
are all
fully retracted, and the array of inner electrodes 108, 510, and 512 has been
moved to
the right relative to the vessel holder 48 and electrode cleaning station 528,
compared
to the positions of each in FIG. 47, so the inner electrode 108 has been moved
out of
position and the inner electrode 510 has been moved into position with respect
to the
vessel holder 48.
[493] IV.A. It should be understood that the movement of the array of Inner
electrodes can be independent of the movement of the vessel holders. They can
be
roved together or independently, to simultaneously or independently switch to
a new
vessel holder and/or a new inner electrode.
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[494] IV.A. An array of two or more inner electrodes 108, 510, and 512 is
useful
because the individual combined gas delivery tubes / inner electrodes 108,
510, and
512 will in some instances tend to accumulate polymerized reactant gases or
some
other type of deposits as they are used to coat a series of vessels such as
80. The
deposits can accumulate to the point at which they detract from the coating
rate or
uniformity produced, which can be undesirable. To maintain a uniform process,
the
inner electrodes can be periodically removed from service, replaced or
cleaned, and a
new or cleaned electrode can be put into service. For example, going from FIG.
46 to
FIG. 48, the inner electrode 108 has been replaced with a fresh or
reconditioned inner
electrode 510, which is ready to be extended into the vessel holder 48 and the
vessel
80 to apply an interior coating to the new vessel.
[495] IV.A. Thus, an inner electrode drive 530 is operable in conjunction
with the
inner electrode extender and retractor 514 for removing a first inner
electrode 108 from
its extended position to its retracted position, substituting a second inner
electrode 510
for the first inner electrode 108, and advancing the second inner electrode
510 to its
extended position (analogous to FIGS. 46 and 56 except for the substitution of
electrode).
[496] IV.A. The array of gas delivery tubes of FIGS. 46-48 and inner
electrode
drive 530 are usable, for example, with the embodiments of FIGS. 1, 2,3, 8, 9,
12-16,
18-19, 21-22, 26-28, 33-35, 37-45, 49, and 52-54. The extending and retracting
mechanism 514 of FIGS. 46-48 is usable, for example, with the gas delivery
tube
embodiments of FIGS. 2, 3, 8, 9, 12-16, 18-19, 21-22, 26-28, 33-35, 37-45, 49,
and 52-
54, as well as with the probes of the vessel inspection apparatus of FIGS. 6
and 7.
[497] IV.A The electrode 160 shown in FIG. 2 can be shaped like a "U"
channel
with its length into the page and the puck or vessel holder 50 can move
through the
activated (powered) electrode during the treatment/coating process. Note that
since
external and internal electrodes are used, this apparatus can employ a
frequency
between 50 Hz and 1 GHz applied from a power supply 162 to the U channel
electrode
160. The probe 108 can be grounded to complete the electrical circuit,
allowing current
to flow through the low-pressure gas(es) inside of the vessel 80. The current
creates
94
plasma to allow the selective treatment and/or coating of the interior surface
88 of the
device.
[498] IV.A The electrode in FIG. 2 can also be powered by a pulsed power
supply.
Pulsing allows for depletion of reactive gases and then removal of by-products
prior to
activation and depletion (again) of the reactive gases. Pulsed power systems
are
typically characterized by their duty cycle which determines the amount of
time that the
electric field (and therefore the plasma) is present The power-on time is
relative to the
power-off time. For example a duty cycle of 10% can correspond to a power on
time of
10% of a cycle where the power was off for 90% of the time. As a specific
example, the
power might be on for 0.1 second and off for 1 second. Pulsed power systems
reduce
the effective power input for a given power supply 162, since the off-time
results in
increased processing time. When the system is pulsed, the resulting coating
can be very
pure (no by products or contaminants). Another result of pulsed systems is the
possibility
to achieve atomic layer deposition (ALD). In this case, the duty cycle can be
adjusted so
that the power-on time results in the deposition of a single layer of a
desired material. In
this manner, a single atomic layer is contemplated to be deposited in each
cycle. This
approach can result in highly pure and highly structured coatings (although at
the
tpmppraturps rpryiiirpri fnr rippnsitinn nn pnlymprie. surfanps, tpmppraturps
illiistrativply
are kept low (<100 C) and the low-temperature coatings can be amorphous).
[499] W.A. An alternative coating station is disclosed in FIG. 12, employing a
microwave
cavity instead of an outer electrode. The energy applied can be a microwave
frequency,
for example 2.45 GHz.
IV.B. PECVD Apparatus Using Gripper For Transporting Tube To and From
Coating Station
[500] IV.B. Another embodiment is an apparatus for PECVD treatment of a
vessel,
employing a gripper as previously described. FIGS. 15 and 16 show apparatus
generally
indicated at 202 for PECVD treatment of a first vessel 80 having an open end
82, a
closed end 84, and an interior space defined by the surface 88. This
embodiment
includes a vessel holder 48, at least a first gripper 204 (in this embodiment,
for example,
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a suction cup), a seat defined by the vessel port 92 on the vessel holder 48,
a reactant
supply 144, a plasma generator represented by the electrodes 108 and 160, a
vessel
release, which can be a vent valve such as 534. and either the same gripper
204 or a
second one (in effect, optionally a second gripper 204).
[501] IV.B. The first gripper 204, and as illustrated any of the grippers
204, is
configured for selectively holding and releasing the closed end 84 of a vessel
K. While
gripping the closed end 84 of the vessel, the first gripper 204 can transport
the vessel to
the vicinity of the vessel holder 48. In the illustrated embodiment, the
transportation
function is facilitated by a series conveyor 538 to which the grippers 204 are
attached in
a series.
[502] IV.B. The vessel holder 48 has previously been described in
connection with
other embodiments, and is configured for seating to the open end 82 of a
vessel 80.
The seat defined by the vessel port 92 has previously been described in
connection with
other embodiments, and is configured for establishing sealed communication
between
the vessel holder 48 and the interior space 88 of the first vessel, and in
this case any of
the vessels 80. The reactant supply 144 has previously been described in
connection
with other embodiments, and is operatively connected for introducing at least
one
gaseous reactant within the first vessel 80 through the vessel holder 48. The
plasma
generator defined by the electrodes 108 and 160 has previously been described
in
connection with other embodiments, and is configured for forming plasma within
the first
vessel under conditions effective to form a reaction product of the reactant
on the
interior surface of the first vessel.
[503] IV.B. The vessel release 534 or other expedients, such as introducing
within
the seated vessel 80 a reactant gas, a carrier gas, or an inexpensive gas such
as
compressed nitrogen or air, can be used for unseating the first vessel 80 from
the
vessel holder 48.
[504] IV.B. The grippers 204 are configured for axially transporting the
first vessel
80 away from the vessel holder 48 and then releasing the first vessel 80, as
by
releasing suction from between the gripper 48 and the vessel end 84.
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[505] IV.B. FIGS. 15 and 16 also show a method of PECVD treatment of a
first
vessel, comprising several steps. A first vessel 80 is provided having an open
end 32, a
closed end 84, and an interior surface 88. At least a first gripper 204 is
provided that is
configured for selectively holding and releasing the closed end 84 of the
first vessel 80.
The closed end 84 of the first vessel 80 is gripped with the first gripper 204
and thereby
transported to the vicinity of a vessel holder 48 configured for seating to
the open end of
the first vessel. In the embodiment of FIG. 16, two vessel holders 48 are
provided,
allowing the vessels 80 to be advanced and seated on the vessel holders 48 two
at a
time, thus doubling the effective production rate. Next, the first gripper 204
is used for
axially advancing the first vessel 80 and seating its open end 82 on the
vessel holder
48, establishing sealed communication between the vessel holder 48 and the
interior of
the first vessel. Next, at least one gaseous reactant is introduced within the
first vessel
through the vessel holder, optionally as explained for previous embodiments.
[506] IV.B. Continuing, plasma is formed within me first vessel under
conditions
effective to form a reaction product of the reactant on the interior surface
of the first
vessel, optionally as explained for previous embodiments. The first vessel is
unseated
from the vessel holder, optionally as explained for previous embodiments. The
first
gripper Ur another gripper ib used, optionally as explained for previous
embodiments, to
axially transport the first vessel away from the vessel holder. The first
vessel can then
be released from the gripper used to axially transport it away from the vessel
holder,
optionally as explained for previous embodiments.
[507] IV.B. Further optional steps that can be carried out according to
this method
include providing a reaction vessel different from the first vessel, the
reaction vessel
having an open end and an interior space, and seating the open end of the
reaction
vessel on the vessel holder, establishing sealed communication between the
vessel
holder and the interior space of the reaction vessel. A PECVD reactant conduit
can be
provided within the interior space. Plasma can be formed within the interior
space of
the reaction vessel under conditions effective to remove at least a portion of
a deposit of
a PECVD reaction product from the reactant conduit. These reaction conditions
have
been explained in connection with a previously described embodiment. The
reaction
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vessel then can be unseated from the vessel holder and transported away from
the
vessel holder.
[508] IV.B. Further optional steps that can be carried out according to any
embodiment of this 'method include:
= providing at least a second gripper;
= operatively connecting at least the first and second grippers to a series
conveyor;
= providing a second vessel having an open end, a closed end, and an
interior surface;
= providing a gripper configured for selectively holding and releasIng the
closed end of the second vessel;
= gripping the closed end of the second vessel with the gripper;
= using the gripper, transporting the second vessel to the vicinity of a
vessel
holder configured for seating to the open end of the second vessel;
= using the gripper, axially advancing the second vessel and seating its
open end on the vessel holder, establishing sealed communication
between the vessel holder and the interior of the second vessel;
= introducing at least one gaseous reactant within the second vessel
through the vessel holder;
= forming plasma within the second vessel under conditions effective to
form
a reaction product of the reactant on the interior surface of the second
vessel;
= unseating the second vessel from the vessel holder; and
= using the second gripper or another gripper, axially transporting the
second vessel away from the vessel holder; and
= releasing the second vessel from the gripper used to axially transport it
away from the vessel holder.
[509] IV.13. FIG. 16 is an example of using a suction cup type device to
hold the
end of a sample collection tube (in this example) that can move through a
production
line/system. The specific example shown here is one possible step (of many
possible
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steps as outlined above and below) of coating/treatment. The tube can move
into the
coating step/area and the tube can be lowered into the vessel holder and (in
this
example) the cylindrical electrode. The vessel holder, sample collection tube
and
suction cup can then move together to the next step where the electrode is
powered
and the treatment/coating take place. Any of the above types of electrodes can
be
utilized in this example.
[510] IV.B. Thus, FIGS. 15 and 16 show a vessel holder 48 in a coating
station 28
similar to FIG. 13, employing a vessel transport generally indicated as 202 to
move the
vessel 80 to and from the coating station 28. The vessel transport 202 can be
provided
with a grip 204, which in the illustrated transport 202 can be a suction cup.
An adhesive
pad, active vacuum source (with a pump to draw air from the grip, actively
creating a
vacuum) or other expedient can also be employed as the grip. The vessel
transport 202
can be used, for example, to lower the vessel 80 into a seated position in the
vessel
port 92 to position the vessel 80 for coating. The vessel transport 202 can
also Oe used
to lift the vessel 80 away from the vessel port 92 after processing at the
station 28 can
be complete. The vessel transport 202 also can be used to seat the vessel 80
before
the vessel 80 and vessel transport 48 are advanced together to a station. The
vessel
transport oar] also be used to urge the vessel so against its seat on the
vessel port 92.
Also, although FIG. 15 can be oriented to show vertical lifting of the vessel
80 from
above, an inverted orientation can be or contemplated in which the vessel
transport 202
is below the vessel BO and supports it from beneath.
[511] IV.B. FIG. 16 shows an embodiment of a method in which vessel
transports
202 such as suction cups 204 convey the vessels BO horizontally, as from one
station to
the next, as well as (or instead of) vertically into and out of a station such
as 28. The
vessels 80 can be lifted and transported in any orientation. FIG. 16 thus
represents a
method of PECVD treatment of a first vessel 80, comprising several steps.
[512] IV.B. In the embodiment of FIG. 13, the outer electrode 160 can be
generally
cylindrical with open ends, and can be stationary. The vessel 80 can be
advanced
through the outer electrode 160 until the opening 82 is seated on the vessel
port 96. In
this embodiment, the probe 108 optionally can be permanently molded or
otherwise
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secured into the gas inlet port 104, as opposed to a wiping seal allowing
relative motion
between the port 104 and the probe 108.
[513] IV.B. FIG. 14 shows an additional alternative for coupling electrical
energy
into the plasma at 50Hz - 1GHz. This can consist of a coil that can be either
lowered
into position or the vessel holder (with device) can be pushed up into
position. Coiled
electrodes are referred to as inductive coupling devices and can impart a
magnetic
component to the inside of the device where the plasma can be created.
[514] IV.B. A probe 108 can still be used as discussed In FIG. 2 and FIG.
13.
Other aspects of the vessel holder or vessel holder 48 discussed above can
remain the
same.
[515] IV.B. As FIG. 49 for example shows, a reaction vessel 532 different
from the
first vessel 80 can be provided, also having an open end 540 and an interior
space
defined by the interior surface 542. Like the vessels 80, the reaction vessel
532 can
have its open end 540 on the vessel holder 48 and establish sealed
communication
between the vessel holder 48 and the interior space 542 of the reaction
vessel.
[516] IV.B. FIG. 49 is a view similar to FIG. 16 showing a mechanism for
delivering
vessels 80 to be treated and a cleaning reactor 532 to a PECVD coating
apparatus. In
this embodiment, the inner electrode 108 optionally can be cleaned without
removing it
from the vessel holder 48.
[517] IV.B. FIG. 49 shows that the PECVD reactant conduit 108 as previously
described is positioned to be located within the interior space 542 of the
reaction vessel
532 when the reaction vessel is seated on the vessel holder 48 in place of a
vessel 80
which is provided for coating as described previously. FIG. 49 shows the
reactant
conduit 108 in this configuration, even though the conduit 108 has an exterior
portion,
as well as an interior distal end. It suffices for this purpose and the
present claims if the
reactant conduit 108 extends at least partially into the vessel 80 or 532.
[518] IV.B. The mechanism of FIG. 49 as illustrated is usable with the
embodiments of at least FIGS. 1 and 15-16, for example. The cleaning reactor
532 can
also be provided as a simple vessel seated and transported on a vessel holder
such as
100
48, in an alternative embodiment. In this configuration, the cleaning reactor
532 can be
used with the apparatus of at least FIGS. 1-3, 8, 9, 12-15, 18, 19, 21, 22, 26-
28, 33-35,
37-48, and 52-54, for example.
[519] IV.B. The plasma generator defined by the electrodes 108 and 160 is
configurable
for forming plasma within the interior space of the reaction vessel 532 under
conditions
effective to remove at least a portion of a deposit of a PECVD reaction
product from the
reactant conduit 108. It is contemplated above that the inner electrode and
gas source
108 can be a conductive tube, for example a metallic tube, and that the
reaction vessel
532 can be made of any suitable, illustratively heat-resistant material such
as ceramic,
quartz, glass or other materials that can withstand more heat than a
thermoplastic vessel.
The material of the reaction vessel 532 also can desirably be chemical or
plasma
resistant to the conditions used in the reaction vessel to remove deposits of
reaction
products. Optionally, the reaction vessel 532 can be made of electrically
conductive
material and itself serve as a special-purpose outer electrode for the purpose
of removing
deposits from the reactant conduit 108. As yet another alternative, the
reaction vessel
532 can be configured as a cap that seats on the outer electrode 160, in which
case the
outer electrode 160 would illustratively be seated on the vessel holder 48 to
define a
rinspri ripaning rpantirm nhamhpr
[520] IV.B. It is contemplated that the reaction conditions effective to
remove at least a
portion of a deposit of a PECVD reaction product from the reactant conduit 108
include
introduction of a substantial portion of an oxidizing reactant such as oxygen
or ozone
(either generated separately or by the plasma apparatus), a higher power level
than is
used for deposition of coatings, a longer cycle time than is used for
deposition of
coatings, or other expedients known for removing the type of unwanted deposit
encountered on the reaction conduit 108_ For another example, mechanical
milling can
also be used to remove unwanted deposits. Or, solvents or other agents can be
forced
through the reactant conduit 108 to clear obstructions. These conditions can
be far more
severe than what the vessels 80 to be coated can withstand, since the reaction
vessel
532 does not need to be suitable for the normal uses of the vessel 80.
Optionally,
however, a vessel 80 can be used as the reaction vessel, and if the deposit
101
Date Recue/Date Received 2020-08-17
removing conditions are too severe the vessel 80 employed as a reaction vessel
can be
discarded, in an alternative embodiment.
V. PECVD METHODS FOR MAKING VESSELS
V.1 Precursors for PECVD Coating
[521] The precursor for the PECVD coating of the present invention according
to its
embodiments is broadly defined as an organometallic precursor. An
organometallic
precursor is defined for all purposes in this specification as comprehending
compounds
of metal elements from Group III and/or Group IV of the Periodic Table having
organic
residues, e_g_ hydrocarbon, aminocarbon or oxycarbon residues_ Organometallic
compounds as presently defined include any precursor having organic moieties
bonded
to silicon or other Group III/ IV metal atoms directly, or optionally bonded
through oxygen
or nitrogen atoms. The relevant elements of Group III of the Periodic Table
are Boron,
Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum,
Aluminum
and Boron being illustrative. The relevant elements of Group IV of the
Periodic Table are
Silicon, Germanium, Tin, Lead, Titanium, Zirconium, Hafnium, and Thorium,
Silicon and
Tin being illustrative. Other volatile organic compounds may also be
contemplated.
However, organosilicon compounds are illustrative for performing the present
invention
according to its embodiments.
[522] An organosilicon precursor is illustrative, where an "organosilicon
precursor" is
aenneo tnrougnout tnis specification most Proaaiy as a compouna !laving at
least one or
the linkages:
or
¨NH¨Si¨C¨H
102
Date Recue/Date Received 2020-08-17
[523] The first structure immediately above is a tetravalent silicon atom
connected to
an oxygen atom and an organic carbon atom (an organic carbon atom being a
carbon
atom bonded to at least one hydrogen atom). The second structure immediately
above
is a tetravalent silicon atom connected to an -NH- linkage and an organic
carbon atom
(an organic carbon atom being a carbon atom bonded to at least one hydrogen
atom).
Illustratively, the organosilicon precursor is selected from the group
consisting of a linear
siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane,
a linear
silazane, a monocyclic silazane, a polycyclic silazane, a polysilsesquiazane,
and a
combination of any two or more of these precursors. Also contemplated as a
precursor,
though not within the two formulas immediately above, is an alkyl
trimethoxysilane.
If an oxygen-containing precursor (e_g_ a siloxane) is used, a representative
predicted
empirical formula resulting from PECVD under conditions forming a hydrophobic
or
lubricating coating would be SiwOxCyHz, where w is 1, x for this formula is
from about 0.5
to about 1, y is from about 2 to about 3, and z is from 6 to about 9, while a
representative
predicted empirical composition resulting trom PEGVD unaer conaitions torming
a barrier
coating would be SiOx, where x in this formula is from about 1.5 to about 2.9.
If a nitrogen-
containing precursor (e.g. a silazane) is used, the predicted composition
would be
Siw*Nlx*Cy*Hz*, i.e. in SiwOxCyHz according to the embodiments of the present
invention 0
is replaced by N and the indices are adapted to the higher valency of N as
compared to
0 (3 instead of 2). The latter adaptation will generally follow the ratio of
w, x, y and z in
a siloxane to the corresponding indices in its aza counterpart. In a
particular aspect of
the invention according to its embodiments. Siw*Nlx*Cy*H7* in which w*. x*.
y*. and z* are
defined the same as for the siloxane counterparts, but for an optional
deviation in the
number of hydrogens.
[524] One type of precursor starting material having the above empirical
formula is
a linear siloxane, for example a material having the following formula:
R+ Si-0 In Si R
103
Date Recue/Date Received 2020-08-17
in which each R is independently selected from alkyl, for example methyl,
ethyl, propyl,
isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others, and n is 1, 2,
3, 4, or greater,
illustratively two or greater. Several examples of contemplated linear
siloxanes are
= hexamethyldisiloxane (HMDSO),
= octamethyltrisiloxane,
= decamethyltetrasiloxane,
= dodecamethylpentasiloxane,
or combinations of two or more of these. The analogous silazanes in which ¨NH-
is
substituted for the oxygen atom in the above structure are also useful for
making
analogous coatings. Several examples of contemplated linear silazanes are
octamethyltrisilazane, decamethyltetrasilazane, or combinations of two or more
of these.
[525] V.C. Another type of precursor starting material is a monocyclic
siloxane, for
example a material having the following structural formula:
R
1
R
in which R is defined as for the linear structure and "a" is from 3 to about
10, or the
analogous monocyclic silazanes. Several examples of contemplated hetero-
substituted
and unoubstituted monocyclic eiloxanee and eilazanee include
= 1,3,5-trimethy1-1,3,5-tris(3,3,3-trifluoropropyl)methyl]cyclotrisiloxane
= 2,4,6,8-tetramethy1-2,4,6,8-tetravinylcyclotetrasiloxane,
= pentamethylcyclopentasiloxane,
= pentavinylpentamethylcyclopentasi loxane,
= hexamethylcyclotrisiloxane,
= hexaphenylcyclotrisiloxane,
= octamethylcyclotetrasiloxane (0 MCTS),
= octaphenylcyclotetrasiloxane,
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= decamethylcyclopentasiloxane
= dodecamethylcyclohexasiloxane,
= methyl (3 ,3,3-trifluoropropl)cyclosiloxane,
= Cyclic organosilazanes are also contemplated, such as
= Octamethylcycloietrasilazane,
= 1 ,3,5,7-tetraviny1-1 ,3 ,5,7-tetram ethyl cyclotetrasilazane
hexam ethylcyclotrisilazane,
= octamethylcyclotetrasilazane,
= decamethylcyclopentasilazane,
= dodecamethylcyclohexasilazane, or
combinations of any two or more of these.
[526] V.C. Another type of precursor starting material is a polycyclic
siloxane, for
example a material having one of the following structural formulas:
7
i -Y
in which Y can be oxygen or nitrogen, E is silicon, and Z is a hydrogen atom
or an
organic substituent, for example alkyl such as methyl, ethyl, propyl,
isopropyl, butyl,
isobutyl, t-butyl, vinyl, alkyne, or others. When each Y is oxygen, the
respective
structures, from left to right, are a silatrane, a silquasilatrane, and a
silproatrane. When
Y is nitrogen, the respective structures are an azasilatrane, an
azasilquasiatrane, and
an azasilproatrane.
[527] V.C. Another type of polycyclic siloxane precursor starting material
is a
polysilsesquioxane, with the empirical formula RSi01.5 and the structural
formula:
105
, B
; 1.11 lir
lip
I.L111-'"
i
51 a
in which each R is a hydrogen atom or an organic substituent, for example
alkyl such as
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or
others. Two
commercial materials of this sort are SST-eM01 poly(methylsilsesquioxane), in
which
each R is methyl, and SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which
90%
of the R groups are methyl, 10% are hydrogen atoms. This material is available
in a 10%
solution in tetrahydrofuran, for example. Combinations of two or more of these
are also
contemplated. Other examples of a contemplated precursor are methylsilatrane,
CAS
No. 2286-13-3, in which each Y is oxygen and z is methyl, metnyiazasuatrane,
SST-
eM01 poly(methylsilsesquioxane), in which each R optionally can be methyl, SST-
3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the R groups are
methyl
and 10% are hydrogen atoms, or a combination of any two or more of these.
[528] V.C. The analogous polysilsesquiazanes in which ¨NH- is substituted for
the
oxygen atom in the above structure are also useful for making analogous
coatings.
Examples of contemplated polysilsesquiazanes are a poly(methylsilsesquiazane),
in
wnicn eacn R is methyl, and a poiyovietnyi-Hyanaosusesquiazane, In wnicn 5o%
or tne
R groups are methyl, 10% are hydrogen atoms. Combinations of two or more of
these
are also contemplated.
[529] VC. One particularly contemplated precursor for the lubricity coating
according
to the embodiments of the present invention is a monocyclic siloxane, for
example is
octamethylcyclotetrasi loxane.
[530] One particularly contemplated precursor for the hydrophobic coating
according
to the embodiments of the present invention is a monocyclic siloxane, for
example is
octamethylcyclotetrasi loxane.
106
Date Recue/Date Received 2020-08-17
[531] One particularly contemplated precursor for the barrier coating
according to the
embodiments of the present invention is a linear siloxane, for example is HM
DSO.
[532] V.C. In any of the coating methods according to the embodiments of the
present
invention, the applying step optionally can be carried out by vaporizing the
precursor and
providing it in the vicinity of the substrate. E.g., OMCTS is usually
vaporized by heating
it to about 50 C before applying it to the PECVD apparatus.
V.2 General PECVD Method
[533] In the context of the present invention according to its embodiments,
the following
PECVD method is generally applied, which contains the following steps:
(a) providing a gaseous reactant comprising a precursor as defined herein,
illustratively an organosilicon precursor, and optionally 02 in the vicinity
of the
substrate surface; and
(b) generating a plasma from the gaseous reactant, thus forming a coating on
the
substrate surface by plasma enhanced chemical vapor deposition (PECVD).
[534] In said method, the coating characteristics are set by one or more of
the following
conditions: the plasma properties, the pressure under which the plasma is
applied, the
power applied to generate the plasma, the presence and relative amount of 02
in the
gaseous reactant, the plasma volume, and the organosilicon precursor.
Illustratively, the
coating characteristics are set by the presence and relative amount of 02 in
the gaseous
reactant and/or the power applied to generate the plasma.
[535] In all embodiments of the present invention, the plasma is in a
illustrative aspect a
non-hollow-cathode plasma.
[536] In a further illustrative aspect, the plasma is generated at reduced
pressure (as
compared to the ambient or atmospheric pressure). Illustratively, the reduced
pressure
is less than 300 mTorr, more illustratively less than 200 mTorr, even more
illustratively
less than 100 mTorr_
107
Date Recue/Date Received 2020-08-17
[537] The PECVD illustratively is performed by energizing the gaseous reactant
containing the precursor with electrodes powered at a frequency at microwave
or radio
frequency, and illustratively at a radio frequency. The radio frequency
illustrative to
perforrn an embodiment of the invention will also be addressed as "RF
frequency". A
typical radio frequency range for performing the present invention according
to its
embodiments is a frequency of from
kHz to less than 300 MHz, more illustratively of from 1 to 50 MHz, even more
illustratively of from 10 to 15 MHz. A frequency of 13.56 MHz is most
illustrative, this
being a government sanctioned frequency for conducting PECVD work.
[538] There are several intended advantages for using a RF power source versus
a
microwave source: Since RF operates a lower power, there is less heating of
the
substrate/vessel. Because the focus of the present invention according to its
embodiments is putting a plasma coating on plastic substrates, lower
processing
temperatures are desired to prevent melting/distortion of the substrate. To
prevent
substrate overheating when using microwave PECVD, the microwave PECVD is
applied
in short bursts, by pulsing the power. The power pulsing extends the cycle
time for the
coating, which is undesired in the present invention according to its
embodiments. The
higher frequency microwave may also cause offgassing of volatile substances
like
residual water, oligomers and other materials in the plastic substrate. This
offgassing
may interfere with the PECVD coating. A major concern with using microwave for
PECVD is delamination of the coating from the substrate. Delamination occurs
because
the microwaves change the surtace ot the substrate prior to depositing the
coating layer.
To mitigate the possibility of delamination, interface coating layers have
been developed
for microwave PECVD to achieve good bonding between the coating and the
substrate.
No such interface coating layer is needed with RF PECVD as there is no risk of
delamination. Finally, the lubricity coating and hydrophobic coating according
to the
present invention according to its embodiments are applied using lower power.
RF power
operates at lower power and provides more control over the PECVD process than
microwave power_ Nonetheless, microwave power, though less illustrative, is
usable
under suitable process conditions.
[539] Furthermore, for all PECVD methods described herein, there is a specific
correlation between the power (in Watts) used to generate the plasma and the
volume
of the lumen wherein the plasma is generated. Typically, said lumen is the
lumen of a
108
Date Recue/Date Received 2020-08-17
vessel coated according to the embodiments of the present invention. The RF
power
should scale with the volume of the vessel if the same electrode system is
employed.
Once the composition of a gaseous reactant, for example the ratio of the
precursor to
02, and all other parameters of the PECVD coating method but the power have
been
set, they will typically not change when the geometry of a vessel is
maintained and only
its volume is varied. In this case, the power will be directly proportional to
the volume.
Thus, starting from the power to volume ratios provided by present
description, the power
which has to be applied in order to achieve the same or a similar coating in a
vessel of
same geometry, but different size, can easily be found. The influence of the
vessel
geometry on the power to be applied is illustrated by the results of the
Examples for
tubes in comparison to the Examples for syringe barrels_
[540] For any coating of the present invention according to its embodiments,
the plasma
is generated with electrodes powered with sufficient power to form a coating
on the
substrate surface. For a lubricity coating or hydrophobic coating, in the
method according
to an embodiment of the invention the plasma is illustratively generated (i)
with
electrodes supplied with an electric power of from 0.1 to 25W, illustratively
from 1 to 22
W, more illustratively from 3 to 17 W, even more illustratively of from 5 to
14 W, most
illustratively of from 7 to 11 W, for example of 8 W: and/or (ii) wherein the
ratio of the
electrode power to the plasma volume is less than 10 W/ml, illustratively is
from 5 W/ml
to 0.1 W/ml, more illustratively is from 4 W/ml to 0.1 W/ml, most
illustratively from 2 W/ml
to 0.2 W/ml. For a barrier coating or SiOx coating, the plasma is
illustratively generated
(i) witn eiectroaes suppiiea witn an electric power or rrom o to 500 W,
iiiustrativeiy rrom
20 to 400 W, more illustratively from 35 to 350 W, even more illustratively of
from 44 to
300 W, most illustratively of from 44 to 70 W; and/or (ii) the ratio of the
electrode power
to the plasma volume is equal or more than 5 W/ml, illustratively is from 6
W/ml to 150
W/ml, more illustratively is from 7 W/ml to 100 W/ml, most illustratively from
7 W/ml to
20 W/ml.
[541] The vessel geometry may also influence the choice of the gas inlet used
for the
PECVD coating. In a particular aspect, a syringe may be coated with an open
tube inlet,
and a tube may be coated with a gas inlet having small holes which is extended
into the
tube.
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[542] The power (in Watts) used for PECVD also has an influence on the coating
properties. Typically, an increase of the power will increase the barrier
properties of the
coating, and a decrease of the power will increase the lubricity and
hydrophobicity of the
coating. E.g., for a coating on the inner wall of syringe barrel having a
volume of about 3
ml, a power of less than 30 W will lead to a coating which is predominantly a
barrier
coating, while a power of more than 30 W will lead to a coating which is
predominantly a
lubricity coating (see Examples).
[543] A further parameter determining the coating properties is the ratio of
02 (or another
oxidizing agent) to the precursor (e.g. organosilicon precursor) in the
gaseous reactant
used for generating the plasma. Typically, an increase of the 02 content in
the gaseous
reactant will increase the barrier properties of the coating, and a decrease
of the 02
content will increase the lubricity and hydrophobicity of the coating. Thus,
the PECVD
coating method of present invention according to its embodiments can be used
for setting
the lubricity properties of a coating, the hydrophobicity properties of a
coating, and the
barrier properties of a coating prepared by said method.
[544] If a lubricity coating is desired, then 02 is illustratively present in
a volume- volume
ratio to the gaseous reactant of from 0:1 to 5:1, more illustratively from 0:1
to 1:1, even
more illustratively train u:i to or even from
u:i to 0.1:1. essentially no oxygen is
present in the gaseous reactant. Thus, the gaseous reactant should comprise
less than
1 vol% 02, more particularly less than 0.5 vol% 02, and most illustratively is
02-free.The
same applies to a hydrophobic coating.
[545] If, on the other hand, a barrier or SiOx coating is desired, then the
02i5 illustratively
present in a volume:volume ratio to the gaseous reactant of from 1 : 1 to 100
: 1 in relation to the silicon containing precursor, illustratively in a ratio
of from 5: 1 to 30
: 1, more illustratively in a ratio of from 10 : 1 to 20 : 1, even more
illustratively in a ratio
of 15: 1.
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V.A. PECVD to apply
SiOx barrier coating, using plasma that is substantially
free of hollow cathode plasma
[546] V.A. A specific embodiment is a method of applying a barrier coating of
SiOx,
defined in this specification (unless otherwise specified in a particular
instance) as a
coating containing silicon, oxygen, and optionally other elements, in which x,
the ratio of
oxygen to silicon atoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6,
or about 2.
These alternative definitions of x apply to any use of the term SiOx in this
specification.
The barrier coating is applied to the interior of a vessel, for example a
sample collection
tube, a syringe barrel, or another type of vessel. The method includes several
steps.
[547] V.A. A vessel wall is provided, as is a reaction mixture comprising
plasma forming
gas, i.e. an organosilicon compound gas, optionally an oxidizing gas, and
optionally a
hydrocarbon gas.
[548] V.A. Plasma is formed in the reaction mixture that is substantially free
of hollow
cathode plasma_ The vessel wall is contacted with the reaction mixture, and
the coating
of SiOxis deposited on at least a portion of the vessel wall.
[549] V.A. In certain embodiments, the generation of a uniform plasma
throughout the
portion of the vessel to be coated is illustrative, as it has been found in
certain instances
to generate an SiOx coating providing a better barrier against oxygen. Uniform
plasma
means regular plasma that does not include a substantial amount of hollow
cathode
plasma (which has a higher emission intensity than regular plasma and is
manifested as
a localized area of higher inten_sity interrupting thp more uniform inten_sity
of the regular
plasma).
[550] V.A. The hollow cathode effect is generated by a pair of conductive
surfaces
opposing each other with the same negative potential with respect to a common
anode.
If the spacing is made (depending on the pressure and gas type) such that the
space
charge sheaths overlap, electrons start to oscillate between the reflecting
potentials of
the opposite wall sheaths leading to multiple collisions as the electrons are
accelerated
by the potential gradient across the sheath region_ The electrons are confined
in the
space charge sheath overlap which results in very high ionization and high ion
density
plasmas. This phenomenon is described as the hollow cathode effect. Those
skilled in
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the art are able to vary the processing conditions, such as the power level
and the feed
rates or pressure of the gases, to form uniform plasma throughout or to form
plasma
including various degrees of hollow cathode plasma.
[551] V.A. In an alternate method, using for example the apparatus of FIG.
12
previously described, microwave energy can be used to generate the plasma in a
PECVD process. The processing conditions may be different, however, as
microwave
energy applied to a thermoplastic vessel will excite (vibrate) water
molecules. Since
there is a small amount of water in all plastic materials, the microwaves will
heat the
plastic. As the plastic heats, the large driving force created by the vacuum
inside of the
device relative to atmospheric pressure outside the device will pull free or
easily desorb
materials to the interior surface 88 where they will either become volatile or
will be
weakly bound to the surface. The weakly bound materials will then create an
interface
that can hinder subsequent coatings (deposited from the plasma) from adhering
to the
plastic interior surface 88 of the device.
[552] V.A. As one way to negate this coating hindering effect, a coating
can be
deposited at very low power (in the example above 5 to 20 Watts at 2.45 G Hz)
creating
a cap onto which subsequent coatings can adhere. This results in a two-step
coating
process (and two coating layers). In the example above, the initial gas flows
(for the
capping layer) can be changed to 2 sccm ("standard cubic centimeters per
minute")
HIVIDSO and 20 sccm oxygen with a process power of 5 to 20 Watts for
approximately
2-10 seconds. Then the gases can be adjusted to the flows in the example above
and
the power level increased to, e.g., 35 to 50 W, so that an SIC). coating, in
which x in this
formula is from about 1.5 to about 2.9, alternatively from about 1.5 to about
2.6,
alternatively about 2, can be deposited. Note that the capping layer might
provide little
to no functionality in certain embodiments, except to stop materials from
migrating to the
vessel interior surface 88 during the higher power SiOx coating deposition.
Note also
that migration of easily desorbed materials in the device walls typically is
not an issue at
lower frequencies such as most of the RF range, since the lower frequencies do
not
excite (vibrate) molecular species.
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[553] V.A. As another way to negate the coating hindering effect described
above,
the vessel 80 can be dried to remove embedded water before applying microwave
energy. Desiccation or drying of the vessel 80 can be accomplished, for
example, by
thermally heating the vessel 80, as by using an electric heater or forced air
heating.
Desiccation or drying of the vessel 80 also can be accomplished by exposing
the
interior of the vessel 80, or gas contacting the interior of the vessel 80, to
a desiccant.
Other expedients for drying the vessel, such as vacuum drying, can also be
used.
These expedients can be carried out in one or more of the stations or devices
illustrated
or by a separate station or device.
[554] V.A. Additionally, the coating hindering effect described above can
be
addressed by selection or processing of the resin from which the vessels 80
are molded
to minimize the water content of the resin.
V.B. PECVD Coating Restricted Opening of Vessel (Syringe Capillary)
[555] V.B. FIGS. 26 and 27 show a method and apparatus generally indicated
at
290 for coating an inner surface 292 of a restricted opening 294 of a
generally tubular
vessel 250 to be processed, for example the restricted front opening 294 of a
syringe
barrel 250, by PECVD. The previously described process is modified by
connecting the
restricted opening 294 to a processing vessel 296 and optionally making
certain other
modifications.
F5561 V.B. The generally tubular vessel 250 to be processed includes an
outer
surface 298, an inner or interior surface 254 defining a lumen 300, a larger
opening 302
having an inner diameter, and a restricted opening 294 that is defined by an
inner
surface 292 and has an inner diameter smaller than the inner diameter of the
larger
opening 302.
[557] V.B. The processing vessel 296 has a lumen 304 and a processing
vessel
opening 306, which optionally is the only opening, although in other
embodiments a
second opening can be provided that optionally is closed off during
processing. The
processing vessel opening 306 is connected with the restricted opening 294 of
the
vessel 250 to be processed to establish communication between the lumen 300 of
the
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vessel 250 to be processed and the processing vessel lumen via the restricted
opening
294.
[558] V.B. At least a partial vacuum is drawn within the lumen 300 of the
vessel
250 to be processed and lumen 304 of the processing vessel 296. A PECVD
reactant
is flowed from the gas source 144 (see FIG. 7) through the first opening 302,
then
through the lumen 300 of the vessel 250 to be processed, then through the
restricted
opening 294, then into the lumen 304 of the processing vessel 296.
[559] V.B. The PECVD reactant can be introduced through the larger opening
302
of the vessel 250 by providing a generally tubular inner electrode 308 having
an interior
passage 310, a proximal end 312, a distal end 314, and a distal opening 316,
in an
alternative embodiment multiple distal openings can be provided adjacent to
the distal
end 314 and communicating with the interior passage 310. The distal end of the
electrode 308 can be placed adjacent to or into the larger opening 302 of the
vessel 250
to be processed. A reactant gas can be fed through the distal opening 316 of
the
electrode 308 into the lumen 300 of the vessel 250 to be processed. The
reactant will
flow through the restricted opening 294, then into the lumen 304, to the
extent the
PECVD reactant is provided at a higher pressure than the vacuum initially
drawn before
introducing the PECVD reactant.
[560] V.B. Plasma 318 is generated adjacent to the restricted opening 294
under
conditions effective to deposit a coating of a PECVD reaction product on the
inner
surface 292 of the restricted opening 294. In the embodiment shown in FIG. 26,
the
plasma is generated by feeding RF energy to the generally U-shaped outer
electrode
160 and grounding the inner electrode 308. The feed and ground connections to
the
electrodes could also be reversed, though this reversal can introduce
complexity If the
vessel 250 to be processed, and thus also the inner electrode 308, are moving
through
the U-shaped outer electrode while the plasma is being generated.
[561] V.B. The plasma 318 generated in the vessel 250 during at least a
portion of
processing can include hollow cathode plasma generated inside the restricted
opening
294 and/or the processing vessel lumen 304. The generation of hollow cathode
plasma
318 can contribute to the ability to successfully apply a barrier coating at
the restricted
114
opening 294, although the invention according to its embodiments is not
limited
according to the accuracy or applicability of this theory of operation. Thus,
in one
contemplated mode of operation, the processing can be carried out partially
under
conditions generating a uniform plasma throughout the vessel 250 and the gas
inlet, and
partially under conditions generating a hollow cathode plasma, for example
adjacent to
the restricted opening 294.
[562] V.B. The process is desirably operated under such conditions, as
explained here
and shown in the drawings, that the plasma 318 extends substantially
throughout the
syringe lumen 300 and the restricted opening 294. The plasma 318 also
desirably
extends substantially throughout the syringe lumen 300, the restricted opening
294, and
the lumen 304 of the processing vessel 296. This assumes that a uniform
coating of the
interior 254 of the vessel 250 is desired. In other embodiments non-uniform
plasma can
be desired.
[563] VB. It is generally desirable that the plasma 318 have a substantially
uniform color
throughout the syringe lumen 300 and the restricted opening 294 during
processing, and
illustratively a substantially uniform color substantially throughout the
syringe lumen 300,
the restricted opening 294, and the lumen 304 of the processing vessel 296.
The plasma
aesirabiy is substantially stable tnrougnout tne syringe lumen Jou and tne
restricted
opening 294, and illustratively also throughout the lumen 304 of the
processing vessel
296.
[564] \LB_ The order of steps in this method is not contemplated to be
critical_
[565] V.B. In the embodiment of FIGS. 26 and 27, the restricted opening 294
has a
first fitting 332 and the processing vessel opening 306 has a second fitting
334 adapted
to seat to the first fitting 332 to establish communication between the lumen
304 of the
processing vessel 296 and the lumen 300 of the vessel 250 to be processed.
[566] V.B. In the embodiment of FIGS. 26 and 27, the first and second fittings
are male
and female Luer lock fittings 332 and 334, respectively integral with the
structure defining
the restricted opening 294 and the processing vessel opening 306. One of the
fittings, in
this case the male Luer lock fitting 332, comprises a locking collar 336 with
a threaded
inner surface and defining an axially facing, generally annular first abutment
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338 and the other fitting 334 comprises an axially facing, generally annular
second
abutment 340 facing the first abutment 338 when the fittings 032 and 334 are
engaged.
[567] V.B. In the illustrated embodiment a seal, for example an 0-ring 342
can be
positioned between the first and second fittings 332 and 334. For example, an
annular
seal can be engaged between the first and second abutments 338 and 340. The
female
Luer fitting 334 also includes dogs 344 that engage the threaded inner surface
of the
locking collar 336 to capture the 0-ring 342 between the first and second
fittings 332
and 334. Optionally, the communication established between the lumen 300 of
the
vessel 250 to be processed and the lumen 304 of the processing vessel 296 via
the
restricted opening 294 is at least substantially leak proof.
[568] V.B. As a further option, either or both of the Luer lock fittings
332 and 334
can be made of electrically conductive material, for example stainless steel.
This
construction material forming or adjacent to the restricted opening 294 might
contribute
to formation of the plasma in the restricted opening 294.
[569] V.B. The desirable volume of the lumen 304 of the processing vessel
296 is
contemplated to be a trade-off between a small volume that will not divert
much of the
reactant flow away from the product surfaces desired to be coated and a large
volume
that will support a generous reactant gas flow rate through the restricted
opening 294
before filling the lumen 304 sufficiently to reduce that flow rate to a less
desirable value
(by reducing the pressure difference across the restricted opening 294).
The
contemplated volume of the lumen 304, in an embodiment, is less than three
times the
volume of the lumen 300 of the vessel 250 to be processed, or less than two
times the
volume of the lumen 300 of the vessel 250 to be processed, or less than the
volume of
the lumen 300 of the vessel 250 to be processed, or less than 50% of the
volume of the
lumen 300 of the vessel 250 to be processed, or less than 25% of the volume of
the
lumen 300 of the vessel 250 to be processed. Other effective relationships of
the
volumes of the respective lumens are also contemplated.
[570] V.B. The inventors have found that the uniformity of coating can be
improved
in certain embodiments by repositioning the distal end of the electrode 308
relative to
the vessel 250 so it does not penetrate as far into the lumen 300 of the
vessel 250 as
116
the position of the inner electrode shown in previous Figures. For example,
although in
certain embodiments the distal opening 316 can be positioned adjacent to the
restricted
opening 294, in other embodiments the distal opening 316 can be positioned
less than
7/8 the distance, optionally less than Y4 the distance, optionally less than
half the distance
to the restricted opening 294 from the larger opening 302 of the vessel to be
processed
while feeding the reactant gas. Or, the distal opening 316 can be positioned
less than
40%, less than 30%, less than 20%, less than 15%, less than 10%, less than 8%,
less
than 6%, less than 4%, less than 2%, or less than 1% of the distance to the
restricted
opening 294 from the larger opening of the vessel to be processed while
feeding the
reactant gas.
[571] V.B. Or, the distal end of the electrode 308 can be positioned either
slightly inside
or outside or flush with the larger opening 302 of the vessel 250 to be
processed while
communicating with, and feeding the reactant gas to, the interior of the
vessel
250. The positioning of the distal opening 316 relative to the vessel 250 to
be processed
can be optimized for particular dimensions and other conditions of treatment
by testing
it at various positions. One particular position of the electrode 308
contemplated for
treating syringe barrels 250 is with the distal end 314 penetrating about a
quarter inch
(ahni R mm) intn thp opsspl himpn f-inn ahnop thp largpr nppning f-in2
[572] V.B. The inventors presently contemplate that it is intended to be
advantageous
to place at least the distal end 314 of the electrode 308 within the vessel
250 so it will
function suitably as an electrode, though that is not necessarily a
requirement.
Surprisingly, the plasma 318 generated in the vessel 250 can be made more
uniform,
extending through the restricted opening 294 into the processing vessel lumen
304, with
less penetration of the electrode 308 into the lumen 300 than has previously
been
employed_ With other arrangements, such as processing a closed-ended vessel,
the
distal end 314 of the electrode 308 commonly is placed closer to the closed
end of the
vessel than to its entrance.
[573] V. B. Or, the distal end 314 of the electrode 308 can be positioned at
the restricted
opening 294 or beyond the restricted opening 294, for example within the
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processing vessel lumen 304, as illustrated for example in FIG. 33. Various
expedients
can optionally be provided, such as shaping the processing vessel 296 to
improve the
gas flow through the restricted opening 294.
[574] V.B. As another alternative, Illustrated in FIGS. 34-35, the
composite Inner
electrode and gas supply tube 398 can have distal gas supply openings such as
400,
optionally located near the larger opening 302, and an extension electrode 402
extending distal of the distal gas supply openings 400, optionally extending
to a distal
end adjacent to the restricted opening 294, and optionally further extending
into the
processing vessel 324. This construction is contemplated to facilitate
formation of
plasma within the inner surface 292 adjacent to the restricted opening 294.
[575] V.B. In yet another contemplated embodiment, the inner electrode 308,
as in
FIG. 26, can be moved during processing, for example, at first extending into
the
processing vessel lumen 304, then being withdrawn progressively proximally as
the
process proceeds. This expedient is particularly contemplated if the vessel
250, under
the selected processing conditions, is long, and movement of the inner
electrode
facilitates more uniform treatment of the interior surface 254. Using this
expedient, the
processing conditions, such as the gas feed rate, the vacuum draw rate, the
electrical
energy applied to the outer electrode 160, the rate of withdrawing the inner
electrode
308, or other factors can be varied as the process proceeds, customizing the
process to
different parts of a vessel to be treated.
[576] V.B. Conveniently, as in the other processes described in this
specification,
the larger opening of the generally tubular vessel 250 to be processed can be
placed on
a vessel support 320, as by seating the larger opening 302 of the vessel 250
to be
processed on a port 322 of the vessel support 320. Then the inner electrode
308 can be
positioned within the vessel 250 seated on the vessel support 320 before
drawing at
least a partial vacuum within the lumen 300 of the vessel 250 to be processed.
[577] V.B. In an alternative embodiment, illustrated in FIG. 28, the
processing
vessel 324 can be provided in the form of a conduit having a first opening 306
secured
to the vessel 250 to be processed, as shown in FIG. 26, and a second opening
328
communicating with a vacuum port 330 in the vessel support 320. In this
embodiment,
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the PECVD process gases can flow into the vessel 250, then via the restricted
opening
294 into the processing vessel 324, then return via the vacuum port 330.
Optionally, the
vessel 250 can be evacuated through both openings 294 and 302 before applying
the
PECVD reactants.
[578] V.B. Or, an uncapped syringe barrel 250, as shown in FIG. 22, can be
provided with an interior coating of SiO., in which x in this formula is from
about 1.5 to
about 2.9, alternatively from about 1.5 to about 2.6, alternatively about 2,
barrier or
other type of PECVD coating by introducing the reactants from the source 144
through
the opening at the back end 256 of the barrel 250 and drawing a vacuum using
the
vacuum source 98 drawing through the opening at toe front end 260 of Me
barrel. For
example, the vacuum source 98 can be connected through a second fitting 266
seated
on the front end 260 of the syringe barrel 250. Using this expedient, the
reactants can
flow through the barrel 250 in a single direction (upward as shown in FIG. 22,
though
tne orientation is not critical), and tnere is no need to convey toe reactants
through a
probe that separates the fed gas from the exhausted gas within the syringe
barrel 250.
The front and back ends 260 and 256 of the syringe barrel 250 can also be
reversed
relative to the coating apparatus, in an alternative arrangement. The probe
108 can act
simply as an electrode, and can either be tubular or a solid rod in this
embodiment. As
before, the separation between the interior surface 254 and the probe 108 can
be
uniform over at least most of the length of the syringe barrel 250.
[579] V.B. FIG. 37 is a view similar to FIG. 22 showing another embodiment
in
which the fitting 266 is independent of and not attached to the plate
electrodes 414 and
416. The fitting 266 can have a Luer lock fitting adapted to be secured to the
corresponding fitting of the syringe barrel 250. This embodiment allows the
vacuum
conduit 418 to pass over the electrode 416 while the vessel holder 420 and
attached
vessel 250 move between the electrodes 414 and 416 during a coating step.
[580] V.B. FIG. 38 is a view similar to FIG. 22 showing still another
embodiment in
which the front end 260 of the syringe barrel 250 is open and the syringe
barrel 250 is
enclosed by a vacuum chamber 422 seated on the vessel holder 424. In this
embodiment the pressures P1 within the syringe barrel 250 and within the
vacuum
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chamber 422 are approximately identical, and the vacuum in the vacuum chamber
422
optionally is drawn through the front end 260 of the syringe barrel 250. When
the
process gases flow into the syringe barrel 250, they flow through the front
end 260 of
the syringe barrel 250 until a steady composition is provided within the
syringe barrel
250, at which time the electrode 160 is energized to form the coating. It is
contemplated
that due to the larger volume of the vacuum chamber 422 relative to the
syringe barrel
250, and the location of the counter electrode 426 within the syringe barrel
250, the
process gases passing through the front end 260 will not form substantial
deposits on
the walls of the vacuum chamber 422.
[581] V.B. FIG. 39 is a view similar to FIG. 22 snowing yet anotner
embodiment in
which the back flange of the syringe barrel 250 is clamped between a vessel
holder 428
and an electrode assembly 430 to which a cylindrical electrode or pair of
plate
electrodes indicated as 160 and a vacuum source 98 are secured. The volume
generally indicated as 432 enclosed outside toe syringe barrel 250 is
relatively small in
this embodiment to minimize the pumping needed to evacuate the volume 432 and
the
interior of the syringe barrel 250 to operate the PECVD process.
[582] V.B. FIG. 40 is a view similar to FIG. 22 and FIG. 41 is a plan view
showing
even another embodiment as an alternative to FIG. 38 in which the ratio of
pressures
P1/P2 is maintained at a desired level by providing a pressure proportioning
valve 434.
It is contemplated that 131 can be a lower vacuum, i.e. a higher pressure,
than P2 during
a PECVD process so the waste process gases and by-products will pass through
the
front end 260 of the syringe barrel 250 and be exhausted. Also, the provision
of a
separate vacuum chamber conduit 436 to serve the vacuum chamber 422 allows the
use of a separate vacuum pump to evacuate the greater enclosed volume 432 more
quickly.
[583] V.B. FIG. 41 is a plan view of the embodiment of FIG. 40, also
showing the
electrode 160 removed from FIG. 40.
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V.C. Method of Applying a Lubricity Coating
[584] V.C. Another embodiment is a method of applying a lubricity coating
derived
from an organosilicon precursor. A "lubricity coaling" or any similar term is
generally
defined as a coating that reduces the frictional resistance of the coated
surface, relative
to the uncoated surface. If the coated object is a syringe (or syringe part,
e.g. syringe
barrel) or any other item generally containing a plunger or movable part in
sliding
contact with the coated surface, the frictional resistance has two main
aspects ¨
breakout force and plunger sliding force.
[585] The plunger sliding force test is a specialized test of the
coefficient of sliding
friction of the plunger within a syringe, accounting for the fact that the
normal force
associated with a coefficient of sliding friction as usually measured on a
flat surface is
addressed by standardizing the fit between the plunger or other sliding
element and the
tube or other vessel within which it slides. The parallel force associated
with a
coefficient of slicing friction as usually measured is comparable to the
plunger sliding
force measured as described in this specification. Plunger sliding force
can be
measured, for example, as provided in the ISO 7886-1:1993 test.
[586] The plunger sliding force test can also be adapted to measure other
types of
frictional resistance, for example the friction retaining a stopper within a
tube, by
suitable variations on the apparatus and procedure. In one embodiment, the
plunger
can be replaced by a closure and the withdrawing force to remove or insert the
closure
can he measured as the counterpart of plunger sliding force_
[587] Also or instead of the plunger sliding force, thebreakout force can
be
measured. The breakout force is the force required to start a stationary
plunger moving
within a syringe barrel, or the comparable force required to unseat a seated,
stationary
closure and begin its movement. The breakout force is measured by applying a
force to
the plunger that starts at zero or a low value and increases until the plunger
begins
moving. The breakout force tends to increase with storage of a syringe, after
the
prefilled syringe plunger has pushed away the intervening lubricant or adhered
to the
barrel due to decomposition of the lubricant between the plunger and the
barrel. The
breakout force is the force needed to overcome "sticktion," an industry term
for the
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adhesion between the plunger and barrel that needs to be overcome to break out
the
plunger and allow it to begin moving.
[588] V.C. Some utilities of coating a vessel in whole or in part with a
lubricity
coating, such as selectively at surfaces contacted in sliding relation to
other parts, is to
ease the insertion or removal of a stopper or passage of a sliding element
such as a
piston in a syringe or a stopper in a sample tube. The vessel can be made of
glass or a
polymer material such as polyester, for example polyethylene terephthalate
(PET), a
cyclic olefin copolymer (COC), an olefin such as polypropylene, or other
materials.
Applying a lubricity coating by PECVD can avoid or reduce the need to coat the
vessel
wail or closure with a sprayed, dipped, or otherwise applied organosilicon or
other
lubricant that commonly is applied in a far larger quantity than would be
deposited by a
PECVD process.
[589] V.C. In any of the above embodiments V.C., a plasma, optionally a non-
hollow-cathode plasma, optionally can be formed in the vicinity of the
substrate
[590] V.C. In any of embodiments V.C., the precursor optionally can be
provided in
the substantial absence of oxygen. V.C. In any of embodiments
V.C., the precursor
optionally can be provided in the substantial absence of a carrier qas. V.C.
In any of
embodiments V.C., in which the precursor optionally can be provided in the
substantial
absence of nitrogen. V.C. In any of embodiments
V.C., in which the precursor
optionally can be provided at less than 1 Torr absolute pressure.
[501] V.C. In any of
embodiments V.C., the precursor optionally can be provided to
the vicinity of a plasma emission.
[592] V.C. In any of embodiments V.C., the coating optionally can be
applied to the
substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10-200 nm, or
20 to 100
rum thick. The thickness of this and other coatings can be measured, for
example, by
transmission electron microscopy (TEM).
[593] V.C. The TEM can be carried out, for example, as follows. Samples can
be
prepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Either the
samples
can be first coated with a thin layer of carbon (50-100nm thick) and then
coated with a
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sputtered layer of platinum (50-100nm thick) using a K575X Emltech coating
system, or
the samples can be coated directly with the protective sputtered Pt layer. The
coated
samples can be placed in an FEI FIB200 FIB system. An additional layer of
platinum
can be FIB-deposited by injection of an organo-metallic gas while rastering
the 30kV
gallium ion beam over the area of interest. The area of interest for each
sample can be
chosen to be a location half way down the length of the syringe barrel. Thin
cross
sections measuring approximately 15pm ("micrometers") long, 2pm wide and 15pm
deep can be extracted from the die surface using a proprietary in-situ FIB
lift-out
technique. The cross sections can be attached to a 200 mesh copper TEM grid
using
RP-deposited platinum. One or two windows in each section, measuring - 81.rm
wide,
can be thinned to electron transparency using the gallium ion beam of the FE I
FIB.
[594] V.C. Cross-sectional image analysis of the prepared samples can be
performed utilizing either a Transmission Electron Microscope (TEM), or a
Scanning
Transmission Electron Microscope (STEM), or both. All imaging data can be
recorded
digitally. For STEM imaging, the grid with the thinned foils can be
transferred to a
Hitachi HD2300 dedicated STEM. Scanning transmitted electron images can be
acquired at appropriate magnifications in atomic number contrast mode (ZC) and
transmittal electron mode (TE). The following instrument settings cart be
used.
Scanning Transmission Electron
1. Instrument Microscope
Manufacturer/Model Hitachi HD2300
Accelerating Voltage 200kV
Objective Aperture #2
Condenser Lens 1 Setting 1.672
Condenser Lens 2 Setting 1.747
Approximate Objective Lens Setting 5.86
ZC Mode Projector Lens 1.149
TE Mode Projector Lens 0.7
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Image Acquisition
Pixel Resolution 1280x960
Aquisition Time 20sec.(x4)
[595] V.C. For TEM analysis the sample grids can be transferred to a
Hitachi
HF2000 transmission electron microscope. Transmitted electron images can be
acquired at appropriate magnifications. The relevant instrument settings used
during
image acquisition can be those given below.
Transmission Electron
Instrument Microscope
Manufacturer/Model Hitachi HF2000
Accelerating Voltage 200 kV
Condenser Lens 1 0.78
Condenser Lens 2 0
Objective Lens 6.34
Condenser Lens Aperture #1
Objective Lens Aperture for #3
im aging
Selective Area Aperture for N/A
SAD
[596] V.C. In any of embodiments V.C., the substrate can comprise glass or
a
polymer, for example a polycarbonate polymer, an olefin polymer, a cyclic
olefin
124
copolymer, a polypropylene polymer, a polyester polymer, a polyethylene
terephthalate
polymer or a combination of any two or more of these.
[597] V.C. In any of embodiments VC, the PECVD optionally can be performed by
energizing the gaseous reactant containing the precursor with electrodes
powered at a
RF frequency as defined above, for example a frequency from 10 kHz to less
than 300
MHz, more illustratively of from 1 to 50 MHz, even more illustratively of from
10 to 15
MHz, most illustratively a frequency of 13_56 MHz.
[598] V.C. In any of embodiments VC, the plasma can be generated by energizing
the gaseous reactant comprising the precursor with electrodes supplied with
electric
power sufficient to form a lubricity coating. Optionally, the plasma is
generated by
energizing the gaseous reactant containing the precursor with electrodes
supplied with
an electric power of from 0.1 to 25 W, illustratively from 1 to 22 W, more
illustratively from
3 to 17W, even more illustratively of from 5 to 14 W, most illustratively of
from 7 to 11
W, in particular of 8 W. The ratio of the electrode power to the plasma volume
may be
less than 10 W/ml, illustratively is from 5 W/ml to 0.1 W/ml, more
illustratively is from 4
W/ml to 0.1 W/ml, most illustratively from 2 W/ml to 0.2 W/ml. These power
levels are
suitable for applying lubricity coatings to syringes and sample tubes and
vessels of
similar geometry flaying a voia volume or 1 to 3 m in wnicn PEUVU piasma is
generatea.
It is contemplated that for larger or smaller objects the power applied should
be increased
or reduced accordingly to scale the process to the size of the substrate.
[599] V.C. One contemplated product optionally can be a syringe having a
barrel treated
by the method of any one or more of embodiments V.C.
V.D. Liquid-applied Coatings
[600] V.D. Another example of a suitable barrier or other type of coating,
usable in
conjunction with PECVD-applied coatings or other PECVD treatment as disclosed
here,
can be a liquid barrier, lubricant, surface energy tailoring, or other type of
coating 90
applied to the interior surface of a vessel, either directly or with one or
more intervening
PECVD-applied coatings of SiwOxCyHz, SiOx, a lubricity coating, or both.
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[601] V.D. Suitable liquid barriers or other types of coatings 90 also
optionally can be
applied, for example, by applying a liquid monomer or other polymerizable or
curable
material to the interior surface of the vessel 80 and curing, polymerizing, or
crosslinking
the liquid monomer to form a solid polymer. Suitable liquid barrier or other
types of
coatings 90 can also be provided by applying a solvent-dispersed polymer to
the surface
88 and removing the solvent.
[602] V.D. Either of the above methods can include as a step forming a coating
90 on
the interior 88 of a vessel 80 via the vessel port 92 at a processing station
or device
28. One example is applying a liquid coating, for example of a curable
monomer,
prepolymer, or polymer dispersion, to the interior surface 88 of a vessel 80
and curing it
to forma film that physically isolates the contents of the vessel 60 from its
interior surface
88. The prior art describes polymer coating technology as suitable for coating
plastic
blood collection tubes. For example, the acrylic and polyvinylidene chloride
(PVdC)
coating materials and coating methods described in US Patent 6,165,566,
optionally can
be used.
[603] V.D. Either of the above methods can also or include as a step forming a
coating
on the exterior outer wall of a vessel 80. The coating optionally can be a
barrier coating,
optionaiiy an oxygen barrier coating, or optionany a water barrier coating.
one exampie
of a suitable coating is polyvinylidene chloride, which functions both as a
water barrier
and an oxygen barrier. Optionally, the barrier coating can be applied as a
water- based
coating. The coating optionally can be applied by dipping the vessel in it,
spraying it on
the vessel, or other expedients. A vessel having an exterior barrier coating
as described
above is also contemplated.
VI. VESSEL INSPECTION
[604] VI. One station or device shown in FIG. 1 is the processing station or
device 30,
which can be configured to inspect the interior surface of a vessel 80 for
defects, as by
measuring the air pressure loss or mass flow rate or volume flow rate through
a vessel
wall or outgassing of a vessel wall. The device 30 can operate similarly to
the device 26,
except that better performance (less leakage or permeation at given process
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conditions) can be required of the vessel to pass the inspection provided by
the device
00, since in the illustrated embodiment a barrier or other type of coating has
been
applied by the station or device 28 before the station or device 30 is
reached. In an
embodiment, this inspection of the coated vessel 80 can be compared to the
inspection
of the same vessel 80 at the device or station 26. Less leakage or permeation
at the
station or device 30 indicates that the barrier coating is functioning at
least to a degree.
[605] VI. The identity of a vessel 80 measured at two different stations or
by two
different devices can be ascertained by placing individual identifying
characteristics,
such as a bar code, other marks, or a radio frequency identification (RFID)
device or
marker, on each of the vessel holders 38-68 and matching up the identity of
vessels
measured at two or more different points about the endless conveyor shown in
FIG. 1.
Since the vessel holders can be reused, they can be registered in a computer
database
or other data storage structure as they reach the position of the vessel
holder 40 in FIG.
1, just after a new vessel 80 has been seated on the vessel holder 40, and
removed
from the data register at or near the end of the process, for example as or
after they
reach the position of the vessel holder 66 in FIG. 1 and the processed vessel
80 is
removed by the transfer mechanism 74.
[606] VI. The processing station or device 32 can be configured to inspect
a
vessel, for example a barrier or other type of coating applied to the vessel,
for defects.
In the illustrated embodiment, the station or device 32 determines the optical
source
transmission of the coating, as a measurement of the thickness of the coating.
The
barrier or other type of coating, if suitably applied, can make the vessel 80
more
transparent, even though additional material has been applied, as it provides
a more
uniform surface.
[607] VI. Other measures of the thickness of the coating are also
contemplated, as
by using interference measurements to determine the difference in travel
distance
between an energy wave that bounces off the inside of the coating 90
(interfacing with
the atmosphere within the vessel interior 154) and an energy wave that bounces
off the
interior surface 88 of the vessel 80 (interfacing with the outside of the
coating 90). As is
well known, the difference in travel distance can be determined directly, as
by
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measuring the time of arrival of the respective waves with high precision, or
indirectly,
as by determining what wavelengths of the incident energy are reinforced or
canceled,
in relation to the test conditions.
[608] VI. Another measurement technique that can be carried out to check
coating
integrity is an ellipsometric measurement on the device. In this case, a
polarized laser
beam can be projected either from the inside or the outside of the vessel 80.
In the
case of a laser beam projected from the inside, the laser beam can be pointed
orthogonally at the surface and then either the transmitted or reflected beam
can be
measured. The change in beam polarity can be measured. Since a coating or
treatment on the surface of the device will impact (change) the polarization
of the laser
beam, changes in the polarity can be the desired result. The changes in the
polarity are
a direct result of the existence of a coating or treatment on the surface and
the amount
of change is related to the amount of treatment or coating.
[609] VI. If the polarized beam is projected from the outside of the
device, a
detector can be positioned on the inside to measure the transmitted component
of the
beam (and the polarity determined as above). Or, a detector can be placed
outside of
the device in a position that can correspond to the reflection point of the
beam from the
interface between the treatment/coating (on the inside of the device). The
polarity
change(s) can then be determined as detailed above.
[610] VI. In addition to measuring optical properties and/or leak rates as
described
above, other probes and/or devices can be inserted into the inside of the
device and
measurements made with a detector apparatus. This apparatus is not limited by
the
measurement technique or method. Other test methods that employ mechanical,
electrical, or magnetic properties, or any other physical, optical, or
chemical property,
can be utilized.
[611] VI. During the plasma treatment setup, an optical detection system
optionally
can be used to record the plasma emission spectrum (wavelength and intensity
profile),
which corresponds to the unique chemical signature of the plasma environment.
This
characteristic emission spectrum provides confirmation that the coating has
been
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applied and treated. The system also offers a real-time precision measurement
and
data archive tool for each part processed.
[612] VI. Any of the above methods can include as a step inspecting the
interior
surface 88 of a vessel 80 for defects at a processing station such as 24, 26,
30, 32, or
34. Inspecting can be carried out, as at the stations 24, 32, and 34, by
inserting a
detection probe 172 into the vessel 80 via the vessel port 92 and detecting
the condition
of the vessel interior surface 88 or a barrier or other type of coating 90
using the probe
172. Inspecting can be carried out, as shown in FIG. 11, by radiating energy
inward
through the vessel wall 86 and vessel interior surface 88 and detecting the
energy with
the probe 172. Or, inspecting can be carried out by reflecting toe radiation
from me
vessel interior surface 88 and detecting the energy with a detector located
inside the
vessel 80. Or, inspecting can be carried out by detecting the condition of the
vessel
interior surface 88 at numerous, closely spaced positions on the vessel
interior surface.
[613] VI. Any of the above methods can include carrying out the inspecting
step at
a sufficient number of positions throughout the vessel interior surface 88 to
determine
that the barrier or other type of coating 90 will be effective to prevent the
pressure within
the vessel, when it is initially evacuated and its wall is exposed to the
ambient
atmosphere, from increasing to more than 20% of the ambient atmospheric
pressure
during a shelf life of a year.
[614] VI. Any of the above methods can include carrying out the inspecting
step
within an elapsed time of 30 or fewer seconds per vessel, or 25 or fewer
seconds per
vessel, or 20 or fewer seconds per vessel, or 15 or fewer seconds per vessel,
or 10 or
fewer seconds per vessel, or 5 or fewer seconds per vessel, or 4 or fewer
seconds per
vessel, or 3 or fewer seconds per vessel, or 2 or fewer seconds per vessel, or
1 or
fewer seconds per vessel. This can be made possible, for example, by measuring
the
efficacy of the barrier or other type of coated vessel wall, as shown in FIG.
7, which can
involve one measurement for the entire vessel 80, or by inspecting many or
even all the
points to be inspected in parallel, as by using the charge coupled device as
the detector
172 shown or substitutable in FIGS. 6, 10, and 11. The latter step can be used
for
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detecting the condition of the barrier or other type of coating at numerous,
closely
spaced positions on the vessel interior surface se in a very short overall
time.
[615] VI. In any embodiment of the method, a multi-point vessel inspection
can be
further expedited, if desired, by collecting data using a charge coupled
device 172,
transporting away the vessel 80 that has just been inspected, and processing
the
collected data shortly thereafter, while the vessel 80 is moving downstream.
If a defect
in the vessel 80 is later ascertained due to the data processing, the vessel
80 that is
defective can be moved off line at a point downstream of the detection station
such as
34 (FIG. 10).
[616] VI. In any of the above embodiments, the inspecting step can be
carried out
at a sufficient number of positions throughout the vessel 80 interior surface
88 to
determine that the barrier or other type of coating 90 will be effective to
prevent the
initial vacuum level (i.e. initial reduction of pressure versus ambient)
within the vessel
80, when it is initially evacuated and its wall 86 is exposed to the ambient
atmosphere,
from decreasing more than 20%, optionally more than 15%, optionally more than
10%,
optionally more than 5%, optionally more than 2%, during a shelf life of at
least 12
months, or at least 18 months, or at least two years.
[617] VI. The initial vacuum level can be a high vacuum, i.e. a remaining
pressure
of less than 10 Tom or a lesser vacuum such as less than 20 Torr of positive
pressure
(i.e. the excess pressure over a full vacuum), or less than 50 Torr, or less
than 100 Torr,
or less than 150 Torr, or less than 200 Torr, or less than 250 Torr, or less
than 300 Torr,
or less than 350 Torr, or less than 380 Torr of positive pressure. The initial
vacuum
level of evacuated blood collection tubes, for example, is in many instances
determined
by the type of test the tube is to be used for, and thus the type and
appropriate amount
of a reagent that is added to the tube at the time of manufacture. The initial
vacuum
level is commonly set to draw the correct volume of blood to combine with the
reagent
charge in the tube.
[618] VI. In any of the above embodiments, the barrier or other type of
coating 90
inspecting step can be carried out at a sufficient number of positions
throughout the
vessel interior surface 88 to determine that the barrier or other type of
coating 90 will be
130
effective to prevent the pressure within the vessel 80, when it is initially
evacuated and
its wall is exposed to the ambient atmosphere, from increasing to more than
15%, or
more than 10%, of the ambient atmospheric pressure of the ambient atmospheric
pressure during a shelf life of at least one year.
VI.A. Vessel Processing
Including Pre-Coating and Post-Coating Inspection
[619] VI _A_ Even another embodiment is a vessel processing method for
processing a
molded plastic vessel having an opening and a wall defining an interior
surface. The
method is carried out by inspecting the interior surface of the vessel as
molded or just
before coating for defects; applying a coating to the interior surface of the
vessel after
inspecting the vessel as molded; and inspecting the coating for defects.
[620] VI.A. Another embodiment is a vessel processing method in which a
barrier coating
is applied to the vessel after inspecting the vessel as molded, and the
interior surface of
the vessel is inspected for defects after applying the barrier coating_
[621] VI.A. In an embodiment, the station or device 26 (which can also
function as the
station or device 28 for applying a coating) can be used as follows for
barometric vessel
inspection. With either or both of the valves 136 and 148 open, the vessel 80
can be
evacuated to a desired degree, illustratively to a very low pressure such as
less than 10
Torr, optionally less than 1 Torr. Whichever of the valves 136 and 148 is
initially open
can then be closed, isolating the evacuated interior 154 of the vessel 80 and
the pressure
gauge 152 from ambient conditions and from the vacuum source Q8. The change in
pressure over a measurement time, whether due to the ingress of gas through
the vessel
wall or outgassing from the material of the wall and/or a coating on the
vessel wall, can
then be sensed and used to calculate the rate of ingress of ambient gas into
the vessel
80 as mounted on the vessel holder 44. For the present purpose, outgassing is
defined
as the release of adsorbed or occluded gases or water vapor from the vessel
wall,
optionally in at least a partial vacuum.
[622] VIA_ Another optional modification can be to provide the ambient gas at
a higher
pressure than atmospheric pressure. This again can increase the rate of gas
transfer
through a barrier or other type of layer, providing a measurable difference in
a
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shorter time than if a lower ambient pressure were provided. Or, gas can be
introduced
into the vessel 80 at a higher than atmospheric pressure, again increasing the
transfer
rate through the wall 86.
[623] VIA. Optionally, the vessel inspection at the station or by the
device 26 can
be modified by providing an inspection gas, such as helium, on an upstream
side with
respect to the substrate, either within or outside the vessel 80, and
detecting it on the
downstream side. A low-molecular-weight gas, such as hydrogen, or a less
expensive
or more available gas, such as oxygen or nitrogen, can also be used as an
inspection
gas.
[624] VIA. Helium is contemplated as an inspection gas that can increase
the rate
of leak or permeation detection, as it will pass through an imperfect barrier
or other type
of coating, or past a leaking seal, much more quickly than the usual ambient
gases such
as nitrogen and oxygen in ordinary air. Helium has a high transfer rate
through many
solid substrates or small gaps because it: (1) is inert, so it is not adsorbed
by the
substrate to any great degree, (2) is not ionized easily, so its molecules are
very
compact due to the high level of attraction between its electrons and nucleus,
and (3)
has a molecular weight of 4, as opposed to nitrogen (molecular weight 28) and
oxygen
(molecular weight 32), again making the molecules more compact and easily
passed
through a porous substrate or gap. Due to these factors, helium will travel
through a
barrier having a given permeability much more quickly than many other gases.
Also,
the atmosphere contains an extremely small proportion of helium naturally, so
the
presence of additional helium can be relatively easy to detect, particularly
if the helium
is introduced within the vessel 80 and detected outside the vessel 80 to
measure
leakage and permeation. The helium can be detected by a pressure drop upstream
of
the substrate or by other means, such as spectroscopic analysis of the
downstream gas
that has passed through the substrate.
[625] VIA. An example of barometric vessel inspection by determining the
oxygen
concentration from 02 fluorescence detection follows.
[626] VIA. An Excitation Source (Ocean Optics LISB-LS-450 Pulsed Blue LED),
fiber assembly (Ocean Optics QBIF6000-VIS-NIR), a spectrometer (USB4000-FL
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Fluorescence Spectrometer), an oxygen sensor probe (Ocean Optics FOXY-R). and
a
vacuum feed through adaptor (like VFT-1000-VIS-275) connected to a vacuum
source
are used. A vacuum can be applied to remove the ambient air, and when the
vessel is
at a defined pressure any oxygen content that has leaked or permeated in to
refill the
vessel from the ambient air can be determined using the detection system. A
coated
tube replaces the uncoated tube and 02 concentration measurement can be taken.
The
coated tube will demonstrate reproducibly different atmospheric oxygen content
than
the uncoated sample due to differential 02 surface absorption on the coated
tube (an
SiOx surface, versus the uncoated PET or glass surface) and/or a change in 02
diffusion rate from the surface. Detection time can be less than one second.
[627] VIA. These barometric methods should not be considered limited to a
specific gas sensed (helium detection or other gases can be considered) or a
specific
apparatus or arrangement.
[628] VIA. The processing station or device 34 also can be configured to
inspect a
barrier or other type of coating for defects. In the embodiment of FIGS. 1 and
10, the
processing station or device 34 can be another optical inspection, this time
intended to
scan or separately measure the properties of at least a portion of the barrier
or other
type of coating 90, or substantially the entire barrier or other type of
coating 90, at
numerous, closely spaced positions on the barrier or other type of coating 90.
The
numerous, closely spaced positions can be, for example, spaced about 1 micron
apart,
or about 2 microns apart, or about 3 microns apart, or about 4 microns apart,
or about 5
microns apart, or about 6 microns apart, or about 7 microns apart, either in
every case
or on average over at least part of the surface, thus separately measuring
some or all
small portions of the barrier or other type of coating 90. In an embodiment, a
separate
scan of each small area of the coating can be useful to find individual
pinholes or other
defects, and to distinguish the local effects of pinhole defects from more
general
defects, such as a large area with a coating that is too thin or porous.
[629] VIA. The inspection by the station or device 34 can be carried out by
inserting a radiation or light source 170 or any other suitable radio
frequency,
microwave, infrared, visible light, ultraviolet, x-ray, or electron beam
source, for
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example, into the vessel 80 via the vessel port 92 and detecting the condition
of the
vessel interior surface, for example the barrier coating 90, by detecting
radiation
transmitted from the radiation source using a detector.
[630] VIA. The above vessel holder system can also be used for testing the
device. For example, the probe 108 of FIG. 2 having a gas delivery port 110
can be
replaced by a light source 170 (FIG. 10). The light source 170 can irradiate
the inside of
the tube and then subsequent testing can be completed outside of the tube,
measuring
transmission or other properties. The light source 170 can be extended into
the inside
of the tube in the same manner that the probe 108 is pushed into the puck or
vessel
holder 62, although a vacuum and seals are not necessarily required. The light
source
170 can be an optical fiber source, a laser, a point (such as an LED) source
or any
other radiation source. The source can radiate at one or more frequencies from
the
deep UV (100m) into the far infra red (100 microns) and all frequencies in
between.
There is no limitation on the source that can be used.
[631] VIA. As a specific example see FIG. 10. In FIG. 10 the tube or vessel
80 is
positioned in the puck or vessel holder 62 and a light source 170 at the end
of the probe
108 has been inserted into the tube. The light source 170 in this case can be
a blue
LED source of sufficient intensity to be received by the detector 172
surrounding the
outside of the vessel 80. The light source 170 can be, for example, a three
dimensional
charge-coupled-device (COD) comprising an array of pixels such as 174 on its
interior
surface 176. The pixels such as 174 receive and detect the illumination
radiated
through the barrier or other type of coating 90 and vessel wall 86. In this
embodiment
the detector 172 has a larger inner diameter relative to the vessel 80 than
the
separation of the electrode 164 and vessel 80 of FIG. 2, and has a cylindrical
top
portion adjacent to the closed end 84 instead of a hemispherical top portion.
The
outside detector 172 or can have a smaller radial gap from the vessel 80 and a
gap of
more uniform dimension at its top portion adjacent to the closed end 84. This
can be
accomplished, for example, by providing a common center of curvature for the
closed
end 84 and the top of the detector 172 when the vessel 80 is seated. This
variation
right provide more uniform inspection of the curved closed end 84 of the
vessel 80,
although either variation is contemplated to be suitable.
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[632] VIA. Prior to the light source being turned on, the COD is measured
and the
resulting value stored as a background (which can be subtracted from
subsequent
measurements). The light source 170 is then turned on and measurements taken
with
the CCD. The resulting measurements can then be used to compute total light
transmission (and compared to an uncoated tube to determine the average
coating
thickness) and defect density (by taking individual photon counts on each
element of the
CCD and comparing them to a threshold value - if the photon count is lower,
then this
corresponds to not enough light being transmitted). Low light transmission
likely is the
result of no or too-thin coating -- a defect in the coating on the tube. By
measuring the
number of adjacent elements that have a low photon count, the defect size can
be
estimated. By summing the size and number of defects, the tube's quality can
be
assessed, or other properties determined that [Tight be specific to the
frequency of the
radiation from the light source 170.
[633] VIA. In toe embodiment of HO. 10, energy can be radiated outward
through
the vessel interior surface, such as through the coating 90 and the vessel
wall 86, and
detected with a detector 172 located outside the vessel. Various types of
detectors 172
can be used.
[634] VIA. Since the incident radiation from the source 170 transmitted
through the
barrier or other type of coating 90 and vessel wall 80 can be greater for a
lower angle of
incidence (compared to a reference line normal to the vessel wall 80 at any
given point),
the pixels such as 174 lying on a normal line through the vessel wall 86 will
receive
more of the radiation than neighboring pixels, though more than one pixel can
receive
some of the light passing through a given portion of the barrier or other type
of coating,
and the light passing through more than one given portion of the barrier or
other type of
coating 90 and vessel wall 80 will be received by a particular pixel such as
174.
[635] VIA. The degree of resolution of the pixels such as 174 for detecting
radiation passing through a particular portion of the barrier or other type of
coating 90
and vessel wall 86 can be increased by placing the CCD so its array of pixels
such as
174 is very close to and closely conforms to the contours of the vessel wall
86. The
degree of resolution can also be increased by selecting a smaller or
essentially point
135
source of light, as shown diagrammatically in FIG. 6, to illuminate the
interior of the vessel
80. Using smaller pixels will also improve the resolution of the array of
pixels in the CCD.
[636] VI.A. In Figure 6 a point light source 132 (laser or LED) is positioned
at the end
of a rod or probe. ("Point source" refers either to light emanating from a
small- volume
source resembling a mathematical point, as can be generated by a small LED or
a
diffusing tip on an optical fiber radiating light in all directions, or to
light emanated as a
small-cross-section beam, such as coherent light transmitted by a laser.) The
point
source of light 132 can be either stationary or movable, for example axially
movable,
while the characteristics of the barrier or other type of coating 90 and
vessel wall 80 are
being measured. If movable, the point light source 132 can be moved up and
down inside
of the device (tube) O. In a similar manner described above, the interior
surface
88 of the vessel 80 can be scanned and subsequent measurements made by an
external
detector apparatus 134 to determine coating integrity. An intended advantage
of this
approach is that a linearly polarized or similar coherent light source with
specific
directionality can be used.
[637] VI.A. The position of the point source of light 132 can be indexed to
the pixels
such as 174 so the illumination of the detectors can be determined at the time
the
aetector is at a normal angie witn respect to a particular area or tne coating
U. in tne
embodiment of FIG. 10, a cylindrical detector 172, optionally with a curved
end matching
the curve (if any) of the closed end 84 of a vessel 80, can be used to detect
the
characteristics of a cylindrical vessel 80.
[638] VI.A. It will be understood, with reference to FIG. 10, that the
inspection station or
device 24 or 34 can be modified by reversing the positions of the light or
other radiation
source 170 and detector 172 so the light radiates through the vessel wall 86
from the
exterior to the interior or the vessel O. If this expedient is selected, in an
embodiment a
uniform source of incident light or other radiation can be provided by
inserting the vessel
80 into an aperture 182 through the wall 184 of an integrating sphere light
source 186.
An integrating sphere light source will disperse the light or radiation from
the source 170
outside the vessel 80 and inside the integrating sphere,
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so the light passing through the respective points of the wall 86 of the
vessel 80 will be
relatively uniform. This will tend to reduce the distortions caused by
artifacts relating to
portions of the wall 86 having different shapes.
[639] VI.A. In the embodiment of FIG. 11, the detector 172 can be shown to
closely
conform to the barrier or other type of coating 90 or interior surface 88 of
the vessel 80.
Since the detector 172 can be on the same side of the vessel wall 86 as the
barrier or
other type of coating 80, this proximity will tend to increase the resolution
of the pixels
such as 174, though in this embodiment the detector 172 illustratively will be
precisely
positioned relative to the barrier or other type of coating 90 to avoid
scraping one against
the other, possibly damaging either the coating or the CCD array. Placing the
detector
172 immediately adjacent to the coating 90 also can reduce the effects of
refraction by
the vessel wall 86, which in the embodiment of FIG. 10 occurs after the light
or other
radiation passes through the barrier or other type of coating 90, so the
signal to be
detected can be differentially refracted depending on the local shape of the
vessel 80
and the angle of incidence of the light or other radiation.
[640] VI.A. Other barrier or other type of coating inspection techniques and
devices can
also, or, be used. For example, fluorescence measurements can be used to
characterize
tne treatmenticoating on tne aevice. using tne same apparatus aescrinea in mu.
10 and
6, a light source 132 or 170 (or other radiation source) can be selected that
can interact
with the polymer material of the wall 86 and/or a dopant in the polymer
material of the
wall 86. Coupled with a detection system, this can be used to characterize a
range of
properties including defects, thicknesses and other performance factors.
[641] VI.A. Yet another example of inspection is to use x-rays to characterize
the
treatment/coating and/or the polymer itself. In FIGS. 10 or 6, the light
source can be
replaced with an x-radiation source and Me external detector can be of a type
to measure
the x-ray intensity. Elemental analysis of the barrier or other type of
coating can be
carried out using this technique.
[642] VIA_ After molding a device 80, as at the station 22, several potential
issues
can arise that will render any subsequent treatment or coating imperfect, and
possibly
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ineffective. If the devices are inspected prior to coating for these issues,
the devices
can be coated with a highly optimized, optionally up to 6-sigma controlled
process that
will ensure a desired result (or results).
[643] VIA. Some of the potential problems that can interfere with treatment
and
coating include (depending on the nature of the coated article to be
produced):
[644] VIA. 1. Large density of particulate contamination defects (for
example,
each more than 10 micrometers in its longest dimension), or a smaller density
of large
particulate contamination (for example, each more than 10 micrometers in its
longest
ension).
[645] VIA. 2. Chemical or other surface contamination (for example silicone
mold
release or oil).
[646] VIA. 3. High surface roughness, characterized by either a high/large
number of sharp peaks and/or valleys. This can also be characterized by
quantifying
the average roughness (Ra) which should be less than 100nm.
[647] VIA. 4. Any defect in the device such as a hole that will not allow a
vacuum
to be created.
[648] VIA. 5. Any defect on the surface of the device that will be used to
create a
seal (for example the open end of a sample collection tube).
[649] VIA. 6. Large wall thickness non-uniformities which can impede or
modify
power coupling through the thickness during treatment or coating.
[650] VIA. 7. Other defects that will render the barrier or other type of
coating
ineffective.
[651] VIA. To assure that the treatment/coating operation is successful
using the
parameters in the treatment/coating operation, the device can be pre-inspected
for one
or more of the above potential issues or other issues. Previously, an
apparatus was
disclosed for holding a device (a puck or vessel holder such as 38-68) and
moving it
through a production process, including various tests and a treatment/coating
operation.
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Several possible tests can be implemented to ensure that a device will have
the
appropriate surface for treatment/coating. These include:
[652] VIA. 1. Optical Inspection, for example, transmission of radiation
through
the device, reflection of radiation from the inside of the device or from the
outside,
absorption of radiation by the device, or interference with radiation by the
device.
[653] VIA. 2. Digital Inspection ¨ for example, using a digital camera that
can
[treasure specific lengths and geometries (for example how "round" or
otherwise evenly
or correctly shaped the open end of a sample collection tube is relative to a
reference).
[6541 VIA. 3. Vacuum leak checkinq or pressure testinq.
[655] VIA. 4. Sonic (ultra sonic) testing of the device.
[656] VIA. 5. X-ray analysis.
[657] VIA. 6. Electrical conductivity of the device (the plastic tube
material and
Sia, have different electrical resistance ¨ on the order of 1020 Ohm-cm for
quartz as a
bulk material and on the order of 1014 Ohm-cm for polyethylene terephthalate,
for
example).
[658] VIA. 7. Thermal conductivity of the device (for example, the thermal
conductivity of quartz as a bulk material is about 1.3 W- K/m, while the
thermal
conductivity of polyethylene terephthalate is 0.24 W- K/m).
[659] VIA. 8. Outgassing of the vessel wall, which optionally can be
measured as
described below under post-coating inspection to determine an outgassing
baseline.
[660] VIA. The above testing can be conducted in a station 24 as shown in
FIG. 6.
In this figure the device (for example a sample collection tube 80) can be
held in place
and a light source (or other source) 132 can be inserted into the device and
an
appropriate detector 134 positioned outside of the device to measure the
desired result.
[661] VIA. In the case of vacuum leak detection, the vessel holder and
device can
be coupled to a vacuum pump and a measuring device inserted into the tube. The
testing can also be conducted as detailed elsewhere in the specification.
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[662] VIA. The processing station or device 24 can be a visual inspection
station,
and can be configured to inspect one or more of the interior surface 88 of a
vessel, its
exterior surface 118, or the interior of its vessel wall 86 between its
surfaces 88 and 118
for defects. The inspection of the exterior surface 118, the interior surface
88, or the
vessel wall 86 can be carried out from outside the vessel 80, particularly if
the vessel is
transparent or translucent to the type of radiation and wavelength used for
inspection.
The inspection of the interior surface 88 can or be facilitated, if desired,
by providing an
optical fiber probe inserted into the vessel 80 via the vessel port 92, so a
view of the
inside of the vessel 80 can be obtained from outside the vessel 80. An
endoscope or
borescope can be used in this environment, for example.
[663] VIA. Another expedient illustrated in FIG. 6 can be to insert a light
source
132 within a vessel 80. The light transmitted through the vessel wall 86, and
artifacts of
the vessel 80 made apparent by the light, can be detected from outside the
vessel 80,
as by using a detector measuring apparatus 134. This station or device 24 can
be
used, for example, to detect and correct or remove misaligned vessels 80 not
properly
seated on the vessel port 96 or vessels 80 that have a visible distortion,
impurity, or
other defect in the wall 86. Visual inspection of the vessel 80 also can be
conducted by
a worker viewing the vessel 80, instead or in addition to in aorrine
inspection.
[664] VIA. The processing station or device 26, shown in more detail in
FIG. 7,
can be optionally configured to inspect the interior surface 88 of a vessel 80
for defects,
and for example to measure the gas pressure loss through the vessel wall 86,
which
can be done before a barrier or other type of coating is provided. This test
can be
carried out by creating a pressure difference between the two sides of the
barrier
coating 90, as by pressurizing or evacuating the interior of the vessel 80,
isolating the
interior 154 of the vessel 80 so the pressure will remain constant absent
leakage around
the seal or permeation of gas through the vessel wall, and measuring the
pressure
change per unit time accumulating from these problems. This measurement will
not
only reveal any gas coming through the vessel wall 86, but will also detect a
leaking
seal between the mouth 82 of the vessel and the 0-ring or other seal 100,
which might
indicate either a problem with the alignment of the vessel 80 or with the
function of the
seal 100. In either case, the tube m is-seating can be corrected or the tube
taken out of
140
the processing line, saving time in attempting to achieve or maintain the
proper
processing vacuum level and preventing the dilution of the process gases by
air drawn
through a malfunctioning seal.
[665] VI.A. The above systems can be integrated into a manufacturing and
inspection
method comprising multiple steps.
[666] VI.A. FIG. 1 as previously described shows a schematic layout of the
steps of one
possible method (although this invention according to its embodiments is not
limited to a
single concept or approach). First the vessel 80 is visually inspected at the
station or by
the device 24, which can include dimensional measurement of the vessel 80. If
there are
any defects found, the device or vessel 80 is rejected and the puck or vessel
holder such
as 38 is inspected for defects, recycled or removed.
[667] VI A. Next the leak rate or other characteristics of the assembly of a
vessel holder
38 and seated vessel 80 is tested, as at the station 26, and stored for
comparison after
coating. The puck or vessel holder 36 then moves, for example, into the
coating step 20.
The device or vessel 80 is coated with a SiOx or other barrier or other type
of coating at
a power supply frequency of, for example, 13.56 MHz. Once coated, the vessel
holder
is retested for its leak rate or other characteristics (this can be carried
out as a second
test at the testing station 26 or a duplicate or similar station such as 30 ¨
the use of a
duplicate station can increase the system throughput).
[668] VLA. The coated measurement can be compared to the uncoated measurement.
IT the ratio ot tnese values exceeds a pre-set required level, indicating an
acceptable
overall coating performance, the vessel holder and device move on. An optical
testing
station 32, for example, follows with a blue light source and an external
integrating sphere
detector to measure the total light transmitted through the tube. The value
can be
required to exceed a pre-set limit at which the device is rejected or recycled
for additional
coating. Next (for devices that are not rejected), a second optical testing
station 34 can
be used. In this case a point light source can be inserted inside of the tube
or vessel 80
and pulled out slowly while measurements are taken with a tubular CCD detector
array
outside of the tube. The data is then computationally analyzed to
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determine the defect density distribution. Based on the measurements the
device is
either approved for final packaging or rejected.
[669] VIA. The above data optionally can be logged and plotted (for
example,
electronically) using statistical process control techniques to ensure up to 6-
sigma
quality.
VI.B. Vessel Inspection By Detecting Outgassing Of Container Wall Through
Barrier Layer
[670] VI.B. Another embodiment is a method for inspecting a barrier or
other type
of layer on a material that outgasses a vapor, having several steps. A sample
of
material that outgasses a gas and has at least a partial barrier layer is
provided.
Optionally, a pressure differential can be provided across the barrier layer,
such that at
least some of the material that outgasses is on the higher-pressure side of
the barrier
layer. In another option, the outgassed gas can be allowed to diffuse without
providing
a pressure difference. The outgassed gas is measured. If a pressure
differential is
provided across the barrier layer, the outgassing can be measured on the
higher-
pressure or lower-pressure side of the barrier layer.
[671] VI.B. In addition a measurement of the efficacy of the interior
coating
(applied above) can be made by measuring the diffusion rate of a specific
species or
adsorbed materials in the wall of the device (prior to coating). When compared
to an
uncoated (untreated) tube, this type of measurement can provide a direct
measurement
of the barrier or other type of properties of the coating or treatment, or the
presence or
absence of the coating or treatment. The coating or treatment detected, in
addition to or
instead of being a barrier layer, can be a lubricity layer, a hydrophobic
layer, a
decorative coating, or other types of layers that modify the outgassing of the
substrate,
ether by increasing or decreasing it.
[672] VI.B. As a specific example using the vessel holder from FIG. 2 and
referring
again to FIG. 7, a device or vessel 80 can be inserted into the puck or vessel
holder 44
(the test can also be carried out on a seated vessel 80 carried in a puck or
vessel holder
such as 44 moving from another operation such as coating/treatment). Once the
vessel
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holder moves into the barrier testing area, the measurement tube or probe 108
can be
inserted into the inside (in a similar manner as the gas tube for coating,
although the
measurement tube does not need to extend as far into the tube). Valves 136 and
148
can both be opened and the interior of the tube can be evacuated (a vacuum
created).
[673] VI.B. Once a desired measurement pressure is reached, the valves 136
and
148 can be closed and the pressure gauge 152 can begin measuring the pressure.
By
measuring the time that a particular pressure (higher than the starting
pressure) is
reached or by measuring the pressure reached after a given amount of time, the
rate of
rise (or leak-rate) of the tube, vessel holder, pump channel and all other
parts
connected to toe interior volume Out isolated by valve 1 and 2 can be
measured. If this
value is then compared to an uncoated tube, the ratio of the two measurements
(the
coated tube value divided by the uncoated tube value) can yield a measurement
of the
leak rate through the coated surface of the tube. This measurement technique
can
require the minimization of the interior volume of toe vessel holder, pump
channel and
all other parts connected to the interior volume but isolated by valve 1 and 2
(except the
tube/device) to minimize the impact of gas permeation or outgassing from these
surfaces.
[674] VI.B. Distinctions are made in this disclosure among "permeation,"
"leakage,"
and "surface diffusion" or "outgassing."
[675] "Permeation" as used here in reference to a vessel is traverse of a
material
through a wall 346 or other obstruction, as from the outside of the vessel to
the inside or
vice versa along the path 350 in FIG. 29 or the reverse of that path.
[676] Outgassing refers to the movement of an absorbed or adsorbed material
such
as the gas molecule 354 or 357 or 359 outward from within the wall 346 or
coating 348
in FIG. 29, for example through the coating 348 (if present) and into the
vessel 358 (to
the right in FIG. 29). Outgassing can also refer to movement of a material
such as 354
or 357 out of the wall 346, to the left as shown in FIG. 29, thus to the
outside of the
vessel 357 as illustrated. Outgassing can also refer to the removal of
adsorbed material
from the surface of an article, for example the gas molecule 355 from the
exposed
surface of the barrier coating 90.
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[677] Leakage refers to the movement of a material around the obstruction
represented by the wall 346 and coating 348 rather than through or off the
surface of
the obstruction, as by passing between a closure and the wall of a vessel
closed with a
closure.
[678] VI.B. Permeation is indicative of the rate of gas movement through a
rnaterial, devoid of gaps/defects and not relating to leaks or outgassing.
Referring to
FIG. 29, which shows a vessel wall or other substrate 346 having a barrier
coating 348,
permeation is traverse of a gas entirely through the substrate 346 and coating
348
along the path 350 through both layers. Permeation is regarded as a
thermodynamic,
thus relatively slow, process.
[679] VI.B. Permeation measurements are very slow, as the permeating gas
must
past entirely through an unbroken wall of the plastic article. In the case of
evacuated
blood collection tubes, a measurement of permeation of gas through its wall is
conventionally used as a direct indication of the propensity of the vessel to
lose vacuum
over time, but commonly is an extremely slow measurement, commonly requiring a
test
duration of six days, thus not fast enough to support on-line coating
inspection. Such
testing is ordinarily used for off-line testing of a sample of vessels.
[680] VI.B. Permeation testing also is not a very sensitive measurement of
the
barrier efficacy of a thin coating on a thick substrate. Since all the gas
flow is through
both the coating and the substrate, variations in flow through the thick
substrate will
introduce variation that is not due to the barrier efficacy of the coating per
se.
[681] VI.B. The inventors have found a much quicker and potentially more
sensitive way of measuring the barrier properties of a coating ¨ measuring
outgassing
of quickly-separated air or other gaseous or volatile constituents in the
vessel wall
through the coating. The gaseous or volatile constituents can be any material
that in fact
outgasses, or can be selected from one or more specific materials to be
detected. The
constituents can include, but are not limited to, oxygen, nitrogen, air,
carbon dioxide,
water vapor, helium, volatile organic materials such as alcohols, ketones,
hydrocarbons,
coating precursors, substrate components, by-products of the preparation of
the coating
such as volatile organosilicons, by-products of the preparation of the coated
substrate,
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other constituents that happen to be present or are introduced by spiking the
substrate,
or mixtures or combinations of any of these.
[682] Surface diffusion and outgassing are synonyms. Each term refers to
fluid
initially adsorbed on or absorbed in a wall 346, such as the wall of a vessel,
and caused
to pass into the adjacent space by some motivating force, such as drawing a
vacuum
(creating air movement indicated by the arrow 352 of FIG. 29) within a vessel
having a
wall to force fluid out of the wall into the Interior of the vessel.
Outgassing or diffusion is
regarded as a kinetic, relatively quick process. It is contemplated that, for
a wall 346
having substantial resistance to permeation along the path 350, outgassing
will quickly
dislodge Ire molecules such as 354 that are closest to the interface 356
between tne
wall 346 and the barrier layer 348. This differential outgassing is suggested
by the large
number of molecules such as 354 near the interface 356 shown as outgassing,
and by
the large number of other molecules such as 358 that are further from the
interface 356
and are not shown as outgassing.
[683] VI.B. Accordingly, yet another method is contemplated for inspecting
a
barrier layer on a material that outgasses a vapor, including several steps. A
sample of
rnaterial is provided that outgasses a gas and has at least a partial barrier
layer. A
pressure differential is provided across the barrier layer, such that at least
some of the
rnaterial that outgasses initially is on the higher-pressure side of the
barrier layer. The
outgassed gas transported to the lower-pressure side of the barrier layer
during a test is
treasured to determine such information as whether the barrier is present or
how
effective it is as a barrier.
[684] VI.B. In this method, the material that outgasses a gas can include a
polymeric compound, a thermoplastic compound, or one or more compounds having
both properties. The material that outgasses a gas can include polyester, for
example
polyethylene terephthalate. The material that outgasses a gas can include a
polyolefin,
for two examples polypropylene, a cyclic olefin copolymer, or a combination of
these.
The material that outgasses a gas can be a composite of two different
materials, at least
one of which outgasses a vapor. One example is a two layer structure of
polypropylene
and polyethylene terephthalate. Another example is a two layer structure of
cyclic olefin
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copolymer and polyethylene terephthalate. These materials and composites are
exemplary; any suitable material or combination of materials can be used.
[685] VI.B. Optionally, the material that outgasses a gas is provided in
the form of
a vessel having a wall having an outer surface and an inner surface, the inner
surface
enclosing a lumen. In this embodiment, the barrier layer optionally is
disposed on the
vessel wall, optionally on the inner surface of the vessel wall. The barrier
layer could or
also be disposed on the outer surface of the vessel wall. Optionally, the
material that
outgasses a gas can be provided in the form of a film.
[686] VI.B. The barrier layer can be a full or partial coating of any of
the presently
described barrier layers. The barrier layer can be less than 500 nm thick, or
less than
300 nm thick, or less than 100 nm thick, or less than 80 nm thick, or less
than 60 nm
thick, or less than 50 nm thick, or less than 40 nm thick, or less than 30 nm
thick, or less
than 20 nm thick, or less than 10 nm thick, or less than 5 nm thick.
[687] VI.B. In the case of a coated wall, the inventors have found that
diffusion/
outgassing can be used to determine the coating integrity. Optionally, a
pressure
differential can be provided across the barrier layer by at least partially
evacuating the
lumen or interior space of the vessel. This can be done, for example, by
connecting the
lumen via a duct to a vacuum source to at least partially evacuate the lumen.
For
example, an uncoated PET wall 346 of a vessel that has been exposed to ambient
air
will outgas from its interior surface a certain number of oxygen and other gas
molecules
such as 354 for some time after a vacuum is drawn. If the same PET wall is
coated on
the interior with a barrier coating 348, the barrier coating will stop, slow
down, or reduce
this outgassing. This is true for example of an SiOx barrier coating 348,
which
outgasses less than a plastic surface. By measuring this differential of
outgassing
between coated and uncoated PET walls, the barrier effect of the coating 348
for the
outgassed material can be rapidly determined.
[688] VI.B. If the barrier coating 348 is imperfect, due to known or
theoretical holes,
cracks, gaps or areas of insufficient thickness or density or composition, the
PET wall
will outgas preferentially through the imperfections. thus increasing the
total amount of
outgassing. The primary source of the collected gas is from the dissolved gas
or
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vaporizable constituents in the (sub)surface of the plastic article next to
the coating, not
from outsde the article. The amount of outgassing beyond a basic level (for
example
the amount passed or released by a standard coaling with no imperfections, or
the least
attainable degree of imperfection, or an average and acceptable degree of
imperfection)
can be measured in various ways to determine the integrity of the coating.
[689] VI.B. The measurement can be carried out, for example, by providing
an
outgassing measurement cell communicating between the lumen and the vacuum
source.
[690] VI.B. The measurement cell can implement any of a variety of
different
measurement technologies. One example of a suitable measurement technology is
micro-flow technology. For example, the mass flow rate of outgassed material
can be
measured. The measurement can be carried out in a molecular flow mode of
operation.
An exemplary measurement is a determination of the volume of gas outgassed
through
the barrier layer per interval of time.
[691] VI.B. The outgassed gas on the lower-pressure side of the barrier
layer can
be measured under conditions effective to distinguish the presence or absence
of the
barrier layer. Optionally, the conditions effective to distinguish the
presence or absence
of the barrier layer include a test duration of less than one minute, or less
than 50
seconds, or less than 40 seconds, or less than 30 seconds, or less than 20
seconds, or
less than 15 seconds, or less than 10 seconds, or less than 8 seconds, or less
than 6
seconds, or less than 4 seconds. or less than 3 seconds, or less than 2
seconds, or less
than 1 second.
[692] VI.B. Optionally, the measurement of the presence or absence of the
barrier
layer can be confirmed to at least a six-sigma level of certainty within any
of the time
intervals identified above.
[693] VI.B. Optionally, the outgassed gas on the lower-pressure side of the
barrier
layer is measured under conditions effective to determine the barrier
improvement
factor (BIF) of the barrier layer, compared to the same material without a
barrier layer.
ADIF can be determined, for example, by providing two groups of identical
containers,
adding a barrier layer to one group of containers, testing a barrier property
(such as the
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rate of outgassing in micrograms per minute or another suitable measure) on
containers
having a barrier, doing the same test on containers lacking a barrier, and
taking a ratio
of the properties of the materials with versus without a barrier. For example,
if the rate
of outgassing through the barrier is one-third the rate of outgassing without
a barrier, the
barrier has a BIF of 3.
[694] VI.B. Optionally, outgassing of a plurality of different gases can be
measured,
in instances where more than one type of gas is present, such as both nitrogen
and
oxygen in the case of outgassed air. Optionally, outgassing of substantially
all or all of
the outgassed gases can be measured. Optionally, outgassing of substantially
all of the
outgassed gases can be measured simultaneously, as by using a physical
measurement like the combined mass flow rate of all gases.
[695] VI.B. Nleasuring the number or partial pressure of individual gas
species
(such as oxygen or helium) outgassed from the sample can be done more quickly
than
barometric testing, but the rate of testing is reduced to the extent that only
a fraction of
the outgassing is of the measured species. For example, if nitrogen and oxygen
are
outgassed from the PET wall in the approximately 4:1 proportion of the
atmosphere, but
only oxygen outgassing is measured, the test would need to be run five times
as long as
an equally sensitive test (in terms of number of molecules detected to obtain
results of
sufficient statistical quality) that measures all the species outgassed from
the vessel
wall.
[696] VI.B. For a given level of sensitivity, it is contemplated that a
method that
accounts for the volume of all species outgassed from the surface will provide
the
desired level of confidence more quickly than a test that measures outgassing
of a
specific species, such as oxygen atoms. Consequently, outgassing data having
practical utility for in-line measurements can be generated. Such in-line
measurements
can optionally be carried out on every vessel manufactured, thus reducing the
number
of idiosyncratic or isolated defects and potentially eliminating them (at
least at the time
of measurement).
[697] VI.B. In a practical measurement, a factor changing the apparent
amount of
outgassing is leakage past an imperfect seal, such as the seal of the vessel
seated on a
148
vacuum receptacle as the vacuum is drawn in the outgassing test. Leakage means
a
fluid bypassing a solid wall of the article, for example fluid passing between
a blood tube
and its closure, between a syringe plunger and syringe barrel, between a
container and
its cap, or between a vessel mouth and a seal upon which the vessel mouth is
seated
(due to an imperfect or mis-seated seal). The word "leakage" is usually
indicative of the
movement of gas/gas through an opening in the plastic article.
[698] VI.B. Leakage and (if necessary in a given situation) permeation can be
factored
into the basic level of outgassing, so an acceptable test result assures both
that the
vessel is adequately seated on the vacuum receptacle (thus its seated surfaces
are intact
and properly formed and positioned), the vessel wall does not support an
unacceptable
level of permeation (thus the vessel wall is intact and properly formed), and
the coating
has sufficient barrier integrity.
[699] VI.B. Outgassing can be measured in various ways, as by barometric
measurement (measuring the pressure change within the vessel in a given amount
of
time after the initial vacuum is drawn) or by measuring the partial pressure
or flow rate
of gas outgassed from the sample. Equipment is available that measures a mass
flow
rate in a molecular flow mode of operation. An example of commercially
available
equipment or tnis type employing micro-Flow -recnnoiogy is available from
AIL:, inc.,
Indianapolis, IN. See U.S. Patent Nos. 5861546, 6308556, 6584828 and
EP1356260,
for a further description of this known equipment. See also Example 8 in this
specification, showing an example of outgassing measurement to distinguish
barrier
coated polyethylene terephthalate (PET) tubes from uncoated tubes very rapidly
and
reliably.
[700] VI.B. For a vessel made of polyethylene terephthalate (PET), the
microflow rate
is much different for the SiOx coated surface versus an uncoated surface. For
example,
in Working Example 8 in this specification, the microflow rate for PET was 8
or more
micrograms after the test had run for 30 seconds, as shown in FIG. 31. This
rate for
uncoated PET was much higher than the measured rate for SiOx-coated PET, which
was
less than 6 micrograms after the test had run for 30 sec, again as shown in
FIG. 31.
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[701] VI.B. One possible explanation for this difference in flow rate is that
uncoated PET
contains roughly 0/ percent equilibrium moisture; this high moisture content
is believed
to cause the observed high microflow rate. With an SiOx-coated PET plastic,
the SiOx
coating may have a higher level of surface moisture than an uncoated PET
surface.
Under the testing conditions, however, the barrier coating is believed to
prevent
additional desorption of moisture from the bulk PET plastic, resulting in a
lower microflow
rate. The microflow rates of oxygen or nitrogen from the uncoated PET plastic
versus the
SiOx coated PET would also be expected to be distinguishable.
[702] VI.B. Modifications of the above test for a PET tube might be
appropriate when
using other materials. For example, polyolefin plastics tend to have little
moisture
content An example of a polyolefin having low moisture content is TOPASO
cyclic olefin
copolymer (COC), having an equilibrium moisture content (0.01 percent) and
moisture
permeation rate much lower than for PET. In the case of COC, uncoated COC
plastic
can have microflow rate similar to, or even less than, SiOx-coated COC
plastic. This is
most likely due to the higher surface moisture content of the SiOx-coating and
the lower
equilibrium bulk moisture content and lower permeation rate of an uncoated COC
plastic
surface. This makes differentiation of uncoated and coated COC articles more
difficult.
[703] The present invention according to its embodiments shows that exposure
of the
to-be-tested surfaces of COC articles to moisture (uncoated and coated)
results in
improved and consistent microflow separation between uncoated and SiOx-coated
COC
plastics. This is shown in Example 19 in this specification and FIG. 57. The
moisture
exposure can be simply exposure to relative humidity ranging from 35%-100%,
either in
a controlled relative humidity room or direct exposure to a warm (humidifier)
or cold
(vaporizer) moisture source, with the latter being illustrative.
[704] VI.B. While the validity and scope of the invention according to its
embodiments
are not limited according to the accuracy of this theory, it appears the
moisture doping
or spiking of the uncoated COC plastic increases its moisture or other
outgassable
content relative to the already saturated SiOx-coated COC surface. This can
also be
accomplished by exposing the
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coated and uncoated tubes to other gases including oxygen, nitrogen, or their
mixtures,
for example air.
[705] VI.B Thus, before measuring the outgassed gas, the barrier layer can
be
contacted with water, for example water vapor. Water vapor can be provided,
for
example, by contacting the barrier layer with air at a relative humidity of
35% to 100%,
alternatively 40% to 100%, alternatively 40% to 50%. Instead of or in addition
to water,
the barrier layer can be contacted with oxygen, nitrogen or a mixture of
oxygen and
nitrogen, for example ambient air. The contacting time can be from 10 seconds
to one
hour, alternatively from one minute to thirty minutes, alternatively from 5
minutes to 25
minutes, alternatively from 10 minutes to 20 minutes.
[706] Alternatively, the wall 346 which will be outgassing can be spiked or
supplemented from the side opposite a barrier layer 348, for example by
exposing the
left side of the wall 346 as shown in FIG. 11 to a material that will ingas
into the wall
346, then outgas either to the left or to the right as shown in FIG. 29.
Spiking a wall or
other material such as 346 from the left by ingassing, then measuring
outgassing of the
spiked material from the right (or vice versa) is distinguished from
permeation
measurement because the material spiked is within the wall 346 at the time
outgassing
is measured, as opposed to material that travels the full path 350 through the
wall at the
time gas presented through the coating is being measured. The ingassing can
take
place over a long period of time, as one embodiment before the coating 348 is
applied,
and as another embodiment after the coating 348 is applied and before it is
tested for
outgassing.
[707] VI.B. Another potential method to increase separation of microflow
response
between uncoated and Si0.-coated plastics is to modify the measurement
pressure
and/ or temperature. Increasing the pressure or decreasing the temperature
when
measuring outgassing may result in greater relative binding of water molecules
in Si0,,-
coated COC than in uncoated COC. Thus, the outgassed gas can be measured at a
pressure from 0.1 Torr to 100 Torr, alternatively from 0.2 Torr to 50 Torr,
alternatively
from 0.5 Torr to 40 Torr, alternatively from 1 Torr to 30 Torr, alternatively
from 5 Torr to
100 Torr, alternatively from 10 Torr to 80 Torr, alternatively from 15 Torr to
50 Torr. The
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outgassed gas can be measured at a temperature from 0 C to 50 CC,
alternatively from
o C to 21 C, alternatively from 5cC to 20 C.
[708] VI.B. Another way contemplated for measuring outgassing, in any
embodiment of the present disclosure, is to employ a microcantilever
measurement
technique. Such a technique is contemplated to allow measurement of smaller
mass
differences in outgassing, potentially on the order of 10-12 g. (picograms) to
10-15 g.
(femtograrns). This smaller mass detection permits differentiation of coated
versus
uncoated surfaces as well as different coatings in less than a second,
optionally less
than 0.1 sec., optionally a matter of microseconds.
[709] VI.B. Microcantilever (MCL) sensors in some instances can respond to
the
presence of an outgassed or otherwise provided material by bending or
otherwise
roving or changing shape due to the absorption of molecules. Microcantilever
(MCL)
sensors in some instances can respond by shifting in resonance frequency. In
other
instances, the MCL sensors may change in both these ways or in other ways.
They can
be operated in different environments such as gaseous environment, liquids, or
vacuum. In gas, microcantilever sensors can be operated as an artificial nose,
whereby
the bending pattern of a microfabricated array of eight polymer-coated silicon
cantilevers is characteristic of the different vapors from solvents, flavors,
and
beverages. The use of any other type of electronic nose, operated by any
technology,
is also contemplated.
[710] Several MCL electronic designs, including piezoresistive,
piezoelectric, and
capacitive approaches, have been applied and are contemplated to measure the
rovement, change of shape, or frequency change of the MCLs upon exposure to
chemicals.
[711] VI.R. One specific example of measuring outgassing can be carried out
as
follows. At least one microcantilever is provided that has the property, when
in the
presence of an cutgassed material, of moving or changing to a different shape.
The
r icrocantilever is exposed to the outgassed material under conditions
effective to cause
the microcantilever to move or change to a different shape. The movement or
different
shape is then detected.
152
[712] VI.B. As one example, the movement or different shape can be detected by
reflecting an energetic incident beam from a portion of the microcantilever
that moves or
changes shape, before and after exposing the microcantilever to outgassing,
and
measuring the resulting deflection of the reflected beam at a point spaced
from the
cantilever. The shape is illustratively measured at a point spaced from the
cantilever
because the amount of deflection of the beam under given conditions is
proportional to
the distance of the point of measurement from the point of reflection of the
beam.
[713] VI.B. Several suitable examples of an energetic incident beam are a beam
of
photons, a beam of electrons, or a combination of two or more of these.
Alternatively,
two or more different beams can be reflected from the MCL along different
incident and/or
reflected paths, to determine movement or shape change from more than one
perspective. One specifically contemplated type of energetic incident beam is
a beam
of coherent photons, such as a laser beam. "Photons" as discussed in this
specification
are inclusively defined to include wave energy as well as particle or photon
energy per
se.
[714] VI.B. An alternative example of measurement takes is intended to take of
the
property of certain MCLs of changing in resonant frequency when encountering
an
environmental material in an effective amount to accompiisn a cnange in
resonant
frequency. This type of measurement can be carried out as follows. At least
one
microcantilever is provided that resonates at a different frequency when in
the presence
of an outgassed material. The microcantilever can be exposed to the outgassed
material
under conditions effective to cause the microcantilever to resonate at a
different
frequency. The different resonant frequency is then detected by any suitable
means.
[715] VI.B. As one example, the different resonant frequency can be detected
by
inputting energy to the microcanti lever to induce it to resonate before and
after exposing
the microcantilever to outgassing. The differences between the resonant
frequencies of
the MCLbefore and after exposure to outgassing are determined. Alternatively,
instead
of determining the difference in resonant frequency, an MCL can be provided
that is
known to have a certain resonant frequency when in the presence of a
sufficient
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concentration or quantity of an outgassed material. The different resonant
frequency or the
resonant frequency signaling the presence of a sufficient quantity of the
outgassed material
is detected using a harmonic vibration sensor.
[716] As one example of using MCL technology for measuring outgassing, an
MCL
device can be incorporated into a quartz vacuum tube linked to a vessel and
vacuum
pump. A harmonic vibration sensor using a commercially available
piezoresistive
cantilever, Wheatstone bridge circuits, a positive feedback controller, an
exciting
piezoactuator and a phase-locked loop (PLL) demodulator can be constructed.
See,
e.g.,
= Hayato Sone, Yoshinori Fujinuma and Sumio Hosaka Picogram Mass
Sensor Using Resonance Frequency Shift of Cantilever, Jpn. J. Appl.
Phys. 43 (2004) 3648;
= Hayato Sone, Ayumi lkeuchi, Takashi lzumil, Haruki 0kano2 and Sumio
Hosaka Femtogram Mass Biosensor Using Self-Sensing Cantilever for Allergy
Check, Jpn. J. Appl. Phys. 43 (2006) 2301).
To prepare the MCL for detection, one side of the microcantilever can be
coated with
gelatin. See, e.g., Hans Peter Lang, Christoph Gerber, STM and AFM Studies on
(Bio)molecular Systems: Unravelling the Nanoworld, Topics in Current
Chemistry,
Volume 285/2008. Water vapor desorbing from the evacuated coated vessel
surface
binds with the gelatin, causing the cantilever to bend and its resonant
frequency to
change, as measured by laser deflection from a surface of the cantilever. The
change in
mass of an uncoated vs coated vessel is contemplated In he resolvable in
fractions of
seconds and be highly reproducible. The articles cited above in connection
with
cantilever technology are cited for their disclosures of specific MCLs and
equipment
arrangements that can be used for detecting and quantifying outgassed species.
[717] Alternative coatings for moisture detection (phosphoric acid) or
oxygen
detection can be applied to MCLs in place of or in addition to the gelatin
coating
described above.
154
[718] VI.B. It is further contemplated that any of the presently contemplated
outgassing
test set-ups can be combined with an SiOx coating station. In such an
arrangement, the
measurement cell 362 could be as illustrated above, using the main vacuum
channel for
PECVD as the bypass 386. In an embodiment, the measurement cell generally
indicated
as 362 of FIG. 30 can be incorporated in a vessel holder such as 50 in which
the bypass
channel 386 is configured as the main vacuum duct 94 and the measurement cell
362 is
a side channel.
[719] VI.B. This combination of the measurement cell 362 with the vessel
holder 50
would optionally allow the outgassing measurement to be conducted without
breaking
the vacuum used for PECVD. Optionally, the vacuum pump for PECVD would be
operated for a short, illustratively standardized amount of time to pump out
some or all
of the residual reactant gases remaining after the coating step (a pump-down
of less
than one Torr, with a further option of admitting a small amount of air,
nitrogen, oxygen,
or other gas to flush out or dilute the process gases before pumping down).
This would
expedite the combined processes of coating the vessel and testing the coating
for
presence and barrier level.
[720] VI.B. It will be further appreciated by those skilled in the art, after
review of this
specification, that outgassing measurements and all the other aescribea
barrier
measurement techniques can be used for many purposes other than or in addition
to
determining the efficacy of a barrier layer. For one example, the test can be
used on
uncoated or coated vessels to determine the degree of outgassing of the vessel
walls.
This test can be used, for example, in cases in which an uncoated polymer is
required
to outgas less than a specified amount.
[721] VI.B. For another example, these outgassing measurements and all the
other
described barrier measurement techniques can be used on barrier coated or
uncoated
films, either as a static test or as an in-line test to measure variations in
outgassing of a
film as it traverses the measurement cell. The test can be used for
determining the
continuity or barrier efficacy of other types of coatings, such as aluminum
coatings or
EVOH barrier coatings or layers of packaging films.
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[722] VI.B. These outgassing measurements and all the other described
barrier
measurement techniques can be used to determine the efficacy of a barrier
layer
applied on the side of a vessel wall, film, or the like opposite the
measurement cell,
such as a barrier layer applied on the outside of a vessel wall and
interrogated for
outgassing to the interior of the vessel wall. In this instance, the flow
differential would
be for permeation through the barrier coating followed by permeation through
the
substrate film or wall. This measurement would be particularly useful in
instances
where the substrate film or wall is quite permeable, such as a very thin or
porous film or
wall.
[723] VI.B. These outgassing measurements and all the other described
barrier
measurement techniques can be used to determine the efficacy of a barrier
layer which
is an interior layer of a vessel wall, film, or the like, in which case the
measurement cell
would defect any outgassing through the layer adjacent to the measurement cell
plus
outgassing, through the barrier layer, of me layer or layers more remote from
me
measurement cell than the barrier layer.
[724] VI.B. These outgassing measurements and all the other described
barrier
measurement techniques can be used to determine the percentage of coverage of
a
pattern of barrier material over a material that outgasses, as by determining
the degree
of outgassing of the partially barrier coated material as a proportion of the
amount of
outgassing expected if no barrier were present over any part of the material.
[725] VI.B. One test technique that can be used to increase the rate of
testing for
outgassing of a vessel, usable with any outgassing test embodiment in the
specification,
is to reduce the void volume of the vessel, as by inserting a plunger or
closure into the
vessel to reduce the void volume of the portion of the vessel tested.
Decreasing the
void volume allows the vessel to be pumped down more quickly to a given vacuum
level, thus decreasing the test interval.
[726] VI.B. Many other applications for the presently described outgassing
measurements and all the other described barrier measurement techniques will
be
evident to the skilled person after reviewing this specification.
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VII. PECVD TREATED VESSELS
[727] VII. Vessels are contemplated having a barrier coating 90 (shown in
FIG. 2,
for example), which can be an SiOx coating applied to a thickness of at least
2 nm, or at
least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm, or at
least 30 nm, or at
least 40 nm, or at least 50 nm, or at least 100 nm, or at least 150 nm, or at
least 200
nm, or at least 300 nm, or at least 400 nm, or at least 500 nm, or at least
600 nm, or at
least 700 nm, or at least 800 nrn, or at least 900 nm. The coating can be up
to 1000
nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or at most 600
nm, or at
most 500 nm, or at most 400 nm, or at most 300 nm, or at most 200 nm, or at
most 100
nm, or at most 90 nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or
at most
50 nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm,
or at
most 5 nm thick. Specific thickness ranges composed of any one of the minimum
thicknesses expressed above, plus any equal or greater one of the maximum
thicknesses expressed above, are expressly contemplated. The thickness of the
SiOx
or other coating can be measured, for example, by transmission electron
microscopy
(TEM), and its composition can be measured by X-ray photoelectron spectroscopy
(XPS).
[728] VII. It is contemplated that the choice of the material to be barred
from
permeating the coating and the nature of the SiOx coating applied can affect
its barrier
efficacy. For example, two examples of material commonly intended to be barred
are
oxygen and water/water vapor. Materials commonly are a better barrier to one
than to
the other. This is believed to be so at least in part because oxygen is
transmitted
through the coating by a different mechanism than water is transmitted.
[729] VII. Oxygen transmission is affected by the physical features of the
coating,
such as its thickness, the presence of cracks, and other physical details of
the coating.
Water transmission, on the other hand, is believed to commonly be affected by
chemical
factors, i.e. the material of which the coating is made, more than physical
factors. The
inventors also believe that at least one of these chemical factors is a
substantial
concentration of OH moieties in the coating, which leads to a higher
transmission rate of
water through the barrier. An SiOx coating often contains OH moieties, and
thus a
157
physically sound coating containing a high proportion of OH moieties is a
better barrier
to oxygen than to water. A physically sound carbon-based barrier, such as
amorphous
carbon or diamond-like carbon (DLC) commonly is a better barrier to water than
is a SiOx
coating because the carbon-based barrier more commonly has a lower
concentration of
OH moieties.
[730] VII. Other factors lead to a consideration for an SiOx coating, however,
such as
its oxygen barrier efficacy and its close chemical resemblance to glass and
quartz_ Glass
and quartz (when used as the base material of a vessel) are two materials long
known
to present a very high barrier to oxygen and water transmission as well as
substantial
inertness to many materials commonly carried in vessels. Thus, it is commonly
desirable
to optimize the water barrier properties such as the water vapor transmission
rate
(VVVTR) of an SiOx coating, rather than choosing a different or additional
type of coating
to serve as a water transmission barrier.
[731] VII. Several ways contemplated to improve the VVVTR of an SiOx coating
are
as follow.
[732] VII. The concentration ratio of organic moieties (carbon and hydrogen
compounds)
to OH moieties in the deposited coating can be increased. This can be done,
for example,
by increasing the proportion of oxygen in the feed gases (as by increasing the
oxygen
feed rate or by loweling the feed rate of one or more other constituents). The
lowered
incidence of OH moieties is believed to result from increasing the degree of
reaction of
the oxygen feed with the hydrogen in the silicone source to yield more
volatile water in
the PECVD exhaust and a lower concentration of OH moieties trapped or
incorporated
in the coating.
[733] VII. Higher energy can be applied in the PECVD process, either by
raising the
plasma generation power level, by applying the power for a longer period, or
both. An
increase in the applied energy must be employed with care when used to coat a
plastic
tube or other device, as it also has a tendency to distort the vessel being
treated, to the
extent the tube absorbs the plasma generation power. This is why RF power is
illustrative
in the context of present application. Distortion of the medical devices can
be reduced or
eliminated by employing the energy in a series of two or more pulses
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separated by cooling time, by cooling the vessels while applying energy, by
applying the
coating in a shorter time (commonly thus making it thinner), by selecting a
frequency of
the applied coating that is absorbed minimally by the base material selected
for being
coated, and/or by applying more than one coating, with time in between the
respective
energy application steps. For example, high power pulsing can be used with a
duty
cycle of 1 millisecond on, 99 milliseconds off, while continuing to feed the
process gas.
The process gas is then the coolant, as it keeps flowing between pulses.
Another
alternative is to reconfigure the power applicator, as by adding magnets to
confine the
plasma increase the effective power application (the power that actually
results in
incremental coating, as opposed to waste power that results in heating or
unwanted
coating). This expedient results in the application of more coating-formation
energy per
total Watt-hour of energy applied. See for example U.S. Patent 5,904,952.
[734] VII. An oxygen post-treatment of the coating can be applied to remove
OH
moieties from Me previously-deposited coating. This treatment is also
contemplated to
remove residual volatile organosilicon compounds or silicones or oxidize the
coating to
form additional SiOx.
[735] VII. The plastic base material tube can be preheated.
[736] VII. A different volatile source of silicon, such as
hexamethyldisilazane
(HMDZ), can be used as part or all of the silicone feed. It is contemplated
that changing
the feed gas to HMDZ will address the problem because this compound has no
oxygen
moieties in it, as supplied. It is contemplated that one source of OH moieties
in the
HMDSO-sourced coating is hydrogenation of at least some of the oxygen atoms
present
in unreacted HMDSO.
[737] VII. A composite coating can be used, such as a carbon-based coating
combined with Si0. This can be done, for example, by changing the reaction
conditions or by adding a substituted or unsubstituted hydrocarbon, such as an
alkane,
alkene, or alkyne, to the feed gas as well as an organosilicon-based compound.
See
for example U.S. Patent 5,904,952, which states in relevant part: For example,
inclusion of a lower hydrocarbon such as propylene provides carbon moieties
and
improves most properties of the deposited films (except for light
transmission), and
159
bonding analysis indicates the film to be silicon dioxide in nature. Use of
methane,
methanol, or acetylene, however, produces films that are silicone in nature.
The
inclusion of a minor amount of gaseous nitrogen to the gas stream provides
nitrogen
moieties in the deposited films and increases the deposition rate, improves
the
transmission and reflection optical properties on glass, and varies the index
of refraction
in response to varied amounts of Nz. The addition of nitrous oxide to the gas
stream
increases the deposition rate and improves the optical properties, but tends
to decrease
the film hardness."
[738] VII. A diamond-like carbon (DLC) coating can be formed as the primary or
sole
coating deposited. This can be done, for example, by changing the reaction
conditions
or by feeding methane, hydrogen, and helium to a PECVD process. These reaction
feeds
have no oxygen, so no OH moieties can be formed. For one example, an SiOx
coating
can be applied on the interior of a tube or syringe barrel and an outer DLC
coating can
be applied on the exterior surface of a tube or syringe barrel. Or, the SiOx
and DLC
coatings can both be applied as a single layer or plural layers of an interior
tube or syringe
barrel coating.
[739] VII. Referring to FIG. 2, the barrier or other type of coating 90
reduces the
transmission of atmospheric, gases into the vessel 00 through its interior
surface 00. Or,
the barrier or other type of coating 90 reduces the contact of the contents of
the vessel
80 with the interior surface 88. The barrier or other type of coating can
comprise, for
example, SiOx, amorphous (for example, diamond-like) carbon, or a combination
of
these.
[740] VII. Any coating described herein can be used for coating a surface, for
example
a plastic surface. It can further be used as a barrier layer, for example as a
barrier against
a gas or liquid, illustratively against water vapor, oxygen and/or air. It can
also be used
for preventing or reducing mechanical and/or chemical effects which the coated
surface
would have on a compound or composition if the surface were uncoated. For
example,
it can prevent or reduce the precipitation of a compound or composition, for
example
insulin precipitation or blood clotting or platelet activation.
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VII.A. Evacuated Blood Collection Vessels
VII.A.1. Tubes
[741] VILA" Referring to FIG. 2, more details of the vessel such as 80 are
shown.
The illustrated vessel 80 can be generally tubular, having an opening 82 at
one end of
the vessel, opposed by a closed end 84. The vessel 80 also has a wall 86
defining an
interior surface 88. One example of the vessel 80 is a medical sample tube,
such as an
evacuated blood collection tube, as commonly is used by a phlebotomist for
receiving a
venipuncture sample of a patient's blood for use in a medical laboratory.
[742] VII.A.1. The vessel 80 can be made, for example, of thermoplastic
material.
Some examples of suitable thermoplastic material are polyethylene
terephthalate or a
polyolefin such as polypropylene or a cyclic polyolefin copolymer.
[743] VII.A.1. The vessel 80 can be made by any suitable method, such as by
injection molding, by blow molding, by machining, by fabrication from tubing
stock, or by
other suitable means. PECVD can be used to form a coating on the internal
surface of
SiOx.
[744] VII.A.1. If intended for use as an evacuated blood collection tube,
the vessel
80 desirably can be strong enough to withstand a substantially total internal
vacuum
substantially without deformation when exposed to an external pressure of 760
Torr or
atmospheric pressure and other coating processing conditions. This property
can be
provided, in a thermoplastic vessel 80, by providing a vessel 80 made of
suitable
materials having suitable dimensions and a glass transition temperature higher
than the
processing temperature of the coating process, for example a cylindrical wall
86 having
sufficient wall thickness for its diameter and material.
[745] VII.A.1. Medical vessels or containers like sample collection tubes
and
syringes are relatively small and are injection molded with relatively thick
walls, which
renders them able to be evacuated without being crushed by the ambient
atmospheric
pressure. They are thus stronger than carbonated soft drink bottles or other
larger or
thinner-walled plastic containers. Since sample collection tubes designed for
use as
161
evacuated vessels typically are constructed to withstand a full vacuum during
storage,
they can be used as vacuum chambers.
[746] VII.A.1. Such adaptation of the vessels to be their own vacuum chambers
might
eliminate the need to place the vessels into a vacuum chamber for PECVD
treatment,
which typically is carried out at very low pressure. The use of a vessel as
its own vacuum
chamber can result in faster processing time (since loading and unloading of
the parts
from a separate vacuum chamber is not necessary) and can lead to simplified
equipment
configurations. Furthermore, a vessel holder is contemplated, for certain
embodiments,
that will hold the device (for alignment to gas tubes and other apparatus),
seal the device
(so that the vacuum can be created by attaching the vessel holder to a vacuum
pump)
and move the device between molding and subsequent processing steps.
[747] VII.A.1. A vessel 80 used as an evacuated blood collection tube should
be able
to withstand external atmospheric pressure, while internally evacuated to a
reduced
pressure useful for the intended application, without a substantial volume of
air or other
atmospheric gas leaking into the tube (as by bypassing the closure) or
permeating
through the wall 86 during its shelf life. If the as-molded vessel 80 cannot
meet this
requirement, it can be processed by coating the interior surface 88 with a
barrier or other
type orcoating U. it is desirable to treat and/or coat tne interior surfaces
or tnese 'devices
(such as sample collection tubes and syringe barrels) to impart various
properties that
will offer intended advantages over existing polymeric devices and/or to mimic
existing
glass products. It is also desirable to measure various properties of the
devices before
and/or after treatment or coating.
VII.A.1.a. Coating
Deposited from an Organosilicon Precursor Made By In Situ
Polymerizing Organosilicon Precursor
[748] VII.A.1.a. A process is contemplated for applying a lubricity coating on
a substrate,
for example the interior of the barrel of a syringe, comprising applying one
of the
described precursors on or in the vicinity of a substrate at a thickness of 1
to 5000 nm,
optionally 10 to 1000 nm, optionally 10-200 nm, optionally 20 to 100 nm thick
and
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Date Recue/Date Received 2020-08-17
crosslinking or polymerizing (or both) the coating, optionally in a PECVD
process, to
provide a lubricated surface. The coating applied by this process is also
contemplated to
be new.
[749] VII.A.1.a. A coating of SiwOxCyHz, where w is 1, x in this formula is
from about 0.5
to 2.4, y is from about 0.6 to about 3, and z is from 2 to about 9,
illustratively where w is
1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from 6 to
about 9, applied
by PECVD, further has utility as a hydrophobic coating. Coatings of this kind
are
contemplated to be hydrophobic, independent of whether they function as
lubricity
coatings. A coating or treatment is defined as "hydrophobic" if it lowers the
wetting
tension of a surface, compared to the corresponding uncoated or untreated
surface.
Hydrophobicity is thus a function of both the untreated substrate and the
treatment.
[750] The degree of hydrophobicity of a coating can be varied by varying its
composition,
properties, or deposition method. For example, a coating of SiOx having little
or no
hydrocarbon content is more hydrophilic than a coating of SiwOxCyHz with the
substituent
values as defined in this specification. Generally speaking, the higher the C-
Hx (e.g. CH,
CH2, or CH3) moiety content of the coating, either by weight, volume, or
molarity, relative
to its silicon content, the more hydrophobic the coating.
[751] A hydrophobic
coating can be very thin, having a thickness of at least 4 nm, or
at least 7 nm, or at least 10 nm, or at least 20 nm, or at least 30 nm, or at
least 40 nm,
or at least 50 nm, or at least 100 nm, or at least 150 nm, or at least 200 nm,
or at least
300 nm, or at least 400 nm, or at least 500 nm, or at least 600 nm, or at
least 700 nm, or
at least 800 nm, or at least 900 nm. The coating can be up to 1000 nm, or at
most 900
nm, or at most 800 nm, or at most 700 nm, or at most 600 nm, or at most 500
nm, or at
most 400 nm, or at most 300 nm, or at most 200 nm, or at most 100 nm, or at
most 90
nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50 nm, or
at most
40 nm, or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nm
thick.
Specific thickness ranges composed of any one of the minimum thicknesses
expressed
above, plus any equal or greater one of the maximum thicknesses expressed
above, are
expressly contemplated.
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[752] VII.A.1.a. One
utility for such a hydrophobic coating is to isolate a
thermoplastic tube wail, made for example of polyethylene terephthalate (PET),
from
blood collected within the tube. The hydrophobic coating can be applied on top
of a
hydrophilic SiOõ coaling on the internal surface of the tube. The SiOõ coating
increases
the barrier properties of the thermoplastic tube and the hydrophobic coating
changes
the surface energy of blood contact surface with the tube wall. The
hydrophobic coating
can be made by providing a precursor selected from those identified in this
specification. For example, the
hydrophoblc coating precursor can comprise
hexamethyldisiloxane (HMDSO) or octamethylcyclotetrasiloxane (OMCTS).
[753] VII.A.1.a. Another use for a hydrophoblc coating is to prepare a
glass cell
preparation tube. The tube has a wall defining a lumen, a hydrophobic coating
in the
internal surface of the glass wall, and contains a citrate reagent. The
hydrophobic
coating can be made by providing a precursor selected from those identified
elsewhere
in this specification. For another example, the hydrophobic coating precursor
can
comprise hexamethyldisiloxane (HMDSO) or octamethylcyclotetrasiloxane (OMCTS).
Another source material for hydrophobic coatings is an alkyl trimethoxysilane
of the
formula:
R-Si(OCH3)3
in which R is a hydrogen atom or an organic substituent, for example methyl,
ethyl,
propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, epoxide, or
others. Combinations
of two or more of these are also contemplated.
[754] VII.A.1.a. Combinations of acid or base catalysis and heating, using
an alkyl
trimethoxysilane precursor as described above, can condense the precursor
(removing
ROH by-products) to form crosslinked polymers, which can optionally be further
crosslinked via an alternative method. One specific example is by Shimojima
et. al. J.
Mater. Chem., 2007, 17, 658¨ 663.
[755] VII.A.1.a. A coating of Si,,O.CyHz can be applied as a subsequent
coating
after applying an SiO, barrier coating to the interior surface 88 of the
vessel 80 to
provide a lubricity surface, particularly if the surface coating is a liquid
organosiloxane
compound at the end of the coating process.
164
[756] VII.A.1.a. Optionally, after the coating of SiwOxCyHz is applied, it can
be post- cured
after the PECVD process. Radiation curing approaches, including UV-initiated
(free
radial or cationic), electron-beam (E-beam), and thermal as described in
Development
Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications
(Ruby
Chakraborty Dissertation, can 2008) be utilized.
[757] VII.A.1.a. Another approach for providing a lubricity coating is to use
a silicone
demolding agent when injection-molding the thermoplastic vessel to be
lubricated_ For
example, it is contemplated that any of the demolding agents and latent
monomers
causing in-situ thermal lubricity coating formation during the molding process
can be
used. Or, the aforementioned monomers can be doped into traditional demolding
agents
to accomplish the same result.
[758] VII.A.1.a. A lubricity surface is particularly contemplated for the
internal surface
of a syringe barrel as further described below. A lubricated internal surface
of a syringe
barrel can reduce the plunger sliding force needed to advance a plunger in the
barrel
during operation of a syringe, or the breakout force to start a plunger moving
after the
prefilled syringe plunger has pushed away the intervening lubricant or adhered
to the
barrel, for example due to decomposition of the lubricant between the plunger
and the
bar rel. As explained elsewhere lii this specification, a coating of SiwOxCyl-
lz, where w is
1, X in this formula is from about 0.5 to about 2.4, y is from about 0.6 to
about 3, and z is
from 2 to about 9, also can be applied to the interior surface 88 of the
vessel 80 to
improve adhesion of a subsequent coating of SiOx.
[759] VII.A.1.a. Thus, the coating 90 can comprise a layer of SiOx and a layer
of
SiwOxCyHz, where w is 1, x in this formula is from about 0.5 to 2.4, y is from
about 0.6 to
about 3, and z is from 2 to about 9, illustratively where w is 1, xis from
about 0.5 to 1, y
is from about 2 to about 3, and z is from 6 to about 9. The layer of SiwOxCyHz
can be
deposited between the layer of SiOx and the interior surface of the vessel.
Or, the layer
of SiOx can be deposited between the layer of SiwOxCyHz and the interior
surface of the
vessel. Or, three or more layers, either alternating or graduated between
these two
coating compositions, can also be used. The layer of SiOx can be deposited
adjacent to
the layer of SiwOxCyHz or remotely, with at least one intervening layer of
another
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material. The layer of SiOx can be deposited adjacent to the interior surface
of the vessel.
Or, the layer of SiwOxCyHz can be deposited adjacent to the interior surface
of the vessel.
[760] VII.A.1.a. Another expedient contemplated here, for adjacent layers of
SiOx and
SiwOxCyHz, is a graded composite of SiwOxCyHz, where w is 1, x in this formula
is from
about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2 to about 9õ
illustratively
where w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is
from 6 to
about 9, to SiOx. A graded composite can be separate layers of SiwOxCyHz and
SiOx with
a transition or interface of intermediate composition between them, or
separate layers of
SiwOxCyHz and SiOx with an intermediate distinct layer of intermediate
composition
between them, or a single layer that changes continuously or in steps from a
composition
of SiwOxCyHz to a composition more like SiOx, going through the coating in a
normal
direction.
[761] VII.A.1.a. The grade in the graded composite can go in either direction.
For
example, the composition SiwOxCyHz can be applied directly to the substrate
and
graduate to a composition further from the surface of SiOx. Or, the
composition of SiOx
can be applied directly to the substrate and graduate to a composition further
from the
surface of SiwOxCyHz. A graduated coating is particularly contemplated if a
coating of
one composition is better for adhering to the substrate than the other, in
which case the
better-adhering composition can, for example, be applied directly to the
substrate. It is
contemplated that the more distant portions of the graded coating can be less
compatible
with the substrate than the adjacent portions of the graded coating, since at
any point
the coating is changing gradually in properties, so adjacent portions at
nearly the same
depth of the coating have nearly identical composition, and more widely
physically
separated portions at substantially different depths can have more diverse
properties. It
is also contemplated that a coating portion that forms a better barrier
against transfer of
material to or from the substrate can be directly against the substrate, to
prevent the
more remote coating portion that forms a poorer barrier from being
contaminated with
the material intended to be barred or impeded by the barrier.
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[762] VII.A.1.a. The coating, instead of being graded, optionally can have
sharp
transitions between one layer and the next, without a substantial gradient of
composition.
Such coatings can be made, for example, by providing the gases to produce a
layer as
a steady state flow in a non-plasma state, then energizing the system with a
brief plasma
discharge to form a coating on the substrate. If a subsequent coating is to be
applied,
the gases for the previous coating are cleared out and the gases for the next
coating are
applied in a steady-state fashion before energizing the plasma and again
forming a
distinct layer on the surface of the substrate or its outermost previous
coating, with little
if any gradual transition at the interface.
VII.A.1.b. Citrate Blood Tube Having Wall Coated With Hydrophobic Coating
Deposited from an Organosilicon Precursor
[763] VII.A.1.b. Another embodiment is a cell preparation tube having a wall
provided
with a hydrophobic coating on its inside surface and containing an aqueous
sodium
citrate reagent. The hydrophobic coating may be also be applied on top of a
hydrophilic
SiOx coating on the internal surface of the tube. The SiOx coating increases
the barrier
properties of the thermoplastic tube and the hydrophobic coating changes the
surface
energy of blood contact surface with the tube wall.
[764] VII.A.1.b. The wall is made of thermoplastic material having an internal
surface
defining a lumen.
[765] VII.A.1.b. A blood collection tube according to the embodiment VII.A.1.b
can have
a first layer of SiOx on the internal surface of the tube, applied as
explained in this
specification, to function as an oxygen barrier and extend the shelf life of
an evacuated
blood collection tube made of thermoplastic material. A second layer of
SiwOxCyHz,
where w is 1, x in this formula is from about 0.5 to 2.4, y is from about 0.6
to about 3,
and z is from 2 to about 9, illustratively where w is 1, x is from about 0.5
to 1, y is from
about 2 to about 3, and z is from 6 to about 9, can then be applied over the
barrier layer
on the internal surface of the tube to provide a hydrophobic surface. The
coating is
effective to reduce the platelet activation of blood plasma treated with a
sodium citrate
additive and exposed to the inner surface, compared to the same type of wall
uncoated.
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[766] VII.A.1.b. PECVD is used to form a coating on the internal surface
having the
structure: SiwOõCy1-12. Unlike conventional citrate blood collection tubes,
the blood
collection tube having a hydrophobic layer of Siõ,0xCyHz does not require a
coating of
baked on silicone on the vessel wall, as is conventionally applied to make the
surface of
the tube hydrophobic.
[767] VII.A.1.b. Both layers can be applied using the same precursor, for
example
HMOS or OFV1CTS, and different PECVD reaction conditions.
[768] VII.A.1.b. A sodium citrate anticoagulation reagent is then placed
within the
tube and it is evacuated and sealed with a closure to produce an evacuated
blood
collection tube. The components and formulation of the reagent are known to
those
skilled in the art. The aqueous sodium citrate reagent is disposed in the
lumen of the
tube in an amount effective to inhibit coagulation of blood introduced into
the tube.
VII.A.1.c. SiO, Barrier Coated Double Wall Plastic Vessel¨ COC, PET, SiO,
layers
[769] VII.A.1.c. Another embodiment is a vessel having a wall at least
partially
enclosing a lumen. The wall has an interior polymer layer enclosed by an
exterior
polymer layer. One of the polymer layers is a layer at least 0.1 mm thick of a
cyclic
olefin copolymer (COC) resin defining a water vapor barrier. Another of the
polymer
layers is a layer at least 0.1 mm thick of a polyester resin.
[770] VII.A.1.c. The wall includes an oxygen barrier layer of SiOx having a
thickness of from about 10 to about 500 angstroms.
[771] VII.A.1.c. In an embodiment, illustrated in FIG. 36, the vessel 80
can be a
double-walled vessel having an inner wall 408 and an outer wall 410,
respectively made
of the same or different materials. One particular embodiment of this type can
be made
with one wall molded from a cyclic olefin copolymer (COO) and the other wall
molded
from a polyester such as polyethylene terephthalate (PET), with an SiOx
coating as
previously described on the interior surface 412. As needed, a tie coating or
layer can
be inserted between the inner and outer walls to promote adhesion between
them. An
168
intended advantage of this wall construction is that walls having different
properties can
be combined to form a composite having the respective properties of each wall.
[772] VII.A.1.c. As one example, the inner wall 408 can be made of PET coated
on
the interior surface 412 with an SiOx barrier layer, and the outer wall 410
can be made of
COC. PET coated with SiOx, as shown elsewhere in this specification, is an
excellent
oxygen barrier, while COC is an excellent barrier for water vapor, providing a
low water
vapor transition rate (VVVTR). This composite vessel can have superior barrier
properties
for both oxygen and water vapor. This construction is contemplated, for
example, for an
evacuated medical sample collection tube that contains an aqueous reagent as
manufactured, and has a substantial shelf life, so it should have a barrier
preventing
transfer of water vapor outward or transfer of oxygen or other gases inward
through its
composite wall during its shelf life.
[773] VII.A.1.c. As another example, the inner wall 408 can be made of COC
coated on
the interior surface 412 with an SiOx barrier layer, and the outer wall 410
can be made of
PET. This construction is contemplated, for example, for a prefilled syringe
that contains
an aqueous sterile fluid as manufactured. The SiOx barrier will prevent oxygen
from
entering the syringe through its wall. The COC inner wall will prevent ingress
or egress
of other materials suuh as water, thus preventing the water in the aqueous
sterile fluid
from leaching materials from the wall material into the syringe. The COC inner
wall is
also contemplated to prevent water derived from the aqueous sterile fluid from
passing
out of the syringe (thus undesirably concentrating the aqueous sterile fluid),
and will
prevent non-sterile water or other fluids outside the syringe from entering
through the
syringe wall and causing the contents to become non-sterile. The COC inner
wall is also
contemplated to be useful for decreasing the breaking force or friction of the
plunger
against the inner wall of a syringe.
VII.A.1.d. Method of Making
Double Wall Plastic Vessel¨ COC, PET, SiOx
Layers
[774] VII.A.1.d. Another embodiment is a method of making a vessel having a
wall having
an interior polymer layer enclosed by an exterior polymer layer, one layer
made
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of COO and the other made of polyester. The vessel is made by a process
including
introducing COO and polyester resin layers into an injection mold through
concentric
injection nozzles.
[775] VII.A.1.d. An optional additional step is applying an amorphous
carbon
coating to the vessel by PECVD, as an inside coating, an outside coating, or
as an
interlayer coating located between the layers.
[776] VII.A.1.d. An optional additional step is applying an SiO, barrier
layer to the
inside of the vessel wall, where SiOx is defined as before. Another optional
additional
step is post-treating the SiO, layer with a process gas consisting essentially
of oxygen
and essentially free of a volatile silicon compound.
[777] VII.A.1.d. Optionally, the SiOx coating can be formed at least
partially from a
sllazane feed gas.
[778] VII.A.1.d. The vessel 80 shown in FIG. 36 can be made from the inside
out,
for one example, by injection molding the inner wall in a first mold cavity,
then removing
the core and molded inner wall from the first mold cavity to a second, larger
mold cavity,
then injection molding the outer wall against the inner wall in the second
mold cavity.
Optionally, a tie layer can be provided to the exterior surface of the molded
inner wall
before over-molding the outer wall onto the tie layer.
[779] VII.A.1.d. Or, the vessel 80 shown in FIG. 36 can be made from the
outside
in, for one example, by inserting a first core in the mold cavity, injection
molding the
outer wall in toe mold cavity, tnen removing toe first core from Me molded
first wall and
inserting a second, smaller core, then injection molding the inner wall
against the outer
wall still residing in the mold cavity. Optionally, a tie layer can be
provided to the interior
surface of the molded outer wall before over-molding the inner wall onto the
tie layer.
[780] VII.A.1.d. Or, the vessel 80 shown in FIG. 36 can be made in a two
shot
[Told. This can be done, for one example, by injection molding material for
the Inner
wall from an inner nozzle and the material for the outer wall from a
concentric outer
nozzle. Optionally, a tie layer can be provided from a third, concentric
nozzle disposed
between the inner and outer nozzles. The nozzles can feed the respective wall
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materials simultaneously. One useful expedient is to begin feeding the outer
wall
material through the outer nozzle slightly before feeding the inner wall
material through
the inner nozzle. If there is an intermediate concentric nozzle, the order of
flow can
begin with the outer nozzle and continue in sequence from the intermediate
nozzle and
then from the inner nozzle. Or, the order of beginning feeding can start from
the inside
nozzle and work outward, in reverse order compared to the preceding
description.
VII.A.1.e. Barrier Coating Made Of Glass
[781] VII.A.1.e. Another embodiment is a vessel including a vessel, a
barrier
coating, and a closure. The vessel is generally tubular and made of
thermoplastic
material. The vessel has a mouth and a lumen bounded at least in part by a
wall having
an inner surface Interfacing with the lumen. There is an at least essentially
continuous
barrier coating made of glass on the inner surface of the wall. A closure
covers the
mouth and isolates the lumen of the vessel from ambient air.
[782] VII.A.1.e. The vessel 80 can also be made, for example of glass of
any type
used in medical or laboratory applications, such as soda-lime glass,
borosilicate glass,
or other glass formulations. Other vessels having any shape or size, made of
any
material, are also contemplated for use in the system 20. One function of
coating a
glass vessel can be to reduce the ingress of ions in the glass, either
intentionally or as
impurities, for example sodium, calcium, or others, from the glass to the
contents of the
vessel, such as a reagent or blood in an evacuated blood collection tube.
Another
function of coating a glass vessel in whole or in part, such as selectively at
surfaces
contacted in sliding relation to other parts, is to provide lubricity to the
coating, for
example to ease the insertion or removal of a stopper or passage of a sliding
element
such as a piston in a syringe. Still another reason to coat a glass vessel is
to prevent a
reagent or intended sample for the vessel, such as blood, from sticking to the
wall of the
vessel or an increase in the rate of coagulation of the blood in contact with
the wall of
the vessel.
171
[783] VII.A.1.e.i. A related embodiment is a vessel as described in the
previous
paragraph, in which the barrier coating is made of soda lime glass,
borosilicate glass, or
another type of glass.
VII.A.2. Stoppers
[784] VII.A.2. FIGS. 23-25 illustrate a vessel 268, which can be an evacuated
blood
collection tube, having a closure 270 to isolate the lumen 274 from the
ambient
environment. The closure 270 comprises a interior-facing surface 272 exposed
to the
lumen 274 of the vessel 268 and a wall-contacting surface 276 that is in
contact with the
inner surface 278 of the vessel wall 280. In the illustrated embodiment the
closure 270
is an assembly of a stopper 282 and a shield 284.
VII.A.2.a. Method of Applying Lubricity Coating to Stopper In Vacuum
Chamber
[785] VII.A.2.a. Another embodiment is a method of applying a coating on an
elastomeric
stopper such as 282. The stopper 282, separate from the vessel 268, is placed
in a
substantially evacuated chamber. A reaction mixture is provided including
plasma
folminy gas, i.e. an oiyanosilioon oompound yd, optionally an oxidiziny gas,
and
optionally a hydrocarbon gas. Plasma is formed in the reaction mixture, which
is
contacted with the stopper. A coating of SiwOxCyHz, where w is 1, x in this
formula is from
about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2 to about 9,
illustratively
where w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is
from 6 to
about 9, is deposited on at least a portion of the stopper.
[786] VII.A.2.a. In the illustrated embodiment, the wall-contacting surface
276 of the
closure 270 is coated with a lubricity coating 286.
[787] VII.A.2.a. In some embodiments, the coating of SiwOxCyHz is effective to
reduce
the transmission of one or more constituents of the stopper, such as a metal
ion
constituent of the stopper, or of the vessel wall, into the vessel lumen.
Certain
elastomeric compositions of the type useful for fabricating a stopper 282
contain trace
amounts of one or more metal ions. These ions sometimes should not be able to
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migrate into the lumen 274 or come in substantial quantities into contact with
the vessel
contents, particularly if the sample vessel 268 is to be used to collect a
sample for trace
metal analysis. It is contemplated for example that coatings containing
relatively little
organic content, i.e. where y and z are low or zero, are particularly useful
as a metal ion
barrier in this application. Regarding silica as a metal ion barrier see, for
example,
Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka, and
Toh-
Ming Lu, The Effect of Interfacial Chemistry on Metal Ion Penetration into
Polymeric
Films, Mat. Res. Soc. Symp. Proc., Vol. 734, pp. B9.60.1 to B9.60.6 (Materials
Research Society, 2003); U.S. Patents 5578103 and 6200658, and European Appl.
EP0697378 A2. It is contemplated, however, that some organic content can be
useful to
provide a more elastic coating and to adhere the coating to the elastomeric
surface of
the stopper 282.
[788] VII.A.2.a. In some embodiments, the coating of Siw0x0e1-1z can be
a
composite of material having first and second layers, in which the first or
inner layer 288
interfaces with the elastomeric stopper 282 and is effective to reduce the
transmission of
one or more constituents of the stopper 282 into the vessel lumen. The second
layer
286 can interface with the inner wall 280 of the vessel and is effective to
reduce friction
between the stopper 282 and the inner wall 280 of the vessel when the stopper
282 is
seated on or in the vessel 268. Such composites are described in connection
with
syringe coatings elsewhere in this specification.
[789] VII.A.2.a. Or, the first and second layers 288 and 286 are defined by
a coating of
graduated properties, in which the values of y and z are greater in the first
layer than in the
second layer.
[790] VII.A.2.a. The coating of SiO.Cy1-1, can be applied, for example, by
PECVD
substantially as previously described. The coating of Si30,CyH, can be, for
example,
between 0.5 and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and 5000
nm
thick, or between 5 and 5000 nm thick, or between 10 and 5000 nm thick, or
between 20
and 5000 nm thick, or between 50 and 5000 nm thick, or between 100 and 5000 nm
thick, or between 200 and 5000 nm thick, or between 500 and 5000 nm thick, or
1 7 3
between 1000 and 5000 nm thick, or between 2000 and 5000 nm thick, or between
3000
and 5000 nm thick, or between 4000 and 10,000 nm thick.
[791] VII.A.2.a. Certain intended advantages are contemplated for plasma
coated
lubricity layers, versus the much thicker (one micron or greater) conventional
spray
applied silicone lubricants. Plasma coatings have a much lower migratory
potential to
move into blood versus sprayed or micron-coated silicones, both because the
amount of
plasma coated material is much less and because it can be more intimately
applied to
the coated surface and better bonded in place.
[792] VII.A.2.a. Nanocoatings, as applied by PECVD, are contemplated to offer
lower
resistance to sliding of an adjacent surface or flow of an adjacent fluid than
micron
coatings, as the plasma coating tends to provide a smoother surface.
[793] VII.A.2.a. Still another embodiment is a method of applying a coating of
SiwOxCyHz
on an elastomeric stopper. The stopper can be used, for example, to close the
vessel
previously described. The method includes several parts. A stopper is placed
in a
substantially evacuated chamber. A reaction mixture is provided comprising
plasma
forming gas, i.e. an organosilicon compound gas, optionally an oxidizing gas,
and
optionally a hydrocarbon gas. Plasma is formed in the reaction mixture. The
stopper is
contacted with the reaction mixture, depositing the coating of SiwOxCyHz on at
least a
portion of the stopper.
[794] VII.A.2.a. In practicing this method, to obtain higher values of y and
z, it is
contemplated that the reaction mixture can comprise a hydrocarbon gas, as
further
described above and below. Optionally, the reaction mixture can contain
oxygen, if lower
values of y and z or higher values of x are contemplated. Or, particularly to
reduce
oxidation and increase the values of y and z, the reaction mixture can be
essentially free
of an oxidizing gas.
[795] VII.A.2.a. In practicing this method to coat certain embodiments of the
stopper such
as the stopper 282, it is contemplated to be unnecessary to project the
reaction mixture
into the concavities of the stopper. For example, the wall-contacting and
interior facing
surfaces 276 and 272 of the stopper 282 are essentially convex, and thus
readily treated
by a batch process in which a multiplicity of stoppers such as 282
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can be located and treated in a single substantially evacuated reaction
chamber. It is
further contemplated that in some embodiments the coatings 286 and 288 do not
need
to present as formidable a barrier to oxygen or water as the barrier coating
on the
interior surface 280 of the vessel 268, as the material of the stopper 282 can
serve this
function to a large degree.
[796] VII.A.2.a. Many variations of the stopper and the stopper coating
process are
contemplated. The stopper 282 can be contacted with the plasma. Or, the plasma
can
be formed upstream of the stopper 282, producing plasma product, and the
plasma
product can be contacted with the stopper 282. The plasma can be formed by
exciting
tre reaction mixture with electromagnetic energy and/or microwave energy.
[797] VII.A.2.a. Variations of the reaction mixture are contemplated. The
plasma
forming gas can include an inert gas. The inert gas can be, for example, argon
or
helium, or other gases described in this disclosure. The organosilicon
compound gas
can be, or include, HMDSO, OMCTS, any of the other organosilicon compounds
mentioned in this disclosure, or a combination of two or more of these. The
oxidizing
gas can be oxygen or the other gases mentioned in this disclosure, or a
combination of
two or more of these. The hydrocarbon gas can be, for example, methane,
methanol,
ethane, ethylene, ethanol, propane, propylene, propanol, acetylene, or a
combination of
two or more of these.
VII.A.2.b. Applying by PECVD a Coating of Group III or IV Element and
Carbon
on a Stopper
[798] VII.A.2.b. Another embodiment is a method of applying a coating of a
composition including carbon and one or more elements of Groups III or IV on
an
elastomeric stopper. To carry out the method, a stopper is located in a
deposition
chamber.
[799] VII.A.2.b. A reaction mixture is provided in the deposition chamber,
including
a plasma forming gas with a gaseous source of a Group III element, a Group IV
element, or a combination of two or more of these. The reaction mixture
optionally
contains an oxidizing gas and optionally contains a gaseous compound having
one or
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more C-H bonds. Plasma is formed in the reaction mixture, and the stopper is
contacted with the reaction mixture. A coating of a Group Ill element or
compound, a
Group IV element or compound, or a combination of two or more of these is
deposited
on at least a portion of the stopper.
VII.A.3. Stoppered Plastic Vessel Having Barrier Coating Effective To
Provide
95% Vacuum Retention for 24 Months
[800] Another embodiment is a vessel including a vessel, a barrier coating,
and a closure. The vessel is generally tubular and made of thermoplastic
material. The
vessel has a mouth and a lumen bounded at least in part by a wall. The wall
has an
inner surface interfacing with the lumen. An at least essentially continuous
barrier
coating is applied on the inner surface of the wall. The barrier coating is
effective to
provide a substantial shelf life. A closure is provided covering the mouth of
the vessel
and isolating the lumen of the vessel from ambient air.
[801] Referring to FIGS. 23-25, a vessel 268 such as an evacuated blood
collection tube or other vessel is shown.
[802] The vessel is, in this embodiment, a generally tubular vessel having
an at least essentially continuous barrier coating and a closure. The vessel
is made of
thermoplastic material having a mouth and a lumen bounded at least in part by
a wall
having an inner surface interfacing with the lumen. The barrier coating is
deposited on
the inner surface of the wall, and is effective to maintain at least 95%, or
at least 90%,
of the initial vacuum level of the vessel for a shelf life of at least 24
months, optionally at
least 30 months, optionally at least 36 months. The closure covers the mouth
of the
vessel and isolates the lumen of the vessel from ambient air.
[803] The closure, for example the closure 270 illustrated in the Figures
or
another type of closure, is provided to maintain a partial vacuum and/or to
contain a
sample and limit or prevent its exposure to oxygen or contaminants. FIGS. 23-
25 are
based on figures found in U.S. Patent No. 6,602,206, but the present discovery
is not
limited to that or any other particular type of closure.
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[804] VII.A.3. The closure 270 comprises a interior-facing surface 272
exposed to
the lumen 274 of the vessel 268 and a wall-contacting surface 276 that is in
contact with
the inner surface 278 of the vessel wall 280. In the illustrated embodiment
the closure
270 is an assembly of a stopper 282 and a shield 284.
[805] VII.A.3. In the illustrated embodiment, the stopper 282 defines the
wall-
contacting surface 276 and the inner surface 278, while the shield is largely
or entirely
outside the stoppered vessel 268, retains and provides a grip for the stopper
282, and
shields a person removing the closure 270 from being exposed to any contents
expelled
from the vessel 268, such as due to a pressure difference inside and outside
of the
vessel 268 when the vessel 268 is opened and air rushes in or out to equalize
Ine
pressure difference.
[806] VII.A.3. It is further contemplated that the coatings on the vessel
wall 280
and the wall contacting surface 276 of the stopper can be coordinated. The
stopper can
be coated with a lubricity silicone layer, and the vessel wall 280, made for
example of
PET or glass, can be coated with a harder SiOx layer, or with an underlying
SiO, layer
and a lubricity overcoat.
VII.B. Syringes
[807] VII.B. The foregoing description has largely addressed applying a
barrier
coating to a tube with one permanently closed end, such as a blood collection
tube or,
more generally, a specimen receiving tube 80. The apparatus is not limited to
such a
device.
[808] VII.B. Another example of a suitable vessel, shown in FIGS 20-22, is
a
syringe barrel 250 for a medical syringe 252. Such syringes 252 are sometimes
supplied prefilled with saline solution, a pharmaceutical preparation, or the
like for use in
medical techniques. Pre-filled syringes 252 are also contemplated to benefit
from an
SiOx barrier or other type of coating on the interior surface 254 to keep the
contents of
the prefilled syringe 252 out of contact with the plastic of the syringe, for
example of the
syringe barrel 250 during storage. The barrier or other type of coating can be
used to
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avoid leaching components of the plastic into the contents of the barrel
through the
interior surface 254.
[809] VII.B. A syringe barrel 250 as molded commonly can be open at both
the
back end 256, to receive a plunger 258, and at the front end 260, to receive a
hypodermic needle, a nozzle, or tubing for dispensing the contents of the
syringe 252 or
for receiving material into the syringe 252. But the front end 260 can
optionally be
capped and the plunger 258 optionally can be fitted in place before the
prefilled syringe
252 is used, closing the barrel 250 at both ends. A cap 262 can be installed
either for
the purpose of processing the syringe barrel 250 or assembled syringe, or to
remain in
place during storage of the prefilled syringe 252, up to tne time tne cap 262
is removed
and (optionally) a hypodermic needle or other delivery conduit is fitted on
the front end
260 to prepare the syringe 252 for use.
VII.B.1. Assemblies
[810] VII.B.1. FIG. 42 also shows an alternative syringe barrel
construction usable,
for example, with the embodiments of FIGS. 21, 26, 28, 30, and 34 and adapted
for use
with the vessel holder 450 of that Figure..
[811] VII.B.1. FIG. 50 is an exploded view and FIG. 51 is an assembled view
of a
syringe. The syringe barrel can be processed with the vessel treatment and
inspection
apparatus of FIGS. 1-22, 26-28, 33-35, 37-39, 44, and 53-54.
[012] VII.D.1. The installation of a cap 202 makes the barrel 250 a closed-
end
vessel that can be provided with an SiOx barrier or other type of coating on
its interior
surface 254 in the previously illustrated apparatus, optionally also providing
a coating on
the interior 264 of the cap and bridging the interface between the cap
interior 264 and
the barrel front end 260. Suitable apparatus adapted for this use is shown,
for example,
in FIG. 21, which is analogous to FIG. 2 except for the substitution of the
capped
syringe barrel 250 for the vessel 80 of FIG. 2. VII.B.
[813] VII.B.1 FIG. 52 is a view similar to FIG. 42, but showing a syringe
barrel
being treated that has no flange or finger stops 440. The syringe barrel is
usable with
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the vessel treatment and inspection apparatus of FIGS. 1-19, 27, 33, 35, 44-
51, and 53-
54.
VII.B.1.a. Syringe Having Barrel
Coated With Lubricity Coating Deposited from
an Organosilicon Precursor
[814] VII.B.1.a. Still another embodiment is a vessel having a lubricity
coating of
SiwOxCyHz, of the type made by the following process.
[815] VII.B.1.a. A precursor is provided as defined above.
[816] VII.B.1.a. The precursor is applied to a substrate under conditions
effective
to form a coating. The coating is polymerized or crosslinked, or both, to form
a
lubricated surface having a lower plunger sliding force or breakout force than
the
untreated substrate.
[817] VII.R.1.a. Respecting any of the Embodiments VII and sub-parts,
optionally
the applying step is carried out by vaporizing the precursor and providing it
in the vicinity
of the substrate.
[818] VII.B.1.a.
Respecting any of the Embodiments VII.A.1.a.i, optionally a
plasma, optionally a non-hollow-cathode plasma, is formed in the vicinity of
the
substrate. Optionally, the precursor is provided in the substantial absence of
oxygen.
Optionally, the precursor is provided in the substantial absence of a carrier
gas.
Optionally, the precursor is provided in the substantial absence of nitrogen.
Optionally,
thc precursor is provided at loss than 1 Torr absolute pressure. Optionally,
the
precursor is provided to the vicinity of a plasma emission. Optionally, the
precursor its
reaction product is applied to the substrate at a thickness of 1 to 5000 nm
thick, or 10 to
1000 nm thick, or 10-200 nm thick, or 20 to 100 nm thick. Optionally, the
substrate
comprises glass. Optionally, the substrate comprises a polymer, optionally a
polycarbonate polymer, optionally an olefin polymer, optionally a cyclic
olefin copolymer,
optionally a polypropylene polymer, optionally a polyester polymer, optionally
a
polyethylene terephthalate polymer.
[819] Optionally, the plasma is generated by energizing the gaseous
reactant
containing the precursor with electrodes powered, for example, at a RF
frequency as
179
defined above, for example a frequency of from 10 kHz to less than 300 MHz,
more
illustratively of from 1 to 50 MHz, even more illustratively of from 10 to 15
MHz, most
illustratively a frequency of 13.56 MHz.
[820] Optionally, the plasma is generated by energizing the gaseous reactant
containing
the precursor with electrodes supplied with an electric power of from 0.1 to
25 W,
illustratively from 1 to 22 W, more illustratively from 3 to 17 W, even more
illustratively of
from 5 to 14W, most illustratively of from 7 toll W, in particular of 8 W. The
ratio of the
electrode power to the plasma volume may be less than 10 W/ml, illustratively
is from 5
W/ml to 0.1 W/ml, more illustratively is from 4 W/ml to 0.1 W/ml, most
illustratively from
2 W/ml to 0.2 W/ml. These power levels are suitable for applying lubricity
coatings to
syringes and sample tubes and vessels of similar geometry having a void volume
of 1 to
3 mL in which PECVD plasma is generated. It is contemplated that for larger or
smaller
objects the power applied should be increased or reduced accordingly to scale
the
process to the size of the substrate.
[821] VII.B.1.a Another embodiment is a lubricity coating on the inner wall of
a syringe
barrel. The coating is produced from a PECVD process using the following
materials and
conditions. A cyclic precursor is illustratively employed, selected from a
monocyclic
siioxane, a poiycyciic siioxane, or a combination or two or more or tnese, as
aermea
elsewhere in this specification for lubricity coatings. One example of a
suitable cyclic
precursor comprises octamethylcyclotetrasiloxane (OMCTS), optionally mixed
with other
precursor materials in any proportion. Optionally, the cyclic precursor
consists essentially
of octamethycyclotetrasiloxane (OMCTS), meaning that other precursors can be
present
in amounts which do not change the basic and novel properties of the resulting
lubricity
coating, i.e. its reduction of the plunger sliding force or breakout force of
the coated
su rface_
[822] VII.B.1.a At least essentially no oxygen is added to the process. Some
residual
atmospheric oxygen can be present in the syringe barrel, and residual oxygen
fed in a
previous step and not fully exhausted can be present in the syringe barrel,
which are
defined here as essentially no oxygen present. If no oxygen is added to the
process, this
is also within the scope of "essentially no oxygen."
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[823] VII.B.1.a A sufficient plasma generation power input, for example any
power
level successfully used in one or more working examples of this specification
or
described in the specification, is provided to induce coating formation.
[824] VII.B.1.a The materials and conditions employed are effective to
reduce the
syringe plunger sliding force or breakout force moving through the syringe
barrel at least
25 percent, alternatively at least 45 percent, alternatively at least 60
percent,
alternatively greater than 60 percent, relative to an uncoated syringe barrel.
Ranges of
plunger sliding force or breakout force reduction of from 20 to 95 percent,
alternatively
from 30 to 80 percent, alternatively from 40 to 75 percent, alternatively from
60 to 70
percent, are contemplated.
[825] VII.B.1.a. Another embodiment is a vessel having a hydrophobic
coating on
the inside wall having the structure: Si,õ0õCy1-1,, where w, x, y, and z are
as previously
defined. The coating is made as explained for the lubricant coating of similar
composition, but under conditions effective to form a hydrophobic surface
having a
higher contact angle than the untreated substrate.
[826] VII.B.1.a. Respecting any of the Embodiments VII.A.1.a.ii,
optionally the
substrate comprises glass or a polymer. The glass optionally is borosilicate
glass. The
polymer is optionally a polycarbonate polymer, optionally an olefin polymer,
optionally a
cyclic olefin copolymer, optionally a polypropylene polymer, optionally a
polyester
polymer, optionally a polyethylene terephthalate polymer.
[827] Another embodiment is a syringe including a plunger, a syringe
barrel, and a lubricity layer. The syringe barrel includes an interior surface
slidably
receiving the plunger. The lubricity layer is disposed on the interior surface
of the
syringe barrel and includes a coating of an Siõõ0,<C,H, lubricity layer. The
lubricity layer
is less than 1000 rim thick and effective to reduce the breakout force or the
plunger
sliding force necessary to move the plunger within the barrel. Reducing the
plunger
sliding force is alternatively expressed as reducing the coefficient of
sliding friction of the
plunger within the barrel or reducing the plunger force; these terms are
regarded as
having the same meaning in this specification.
181
[828] VII.B.1.a. The syringe 544 of FIGS. 50-51 comprises a plunger 546 and a
syringe
barrel 548. The syringe barrel 548 has an interior surface 552 slidably
receiving the
plunger 546. The interior surface 552 of the syringe barrel 548 further
comprises a
lubricant coating 554 of SiwOxCyHz. The lubricity layer is less than 1000 nm
thick,
optionally less than 500 nm thick, optionally less than 200 nm thick,
optionally less than
100 nrn thick, optionally less than 50 nm thick, and is effective to reduce
the breakout
force necessary to overcome adhesion of the plunger after storage or the
plunger sliding
force necessary to move the plunger within the barrel after it has broken
away. The
lubricity coating is characterized by having a plunger sliding force or
breakout force lower
than that of the uncoated surface.
[829] VII.B.1.a. Any of the above precursors of any type can be used alone or
in
combinations of two or more of them to provide a lubricity coating.
[830] VII.B.1.a. In addition to utilizing vacuum processes, low temperature
atmospheric
(non-vacuum) plasma processes can also be utilized to induce molecular
ionization and
deposition through precursor monomer vapor delivery illustratively in a non-
oxidizing
atmosphere such as helium or argon. Separately, thermal CVD can be considered
via
flash thermolysis deposition.
[831] VII.B.1.a. The approaches above are similar to vacuum PECVD in that the
surface
coating and crosslinking mechanisms can occur simultaneously.
[832] VII.B.1.a. Yet another expedient contemplated for any coating or
coatings
desoribed here is a coating that is not uniformly applied over the entire
interior 00 of a
vessel. For example, a different or additional coating can be applied
selectively to the
cylindrical portion of the vessel interior, compared to the hemispherical
portion of the
vessel interior at its closed end 84, or vice versa. This expedient is
particularly
contemplated for a syringe barrel or a sample collection tube as described
below, in
which a lubricity surface might be provided on part or all of the cylindrical
portion of the
barrel, where the plunger or piston or closure slides, and not elsewhere.
[833] N/11.13.1.a. Optionally, the precursor can be provided in the presence,
substantial
absence, or absence of oxygen, in the presence, substantial absence, or
absence of
nitrogen, or in the presence, substantial absence, or absence of a carrier
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gas. In one contemplated embodiment, the precursor alone is delivered to the
substrate
and subjected to PECVD to apply and cure the coating.
[834] VII.B.1.a. Optionally, the precursor can be provided at less than 1 Torr
absolute
pressure.
[835] VII.B.1.a. Optionally, the precursor can be provided to the vicinity of
a plasma
emission.
[836] VII.B.1.a. Optionally, the precursor its reaction product can be applied
to the
substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm., or 10-200 nm, 01
20 to 100
nm.
[837] VI 1.13.1.a. In any of the above embodiments, the substrate can comprise
glass, or
a polymer, for example one or more of a polycarbonate polymer, an olefin
polymer (for
example a cyclic olefin copolymer or a polypropylene polymer), or a polyester
polymer
(for example, a polyethylene terephthalate polymer).
[838] VII.B.1.a. In any of the above embodiments, the plasma is generated by
energizing
the gaseous reactant containing the precursor with electrodes powered at a RF
frequency as defined in this description.
[839] VII.B.1.a. In any of the above embodiments, the plasma is generated by
energizing
the gaseous reactant containing the precursor with electrodes supplied with
sufficient
electric power to generate a lubricity coating. Optionally, the plasma is
generated by
energizing the gaseous reactant containing the precursor with electrodes
supplied with
an electric power of from 0.1 to 25 W, illustratively from 1 to 22 W, more
illustratively from
3 to 17W, even more illustratively of from 5 to 14 W, most illustratively of
from 7 to 11
W, in particular of 8 W. The ratio of the electrode power to the plasma volume
may be
less than 10 VV/ml, illustratively is from 5 VV/ml to 0.1 VV/ml, more
illustratively is from 4
Wird to 0.1 W/ml, most illustratively from 2 W/ml to 0.2 W/ml. These power
levels are
suitable for applying lubricity coatings to syringes and sample tubes and
vessels of
similar geometry having a void volume of 1 to 3 mL in which PECVD plasma is
generated.
It is contemplated that for larger or smaller objects the power
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applied should be increased or reduced accordingly to scale the process to the
size of
the substrate.
[840] VII.B.1.a. The coating can be cured, as by polymerizing or
crosslinking the
coating, or both, to form a lubricated surface having a lower plunger sliding
force or
breakout force than the untreated substrate. Curing can occur during the
application
process such as PECVD, or can be carried out or at least completed by separate
processing.
[841] VII.B.1.a. Although plasma deposition has been used herein to
demonstrate
the coating characteristics, alternate deposition methods can be used as long
as the
chemical composition of the starting material is preserved as much as possible
while
still depositing a solid film that is adhered to the base substrate.
[842] VII.B.1.a. For example, the coating material can be applied onto the
syringe
barrel (from the ligub state) by spraying the coating or dipping the substrate
into the
coating, where the coating is either the neat precursor a solvent-diluted
precursor
(allowing the mechanical deposition of a thinner coating). The coating
optionally can be
crosslinked using thermal energy, UV energy, electron beam energy, plasma
energy, or
any combination of these.
[843] VII.B.1.a. Application of a silicone precursor as described above
onto a
surface followed by a separate curing step is also contemplated. The
conditions of
application and curing can be analogous to those used for the atmospheric
plasma
curing of pre-coated polyflucroalkyl ethers, a process practiced under the
trademark
TriboGlide . More details of this process can be found at
http://www.tribogIlde.com/process.htm.
[844] VII.B.1.a. In such a process, the area of the part to be coated can
optionally
be pre-treated with an atmospheric plasma. This pretreatment cleans and
activates the
surface so that it is receptive to the lubricant that is sprayed in the next
step.
[845] VII.B.1.a. The lubrication fluid, in this case one of the above
precursors or a
polymerized precursor, is then sprayed on to the surface to be treated. For
example,
184
IVEK precision dispensing technology can be used to accurately atomize the
fluid and
create a uniform coating.
[846] VII.B.1.a. The coating is then bonded or crosslinked to the part, again
using an
atmospheric plasma field. This both immobilizes the coating and improves the
lubricant's
performance.
[847] VII.B.1.a. Optionally, the atmospheric plasma can be generated from
ambient air in the vessel, in which case no gas feed and no vacuum drawing
equipment
is needed. Illustratively, however, the vessel is at least substantially
closed while plasma
is generated, to minimize the power requirement and prevent contact of the
plasma with
surfaces or materials outside the vessel.
VII.B.1.a.i. Lubricity Coating: SiOx Barrier, Lubricity Layer, Surface
Treatment
Surface treatment
[848] VII.B.1.a.i. Another embodiment is a syringe comprising a barrel
defining a lumen
and having an interior surface slidably receiving a plunger, i.e. receiving a
plunger for
sliding contact to the interior surface.
[849] VII.B.1.a.i. The syringe barrel is made of thermoplastic base
material.
[850] VII.B.1.a.i. Optionally, the interior surface of the barrel is coated
with an SiOx barrier
layer as described elsewhere in this specification.
[851] VII.B.1.a.i. A lubricity coating is applied to the barrel interior
surface, the plunger,
or both, or to the previously applied SiOx barrier layer. The lubricity layer
can be provided,
applied, and cured as set out in embodiment VII.B.1.a or elsewhere in this
specification.
[852] VII Btai For example, the lubricity coating can be applied, in any
embodiment,
by PECVD. The lubricity coating is deposited from an organosilicon precursor,
and is
less than 1000 nm thick.
[853] VII.B.1.a.i. A surface treatment is carried out on the lubricity coating
in an amount
effective to reduce the leaching or extractables of the lubricity coating, the
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thermoplastic base material, or both. The treated surface may thus act as a
solute
retainer. This surface treatment may result in a skin coating, e.g. a skin
coating which is
at least 1 nm thick and less than 100 nm thick, or less than 50 nm thick, or
less than 40
nm thick, or less than 30 nm thick, or less than 20 nm thick, or less than 10
nm thick, or
less than 5 nm thick, or less than 3 nm thick, or less than 2 nm thick, or
less than 1 nm
thick, or less than 0.5 rim thick.
[854] As used herein, "leaching" refers to material transferred out of a
substrate,
such as a vessel wall, into the contents of a vessel, for example a syringe.
Commonly,
leachables are measured by storing the vessel filled with intended contents,
then
analyzing toe contents to determine wnat material leached from tne vessel wall
into the
intended contents. "Extraction" refers to material removed from a substrate
by
introducing a solvent or dispersion medium other than the intended contents of
the
vessel, to determine what material can be removed from the substrate into the
extraction medium under toe conditions of toe test.
[855] V11.13.1.a.i. The surface treatment resulting in a solute retainer
optionally can
be a SiOx or SivõOxCyHz coating, each as previously defined in this
specification. In one
embodiment, the surface treatment can be applied by PECVD deposit of SiOx or
SiwOxCyHz. Optionally, the surface treatment can be applied using higher power
or
stronger oxidation conditions than used for creating the lubricity layer, or
both, thus
providing a harder, thinner, continuous solute retainer 539. Surface treatment
can be
less than 100 nm deep, optionally less than 50 nm deep, optionally less than
40 nm
deep, optionally less than 30 nm deep, optionally less than 20 nm deep,
optionally less
than 10 nm deep, optionally less than 5 nm deep, optionally less than 3 nm
deep,
optionally less than 1 nm deep, optionally less than 0.5 nm deep, optionally
between 0.1
and 50 nm deep in the lubricity coating.
[856] VII.B.1.a.i. The solute retainer is contemplated to provide low
solute leaching
performance to the underlying lubricity and other layers, including the
substrate, as
required. This retainer would only need to be a solute retainer to large
solute molecules
and oligomers (for example siloxane monomers such as HMDSO, OMCTS, their
fragments and mobile oligomers derived from lubricants, for example a
"leachables
186
retainer") and not a gas (02/N2/CO2/water vapor) barrier layer. A solute
retainer may,
however, also be a gas barrier (e.g. the SiOx coating according to the
embodiments of
the present invention. One can create a good leachable retainer without gas
barrier
performance, either by vacuum or atmospheric-based PECVD processes. It is
desirable
that the "leachables barrier" will be sufficiently thin that, upon syringe
plunger movement,
the plunger will readily penetrate the "solute retainer" exposing the sliding
plunger nipple
to the lubricity layer immediately below to form a lubricated surface having a
lower
plunger sliding force or breakout force than the untreated substrate.
[857] VII.B.1.a.i. In another embodiment, the surface treatment can be
performed by
oxidizing the surface of a previously applied lubricity layer, as by exposing
the surface to
oxygen in a plasma environment. The plasma environment described in this
specification
for forming SiOx coatings can be used. Or, atmospheric plasma conditions can
be
employed in an oxygen-rich environment.
[858] VII.B.1.a.i. The lubricity layer and solute retainer, however formed,
optionally can
be cured at the same time. In another embodiment, the lubricity layer can be
at least
partially cured, optionally fully cured, after which the surface treatment can
be provided,
applied, and the solute retainer can be cured.
[859] VII.B.1.a.i. The lubricity coating and solute retainer are composed, and
present in
relative amounts, effective to provide a breakout force, plunger sliding
force, or both that
is less than the corresponding force required in the absence of the lubricity
coating and
surface treatment. In other words, the thickness and composition of the solute
retainer
are such as to reduce the leaching of material from the lubricity layer into
the contents of
the syringe, while allowing the underlying lubricity coating to lubricate the
plunger. It is
contemplated that the solute retainer will break away easily and be thin
enough that the
lubricity layer will still function to lubricate the plunger when it is moved.
[860] VII.B.1.a.i. In one contemplated embodiment, the lubricity and surface
treatments
can be applied on the barrel interior surface. In another contemplated
embodiment, the
lubricity and surface treatments can be applied on the plunger_ In still
another
contemplated embodiment, the lubricity and surface treatments can be applied
both on
the barrel interior surface and on the plunger. In any of these embodiments,
the
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optional SiOx barrier layer on the interior of the syringe barrel can either
be present or
absent.
[861] VII.B.1.a.i. One embodiment contemplated is a plural-layer, e.g. a 3-
layer,
configuration applied to the inside surface of a syringe barrel. Layer 1 can
be an Si
Ox
gas barrier made by PECVD of HMDSO, OMCTS, or both, in an oxidizing
atmosphere.
Such an atmosphere can be provided, for example, by feeding HMDSO and oxygen
gas
to a PECVD coating apparatus as described in this specification. Layer 2 can
be a
lubricity layer using OMCTS applied in a non-oxidizing atmosphere. Such a non-
oxidizing atmosphere can be provided, for example, by feeding OMCTS to a PECVD
coating apparatus as described in this specification, optionally in the
substantial or
complete absence of oxygen. A subsequent solute retainer can be formed by a
treatment
forming a thin skin layer of SiOx or SiwOxCyHz as a solute retainer using
higher power and
oxygen using OMCTS and/or HMDSO.
[862] VII.B.1.a.i. Certain of these plural-layer coatings are contemplated to
have one
or more of the following optional intended advantages, at least to some
degree. They
may address the reported difficulty of handling silicone, since the solute
retainer may
confine the interior silicone and prevent if from migrating into the contents
of the syringe
or elsewhere, resulting in fewer bilic,one particles in the deliverable
contents of the
syringe and less opportunity for interaction between the lubricity coating and
the contents
of the syringe. They may also address the issue of migration of the lubricity
layer away
from the point of lubrication, improving the lubricity of the interface
between the syringe
barrel and the plunger. For example, the break-free force may be reduced and
the drag
on the moving plunger may be reduced, or optionally both.
[863] VII.B.1.a.i. It is contemplated that when the solute retainer is broken,
the solute
retainer will continue to adhere to the lubricity coating and the syringe
barrel, which may
inhibit any particles from being entrained in the deliverable contents of the
syringe.
[864] VII.B.1.a.i. Certain of these coatings will also provide intended
manufacturing
advantages, particularly if the barrier coating, lubricity coating and surface
treatment are
applied in the same apparatus, for example the illustrated PECVD apparatus.
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Optionally, the SiOx barrier coating, lubricity coating, and surface treatment
can all be
applied in one PECVD apparatus, thus greatly reducing the amount of handling
necessary.
[865] Further intended advantages can be obtained by forming the barrier
coating,
lubricity coating, and solute retainer using the same precursors and varying
the process.
For example, an SiOx gas barrier layer can be applied using an OMCTS precursor
under
high power/high 02 conditions, followed by applying a lubricity layer applied
using an
OMCTS precursor under low power and/or in the substantial or complete absence
of
oxygen, finishing with a surface treatment using an OMCTS precursor under
intermediate power and oxygen.
VII.B.1.b Syringe having barrel with SiOx coated interior and barrier
coated
exterior
[866] VII.B.1.b. Still another embodiment, illustrated in FIG. 50, is a
syringe 544 including
a plunger 546, a barrel 548, and interior and exterior barrier coatings 554
and 602. The
barrel 548 can be made of thermoplastic base material defining a lumen 604.
The barrel
548 can have an interior surface 552 slidably receiving the plunger 546 and an
exterior
surface 606 A barrier coating 554 of Si0v, in which x is from about 1 5 to
about 29. can
be provided on the interior surface 552 of the barrel 548. A barrier coating
602 of a resin
can be provided on the exterior surface 606 of the barrel 548.
[867] VII.B.1.b. In any embodiment, the thermoplastic base material optionally
can
include a polyolefin, for example polypropylene or a cyclic olefin copolymer
(for example
the material sold under the trademark TOPASO), a polyester, for example
polyethylene
terephthalate, a polycarbonate, for example a bisphenol A polycarbonate
thermoplastic,
or other materials Composite syringe barrels are contemplated haying any one
of these
materials as an outer layer and the same or a different one of these materials
as an inner
layer. Any of the material combinations of the composite syringe barrels or
sample tubes
described elsewhere in this specification can also be used.
[868] VII.B.1.b. In any embodiment, the resin optionally can include
polyvinylidene
chloride in homopolymer or copolymer form. For example, the PvDC homopolymers
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Date Recue/Date Received 2020-08-17
(trivial name: Saran) or copolymers described in US Patent 6,165,566, can be
employed.
The resin optionally can be applied onto the exterior surface of the barrel in
the form of
a latex or other dispersion.
[869] VII.B.1.b. In any embodiment, the syringe barrel 548 optionally can
include a
lubricity coating disposed between the plunger and the barrier coating of
SiOx. Suitable
lubricity coatings are described elsewhere in this specification.
[870] VII.B.1.b. In any embodiment, the lubricity coating optionally can be
applied by
PECVD and optionally can include material having the composition SiwOxCyHz.
[871] VII.B.1.b. In any embodiment, the syringe barrel 548 optionally can
include a
surface treatment covering the lubricity coating in an amount effective to
reduce the
leaching of the lubricity coating, constituents of the thermoplastic base
material, or both
into the lumen 604.
Method of Making Syringe having barrel with SiO.coated interior
and barrier coated exterior
[872] VII.B.1.c. Even another embodiment is a method of making a syringe as
described
in any of the embodiments of part VII.B.1.b, including a plunger, a barrel,
and interior
and exterior barrier coatings. A barrel is provided having an interior surface
for slidably
receiving the plunger and an exterior surface. A barrier coating of SiOx is
provided on the
interior surface of the barrel by PECVD. A barrier coating of a resin is
provided on the
Gxterior surface of the barrel. The plunger and barrel are assembled to
provide 2 syringe.
[873] VII.B.1.c. For effective coating (uniform wetting) of the plastic
article with the
aqueous latex, it is contemplated to be useful to match the surface tension of
the latex
to the plastic substrate. This can be accomplished by several approaches,
independently
or combined, for example, reducing the surface tension of the latex (with
surfactants or
solvents), and/or corona pretreatment of the plastic article, and/or chemical
priming of
the plastic article.
[874] VII.B.1.c. The resin optionally can be applied via dip coating of the
latex onto the
exterior surface of the barrel, spray coating of the latex onto the exterior
surface of
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the barrel, or both, providing plastic-based articles offering improved gas
and vapor
barrier performance. Polyvinyl idene chloride plastic laminate articles can be
made that
provide significantly improved gas barrier performance versus the non-
laminated plastic
article.
[875] VII.B.1.c. In any embodiment, the resin optionally can be heat cured.
The
resin optionally can be cured by removing water. Water can be removed by heat
curing
the resin, exposing the resin to a partial vacuum or low-humidity environment,
catalytically curing the resin, or other expedients.
[876] VII.B.1.c. An effective thermal cure schedule is contemplated to
provide final
drying to permit PvDC crystallization, offering barrier performance. Primary
curing can
be carried out at an elevated temperature, for example between 180-310 F (82-
154`C),
of course depending on the heat tolerance of the thermoplastic base material.
Barrier
performance after the primary cure optionally can be about 85% of the ultimate
barrier
performance achieved after a final cure.
[877] VII.B.1.c. A final cure can be carried out at temperatures ranging
from
ambient temperature, such as about 65-75 F (18-24 C) for a long time (such as
2
weeks) to an elevated temperature, such as 122 F (50 C), for a short time,
such as four
hours.
[878] VII.B.1.c. The PvDC-plastic laminate articles, in addition to
superior barrier
performance, are optionally contemplated to provide one or more desirable
properties
such as colorless transparency, good gloss, abrasion resistance, printability,
and
mechanical strain resistance.
VII.B.2. Plungers
VII.B.2.a. With Barrier Coated Piston Front Face
[879] VII.B.2.a. Another embodiment is a plunger for a syringe, including a
piston
and a push rod. The piston has a front face, a generally cylindrical side
face, and a
back porton, the side face being configured to movably seat within a syringe
barrel.
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The front face has a barrier coating. The push rod engages the back portion
and is
configured for advancing the plston in a syringe barrel.
VII.B.2.b. With Lubricity Coating Interfacing With Side Face
[880] VII.B.2.b. Yet another embodiment is a plunger for a syringe,
including a
pston, a lubricity coating, and a push rod. The piston has a front face, a
generally
cylindrical side face, and a back portion. The side face is configured to
movably seat
within a syringe barrel. The lubricity coaling interfaces with the side face.
The push rod
engages the back portion of the piston and is configured for advancing the
piston in a
syringe barrel.
VII.B.3. Two Piece Syringe and Luer Fitting
[881] VII.B.3. Another embodiment is a syringe including a plunger, a
syringe
barrel, and a Luer fitting. The syringe includes a barrel having an interior
surface
slidably receiving the plunger. The Luer fitting includes a Luer taper having
an internal
passage defined by an internal surface. The Luer fitting is formed as a
separate piece
from the syringe barrel and joined to the syringe barrel by a coupling. The
internal
passage of the Luer taper has a barrier coating of SiOx.
[882] VII.B.3. Referring to FIGS. 50-51, the syringe 544 optionally can
include a
Luer fitting 556 comprising a Luer taper 558 to receive a cannula mounted on a
complementary Luer taper (not shown, conventional) The Luer taper 558 has an
internal passage 560 defined by an internal surface 562. The Luer fitting 556
optionally
is formed as a separate piece from the syringe barrel 548 and joined to the
syringe
barrel 548 by a coupling 564. As illustrated in FIGS. 50 and 51, the coupling
564 in this
instance has a rnale part 566 and a female part 568 that snap together to
secure the
Luer fitting in at least substantially leak proof fashion to the barrel 548.
The internal
surface 562 of the Luer taper can include a barrier coating 570 of SiOx. The
barrier
coating can be less than 100 nm thick and effective to reduce the ingress of
oxygen into
the internal passage of the Luer fitting. The barrier coating can be applied
before the
Luer fitting is joined to the syringe barrel. The syringe of FIGS. 50-51 also
has an
192
optional locking collar 572 that is internally threaded so to lock the
complementary Luer
taper of a cannula in place on the taper 558.
VII.B.4. Lubricant Compositions ¨ Lubricity Coating Deposited from an
Organosilicon Precursor Made By In Situ Polymerizing Organosilicon
Precursor
VII.B.4.a. Product By Process and Lubricity
[883] VII.B.4.a. Still another embodiment is a lubricity coating. This
coating can be of
the type made by the following process.
[884] VII.B.4.a. Any of the precursors mentioned elsewhere in this
specification can
be used, alone or in combination. The precursor is applied to a substrate
under
conditions effective to form a coating. The coating is polymerized or
crosslinked, or both,
to form a lubricated surface having a lower plunger sliding force or breakout
force than
the untreated substrate.
[885] VII.B.4.a. Another embodiment is a method of applying a lubricity
coating. An
organosilicon precursor is applied to a substrate under conditions effective
to form a
coating. The coating is polymerized or crosslinked, or both, to form a
lubricated surface
having a lower plunger sliding force or breakout force than the untreated
substrate.
VII.B.4.b. Product by Process and Analytical Properties
[886] VII.B.4.b. Even another aspect of the invention according to its
embodiments is
a lubricity coating deposited by PECVD from a feed gas comprising an
organometallic
precursor, illustratively an organosilicon precursor, illustratively a linear
siloxane, a linear
siiazane, a monocyciic siloxane, a monocyciic siiazane, a polycyclic siloxane,
a
polycyclic silazane, or any combination of two or more of these. The coating
has a
density between 1.25
and 1.65 g/cm3 optionally between 1.35 and 1.55 g/cm3, optionally between 1.4
and 1.5
g/cm3, optionally between 1.44 and 1.48 g/cm3 as determined by X-ray
reflectivity (XRR).
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Date Recue/Date Received 2020-08-17
[887] VII.B.4.b. Still another aspect of the invention according to its
embodiments is
a lubricity coating deposited by PECVD from a feed gas comprising an
organometallic
precursor, illustratively an organosilicon precursor, illustratively a linear
siloxane, a linear
silazane, a monocyclic siloxane, a monocyclic silazane, a polycyclic siloxane,
a
polycyclic silazane, or any combination of two or more of these. The coating
has as an
outgas component one or more oligomers containing repeating -(Me)25i0-
moieties, as
determined by gas chromatography / mass spectrometry. Optionally, the coating
meets
the limitations of any of embodiments VII.B.4.a or VII.B.4.b.. Optionally, the
coating
outgas component as determined by gas chromatography / mass spectrometry is
substantially free of trimethylsilanol.
[888] VII.B.4.b. Optionally, the coating outgas component can be at least 10
ng/test of
oligomers containing repeating -(Me)25i0- moieties, as determined by gas
chromatography / mass spectrometry using the following test conditions:
= GC Column: 30m X 0.25mm DB-5M5 (J&W Scientific),
0.25pm film thickness
= Flow rate: 1.0 ml/min, constant flow mode
= Detector: Mass Selective Detector (MSD)
= Injection Mode: Split injection (10:1 split ratio)
= Outgassing Conditions: 1W (37mm) Chamber, purge for three hour at 85 C,
flow GO ml/min
= Oven temperature: 40 C (5 min.) to 300 C at 10
C/min.; hold for 5 min. at
300 C.
[889] VII.B.4.b. Optionally, the outgas component can include at least 20
ng/test of
oligomers containing repeating -(Me)25i0- moieties.
[890] VII.B.4.b. Optionally, the feed gas comprises a monocyclic siloxane, a
monocyclic
silazane, a polycyclic siloxane, a polycyclic silazane, or any combination of
two or more
of these, for example a monocyclic siloxane, a monocyclic silazane, or any
combination
of two or more of these, for example octamethylcyclotetrasiloxane.
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Date Recue/Date Received 2020-08-17
[891] VII.B.4.b. The lubricity coating of any embodiment can have a thickness
measured
by transmission electron microscopy (TEM) between 1 and 500 nm, optionally
between
20 and 200 nm, optionally between between 20 and 100 nm,
optionally between 30 and 100 nm.
[892] VII.B.4.b. Another aspect of the invention according to its embodiments
is a
lubricity coating deposited by PECVD from a feed gas comprising a monocyclic
siloxane,
a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane, or any
combination
of two or more of these. The coating has an atomic concentration of carbon,
normalized
to 100% of carbon, oxygen, and silicon, as determined by X-ray photoelectron
spectroscopy (XPS), greater than the atomic concentration of carbon in the
atomic
formula for the feed gas. Optionally, the coating meets the limitations of
embodiments
VII.B.4.a or VII.B.4.b.
[893] VII.B.4.b. Optionally, the atomic concentration of carbon increases
by from 1
to 80 atomic percent (as calculated and based on the XPS conditions in Example
15),
alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic
percent,
alternatively from 30 to 50 atomic percent, alternatively from 35 to 45 atomic
percent,
alternatively from 37 to 41 atomic percent.
[894] VII.B.4.b. An additional aspect of the invention according to its
embodiments is
a lubricity coating deposited by PECVD from a feed gas comprising a monocyclic
siloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclic silazane,
or any
combination of two or more of these_ The coating has an atomic concentration
of silicon,
normalized to 100% of carbon, oxygen, and silicon, as determined by X-ray
photoelectron spectroscopy (XPS), less than the atomic concentration of
silicon in the
atomic formula for the feed gas. Optionally, the coating meets the limitations
of
embodiments vii.B.4.a or vii.13.4.b.
[895] VII.B.4.b. Optionally, the atomic concentration of silicon decreases
by from 1
to 80 atomic percent (as calculated and based on the XPS conditions in Example
15),
alternatively from 10 to 70 atomic percent, alternatively from 20 to 60 atomic
percent,
alternatively from 30 to 55 atomic percent, alternatively from 40 to 50 atomic
percent,
alternatively from 42 to 46 atomic percent.
[896] VII.B.4.b. Lubricity coatings having combinations of any two or more
properties
recited in Section VII.B.4 are also expressly contemplated.
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VII.C. Vessels Generally
[897] VII.C. A coated vessel or container as described herein and/or prepared
according
to a method described herein can be used for reception and/or storage and/or
delivery
of a compound or composition. The compound or composition can be sensitive,
for
example air-sensitive, oxygen-sensitive, sensitive to humidity and/or
sensitive to
mechanical influences. It can be a biologically active compound or
composition, for
example a medicament like insulin or a composition comprising insulin. In
another
aspect, it can be a biological fluid, illustratively a bodily fluid, for
example blood or a blood
fraction. In certain aspects of the present invention according to its
embodiments, the
compound or composition is a product to be administrated to a subject in need
thereof,
for example a product to be injected, like blood (as in transfusion of blood
from a donor
to a recipient or reintroduction of blood from a patient back to the patient)
or insulin.
[898] VII.C. A coated vessel or container as described herein and/or prepared
according
to a nnethod described herein can further be used for protecting a compound or
composition contained in its interior space against mechanical and/or chemical
effects
of the surface of the uncoated vessel material. For example, it can be used
for preventing
or reducing precipitation and/or clotting or platelet activation of said
compound or a
component of the composition, for example insulin precipitation or blood
clotting or
platelet activation.
[899] VII.C. It can further be used for protecting a compound or composition
contained
in its interior against the environment outside of the vessel, for example by
preventing or
reducing the entry of one or more compounds from the environment surrounding
the
vessel into the interior space of the vessel. Such environmental compound can
be a
gas or liquid, for example an atmospheric gas or liquid containing oxygen,
air, and/or
water vapor.
[900] VII.C. A coated vessel as described herein can also be evacuated and
stored
in an evacuated state. For example, the coating allows better maintenance of
the vacuum
in comparison to a corresponding uncoated vessel. In one aspect of this
embodiment,
the coated vessel is a blood collection tube. Said tube can also contain an
agent for
preventing blood clotting or platelet activation, for example EDTA or heparin.
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Date Recue/Date Received 2020-08-17
[901] VII.C. Any of the above-described embodiments can be made, for example,
by
providing as the vessel a length of tubing from about 1 cm to about 200 cm,
optionally
from about 1 cm to about 150 cm, optionally from about 1 cm to about 120 cm,
optionally
from about 1 cm to about 100 cm, optionally from about 1 cm to about 80 cm,
optionally
from about 1 cm to about 60 cm, optionally from about 1 cm to about 40 cm,
optionally
from about 1 cm to about 30 cm long, and processing it with a probe electrode
as
described below. Particularly for the longer lengths in the above ranges, it
is
contemplated that relative motion between the probe and the vessel can be
useful during
coating formation. This can be done, for example, by moving the vessel with
respect to
the probe or moving the probe with respect to the vessel.
[902] VII.C. In these embodiments, it is contemplated that the coating can be
thinner or
less complete than can be illustrative for a barrier coating, as the vessel in
some
embodiments will not require the high barrier integrity of an evacuated blood
collection
tube.
[903] VII.C. As an optional feature of any of the foregoing embodiments the
vessel has
a central axis.
[904] VII.C. As an optional feature of any of the foregoing embodiments the
vessel wall
is sufficiently flexible to be flexed at least once at 20 C, without breaking
the wall, over a
range from at least substantially straight to a bending radius at the central
axis of not
more than 100 times as great as the outer diameter of the vessel.
[905] VII.C. As an optional l'aLuit uf any uf Elm fulayuitly ailibudiinatiLb
tlit liatiOiny
radius at the central axis is not more than 90 times as great as, or not more
than 80 times
as great as, or not more than 70 times as great as, or not more than 60 times
as great
as, or not more than 50 times as great as, or not more than 40 times as great
as, or not
more than 30 times as great as, or not more than 20 times as great as, or not
more than
times as great as, or not more than 9 times as great as, or not more than 8
times as
great as, or not more than 7 times as great as, or not more than 6 times as
great as, or
not more than 5 times as great as, or not more than 4 times as great as, or
not more than
3 times as great as, or not more than 2 times as great as, or not more than,
the outer
diameter of the vessel.
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[906] VII.C. As an optional feature of any of the foregoing embodiments the
vessel wall
can be a fluid-contacting surface made of flexible material.
[907] VII C. As an optional feature of any of the foregoing embodiments the
vessel lumen
can be the fluid flow passage of a pump.
[908] VII.C. As an optional feature of any of the foregoing embodiments the
vessel can
be a blood bag adapted to maintain blood in good condition for medical use.
[909] VII.C., VII.D. As an optional feature of any of the foregoing
embodiments the
polymeric material can be a silicone elastomer or a thermoplastic
polyurethane, as two
examples, or any material suitable for contact with blood, or with insulin.
[910] VII.C., VII.D. In an optional embodiment, the vessel has an inner
diameter of
at least 2 mm, or at least 4 mm.
[911] VII.C. As an optional feature of any of the foregoing embodiments the
vessel
is a tube.
[912] VII.C. As an optional feature of any of the foregoing embodiments the
lumen has
at least two open ends.
VII.C.1. Vessel Containing Viable Blood, Having a Coating Deposited from
an Organosilicon Precursor
[913] VII.C.1. Even another embodiment is a blood containing vessel. Several
non-
li mitina examples of such a vessel area blood transfusion baa. a blood sample
collection
vessel in which a sample has been collected, the tubing of a heart-lung
machine, a
flexible-walled blood collection bag, or tubing used to collect a patient's
blood during
surgery and reintroduce the blood into the patient's vasculature. If the
vessel includes a
pump for pumping blood, a particularly suitable pump is a centrifugal pump or
a peristaltic
pump. The vessel has a wall; the wall has an inner surface defining a lumen.
The inner
surface of the wall has an at least partial coating of SiwOxCyHz, where
illustratively w is
1, x is from about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2
to about 9,
more illustratively where w is 1, x is from about 0.5 to 1, y is from about 2
to about 3, and
z is from 6 to about 9. The coating can be as thin as
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monornolecular thickness or as thick as about 1000 nm. The vessel contains
blood viable
for return to the vascular system of a patient disposed within the lumen in
contact with
the SiwOxCyHz coating.
[914] VII.C.1. An embodiment is a blood containing vessel including a wall and
having
an inner surface defining a lumen. The inner surface has an at least partial
coating of
SiwOxCyHz. The coating can also comprise or consist essentially of Si Ox,
where x is as
defined in this specification_ The thickness of the coating is within the
range from
monornolecular thickness to about 1000 nm thick on the inner surface. The
vessel
contains blood viable for return to the vascular system of a patient disposed
within the
lumen in contact with the SiwOxCy1-1, coating.
VII.C.2. Coating Deposited from an Organosilicon Precursor Reduces
Clotting or platelet activation of Blood in the Vessel
[915] VII.C.2. Another embodiment is a vessel having a wall. The wall has an
inner
surface defining a lumen and has an at least partial coating of SiwOxCyHz,
where
illustratively w, x, y, and z are as previously defined: w is 1, x is from
about 0.5 to about
2.4, y is from about 0.6 to about 3, and z is from 2 to about 9, more
illustratively where
w is 1, x is from about 0.5 to 1, y is from about 2 to about 3, and z is from
6 to about Q.
The thickness of the coating is from monomolecular thickness to about 1000 nm
thick on
the inner surface. The coating is effective to reduce the clotting or platelet
activation of
blood exposed to the inner surface, compared to the same type of wall uncoated
with
SiwOxCyHz.
[916] VII.C.2. It is contemplated that the incorporation of an SiwOxCyHz
coating will
reduce the adhesion or clot forming tendency of the blood, as compared to its
properties
in contact with an unmodified polymeric or SiO. surface This property is
contemplated
to reduce or potentially eliminate the need for treating the blood with
heparin, as by
reducing the necessary blood concentration of heparin in a patient undergoing
surgery
of a type requiring blood to be removed from the patient and then returned to
the patient,
as when using a heart-lung machine during cardiac surgery. It is contemplated
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that this will reduce the complications of surgery Involving the passage of
blood through
such a vessel, by reducing the bleeding complications resulting from the use
of heparin.
[917] VII.C.2. Another embodiment is a vessel including a wall and having
an Inner
surface defining a lumen. The inner surface has an at least partial coating of
SiwOõCyH,, the thickness of the coating being from monomolecular thickness to
about
1000 nm thick on the inner surface, the coating being effective to reduce the
clotting or
platelet activation of blood exposed to the inner surface.
VII.C.3. Vessel Containing Viable Blood, Having a Coating of Group III or
IV
Element
[918] VII.C.3. Another embodiment is a blood containing vessel having a
wall
having an inner surface defining a lumen. The inner surface has an at least
partial
coating of a composition comprising one or more elements of Group III, one or
more
elements of Group IV, or a combination of two or more of these. The thickness
of the
coating is between monomolecular thickness and about 1000 nrn thick,
inclusive, on the
inner surface. The vessel contaIns blood viable for return to the vascular
system of a
patient disposed within the lumen in contact with the coating.
VII.C.4. Coating of Group III or IV Element Reduces Clotting or platelet
activation of Blood in the Vessel
[919] VII.C.4. Optionally, in the vessel of the preceding paragraph, the
coating of
tne Group III or IV Element is effective to reduce the clotting or platelet
activation of
blood exposed to the inner surface of the vessel wall.
VII.D. Pharmaceutical Delivery Vessels
[920] VII.D. A coated vessel or container as described herein can be used
for
preventing or reducing the escape of a compound or composition contained in
said
vessel into the environment surrounding the vessel.
[921] Further uses of the coating and vessel as descrlbed herein which are
apparent from any part of the description and claims are also contemplated.
200
VII.D.1. Vessel Containing Insulin, Having a Coating Deposited from an
Organosilicon Precursor
[922] VII.D.1. Another embodiment is an insulin containing vessel including a
wall having
an inner surface defining a lumen. The inner surface has an at least partial
coating of
SiwOxCyHz, illustratively where w, x, y, and z are as previously defined: w is
1, x is from
about 0.5 to 2.4, y is from about 0.6 to about 3, and z is from 2 to about 9,
more
illustratively where w is 1, x is from about 0.5 to 1, y is from about 2 to
about 3, and z is
from 6 to about 9. The coating can be from monomolecular thickness to about
1000 nm
thick on the inner surface. Insulin is disposed within the lumen in contact
with the
SiwOxCyHz coating.
[923] VII.D.1. Still another embodiment is an insulin containing vessel
including a wall
and having an inner surface defining a lumen. The inner surface has an at
least partial
coating of SiwOxCyHz, the thickness of the coating being from monomolecular
thickness
to about 1000 nm thick on the inner surface. Insulin, for example
pharmaceutical insulin
FDA approved for human use, is disposed within the lumen in contact with the
SiwOxCyHz
coating.
[924] VII.D.1. It is contemplated that the incorporation of an SiwOxCyHz
coating will
reduce the adhesion or precipitation forming tendency of the insulin in a
delivery tube of
an insulin pump, as compared to its properties in contact with an unmodified
polymeric
surface. This property is contemplated to reduce or potentially eliminate the
need for
filtering the insulin passing through the delivery tube to remove a solid
precipitate.
VII.D.2. Coating Deposited from an Organosilicon Precursor Reduces
Precipitation of Insulin in the Vessel
[925] VII.D.2. Optionally, in the vessel of the preceding paragraph, the
coating of
SiwOxCyHz, is effective to reduce the formation of a precipitate from insulin
contacting the
inner surface, compared to the same surface absent the coating of SiwOxCyHz.
[926] VII.D.2. Even another embodiment is a vessel again comprising a wall and
having
an inner surface defining a lumen. The inner surface includes an at least
partial coating
of SiwOxCyHz. The thickness of the coating is in the range from monomolecular
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thickness to about 1000 nm thick on the inner surface. The coating is
effective to reduce
the formation of a precipitate from insulin contacting the inner surface.
VII.D.3. Vessel Containing Insulin, Having a Coating of Group III or IV
Element
[927] VII.D.3. Another embodiment is an insulin containing vessel including
a wall
having an inner surface defining a lumen. The inner surface has an at least
partial
coating of a composition comprising carbon, one or more elements of Group Ill,
one or
more elements of Group IV, or a combination of two or more of these. The
coating can
be from monomolecular thickness to about 1000 nm thick on the inner surface.
Insulin
is disposed within the lumen in contact with the coating.
VII.D.4. Coating of Group III or IV Element Reduces Precipitation of
Insulin in
the Vessel
[928] VII.D.4. Optionally, in the vessel of the preceding paragraph, the
coating of a
composition comprising carbon, one or more elements of Group Ill, one or more
elements of Group IV, or a combination of two or more of these, is effective
to reduce
the formation of a precipitate from insulin contacting the inner surface,
compared to the
same surface absent the coating.
WORKING EXAMPLES
Example 0: Basic Protocols for Forming and Coating Tubes and Syringe Barrels
[929] The vessels tested in the subsequent working examples were formed and
coated according to the following exemplary protocols, except as otherwise
indicated in
individual examples. Particular parameter values given in the following basic
protocols,
e.g. the electric power and process gas flow, are typical values. Whenever
parameter
values were changed in comparison to these typical values, this will be
indicated in the
subsequent working examples. The same applies to the type and composition of
the
process gas.
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Protocol for Forming COC Tube (used, e.g., in Examples 1, 19)
[930] Cyclic olefin copolymer (COC) tubes of the shape and size commonly
used
as evacuated blood collection tubes ("COC tubes") were injection molded from
Topas
8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG,
Frankfurt am
Main, Germany, having these dimensions: 75 mm length, 13 mm outer diameter,
and
0.85 mm wall thickness, each having a volume of about 7.25 CM3 and a closed,
rounded
end.
Protocol for Forming PET Tube (used, e.g., in Examples 2, 4,8, 9, 10)
[931] Polyethylene terephthalate (PET) tubes of the type commonly used as
evacuated blood collection tubes ("PET tubes") were injection molded in the
same mold
used for the Protocol for Forming COC Tube, having these dimensions: 75 mm
length,
13 mm outer diameter, and 0.85 mm wall thickness, each having a volume of
about
7.25 cm3 and a closed, rounded end.
Protocol for Coating Tube Interior with SiO. (used, e.g., in Examples 1, 2, 4,
8, 9,
10, 18, 19)
[932] The apparatus as shown in FIG. 2 with the sealing mechanism of FIG.
45,
which is a specific contemplated embodiment, was used. The vessel holder 50
was
made from Delrin acetal resin, available from E.I. du Pont de Nemours and
Co.,
Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and
a
height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin0
structure
that allowed the device to move in and out of the electrode (160).
[933] The electrode 160 was made from copper with a Del rin0 shield. The
Del riff)
shield was conformal around the outside of the copper electrode 160. The
electrode
160 measured approximately 3 inches (76 mm) high (inside) and was
approximately
0.75 inches (19 mm) wide.
[934] The tube used as the vessel 80 was inserted into the vessel holder 50
base
sealing with Viton 0-rings 490, 504 (Viton is a trademark of Dupont
Performance
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Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube
(FIG. 45).
The tube 80 was carefully moved into the sealing position over the extended
(stationary)
1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed
against a
copper plasma screen.
[935] The copper plasma screen 610 was a perforated copper foil material
(K&S
Engineering, Chicago Illinois, USA, Part #LXMUVV5 copper mesh) cut to fit the
outside
diameter of the tube, and was held in place by a radially extending abutment
surface
494 that acted as a stop for the tube insertion (see FIG. 45). Two pieces of
the copper
resh were fit snugly around the brass probe or counter electrode 108, insuring
good
electrical contact.
[936] The brass probe or counter electrode 108 extended approximately 70 mm
into the interior of the tube and had an array of #80 wire (diameter = 0.0135
inch or
0.343 mm). The brass probe or counter electrode 108 extended through a
Swagelok
fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom
of the
vessel holder 50, extending through the vessel holder 50 base structure. The
brass
probe or counter electrode 108 was grounded to the casing of the RF matching
network.
[937] The qas delivery port 110 was 12 holes in the probe or counter
electrode 108
along the length of the tube (three on each of four sides oriented 90 degrees
from each
other) and two holes in the aluminum cap that plugged the end of the gas
delivery port
110. The gas delivery port 110 was connected to a stainless steel assembly
comprised
of Swagelok fittings incorporating a manual ball valve for venting, a
thermocouple
pressure gauge and a bypass valve connected to the vacuum pumping line. In
addition,
the gas system was connected to the gas delivery port 110 allowing the process
gases,
oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery
port
110 (under process pressures) into the interior of the tube.
[938] The gas system was comprised of a Aalborg GFC17 mass flow meter
(Part
# EW-32661-34, Cole-Farmer Instrument Co., Barrington Illinois USA) for
controllably
flowing oxygen at 90 sccm (or at the specific flow reported for a particular
example) into
the process and a polyether ether ketone ("PEEK") capillary (outside diameter,
"OD"
1/16-inch (1.5-mm.), inside diameter, "ID" 0.004 inch (0.1 mm)) of length 49.5
inches
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(1.26 m). The PEEK capillary end was inserted into liquid hexamethyldisiloxane
("HMDSO," Alfa Aesar0 Pant Number 1_16970, NmR Grade, available from Johnson
Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to
the
lower pressure in the tube during processing. The HMDSO was then vaporized
into a
vapor at the exit of the capillary as it entered the low pressure region.
[939] To ensure no condensation of the liquid HMDSO past this point, the
gas
stream (including the oxygen) was diverted to the pumping line when it was not
flowing
into the interior of the tube for processing via a Swagelok0 3-way valve. Once
the tube
was installed, the vacuum pump valve was opened to the vessel holder 50 and
the
interior of tie tube.
[940] An Alcatel rotary vane vacuum pump and blower comprised the vacuum
pump system. The pumping system allowed the interior of the tube to be reduced
to
pressure(s) of less than 200 mTorr while the process gases were flowing at the
indicated rates.
[941] Once the base vacuum level was achieved, the vessel holder 50
assembly
was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO
vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way
valve
from the pumping line to the gas delivery port 110). Pressure inside the tube
was
approximately 300 mTorr as measured by a capacitance manometer (MKS) installed
on
the pumping line near the valve that controlled the vacuum. In addition to the
tube
pressure, the pressure inside the gas delivery port 110 and gas system was
also
measured with the thermocouple vacuum gauge that was connected to the gas
system.
This pressure was typically less than 8 Torr.
[942] Once the gas was flowing to the interior of the tube, the RF power
supply was
turned on to its fixed power level. A EN! ACG-G 600 Watt RF power supply was
used
(at 13.56 MHz) at a fixed power level of approximately 50 Watts. The output
power was
calibrated in this and all following Protocols and Examples using a Bird
Corporation
Model 43 RF Watt meter connected to the RF output of the power supply during
operation of the coating apparatus. The following relationship was found
between the
dal setting on the power supply and the output power: RF Power Out = 55 x Dial
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Setting. In the priority applications to the present application, a factor 100
was used,
which was incorrect. The RF power supply was connected to a CONADEL CPY1x1 000
auto match which matched the complex impedance of the plasma (to be created in
the
tube) to the 50 ohm output impedance of the ENI ACG-6 RF power supply. The
forward
power was 50 Watts (or the specific amount reported for a particular example)
and the
reflected power was 0 Watts so that the applied power was delivered to the
interior of
the tube. The RF power supply was controlled by a laboratory timer and the
power on
time set to 5 seconds (or the specific time period reported for a particular
example).
Upon initiation of the RF power, a uniform plasma was established inside the
interior of
the tube. The plasma was maintained for the entire 5 seconds until the RE
power was
terminated by the timer. The plasma produced a silicon oxide coating of
approximately
20 nm thickness (or the specific thickness reported in a particular example)
on the
interior of the tube surface.
[943] After coating, the gas flow was diverted oack to toe vacuum line and
toe
vacuum valve was closed. The vent valve was then opened, returning the
interior of the
tube to atmospheric pressure (approximately 760 Torr). The tube was then
carefully
removed from the vessel holder 50 assembly (after moving the vessel holder 50
a3serribly out of the electrode 160 US3Uf bly).
Protocol for Coating Tube Interior with Hydrophobic Coating (used, e.g., in
Example 9)
[944] The apparatus as shown in FIG. 2 with the sealing mechanism of FIG.
45,
which is a specific contemplated embodiment, was used. The vessel holder 50
was
trade from Delrin acetal resin, available from E.I. du Pont de Nemours and
Co.,
Wilmington Delaware, USA, with an outside diameter of 1.75 inches (44 mm) and
a
height of 1.75 inches (44 mm). The vessel holder 50 was housed in a Delrin
structure
that allowed the device to move in and out of the electrode (160).
[945] The electrode 160 was made from copper with a Delrin shield. The
Delrin
shield was conformal around the outside of the copper electrode 160. The
electrode
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160 measured approximately 3 inches (76 mm) high (inside) and was
approximately
0.75 inches (19 mm) wide.
[946] The tube used as the vessel 80 was inserted into the vessel holder 50
base
sealing with Viton 0-rings 490, 504 (Viton0 is a trademark of Dupont
Performance
Elastomers LLC, Wilmington Delaware, USA) around the exterior of the tube
(FIG. 45).
The tube 80 was carefully moved into the sealing position over the extended
(stationary)
1/8-inch (3-mm) diameter brass probe or counter electrode 108 and pushed
against a
copper plasma screen.
[947] The copper plasma screen 610 was a perforated copper foil material
(K&S
Engineering, Chicago Illinois, USA, Part #LXMUW5 copper mesh) cut to fit the
outside
diameter of the tube, and was held in place by a radially extending abutment
surface
494 that acted as a stop for the tube insertion (see FIG. 45). Two pieces of
the copper
mesh were fit snugly around the brass probe or counter electrode 108, insuring
good
electrical contact.
[948] The brass probe or counter electrode 108 extended approximately 70 mm
into the interior of the tube and had an array of #80 wire (diameter = 0.0135
inch or
0.343 mm). The brass probe or counter electrode 108 extended through a
Swaqelok
fitting (available from Swagelok Co., Solon Ohio, USA) located at the bottom
of the
vessel holder 50, extending through the vessel holder 50 base structure. The
brass
probe or counter electrode 108 was grounded to the casing of the RF matching
network.
[940] The gas delivery port 110 was 12 holes in the probe or counter
electrode 109
along the length of the tube (three on each of four sides oriented 90 degrees
from each
other) and two holes in the aluminum cap that plugged the end of the gas
delivery port
110. The gas delivery port 110 was connected to a stainless steel assembly
comprised
of 9wagelok0 fittings incorporating a manual ball valve for venting, a
thermocouple
pressure gauge and a bypass valve connected to the vacuum pumping line. In
addition,
the gas system was connected to the gas delivery port 110 allowing the process
gases,
oxygen and hexamethyldisiloxane (HMDSO) to be flowed through the gas delivery
port
110 (under process pressures) into the interior of the tube.
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[950] The gas system was comprised of a Aalborg GFC17 mass flow meter
(Part
# EW-32661-34, Cole-Parmer Instrument Co., Barrington 1111nois USA) for
controllably
flowing oxygen at 60 sccm (or at the specific flow reported for a particular
example) into
the process and a polyether ether ketone ("PEEK") capillary (outside diameter,
"OD"
1/16-inch (1.5-mm.), inside diameter, "ID" 0.004 inch (0.1 mm)) of length 49.5
inches
(1.26 nn). The PEEK capillary end was inserted into liquid
hexamethyldisiloxane
("HMDSO," Alfa Aesare Part Number L16970, NMR Grade, available from Johnson
Matthey PLC, London). The liquid HMDSO was pulled through the capillary due to
the
lower pressure in the tube during processing. The HMDSO was then vaporized
into a
vapor at the exit of the capillary as it entered the low pressure region.
[951] To ensure no condensation of the liquid HMDSO past this point, the
gas
stream (including the oxygen) was diverted to the pumping line when it was not
flowing
into the interior of the tube for processing via a Swagelok 3-way valve. Once
the tube
was installed, the vacuum pump valve was opened to the vessel holder 50 and
the
interior of the tube.
[952] An Alcatel rotary vane vacuum pump and blower comprised the vacuum
pump system. The pumping system allowed the interior of the tube to be reduced
to
pressure(s) of less than 200 mTorr while the process gases were flowing at the
indicated rates.
[953] Once the base vacuum level was achieved, the vessel holder 50
assembly
was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO
vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way
valve
from the pumping line to the gas delivery port 110). Pressure inside the tube
was
approximately 270 mTorr as measured by a capacitance manometer (MKS) installed
on
the pumping line near the valve that controlled the vacuum. In addition to the
tube
pressure, the pressure inside the gas delivery port 110 and gas system was
also
'measured with the thermocouple vacuum gauge that was connected to the gas
system.
This pressure was typically less than 8 Torr.
[954] Once the gas was flowing to the interior of the tube, the RF power
supply was
turned on to its fixed power level. A EN I ACG-6 600 Watt RF power supply was
used
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(at 13.56 MHz) at a fixed power level of approximately 39 Watts. The RF power
supply
was connected to a COMDEL CPMX1000 auto match which matched the complex
impedance of the plasma (to be created in the tube) to the 50 ohm output
impedance of
the EN I ACG-6 RF power supply. The forward power was 39 Watts (or the
specific
amount reported for a particular example) and the reflected power was 0 Watts
so that
the applied power was delivered to the interior of the tube. The RF power
supply was
controlled by a laboratory timer and the power on time set to 7 seconds (or
the specific
time period reported for a particular example). Upon initiation of the RF
power, a
uniform plasma was established inside the interior of the tube. The plasma was
maintained for the entire 7 seconds until the RF power was terminated by the
timer.
The plasma produced a silicon oxide coating of approximately 20 nm thickness
(or the
specific thickness reported in a particular example) on the interior of the
tube surface.
[955] After coating, the gas flow was diverted back to the vacuum line and
the
vacuum valve was closed. The vent valve was then opened, returning tne
interior of tne
tube to atmospheric pressure (approximately 760 Torr). The tube was then
carefully
removed from the vessel holder 50 assembly (after moving the vessel holder 50
assembly out of the electrode 160 assembly).
Protocol for Forming COC Syringe Barrel (used, e.g., in Examples 3,5, 11-18,
20)
[956] Syringe barrels ("COC syringe barrels"), CV Holdings Part 11447, each
having a 2.8 mL overall volume (excluding the Luer fitting) and a nominal 1 mL
delivery
volume or plunger displacement, Luer adapter type, were injection molded from
Topas
8007-04 cyclic olefin copolymer (COC) resin, available from Hoechst AG,
Frankfurt am
Main, Germany, having these dimensions: about 51 mm overall length, 8.6 mm
inner
syringe barrel diameter and 1.27 rem wall thickness at the cylindrical
portion, with an
integral 9.5 millimeter length needle capillary Luer adapter molded on one end
and two
finger flanges molded near the other end.
Protocol for Coating COC Syringe Barrel Interior with SiOx (used, e.g. in
Examples
3,5, 18)
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[957] An injection molded COO syringe barrel was interior coated with SiOx.
The
apparatus as shown in FIG. 2 with the sealing mechanism of FIG. 45 was
modified to
hold a COC syringe barrel with butt sealing at the base of the COC syringe
barrel.
Additionally a cap was fabricated out of a stainless steel Luer fitting and a
polypropylene
cap that sealed the end of the COO syringe barrel (illustrated in FIG. 26),
allowing the
interior of the COC syringe barrel to be evacuated.
[958] The vessel holder 50 was made from Delrine with an outside diameter
of 1.75
inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was
housed
in a DeInn structure that allowed the device to move in and out of the
electrode 160.
[959] The electrode 160 was made from copper with a Delrin shield. The
Delrin
shield was conformal around the outside of the copper electrode 160. The
electrode
160 measured approximately 3 inches (76 mm) high (inside) and was
approximately
0.75 inches (19 mrn) wide. The COO syringe barrel was inserted into the vessel
holder
50, base sealing with an Viton 0-rings.
[960] The COO syringe barrel was carefully moved into the sealing position
over
the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter
electrode
108 and pushed acjainst a copper plasma screen. The copper plasma screen was a
perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut
to
fit the outsIde diameter of the COO syringe barrel and was held in place by a
abutment
surface 494 that acted as a stop for the COO syringe barrel insertion. Two
pieces of the
copper mesh were fit snugly around the brass probe or counter electrode 108
insuring
good electrical contact.
[961] The probe or counter electrode 108 extended approximately 20 mm into
the
interior of the COC syringe barrel and was open at its end. The brass probe or
counter
electrode 108 extended through a 9wage1ok0 fitting located at the bottom of
the vessel
holder 50, extending through the vessel holder 50 base structure. The brass
probe or
counter electrode 108 was grounded to the casing of the RF matching network.
[962] The gas delivery port 110 was connected to a stainless steel assembly
comprised of Swagelok fittings incorporating a manual ball valve for venting,
a
thermocouple pressure gauge and a bypass valve connected to the vacuum pumping
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line. In addition, the gas system was connected to the gas delivery port 110
allowing
the process gases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed
through
the gas delivery port 110 (under process pressures) into the interior of the
COC syringe
barrel.
[963] The gas system was comprised of a Aalborg GFC17 mass flow meter
(Cole
Parmer Part # EW-32661-34) for controllably flowing oxygen at 90 sccm (or at
the
specific flow reported for a particular example) into the process and a PEEK
capillary
(OD 1/16-inch (3-mm) 10 0.004 inches (0.1 mm)) of length 49.5 inches (1.26 m).
The
PEEK capillary end was inserted into liquid hexamethyldisiloxane (Alfa Aesar
Part
Number L16970, NMR Grade). The Nina HMDSO was pulled through the capillary due
to the lower pressure in the COO syringe barrel during processing. The HMDSO
was
then vaporized into a vapor at the exit of the capillary as it entered the low
pressure
region.
[964] To ensure no condensation of the liquid HMDSO past this point, the
gas
stream (including the oxygen) was diverted to the pumping line when it was not
flowing
into the interior of the COG syringe barrel for processing via a Swagelok 3-
way valve.
Once the COC syringe barrel was installed, the vacuum pump valve was opened
to the vessel holder 50 and the interior of the COO syringe barrel. An Alcatel
rotary
vane vacuum pump and blower comprised the vacuum pump system. The pumping
system allowed the interior of the COC syringe barrel to be reduced to
pressure(s) of
less than 150 mTorr while the process gases were flowing at the indicated
rates. A
lower pumping pressure was achievable with the COC syringe barrel, as opposed
to the
tube, because the COO syringe barrel has a much smaller internal volume.
[965] After the base vacuum level was achieved, the vessel holder 50
assembly
was moved into the electrode 160 assembly. The gas stream (oxygen and HMDSO
vapor) was flowed into the brass gas delivery port 110 (by adjusting the 3-way
valve
from the pumping line to the gas delivery port 110). The pressure inside the
COO
syringe barrel was approximately 200 mTorr as measured by a capacitance
manometer
(MKS) installed on the pumping line near the valve that controlled the vacuum.
In
addition to the COG syringe barrel pressure, the pressure inside the gas
delivery port
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110 and gas system was also measured with the thermocouple vacuum gauge tha1
was
connected to the gas system. This pressure was typically less than 8 Torr.
[966] When the gas was flowing to the interior of the COO syringe barrel,
the RF
power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF
power
supply was used (at 13.56 MHz) at a fixed power level of approximately 30
Watts. The
RF power supply was connected to a COMDEL CPMX1000 auto match that matched
the complex impedance of the plasma (to be created in the COC syringe barrel)
to the
50 ohm output impedance of the ENI ACG-6 RF power supply. The forward power
was
30 Watts (or whatever value is reported in a working example) and the
reflected power
was o watts so that tne power was delivered to the interior of the COC syringe
barrel.
The RF power supply was controlled by a laboratory timer and the power on time
set to
seconds (or the specific time period reported for a particular example).
[967] Upon initiation of the RF power, a uniform plasma was established
inside the
interior of the COO syringe barrel. The plasma was maintained for the entire 5
seconds
(or other coating time indicated in a specific example) until the RF power was
terminated by the timer. The plasma produced a silicon oxide coating of
approximately
20 nm thickness (or the thickness reported in a specific example) on the
interior of the
COC syringe barrel surface.
[968] After coating, the gas flow was diverted back to the vacuum line and
the
vacuum valve was closed. The vent valve was then opened, returning the
interior of the
COC syringe barrel to atmospheric pressure (approximately 760 Tor). The COC
syringe barrel was then carefully removed from the vessel holder 50 assembly
(after
moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity Coating
(used, e.g., in Examples 11, 12, 15-18, 20)
[969] COO syringe barrels as previously identified were interior coated
with a
lubricity coating. The apparatus as shown in FIG. 2 with the sealing mechanism
of FIG.
45 was modified to hold a COC syringe barrel with butt sealing at the base of
the COO
syringe barrel. Additionally a cap was fabricated out of a stainless steel
Luer fitting and
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a polypropylene cap that sealed the end of the COO syringe barrel (illustrated
in FIG.
26). The installation of a Buna-N 0-ring onto the Luer fitting allowed a
vacuum tight
seal, allowing the interior of the COC syringe barrel to be evacuated.
[970] The vessel holder 50 was made from Delrin0 with an outside diameter
of 1.75
inches (44 mm) and a height of 1.75 inches (44 mm). The vessel holder 50 was
housed
in a Delrin0 structure that allowed the device to move in and out of the
electrode 160.
[971] The electrode 160 was made from copper with a Delrin shield. The
Delrin
shield was conformal around the outside of the copper electrode 160. The
electrode
160 measured approximately 3 inches (76 mm) high (inside) and was
approximately
0.75 inches (19 mm) wide. The COC syringe barrel was inserted into the vessel
holder
50, base sealing with Vitone 0-rings around the bottom of the finger flanges
and lip of
the COC syringe barrel.
[972] The COO syringe barrel was carefully moved into the sealing position
over
the extended (stationary) 1/8-inch (3-mm.) diameter brass probe or counter
electrode
108 and pushed against a copper plasma screen. The copper plasma screen was a
perforated copper foil material (K&S Engineering Part #LXMUW5 Copper mesh) cut
to
fit the outside diameter of the COC syringe barrel and was held in place by a
abutment
surface 494 that acted as a stop for the COC syringe barrel insertion. Two
pieces of the
copper mesh were fit snugly around the brass probe or counter electrode 108
insuring
good electrical contact.
[973] The probe or counter electrode 108 extended approximately 20mm
(unless
otherwise indicated) into the interior of the COC syringe barrel and was open
at its end.
The brass probe or counter electrode 108 extended through a Swagelok0 fitting
located
at the bottom of the vessel holder 50, extending through the vessel holder 50
base
structure. The brass probe or counter electrode 108 was grounded to the casing
of the
RF matching network.
[974] The gas delivery port 110 was connected to a stainless steel assembly
comprised of Swageloke fittings incorporating a manual ball valve for venting,
a
thermocouple pressure gauge and a bypass valve connected to the vacuum pumping
line. In addition; the gas system was connected to the gas delivery port 110
allowing
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the process gas, octamethylcyclotetrasiloxane (OMCTS) (or the specific process
gas
reported for a particular example) to be flowed through the gas delivery port
110 (under
process pressures) into the interior of the COG syringe barrel.
[975] The gas system was comprised of a commercially available Horiba
VC1310/SER8240 OMCTS 10SC 4CR heated mass flow vaporization system that
heated the ()MOTS to about 100`C. The Horiba system was connected to liquid
octamethylcyclotetrasiloxane (Alfa Aesare Part Number A12540, 98%) through a
1/8-
inch (3-mm) outside diameter PFA tube with an inside diameter of 1/16 in (1.5
mm).
The OMCTS flow rate was set to 1.25 sccm (or the specific organosil icon
precursor flow
reported for a particular example). To ensure no condensation of the vaporized
OMCTS flow past this point, the gas stream was diverted to the pumping line
when it
was not flowing into the interior of the COC syringe barrel for processing via
a
Swagelok0 3-way valve.
[976] Once the COG syringe barrel was installed, the vacuum pump valve was
opened to the vessel holder 50 and the interior of the COO syringe barrel. An
Alcatel
rotary vane vacuum pump and blower comprised the vacuum pump system. The
pumping system allowed the interior of the COG syringe barrel to be reduced to
pressure(s) of less than 100 mTorr while the process gases were flowing at the
indicated rates. A lower pressure could be obtained in this instance, compared
to the
tube and previous COG syringe barrel examples, because the overall process gas
flow
rate is lower in this instance.
[977] Once the base vacuum level was achieved, the vessel holder 50
assembly
was moved into the electrode 160 assembly. The gas stream (OMCTS vapor) was
flowed into the brass gas delivery port 110 (by adjusting the 3-way valve from
the
pumping line to the gas delivery port 110). Pressure inside the COG syringe
barrel was
approximately 140 mTorr as measured by a capacitance manometer (MKS) installed
on
the pumping line near the valve that controlled the vacuum. In addition to the
COC
syringe barrel pressure, the pressure inside the gas delivery port 110 and gas
system
was also measured with the thermocouple vacuum gauge that was connected to the
gas system. This pressure was typically less than 6 Torr.
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[978] Once the gas was flowing to the interior of the COO syringe barrel,
the RF
power supply was turned on to its fixed power level. A ENI ACG-6 600 Watt RF
power
supply was used (at 13.56 MHz) at a fixed power level of approximately 7.5
Watts (or
other power level indicated in a specific example). The RF power supply was
connected to a COMDEL CPMX1000 auto match which matched the complex
impedance of the plasma (to be created in the COC syringe barrel) to the 50
ohm output
impedance of the EN I ACG-6 RF power supply. The forward power was 7.5 Watts
and
the reflected power was 0 Watts so that 7.5 Watts of power (or a different
power level
delivered in a given example) was delivered to the interior of the COO syringe
barrel.
The RE power supply was controlled by a laboratory timer and the power on time
set to
seconds (or a different time stated in a given example).
[979] Upon initiation of the RF power, a uniform plasma was established
inside the
interior of the COC syringe barrel. The plasma was maintained for the entire
coating
time, until toe F1F power was terminated IDy toe timer. -me plasma produced a
lubricity
coating on the interior of the COC syringe barrel surface.
[980] After coating, the gas flow was diverted back to the vacuum line and
the
vacuum valve was closed. The vent valve was then opened, returning the
interior of the
COC syringe barrel to atmospheric pressure (approximately 760 Toni. The COC
syringe barrel was then carefully removed from the vessel holder 50 assembly
(after
moving the vessel holder 50 assembly out of the electrode 160 assembly).
Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating (used,
e.g.,
in Examples 12, 15, 16, 17)
[981] The Protocol for Coating COC Syringe Barrel Interior with OMCTS
Lubricity
Coating was also used for applying an HMDSO coating, except substituting HMDSO
for
OMCTS.
Example 1
[982] V. In the following test, hexamethyldisiloxane (HMDSO) was used as
the
organosilicon ("0-Si") feed to PECVD apparatus of FIG. 2 to apply an SiOx
coating on
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the internal surface of a cyclic olefin copolymer (COC) tube as described in
the Protocol
for Forming COC Tube. The deposition conditions are summarized in the Protocol
for
Coating Tube Interior with SiOx and Table 1. The control was the same type of
tube to
which no barrier coating was applied. The coated and uncoated tubes were then
tested
for their oxygen transmission rate (OTR) and their water vapor transmission
rate
(WVTR).
[983] V. Referring to Table 1, the uncoated COC tube had an OTR of 0.215
cc/tube/day. Tubes A and B subjected to PECVD for 14 seconds had an average
OTR
of 0.0235 cc/tube/day. These results show that the Si0), coating provided an
oxygen
transmisslon BIF over tne uncoated tube of 9.1. In otner words, tne &OK
barrier coating
reduced the oxygen transmission through the tube to less than one ninth its
value
without the coating.
[984] V. Tube C subjected to PECVD for 7 seconds had an OTR of 0.026. This
result shows that the Si0,, coating provided an OTR BIF over the uncoated tube
of 8.3.
In other words, the SiOx barrier coating applied in 7 seconds reduced the
oxygen
transmission through the tube to less than one eighth of its value without the
coating.
[985] V. The relative WVTRs of the same barrier coatings on COC tubes were
also
measured. The uncoated COC tube had a WVTR of 0.27 mg/tube/day. Tubes A and B
subjected to PECVD for 14 seconds had an average WVTR of 0.10 mg/tube/day or
less. Tube C subjected to PECVD for 7 seconds had a WVTR of 0.10 mg/tube/day.
This result shows that the SiO, coating provided a water vapor transmission
barrier
improvement factor (WVTR BIF) over the uncoated tube of about 2.7. This was a
surprising result, since the uncoated COC tube already has a very low WVTR.
Example 2
[986] V. A series of PET tubes, made according to the Protocol for Forming
PET
Tube, were coated with SiOõ according to the Protocol for Coating Tube
Interior with
Si0,, under the conditions reported in Table 2. Controls were made according
to the
Protocol for Forming PET Tube, but left uncoated. OTR and WVTR samples of the
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tubes were prepared by epoxy-sealing the open end of each tube to an aluminum
adaptor.
[987] In a separate test, using the same type of coated PET tubes,
mechanical
scratches of various lengths were induced with a steel needle through the
interior
coating, and the OTR BIF was tested. Controls were either left uncoated or
were the
same type of coated tube without an induced scratch. The OTR BIF, while
diminished,
was still improved over uncoated tubes (Table 2A).
[988] V. Tubes were tested for OTR as follows. Each sample/adaptor assembly
was fitted onto a MOCON Cxtran 2/21 Oxygen Permeability Instrument. Samples
were allowed to equilibrate to transmission rate steady state (1-3 days) under
the
following test conditions:
= Test Gas: Oxygen
= Test Gas Concentration: 100%
= Test Gas Humidity: 0% relative humidity
= Test Gas Pressure: 760 mm Hg
= Test Temperature: 23.0"C (73.4"F)
= Carrier Gas: 98% nitrogen, 2% hydrogen
= Carrier Gas Humidity: 0% relative humidity
[089] V. The OTR is reported as average of two determinations in Table 2.
[990] V. Tubes were tested for WVTR as follows. The sample/adaptor assembly
was fitted onto a MOCON Permatran- W 3/31 Water Vapor Permeability
Instrument.
Samples were allowed to equilibrate to transmission rate steady state (1-3
days) under
the following test conditions:
= Test Gas: Water Vapor
= Test Gas Concentration: NA
= Test Gas Hum idity: 100% relative humidity
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= Test Gas Temperature: 37.8( C) 100.0( F)
= Carrier Gas: Dry nitrogen
= Carrier Gas Humidity: 0% relative humidity
[991] The WV-FR is reported as average of two determinations in Table 2.
Example 3
[992] A series of syringe barrels were made according to the Protocol for
Forming
COG Syringe barrel. The syringe barrels were either barrier coated with SiO,
or not
under the conditions reported in the Protocol for Coating COC Syringe barrel
Interior
with SIO, modified as indicated in Table 3.
[993] OTR and WVTR samples of the syringe barrels were prepared by epoxy-
sealing the open end of each syringe barrel to an aluminum adaptor.
Additionally, the
syringe barrel capillary ends were sealed with epoxy. The syringe-adapter
assemblies
were tested for OTR or WVTR in the same manner as the PET tube samples, again
using a MOCON Oxtran 2/21 Oxygen Permeability Instrument and a MOCON
Permatran- W 3/31 Water Vapor Permeability Instrument. The results are
reported in
I able 3.
Example 4
Composition Measurement of Plasma Coatings using X-Ray Photoelectron
Spectroscopy (XPS)/ Electron Spectroscopy for Chemical Analysis (ESCA)
Surface Analysis
[994] V.A. PET tubes made according to the Protocol for Forming PET Tube
and
coated according to the Protocol for Coating Tube Interior with Si0,, were cut
in half to
expose the inner tube surface, which was then analyzed using X-ray
photoelectron
spectroscopy (XPS).
[995] V.A. The XPS data was quantified using relative sensitivity factors
and a
model which assumes a homogeneous layer. The analysis volume is the product of
the
analysis area (spot size or aperture size) and the depth of information.
Photoelectrons
218
are generated within the X-ray penetration depth (typically many microns), but
only the
photoelectrons within the top three photoelectron escape depths are detected.
Escape
depths are on the order of 15-35 A, which leads to an analysis depth of -50-
100 A.
Typically, 95% of the signal originates from within this depth.
[996] V.A. Table 5 provides the atomic ratios of the elements detected. The
analytical
parameters used in for XPS are as follows:
Instrument PHI Quantum 2000
X-ray source Monochromated Alk,(1486.6eV
Acceptance Angle 23
Take-off angle 45
Analysis area 600um
Charge Correction C1s 284.8 eV
Ion Gun Conditions Ark, 1 keV, 2 x 2 mm raster
Sputter Rate 15.6 A/min (SiO2
Equivalent)
[997] V.A. XPS does not detect hydrogen or helium. Values given are normalized
to
Si = 1 for the experimental number (last row) using the elements detected, and
to 0 = 1
for the uncoated polyethylene terephthalate calculation and example. Detection
limits
are approximately 0.05 to 1.0 atomic percent. Values given are alternatively
normalized
to 100% Si + 0 + C atoms.
[998] V.A. The Inventive Example has an Si/0 ratio of 2.4 indicating an SiOx
composition,
with some residual carbon from incomplete oxidation of the coating. This
analysis
demonstrates the composition of an SiOx barrier layer applied to a
polyethylene
terephthalate tube according to the present invention according to its
embodiments.
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[999] V.A. Table 4 shows the thickness of the SiOõ samples, determined
using
TEM according to the following method. Samples were prepared for Focused Ion
Beam
(FIB) cross-sectioning by coating the samples with a sputtered layer of
platinum (50-
100nm thick) using a K575X Emitech coating system. The coated samples were
placed
in an FEI FIB200 FIB system. An additional layer of platinum was FIB-deposited
by
injection of an organo-metallic gas while rastering the 30kV gallium ion beam
over the
area of interest. The area of interest for each sample was chosen to be a
location half
way down the length of the tube. Thin cross sections measuring approximately
15pm
("micrometers") long, 2pm wide and 15pm deep were extracted from the die
surface
using a proprietary in-situ FIR lift-out technique. The cross sections were
attached to a
200 mesh copper TEM grid using FIB-deposited platinum. One or two windows in
each
section, measuring about 8pm wide, were thinned to electron transparency using
the
gallium ion beam of the FEI FIB.
V.C. Cross-sectional image analysis of the prepared samples was performed
utilizing a
Transmission Electron Microscope (TEM). The imaging data was recorded
digitally.
[1000] The sample grids were transferred to a Hitachi HF2000 transmission
electron
microscope. Transmitted electron imaqes were acquired at appropriate
magnifications.
The relevant instrument settings used during image acquisition are given
below.
Transmission Electron
Instrument Microscope
Manufacturer/Model Hitachi H F2000
Accelerating Voltage 200 kV
Condenser Lens 1 0.78
Condenser Lens 2 0
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Objective Lens 6.34
Condenser Lens Aperture #1
Objective Lens Aperture for #3
imaging
Selective Area Aperture for N/A
SAD
Example 5
Plasma Uniformity
[1001] V.A. COO syringe barrels made according to the Protocol for Forming
COO
Syringe barrel were treated using the Protocol for Coating COO Syringe Barrel
Interior
with Si0õ, with the following variations. Three different modes of plasma
generation were
tested tor coating syringe barrels such as 250 with SiUx films. V.A. In Mode
1, hollow
cathode plasma ignition was generated in the gas inlet 310, restricted area
292 and
processing vessel lumen 304, and ordinary or non-hollow-cathode plasma was
generated in the remainder of the vessel lumen 300.
[1002] V.A. In Mode 2, hollow cathode plasma ignition was generated in the
restricted area 292 and processing vessel lumen 304, and ordinary or non-
hollow-
cathode plasma was generated in the remainder of the vessel lumen 300 and gas
inlet
310.
[1003] V.A. In Mode 3, ordinary or non-hollow-cathode plasma was generated
in the
entire vessel lumen 300 and gas inlet 310. This was accomplished by ramping up
power to quench any hollow cathode ignition. Table 6 shows the conditions used
to
achieve these modes.
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[1004] V.A. The syringe barrels 250 were then exposed to a ruthenium oxide
staining technique. The stain was made from sodium hypochlorite bleach and
Ru(111)
chloride hydrate. 0.2g of Ru(III) chloride hydrate was put into a vial. 10m1
bleach were
added and mixed thoroughly until the Rupp chloride hydrate dissolved.
[1005] V.A. Each syringe barrel was sealed with a plastic Luer seal and 3
drops of
the staining mixture were added to each syringe barrel. The syringe barrels
were then
sealed with aluminum tape and allowed to sit for 30-40 minutes. In each set of
syringe
barrels tested, at least one uncoated syringe barrel was stained. The syringe
barrels
were stored with the restricted area 292 facing up.
[1006] V.A. Based on the staining, the following conclusions were drawn:
[1007] V.A. 1. The stain started to attack the uncoated (or poorly coated)
areas
within 0.25 hours of exposure.
[1008] V.A. 2. Ignition in the restricted area 292 resulted in SiOx coating
of the
restricted area 292.
[1009] V.A. 3. The best syringe barrel was produced by the test with no
hollow
cathode plasma ignition in either the gas inlet 310 or the restricted area
292. Only the
restricted opening 294 was stained, most likely due to leaking of the stain.
[1010] V.A. 4. Staining is a good qualitative tool to guide uniformity
work.
[1011] V.A. Based on all of the above, we concluded:
[1012] V.A. 1. Under the conditions of the test, hollow cathode plasma in
either the
gas inlet 310 or the restricted area 292 led to poor uniformity of the
coating.
[1013] V.A. 2. The best uniformity was achieved with no hollow cathode
plasma in
either the gas inlet 310 or the restricted area 292.
Example 6
Interference Patterns from Reflectance Measurements - Prophetic Example
[1014] VIA. Using a UV-Visible Source (Ocean Optics DH2000-BAL Deuterium
Tungsten 200-1000nm), a fiber optic reflection probe (combination
emitter/collector
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Ocean Optics QR400-7 SR/BX with approximately 3mm probe area), miniature
detector
(Ocean Optics HR40000G UV-NIR Spectrometer), and software converting the
spectrometer signal to a transmittance/wavelength graph on a laptop computer,
an
uncoated PET tube Becton Dickinson (Franklin Lakes, New Jersey, USA) Product
No.
366703 13x75 mm (no additives) is scanned (with the probe emitting and
collecting light
radially from the centerline of the tube, thus normal to the coated surface)
both about
the inner circumference of the tube and longitudinally along the inner wall of
the tube,
with the probe, with no observable interference pattern observed. Then a
Becton
Dickinson Product No. 366703 13x75 mm (no additives) Si0,, plasma-coated BD
366703 tube is coated with a 20 nanometer thick Si02 coating as described in
Protocol
for Coating Tube Interior with SiOx. This tube is scanned in a similar manner
as the
uncoated tube. A clear interference pattern is observed with the coated tube,
in which
certain wavelengths were reinforced and others canceled in a periodic pattern,
indicating the presence of a coating on the PET tube.
Example 7
Enhanced Light Transmission from Integrating Sphere Detection
[1015] VIA. The equipment
used was a Xenon light source (Ocean Optics HL-2000-
HP-FHSA - 20W output Halogen Lamp Source (185-2000nm)), an Integrating Sphere
detector (Ocean Optics ISP-80-8-I) machined to accept a PET tube into its
interior,
and HR2000+ES Enhanced Sensitivity UV.VIS
spectrometer, with light
transmission source and light receiver fiber optic sources (0P600-2-UV-VIS -
600um
Premium Optical FIBER, UV/VIS,
2m), and signal conversion software
(SPECTRASUITE - Cross-platform Spectroscopy Operating SOFTWARE). An
uncoated PET tube made according to the Protocol for Forming PET Tube was
inserted
onto a TEFZEL Tube Holder (Puck), and inserted into the integrating sphere.
With
the Spectrasuite software in absorbance mode, the absorption (at 615nm) was
set to
zero. An SiOx coated tube made according to the Protocol for Forming PET Tube
and
coated according to the Protocol for Coating Tube Interior with SiOx (except
as varied in
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Table 16) was then mounted on the puck, inserted into the integrating sphere
and the
absorbance recorded at 615nm wavelength. The data is recorded in Table 16.
[1016] With the SiOx coated tubes, an increase in absorption relative to
the uncoated
article was observed; increased coating times resulted in increased
absorption. The
measurement took less than one second.
[1017] VIA. These spectroscopic methods should not be considered limited by
the
mode of collection (for example, reflectance vs. transmittance vs.
absorbance), the
frequency or type of radiation applied, or other parameters.
Example 8
Outgassing Measurement on PET
[1018] VI.B. Present FIG. 30, adapted from FIG. 15 of U.S. Patent
6,584,828, is a
schematic view of a test set-up that was used in a working example for
measuring
outgassing through an SiOx barrier coating 348 applied according to the
Protocol for
Coating Tube Interior with SiOx on the interior of the wall 346 of a PET tube
358 made
according to the Protocol for Forming PET Tube seated with a seal 360 on the
upstream
end of a Micro-Flow Technology measurement cell generally indicated at 362.
[1019] VI.B. A vacuum pump 364 was connected to the downstream end of a
commercially available measurement cell 362 (an Intelligent Gas Leak System
with
Leak Test Instrument Model ME2, with second generation IMFS sensor, (10p/min
full
range), Absolute Pressure Sensor range: 0-10 Torr, Flow measurement
uncertainty: +/-
5% of reading, at calibrated range, employing the Leak-Tek Program for
automatic data
acquisition (with PC) and signatures/plots of leak flow vs. time. This
equipment is
supplied by ATC Inc.), and was configured to draw gas from the interior of the
PET
vessel 358 in the direction of the arrows through the measurement cell 362 for
determination of the mass flow rate outgassed vapor into the vessel 358 from
its walls.
[1020] VI.B. The measurement cell 362 shown and described schematically
here
was understood to work substantially as follows, though this information might
deviate
somewhat from the operation of the equipment actually used. The cell 362 has a
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conical passage 368 through which the outgassed flow is directed. The pressure
is
tapped at two longitudinally spaced lateral bores 070 and 372 along the
passage 368
and fed respectively to the chambers 374 and 376 formed in part by the
diaphragms
378 and 380. The pressures accumulated in the respective chambers 374 and 376
deflect the respective diaphragms 378 and 380. These deflections are measured
in a
suitable manner, as by measuring the change in capacitance between conductive
surfaces of the diaphragms 378 and 380 and nearby conductive surfaces such as
382
and 384. A bypass 386 can optionally be provided to speed up the initial pump-
down by
bypassing the measurement cell 362 until the desired vacuum level for carrying
out the
test is reached.
[1021] VI.B. The PET walls 350 of the vessels used in this test were on the
order of
1 mm thick, and the coating 348 was on the order of 20 nm (nanometers) thick.
Thus,
the wall 350 to coating 348 thickness ratio was on the order of 50,000 : 1.
[1022] VI.B. To determine the flow rate through the measurement cell 362,
including
the vessel seal 360, 15 glass vessels substantially identical in size and
construction to
the vessel 358 were successively seated on the vessel seal 360, pumped down to
an
internal pressure of 1 Torr, then capacitance data was collected with the
measurement
cell 362 and converted to an "outgassing" flow rate. The test was carried out
two times
on each vessel. After the first run, the vacuum was released with nitrogen and
the
vessels were allowed recovery time to reach equilibrium before proceeding with
the
second run. Since a glass vessel is believed to have very little outgassing,
and is
essentially impermeable through its wall, this measurement is understood to be
at least
predominantly an indication of the amount of leakage of the vessel and
connections
within the measurement cell 362, and reflects little if any true outgassing or
permeation.
The results are in Table 7.
[1023] VI.B. The family of plots 390 in FIG. 31 shows the "outgas" flow
rate, also in
micrograms per minute, of individual tubes corresponding to the second run
data in
previously-mentioned Table 7. Since the flow rates for the plots do not
increase
substantially with time, and are much lower than the other flow rates shown,
the flow
rate is attributed to leakage.
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[1024] VI.B. Table 8 and the family of plots 392 in FIG. 31 show similar
data for
uncoated tubes made according to the Protocol for Forming PET Tube.
[1025] VI.B. This data for uncoated tubes shows much larger flow rates: the
increases are attributed to outgas flow of gases captured on or within the
inner region of
the vessel wall. There is some spread among the vessels, which is indicative
of the
sensitivity of the test to small differences among the vessels and/or how they
are seated
on the test apparatus.
[1026] VI.B. Table 9 and the families of plots 394 and 396 in FIG. 31 show
similar
data for an SiOx barrier coating 348 applied according to the Protocol for
Coating PET
Tube Interior with SiOx on the interior of the wall 346 of a PET tube made
according to
the Protocol for Forming PET Tube.
[1027] VI.B. The family of curves 394 for the SiOx coated, injection-molded
PET
tubes of this example shows that the SiOõ coating acts as a barrier to limit
outoassing
from the PET vessel walls, since the flow rate is consistently lower in this
test than for
the uncoated PET tubes. (The SiOõ coating itself is believed to outgas very
little.) The
separation between the curves 394 for the respective vessels indicates that
this test is
sensitive enough to distinguish slightly differing barrier efficacy of the
SiOx coatings on
different tubes. This spread in the family 394 is attributed mainly to
variations in gas
tightness among the SiOx coatings, as opposed to variations in outgassing
among the
PET vessel walls or variations in seating integrity (which have a much tighter
family 392
of curves). The two curves 396 for samples 2 and 4 are outliers, as
demonstrated
below, and their disparity from other data is believed to show that the SiOx
coatings of
these tubes are defective. This shows that the present test can very clearly
separate
out samples that have been processed differently or damaged.
[1028] VI.R. Referring to Tables 8 and 9 previously mentioned and FIG. 32,
the data
was analyzed statistically to find the mean and the values of the first and
third standard
deviations above and below the mean (average). These values are plotted in
FIG. 32.
[1029] VI.B. This statistical analysis first shows that samples 2 and 4 of
Table 9
representing coated PET tubes are clear outliers, more than +3 standard
deviations
away from the mean. These outliers are, however, shown to have some barrier
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efficacy, as their flow rates are still clearly distinguished from (lower
than) those of the
uncoated PET tubes.
[1030] VI.B. This statistical analysis also shows the power of an
outgassing
measurement to very quickly and accurately analyze the barrier efficacy of
nano-
thickness barrier coatings and to distinguish coated tubes from uncoated tubes
(which
are believed to be indistinguishable using the human senses at the present
coating
thickness). Referring to FIG. 32, coated PET vessels showing a level of
outgassing
three standard deviations above the mean, shown in the top group of bars, have
less
outgassing than uncoated PET vessels showing a level of outgassing three
standard
deviations below Me mean, shown in the bottom group of bars. This data snows
no
overlap of the data to a level of certainty exceeding 60 (six-sigma).
[1031] VI.B. Based on the success of this test, it is contemplated that the
presence
or absence of an SiOx coating on these PET vessels can be detected in a much
shorter
test than this working example, particularly as statistics are generated for a
larger
number of samples. This is evident, for example from the smooth, clearly
separated
families of plots even at a time T = 12 seconds for samples of 15 vessels,
representing
a test duration of about one second following the origin at about T = 11
seconds.
[1032] VI.B. It is also contemplated. based on this data, that a barrier
efficacy for
SiOx coated PET vessels approaching that of glass or equal to glass can be
obtained by
optimizing the SiOx coating.
Example 9
Wetting Tension - Plasma Coated PET Tube Examples
[1033] VII.A.1.a.ii. The wetting tension method is a modification of the
method
described in ASTM D 2578. Wetting tension is a specific measure for the
hydrophobicity or hydrophil icily of a surface. This method uses standard
wetting tension
solutions (called dyne solutions) to determine the solution that comes nearest
to wetting
a plastic film surface for exactly two seconds. This is the film's wetting
tension.
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[1034] VII.A.1.a.ii. The procedure utilized is varied from ASTM D 2578 in
that the
substrates are not flat plastic films, but are tubes made according to the
Protocol for
Forming PET Tube and (except for controls) coated according to the Protocol
for
Coating Tube Interior with Hydrophobic Coating. A silicone coated glass
syringe
(Becton Dickinson Hypake PRTC glass prefillable syringe with Luer-lok@ tip) (1
mL)
was also tested. The results of this test are listed in Table 10.
[1035] Surprisingly, plasma coating of uncoated PET tubas (40 dynes/cm) can
achieve either higher (more hydrophilic) or lower (more hydrophobic) energy
surfaces
using the same hexamethyldisiloxane (HMDSO) feed gas, by varying the plasma
process conditions. A thin (approximately 20-40 nanometers) SiOx coating made
according to the Protocol for Coating Tube Interior with SiOx (data not shown
in the
tables) provides similar wettabllity as hydrophilic bulk glass substrates. A
thin (less than
about 100 nanonneters) hydrophobic coating made according to the Protocol for
Coating
Tube interior with Hydrophobic Coating provides similar non-wenability as
hydrophobic
silicone fluids (data not shown in the tables).
Example 10
Vacuum Retention Study of Tubeo Via Accelerated Ageing
[1036] VII.A.3 Accelerated ageing offers faster assessment of long term
shelf-life
products. Accelerated ageing of blood tubes for vacuum retention is described
in US
Patent 5,792,940, Column 1, Lines 11-49.
[1037] VII.A.3 Three types of polyethylene terephthalate (PET) 13x75 mm
(0.85 mm
thick walls) molded tubes were tested:
= Becton Dickinson Product No. 366703 13x75 mm (no additives) tube
(shelf life 545 days or 18 months), closed with Hemogard@ system red
stopper and uncolored guard [commercial control];
= PET tubes made according to the Protocol for Forming PET Tube, closed
with the same type of Hemogard@ system red stopper and uncolored
guard [internal control]; and
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= injection molded PET 13x75 mm tubes, made according to the Protocol for
Forming PET Tube, coated according to the Protocol for Coating Tube
Interior with SiOx, closed with the same type of Hemogard system red
stopper and uncolored guard [inventive sample].
[1038] VII.A.3 The BD commercial control was used as received. The internal
control and inventive samples were evacuated and capped with the stopper
system to
provide the desired partial pressure (vacuum) inside the tube after sealing.
All samples
were placed into a three gallon (3.8 L) 304 SS wide mouth pressure vessel
(Sterlitech
No. 740340). The pressure vessel was pressurized to 48p5i (3.3 atm, 2482
mm.Hg).
Water volume draw change determinations were made by (a) removing 3-5 samples
at
increasing time intervals, (b) permitting water to draw into the evacuated
tubes through
a 20 gauge blood collection adaptor from a one liter plastic bottle reservoir,
(c) and
measuring the mass change before and after water draw.
[1039] VII.A.3 Results are indicated on Table 11.
[1040] VII.A.3 The Normalized Average Decay Rate is calculated by dividing
the
time change in mass by the number of pressurization days and initial mass draw
[mass
change/(days x initial mass)]. I he Accelerated lime to 10 /,, Loss (months)
is also
calculated. Both data are listed in Table 12.
[1041] VII.A.3 This data indicates that both the commercial control and
uncoated
internal control have identical vacuum loss rates, and surprisingly,
incorporation of a
SIC)), coating on the PET interior walls improves vacuum retention time by a
factor of
2.1.
Example 11
Lubricity Coatings
[1042] VII.B.1.a. The following materials were used in this lest:
= Commercial (BD Hypak PRTC) glass prefillable syringes with Luer-lok
tip) (cal mL)
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= COC syringe barrels made according to the Protocol for Forming COC
Syringe barrel;
= Commercial plastic syringe plungers with elastomeric tips taken from
Becton Dickinson Product No. 306507 (obtained as saline prefilled
syringes);
= Normal saline solution (taken from the Becton-Dickinson Product No.
306507 prefilled syringes);
= Dillon Test Stand with an Advanced Force Gauge (Model AFG-50N)
= Syringe holder and drain jig (fabricated to fit the Dillon Test Stand)
[1043] VII.B.1.a. The following procedure was used in this test.
[1044] VII.B.1.a. The jig was installed on the Dillon Test Stand. The
platform probe
movement was adjusted to 6 inimin (2.5 mm/sec) and upper and lower stop
locations
were set. The stop locations were verified using an empty syringe and barrel.
The
commercial saline-filled syringes were labeled, the plungers were removed, and
the
saline solution was drained via the open ends of the syringe barrels for re-
use. Extra
plungers were obtained in the same manner for use with the COC and glass
barrels.
[1045] VII.B.1.a. Syringe plungers were inserted into the COC syringe
barrels so
that the second horizontal molding point of each plunger was even with the
syringe
barrel lip (about 10 mm from the tip end). Using another syringe and needle
assembly,
the test syringes were filled via the capillary end with 2-3 milliliters of
saline solution,
with the capillary end uppermost. The sides of the syringe were tapped to
remove any
large air bubbles at the plunger/ fluid interface and along the walls, and any
air bubbles
were carefully pushed out of the syringe while maintaining the plunger in its
vertical
orientation.
[1046] VII.B.1.a. Each filled syringe barrel/plunger assembly was installed
into the
syringe jig. The test was initiated by pressing the down switch on the test
stand to
advance the moving metal hammer toward the plunger. When the moving metal
hammer was within 5mm of contacting the top of the plunger, the data button on
the
Dillon module was repeatedly tapped to record the force at the time of each
data button
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depression, from before initial contact with the syringe plunger until the
plunger was
slopped by contact with the front wall of the syringe barrel.
[1047] VII.B.1.a. All benchmark and coated syringe barrels were run with
five
replicates (using a new plunger and barrel for each replicate).
[1048] VII.B.1.a. COC syringe barrels made according to the Protocol for
Forming
COC Syringe barrel were coated with an OMCTS lubricity coating according to
the
Protocol for Coating COC Syringe Barrel Interior with OMCTS Lubricity Coating,
assembled and filled with saline, and tested as described above in this
Example for
lubricity coatings. The polypropylene chamber used per the Protocol for
Coating COC
Syringe Barrel Interior with OMCTS Lubricity Coating allowed the OIVICTS vapor
(and
oxygen, if added ¨ see Table 13) to flow through the syringe barrel and
through the
syringe capillary into the polypropylene chamber (although a lubricity coating
may not
be needed in the capillary section of the syringe in this instance). Several
different
coating conditions were tested, as shown in previously mentioned Table 13. All
of the
depositions were completed on COC syringe barrels from the same production
batch.
[1049] The coated samples were then tested using the plunger sliding force
test per
the protocol of this Example, yielding the results in Table 13, in English and
metric force
units. The data shows clearly that low power arid rio oxygen provided the
lowest
plunger sliding force for COC and coated COC syringes. Note that when oxygen
was
added at lower power (6 W) (the lower power being a favorable condition) the
plunger
sliding force increased from 1.09 lb, 0.49 Kg (at Power = 11 W) to 2.27 lb.,
1.03 Kg.
This indicates that the addition of oxygen may not be desirable to achieve the
lowest
possible plunger sliding force.
[1050] VII.B.1.a. Note also that the best plunger sliding force (Power = 11
W ,
plunger sliding force = 1.09 lb, 0.49 Kg) was very near the current industry
standard of
silicone coated glass (plunger sliding force = 0.58 lb, 0.26 Kg), while
avoiding the
problems of a glass syringe such as breakability and a more expensive
manufacturing
process. With additional optimization, values equal to or better than the
current glass
with silicone performance are expected to be achieved.
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[1051] VII.B.1.a. The samples were created by coating COO syringe barrels
according to the Protocol for Coating COO Syringe Barrel Interior with OMCTS
Lubricity
Coating. An alternative embodiment of the technology herein, would apply the
lubricity
layer over another thin film coating, such as SiOx, for example applied
according to the
Protocol for Coating COC Syringe barrel Interior with SIO.
Example 12
Improved Syringe Barrel Lubricity Coating
[1052] V11.13.1ka. The force required to expel a 0.9 percent saline payload
from a
syringe through a capillary opening using a plastic plunger was determined for
inner
wall-coated syringes.
[1053] VII.13.1.a. Three types of COO syringe barrels made according to the
Protocol for Forming COG Syringe barrel were tested: one type haying no
internal
coating [Uncoated Control], another type with a hexamethyldisiloxane (HMDSO)-
based
plasma coated internal wall coating [HMDSO Control] according to the Protocol
for
Coating COC Syringe Barrel Interior with HMDSO Coating, and a third type with
an
ootam eth ylcyclotetrasiloxane [OMCTS- Inventive Exam pl e]-based plasma
coated
internal wall coating applied according to the Protocol for Coating COO
Syringe Barrel
Interior with OMCTS Lubricity Coating. Fresh plastic plungers with elastomeric
tips
taken from BD Product Becton-Dickinson Product No. 306507 were used for all
cxamplcs. Gahm from Product No. 306507 was also uscd.
[1054] VII.B.1.a. The plasma coating method and apparatus for coating the
syringe
barrel inner walls is described in other experimental sections of this
application. The
specific coating parameters for the HMDSO-based and OMCTS-based coatings are
listed in the Protocol for Coating COG Syringe Barrel Interior with HMDSO
Goering, the
Protocol for Coating COO Syringe barrel Interior with OMCTS Lubricity Coating,
and
Table 14.
[1055] VII.13.1.a. The plunger is inserted into the syringe barrel to about
10
millimeters, followed by vertical filling of the experimental syringe through
the open
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syringe capillary with a separate saline-filled syringe/needle system. When
the
experimental syringe has been filled into the capillary opening, the syringe
is tapped to
permit any air bubbles adhering to the inner walls to release and rSe through
the
capillary opening.
[1056] VII.B.1.a. The filled
experimental syringe barrel/plunger assembly is placed
vertically Into a home-made hollow metal jig, the syringe assembly being
supported on
the jig at the finger flanges. The jig has a drain tube at the base and is
mounted on
Dillon Test Stand with Advanced Force Gauge (Model AFG-50N). The test stand
has a
metal hammer, roving vertically downward at a rate of six inches (152
millimeters) per
minute. The metal hammer contacts the extended plunger expelling the saline
solution
through the capillary. Once the plunger has contacted the syringe
barrel/capillary
interface the experiment is stopped.
[1057] VII.B.1.a. During downward
movement of the metal hammer/extended
plunger, resistance force imparted on the hammer as measured on the Force
Gauge is
recorded on an electronic spreadsheet. From the spreadsheet data, the maximum
force
for each experiment is identified.
[1058] VII.B.1.a. Table 14
lists for each Example the Maximum Force average from
replicate coated COC syringe barrels and the Normalized Maximum Force as
determined by division of the coated syringe barrel Maximum Force average by
the
uncoated Maximum Force average.
[1059] VII.B.1.a. The data
indicates all OMCTS-based inner wall plasma coated
COC syringe barrels (Inventive Examples C,E,F,G,H) demonstrate much lower
plunger
sliding force than uncoated COC syringe barrels (uncoated Control Examples A &
D)
and surprisingly, also much lower plunger sliding force than HMDSO-based inner
wall
plasma coated COC syringe barrels (HMDSO control Example B). More surprising,
an
OMCTS-based coating over a silicon oxide tSi0,) gas barrier coating maintains
excellent low plunger sliding force (Inventive Example F). The best plunger
sliding
force was Example C (Power = 8, plunger sliding force = 1.1 lb, 0.5 Kg). It
was very
near the current industry standard of silicone coated glass (plunger sliding
force = 0.58
lb., 0.26 Kg.), while avoiding the problems of a glass syringe such as
breakability and a
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rrore expensive manufacturing process. With additional optimization, values
equal to or
better than the current glass with silicone performance are expected to be
achieved.
Example 13
Fabrication of COC Syringe Barrel with Exterior Coating ¨ Prophetic Example
[1060] VII.B.1.c. A COC syringe barrel formed according to the Protocol for
Forming
COC Syringe barrel is sealed at both ends with disposable closures. The capped
COC
syringe barrel is passed through a bath of Darane 8100 Saran Latex (Owensboro
Specialty Plastics). This latex contains five percent isopropyl alcohol to
reduce the
surface tension of the composition to 32 dynes/em). The latex composition
completely
wets the exterior of the COC syringe barrel. After draining for 30 seconds,
the coated
COC syringe barrel is exposed to a heating schedule comprising 275 F (135 C)
for 25
seconds (latex coalescence) and 122 F (50 C) for four hours (finish cure) in
respective
forced air ovens. The resulting PvDC film is 1/10 mil (2.5 microns) thick. The
COC
syringe barrel and PvDC-COC laminate COC syringe barrel are measured for OTR
and
VIVTR using a MOCON brand Oxtran 2/21 Oxygen Permeability Instrument and
Permatran- W 3/31 Water Vapor Permeability Instrument, respectively.
[1061] VII.13.1.c. Predicted OT P arid WVTF1 values are libted in Table 15,
which
shows the expected Barrier Improvement Factor (BIF) for the laminate would be
4.3
(OTR-BIF) and 3.0 (WVTR-BIF), respectively.
Example 15
Atomic Compositions of PECVD applied OMCTS and HMDSO Coatings
[1062] VII.B.4. COC syringe barrel samples made according to the Protocol
for
Forming COC Syringe barrel, coated with OMCTS (according to the Protocol for
Coating COC Syringe Barrel Interior with OMCTS Lubricity Coating) or coaled
with
HMDSO according to the Protocol for Coating COC Syringe Barrel Interior with
HMDSO
Coating were provided. The atomic compositions of the coatings derived from
OMCTS
or HMDSO were characterized using X-Ray Photoelectron Spectroscopy (XPS).
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[1063] VII.B.4. XPS data is quantified using relative sensitivity factors
and a model
that assumes a homogeneous layer. The analysis volume is the product of the
analysis
area (spot size or aperture size) and the depth of information. Photoelectrons
are
generated within the X-ray penetration depth (typically many microns), but
only the
photoelectrons within the top three photoelectron escape depths are detected.
Escape
depths are on the order of 15-35 A, which leads to an analysis depth of -50-
100 A.
Typically, 95% of the signal originates from within this depth.
[1064] VII.B.4. The following analytical parameters were used:
= Instrument: PHI Quantum 2000
= X-ray source: Monochromated Alka 1486.6eV
= Acceptance Angle +23
= Take-off angle 45'
= Analysis area 600pm
= Charge Correction C1s 284.8 eV
= Ion Gun Conditions Ar+, 1 keV, 2 x 2 mm raster
= Sputter Rate 15.6 A/min (SiO2 Equivalent)
L1065j I able 11 provides the
atomic concentrations ot the elements
detected. XPS does not detect hydrogen or helium. Values given are normalized
to
100 percent using the elements detected. Detection limits are approximately
0.05 to 1.0
atomic percent.
[1066] VII.B.4.b. From the coating
composition results and calculated starting
monomer precursor elemental percent in Table 17, while the carbon atom percent
of the
HMDSO-based coating is decreased relative to starting HMDSO monomer carbon
atom
percent (54.1% down to 44.4%), surprisingly the OMCTS-based coating carbon
atom
percent is increased relative to the OMCTS monomer carbon atom percent (34.8%
up
to 48.4%), an increase of 39 atomic %, calculated as follows:
1000/0[(48.4/34.8) - 1] - 29 at. /..
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[1067] Also, while the
silicon atom percent of the HMDSO-based coating is almost
unchanged relative to starting HMDSO monomer silicon atom percent (21.8% to
22.2%), surprisingly the OMCTS-based coating silicon atom percent is
significantly
decreased relative to the OMCTS monomer silicon atom percent (42.0% down to
23.6%), a decrease of 44 atomic %. With both the carbon
and silicon changes, the
OMCTS monomer to coating behavior does not trend with that observed in common
precursor monomers (e.g. HMDSO). See, e.g., Hans J. Griesser, Ronald C.
Chatelier,
Chris Martin, Zoran R. Vasic, Thomas R. Gengenbach, George Jessup J. Biomed.
Mater. Res. (Appl Biomater) 53: 235-243, 2000.
Example 16
Volatile Components from Plasma Coatings ("Outgassing")
[1068] VII.3.4. COC syringe barrel samples made according to the Protocol
for
Forming COG Syringe barrel, coated with OMCTS (according to the Protocol for
Coating COC Syringe Barrel Interior with OMCTS Lubricity Coating) or with
HMDSO
(according to the Protocol for Coating COG Syringe Barrel Interior with HMDSO
Coating) were provided. Outgassing gas chromatography/mass spectroscopy
(GC/MS)
analysis was used to measure the volatile components released from the OMCTS
or
HMDSO coatings.
[1069] VII.B.4. The syringe barrel samples (four COC syringe barrels cut in
half
lengthwise) were placed in one of Me 1'/2- (Li/ mm) diameter Members of a
dynamic
headspace sampling system (CDS 8400 auto-sampler). Prior to sample analysis, a
system blank was analyzed. The sample was analyzed on an Agilent 7890A Gas
Chromatograph/ Agilent 5975 Mass Spectrometer, using the following parameters,
producing the data set out in Table 18:
= GC Column: 30m X 0.25mm DB-5MS (J&W Scientific),
0.25pm film thickness
= Flow rate: 1.0 m l/m in, constant flow mode
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= Detector: Mass Selective Detector (MSD)
= Injection Mode: Split injection (10:1 split ratio)
= Outgassing Conditions: 11/2" (37mm) Chamber, purge for three hour
at 85 C, flow 60 ml/mm
= Oven temperature: 40'C (5 min.) to 3002C @102C/m
in.;
hold for 5 min. at 300 C.
[1070] The outgassing results from Table 18 clearly indicated a
compositional
differentiation between the HMDSO-based and OMCTS-based lubricity coatings
tested.
HMDSO-based compositions outgassed trimethylsilanol [(Me)3Si01-1] but
outgassed no
measured higher oligomers containing repeating -(Me)2Si0- moieties, while
OMCTS-
based compositions outgassed no measured trimethylsilanol [(Me)3Si01-1] but
outgassed
higher oligomers containing repeating -(Me)2Si0- moieties. It is contemplated
that this
test may be useful for differentiating HMDSO-based coatings from OMCTS-based
coatings.
[1071] Without limiting the invention according to the scope or accuracy of
the
following theory, it is contemplated that this result can be explained by
considering the
cyclic structure of OMCTS, with only two methyl groups bonded to each silicon
atom,
versus the acyclic structure of HMDSO, in which each silicon atom is bonded to
three
methyl groups. OMCTS is contemplated to react by ring opening to form a
diradical
having repeating -(Me)2Si0- moieties which are already oligomers, and may
condense
to form higher oligomers. HMDSO, on the other hand, is contemplated to react
by
cleaving at one 0-Si bond, leaving one fragment containing a single 0-Si bond
that
recondenses as (Me)3Si0H and the other fragment containing no 0-Si bond that
recondenses as [(Me).8i]e-
[1072] The cyclic nature of OMCTS is believed to result in ring opening and
condensation of these ring-opened moieties with outgassing of higher MW
oligomers
(26 ng/test). In contrast, HMDSO-based coatings are believed not to provide
any higher
oligomers, based on the relatively low-molecular-weight fragments from HMDSO.
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Example 17
Density Determination of Plasma Coatings using X-Ray Reflectivity (XRR)
[1073] Sapphire witness samples (0.5 x 0.5 x 0.1 cm) were glued to the
inner walls
of separate PET tubes, made according to the Protocol for Forming PET tubes.
The
sapphire witness-containing PET tubes were coated with OMCTS or HMDSO (both
according to the Protocol for Coating COO Syringe Barrel Interior with OMCTS
Lubricity
Coating, deviating all with 2x power). The coated sapphire samples were then
removed
and X-ray reflectivity (XRR) data were acquired on a PANalytical X'Pert
diffractometer
equipped with a parabolic multilayer incident beam monochromator and a
parallel plate
diffracted beam collimator. A two layer Sivv0),CyHz model was used to
determine coating
density from the critical angle measurement results. This model is
contemplated to offer
the best approach to isolate the true Siv,0õCyl-lz coatina. The results are
shown in Table
19.
[1074] From Table 17 showing the results of Example 15, the lower oxygen
(28%)
and higher carbon (48.4%) composition of OMCTS versus HMDSO would suggest
OMCTS should have a lower density, due to both atomic mass considerations and
valency (oxygen = 2; carbon = 4). Surprisingly, the XRR density results
indicate the
opposite would be observed, that is, the OMCTS density is higher than HMDSO
density.
[1075] Without limiting the invention according to the scope or accuracy of
the
following theory, it is contemplated that there is a fundamental difference in
reaction
mechanism in the formation of the respective HMDSO-based and OMCTS-based
coatings. HMDSO fragments may more easily nucleate or react to form dense
nanoparticles which then deposit on the surface and react further on the
surface,
whereas ONAGT8 is much less !Rely to form dense gas phase nanopartIcles. OMGTS
reactive species are much more likely to condense on the surface in a form
much more
similar to the original OMCTS monomer, resulting in an overall less dense
coating.
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Example 18
Thickness Uniformity of PECVD Applied Coatings
[1076] Samples were provided of COO syringe barrels made according to the
Protocol for Forming COO Syringe barrel and respectively coated with SlOõ
according to
the Protocol for Coating COO Syringe Barrel Interior with SiOx or an OMCTS-
based
lubricity coating according to the Protocol for Coating COC Syringe Barrel
Interior with
OMCTS Lubricity Coating. Samples were also provided of PET tubes made
according
to the Protocol for Forming PET Tube, respectively coated and uncoated with
SiOx
according to the Protocol for Coating Tube Interior with SiO, and subjected to
an
accelerated aging test. Transmission electron microscopy (TEM) was used to
measure
the thickness of the PECVD-applied coatings on the samples. The previously
stated
TEM procedure of Example 4 was used. The method and apparatus described by the
SiOx and lubricity coating protocols used in this example demonstrated uniform
coating
as shown in Table 20.
Example 19
Outgassing Measurement on coc
[1077] VI.B. COO tubes were made according to the Protocol for Forming COC
Tube. Some of the tubes were provided with an interior barrier coating of SiOx
according to the Protocol for Coating Tube Interior with SiOx, and other COC
tubes were
uncoated. Commercial glass blood collection Eiecton Dickinson iu x (5 mm tubes
having similar dimensions were also provided as above. The tubes were stored
for
about 15 minutes in a room containing ambient air at 45% relative humidity and
70 F
(21 C), and the following testing was done at the same ambient relative
humidity. The
tubes were tested for outgassing following the ATG mioroflow measurement
procedure
and equipment of Example 8 (an Intelligent Gas Leak System with Leak Test
Instrument
Model ME2, with second generation IMFS sensor, (10p/min full range), Absolute
Pressure Sensor range: 0-10 Torr, Flow measurement uncertainty: +/- 5% of
reading, at
calibrated range, employing the Leak-Tek Program for automatic data
acquisition (with
PC) and signatures/plots of leak flow vs. time). In the present case each tube
was
239
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subjected to a 22-second bulk moisture degassing step at a pressure of 1 mm
Hg, was
pressurized with nitrogen gas for 2 seconds (to 760 millimeters Hg), then the
nitrogen
gas was pumped down and the microflow measurement step was carried out for
about
one minute at 1 millimeter Hg pressure.
[1078] VI.B. The result is shown in FIG. 57, which is similar to FIG. 31
generated in
Example B. In FIG. 57, the plots for the uncoated COG tubes are at 630, the
plots for
the SiOx coated COC tubes are at 632, and the plots for the glass tubes used
as a
control are at 634. Again, the outgassing measurement began at about 4
seconds, and
a few seconds later the plots 630 for the uncoated COC tubes and the plots 632
for the
SiOx barrier coated tubes clearly diverged, again demonstrating rapid
differentiation
between barrier coated tubes and uncoated tubes. A consistent separation of
uncoated
COC (>2 micrograms at 60 seconds) versus Si0x-coaled COC (less than 1.6
micrograms at 60 seconds) was realized.
Example 20
Lubricity Coatings
[1079] VII.B.1.a. COC syringe barrels made according to the Protocol for
Fon-ning
COC Syringe Barrel were coated with a lubricity coating according to the
Protocol for
Coating COC Syringe Barrel Interior with OMCTS Lubricity Coating. The results
are
provided in Table 21. The results show that the trend of increasing the power
level, in
thc abschicc of oxygcn, from 8 to 14 Watts was to improvc thc lubricity of thc
coating.
Further experiments with power and flow rates may provide further enhancement
of
lubricity.
240
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Example 21
Lubricity Coatings ¨ Hypothetical Example
[1080] Injection molded cyclic olefin copolymer (COC) plastic syringe
barrels are
rade according to the Protocol for Forming COC Syringe Barrel. Some are
uncoated
("control") and others are PECVD lubricity coated according to the Protocol
for Coating
COO Syringe Barrel Interior with OMCTS Lubricity Coating ("lubricated
syringe"). The
lubricated syringes and controls are tested to measure the force to initiate
movement of
the plunger in the barrel (breakout force) and the force to maintain movement
of the
plunger in the barrel (plunger sliding torce) using a Genesis Packaging
Automated
Syringe Force Tester, Model AST.
[1081] The test is a modified version of the ISO 7886-1:1993 test. The
following
procedure is used for each test. A fresh plastic plunger with elastomeric tip
taken from
Becton Dickinson Product No. 306507 (obtained as saline prefilled syringes) is
removed
from the syringe assembly. The elastomeric tip is dried with clean dry
compressed air.
The elastomeric tip and plastic plunger are then inserted into the COO plastic
syringe
barrel to be tested with the plunger positioned even with the bottom of the
syringe
barrel. The filled syringes are then conditioned as necessary to achieve the
state to be
tested. For example, if the test object is to find out the effect of lubricant
coating on the
breakout force of syringes after storing the syringes for three months, the
syringes are
stored for three months to achieve the desired state.
[1082] The syringe is installed into a Genesis Packaging Automated Syringe
Force
Tester. The tester is calibrated at the start of the test per the
manufacturer's
specification. The tester input variables are Speed = 100mmiminute, Range =
10,000.
The start button is pushed on the tester. At completion of the test, the
breakout force
(to initiate movement of the plunger in the barrel) and the plunger sliding
force (to
maintain movement) are measured, and are found to be substantially lower for
the
lubricated syringes than for the control syringes.
241
[1083] Fig. 59 shows a vessel processing system 20 according to an exemplary
embodiment of the present invention. The vessel processing system 20
comprises, inter
alia, a first processing station 5501 and a second processing station 5502.
Examples for
such processing stations are for example depicted in Fig. 1, reference
numerals 24, 26,
28, 30, 32 and 34.
[1084] The first vessel processing system 5501 contains a vessel holder 38
which holds
a seated vessel 80. Although Fig. 59 depicts a blood tube 80, the vessel may
also be a
syringe body, a vial, a catheter or, for example, a pipette. The vessel may,
for example,
be made of glass or plastic. In case of plastic vessels, the first processing
station may
also comprise a mould for moulding the plastic vessel.
[1085] After the first processing at the first processing station (which
processing may
comprise moulding of the vessel, a first inspection of the vessel for defects,
coating of
the interior surface of the vessel and a second inspection of the vessel for
defects, in
particular of the interior coating), the vessel holder 38 is transported
together with the
vessel 82 a second vessel processing station 5502. This transportation is
performed by
a conveyor arrangement 70, 72, 74. For example, a gripper or several grippers
may be
provided for gripping the vessel holder 38 and/or the vessel 80 in order to
move the
vessel/holder combination to the next processing station 5502. Alternatively,
only the
vessel may be moved without the holder. However, it may be intended to be
advantageous to move the holder together with the vessel in which case the
holder is
adapted such that it can be transported by the conveyor arrangement.
[1086] Fig. 60 shows a vessel processing system 20 according to another
exemplary
embodiment of the present invention. Again, two vessel processing stations
5501, 5502
are provided. Furthermore, additional vessel processing stations 5503, 5504
are
provided which are arranged in series and in which the vessel can be
processed, i.e.
inspected and/or coated.
[1087] A vessel can be moved from a stock to tile left processing station
5504.
Alternatively, the vessel can be moulded in the first processing station 5504.
In any case,
a first vessel processing is performed in the processing station 5504, such as
a
242
Date Recue/Date Received 2020-08-17
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moulding, an inspection and/or a coating, which may be followed by a second
inspection. Then, the vessel is moved to the next processing station 5501 via
the
conveyor arrangement 70, 72, 74. Typically, the vessel is moved together with
the
vessel holder. A second processing is performed in the second processing
station 5501
after which the vessel and holder are moved to the next processing station
5502 in
which a third processing is performed. The vessel is then moved (again
together with
the holder) to the fourth processing station 5503 for a fourth processing,
after which it is
conveyed to a storage.
[1088] Before and after each coating step or moulding step or any other
step which
manipulates the vessel an inspection of the whole vessel, of part of the
vessel and in
particular of an interior surface of the vessel may be performed. The result
of each
inspection can be transferred to a central processing unit 5505 via a data bus
5507.
Each processing station is connected to the data bus 5507. The processor 5505,
which
may be adapted in form Of a central control and regulation unit, processes toe
inspection data, analyzes the data and determines whether the last processing
step was
successful.
[1089] If it is determined that the last processing step was not
successful, because
for example the coating comprises holes or because the surface of the coating
is
determined to be regular or not smooth enough, the vessel does not enter the
next
processing station but is either removed from the production process (see
conveyor
sections 7001, 7002, 7003, 7004) or conveyed back in order to become re-
processed.
[1090] The processor 5505 is connected to a user interface 5506 for
inputting control
or regulation parameters.
[1091] Fig. 61 shows a vessel processing station 5501 according to an
exemplary
embodiment of the present invention. The station comprises a PECVD apparatus
5701
for coating an interior surface of the vessel. Furthermore, several detectors
5702-5707
are provided for vessel inspection. Such detectors may for example be
electrodes for
performing electric measurements, optical detectors, like CCD cameras, gas
detectors
or pressure detectors.
243
[1092] Fig. 62 shows a vessel holder 38 according to an exemplary embodiment
of the
present invention, together with several detectors 5702, 5703, 5704 and an
electrode
with gas inlet port 108, 110.
[1093] The electrode and the detector 5702 may be adapted to be moved into the
interior
space of the vessel 80 when the vessel is seated on the holder 38.
[1094] The optical inspection may be particularly performed during a coating
step, for
example with the help of optical detectors 5703, 5704 which are arranged
outside the
seated vessel 80 or even with the help of an optical detector 5705 arranged
inside the
interior space of the vessel 80.
[1095] The detectors may comprise colour filters such that different
wavelengths can
be detected during the coating process. The processing unit 5505 analyzes the
optical
data and determines whether the coating was successful or not to a
predetermined level
of certainty. If it is determined that the coating was most probably
unsuccessful, the
respective vessel is separated from the processing system or re-processed.
[1096] While the invention according to its embodiments has been illustrated
and
described in detail in the drawings and foregoing description, such
illustration and
description are to be considered illustrative or exemplary and not
restrictive: the invention
is not limited to the disclosed embodiments. Other variations to the disclosed
embodiments can be understood and effected by those skilled in the art and
practising
the claimed invention, from a study of the drawings, the disclosure, and the
appended
ill the claims, the woid "conipiisiny" does not exclude ()Mei elements oi
steps,
and the indefinite article "a" or "an" does not exclude a plurality. The mere
fact that certain
measures are recited in mutually different dependent claims does not indicate
that a
combination of these measures cannot be used to an intended advantage. Any
reference
signs in the claims should not be construed as limiting the scope.
244
Date Recue/Date Received 2020-08-17
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TABLE 1: COATED COC TUBE OTR AND WVTR MEASUREMENT
OTR WVTR
0-Si 02 (cc/ (mg/
Coating Power Flow Flow time Tube. Tube.
ID (Watts) 0-Si (sccm) (sccm) (sec) Day) Day)
No 0.215 0. 27
Coating
A 50 HMOS 6 90 14 0.023 0. 07
50 HMDSO 6 90 14 0.024 O. 10
50 HMDSO 6 90 7 0.026 0. 10
TABLE 2: COATED PET TUBE OTR AND WVTR MEASUREMENT
OTR WVTR
0-Si 02 (cc/ (mg;
Coating Power Flow Flow time Tube. Tube.
ID (Watts) 0-Si (sccm) (sccm) (sec) Day)
Day)
U n- 0.0078 3.65
coated
Control
SiO, 50 HMDSO 6 90 3 0.0035 1.95
TABLE 2 Cont'd.
Coating B IF B IF
ID (OTR) (WVTR)
uncoated --
Control
Si0), 2.2 1.9
245
CA 02761872 2011-11-14
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Table 2A: COATED PET TUBE OTR WITH MECHANICAL SCRATCH
DEFECTS
Mechanical
0-Si 02 treat Scratch OTR
Power Flow Flow time Length (cc/tube OTR
Example 0-Si (Watts) (scorn) (seem) (sec) (mm)
.day)* BIF
Uncoated
Control 0.0052
Inventive HMDSO 50 6 90 3 0 0.0014 3.7
Inventive HMDSO 50 6 90 3 1 0.0039 1.3
Inventive HMDSO 50 6 90 3 2 0.0041 1.3
Inventive HMDSO 50 6 90 3 10 0.0040 1.3
Inventive HMDSO 50 6 90 3 20 0.0037 1.4
average of two tubes
246
TABLE 3: COATED COC COC SYRINGE BARREL OTR AND WVTR MEASUREMENT
0
n.)
0-Si 02 OTR WVTR
1¨,
Flow Flow Coating (cc/ (mg/
1¨,
Syringe 0-Si Power Rate Rate
Time Barrel. Barrel. BIF BIF ,..4
n.)
Example Coating Composition (Watts) (sccm) (sccm) (sec)
Day) Day) (OTR) (WVTR) cm
vz
A uncoated 0.032
0.12 1--.
Control
B SiOx HMDSO 44 6 90
7 0.025 0.11 1.3 1.1
Inventive
Example
C SiOx HMDSO 44 6 105 7 0.021
0.11 1.5 1.1
Inventive
Example
a
D SiOx HMDSO 50 6 90
7 0.026 0.10 1.2 1.2
0
Inventive
n)
...,
Example
al
I-.
E SiOx HMDSO 50 6
90 14 0.024 0.07 1.3 1.7 co
n.J
...3
.6.
"
-_, Inventive
Example
n)
0
F SiOx
HMDSO 52 6 97.5 7 0.022 0.12 1.5 1.0
I-.
I
Inventive
i--µ
I-.
Example
i
1¨
G SiOx HMDSO 61 6 105 7 0.022
0.11 1.4 1.1 Ø
Inventive
Example
H SiOx HMDSO 61 6
120 7 0.024 0.10 1.3 1.2
Inventive
Example
Iv
n
,-i
(7)
=
=
,
t.,
.6.
un
oe
c,
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