US20140017665A1 - Organ transporter with oxygen generation - Google Patents

Abstract

An apparatus for perfusing an organ or tissue includes a perfusion circuit for perfusing the organ or tissue; an oxygenator for oxygenating perfusate that circulates through the perfusion circuit; and an oxygen supply device such as an oxygen concentrator or an oxygen generator configured to supply oxygen to the oxygenator. A method of perfusing an organ or tissue includes producing oxygen from a device such as an oxygen concentrator and an oxygen generator; supplying the produced oxygen, preferably as the oxygen is produced, to a perfusate to oxygenate the perfusate; and perfusing the organ or tissue with the oxygenated perfusate. The produced oxygen preferably has a concentration greater than the oxygen concentration in air.

Description

BACKGROUND
• Related technical fields include organ or tissue perfusion apparatuses that are capable of sustaining and/or restoring viability of organs or tissue and preserving organs or tissues for diagnosis, treatment, storage and/or transport. For convenience, the term “organ” as used herein should be understood to mean organ and/or tissue unless otherwise specified.
• It is an objective of organ perfusion apparatus to mimic the conditions of the human body such that the organ remains viable before being used for research, diagnosis, treatment or transplantation. Many times the organ needs to be stored and/or transported between facilities. A goal of sustaining and restoring organs during perfusion is to reduce ischemia and reperfusion injury. The increase in storage periods in a normal or near normal functioning state also provides certain advantages, for example, organs can be transported greater distances and there is increased time for testing, treatment and evaluation of the organs.
• In maintaining organs in near ideal conditions and physiological states it is known to provide oxygenated perfusate to an organ. U.S. Pat. No. 6,673,594 discloses, for example, a configuration in which an organ is provided with perfusate that is oxygenated by way of gaseous oxygen provided to an oxygenating membrane, which is hereby incorporated by reference in its entirety and in which the present invention could be used.
SUMMARY
• When an organ or tissue has been harvested, it may be beneficial to perfuse the organ with oxygenated perfusate, which may preferably be a liquid perfusate. Although perfusate can be pre-oxygenated, the perfusate may require further oxygen during the perfusion process as the organ uses oxygen from the perfusate. Accordingly, it is desirable to provide a perfusion apparatus that can supply oxygen to the perfusate so that the perfusate can be oxygenated during perfusion. However, pre-stored oxygen has drawbacks. For example, both pressurized and liquefied oxygen have serious flammability risks that can require considerable design efforts to provide adequate safety. Further, considerable logistical efforts are required to provide and maintain an adequate supply of compressed or liquefied oxygen to the point of use of a perfusion apparatus. Compressed or liquefied oxygen requires heavy containers that must be switched out when the container is empty. Extended oxygenation of perfusate may require a large container or plural small containers. Additionally, switching containers provides an opportunity to contaminate the apparatus and/or jeopardize sterility of the apparatus. Thus, disclosed herein is a perfusion apparatus that provides oxygen produced in real time to oxygenate perfusate. An organ perfusion apparatus that is able to produce oxygen to oxygenate the perfusate avoids hazards of high pressure or liquefied oxygen and also avoids logistical difficulties associated with pre-stored oxygen.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a schematic diagram of an organ perfusion apparatus.
DETAILED DESCRIPTION OF EMBODIMENTS
• According to exemplary implementations, an apparatus is provided for producing oxygen, preferably in real time, using oxygen to oxygenate a perfusate, and perfusing the organ with the oxygenated perfusate. The apparatus may include a perfusion circuit for perfusing the organ or tissue, an oxygenator for oxygenating perfusate that recirculates through the perfusion circuit; and an oxygen supply device configured to supply oxygen to the oxygenator. Preferably, the oxygen supply device is at least one member selected from the group consisting of an oxygen concentrator and an oxygen generator. As discussed herein, the term oxygen concentrator refers to a device that uses a source that includes molecular oxygen, and increases the concentration of the oxygen relative to the source; and the term oxygen generator refers to a device that uses a source other than molecular oxygen to produce oxygen from that source.
• One example of an oxygen generator is a device that generates oxygen by decomposing water. Water may be decomposed by applying an electrical charge to water to break the water molecules into hydrogen and oxygen molecules. Another example of an oxygen generator (which also can be considered to decompose water) is an electrochemical device that utilizes a proton exchange membrane to generate oxygen from water such as is disclosed in U.S. Patent Application Publication No. 2010/0330547 to Tempelman et al., which is hereby incorporated by reference in its entirety. One example of an oxygen concentrator is a device that concentrates oxygen by way of pressure swing adsorption. One example of pressure swing adsorption involves passing pressurized air through an adsorbent material such as zeolite or a similar molecular sieve, which selectively adsorbs nitrogen, while allowing oxygen and argon to pass through the adsorbent material, resulting in a product with increased oxygen concentration. As another alternative, an oxygen concentrator may supply oxygen by way of a solid state oxygen pump. As used herein, a solid state oxygen pump refers to a device that passes only oxygen through a ceramic or similar material by applying an electric potential which disassociates oxygen molecules into two oxygen ions, drives the ions across the ceramic, and allows the ions to re-associate as an oxygen molecule. Thus, oxygen can be extracted from air, increasing oxygen concentration. This process is essentially driving a ceramic oxygen sensor in reverse.
• Oxygen concentrators such as pressure swing adsorption devices and solid state oxygen pumps may use air as an input; the air may be stored, compressed prior to use, and/or drawn from the ambient atmosphere. The apparatus may or may not include a container to store the source used to generate or concentrate the oxygen, For example, the apparatus may include a container to store air such as a pressurized air tank. Similarly, a water tank may be provided for an oxygen generator that decomposes water.
• Exemplary implementations may include a method of perfusing an organ or tissue, Such a method may include producing oxygen using at least one device selected from the group consisting of an oxygen concentrator and an oxygen generator, supplying the produced oxygen, preferably as the oxygen is produced, to a perfusate to oxygenate the perfusate, and perfusing the organ or tissue with the oxygenated perfusate. Preferably, the produced oxygen has a concentration greater than the oxygen concentration in air. Any of the devices discussed above, or other devices, may be used in exemplary implementations.
• FIG. 1 is a schematic diagram of anexemplary perfusion apparatus10 for anorgan20. Theorgan20 may preferably be a liver, kidney, heart, lung or intestine, but may be any human or animal, natural or engineered, healthy, injured or diseased organ or tissue. The apparatus includes abasin30 in which the organ may be placed. Thebasin30 may hold a cradle on which theorgan20 is disposed when theorgan20 is in theapparatus10. Thebasin30 may include afirst filter33 that can function as a gross particulate filter. Thebasin30 and/or the cradle are preferably configured to allow a perfusate bath to form around theorgan20. Thebasin30 orapparatus10 may also include atemperature sensor40 located or focused in or near the cradle. Thebasin30 orapparatus10 may includemultiple temperature sensors40, which may provide redundancy in the event of a failure and/or may provide temperature measurement at multiple locations. Preferably, the temperature sensor(s)40 is an infrared temperature sensor. The temperature sensor(s)40 is preferably disposed as close as practical to theorgan20 when theorgan20 is disposed in the cradle in order to improve usefulness and accuracy of thetemperature sensors40, which preferably provide a temperature measurement of the perfusate that may be correlated to a temperature of theorgan20. Alternatively or additionally, the temperature sensor(s)40 may be used to directly measure the temperature of theorgan20.
• Thebasin30 is preferably disposed within a recess of an insulatingcoolant container50 that may contain cold materials such as ice, ice water, brine or the like.Coolant container50 may be permanently or removably attached to, or an integral, monolithic part of,apparatus10. Thus, in use, theorgan20 is disposed within the cradle, which is disposed within thebasin30, which is disposed within thecoolant container50. The configuration of thecoolant container50,basin30 and cradle preferably provides a configuration that provides cooling for theorgan20 without the contents ofcoolant container50 contacting theorgan20 or the cradle. Although thecoolant container50 is described herein as containing ice or ice water, any suitable cooling medium can be used. Ice or ice water may be preferable due to the ease with which ice can 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 thecoolant container50 should be determined based upon the maximum time that cooling is to be provided while theorgan20 will be in theapparatus10.
• The cradle may include components configured to securely restrain theorgan20 in place. Such components may, for example, include user selectable netting that is fastened to the cradle. The user selectable netting keeps theorgan20 in place while theorgan20 is manipulated or moved. For example, the organ may be held in place with the netting on the cradle while being manipulated (e.g., vasculature trimmed, cannulas attached, or the like) before being placed in the basin or perfusion apparatus. Similarly, the organ may be held in place when theorgan20 is moved with the cradle into thebasin30, when thebasin30 is moved into thecoolant container50 and when theapparatus10 itself is moved during transport.
• In theexemplary perfusion apparatus10 ofFIG. 1, after passing through thefilter33, the perfusate flows along a first flow path70 that includes asuitable fluid conduit72, such as flexible or rigid tubing, apump80, apressure sensor90, asecond filter34, anoxygenator100 and abubble trap110, each of which is discussed below. In combination with one or both of theportal flow path120 and the hepatic flow path130 (discussed below), the first flow path70 may form a recirculating perfusate flow path that provides perfusate to theorgan20 and then recirculates the perfusate.
• Thefirst filter33 is preferably a relatively coarse filter (relative to the second filter34). Such a coarse filter may be provided to prevent large particles, which may for example be byproducts of the organ or of the organ being removed from the donor, from entering and clogging fluid paths of theapparatus10. Thefirst filter33 may be an integral part of thebasin30 or thefirst filter33 may be disposed elsewhere in the first flow path70 downstream of thebasin30. For example, thefirst filter33 may also be a separate component from thebasin30 or disposed within thefluid conduit72.
• The first flow path70 may also include apump80. Thepump80 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, parallel 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 flow path70 may include apressure sensor90. Thepressure sensor90 may preferably be disposed after the outlet of thepump80 in order to monitor and/or be used to control the pressure produced at the outlet of the pump by way of asuitable controller400. Thepressure sensor90 may provide continuous or periodic monitoring of pressure.
• The flow path70 may include anoxygenator100 such as an oxygenator membrane or body to provide oxygenation to the perfusate. The oxygen may be provided by way of an oxygen generator oroxygen concentrator102 as shown inFIG. 1, which may be separate from theapparatus10 or integral to theapparatus10. For example, the oxygen generator orconcentrator102 may be contained within theapparatus10 or the oxygen generator orconcentrator102 may be an external device that can be connected to the apparatus to supply oxygen to the apparatus. Oxygen may be generated through any suitable means, some examples of which include through pressure swing adsorption using a molecular sieve (such as a zeolite), through a ceramic oxygen generator (a solid state oxygen pump) or through decomposition of water. Each type of oxygen generator orconcentrator102 discussed above may be adapted to be separate from or integral to theapparatus10; however, some devices may be more advantageously adapted to be integral or separate. For example, an electrochemical oxygen generator may be relatively compact (on the order of a few cubic inches including a water reservoir) and therefore well suited to being integral, whereas a pressure swing adsorption device may be relatively large (due to the size of adsorbent material containers and need for a pressurized air source, such as a compressor) and therefore well suited to be separate.
• The oxygen generator orconcentrator102 preferably produces oxygen in real time to provide oxygenation to the perfusate, but oxygen may also be produced and stored for short or long periods as dictated by the oxygen consumption requirements and the technology selected for producing oxygen. The oxygen generator orconcentrator102 may continuously or non-continuously produce oxygen depending on the need to oxygenate perfusate and/or the type of device used to produce the oxygen. Theapparatus10 may be configured such that there is no oxygen storage for oxygen produced from the oxygen generator orconcentrator102, except for any residual oxygen contained within plumbing or a conduit(s) from an outlet of the oxygen generator orconcentrator102 to theoxygenator100. In other words, it may be preferable that theapparatus10 does not include any structures specifically configured for oxygen storage. Theapparatus10 may include a device, such as a microbial filter, to ensure sterility, or otherwise prevent contamination, of the oxygen supplied to the oxygenator. Preferably such a device is located between the oxygen generator orconcentrator102 and theoxygenator100, but may also be upstream of the oxygen generator orconcentrator102 or in both locations. Preferably, any device utilized to ensure sterility, or otherwise prevent contamination, of the oxygen supply is a disposable component. As would be appreciated by one of ordinary skill, any suitable device to ensure sterility of, or prevent contamination of, the oxygen may be provided instead of a microbial filter.
• The flow path70 may include abubble trap110. Thebubble trap110 preferably separates gas bubbles that may be entrained in the perfusate flow and prevents such bubbles from continuing downstream and entering theorgan20. Thebubble trap110 may also function as an accumulator that reduces or eliminates pulsatility of the perfusate flow. Thebubble trap110 may include a volume of gas, initially or through the accumulation of bubbles, such that pressure fluctuations in the perfusate are dampened or eliminated.
• Thebubble trap110 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 path140 (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 path70. Once the gas is purged from the perfusate path70, the vent may preferably be closed. The vent may be closed manually or may be closed automatically by way ofcontroller400.
• Thebubble trap110 may include alevel sensor112. Alevel sensor112 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 thebubble trap110. Also, through the use of thelevel sensor112 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.
• Thebubble trap110 may have any number of outlets, as needed for a given application of the perfusion apparatus. InFIG. 1, three outlets are shown connected to three different flow paths, which may be particularly suited for the perfusion of a liver. When perfusing a liver, the three paths preferably includeportal flow path120 connected to the portal vein of a liver,hepatic flow path130 connected to the hepatic artery of a liver, andbypass flow path140 that provides a return path to thebasin30. There may also be a port in any fluid path that allows fluid access to the perfusate solution. The port may preferably be located in thebubble trap110. This port may preferably include a luer type fitting such that a user may extract a small a sample of the perfusate for analysis. The port may also be utilized by a user to administer substances to the perfusate without opening the basin. AlthoughFIG. 1 illustrates asingle oxygenator100 andsingle bubble trap110, one of ordinary skill would appreciate that more than oneoxygenator100 and/orbubble trap110 may be provided. For example, anoxygenator100 and abubble trap110 could be provided for each of theportal flow path120 and thehepatic flow path130. Such a configuration may allow for different levels of oxygenation in each of theportal flow path120 andhepatic flow path130. A single oxygen concentrator orgenerator102 may provide oxygen to both theportal flow path120 and thehepatic flow path130, or separate oxygen concentrators orgenerators102 may be provided for each flow path. If a single oxygen concentrator orgenerator102 provides oxygen to both flow paths, suitable valves such as on/off valves and/or pressure regulators may control the oxygen supplied to each flow path to be different.
• As shown inFIG. 1, theportal flow path120 andhepatic flow path130 may optionally include similar or different components such asvalves122,132;bubble sensors124,134; flowsensors126,136; flow control clamps127,137; andpressure sensors128,138. 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.Flow sensors126,136 may preferably be ultrasonic sensors disposed around tubing, although any suitable sensor may be used. Ultrasonic sensors may be advantageous because in normal usage such sensors do not come into contact with the perfusate and therefore are not in the sterile path. Such an implementation of ultrasonic sensors does not require replacement and/or cleaning after use.
• Valves122,132 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.
• Preferably, thebubble sensors124,134 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.
• Flow control clamps127,137 may be used to fine-tune the flow rate in one or both ofportal flow path120 andhepatic flow path130. Preferably, the organ provides self-regulation to control an amount of flow that exits thebubble trap110 and is divided between theportal flow path120 and thehepatic flow path130. In such self regulated flow,pressure sensors128,138 provide overpressure monitoring. In the event that pressure delivered to the organ in either or both of theportal flow path120 or thehepatic flow path130 exceeds a predetermined threshold, theapparatus10 can automatically stop and/or reduce the flow rate provided by thepump80 to prevent damage to the organ. In addition or alternatively, thepressure sensors128,138 may be used to generate warning signals to the user and/or to an appropriate controller as pressures approach the predetermined threshold.
• After exiting one or both of theportal flow path120 andhepatic flow path130, perfusate flows through the organ and returns to thebasin30 to form an organ bath.
• Bypass flow path140 may include avalve142, and/or sensors such asoxygen sensor144 and pH sensor146. Preferably, thevalve142 is a pinch valve and may be of similar configuration tovalves122 and132, but any suitable valve may be used. Theoxygen sensor144 and the pH sensor146 may be used to determine the state of the perfusate. Preferably, the bypass flow path146 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.
• Theorgan perfusion apparatus10 may also include anaccelerometer150. Preferably theaccelerometer150 is a three-axis accelerometer, although multiple single axis accelerometers may be used to the same effect. Theaccelerometer150 may be used to continuously or periodically monitor and/or record the state of theapparatus10. Monitoring may include monitoring for excessive shocks as well as attitude of theapparatus10. By implementing such monitoring, misuse or potentially inappropriate conditions of theapparatus10 can be detected and recorded.
• Theapparatus10 may include storage compartments for items other than theorgan20. For example, theapparatus10 may include a document compartment to store documents and/or charts related to theorgan20. Also, theapparatus10 may include one or more sample compartment. The sample compartment may be configured, for example, to store fluid and/or tissue samples. The sample compartment may be advantageously disposed near thecoolant container50 to provide cooling, which may be similar or equivalent to the cooling provided for theorgan20.
• Theapparatus10 may include one or more tamper evident closures. A tamper evident closure may be used to alert a user that theapparatus10 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 theorgan20 and/or theapparatus10.
• The organ transporter is preferably portable for carrying organs or tissues from place to place, and is sized to be carried by one or two persons and loaded into an automobile or small airplane. Theperfusion apparatus10 preferably may be an organ transporter that is designed to be portable, for example, having dimensions smaller than length 42 inches×width 18 inches×height 14 inches and a weight less than 90 lbs, which includes the weight of the complete loaded system (for example, transporter, disposable components, organ, ice and 3 liters of perfusate solution),
• What has been described and illustrated herein are preferred embodiments of the invention along with some variations. The terms, 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.

Claims (30)

What is claimed is:

1. An apparatus for perfusing an organ or tissue, the apparatus comprising:

a perfusion circuit for perfusing the organ or tissue with liquid perfusate;

an oxygenator for oxygenating perfusate that recirculates through the perfusion circuit; and

an oxygen supply device configured to supply oxygen to the oxygenator, the oxygen supply device comprising at least one member selected from the group consisting of an oxygen concentrator and an oxygen generator.

2. The apparatus according toclaim 1, wherein the oxygen supply device is an oxygen generator that supplies oxygen by decomposing water.

3. The apparatus according toclaim 1, wherein the oxygen supply device is an oxygen concentrator that supplies oxygen by concentrating oxygen by way of pressure swing adsorption.

4. The apparatus according toclaim 1, wherein the oxygen supply device is an oxygen concentrator comprising a solid state oxygen pump.

5. The apparatus according toclaim 1, wherein the oxygen supply device is configured to supply oxygen by starting with an oxygen supply with relatively low oxygen concentration and outputting oxygen with a concentration that is higher relative to the oxygen supply.

6. The apparatus according toclaim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being air.

7. The apparatus according toclaim 6, wherein the air is compressed air.

8. The apparatus according toclaim 6, wherein the air is ambient air.

9. The apparatus according toclaim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being water.

10. The apparatus according toclaim 5, further comprising a container to store the oxygen supply.

11. The apparatus according toclaim 5, further comprising:

a bubble trap disposed within the perfusion circuit downstream of the oxygenator relative to a direction of perfusate flow.

12. The apparatus according toclaim 1, wherein the apparatus does not include an oxygen storage device.

13. The apparatus according toclaim 1, wherein the apparatus is transportable and weighs less than 90 pounds.

14. The apparatus according toclaim 1, configured to sterilize or prevent contamination of oxygen supplied by the oxygen supply device.

15. A method of perfusing an organ or tissue, the method comprising:

producing oxygen from a device comprising at least one member selected from the group consisting of an oxygen concentrator and an oxygen generator;

supplying the oxygen, as the oxygen is produced, to a liquid perfusate to oxygenate the perfusate; and

perfusing the organ or tissue with the oxygenated perfusate,

wherein the oxygen has a concentration greater than the oxygen concentration in air and the perfusate is recirculated.

16. The method according theclaim 15, wherein the device is an oxygen concentrator and the oxygen is produced from air by pressure swing adsorption.

17. The method according toclaim 15, wherein the device is an oxygen generator and the oxygen is produced from water.

18. The method according theclaim 15, wherein the device is an oxygen concentrator and the oxygen is produced from air by way of a solid state oxygen pump.

19. The method according theclaim 15, wherein the oxygen is produced on board a portable organ perfusion apparatus,

20. The method according toclaim 15, wherein the oxygen is produced by starting with an oxygen supply with relatively low oxygen concentration and outputting the oxygen with a concentration that is higher relative to the oxygen supply.

21. The method according toclaim 20, wherein the oxygen supply is air.

22. The method according toclaim 21, wherein the air is compressed air.

23. The method according toclaim 21, wherein the air is drawn from ambient atmosphere.

24. The method according toclaim 15, wherein the oxygen is produced from water.

25. The method according toclaim 15, wherein the oxygen is sterilized or decontaminated.

26. A method of perfusing an organ or tissue, the method comprising:

producing oxygen by a process comprising at least one member selected from the group consisting of pressure swing adsorption, water decomposition, and pumping oxygen by way of a solid state oxygen pump;

supplying the produced oxygen to a liquid perfusate to oxygenate the perfusate;

perfusing the organ or tissue with the oxygenated perfusate; and

recirculating the perfusate.

27. The method according toclaim 26, wherein the process is performed using a transportable perfusion apparatus.

28. The method according toclaim 26, wherein the oxygen is supplied as the oxygen is produced.

29. A method of perfusing an organ or tissue, the method comprising:

producing oxygen on board a portable perfusion apparatus;

oxygenating liquid perfusate in the portable perfusion apparatus with the produced oxygen;

perfusing an organ or tissue with the oxygenated perfusate; and

recirculating the perfusate.

30. The method according toclaim 29, wherein the oxygen is produced by a process comprising at least one member selected from the group consisting of pressure swing adsorption, water decomposition, and pumping oxygen by way of a solid state oxygen pump.

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