U.S. patent application number 13/545598 was filed with the patent office on 2014-01-16 for filtration in organ perfusion apparatus.
This patent application is currently assigned to LIFELINE SCIENTIFIC, INC.. The applicant listed for this patent is Jeffrey S LOUIS, Christopher P STEINMAN. Invention is credited to Jeffrey S LOUIS, Christopher P STEINMAN.
Application Number | 20140017666 13/545598 |
Document ID | / |
Family ID | 48914415 |
Filed Date | 2014-01-16 |
United States Patent
Application |
20140017666 |
Kind Code |
A1 |
STEINMAN; Christopher P ; et
al. |
January 16, 2014 |
FILTRATION IN ORGAN PERFUSION APPARATUS
Abstract
A filter for filtering perfusate is integrated with an exterior
portion of an organ container. The filter may be used in an
apparatus for perfusing an organ. The perfusion apparatus may
include an organ container configured to contain an organ, the
filter integrated with an exterior portion of the organ container,
and another filter. At least the filter integrated with an exterior
portion of the organ container may be provided in a sterilized
disposable kit.
Inventors: |
STEINMAN; Christopher P;
(Sandy, UT) ; LOUIS; Jeffrey S; (Akron,
OH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
STEINMAN; Christopher P
LOUIS; Jeffrey S |
Sandy
Akron |
UT
OH |
US
US |
|
|
Assignee: |
LIFELINE SCIENTIFIC, INC.
Itasca
IL
|
Family ID: |
48914415 |
Appl. No.: |
13/545598 |
Filed: |
July 10, 2012 |
Current U.S.
Class: |
435/1.2 ;
264/279; 435/284.1 |
Current CPC
Class: |
A01N 1/0247
20130101 |
Class at
Publication: |
435/1.2 ;
435/284.1; 264/279 |
International
Class: |
A01N 1/02 20060101
A01N001/02; B29C 45/14 20060101 B29C045/14 |
Claims
1. A filtering apparatus for filtering perfusate, comprising: an
organ container having a connection configured to connect with an
organ perfusion apparatus; and a filter element integrated with an
exterior portion of the organ container.
2. The filter of claim 1, wherein the filter element is molded into
the exterior portion of the organ container.
3. The filter of claim 1, wherein the exterior portion is located
on a bottom of the organ container.
4. The filter of claim 1, wherein the filter element is fitted into
an aperture of the exterior portion of the organ container.
5. The filter of claim 1, wherein the filter element is disposed in
the exterior portion of the organ container such that an outer
circumference or periphery of the filter element is between two
surfaces of the exterior portion of the organ container.
6. The filter of claim 1, wherein the filter element is detachable
from the organ container.
7. The filter of claim 1, wherein the filter element is a screen
filter.
8. The filter of claim 1, wherein the filter element has an average
opening size of 1,000 microns to 3,000 microns.
9. An apparatus for perfusing an organ, comprising: an organ
container configured to contain an organ; a recirculating perfusate
flow path; a first filter integrated with an exterior portion of
the organ container in the perfusate flow path; and a second filter
in the perfusate flow path.
10. The apparatus of claim 9, wherein the second filter is disposed
downstream of the first filter in the perfusate flow path.
11. The apparatus of claim 9, wherein the first filter is a coarser
filter than the second filter.
12. The apparatus of claim 9, further comprising a cradle disposed
within the organ container, the cradle having an organ supporting
surface configured to support an organ.
13. The apparatus of claim 12, wherein the organ container is
configured to hold perfusate to form a perfusate bath around an
organ placed in the cradle.
14. The apparatus of claim 9, wherein the second filter is disposed
within a fluid conduit downstream of the first filter.
15. The apparatus of claim 14, wherein the fluid conduit is in
fluid communication with the first filter.
16. The apparatus of claim 9, further comprising: a pump disposed
between the first filter and the second filter in a perfusate flow
path.
17. The apparatus of claim 9, wherein the first filter is sized to
prevent particles from blocking the first filter.
18. The apparatus of claim 9, further comprising: a pump; a
pressure sensor; an oxygenator; and a combo bubble trap.
19. The apparatus of claim 18, wherein the perfusate flow path
comprises a conduit that begins at the first filter and then
passes, in order, the pump, the pressure sensor, the second filter,
the oxygenator and the bubble trap before returning to the organ
container.
20. The apparatus of claim 9, wherein a diameter of the first
filter is between about 4 and 5 inches.
21. The apparatus of claim 14, wherein the first filter has an area
that is at least two times a cross-sectional area of the fluid
conduit.
22. The apparatus of claim 9, wherein the organ container comprises
an extended portion at the bottom of the organ container and
forming a secondary chamber between the first filter and a fluid
conduit.
23. The apparatus of claim 9, wherein the first filter is a screen
filter.
24. The apparatus of claim 9, wherein the second filter is a
cartridge or capsule filter.
25. The apparatus of claim 9, wherein a filter surface area of the
second filter is about 0.5 ft.sup.2.
26. The apparatus of claim 9, wherein the first filter has an
average mesh opening size of 100 to 1,000 microns.
27. A sterilized disposable kit, comprising: sterilized packaging
containing: a sterilized organ container configured to contain an
organ, the sterilized organ container including a sterilized first
filter configured to filter perfusate and integrated with an
exterior portion of the organ container.
28. The kit of claim 27, further comprising a sterilized second
filter disposed inside of the sterilized packaging.
29. The kit of claim 28, wherein the first filter is coarser than
the second filter.
30. The kit of claim 29, further comprising a fluid conduit, an
oxygenator, and a bubble trap, contained in the sterilized
packaging.
31. A method of perfusing an organ, comprising: (a) perfusing an
organ with a perfusate in an organ container; (b) filtering the
perfusate after it leaves the organ with a first filter integrated
with an exterior portion of the organ container; (c) filtering the
perfusate fluid with a second filter downstream of the first
filter; and (d) returning the perfusate to repeat steps (a) through
(c).
32. The method of claim 31, wherein the first filter is a coarser
filter than the second filter.
33. A method of manufacturing an organ container, comprising:
providing a filter material; securing the filter material in an
exterior portion of the organ container; and forming on the organ
container a connection configured to connect with an organ
perfusion apparatus.
34. The method of claim 33, wherein the organ container is formed
by injection molding.
35. The method of claim 34, wherein the organ container is
injection molded around the filter material.
Description
BACKGROUND
[0001] Related technical fields include organ and tissue perfusion
apparatuses that are capable of sustaining and/or restoring
viability of organs or tissue and preserving organs or tissue for
storage and/or transport, and more particularly that include
filters for filtering perfusate.
[0002] It is known to perfuse an organ or tissue with a perfusate
in order to maintain and sustain the organ or tissue ex vivo. The
perfusate usually contains additives and/or nutrients to help
maintain the organ or tissue. The perfusate enters into the organ,
for example through a blood vessel, and exits the organ through,
for example, another blood vessel or other routes. As a result, the
perfusate that has passed through the organ or tissue may contain
organic matter dispelled from the organ or tissue.
[0003] Known perfusion machines may have one or more filters. See,
for example, U.S. Pat. No. 7,824,848 to Owen et al.
SUMMARY
[0004] In conventional perfusion machines, perfusate is often
recirculated and may lead to clogging and contamination of filters.
Additionally, a problem with integration filters (filters that
stack two filtering mediums directly next to and/or in contact with
one another) is that they limit the amount of effective filtration
area of the finer filter. Accordingly, the filters may frequently
require replacement and also sterilization, along with other parts
of the organ perfusion system that come into contact with the
perfusate, for their continued function. To replace or resterilize
a filter, the sterile environment around the organ or tissue is
compromised because the filter is removed from the fluid circuit.
Removal of the filter from the fluid circuit causes a break in the
fluid circuit and exposes the perfusate in the fluid circuit. As a
result, sterility is compromised and the organ or tissue may no
longer be free from contamination. This could result in loss of or
damage to the organ or tissue.
[0005] For example, a relatively large piece of tissue may break
free from an organ during perfusion. The piece of tissue may be
caught in a filter and/or cover the entire filter, if the piece of
tissue is large enough, blocking the fluid circuit and thereby
stopping perfusion of the organ. In this scenario, the tubing
and/or organ container must be opened to remove the clogged filter
and either replace the filter or clean the filter such that
perfusate may continue to move in the fluid circuit. However, when
the tubing and/or organ container is opened, sterility is
compromised because the perfusate and/or the organ itself are
exposed to contamination.
[0006] A need exists for a perfusion machine that has replaceable
or single-use parts, including filter(s), which come into contact
with the perfusate fluid. Additionally, a need exists for
disposable parts that are easy to replace and that may be easily
integrated in the perfusion machine. For example, a need exists for
a perfusion machine that has a replaceable organ or tissue
container, filter(s), and tubing. It is preferable that the
replaceable or single-use parts be sterilized and placed into a
saleable package prior to use. Once the container, filter(s),
and/or tubing are ready for use, it is desirable that the kit may
be opened and the container, filter(s), and tubing may be used with
the perfusion machine. Accordingly, there is a need for a kit that
allows for the container, filter(s), and tubing to be swapped in
and out of a perfusion machine with ease and without worry of
comprising the sterility of the perfusion machine. Once an organ or
tissue is removed from the perfusion machine, the container,
filter(s), and/or tubing may be discarded and replaced without
being used for another organ or tissue. Additionally, there is a
need for a filter system that has an extended lifetime such that
the filters do not need to be replaced during perfusion, transport,
and/or storage of an organ or tissue inside the perfusion
machine.
[0007] Advantages of various embodiments of the present invention
include an organ or tissue container and a filter that are
integrated together to provide a replaceable unit that improves
ease of manufacturing. Additionally, the filter system and
container improve the life of the filter system because the filter
system is designed to prevent clogging from tissue from the organ
or tissue. The container and filter may be sold together as a
single unit. The container and filter allow for use together with a
single organ or tissue, or multiple organs or tissues, and may
preferably be discarded before another organ or tissue is perfused
in a perfusion machine. For ease of reference herein, the term
"organ" will mean "organ and/or tissue" unless otherwise
indicated.
[0008] According to exemplary implementations, a filter for
filtering perfusate integrated with an exterior portion of an organ
container is provided. The filter may be molded monolithically with
an exterior portion of the organ container. The filter may
alternatively be fastened to an exterior portion of the organ
container. For example, the filter may be fitted into an aperture
of the organ container. The filter may be disposed within the
exterior portion of the organ container. The exterior portion of
the container may be located on a bottom or side of the organ
container. The exterior portion may be a wall of the organ
container. As used herein, the term "wall" includes bottom and/or
side walls unless otherwise indicated.
[0009] In exemplary implementations, an apparatus for perfusing an
organ includes an organ container configured to contain an organ, a
first filter integrated with an exterior portion of the organ
container, and a second filter. The second filter may be disposed
downstream from the first filter. The exterior portion of the organ
container may be a side and/or bottom wall of the organ container.
The first filter may preferably be a coarser filter than the second
filter. The second filter may be disposed within a fluid conduit
downstream of the first filter in a perfusate flow path. Further,
the fluid conduit may be connected to the first filter. A pump may
be disposed between the first filter and the second filter in the
perfusate flow path. The first filter may be configured to block
particles that would clog the fluid conduit of the perfusate flow
path.
[0010] In exemplary implementations, the apparatus may include a
fluid conduit, a pump, a pressure sensor, an oxygenator membrane,
and a combination bubble trap--pressure accumulator to remove
bubbles and reduce pulsatility from the pump. The perfusate flow
path may, for example, begin at the first filter and then pass, in
order, the fluid conduit, the pump, the pressure sensor, the second
filter, the oxygenator membrane and the bubble trap before
returning to the organ container. Moreover, an organ may be
disposed in a perfusate bath inside the organ container. The organ
container may be configured to have an exterior surface in contact
with a cooling medium. The organ perfusion apparatus may have an
organ supporting surface that is one of a plurality of walls of the
organ container. The first filter may be integrated with the organ
supporting surface. The apparatus may further comprise a cradle
disposed within the organ container and having an organ supporting
surface configured to support an organ. The cradle may be
configured to hold an amount of perfusate to form a perfusate bath
around an organ placed inside the cradle.
[0011] Implementations may include a sterilized disposable kit
comprising an organ container configured to contain an organ and a
first filter, configured to filter perfusate, integrated with an
exterior portion of the organ container. The kit may also have a
second filter. The first filter in the kit may be coarser than the
second filter. Additionally, the kit may have an organ supporting
surface. The organ supporting surface may or may not be integrated
with or part of the exterior portion of the organ container.
[0012] In embodiments, a method for perfusing an organ includes
filtering perfusate after it leaves the organ with a first filter
integrated with an exterior portion of an organ container and
filtering the perfusate with a second filter downstream of the
first filter. The method for perfusing the organ may utilize a
filter for filtering perfusate that is integrated with an exterior
portion of an organ container. The filter may, for example, be
gravity fed or pump fed. A step of filtering the perfusate fluid
with the first filter integrated with the exterior portion of an
organ container may be performed before filtering the perfusate
fluid with the second filter.
[0013] A method of manufacturing an organ container may include
forming a filter in an exterior portion of an organ container. The
step of forming may include insert molding the filter in an
exterior portion of the organ container, which organ container may
be injection molded. The method of manufacturing an organ container
may include providing a filter material, securing the filter
material in an exterior portion of the organ container, and forming
a connection on the organ container. The connection may be
configured to connect with an organ perfusion apparatus.
[0014] Other advantages, benefits and features of the present
invention will become apparent to those skilled in the art upon
reading the detailed description of embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a schematic diagram of an exemplary organ
perfusion apparatus.
[0016] FIG. 2 is a perspective view of an assembly of disposable
components of an organ perfusion apparatus.
[0017] FIG. 3 is a view of a filter integrated with a basin of an
organ perfusion apparatus.
[0018] FIG. 4 is a side view of a basin of an organ perfusion
apparatus.
[0019] FIG. 5 is a cross-section of a perspective view of a cradle
and basin of an organ perfusion apparatus.
DETAILED DESCRIPTION OF EMBODIMENTS
[0020] Referring to the accompanying drawings, exemplary
embodiments of a perfusion apparatus, filters, and methods
according to the invention will be described.
[0021] The following description refers to a perfusion apparatus,
which may be a transport apparatus, diagnostic apparatus, and/or
storage apparatus for an organ or tissue. Although the exemplary
systems and methods according to this disclosure may be applicable
to specific applications, the depictions and/or descriptions
included in this disclosure are not intended to be limited to any
specific application. Any perfusion apparatus that may
advantageously include an organ or other biological samples as
described in an exemplary manner in this disclosure is
contemplated.
[0022] A filtering apparatus for filtering perfusate may include an
organ container configured to connect with an organ perfusion
apparatus and having a filter element integrated with an exterior
portion of the organ container. An apparatus for perfusing an organ
may include an organ container configured to contain an organ, a
recirculating perfusate flow path, a first filter integrated with
an exterior portion of the organ container in the perfusate flow
path, and a second filter in the perfusate flow path. The apparatus
may further include a pump, a pressure sensor, an oxygenator, and a
bubble trap.
[0023] FIG. 1 is a schematic diagram of a perfusion apparatus 10
for an organ 20. The organ 20 may preferably be a liver but may be
any human or animal, natural or engineered, healthy, injured or
diseased organ or tissue. The apparatus includes a basin 30 in
which the organ may be placed. As shown in FIG. 2, the basin may
have a lid 38 that covers the basin so as to completely enclose the
organ 20. The organ 20 may be disposed in a perfusate bath inside
the basin 30. In such a configuration, the basin 30 may include an
organ supporting surface configured to hold the organ 20 when the
organ is in the perfusate bath. Referring back to FIG. 1, the basin
30 may hold a cradle 60 (see FIG. 5), which preferably includes a
surface on which the organ 20 is disposed when the organ 20 is in
the apparatus 10. The basin 30 may include a first filter 32 (see
FIG. 3) that can function as a gross particulate filter. The basin
30 and/or the cradle 60 are preferably configured to allow a
perfusate bath to form around the organ 20.
[0024] Preferably, the organ 20 may be disposed in a perfusate bath
inside of the cradle 60. The cradle 60 may be configured to hold an
amount of perfusate to form a perfusate bath around the organ 20
placed inside the cradle 60. The perfusate bath may partially
immerse the organ 20 or may fully immerse the organ 60. The cradle
60 and basin 30 may be designed such that overflow from the
perfusate bath in the cradle 60 is received inside of the basin 30,
which may form a secondary bath.
[0025] The perfusate bath preferably collects in the basin 30
before it passes through the first filter 32. The perfusate flows
through the first filter 32, such as by gravity or by way of pump
80. When the perfusate is gravity fed through the first filter 32,
the first filter 32 may be typically located at or near a bottom
portion of the basin 30 such that gravity pushes the perfusate
through the first filter 32. However, the pump 80 may apply a
pressure or negative pressure (suction) to the perfusate such that
the perfusate passes through the first filter 32. The pump 30 may
be used in configurations in which the first filter 32 is not
located at or near a bottom portion of the basin 30.
[0026] The basin 30 may also include a temperature sensor 40
located in or near the cradle 60. The basin may include multiple
temperature sensors 40, which may provide redundancy in the event
of a failure and/or may provide temperature measurement at multiple
locations. Preferably, the temperature sensor 40 is an infrared
temperature sensor. The temperature sensor 40 is preferably
disposed as close as practical to the organ 20 when the organ 20 is
disposed in the cradle 60 in order to improve the usefulness and
accuracy of the temperature sensor 40, which preferably provides a
temperature measurement of the perfusate that may be correlated to
a temperature of the organ 20. Alternatively or additionally, the
temperature sensor 40 may be used to directly measure the
temperature of the organ 20.
[0027] The basin 30 is preferably disposed within an insulating
cooling container 50 that may contain cold materials such as ice,
ice water, brine or the like, or may be cooled by a cooling device
such as an electrical or gas powered cooling device. Cooling
container 50 may be permanently or removably attached to, or an
integral, monolithic part of, apparatus 10. Thus, in use as shown
in the Figures, the organ 20 is disposed within the cradle 60,
which is disposed within the basin 30, which is disposed within the
cooling container 50. Preferably, each of the basin 30, cradle 60
and cooling container 50 is configured, or keyed, to fit within its
corresponding mating component in a single orientation. The
configuration of the cooling container 50, basin 30 and cradle 60
may provide a configuration that provides cooling for the organ 20
without the contents of cooling container 50 contacting the organ
20 or the cradle 60. The basin 30 may be configured to have an
exterior surface in contact with a surface of the cooling container
50, which provides thermal communication with a cooling medium in
the cooling container 50. Although the cooling container 50 is
described herein as containing ice, any suitable cooling medium can
be used. Ice may be preferable due to the ease with which ice can
be procured, but one of ordinary skill would understand that any
suitable cooling medium, which could be an active cooling medium
(such as a thermo electric cooler or a refrigerant loop) or a
passive cooling medium similar to ice or ice water, or a
combination thereof, may be utilized. The amount of ice, or other
cooling medium, that can be placed within the cooling container 50
may, for example, be determined based upon the maximum time that
cooling is likely to be provided while the organ 20 will be in the
apparatus 10.
[0028] The cradle 60 may include components configured to securely
restrain the organ 20 in place. Such components may, for example,
include user selectable netting that is fastened to the cradle 60.
The cradle 60 may also have an organ supporting surface configured
to support the organ 20. The organ supporting surface may be a
surface that is shaped to receive the organ 20 in a shape that is
complementary to the general shape of the organ in a preferred
orientation of the organ.
[0029] FIG. 2 is a perspective view of an exemplary arrangement of
disposable components 190 of the organ perfusion apparatus 10. The
disposable components 190 preferably include the basin 30, which
may be configured to contain an organ 20. The first filter 32 may
be integrated with an exterior portion of the basin 30 and a second
filter 34 may also be provided. The second filter 34 may be
disposed downstream from the first filter in a fluid conduit 72
that defines a first flow path 70. The fluid conduit 72 may be
connected to the first filter 32 and/or may be connected to an
exterior or interior portion of the basin 30. Preferably, all
components of the apparatus 10 that come into contact with
perfusate and/or the organ 20 are disposable and/or easily
replaced, most preferably as a single unit with most or all parts
connected together as shown in FIG. 2. The components of the organ
perfusion apparatus that are not disposable may be reused
indefinitely.
[0030] The disposable components 190 of the organ perfusion
apparatus 10 may preferably be sterilized prior to use. Some or all
of the disposable components 190 may be provided in the form of a
sterilized disposable kit. For example, the sterilized disposable
kit may comprise the basin 30, the first filter 32, and the second
filter 34. The sterilized disposable kit may further include the
organ supporting surface, and/or other parts of the disposable
components 190 such as the conduits, oxygenator membrane, and
bubble trap. The disposable components 190 are preferably
manufactured in a clean environment and sterilized as a completed
saleable unit with seal packing functioning as a sterile barrier.
The packing protects the sterilized, disposable components from
being contaminated. The disposable components 190 may be sterilized
while in the package. Once the components 190 are ready for use,
the package may be opened and the components 190 may be used with
the organ perfusion apparatus 10. This allows the sterilized,
disposable components to be "single-use" components. That is, once
an organ 20 is removed from the basin 70, the sterilized,
disposable components 190 may be discarded and replaced without
being used for another organ. Accordingly, the organ perfusion
apparatus 10 maintains strict sterility and prevents contamination
of an organ 20 being perfused, transported, and/or stored in the
organ perfusion apparatus 10.
[0031] Such a kit may include packaging such as plastic or shrink
wrap packaging containing some or all of the components that come
into contact with an organ 20 and/or perfusate. In embodiments, the
tubing, filter, oxygenator and bubble trap are packaged together,
and the cradle and basin are packaged individually or together, and
optionally together with the tubing, filter, oxygenator and bubble
trap in a manner preconfigured to be placed into a flow path
arrangement of fixed-location parts in apparatus 10, for example as
shown in FIG. 2.
[0032] After passing through the filter 32, the perfusate flows
along a first flow path 70 that includes a suitable fluid conduit
72, such as flexible or rigid tubing, passing a pump 80, a pressure
sensor 90, a second filter 34, an oxygenator 100, and a bubble trap
110, each of which is discussed below. The second filter 34 may be
gravity fed or pump fed similar to the first filter 32.
[0033] The first filter 32 is preferably a coarser filter than the
second filter 34 such that the first filter 32 preferably blocks
relatively larger particles and the second filter 34 preferably
blocks relatively smaller particles. Accordingly, the mesh,
membrane, or other structure or material used for the first and
second filters 32, 34 may be different and finer in the second
filter 34 than in the first filter 32. In some embodiments, the
first filter 32 can be configured to filter certain types of organ
matter while the second filter 34 is configured to filter different
types of organ matter. The first filter 32 may be a relatively
large filter compared to the second filter 34. The first filter 32
preferably provides filtration that is fine enough to at least
block particles that would clog the fluid conduit 72 of the
perfusate flow path 70 (e.g., particles that are larger than an
interior diameter of the flow path) while the first filter 32
itself does not become clogged. Finer filtration may also be
provided in the first filter.
[0034] For example, the first filter 32 may be a screen filter and
the second filter 34 may be a cartridge or capsule filter. The
first filter 32 may preferably be made of a monofilament fabric and
may be made of a polymer, metallic, or composite material. The
first filter 32 may be any shape, including cylindrical or pleated,
or a non-woven depth filter, preferably round and flat, or insert
molded or potted, and have a diameter between 0.1 to 20 inches,
preferably between 1 to 10 inches, and most preferably between 4 to
5 inches. The first filter may have an average opening size of 10
to 10,000 microns and preferably 100 to 3,000 microns. Such a
coarse filter may be provided to prevent large particles, which may
include byproducts of the organ or of the organ being removed from
the donor, from entering and clogging fluid paths of the apparatus
10.
[0035] The apparatus 10 may include upstream tubing and peristaltic
pump segment tubing that may be any diameter. For example, upstream
tubing that is located between the first filter 32 and the bubble
trap 110 may be nominally between 0.03 to 1 inch inner diameter,
preferably 0.1 to 0.5 inches inner diameter, and more preferably
between 0.35 to 0.4 inches inner diameter. For example, the
upstream tubing may be about 0.375 inches in inner diameter with a
cross sectional area of 0.110 square inch. The upstream tubing is
preferably clear, with a controlled wall thickness and controlled
stiffness (durometer) preferably about Shore-A-40. This tubing may
preferably be PVC but can be made of any TPE or thermoplastic,
medical grade material. For example, peristaltic pump segment
tubing may be nominally between 0.01 to 1 inch inner diameter,
preferably 0.1 to 0.5 inches inner diameter, and more preferably
0.3 to 0.325 inches inner diameter. For example, the peristaltic
pump segment tubing may be about 0.312 in inner diameter and is a
thermoplastic set such as silicone but can be any other plastic
material such as PVC or a TPE. This material is also a controlled
durometer and wall thickness. With a 4.5 inch diameter filter
having a cross sectional surface area of 15.9 square inches, the
ratio of cross sectional areas between the first filter 32 and the
upstream tubing is 144:1. However, the ratio of cross sectional
area between the first filter 32 and the upstream tubing may be any
ratio such that the first filter 32 prevents pieces of tissue from
clogging the upstream tubing.
[0036] The first filter 32 may be an integral part of the basin 30
or the first filter may be disposed elsewhere in the first flow
path 70 downstream of the basin 30. The first filter 32 may also be
a separate component disposed on, inside or outside of the basin 30
or disposed within the fluid conduit 72.
[0037] The second filter 34 may be any filter capable of filtering
perfusate. For example, the second filter 34 may be a compact,
pleated filter element that is integrally sealed into a housing.
The housing may be, for example, polypropylene or any other
suitable polymer or composite material. The filter element and
housing may be thermally bonded into a self-contained unit to form
a cartridge and capsule. The second filter 34 may preferably have a
filter surface area of 0.25 ft.sup.2 to 0.75.sup.2 and more
preferably about 0.45 ft.sup.2 to 0.55 ft.sup.2, such as 0.5
ft.sup.2.
[0038] The first filter 32 may be made integral with the basin 30
in numerous ways. For example, the first filter 32 may be molded
into or as part of a molded basin 30. Examples of molding
techniques include injection molding, cast molding, compression
molding, and other molding techniques appreciated by one skilled in
the art. The basin 30 may be molded around the first filter 32 such
that the basin 30 is integrated with the first filter 32 around a
perimeter edge or circumference of the first filter 32. The first
filter 32 may be placed in a mold cavity or die and subsequently
have a resin, polymer, or metallic material formed around the first
filter 32 such that the first filter 32 is connected to the basin
30. The first filter 32 may alternatively be inserted and held in
place with a separate, molded, retaining feature such as a simple
ring or snap ring. The first filter 32 may also be fastened to the
basin 30 in other ways. For example, the first filter 32 may be
fastened by threaded (such as screws, nuts and bolts) or
non-threaded fasteners, adhesives, hook-and-loop fasteners, or
other fastening techniques appreciated by one skilled in the art.
Moreover, the first filter 32 may be fitted into an aperture of the
basin 30. The first filter 32 may be dimensioned such that the
aperture within the basin is slightly larger, exactly the same
size, or slightly smaller than the dimensions of the first filter
32. The first filter 32 may then be pushed and/or placed inside the
aperture with enough force to fit the first filter 32 securely
within the basin 30. The first filter 32 may, for example, be
press-fitted, snap-fitted, or screwed into the aperture of the
basin 30. Additional ways of securing the first filter 32 into the
basin may employ hooks, tabs, covers, and/or other securing devices
appreciated by those skilled in the art. The first filter 32 may
also be disposed inside of an exterior portion of the basin 30. For
example, the first filter 32 may be disposed inside a wall of the
basin 30 such that the outer circumference or periphery of the
first filter 32 is between two surfaces of the wall (as shown in
FIG. 3).
[0039] The exterior portion of the basin 30 may be a wall of the
basin or may be another structure attached to the basin 30 or a
part of the basin 30. For example, the exterior portion may be a
structure configured specifically to hold the first filter 32. The
first filter 32 may be detachable from the basin 30 or may be
permanently integrated with the basin 30. The exterior portion may
also be other structure that has an exterior surface facing an
outside of the basin 30. The exterior portion of the basin 30 may
be located on a bottom of the basin 30. The exterior portion of the
basin 30 may be the bottommost structure of the basin 30 and/or it
may be an intermediate structure of the basin 30. The exterior
portion may be a wall of the basin 30. Additionally, as discussed
above, the basin 30 may have an organ supporting surface upon which
the organ 20 is placed and this organ supporting surface may be an
inner surface of the basin with which the first filter is
integrated.
[0040] FIG. 3 shows an example of the first filter 32 integrated
with an exterior portion of the basin 30. FIG. 4 shows an extended
portion 42 of the basin 30. As illustrated, the extended portion 42
generally has a cylindrical or other shape and is located on a
bottom of the basin 30. The extended portion 42 may be in the shape
of a cup on the bottom of the basin 30. The extended portion 42 may
have an end surface that is angled (e.g., substantially
perpendicular) relative to the length of the extended portion 42.
The end surface may be partially or completely angled such that all
or part of the end surface of the extended portion 42 is not
perpendicular to a side wall of the extended portion 42. One side
of the extended portion 42 may be open and the other end of the
extended portion 42 may be closed or sealed. The extended portion
42 may be located in a substantially center area or at a side of a
bottom of the basin 30. A width or diameter of the extended portion
42 may preferably be larger than the height or length of the
extended portion 42. The extended portion 42 may be integral with
the basin 30 and may be molded monolithically with or attached to
the basin. The extended portion 42 may define a secondary chamber
between the first filter 32 and the fluid conduit 72. Various
manufacturing techniques may be used to form the extended portion
42 of the basin 30. The extended portion 42 preferably has a port
44 that is connected to the fluid conduit 72 (not shown in FIG. 4).
This configuration and structure of the first filter 32 and basin
30 may allow for organ matter that is larger than a diameter of the
fluid conduit 72 to be filtered out by the first filter 32 without
clogging the first filter 32 due to the diameter of the first
filter being relatively larger than the diameter of the fluid
conduit 72.
[0041] The first flow path 70 may also include a pump 80. The pump
80 may be any pump that is suitable in connection with perfusing of
organs. Examples of suitable pumps may include hand operated pumps,
centrifugal pumps and roller pumps. If a roller pump is included,
the roller pump may include a single channel or flow path (where
only one tube is compressed by the rollers) or the roller pump may
include multiple channels or flow paths (where multiple tubes are
compressed by the rollers). If multiple, parallel channels or flow
paths are included, the rollers may preferably be disposed out of
phase or offset so that pulses created by the rollers are out of
phase, which may result in a fluid flow out of the roller pump that
is relatively less pulsatile than would be the case with a single
roller. Such a multiple channel roller pump may achieve a constant
flow rate or a minimally pulsatile flow rate, which may be
advantageous depending on the other components in the flow path
and/or the type of organ being perfused. The pump 80 is shown as
being disposed between the first filter 32 and the second filter
34, but may be disposed anywhere along the flow path. For example,
the pump 80 may be disposed downstream of both the first filter 32
and the second filter 34.
[0042] The flow path 70 may include a pressure sensor 90. The
pressure sensor 90 may preferably be disposed after the outlet of
the pump 80 in order to be used to monitor and/or control the
pressure produced at the outlet of the pump by way of a suitable
controller, such as a computer, microprocessor, central processing
unit, and/or workstation. The pressure sensor 90 may provide
continuous or periodic monitoring of pressure.
[0043] The flow path 70 may include an oxygenator 100 such as an
oxygenator membrane or body to provide oxygenation to the
perfusate. Oxygen may be provided to the oxygenator 100 by any
suitable means. Suitable oxygen sources may provide pure oxygen or
mixed gases such as air. The gas may be compressed, such as in a
high-pressure cylinder, liquefied as would be stored in a dewar, or
drawn from the surrounding atmosphere. Preferably, the oxygen may
be provided by way of an oxygen generator, which may be separate
from the apparatus 10 or integral to the apparatus 10. Oxygen may
be generated through any suitable means, some examples of which
include through pressure swing adsorption using a molecular sieve,
through a ceramic oxygen generator (a solid state oxygen pump) or
through decomposition of water.
[0044] The flow path 70 may include a bubble trap 110. The bubble
trap 110 preferably separates gas bubbles that may be entrained in
the perfusate flow and prevents such bubbles from continuing
downstream and entering the organ 20. The bubble trap 110 may also
function as an accumulator that reduces or eliminates pulsatility
of the perfusate flow. The bubble trap 110 may include a volume of
gas, initially or through the accumulation of bubbles, such that
pressure fluctuations in the perfusate are dampened or
eliminated.
[0045] The bubble trap 110 may include a vent that allows purging
of gas during start up or a purging process. The vent may be
connected to or part of purge flow path 140 (which is discussed in
detail below). The vent is preferably open during a start up
process so that any air or other gas may be purged from the
perfusate path 70. Once the gas is purged from the perfusate path
70, the vent may preferably be closed. The vent may be closed
manually or may be closed automatically by way of a suitable
controller.
[0046] The bubble trap 110 may include a level sensor 112 to ensure
that at least a predetermined air space above the fluid level is
maintained. The level sensor 112 may, for example, include a float
that includes a magnet that interacts with Hall Effect sensors in
the transporter. A level sensor 112 may optionally be used during
the purging process to determine when the purging is complete
and/or may be used to determine when the purging process needs to
be repeated, which may happen after bubbles have been trapped in
the bubble trap 110. Also, through use of the level sensor 112 and
the vent, the accumulator function of the bubble trap can be tuned
to account for differing amplitudes and frequencies of pulsatility
in the perfusate flow.
[0047] The bubble trap 110 may have any number of outlets, as
needed for a given application of the perfusion apparatus. In FIG.
1, three outlets are shown connected to three different flow paths,
which may be particularly suited for perfusion of a liver. When
perfusing a liver, the three paths preferably include portal flow
path 120 connected to the portal vein of a liver, hepatic flow path
130 connected to the hepatic artery of a liver, and bypass flow
path 140 that provides a return path to the basin 30.
[0048] As shown in FIG. 1, the portal flow path 120 and hepatic
flow path 130 may optionally include similar or different
components such as valves 122, 132; bubble sensors 124, 134; flow
sensors 126, 136; flow control clamps 127, 137; and pressure
sensors 128, 138. Each similar component may function in a similar
manner, and such pairs of components may optionally be structurally
and/or functionally identical to reduce manufacturing costs.
[0049] Valves 122, 132 may be pinch valves that function to squeeze
tubing and reduce or shut off flow, but any suitable valve may be
used. Pinch valves may be advantageous because in normal usage they
do not come into contact with the perfusate and therefore do not
require replacement and/or cleaning after use.
[0050] Preferably, the bubble sensors 124, 134 are ultrasonic
sensors disposed around tubing, although any suitable sensor may be
used. Similar to pinch valves, ultrasonic sensors may be
advantageous because in normal usage they do not come into contact
with the perfusate and therefore do not require replacement and/or
cleaning after use. Instead, ultrasonic sensors can be disposed in
contact with, adjacent to or around an external surface of tubing
in order to sense bubbles.
[0051] Flow control clamps 127, 137 are optional and may be used to
fine-tune the flow rate in one or both of portal flow path 120 and
hepatic flow path 130. Preferably, the organ provides
self-regulation to control an amount of flow that exits the bubble
trap 110 and is divided between the portal flow path 120 and the
hepatic flow path 130. In such self regulated flow, pressure
sensors 128, 138 provide overpressure monitoring. In the event that
pressure delivered to the organ in either or both of the portal
flow path 120 or the hepatic flow path 130 exceeds a predetermined
threshold, the apparatus 10 can automatically stop and/or reduce
the flow rate provided by the pump 80 to prevent damage to the
organ. In addition or alternatively, the pressure sensors 128, 138
may be used to generate warning signals to the user and/or to an
appropriate controller as pressures approach the predetermined
threshold.
[0052] After exiting one or both of the portal flow path 120 and
hepatic flow path 130, pefusate flows through the organ and returns
to the basin 30 to form an organ bath.
[0053] Bypass flow path 140 may include a valve 142, and/or sensors
such as oxygen sensor 144 and pH sensor 146. Preferably, the valve
142 is a pinch valve and may be of similar configuration to valves
122 and 132, but any suitable valve may be used. The oxygen sensor
144 and the pH sensor 146 may be used to determine the state of the
perfusate. Preferably, the bypass flow path 140 is only used during
a purging or priming process, although it may also be used during
perfusion, preferably continuously, to monitor perfusate properties
in real time.
[0054] The organ perfusion apparatus 10 may also include an
accelerometer 150. Preferably the accelerometer 150 is a three-axis
accelerometer, although multiple single axis accelerometers may be
used to the same effect. The accelerometer 150 may be used to
continuously or periodically monitor and/or record the state of the
apparatus 10. Monitoring may include monitoring for excessive
shocks as well as attitude (e.g., pitch and yaw) of the apparatus
10. By implementing such monitoring, misuse or potentially
inappropriate conditions of the apparatus 10 can be detected and
recorded.
[0055] The apparatus 10 may include storage compartments for items
other than the organ 20. For example, the apparatus 10 may include
a document compartment 160 to store documents and/or charts related
to the organ 20. Also, the apparatus 10 may include one or more
sample compartment 170. The sample compartment 170 may be
configured, for example, to store fluid and/or tissue samples. The
sample compartment 170 may be advantageously disposed near the
cooling container 50 to provide cooling, which may be similar or
equivalent to the cooling provided for the organ 20.
[0056] The apparatus 10 may include one or more tamper evident
closures 180. A tamper evident closure 180 may be used to alert a
user that the apparatus 10 has been opened at an unauthorized time
and/or location and/or by an unauthorized person. Evidence of
tampering may alert the user to perform additional testing,
screening, or the like before using the organ 20 and/or the
apparatus 10.
[0057] What has been described and illustrated herein are preferred
embodiments of the invention along with some variations. The
descriptions and figures used herein are set forth by way of
illustration only and are not meant as limitations. Those skilled
in the art will recognize that many variations are possible within
the spirit and scope of the invention.
* * * * *