U.S. patent application number 11/680308 was filed with the patent office on 2007-08-30 for disposable pumping apparatus based on flexible vessels in pressurized containers.
Invention is credited to Alexandre N. Terentiev, Sergey Terentyev.
Application Number | 20070201993 11/680308 |
Document ID | / |
Family ID | 38459812 |
Filed Date | 2007-08-30 |
United States Patent
Application |
20070201993 |
Kind Code |
A1 |
Terentiev; Alexandre N. ; et
al. |
August 30, 2007 |
DISPOSABLE PUMPING APPARATUS BASED ON FLEXIBLE VESSELS IN
PRESSURIZED CONTAINERS
Abstract
An apparatus is provided for intended use in pumping a fluid
under sterile conditions. In one embodiment, a first rigid
container is internally pressurized to pump fluid through a first
flexible vessel within the rigid container. In another embodiment,
first and second containers are provided, each for receiving
flexible vessels that create independent pumping chambers upon the
selective or periodic internal pressurization of the containers.
Related aspects and methods are also provided.
Inventors: |
Terentiev; Alexandre N.;
(Lexington, KY) ; Terentyev; Sergey; (Lexington,
KY) |
Correspondence
Address: |
KING & SCHICKLI, PLLC
247 NORTH BROADWAY
LEXINGTON
KY
40507
US
|
Family ID: |
38459812 |
Appl. No.: |
11/680308 |
Filed: |
February 28, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60777376 |
Feb 28, 2006 |
|
|
|
Current U.S.
Class: |
417/393 ;
417/394 |
Current CPC
Class: |
F17C 2205/0146 20130101;
F17C 9/00 20130101; F17C 2227/0135 20130101; F17C 2205/0323
20130101; F17C 2203/0685 20130101; F17C 2250/0636 20130101; F17C
2221/05 20130101; F17C 2270/02 20130101; F04B 43/1136 20130101;
F17C 5/06 20130101; F04B 43/113 20130101; F17C 2227/0157 20130101;
F17C 2227/0142 20130101; F17C 2205/0341 20130101; F17C 2227/0185
20130101; F17C 2270/05 20130101; F17C 2205/0364 20130101 |
Class at
Publication: |
417/393 ;
417/394 |
International
Class: |
F04B 17/00 20060101
F04B017/00 |
Claims
1. An apparatus for intended use in pumping a fluid under sterile
conditions, comprising: a first rigid container having an interior
capable of being pressurized; a first flexible vessel positioned at
least partially within the interior of the first rigid container
and for receiving and holding the fluid, said first flexible vessel
having an outlet; and at least one pressure source for pressurizing
the interior of the rigid container to cause the fluid to move
through the outlet of the first flexible vessel.
2. The apparatus of claim 1, further including a feed vessel
connected to an inlet of the first flexible vessel.
3. The apparatus of claim 2, further including a pump for
delivering the fluid from the feed vessel to an inlet of the first
flexible vessel.
4. The apparatus of claim 2, further including a filter for
receiving fluid from the outlet of the first flexible vessel, and a
return line for delivering fluid from the filter to the feed
vessel.
5. The apparatus of claim 1, wherein the pressure created in the
interior of the first rigid container comprises hydrostatic
pressure.
6. The apparatus of claim 1, further comprising a second container
having an interior capable of being pressurized by the pressure
source and a second flexible vessel for positioning at least
partially within the second container, said second flexible vessel
having an outlet for discharging the fluid to a line in common with
the outlet of the first flexible vessel.
7. The apparatus of claim 6, wherein the pressure source
alternately pressurizes the first and second containers.
8. The apparatus of claim 1, wherein the at least one pressure
source comprises a vacuum pump.
9. An apparatus for intended use in pumping a fluid under sterile
conditions, comprising: at least two containers, each having an
interior capable being pressurized; a flexible vessel positioned at
least partially within the interior of each container and for
receiving and holding the fluid, each said flexible vessel having
an outlet; and at least one pressure source for selectively
pressurizing the interiors of the containers to cause the fluid to
move through the outlets of the corresponding flexible vessels.
10. The apparatus of claim 9, wherein the pressure source
alternatively pressurizes the containers.
11. The apparatus of claim 9, further including a common line
connected to the outlets of the flexible vessels.
12. The apparatus of claim 9, further including a feed vessel for
feeding fluid to the inlets of the flexible vessels.
13. The apparatus of claim 12, further including a filter for
receiving fluid from the outlet of one or both of the flexible
vessels, and a return line for returning fluid from the filter to
the feed vessel.
14. The apparatus of claim 9, further including a chromatography
column for receiving fluid from the outlets of the flexible
vessels.
15. The apparatus of claim 9, wherein the at least one pressure
source comprises a vacuum pump.
16. A method of pumping a fluid, comprising: providing the fluid in
a first flexible vessel positioned at least partially within a
first rigid container; and pressurizing an interior of the first
rigid container to pump the fluid from the first flexible
vessel.
17. The method of claim 16, further including the steps of at least
partially relieving the pressure in the first rigid container,
allowing fluid to enter the first flexible vessel through an inlet,
and then pressurizing the interior of the first rigid
container.
18. The method of claim 16, further including the steps of
delivering the fluid to a second flexible vessel positioned at
least partially within a second rigid container, and pressurizing
an interior of the second rigid container to pump the fluid from
the second flexible vessel.
19. A method of pumping a fluid, comprising: delivering the fluid
to a first flexible vessel positioned at least partially within an
interior of a first rigid container; pressurizing the interior of
the first rigid container to move fluid through an outlet of the
first flexible vessel; delivering the fluid to a second flexible
vessel positioned at least partially within an interior of a second
rigid container; and pressurizing the interior of the second rigid
container to move fluid through an outlet of the second flexible
vessel.
20. The method of claim 19, wherein the step of delivering the
fluid to the second flexible vessel occurs concurrently with the
step of pressurizing the first rigid container.
21. The method of claim 19, wherein the delivering step comprises
delivering fluid from a common feed vessel.
22. The method of claim 19, further including the step of
delivering the fluid from the outlet of the first or second
flexible vessel to a filter, and then delivering the fluid to a
vessel for feeding either the first or second flexible vessel.
23. The method of claim 19, wherein the pressurizing steps are
performed to create a substantially constant flow of fluid along a
common line associated with the outlets of the flexible vessels.
Description
[0001] This application claims the benefit of U.S. Provisional
Patent App. Ser. No. 60/777,376, filed Feb. 28, 2006, the
disclosure of which is incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention relates generally to fluid pumping
and, more particularly, to a disposable pumping apparatus.
BACKGROUND OF THE INVENTION
[0003] A number of applications in the bioprocessing industry exist
where process fluids must be pumped from one location or vessel to
another in a sterile, non-invasive and measured fashion. Such
pumping must occur in multiple upstream and downstream
applications. Typical upstream pumping applications include: buffer
preparation, media preparation, bioreactor media feed and
supplement addition. Typical downstream applications include
pumping the cell suspensions, protein solutions or buffers to or
through purification devises such as centrifuges, filters,
membranes, chromatography columns or formulation and fill
vessels.
[0004] It is advantageous to use disposable pumps in the above
pumping applications in an effort to eliminate cross contamination
risks between the batches, as well as to reduce cleaning and
validation downtime and overall manufacturing cost for
biopharmaceuticals. One popular disposable pumping technology in
the bioprocess industry is a peristaltic pump. In one form, such as
is shown in U.S. Pat. No. 3,737,251 (the disclosure of which is
incorporated herein by reference to the extent not inconsistent
with the present teachings), such a pump uses a flexible tube as a
pumping chamber, as well as the pumping line to move the fluid from
one location to another. Compressing the tube with a driving head
produces the desired pumping action.
[0005] Despite the number of advantages of the peristaltic pump
which include simplicity, low cost and sterility, limitations
restrict the usage of such a pump in a number of important
bioprocessing steps. These include relatively low pressure, low
flow rate and pulsations of the transported liquid. For these
reasons, such pumps are rarely used in applications such as cross
flow filtration or chromatography columns.
[0006] Accordingly, a need is identified for a pumping apparatus
that addresses and overcomes the foregoing limitations, while still
being disposable and usable under sterile conditions.
SUMMARY OF THE INVENTION
[0007] In accordance with a first aspect of the invention, an
apparatus for intended use in pumping a fluid under sterile
conditions is disclosed. The apparatus comprises a first rigid
container having an interior capable of being pressurized (either
positively or negatively). A first flexible vessel is positioned at
least partially within the interior of the first rigid container,
and includes an outlet for discharging the fluid. At least one
pressure source, such as a gas cylinder, compressor, or even a
vacuum pump, is provided for pressurizing the interior of the rigid
container to cause the fluid to move through the outlet of the
flexible vessel.
[0008] In one embodiment, the apparatus further includes a feed
vessel connected to an inlet of the first flexible vessel, as well
as a pump for delivering the fluid from the feed vessel to an inlet
of the first flexible vessel. A filter may also be provided for
receiving fluid from the outlet of the first flexible vessel, along
with a return line for delivering fluid from the filter to the feed
vessel. Preferably, the pressure created in the interior of the
first rigid container comprises hydrostatic pressure to create a
substantially constant flow of fluid through the outlet of the
first flexible vessel.
[0009] In this or another embodiment, the apparatus may further
comprise a second container having an interior capable of being
pressurized by the pressure source, as well as a second flexible
vessel for positioning at least partially within the second
container. The second flexible vessel further includes an outlet
for discharging the fluid to a line in common with the outlet of
the first flexible vessel. Preferably, the pressure source
alternately pressurizes the first and second containers, such as
through the use of valves.
[0010] In accordance with another aspect of the invention, an
apparatus for intended use in pumping a fluid is provided. The
apparatus comprises at least two containers, each having an
interior capable being pressurized. A flexible vessel is positioned
at least partially within the interior of each container and is
capable of receiving and holding the fluid. Each flexible vessel
further includes an outlet. At least one pressure source is
provided for selectively pressurizing the interiors of the
containers to cause the fluid to move through the outlets of the
corresponding flexible vessels.
[0011] Preferably, the pressure source alternatively pressurizes
the containers. The apparatus may further include a common line
connected to the outlets of the flexible vessels, or a feed vessel
for feeding fluid to the inlets of the flexible vessels. In the
latter case, a filter may receive fluid from the outlet of one or
both of the flexible vessels, and a return line may be provided for
returning fluid from the filter to the feed vessel. Alternatively,
a chromatography column may be provided for receiving fluid from
the outlets of the flexible vessels.
[0012] In accordance with still another aspect of the invention, a
method of pumping a fluid is disclosed. The method comprises
providing the fluid in a first flexible vessel positioned at least
partially within a first rigid container, and pressurizing an
interior of the first rigid container to pump the fluid from the
first flexible vessel. The method may further include the steps of
at least partially relieving the pressure in the first rigid
container, allowing fluid to enter the first flexible vessel
through an inlet, and then pressurizing the interior of the first
rigid container. Alternatively or additionally, the method may
further include the steps of delivering the fluid to a second
flexible vessel positioned at least partially within a second rigid
container, and pressurizing an interior of the second rigid
container to pump the fluid from the second flexible vessel.
[0013] In accordance with yet a further aspect of the invention, a
method of pumping a fluid is disclosed. The method comprises
delivering the fluid to a first flexible vessel positioned at least
partially within an interior of a first rigid container;
pressurizing the interior of the first rigid container to move
fluid through an outlet of the first flexible vessel; delivering
the fluid to a second flexible vessel positioned at least partially
within an interior of a second rigid container; and pressurizing
the interior of the second rigid container to move fluid through an
outlet of the second flexible vessel.
[0014] Preferably, the step of delivering the fluid to the second
flexible vessel is concurrent with the step of pressurizing the
first rigid container. The delivering step may comprise delivering
step comprises delivering fluid from a common feed vessel. The
method may further include the step of delivering the fluid from
the outlet of the first or second flexible vessel to a filter, and
then delivering the fluid to a vessel for feeding either the first
or second flexible vessel. Preferably, the pressurizing steps are
performed to create a substantially constant flow of fluid along a
common line associated with the outlets of the flexible
vessels.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic diagram of one pumping apparatus
forming one aspect of the invention;
[0016] FIG. 2 is a schematic diagram of a pumping apparatus forming
another aspect of the invention;
[0017] FIGS. 3a and 3b are graphical illustrations of the flow rate
versus time created from the use of a pumping apparatus of FIG. 1
or 2;
[0018] FIGS. 4, 5, and 6 schematically illustrate various
configurations usable with the disclosed pumping apparatus.
DETAILED DESCRIPTION OF THE INVENTION
[0019] In accordance with one aspect of the invention, the general
nature of the proposed pumping apparatus comprises a container
capable of being pressurized, such as for example with a
periodically oscillating internal pressure. The pressure is of a
hydrostatic nature and maybe created by introducing gas or fluid
media to the interior of the pressure container. A hermetically
closed or scaled collapsible container, such as a flexible bag, is
placed at least partially and preferably entirely inside the
pressure container. When used in connection with pumping sterile
fluids or fluids under sterile conditions, the outer surface of the
flexible vessel is in contact with pressure transferring media and
need not be sterile, but the inner surface of the flexible vessel
may be in contact with the pumped sterile fluid so it must also be
sterile.
[0020] When the pressure container is periodically or selectively
pressurized, the flexible vessel then works as a fluid pumping
chamber The flexible vessel and the chamber have an inlet port and
a discharge port. The pumped fluid is introduced into the flexible
vessel by an inlet port connected to an inlet line (such as
flexible tubing) via an inlet valve. The pumped fluid discharges
from the flexible vessel via the discharge port connected to a
discharge line by a discharge valve. These lines may penetrate into
the pressure container, which may be hermetically sealed from the
outside environment in the entire range of the pressure developed
inside the container.
[0021] To illustrate and describe a more specific and preferred
implementation, and with reference to FIG. 1, one embodiment of the
pumping apparatus 10 includes two flexible vessels 11, 12, such as
disposable plastic bags, that create pumping chambers. These
flexible vessels 11, 12 are preferably hermetically sealed and at
least partially (and most preferably) fully contained within
separate rigid pressure containers 13, 14 capable of being
pressurized (positively or negatively).
[0022] Both pressure containers 13, 14 are preferably connected
with an external pressure source P for delivering a media under
pressure by lines with valves 21, 22. The pressure source P can be
a compressed gas cylinder, a gas compressor, a hydraulic press, or
the like. The media producing hydrostatic pressure to the bag
chambers is preferably air, but can be any suitable gas or liquid
capable of creating the desired hydrostatic pressure.
[0023] Preferably, valves 15, 16 open and close the outlets of the
flexible vessels 11, 12, while valves 17, 18 open and close the
associated inlets. Vent valves 19, 20 open or close the lines
connecting the internal volume or space of the rigid pressure
containers 13, 14 with the atmosphere. A feeding vessel V may
contain the fluid to be pumped, and a low pressure pump 23 may be
used to fill the pumping chambers 11, 12 with fluid prior to high
pressure pumping action. In one of the possible embodiments, this
pump 21 may comprise a peristaltic pump.
[0024] Operation of the pumping apparatus 10 described above may
proceed as outlined in the following description. During the
initial cycle, the pumping chamber formed by one of the flexible
vessels 11 is filled with a fluid, such as a liquid, preferably to
capacity. Pumping chamber formed by the other flexible vessel 12
may be initially empty. Fluid valves 16 and 17 are closed while
valves 15 and 18 are open. The vent valve 20 is open, while vent
valve 19 is closed.
[0025] Initially, pressure valve 22 is open while valve 21 is
closed. Accordingly, pressure developed in pressure container 13
results in the discharge of the fluid from the vessel 11 through
the outlet line. Since the pressure in the container 13 remains
constant, the flow rate of the fluid pumped is also constant until
all the fluid from the vessel 11 is pumped out and it collapses.
During this cycle, the other pressure chamber within vessel 12
maybe filled to capacity with fluid by the pump 23.
[0026] Once pumping chamber 12 is filled to capacity with the fluid
and pumping chamber of vessel 11 is empty, fluid valves 16 and 17
are opened while valves 15 and 18 are closed. Furthermore, vent
valve 20 is closed while valve 19 is opened, and pressure valve 22
is closed while valve 21 is open. The pressure developed in the
rigid container 14 results in discharge of the fluid from the
pressure chamber of vessel 12 through the outlet line. During this
cycle, pressure chamber of vessel 11 is filled to capacity with
fluid, such as by the pump 23.
[0027] Turning now to FIG. 2, this alternative embodiment of the
pumping apparatus 10 is similar in many respects to the embodiment
in FIG. 1. However, the low pressure pump 23 on the FIG. 1 is
replaced with vacuum pump 24 that creates negative pressure in the
pressure containers 13, 14 during the filling steps. The vacuum
line from the pump 24 is connected to the pressure containers 13,
14 and controlled by valves 25 and 26. During pressurization,
negative pressure within the containers 13, 14 thus forces the
fluid to exit through the corresponding outlet(s) of the flexible
vessels 11, 12 (provided, of course, the associated valves 15, 16
are selectively opened).
[0028] The sequence of pumping actions in an arrangement of two
flexible vessels 11, 12 in rigid containers 13, 14 that are
periodically pressurized, such as is described above, is shown in
the FIG. 3a. FIG. 3b shows the resultant flow rate in the discharge
line D of the pumping apparatus 10 (see also FIG. 1). The resultant
flow rate is constant as long as the spikes resulting from
switching from one pumping chamber to another can be minimized by
proper synchronization of the valves.
[0029] Turning to FIG. 4, an illustration is provided of a
pre-sterilized (by means of gamma radiation or other methods)
disposable flexible bag assembly 40 consisting of the feed bag
serving as the vessel V containing the fluid to be pumped and two
pumping vessels 11, 12. The two pumping vessels 11, 12 forming the
pressure chambers of this assembly 40 maybe introduced into the two
rigid pressure containers 13, 14 of the pumping apparatus 10 shown
on FIG. 1 or FIG. 2 to pump the fluid from the feed bag.
[0030] FIG. 5 shows a pre-sterilized (by means of gamma radiation
or other methods) disposable bag assembly 50 consisting of a bag as
the feed vessel V with the fluid to be pumped, two flexible pumping
vessels 11, 12 forming the pressure chambers and a filter F, such
as for example a tangential flow filter. In this embodiment, a
re-circulating, disposable filtration loop is described. The two
pumping vessels 11, 12 of the assembly 50 maybe introduced into the
pressure containers 13, 14 of the pumping apparatus 10 shown in
FIG. 1 or FIG. 2 for re-circulation of the fluid from the feed bag
serving as the feed vessel V, through the filter F, and back
again.
[0031] Illustrated in FIGS. 6 is a disposable bag assembly 60
connected to a chromatography column C. As in FIG. 5, the bag
serving as the feed vessel V contains the fluid to be processed.
Flexible vessels 11, 12 maybe introduced in the pumping apparatus
10 shown in FIG. 1 or FIG. 2 to activate the pumping of the fluid
through the chromatography column C. In one embodiment, the
chromatography column C can be re-usable. In another embodiment,
the bag assembly 60 and the column C are single use components.
[0032] In the embodiments of FIGS. 1 and 2, the pumping apparatus
10 is based on two chambers created by separate flexible vessels
11, 12. However, pumping with a single vessel having chamber is
also possible. With one chamber pumping, greater pulsation of the
flow through the outlet will result due to the pressurization of
the rigid container, but would be acceptable for certain
applications. Pumping using three or more chambers is also possible
and would have the same principle of operation based on disposable
flexible pumping bags placed inside the periodically pressurized
containers where pressurization cycles are synchronized with valve
operations.
[0033] The foregoing descriptions of various embodiments of the
present inventions have been presented for purposes of illustration
and description. These descriptions are not intended to be
exhaustive or to limit the invention to the precise forms
disclosed. All the pumping apparatuses described above may have
single-use fluid path components and thus eliminate cleaning
sterilization and validation procedures. The embodiments described
provide the best illustration of the principles of the invention
and its practical applications to thereby enable one of ordinary
skill in the art to utilize the invention in various embodiments
and with various modifications as are suited to the particular use
contemplated.
* * * * *