U.S. patent application number 10/892023 was filed with the patent office on 2004-12-23 for pipet for liquid exchange.
This patent application is currently assigned to Biodevices, Inc., a Massachusetts corporation. Invention is credited to Kang, Jing X..
Application Number | 20040258574 10/892023 |
Document ID | / |
Family ID | 26870275 |
Filed Date | 2004-12-23 |
United States Patent
Application |
20040258574 |
Kind Code |
A1 |
Kang, Jing X. |
December 23, 2004 |
Pipet for liquid exchange
Abstract
The invention features pipets for fast and efficient liquid
exchange, pipet controllers for use with such pipets and pipetting
systems utilizing pipets and/or pipet controllers of the
invention.
Inventors: |
Kang, Jing X.; (North
Andover, MA) |
Correspondence
Address: |
FISH & RICHARDSON PC
225 FRANKLIN ST
BOSTON
MA
02110
US
|
Assignee: |
Biodevices, Inc., a Massachusetts
corporation
|
Family ID: |
26870275 |
Appl. No.: |
10/892023 |
Filed: |
July 15, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10892023 |
Jul 15, 2004 |
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10169636 |
Nov 25, 2002 |
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6810923 |
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10169636 |
Nov 25, 2002 |
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PCT/US01/00139 |
Jan 2, 2001 |
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60174490 |
Jan 4, 2000 |
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60250285 |
Nov 30, 2000 |
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Current U.S.
Class: |
422/400 |
Current CPC
Class: |
B01L 2400/049 20130101;
C12M 29/00 20130101; B01L 3/0203 20130101; B01L 3/021 20130101;
B01L 2300/0861 20130101; B01L 2400/0605 20130101; B01L 3/0213
20130101; Y10S 604/902 20130101 |
Class at
Publication: |
422/100 ;
422/099 |
International
Class: |
B01L 003/02 |
Claims
What is claimed is:
1.-12. (cancelled)
13. A pipet controller comprising a housing having an inlet port
and an outlet port, the inlet port adapted to engage a pipet and
the outlet port adapted for attachment to a vacuum source; a
conduit within the housing and connected to the inlet port and the
outlet port; and an adjustable valve system for controlling liquid
flow through the conduit, the valve system having at least a first
setting in which the vacuum source applies a vacuum to the pipet
through the conduit, thereby allowing suctioning of liquid from the
pipet through the conduit, and a second setting in which the vacuum
source is disconnected from the conduit, thereby releasing liquid
in the pipet.
14. The controller of claim 13, wherein the valve system further
has a third setting in which the vacuum source is disconnected but
a homeostatic suction is maintained on the pipet.
15. The controller of any one of claims 13 and 14, wherein the
valve system includes at least one spring-loaded piston.
16. The controller of claim 13 or 14, wherein the controller is
formed of only autoclavable materials
17.-24. (cancelled).
25. The controller of claim 13 in which the adjustable value system
comprises a passage in the housing to the ambient atmosphere, and
the second setting exposes the conduit to ambient atmospheric
pressure.
26. The controller of claim 14 in which the adjustable valve system
comprises two pistons.
27. The controller of claim 26 in which each of the pistons is
biased by a spring.
28. The controller of claim 13 that is a handheld controller.
29. The controller of claim 13 further comprising a bulb integrated
in the conduit.
30. The controller of claim 29 wherein the bulb is depressible by a
lever.
31. The controller of claim 26 wherein one of the pistons comprises
a lever that is adapted to pressure a bulb integrated in the
conduit.
32. A method of pipetting liquid, the method comprising: providing
a pipet that comprises the controller of claim 13; positioning the
adjustable valve system at the first setting, thereby applying a
vacuum that suctions liquid; positioning the adjustable value
system at the second setting, thereby releasing the vacuum.
33. The method of claim 32 wherein the vacuum removes liquid from a
vessel to a discard location.
34. The method of claim 33 wherein the vacuum both removes liquid
from a vessel to a discard location and fills a reservoir in the
pipet with liquid, and the vacuum release enables liquid in the
reservoir to flow into the vessel.
35. The method of claim 32 or 34 further comprising positioning the
adjustable valve system at a third position, prior to positioning
it at the second position, wherein the third position disconnects
the vacuum, but maintains a homeostatic suction.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional
Application Ser. No. 60/250,285, filed Nov. 30, 2000; and U.S.
Provisional Application Ser. No. 60/174,490, filed Jan. 4,
2000.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to laboratory pipets for
changing liquid residing in a vessel, e.g., a tissue culture
vessel. Changing liquid medium is routine (often called cell
feeding) in laboratories that use cell/tissue cultures and is
generally performed every other day. The conventional operation of
cell feeding typically involves at least two separate steps: 1)
removal or aspiration of the old medium from a culture vessel by
means of vacuum suction or pipetting; and 2) addition of new medium
to the culture vessel using another pipet to transfer medium from a
liquid container to the culture vessel.
[0003] Conventional laboratory pipets, which are usually used with
an electrica/mechanical pipetter for drawing and expelling fluids,
have a single barrel and therefore can handle (take and discharge)
only one liquid at a time. This process requires a change of
pipets, thereby rendering the process discontinuous and requiring
many actions, pauses, openings of culture vessels and medium
containers, and seconds or minutes of prolonged exposure of
cultured cells to air. Consequently, cell feeding is time
consuming, material-wasting, and potentially harmful to cultured
cells, particularly when a large volume of medium or a large number
of vessels are involved.
[0004] To solve the aforementioned problems, a method and apparatus
for a one-step liquid medium exchange is described in U.S. Pat. No.
5,874,296, which is hereby incorporated by reference. The apparatus
comprises a vacuum controller, a pipe, and a reservoir. The
apparatus is capable of suctioning a liquid (old medium) from a
container using a vacuum and simultaneously drawing a second liquid
(new medium) from a liquid source to fill the reservoir. When the
old medium is completely extracted and sufficient new medium fills
the reservoir, the vacuum controller disengages the vacuum to stop
fluid transfer. Activation of another controller allows the new
medium to drain from the reservoir into the now empty container
which formerly contained the old medium. Use of this apparatus can
now accomplish the task of changing liquid media in essentially one
step. An installed vacuum source is generally required for
operation of the apparatus.
SUMMARY OF THE INVENTION
[0005] The present invention is based on a variety of new features
that increase the flexibility and efficiency of the one-step liquid
medium exchange system described in U.S. Pat. No. 5,874,296. In one
embodiment, a pipet includes a first reservoir for holding the
liquid to be freshly added to a vessel, and a second reservoir for
holding the waste liquid removed from the vessel. Visual inspection
of the fluid levels in the first and second reservoirs helps the
user confirm both the volume of liquid removed from the vessel and
the volume of liquid to be introduced into the vessel. In another
embodiment, a pipet controller includes a conduit and valve control
system for controlling liquid flow through the controller, in
contrast to previously available pipet controllers that do not
allow liquid to flow through the controller.
[0006] Accordingly, the invention features a pipet having (1) a
delivery reservoir including an inlet port that allows passage of
liquid into but not out of the delivery reservoir, the inlet port
adapted for attachment to a liquid source, and an outlet port that
allows passage of liquid out of but not into the delivery
reservoir, the delivery reservoir formed of a material
substantially transparent to allow visual inspection of liquid
level within the delivery reservoir, (2) a disposal reservoir
including an inlet port that allows passage of liquid into but not
out of the disposal reservoir, and an outlet port that allows
passage of liquid out of but not into the disposal reservoir, the
outlet port adapted for attachment to a waste receptacle, and the
disposal reservoir formed of a material substantially transparent
to allow visual inspection of liquid level within the disposal
reservoir, (3) a tube having a distal end and proximal end, the
distal end adapted for suction of liquid from and delivery of
liquid to a vessel, and the proximal end in communication with the
outlet port of the delivery reservoir and the inlet port of the
disposal reservoir, and (4) a vacuum port contiguous with the
delivery reservoir and the disposal reservoir and adapted for
attachment to a vacuum source.
[0007] In an alternative embodiment, the invention includes a pipet
having (1) a delivery reservoir including an inlet port that allows
passage of liquid into but not out of the delivery reservoir, the
inlet port adapted for attachment to a liquid source, and an outlet
port that allows passage of liquid out of but not into the delivery
reservoir, the delivery reservoir formed of a material
substantially transparent to allow visual inspection of liquid
level within the delivery reservoir, (2) a disposal reservoir
including
[0008] an inlet port that allows passage of liquid into but not out
of the disposal reservoir, and
[0009] an outlet port that allows passage of liquid out of but not
into the disposal reservoir, the outlet port adapted for attachment
to a waste receptacle, and the disposal reservoir formed of a
material substantially transparent to allow visual inspection of
liquid level within the disposal reservoir, (3) a suction tube
having a distal end adapted for suction of liquid from a vessel and
a proximal end in communication with the inlet port of the disposal
reservoir, (4) a delivery tube having a distal end adapted for
delivery of liquid from a vessel and a proximal end in
communication with the outlet port of the delivery reservoir, and
(5) a vacuum port contiguous with the delivery reservoir and the
disposal reservoir and adapted for attachment to a vacuum
source,
[0010] Application of a vacuum to the pipets via the vacuum port
causes passage of liquid from the liquid source into the delivery
reservoir via its inlet port and simultaneous passage of liquid
from the vessel through the tube and into the disposal reservoir
via its inlet port. In addition and optionally, release of the
vacuum subsequent to the application of the vacuum causes passage
of liquid from the delivery reservoir via its outlet port through
the tube and into the vessel and simultaneous passage of liquid
from the disposal reservoir via its outlet port to the waste
receptacle.
[0011] The pipets of the invention can include one or more of the
following optional features: The delivery and disposal reservoir
are arranged side by side. The inlet port and outlet port of the
delivery reservoir each includes a clack valve. The inlet port and
the outlet port of the disposal reservoir each includes a clack
valve. The tube is substantially rigid. The vacuum port includes a
filter that blocks the passage of liquid and/or air particles into
and out of the pipets. The distal end of the tube is adapted for
simultaneous suction of liquid from and simultaneous delivery of
liquid to a plurality of vessels (e.g., a two-dimensional array of
vessels). The distal end of the tube includes a filter that blocks
passage of cells while allowing liquid to flow through the
tube.
[0012] The invention further includes a pipet controller having (1)
a housing including an inlet port and an outlet port, the inlet
port adapted to engage a pipet and the outlet port adapted for
attachment to a vacuum source; (2) a conduit within the housing and
connected to the inlet port and the outlet port; and (3) an
adjustable valve system for controlling liquid flow through the
conduit, the valve system having at least a first setting in which
the vacuum source applies a vacuum to the pipet through the
conduit, thereby allowing suctioning of liquid from the pipet
through the conduit, and a second setting in which the vacuum
source is disconnected from the conduit, thereby releasing liquid
in the pipet.
[0013] The controller can have one or more of the following
optional features: The valve system further has a third setting in
which the vacuum source is disconnected but a homeostatic suction
is maintained on the pipet the valve system includes at least one
spring-loaded piston. The controller is formed of only autoclavable
materials.
[0014] Also featured in the invention is a container lid having a
housing defining at least a first and second passage, the first
passage configured to seal a container opening having a first
configuration, and the second passage configured to seal a
container opening having a second configuration different from the
first configuration.
[0015] The lids of the invention can have one or more of the
following optional features: The first and second configurations
are cylindrical but are of different diameters. The first and
second passages are threaded and configured to seal a screw-top
bottle. The lids further include an outlet port adapted for
dispensing of liquid from the container. The outlet port is
sealable. The lids further include a suction tube extending from
the outlet port and into a container.
[0016] The invention also includes a pipet having (1) a delivery
reservoir including an inlet port adapted for connection to a
liquid source, and an outlet port including a valve that allows
passage of liquid out of but not into the delivery reservoir, (2) a
tube having a distal end and proximal end, the distal end adapted
for suction of liquid from and delivery of liquid to a vessel, and
the proximal end in communication with the outlet port of the
delivery reservoir, and (4) a vacuum port contiguous with the
delivery reservoir and adapted for attachment to a disposal
receptacle and a vacuum source. Application of a vacuum to the
pipet via the vacuum port causes passage of liquid from the liquid
source into the delivery reservoir via its inlet port and
simultaneous passage of liquid from the vessel through the tube,
out of the vacuum port, and into the disposal receptacle.
[0017] The present pipet can be used with a mechanical pipetter
widely used in laboratories, any installed vacuum source, or a
pipet controller described herein. This pipet has a simple
construction that can be operated easily and accurately and is
versatile. Other features and advantages will be apparent from the
following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a perspective view of a pipet system of the
invention.
[0019] FIGS. 2A-2C are cross-sectional views through the center of
the pipet in the system shown in FIG. 1.
[0020] FIGS. 3A and 3B are cross-sectional views of alternative
embodiments of the pipet shown in FIG. 1.
[0021] FIG. 4A is a perspective view of a pipet of the invention.
FIG. 4B is a vertical cross-section along the length of the pipet
at line A-A shown in FIG. 4A, and FIG. 4C is a horizontal
cross-section of the pipet along line B-B shown in FIG. 4B.
[0022] FIGS. 5A-5C are perspective views of container lids of the
invention. FIGS. 5D-5F are cross-sectional views of the container
lids, cut along line A-A, as shown in FIGS. 5A-5C,
respectively.
[0023] FIGS. 6A and 6B illustrate attachment devices for use in
suctioning suspension cell cultures without removing cells in the
culture.
[0024] FIG. 7A is a perspective view of a pipet system, including a
pipet controller of the invention. FIG. 7B is a cross-sectional
view of the pipet controller shown in FIG. 7A. FIG. 7C is a
cross-sectional view of a portion of a pipet controller having an
alternative valve system.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Referring to FIGS. 1 and 2A-2C, a liquid exchange system 32
includes a pipet 30 having a tube 1, semi-circular reservoirs 2 and
3, a vacuum port 4, inlet/outlet passages 5, 6, 7, and 8, and
one-way control valves 9, 10, 11, and 12. A dividing wall 15
separates reservoirs 2 and 3 from each other in pipet 30. Of
course, in a separate embodiment, reservoirs 2 and 3 can be two
individual cylinders coupled longitudinally, or even two reservoirs
spaced apart.
[0026] Tube 1 has a distal end 13 used for drawing and delivery of
liquid into and out of pipet 30 and an opening 14 (FIGS. 2A-2C) in
communication with reservoirs 2 and 3 via outlet passage 6 and
inlet passage 7. Graduation markings 16 on the exterior surface of
pipet 30 are used for determining, by visual inspection, the volume
of liquid contained in the reservoirs. The walls of pipet 30 are
sufficiently transparent so that the liquid level can be seen by
the user.
[0027] Each of reservoirs 2 and 3 have distal portions 17 and
proximal portions 18. The proximal portions 18 of reservoirs 2 and
3 join together to form a common channel or passage, i.e., the
vacuum port 4 for mounting of tube 30 onto a pipet controller 20.
Vacuum port 4 includes a filter plug 19 (e.g., absorbent cotton,
etc.) in its bore to block passage of particulates or liquid
through the pipet. The distal portions 17 of reservoirs 2 and 3
have inlet 5 and 7 and outlet 6 and 8, respectively.
[0028] Reservoir 2 is used for temporarily storing new or
replacement liquid medium, whereas reservoir 3 is used for
temporarily storing the old liquid medium to be disposed. Inlet 5
of reservoir 2 is connected to a replacement liquid container 21
via a sterile tubing 22. Outlet 6 of the reservoir 2 is connected
to tube 1 for draining the new medium into a culture vessel. Inlet
7 of reservoir 3 is also connected to tube 1 for drawing the old
medium from the culture vessels into reservoir 3. Outlet 8 of
reservoir 3 is connected to a waste collecting bottle 23 via a
tubing 24. Although container 21 hold fresh medium, it is
understood that any useful liquid, such as saline, can be provided
in the container.
[0029] Opening or closing of each passage of the inlets 5 and 7 and
outlets 6 and 8 is automatically controlled by shutter or clack
valves 9, 10, 11, and 12. The valves serve as one-way controllers
that open or close in response to pressure differences inside
reservoirs 2 and 3. Indeed, any valve can be used, so long as the
valve is formed of a non-toxic material, is stable in liquid and
air, and provides one-way closure.
[0030] The pressure state (either vacuum or high pressure) is
provided by pipet controller 20. As shown in FIG. 2B, when vacuum
is applied to reservoirs 2 and 3, valves 9, 10, 11, and 12 move
upward to open inlets 5 and 7 and close outlets 6 and 8, thereby
drawing new medium into reservoir 2 and old medium into reservoir 3
via inlet 5 and the inlet 7, respectively. Conversely, as shown in
FIG. 2C, when the vacuum is eliminated and a high (or positive)
atmospheric pressure is applied, valves 9, 10, 11, and 12 move
downward to open outlets 6 and 8 and close inlets 5 and 7. Now the
new medium and the old medium are simultaneously drained from
reservoir 2 and reservoir 3 via outlet 6 and outlet 8 into culture
vessel (not shown) and disposal receptacle 23, respectively.
However, other mechanisms for accomplishing the same result can be
envisioned by those skilled in the art and consequently are
considered a part of this invention as well.
[0031] System 32 can be used as follows.
[0032] 1) Hold pipet controller 20 with one hand and immerse tip 13
of tube 1 into the old liquid medium to be disposed.
[0033] 2) Press a button 25 on pipet controller 20 to apply vacuum
to reservoirs 2 and 3, thereby drawing the new medium and the old
medium simultaneously into reservoir 2 and reservoir 3 via inlet 5
and inlet 7, respectively.
[0034] 3) Release button 25 (now the fluid flow stops) and press
another control button 26 of pipet controller 20 to apply a high
(or positive) atmospheric pressure to reservoirs 2 and 3, thereby
expelling or discharging the new medium and the old medium
simultaneously from reservoir 2 and reservoir 3 via outlet 6 and
outlet 8 into culture vessel and disposal receptacle 23,
respectively.
[0035] Thus, the operator can accomplish the task of changing
liquid medium in one single step without the need for changing
pipets. In addition, the pipet of the present invention can be used
solely for aspiration of a liquid for disposal or solely for
addition or dispensation of a liquid.
[0036] Other options which may be desirable include a second tube
27 (FIG. 3A) connected to outlet 6 and in parallel with first tube
1 (which is connected to inlet 7) but shorter. This separation of
the passages for outlet 6 and inlet 7 helps eliminate
cross-contamination as pipet 30 is moved from one vessel to
another.
[0037] In another embodiment, a manifold 28 (FIG. 3B) with
different number of ports spaced to fit the wells of a microplate
can be attached to tip 13 of the tube 1. Manifold 28 is useful for
changing medium in multiple-well microplates (e.g., 96 well
plate).
[0038] Referring to FIGS. 4A-4C, a liquid exchange system includes
an alternative form of a pipet 100. Pipet 100 includes a mounting
tube 102 for coupling to a vacuum source and waste receptacle.
Mounting tube 102 is in communication with a reservoir 116, which
is formed by housing 104, via an opening 114 in a passage 106
embedded in wall of housing 104. A tube 108 is in communication
with reservoir 116 via an outlet 110, passage of liquid through
which is controlled by clack valve 112. Alternative valves suitable
for use in the pipets of the invention (e.g., shutter valves) are
know to one skilled in the art. Medium or liquid enters reservoir
116 through inlet 118, which during operation is connected to a
source of liquid.
[0039] In actual use, pipet 100 operates similarly to pipet 30
shown in FIG. 1, except that the waste liquid is not held in a
reservoir within pipet 100. In other words, when vacuum is applied
to pipet 100 via vacuum port 102, liquid is immediately suctioned
into member 108, through passage 106 and port 102 and into a waste
receptacle (not shown). Simultaneously, the vacuum is also applied
to reservoir 116 via opening 114, resulting in the introduction of
fresh medium from a liquid source (not shown) into reservoir 116
via inlet 118. When vacuum pressure ceases and vacuum port 102 is
exposed to ambient air, fresh medium flows through outlet 110 into
member 108 and out of pipet 100.
[0040] Referring back to FIG. 1 and replacement liquid container
21, it is understood that tissue culture medium is often purchased
in bottles with standard screw-top caps. Thus, an additional
feature of the invention is a multi-size screw top cap adapted to
fit and seal two or more standardized bottle sizes. A dual-size
screw top cap is shown in FIGS. 5A and 5D. Cap 200 is formed of
housing 202, which defines a large-diameter cylindrical threaded
passage 204 having threads 208 and a smaller diameter cylindrical
passage 206 having threads 210. In the case of tissue culture
medium bottles, passage 204 can have a diameter of about 3.8 cm,
and passage 206 can have a diameter of about 3.0 cm, both diameters
corresponding to standard tissue culture medium bottles. Thus, the
single cap 200 can be used to seal bottles have mouths of different
sizes. Of course, instead of threads, the passages can be
configured to seal a container opening using any other mechanisms
or configurations, including a detent mechanism.
[0041] For the replacement liquid container 21 shown in FIG. 1 to
be useful in system 32, the bottle cap must contain an outlet for
the medium. In the configuration shown in FIGS. 5B and 5E, bottle
cap 300 includes a housing 302 defining a cylindrical passage 304
having threads 316 that are adapted to couple with a mouth of a
bottle containing medium. Cap 300 also includes outlet port 306,
which has an exterior portion 308 and an interior portion 310.
Outlet port 306 includes a removable cover 314 for capping an
opening 316 in exterior portion 308. Cover 314 is attached to a
portion of outlet port 306 by tether 318. During operation within
system 32, interior portion 310 is coupled to a tubing 312, which
is immersed in the medium to be transferred, and cover 314 is
removed so that, e.g., tubing 22 in system 32 of FIG. 1 can be
connected to outlet port 306. Although exterior portion 308 is bent
90.degree. relative to interior portion 310 so that the tube
leading from the exterior portion 308 can be positioned away from
the user's moving hands, it is understood that other configurations
for outlet port 306 are suitable for use in the invention.
[0042] For example, the features of the dual-size screw top cap
shown in FIGS. 5A and 5D can be combined with the outlet port
arrangement shown in FIGS. 5B and 5E to provide a cap 600 as shown
in FIGS. 5C and 5F. Cap 600 is formed of a housing 602 that defines
a larger diameter cylindrical, threaded passage 604 and a smaller
diameter cylindrical, threaded passage 606. Cap 600 also includes
outlet port 608, which is embedded in housing 602 and does not
extend from the top of the cap, as is shown for cap 300 in FIG. 5B.
Instead, outlet port 608 emerges from the side of cap 600.
[0043] Another feature of the invention is an attachment, e.g., for
distal tip 13 of tube 1 of pipet 30 (FIG. 1), that allows suction
of suspension cell cultures without removing the cells in the
culture. This is desirable when the number of cells in culture
should be maximized. Two embodiments of such an attachment are
shown in FIGS. 6A and 6B. In FIG. 6A, attachment 400 includes a
neck 402 adapted to be removably coupled to tip 13 of tube 1 (FIG.
1) and conical section 404 having mouth 406. Attachment 400 has a
grate 408 covering mouth 406 and supporting a membrane 410.
Membrane 410 contains pores of a size that allows suction of medium
but not cells through attachment 400.
[0044] To increase the surface area through which old media can be
suctioned and to minimize the clogging of the membrane by cells,
another embodiment of an attachment is shown in FIG. 6B. Attachment
500 includes neck 502 adapted to be removably coupled to tip 13 of
tube 1 (FIG. 1), a support scaffold 504, and a membrane 506 having
pores of a size that allows suction of medium but not cells through
attachment 500.
[0045] It is noted that attachments need not be used when feeding
suspension cell cultures, especially when loss of cells is not a
problem. In addition, the attachment can be formed of inexpensive
materials so that a user can discard the attachment after a first
use, or formed of relatively strong materials that can survive
sterilization techniques, such as autoclaving. In addition, the
attachments can be integrated with tube 1 to form a single
non-removable piece.
[0046] The pipet controllers of the invention differ from
previously available pipet controllers because the present
controllers allows liquid flow through the controller, while
previous controllers are designed to specifically block passage of
liquid into the controller. Referring to FIGS. 7A-7C, the invention
includes a pipet controller 700 that can be used with pipet 100
shown in FIGS. 4A-4C. Controller 700 is formed of housing 702,
which is shaped for hand operation. Housing 702 includes an inlet
port 704 and an outlet port 706. Inlet port 704 includes a rubber
stopper 708 designed to accommodate and seal around a vacuum port
of a pipet (e.g., vacuum port 102 of pipet 100 shown in FIGS.
4A-4C). Outlet port 706 is adapted to fit a standard vacuum tubing
710, leading to a waste receptacle 710 and vacuum source 714 (e.g.,
a standard house vacuum line often found in laboratories).
[0047] A conduit 716 within housing 702 links inlet port 704 and
outlet port 706. Connected to conduit 716 is a valve system 718,
which includes a spring 720 and a piston 722. The position of
piston 722 is biased by spring 720. In normal operation the user's
fingers depresses piston 722 to position A, thereby applying a
vacuum to conduit 716 and pipet 100. Liquid is then suctioned from
a vessel using tube 108 of pipet 100. This disgarded liquid travels
through housing 702 via conduit 716, out through vacuum tubing 710
and into waste receptacle 712. Simultaneously, liquid flows from
container 724, through tubing 726, and into pipet 100 as described
above. The user can then temporarily hold liquid in reservoir 116
of pipet 100 by allowing piston 722 to move to position B, where
the pressure in conduit 716, and consequently in pipet 100, is
homeostatic. The user then fully releases piston 722 to rest in
position C, where conduit 716 is exposed to the ambient atmosphere
through hole 724 in housing 702. Accordingly, liquid flows from
pipet 100 into a vessel via tube 108.
[0048] FIG. 7C shows an alternative valve system 718' that can be
used in place of valve system 718 described above. In this
embodiment, valve system 718' includes pistons 730 and 732, each of
which are biased by springs 734 and 736, respectively. In typical
operation using valve system 718', piston 732 is depressed to
connect conduit 716' with a vacuum source via outlet port 706'.
Accordingly, liquid flows from pipet 100, through conduit 716' and
out of the controller through outlet port 706'. Next, the user can
temporarily pause the operation by releasing piston 732 to its
resting position, thereby applying homeostatic pressure to pipet
100. To release liquid from pipet 100, piston 730 is depressed,
exposing conduit 716' to ambient atmosphere through hole 724' in
housing 702'. To accomplish this release, piston 730 contains a
passage 738 along one side. When piston 730 is depressed, passage
738 is in communication with both conduit 716' and hole 724'.
[0049] Piston 730 also includes a lever arm 740. When piston 730 is
depressed to release liquid in pipet 100, lever arm 740 presses a
bulb 742 integrated into conduit 716' to expel a final volume of
air into pipet 100. This final volume of air aides delivery of the
very last amount of liquid in tube 108 of pipet 100 to a
vessel.
[0050] The liquid exchange systems described above can also be used
in conjunction with robotic or automated pipetting systems that
employ pipets as described above. For example, manifold 28 shown in
FIG. 3B can contain multiple ports in one dimension (FIG. 3B) or
two dimensions, such as a 8.times.12-port configuration
corresponding to a standard 96-well microplate. In addition, pipet
30 can be mounted onto an addressable carrier and can position a
manifold anywhere within two or three dimensions. Although in the
above configuration one pipet is connected to 96 ports, it is
understood that the port:pipet ratio can range from 1:1 to greater
than 96:1 by miniaturizing the various components and mounting the
components on an addressable robotic arm. Robotic machines that can
be adapted for use in such an addressable, high throughput
pipetting system include automated microplate pipetting and washer
systems available from Bio-Tek, Inc.; Plate Track, Inc.; and
Packard Instruments, Inc.
[0051] The pipets, systems, pipet controllers, or accessories
described herein can be formed of materials that can be easily
sterilized, e.g., by autoclaving. However, if sterilization is not
a consideration, then more advanced but more fragile components can
be used. For example, the valves, ports, actuators, and other
controls can be electro-mechanical and contain electronic
circuits.
[0052] While the invention has been described and illustrated with
reference to specific embodiments, it is understood that other
embodiments may be resorted to without departing from the
invention. Therefore the form of the invention set out above should
be considered only illustrative and not limiting. Additional
embodiments of the invention are included in the claims below.
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