Note: Descriptions are shown in the official language in which they were submitted.
Background of the Invention
Much progress has been made in the handling of plasma and
whole blood obtained from human donors. Especially, considerable
activity has been generated with respect to the collection of plasma which
has a con.siderably longer shelf life than whole blood. Whole blood is
collected by conventional means well known in the art. ~he plasma is
removed from the whole blood by centrifugation, again, employing con-
ventional devices. As an aside, new concepts include the removal of the
cells from plasma through centrifugation and the reintroduction of the
cells to the donor, thereby permitting the donor to recoup a good portion
of that which has been donated. In that way the donor may give blood on
more occasions than would heretofore be possible.
~he need for the reintroduction of the blood cells to the donor has
become extremely important in view of the paucity of blood that is
available, Secondly, there has been a considerable increase in the need
for plasma in view of the beneficial fractions that may be obtained there-
from through various sophisticated processes. Blood plasma is collected
at many areas throughout the world for use in central laboratories that
may be located quite remote from the site of collection. Consequently,
the plasma, having an already long shelf life, is further enhanced in being
able to be frozen. ~he plasma is shipped in the frozen state to the labor-
atory at which the plasma is thawed and fractionated by well known methods
~38313
such as described, for example, in U. S. Patents 3, 560, 475; 3, 631, 018;
3, 682, 881; and 3, 763, 135.
In order to provide sterility at the collection point and to retain
the plasma in separated noncommingled condition, it is desirable to collect
the plasma in separate bottles containing approximately one quart of plasma
and to freeze the plasma in such bottles until they are thawed. ~he bottles
are then opened and the plasma is dumpèd into a single collection vat.
Ordinary use of bottles provides unsterile conditions at the site of collection.In many instances, blood is collected in an open system in which the liklihood
of bacterial contamination exists throughout the bottle and it therefore is
necessary to autoclave or gas sterilize the entire bottle and its contents.
In other cases, the bottles merely have a c ap which has been screwed on to
the mouth of the bottle and the bottles then must be opened prior to filling.
It has been found on occasion that bacteria may be harbored on the thread of
the bottle or under the underside of the cap. In order to avoid such contam-
ination, the mouth of the bottle must be sterilized prior to use.
Ihe U. S. government has promulgated regulations that require plasma
collection bottles to be in a sterile condition, even though the plasma subse-
quently will be treated in a manner that will certainly insure sterility.
Accordingly, the plasma collection bottle included in the present concept is
blow-molded with an integrally formed cap under sterilizing conditions.
Summary of the Invention
~he present invention provides an ingenious plasma collection system
and a bottle for use in connection therewith. ~he bottle is manufactured by
blow-molding techniques from thermoplastic resins suitable for blow-molding
such as the polyolefin resins, for example, polyethylene or polypropylene,
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and other materials which are compatible with plasma. U. S.
Patents 3,597,793; 3,730,372; and Re. 27,155; and British Patent
No. 1,318,030 illustrate blow-molding apparatus which can be
adapted for blow-molding and heat sealing the bottle. The bottle
has an essentially cylindrical configuration wit,h a neck portion
that is not cylindrical but' has been flattened to a considerable
degree. Above the neck is what can be termed a mouth portion
which ln one embodiment has a pierceable membrane. In another
embodiment the mouth portion has a threaded area and a breakaway
cap po3itioned thereon.
In both embodiments, the thermoplastic bottle is sterile
blow-molded and hermetically sealed in a single operation whereby
there is no contamination of the inside of the bottle due to the
conditions employed turing the blow-molding and heat sealing of the
bottle. These conditions include the high temperature of the resin
during molding; steam ~terilization of the blow lines; use of
" filtered air or sterilizing gas during blow-molding; and provision
...
of a bottle configuration adapted to heat sealing after filling
with plasma. The bottle 80 formed can then be transported to the
situs of a blood collection room anywhere in the world. In one em-
bodiment the cap is broken away from the mouth and a second cap is
attached thereto which has been previously packaged and maintained
in a sterile condition. The new cap p'ossesses an area for venting
containing a plug of a fibrous filter material and an area through
which a plastic spike or a sharpened hypodermlc-like needle can be
plunged wherein the proximal end has a flexible conduit attached
thereto which has been previously attached to a source of plasma.
The plasma is pumped from the source into the thermoplastic bottle.
Thereafter, the bottle is subjected at the flattened neck portion
thereof to compression and heating, whereby the flat portion is
further compressed into
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1038313
touchlng relatlonshlp, The part above the hest sesled ~rea
containing the puncture sp~ke or needle then can be severed
as desired. The plasma filled bottle is subsequently frozen,
after whlch lt can be transported to the place for further
collection. The plasma ln the bottle is then thawet prlor
to emptylng the contents therefrom.
For ease of removal of the contents, the filled bottles
are positioned on a conveyor so that they can be transported
to a position where a cutting tevice severs a portion of the
bottom of the bottle thereby permitting the liquefied plasms
to flow therefrom unter the aegis of gravity into a central
collection vessel.
Thus, in brosd terms this aspect of the invention maybe
tescribet as a thermoplastic blow-moltet bottle containing a
msmmalian liquid comprising a cylintrical main body, a bottom,
sait main boty at the entire top thereof converging upwardly
ant inwartly terminating in a completely flattenet portion
whereby a portlon of the inner surfaces are atheringly engaged
to one another along an area perpendicular with respect to
the longitutinal axis of sait bottle.
Another aspect of this invention maybe broadly describet
as a method for collecting, storing and utilizing a liquit
obtained from a mammalian donor comprising providing a tubular
means having two open ends, connecting one end of the tubular
means with an opening through the top of a thermoplastic
bottle, which has been sterile blow-molded and hermetically
sealed without a port and with a flattened constrictet neck
portion, connecting the other end to a source of the mammalian
liquid, introducing a quantity of the mammalian liquit from
the source through the tubular means into the bottle, further
flattenlng the constricted neck portlon whereby the inner
surfaces of the opposltely dlsposed flattened constrlcted neck
portion sealingly abut, slmultaneously applying heat to the
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1038313
flattened neck portlon whereby the abuttlng surfaces adhere
to one another, then freezlng the mammallan liquid ln the
bottle, and storlng the frozen mammalian llquld.
Brief DescrlPtlon of the Drawlngs
Flgure l 18 a perspective vlew of one embodlment of
the thermoplastic blow-molded bottle of the present lnventlon.
Flgure 2 i8 one slte vlew of the bottle of Figure 1.
Flgure 3 is another slde vlew of the bottle of Flgure 1,
Figure 4 is a top view of the bottle of Flgure l.
Flgure 5 ls a bottom vlew of the bottle of Flgure 1.
Flgure 6 is a perspective fragmentary view of another
embodiment of the bottle of the present invention.
Figure 7 is a perspective view illustrating the removal of
the cap from the embodiment shown in Figure 6.
Figure 8 is a perspective view of a screw-on cap having
a suitable vent and two capped ports therein.
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Figure 9 is a perspective view of the bottle of the present invention
having a screw cap thereon and a conduit having at one end a plastic spike
thrusted therethrough and wherein the conduit at the other end is secured to
a source of plasma, said source being in a press for expressing the plasma
therefrom.
Figure 10 is a cross-sectional view of the neck portion of the bottle
of the present invention,
Figure 11 is the same view as in Figure 10 wherein means is included
to compress and heat seal said neck portion.
Figure 12 is a similar view as Figures 10 and 11 but wherein a cutting
device is employed to sever the bottle through said heat sealed and compressed
neck portion.
Figure 13 is a perspective view after the severing step,
Figure 14 is a perspective view of a conveyor system and one embodi-
ment of a cutting means for severing through the bottom portion of the thermo-
plastic bottle and a collection vessel in association therewith,
Figure 15 is a cross-sectional view taken along line 15-15 of Figure 14.
Figure 17 is a perspective view of the use of the bottle shown in Figure
1 wherein the plastic spike is seen to be plunged into the pierceable membrane
and the spike has attached at the other end thereof a flexible conduit.
Figure 18 is a flow diagram showing the steps of the method of the
present invention,
Figure l9 is a perspective view of a bottle holding means and a thermo-
plastic bottle held in an upside down position.
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Figure 20 is a perspective view of another embodiment of a cutting
means for severing through the bottom of the thermoplastic bottle held in
the bottle holder of Figure 19.
Figure 21 is a perspective view of the severed bottle being inverted
.~ to dump plasma into a collection vessel.
Figure 22 is a perspective view of the severed bottle of Figure 21
held inverted until all the plasma has been dumped.
DE~AILED DESCRIPl~ION OF ~HE INVEN~ION
~he present invention relates to an ingenious method for collecting
plasma and, especially, the bottle which is to be used to store the plasma
during the transportation thereof from the collection site to the laboratory
for utilization. With regard thereto, attention is directed to Figures 1-5
for further understanding the bottle of the present invention.
~he bottle is shown generally by reference numeral 11. ~he bottle
11 has a body 12 having a cylindrical configuration. The bottle has a con-
verging shoulder portion 13 at the upper end thereof. ~he shoulder portion
is flattened at neck 14 to produce a constriction area of a flattened config-
uration. l he portion above the flattened area widens and terminates in a
cylindrical upper portion 15 to which a widened portion 16 is integral. ~he
top of the bottle terminates in a pierceable membrane 17. ~he bottom 19
of the bottle has depending semi-annular members 18 which is somewhat
dictated for construction purposes in order to obtain strength as a result
of the type of mold being used.
From Figures 6 and 7, it will be appreciated that the bottle in this
embodiment of the present invention has a somewhat different configuration
than the embodiment of Figures 1 to 5 above the flattened neck portion 14
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1036U13
where it has become wider again, Instead of having the cylindrical portion
15, the embodiment of Figures 6 and 7 possesses a cylindrical portion 21
having screw threads 22 thereon. Again, a widened portion is included as
identified by reference numeral 23. This portion constitutes a cap which
can be broken away as is seen from Figure 7 to reveal an open mouth 24.
Inasmuch as this embodiment has screw threads 22, it will be seen that a
screw cap can be affixed thereto after said cap is broken away. Accord-
ingly, attention is now directed to Figure 8 which illustrates a screw cap
26 having a top 27 and a depending skirt 28 having a plurality of knurls thereonto facilitate gripping thereof. Not shown are the screw threads for mating
with the screw threads 22 on the bottle of the embodiment shown in Figures
6 and 7. ~he screw threads are located internally with respect to skirt 28
At the top of the cap 26 ther0 is a short tubular extension 29 which is open
at one end but is capped with a plastic or a rubber cap~, After removal
of cap 30, a plastic spike or metal needle can be plunged through tubular
extension 29, Additionally, a vent 31 is positioned at the top 27 so that air
can be expelled from the bottle as the bottle is filled through cap 30.
In order to illustrate the filling technique to be utilized in conjunction
with the present invention, plasma is collected or charged into a flexible
thermoplastic bag 40 which is mounted between a fixed upright wall 41 and a
hinged second wall 42 of a plasma extractor 48. ~he hinged wall 42 is hinged
at 43 and has a lever 44 so that between the fixed wall and the hinged wall the
thermoplastic bag 40 containing the plasma is squeezed therebetween. ~he
plasma is flowed through flexible conduit 45 in the direction of the thermoplastic
bottle 11. Prior to the squeezing, cap 30 is removed and a plastic spike 46
is plunged through tubular extension 29. ~he spike can also be a metal needle
of the hypodermic type so that it is sharpened with a bevel at one end in a
~03W13
conventional manner and the other end is affixed to the conduit 45. A radially
extending flange 47is utili~ed to facilitate gripping. When the conduit has
been suitably connected to the bottle 11 the lever 44 is pushed upwardly,
thereby squeezing hinged wall 42 against the outer surface of thermoplastic bag
S 40, and thus extracting out the plasma into the bottle 11. A second unit of plasma
collected in a thermoplastic bag 40 can be similarly extracted and transferred to
bottle 11 with another such transfer set with a spike plunged through the secondtubular extension 29.
After the bottle has been suitably filled, it is positioned in a manner so
that the flattened neck portion 14 has one side thereof in abutment with heat
sealing bars 50 and 51, one of which is shown as a fixed member 50 and the
other as a movable member 51 at the other side thereof. ~he members 50 and
51 are suitably heated as by electric resistance means (not shown). ~he heated
members soften the thermoplastic material of the flattened portion 14 of the
neck so that as lateral pressure is applied to member 51 to move it in the
direction shown by the arrow, that is, towards member 50, the flattened portion
14 of the neck will be further compressed and crushed. It can be readily seen
from Figure 11, that the neck has been completely collapsed so that the internal~urfaces thereof are in abutment; and because they have been heated, they will
now become heat sealed together.
~hereafter, the bottle is severed at flattened neck portion 14 such as by
shearing or cutting. 'rhis is illustrated in Figure 12 wherein blade 53 of a
cutting tool is positioned against one side of the collapsed and heat sealed neck
and blade 54 of the cutting tool is at the other side thereof. By closing the blades
of the cutting tool, the upper portion of the bottle is severed from the remaining
main body as can be seen from Figure 13 which is a perspective view showing
the fact that the top of the bottle has been severed.
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1038313
After the top has been severed as indicated heretofo~e, the th~rmo-
plastic bottle containing the plasma is subjected to a quick freezing step so
that the plasma therein is frozen. By employing a thermoplastic bottle, the
plasma does not cause an untoward expansion such as would burst a conven-
tional glass bottle. Moreover, the bottle is preferably only partially filled,
such as about one-half filled, to allow for plasma expansion, ~he frozen
plasma is then transported to the laboratory for utilization as desired at a
time remote in time from the period of collection.
When it is desired to utilize the plasma and to remove the contents from
the thermoplastic bottle, the plasma is permitted to become thawed by conven-
tional methods and means. When it has became suitably thawed, it can be fed
along with a number of other such thermoplastic bottles to a conveyor system
which can be a belt conveyor system as illustrated by Figure 14. In the
embodiment shown in Figure 14, the thermoplastic bottles containing plasma
are moved in the direction of a cutting tool while the thermoplastic bottles
A containing the plasma are in a slightly inclined position. ~he belJis shown by
Figure 17 and the cutting tool is a circular device 61 which is powered by a
suitable motor means 62. Hold down rods 63 are positioned so that the cutting
tool 61 can penetrate the cylindrical portion of the bottle near the bottom thereof
as is more fully understood from Figure 15.
Inasmuch as the cutting tool 61 desirably is extremely thin and sharp
so that none of the thermoplastic material is severed therefrom as shavings,
the slit under ordinary conditions will be very thin so that it is desirable to
open up the cut to more efficaciously permit the removal of the plasma.
Accordingly, as the thermoplastic bottles are transported after the cutting
stage, a cam surface 64 is provided which is designed to move the bottom
portion that has been severed into a more horizontal condition while the hold
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down means 63 maintain the bottle in the inclined position taken in conjunction
with the moving belt 60. By opening up the bottle in the manner shown in
Figure 16, the plasma 65 is permitted to drop out of the bottle into a collection
vessel 66 from which the plasma is commingled with a plurality of plasma
collected from many thermoplastic bottles of the same type with which the
present invention is concerned.
Another embodiment for cutting the thermoplastic bottle and removing
the contents is illustrated by Figures 19 to 22. In this embodiment, the bottle
is held vertically upside down in fingers 73 of holder 74. ~he bottle is then
fed through band saw 75 whereby the bottom (which appears at the top in the
-upside down position) is cut off. ~he bottle is then carried to a position above
a collection vessel and inverted in the direction of the arrow as shown in
Figure 21, whereby the entire plasma contents are dumped into the collection
vessel as shown in Figure 22.
As was stated in the above, another embodime~1t of the present invention
concerns! a bottle of the thermoplastic type constructed in the same manner as
above, Accordingly, attention is directed to Figure 17 to show the use of the
bottle as a receptacle for plasma. Figure 17 shows a bottle having a config-
uration of the type shown by Figures 1-5. ~he pierceable membrane 17 is
seen to about to be plunged therethrough by means of a plastic spike 68 which
can also be, as stated herein before, a metal hypodermic needle. ~he plastic
spike 68 has an outwardly radiating flange of an annular configuration 69 so
that it can be easily gripped. ~he proximal end of the spike has a conduit 70
attached thereto whose end terminates at a source of plasma such as shown in
Figure 9. ~he arrow indicates the fact that the spike 68 is about to be plunged
into the pierceable membrane 17. Additionally, the pierceable membrane
already has been punctured with a short sterile tube 71 having a sterile fibrous
~3
plug 72 therein. l~he tube 71 acts as a venting means so that the air captured
in the thermoplastic bottle can be vented to the atmosphere as the plasma is
pumped therein.
In the foregoing, considerable attention has been directed to the
embodiments of the thermoplastic bottle which include the concept of a method
for collecting and storing plasma, With special reference to the method of the
present invention as herein disclosed, attention is specifically called to
Figure 18 for a diagrammatic flow diagram to show the manner in which the
thermoplastic bottle is used in the collection of plasma. It will be seen that
as an initial step after the thermoplastic bottle has been attached to a source of
plasma, the thermoplastic bottle is filled with plasma. As a next step, the
neck portion which has been previously flattened is sealed. l~he portion of the
bottle above the heat sealed area is then severed by suitable means as has been
heretofore discussed. 'rhereafter, the contents in the thermoplastic bottle are
subjected to freezing temperatures in order to freeze the plasma. After
freezing, the thermoplastic bottle containing the plasma can be transported in
the frozen state or can be stored as desired. Prior to emptying of the thermo-
plastic bottle, the plasma is stored in a suitable and conventional manner. As
a further step in the method of carrying out the present invention, the bottom
portion of the thermoplastic bottle can be cut in order to provide an opening
from which the plasma can be obtained which is then collected in a suitable
vessel from which the plasma can be removed for fractionating purposes as
desired.
It will be appreciated that the present invention is not limited to the
specific examples set forth above and that various other examples and
modifications of the foregoing examples will be apparent to the person skilled
in the art after reading the foregoing specification without departing from the
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:1038313
spirit and scope of the invention. All such further examples and modifications
thereof are included within the scope of the invention as defined in the appended
claims.
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