Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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CA 02218366 1997-10-16
W 096133805 PCT/Ib~G10048~
Plr~ ~lN~i; ~P~nT-~ AND RTr'c:T' STATION THEREFOR FOR
F~UID TRA~K u~ INERT ATMOSPHERE OPERATIONS
FIEI~D OF Tl~E lWV~ ION
The present invention relates generally to methods
and apparatus for use in pipetting work stations, and
more specifically to pipetting needles, useful in
anhydrous and inert atmosphere operations as well as
rinse stations for said needles.
BACRGROUND
Chemical reagents (which may include solvents,
reactants, or reactants dissolved in solvents) are used
in a wide range of chemical processes. Certain processes
and chemistries require that the chemical reagents be
kept under an inert or anhydrous atmosphere to prevent
reactive groups from reacting with molecular oxygen,
water vapor, or other agents commonly found in air.
Examples of atmosphere or moisture sensitive chemistries
include peptide chemistry, nucleic acid chemistry,
organometallic chemistry, heterocyclic chemistry, and
chemistries commonly used to construct combinatorial
chemistry libraries (see, e.g., co-p~n~;ng application
serial no. 08/422,869 entitled "Methods and Apparatus for
the Generation of Chemical Libraries," assigned to the
assignee of the present invention and incorporated herein
by reference). Accordingly, such reagents must be stored
and used under an anhydrous or inert atmosphere, such as
one of argon, nitrogen, or other gases or mixtures of
gases. Typically, cont~; n~rs of such reagents (and
containers in which reactions using these reagents take
place) are sealed from outside air by a gas impermeable
septum.
As is known to those skilled in the art, a liquid
reagent may be removed from or deposited into a container
sealed with a septum through the use of a pipetting
needle (and its associated pipetting syringe). When such
a needle pierces a septum, the septum forms a gas-tight
(or nearly gas-tight) seal around the needle, preventing
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or inhibiting gas flow around the needle. As the needle
is removed, the septum seals itself to prevent or inhibit
gas leakage.
When a pipetting needle is used to remove a volume
of liquid from a septum-sealed container, a partial
vacuum is created within that container. If the pressure
difference between the inside of the container and the
external atmosphere is great enough, outside air may seep
into the container through needle holes previously made
in the septum. This problem can be reduced or prevented
by replacing the volume of liquid removed with an equal
or slightly greater volume of inert (or other) gas.
In the past, inert gas has been pumped into septum-
sealed containers through the use of two separate
needles, or through the use of two needles soldered
together. Such soldered needles, called "double-needle
liquid-transfer/gas-purge units" are produced by the
Aldrich Corporation of Milwaukee, Wisconsin. In these
configurations, one needle is used to remove liquid
(i.e., perform the pipetting function), and the other
needle is used to pump inert gas into the sealed
container. Furthermore, the needles need to rinsed in-
between the pipetting operations.
Referring now to Figure 1, a prior art double
pipetting needle 100 is shown. Pipetting needle 100
includes a relatively long, hollow needle 102 used for
the transfer of liquids, and a relatively short, hollow
needle 104 used for the transfer of gas. Needle 102
typically has a non-coring tip 106 and a luer connector
fluid port 108, for connection to a pipetting syringe
(not shown). Needle 104 typically has a non-coring tip
110 and a luer connector gas port 112 for connection to
a source of inert gas (not shown).
The use of a separate needle to pump inert gas into
a septum sealed container presents many disadvantages.
For example, the use of such an arrangement may require
modification of existing pipetting work stations, such as
the TECAN model 5032 (manufactured by TECAN AG,
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Feldbachstrasse 80, CH-8634 Hombrechtikon, Switzerland).
In addition, the use of two needles soldered together
may cause significant damage to the septum, thereby
reducing its effective life span.
Accordingly, there r~m~;n~ a need in the art for a
pipetting needle ~or use in inert atmosphere operations
that causes m;n;m~l damage to a septum, and that requires
little or no modification to existing pipetting work
stations.
Many chemical processes performed using pipetting
work stations require the use of multiple reagents which
must be transferred using the same pipetting needle. To
prevent cross cont~m;nAtion of reagents, the pipetting
needle must be cleaned after exposure to each reagent.
In the past, specialized rinse stations have been used to
clean the inside and outside of a cont~m;n~ted pipetting
needle.
Referring now to Figure 5, a cross sectional view
of a prior art rinse station 50 as used in the Model 396
MPS ~ully automated multiple peptide synthesizer
(manufactured by Advanced ChemTech, Inc. of Louisville,
Kentucky) is shown. Rinse station 50 includes a cavity
52 in a rinse cup 53, a waste trough 54, and a drain
tube 55. To clean a pipetting needle, the tip of the
pipetting needle is placed in cavity 52. C~ n;ng
solvent is pumped out of the tip of the pipetting needle
into cavity 52, forcing the solvent upward to wash the
outside tip of the pipetting needle before spilling into
waste trough 54, and then out drain tube 55.
This prior art rinse station only cleans the
interior and tip of a pipetting needle. While this may
be adequate in situations where a pipetting needle can be
precisely controlled so as to only cont~m;n~te the tip
(as is done in pipetting works station that can detect
the reagent surface), this may be inadequate where a
relatively large portion of the pipetting needle becomes
contaminated. For example, it may be desirable in some
circumstances to remove reagents from near the bottom of
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the container, where the reagent is less likely to have
been exposed to outside air.
Further disadvantages of prior art rinse station 50
are that a relatively large amount of cle~n;ng solvent is
reguired to clean a pipetting needle, and a cle~n;n~
operation takes a relatively long time.
Accordingly, there r~m~;nq a need in the art for a
pipetting needle rinse station that can quickly and
effectively cleanse the entire contaminated portion of a
pipetting needle without using large amounts of cleaning
solvent.
SUMMARY
The present invention meets these needs by providing
a coaxial needle assembly that includes both a pipetting
needle, a gas pressurization needle and a needle rinsing
station.
A preferred embodiment of the needle assembly
includes a pipetting needle having a body portion, a
first end with a non-coring tip, and a second end with a
fluid port in commlln;cation with the non-coring tip. The
preferred needle asse-m-bly also includes a gas
pressurization needle coaxial with and of larger diameter
than the pipetting needle. The gas pressurization needle
includes a body portion, a frustum, or tapered section
extending from the body of the gas pressurization needle
to the body of the pipetting needle, a gas inlet port,
and a gas outlet port in c~mmlln;cation with the gas inlet
port.
A preferred embodiment of a rinse station uses
cleaning solvent driven by a pipetting syringe to cleanse
the interior and exterior of a cont~m;n~ted pipetting
needle.
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BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a side view of a prior art double
pipetting needle for use in inert atmosphere operations.
Figure 2 is a side view of a coaxial pipetting
needle for use in inert atmosphere operations according
to a preferred embodiment.
Figure 3 is a side cross sectional view of
portions of the coaxial pipetting needle shown in Figure
2.
Figure 4 is a side view of the coaxial pipetting
needle shown in Figure 2 as used with a septum sealed
cont~;ner.
Figure 5 is a side cross sectional view of a prior
art pipetting needle rinse station.
Figure 6 is a side cross sectional view of an
alternative pipetting needle rinse station according to a
preferred embodiment.
Figure 7 is a side cross sectional view of a
pipetting needle rinse station according to a preferred
embodiment.
Figure 8 is top view (taken along line A - A) of
the alternative pipetting needle rinse station shown in
Figure 7.
DETAILED D.SCRIPTION
The structure and function of the preferred
embodiments can best be understood by reference to the
drawings. The reader will note that the same reference
numerals appear in multiple figures. Where this is the
case, the numerals refer to the same or corresponding
structure in those figures.
COA~TAT~ NEEDLE AS,ST.~MRT.y
Referring now to Figures 2 and 3, a coaxial needle
assembly 20 according to a preferred embodiment is
shown. Coaxial needle assembly 20 includes a pipetting
needle 22, preferably having a piercing tip 24.
Piercing tip 24 is preferably a non-coring tip.
Pipetting needle 22 is connected to a conventional
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pipetting syringe or automated pipetting work station
(not shown) through fluid port 26. Fluid port 26 may be
a standard female luer connector such that pipetting
needle 22 can be connected to a pipetting syringe having
a st~n~d male luer connector. Fluid port 26 may also
be a stAn~Ard hose barb connector.
Mounted externally to and coaxially with pipetting
needle 22 is gas pressurization needle 32.
Pressurization needle 32 includes a gas inlet port 30
and a body 28. Gas inlet port 30 may be a standard male
or female luer connector. Gas inlet port 30 may also be
a standard hose barb connector. Pressurization from
needle 32 terminates at one end with frustum, or tapered
section 34, which tapers to meet the exterior of
pipetting needle 22. Tapered section 34 may include one
or more outlet vents 36 which connect to inlet port 30
via one or more passages 38 in presurization needle 32.
Alternatively, body 32 may include one or more outlet
vents 36A which connect to inlet port 30 via one or more
passages 38. Needle assembly 20 may also include both
outlet vents 36 and outlet vents 36A.
Above inlet port 30 is an upper body portion 40.
Upper body portion 40 is sealed, preferably with solder,
to pressurization needle 22 to prevent gas leakage.
Referring now to Figure 4, the operation of
coaxial needle assembly 20 will be described. In a
typical operation, a quantity of liquid reagent 42 is
stored in a container 44. The interior of container 44
is sealed from outside air by a septum 46.
To remove reagent 42 from container 44, a lower
portion of pipetting needle 22 and body 32 of
pressurization needle 32 pierce septum 46. Tip 24 is
placed in reagent 42, and reagent 42 is removed from
container 44 preferably through the action of a
pipetting syringe (not shown) in commlln;cation with fluid
port 26.
While reagent 42 is being removed, inert (or other)
gas is simultaneously pumped into container 44 through
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vents 36. In a preferred embodiment, the pressure
inside cont~; ne~ 44 is regulated to be approximately two
pounds per square inch greater than the ambient pressure
of the outside air. The maintenance of a slight
overpressure within container 44 reduces the chance of
cont~m;n~tion with outside air should the integrity of
septum 46 be momentarily breached. And should there be
a small amount of outside air within container 44,
drawing reagent from near the bottom of the cont~; n~r
10 will m;n;m; ze the possibility of withdrawing reagent that
has been exposed to outside air.
As will be apparent to those skilled in the art,
needle assembly 20 may be used with automated pipetting
stations such as the TECAN Model 5032, or may be used
with standard syringes or other pipetting devices as are
commonly employed in the art to transport chemical
reagents.
RINSE STATIONS
As was discussed above, a pipetting needle may be
used with a variety of reagents. Accordingly, it is
necessary to cleanse the inside and outside of a
pipetting needle between uses to prevent cross
cont~m;n~tion between reagents.
Referring now to Figure 2, a portion of a rinse
station 60 according to a preferred embodiment is shown.
Rinse station 60 includes a relatively long tube 62
having a closed end 64 and an open, flared end 66. Rinse
station 60 may also include a mounting adapter 68 to
allow rinse station 60 to fit onto an existing rinse
station mount (not shown). Mounting adapter 68 could
also be modified to fit in cavity 52 of prior art rinse
station 50 (see Figure 1).
The operation of rinse station 60 is as follows:
The entire cont~m;n~ted portion of a pipetting needle
(not shown) is placed into tube 62.
A cleaning solvent is then pumped out of the tip of
the pipetting needle, cleansing the inside of the needle.
Solvent then flows up tube 62, cleansing the entire
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cont~m;n~ted exterior portion of the pipetting needle.
CleAn;ng solvent then flows out of end 66 into a waste
trough (not shown).
Figure 7 shows a cross sectional view of a
preferred embodiment of an alternative rinse station 70.
Rinse station 70 includes a tube 72, a cleAn;ng
solvent inlet port 74, and one or more cleAn;ng jets 76
connected to inlet port 74 via passages 77 (see Figure
8). In a preferred e-mbodiment~ there are two cleaning
jets 76 placed 180 degrees apart from each other.
Cleaning solvent may be supplied to inlet port 74 via
supply tube 75. Tube 72 has an open end 78 for
receiving a pipetting needle, and a second open end 80,
which is a drain for waste cleaning solvent. Rinse
station 70 may also include a mounting adapter 71 to
allow rinse station 70 to fit onto an existing rinse
station mount (not shown).
A cle~n; ~g operation using rinse station 70 is
performed as follows: a pipetting needle (not shown) is
inserted into tube 72 via open end 78. Cl~An; ng solvent
is pumped through the inside of the needle. At the same
time, or at a point close in time, cleaning solvent is
pumped into port 74 and out through jets 76, preferably
generating two streams or jets 79 of cleaning fluid that
meet in the center of tube 72. Streams 79 of cleaning
fluid spray the exterior of the pipetting needle with
cleaning solvent as the needle is moved past cleaning
jets 76. The use of cl~An;ng jets 76 allows the
exterior of the pipetting needle to be cleansed very
quickly and thoroughly with a relatively small amount of
cleaning solvent. In addition, the use of cleaning jets
76 allows the interior and exterior of the pipetting
needle to be cleansed independently of one another.
Thus, the exterior of the cont~m;nAted pipetting needle
is washed with fresh cleaning solvent rather than solvent
that may have previously contacted the contAm;n~ted
interior of the pipetting needle.
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As will be apparent to those skilled in the art, the
rinse stations 60 and 70 of Fisures 6 and 7 may be used
with a coaxial pipetting needle assembly, as described
above. Rinse stations 60 and 70 may also be used with
conventional pipetting needles.
The present invention has been described in terms of
a preferred embodiment. The invention, however, is not
limited to the embodiment depicted and described.
Rather, the scope of the invention is defined by the
appended claims.
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