Oxygen supply device

The oxygen supply device addresses the slow oxygenation and impracticality issues of conventional devices by using a tube with multiple holes to rapidly oxygenate perfusion solutions, integrating seamlessly with existing perfusion circuits and disposable supplies.

JP7691370B2Active Publication Date: 2025-06-11LIFELINE SCIENTIFIC INC
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Patent Information

Application Number
JP2021555337
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2019-03-14
Filing Date
2020-03-06
Publication Date
2025-06-11
Estimated Expiration
2040-03-06

AI Technical Summary

Technical Problem

Conventional oxygenation devices for organ perfusion solutions are slow in oxygenating the perfusion solution, which is critical during organ transplantation, and they often require replacing existing disposable supplies, making them impractical for immediate use.

Method used

An oxygen supply device that includes an inlet for receiving oxygen from an oxygen supply source and a tube with multiple holes to rapidly oxygenate the perfusion solution, which can be integrated with existing perfusion circuits and disposable supplies.

Benefits of technology

The device rapidly increases the oxygen concentration in the perfusion solution, reducing the time required for oxygenation and allowing for immediate use without the need to replace existing disposable supplies, thereby supporting efficient organ transplantation processes.

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Abstract

An oxygenator is disclosed for oxygenating a perfusion solution perfused through an organ or tissue. The device includes an inlet (160) configured to receive oxygen from an oxygen source and a tube (180) connected to the inlet, the tube including a plurality of holes allowing the received oxygen to exit the tube. The tube can be secured in place under a top (120) of the oxygenator by a plurality of holders (170), and the top can be sized to accommodate a reservoir of an organ perfusion device, allowing the oxygenator to form a lid for the reservoir. The oxygenator allows for rapid oxygenation of the perfusion solution and works with existing perfusion circuits. A method of oxygenating a perfusion solution is also disclosed, in which the oxygenator is placed in a reservoir such that the tube and its holes are immersed in a bath of perfusion solution within the reservoir.
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Description

Technical Field

[0001] The related technical field includes an organ or tissue perfusion device capable of maintaining and / or restoring the viability of an organ or tissue and organ or tissue preservation for diagnosis, treatment, storage, and / or transportation. For convenience, the term "organ" as used herein should be understood to mean an organ and / or tissue unless otherwise specified.

Background Art

[0002] The purpose of an organ perfusion device is to mimic the human body's condition so that the organ can continue to survive until use in research, diagnosis, treatment, or transplantation. Often, organs must be stored and / or transported between facilities. The purpose of maintaining and restoring the perfused organ is to reduce ischemia-reperfusion injury. Extending the storage period in a normal or nearly normal functional state is also somewhat advantageous. For example, the transport distance of the organ can be increased, and the time for organ inspection, treatment, and evaluation can be increased.

[0003] Various organ perfusion devices are known. Patent Document 1, Patent Document 2, and Patent Document 3 disclose, for example, a perfusion device using a disposable perfusion circuit in which an organ can be stored during perfusion. This circuit includes an organ cradle in which the organ can be placed and a container that can serve as a receptacle for a perfusion fluid bath that can be formed around the organ. Using an inner lid and an outer lid, the receptacle can be closed during perfusion, and the receptacle can be fitted into a coolant container so that both the perfusion fluid bath and the organ are in a hypothermic region. The entire contents of these prior patents are incorporated herein by reference.

[0004] The use of hypothermic temperatures during transportation and perfusion significantly improves organ preservation by reducing the oxygen demand and metabolic activity of the organ, but does not eliminate them completely. The corresponding oxygen deficiency can promote the anaerobic activity of the cells of the organ, leading to the accumulation of lactic acid, mitochondrial uncoupling, and a decrease in the amount of adenosine triphosphate ("ATP"), which in turn leads to the release of toxic molecules such as reactive oxygen species, inflammatory cytokines, and lactic acid. These toxic molecules and mitochondrial activity increase the production of reactive oxygen molecules, which can further lead to harmful ischemia-reperfusion injury.

[0005] Given that oxygen deficiency promotes the anaerobic activity of cells and exacerbates ischemia-reperfusion injury, there is high interest in the benefits associated with increasing oxygen in hypothermically perfused organs, for example by introducing additional oxygen into the perfusion solution. Patent Document 4, which is incorporated herein by reference in its entirety, discloses an oxygen generating or concentrating unit in which it is preferable to generate oxygen in real time and oxygenate the perfusion fluid.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0007] However, there are at least two difficulties associated with conventional oxygenation devices and methods. The first is the amount of time required for sufficient oxygenation of the perfusion solution. Since time is precious during organ transplantation, the oxygen supply device should be able to rapidly oxygenate the perfusion solution. Further, hospitals and clinics may have obtained or purchased a significant amount of disposable supplies for use during perfusion and may be reluctant to discard these expensive disposable supplies for oxygenating the perfusion solution. Therefore, there is also a need for an oxygen supply device that can be used in combination with existing equipment and disposable supplies for oxygenating the perfusion solution.

Means for Solving the Problems

[0008] Accordingly, this specification discloses an oxygen supply device for oxygenating a perfusion solution to be perfused into an organ or tissue. The device can include an inlet configured to receive oxygen from an oxygen supply source and can also include a tube connected to the inlet, the tube including a plurality of holes through which the received oxygen can exit the tube.

[0009] In any combination of the above or below features, the oxygen supply device can also include a top starting from the inlet and can further include a plurality of holders extending under the top for fixing the tube under the top.

[0010] In any combination of the above or below features, each of the plurality of holders can also include (i) a vertical portion extending substantially perpendicular to the top and (ii) an inclined portion extending at an outward angle with respect to the vertical portion. The tube can be fixed by the inclined portions of the plurality of holders.

[0011] In any combination of the above or below features, the plurality of holders can fix the tube in a loop shape having a circumference sufficient to surround the organ or tissue during use, and most of this loop can be substantially parallel to a virtual plane formed by the top.

[0012] In any combination of one or more of the above or below features, the oxygen supply device can be configured to be attached to an organ perfusion circuit, and the top of the oxygen supply device starting from the inlet can form a lid for the container of the organ perfusion circuit configured to hold an organ or tissue during perfusion.

[0013] In any combination of one or more of the above or below features, the tube can be fixed below the top such that when the oxygen supply device is disposed in the container, the tube and its plurality of holes can be immersed in the perfusion solution bath within the container.

[0014] In any combination of one or more of the above or below features, the tube can be fixed in a predetermined position by a plurality of holders such that when the oxygen supply device is disposed in the container, the tube does not interfere with an organ cradle in which the tube can be positioned within the container.

[0015] In any combination of one or more of the above or below features, the oxygen supply device can further include a hydrophobic vent at the top, and the vent is configured to limit the pressure rise within the container when oxygen flows from the plurality of holes of the tube into the perfusion solution when the oxygen supply device is disposed in the container.

[0016] In any combination of one or more of the above or below features, the holes can be arranged in a plurality of groups spaced along the length of the tube.

[0017] In any combination of one or more of the above or below features, each of the groups can include a plurality of holes spaced around the tube.

[0018] In any combination of one or more of the above or below features, each pair of the plurality of groups can be spaced about 34.79 mm on the tube, and the average diameter of the plurality of holes can be about 0.10 mm to 0.18 mm.

[0019] This specification also discloses a method of using an oxygen supply device according to any of the above features. The method may include disposing the oxygen supply device in a receiving tank such that the tube and its holes are immersed in a bath of perfusion solution within the receiving tank of the organ perfusion circuit; connecting an inlet of the oxygen supply device to an oxygen supply source; and administering oxygen from the oxygen supply source through the inlet, through the holes of the tube, into the perfusion fluid bath so as to increase the oxygen concentration of the perfusion solution constituting the bath.

[0020] The method may also include administering oxygen from the oxygen source at a rate of about 10 liters per minute for 10 minutes or more.

[0021] The method may further include, prior to the disposing step, removing the lid of the receiving tank. Thus, the disposing step may include replacing the lid of the receiving tank with the oxygen supply device.

[0022] The method may further also include stopping the administration of oxygen from the oxygen supply source and subsequently disposing an organ or tissue within the receiving tank of the organ perfusion circuit.

[0023] Alternatively, oxygen may be administered during perfusion of an organ or tissue in the organ perfusion circuit.

[0024] These and other aspects of the disclosure will be described with reference to the accompanying drawings and the following detailed description.

Brief Description of the Drawings

[0025]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Embodiments for Carrying Out the Invention

[0026] FIGS. 1 and 2 show an exemplary perfusion device 10 for an organ. The organ may preferably be a liver, kidney, heart, lung, or intestine, but can be any natural or artificial, healthy, damaged, or diseased organ or tissue of a human or animal. The device 10 may include a storage tank 30 (see FIG. 2) in which the organ can be disposed. The storage tank 30 can hold a removable cradle 60, and the cradle 60 preferably includes a surface 60a on which the organ can be placed when the organ is within the device 10. The storage tank 30 and / or the cradle 60 are preferably configured to contain a perfusion fluid bath of a perfusion solution such as VASOSOL (registered trademark) around the organ.

[0027] The storage tank 30 is preferably placed inside an insulating coolant container 50 that can hold low-temperature materials such as ice, ice water, and brine. The coolant container 50 may be permanently or removably attached to the apparatus 10, or may be an integral monolithic part of the apparatus 10. Thus, as shown in FIG. 2, during use, the organ can be placed in the cradle 60, the cradle 60 can be placed in the storage tank 30, and the storage tank 30 can be placed in the coolant container 50. The arrangement of the coolant container 50, the storage tank 30, and the cradle 60 preferably provides a configuration for cooling the organ without the contents of the coolant container 50 contacting the organ or the cradle 60. Although the coolant container 50 is described herein as containing ice or ice water, any suitable cooling medium can be used.

[0028] As shown in FIG. 2, an inner lid 66 and an outer lid 67 can be provided on the upper surface of the storage tank 30. The inner lid 66 can be sized to be close to the periphery of the upper surface of the cradle 60 to help maintain the stability of the organ in case of mechanical collisions or impacts during transportation. More specifically, the inner lid 66 can have a downward protruding extension 66a configured to match the circumferential shape of the peripheral edge 60b of the cradle 60 and contact the peripheral edge 60b to help hold the cradle 60 in place. The lids 66 and 67 can form a substantially fluid-tight seal with the storage tank 30 and prevent contamination. The lids 66 and 67 can also serve as a backup airtight seal in case they are not sealed by the lid 66 or 67. It is preferable that both the inner lid 66 and the outer lid 67 contain an air vent, such as a porous hydrophobic membrane, that allows gas movement to maintain pressure equilibrium.

[0029] Preferably, all components of the perfusion solution and / or the device 10 that come into contact with the organ are disposable and / or easily replaceable. These components may include a receptacle 30 that can form part of a disposable organ perfusion circuit, an organ cradle 60, and lids 66 and 67. In use, this disposable organ perfusion circuit can be disposed within the non-disposable portion of the device 10, and the organ can be disposed in the organ cradle 60 within the receptacle 30. Since there is a coolant container 50, both the organ and the perfusion fluid bath within the receptacle 30 are brought into the hypothermic range. Subsequently, the perfusion solution can be circulated through the disposable perfusion circuit and the organ.

[0030] Figures 3 and 4 show an oxygen supply device 100 according to one or more aspects of the present disclosure. The device 100 can be designed to cooperate with the perfusion device 10 to increase the oxygen concentration of the perfusion fluid bath within the receptacle 100. The device 100 can generally be constituted by a main body 110 and an oxygenation component 150. The main body 110 may further include a top portion 120 including a radially inner portion 122 and an outer portion 124 as shown in FIG. 5. The main body 110 may also include a bottom portion 130 protruding downward from the top portion 120 as shown in FIG. 6. The main body 110 can be formed, for example, from a transparent polycarbonate plastic resin.

[0031] The top 120 can be sized to correspond to the receiving tank 30, such as the inner lid 66. More specifically, the lower lip 126 (see FIG. 4) of the radially outer portion 124 of the top 120 can be sized to be received in the recess 36 (see FIG. 2) on the upper surface of the receiving tank 30, enabling the oxygen supply device 100 to form the lid of the receiving tank instead of the inner lid 66. Using a latch (not shown) of the receiving tank 30, the oxygen supply device 100 can be locked in place with respect to the receiving tank 30. As shown in FIGS. 7 and 8, the top 120 can be substantially planar. That is, the surface of at least one of the radially inner portion 122 and the outer portion 124 can be slightly inclined, but the overall shape of the top 120 forms a virtual plane protruding into the paper surface of FIGS. 7 and 8. For example, the outer portion 124 can be flat, while the inner portion 122 can be convex outward. A vent 128 (see FIGS. 5 and 6) can also be provided in the top 120. Similar to the air vents of the lids 66 and 67, the vent 128 can include a porous hydrophobic membrane that allows gas movement to maintain pressure balance. More specifically, the membrane of the vent 128 can be an acrylic copolymer treated for hydrophobicity and oleophobicity, and the membrane can be attached and adhered to a non-woven nylon substrate. The membrane itself can have an average pore size of 0.45 microns, and can be oleophobic, hydrophobic, organic solvent repellent, oil resistant, water resistant, and organic solvent resistant, and non-wetting with most low surface tension liquids. This is in contrast to, for example, a hydrophilic membrane that tends to mix with or be wet by such liquids. An adhesive can be provided around the vent 128 to ensure a sealed and attached state by fixing the vent 128 to the rest of the top 120.

[0032] The bottom 130 can be formed in the space between the radially inner portion 122 and the outer portion 124 of the top 120 and can have a substantially triangular cross-section. More specifically, the radially outer wall 132 of the bottom 130 (see FIG. 4) can extend downward substantially perpendicular to the virtual plane of the top 120, and the radially inner wall 134 of the bottom 130 can extend downward from the top 120 at an angle inclined with respect to the outer wall 132. By joining at the vertex 136, the walls 132 and 134 can ensure that the main body 110 forms a substantially fluid-tight seal with the receiving tank 30, thereby preventing contamination. Finally, the bottom 130 (and in particular the vertex 136) can also conform to the circumferential shape of the periphery 60b of the cradle 60, such as the downward protruding extension 66a of the inner lid 66, and thus can similarly be configured to contact the periphery to assist in holding the cradle 60 and the organs thereon in place.

[0033] The oxygenation component 150 can further include, as shown in FIG. 7, an oxygen inlet 160, a T-fitting 162, a holder 170, and a tube 180. The oxygen inlet 160 can be an oxygen valve fitting that protrudes from a bridge portion 129 (see FIG. 5) connecting the radially inner portion 122 and the outer portion 124 of the top 120. The oxygen inlet 160 can be at an angle substantially perpendicular to the virtual plane of the top 120 so as to improve ease of use and reduce the risk of kinking of the tube that delivers oxygen to the inlet. The T-fitting 162 can further be fluidly connected to the oxygen inlet 160 and can be formed within a gap 138 formed in the bottom 130 under the bridge portion 129.

[0034] The tube 180 can be fluidly connected to the T fitting 162 and can be fixed in place by a plurality of holders 170. As shown in FIG. 8, each of these holders 170 can include an upper vertical portion 172 that is fixed to the bottom 130 of the main body 110 and projects in a direction substantially perpendicular to the virtual vertical plane of the top 120 from the top 120. The holder 170 can fix the tube 180 under the bottom 130, and each of the holders 170 can also include an inclined portion 174 with an outward angle with respect to the vertical portion 172. The inclined portion 174 can be, for example, at an angle of 2.5° with respect to the vertical portion 172, but other angles are also possible. Each inclined portion 174 of the holder 170 can include a hole through which the tube 180 can pass. As will be described later, by angling the inclined portion 174 with respect to the vertical portion 172, it can help ensure that neither the holder 170 nor the tube 180 interferes with the organ cradle 60, the organs or vasculature above it, or the cannula that can be placed in the receiving tank 30 during use. The rounded end of the inclined portion 174 where the hole is located can also ensure that there is no collision or interference with the receiving tank 30 during use.

[0035] The tube 180 can be formed from an aromatic polyether-based polyurethane and can be long enough to surround the bottom 130 when the oxygen supply device 100 serves as the lid of the storage tank 30, and thus surround the perfused organ. Preferably, the total length of the tube 180 can be about 1,054.10 mm or so, but other lengths are also possible. FIG. 9 shows an enlarged view of part IX of the tube 180 shown in FIG. 8. As shown in this figure, the tube 180 can include a plurality of groups 182 of holes 184 that can be spaced apart by a distance 186 along the length of the tube 180. Preferably, the distance 186 can be about 34.79 mm or so, but other distances are also possible. Twenty-four groups 182 can be formed in the tube 180. As shown in FIG. 10, which shows a cross-section of the tube 180 in one of the groups 182, each group can include five equally spaced holes 184 around the tube 180. Thus, the tube 180 can include a total of 120 holes 184. Each of the holes 184 can be formed in the tube 180 by laser ablation. Also, each hole 184 can be in the range of 0.10 mm to 0.18 mm in diameter, which has been found to be reproducible within the capabilities of the laser ablation process. Instead of the tube 180, a hollow fiber filter may be used to supply oxygen to the perfusion solution. The hollow fiber filter can prevent foaming of the perfusion solution during the oxygenation process. However, if the perfusion solution is not whole blood, this potential difference may be insufficient to justify a substantial increase in the cost of the hollow fiber filter over the tube 180.

[0036] The above configuration of the holes 184, particularly their number and diameter, while maintaining an appropriate cost, significantly shortens the time for "foaming" and thus for saturating the perfusion solution of the perfusion fluid bath with oxygen. Preferably, for example, with an oxygen flow rate of 10 liters per minute, the holes 184 ensure that the perfusion solution of the bath is saturated within 10 to 15 minutes, and since the surgical procedures performed simultaneously can take substantially longer, this time is acceptable in most hospitals. Other numbers of holes 184 and other sizes of these holes are also possible. However, there are various considerations. For example, increasing the number of holes 184 of the same diameter can shorten the time required to fully saturate the perfusion solution. However, since the cost of the tube 180 is directly proportional to the number of holes 184, increasing the number can increase the cost of the tube. On the other hand, a significantly smaller number of holes 184 can disadvantageously increase the time required to saturate the perfusion solution of the bath.

[0037] Other configurations of the holes 184 are also possible. The holes 184 may be positioned linearly, for example, along the length of the tube 180. However, the above configuration with five groups 182 of holes 184 spaced around the tube 180 helps ensure that at least the majority of the holes 184 are below the surface of the perfusion fluid during use. Spacing the groups 182 at equal distances 186 along the length of the tube 182 can also help prevent the formation of under-concentration regions by ensuring that the majority of the perfusion solution receives oxygen gas uniformly.

[0038] Figure 11 shows a method capable of increasing the amount of dissolved oxygen in a perfusion solution that constitutes a perfusion fluid bath by using the oxygen supply device 100 together with a perfusion device, for example, the perfusion device 10. In the first step 210, the oxygen supply device 100 can be arranged in the storage tank 30. This configuration is shown in cross section in Figure 12. As shown in this figure, the lower lip 126 of the oxygen supply device 100 can be sized to correspond to the recess 36 on the upper surface of the storage tank 30. The holder 170 can also be fixed low enough so that the tube 180 and its hole 184 are immersed in the perfusion fluid bath within the container 30, and the possible level thereof is shown as 190 in Figure 12. Also, due to the inclined portion 174 of the holder 170, the tube 180 can be positioned outwardly so as not to interfere with the organ cradle 60, the organ or vascular system thereon, or the cannula in the assembled position shown in Figure 12. The oxygen supply device 100 can be fixed to the storage tank 30 by the above latch.

[0039] In the next step 220, the oxygen supply device 100 can be connected to an external oxygen source. The oxygen source is not particularly limited, except that preferably regulated medical oxygen is supplied. This can be, for example, an oxygen cylinder or a wall valve in a hospital or hospital situation. To connect the oxygen supply device 100 and the oxygen source, the user of the device 100 can attach one end of an extension tube to the oxygen inlet 160 and the other end of the tube to the oxygen source.

[0040] Following step 220, oxygen can be administered in step 230. Preferably, oxygen can be administered from an oxygen source at a rate of 10 liters per minute or so for 10 minutes or more, more preferably 15 minutes or more, and even more preferably 20 minutes or more. However, other oxygen flow rates are also possible. For example, oxygen may be administered from an oxygen source at a rate of 1 liter per minute, 2 liters per minute, or 3 liters per minute. However, this may make the period required to sufficiently saturate the perfusion solution in the perfusion bath unacceptably long. On the other hand, an oxygen flow rate of up to 20 liters per minute or more is conceivable. However, a flow rate exceeding 20 liters per minute may risk applying a high back pressure to the connection between the tube 180 and the T-fitting 162, and there is a possibility that the perfusion bath may not be sufficiently saturated with oxygen due to leakage caused by the high pressure. By administering oxygen at the above preferred rate for a preferred period, the dissolved oxygen level in the perfusion solution can reach 600 mmHg to 800 mmHg, which is considered desirable for organ perfusion. Despite the additional oxygen being introduced into the receiving tank 30 through the tube 180 and its holes 184, the vent 128 can prevent a significant increase in the pressure of the atmosphere inside the receiving tank 30 and above the perfusion bath by venting most of the introduced oxygen to the atmosphere. In practice, the increase in the air pressure inside the receiving tank 30 can be less than 5 mmHg. When the administration of oxygen is stopped, the pressure inside the receiving tank 30 can be balanced with the pressure of the external atmosphere by the vent 128.

[0041] Once the desired oxygenation level is reached, oxygen administration can be stopped and the oxygen supply device 100 can be removed from the storage tank 30. Since the oxygenated perfusion fluid is vented to the atmosphere, it is preferable that the inner lid 66 can be placed on the storage tank 30 as soon as possible. Subsequently, the organ can be placed in the storage tank 30 and perfused with the oxygenated perfusion solution. It is also conceivable that there may be some delay in placing the organ in the storage tank 30 and starting perfusion after stopping the oxygen administration. Therefore, it may be necessary to re-oxygenate the perfusion solution after a certain period so as to maintain the desired oxygenation level. Preferably, this re-administration is performed before removing the oxygen supply device 100 from the storage tank 30 because removing it from the storage tank may compromise the sterility of the device.

[0042] Therefore, the process 200 shown in FIG. 11 also provides means for pre-filling the perfusion solution with oxygen prior to placement of the organ into the perfusion circuit and subsequent perfusion of the organ. However, various modifications are envisioned. For example, the oxygen supply device 100 may not be removed from the storage tank 30 after pre-filling is complete and can thus serve as the lid of the storage tank during perfusion of the organ. The oxygen supply device 100 can also continue to oxygenate the perfusion fluid during perfusion and / or transportation of the organ. This oxygenation during perfusion can help maintain a high oxygen level in the perfusion fluid throughout transportation. Naturally, a portable oxygen source would be beneficial for this modification. Prior to step 210 of the process 200, steps 205 and 207 may also be present. In step 205, after priming and cooling of the perfusion circuit, the inner lid 66 of the perfusion circuit can be removed to make room for the oxygen supply device 100. Also, in step 207, the perfusion solution can be poured into the storage tank 30 to form a perfusion fluid bath.

[0043] Therefore, as described above, the oxygen supply device 100 provides a mechanism that rapidly oxygenates the perfusion solution, providing the benefits of oxygen while avoiding risks associated with delays in the transplantation process. The oxygen supply device 100 also cooperates with existing perfusion circuits so that hospitals or medical facilities do not need to replace these expensive disposable supplies to obtain the benefits of oxygen.

[0044] This specification has described and illustrated several variations of embodiments of the present invention. The terms, descriptions, and figures used in this specification are provided by way of example only and are not limiting. Those skilled in the art will recognize that many variations are possible within the spirit and scope of the present invention.

Claims

1. An oxygen supply device for oxygenating a perfusion solution to be perfused into an organ or tissue, comprising: an inlet configured to receive oxygen from an oxygen source; a tube connected to the inlet, the tube including a plurality of holes through which oxygen received from the oxygen supply device can exit the tube; a top starting from the inlet; a plurality of holders extending below the top so as to fix the tube below the top; and each of the plurality of holders includes (i) a vertical portion extending perpendicular to the top and (ii) an inclined portion extending at an outward angle with respect to the vertical portion; the tube is fixed by the inclined portions of the plurality of holders, the oxygen supply device.

2. The oxygen supply device according to claim 1, wherein the plurality of holders fix the tube in a loop shape having a circumference sufficient to surround the organ or tissue, and most of the loop is parallel to a virtual plane formed by the top, the oxygen supply device.

3. An oxygen supply device for oxygenating a perfusion solution to be perfused into an organ or tissue, comprising: an inlet configured to receive oxygen from an oxygen source; a tube connected to the inlet, the tube including a plurality of holes through which oxygen received from the oxygen supply device can exit the tube; and the oxygen supply device is configured to be attached to an organ perfusion circuit, the top of the oxygen supply device starting from the inlet constitutes a lid for a receiving tank of the organ perfusion circuit configured to hold the organ or tissue during perfusion, the oxygen supply device.

4. The oxygen supply device according to claim 3, wherein the tube is fixed below the top such that when the oxygen supply device is disposed in the receiving tank, the tube and its plurality of holes are immersed in a bath of the perfusion solution in the receiving tank, the oxygen supply device.

5. The oxygen supply device according to claim 4, wherein the tube is fixed in a predetermined position by a plurality of holders such that when the oxygen supply device is disposed in the receiving tank, the tube does not interfere with an organ cradle in which the tube can be positioned in the receiving tank, the oxygen supply device.

6. The oxygen supply device according to claim 4, further comprising a hydrophobic vent in the top, the vent being configured to limit a pressure increase in the receiving tank when oxygen flows from the plurality of holes of the tube into the perfusion solution with the oxygen supply device disposed in the receiving tank, the oxygen supply device.

7. The oxygen supply device according to claim 1, wherein the holes are arranged in a plurality of groups spaced along the length of the tube.

8. The oxygen supply device according to claim 7, wherein each of the groups includes a plurality of holes spaced around the tube.

9. In the oxygen supply device according to claim 8, each pair of the plurality of groups is spaced 34.79 mm apart on the tube, and the average diameter of the plurality of holes is 0.10 mm to 0.18 mm.

10. A method for oxygenating a perfusion solution for perfusion of an in vitro organ or tissue, comprising: placing the oxygen supply device according to claim 1 or 3 in the storage tank such that the tube and its holes are immersed in the bath of the perfusion solution in the storage tank of the organ perfusion circuit; connecting the inlet of the oxygen supply device to an oxygen supply source; administering oxygen from the oxygen supply source through the inlet, through the holes of the tube, and into the bath of the perfusion solution to increase the oxygen concentration of the perfusion solution constituting the bath.

11. The method according to claim 10, further comprising administering oxygen at a rate of 10 liters per minute from the oxygen supply source for 10 minutes or more.

12. The method according to claim 10, further comprising removing the lid of the storage tank before the placing step, wherein the placing step comprises replacing the lid of the storage tank with the oxygen supply device.

13. In the method according to claim 10, stopping the administration of oxygen from the oxygen supply source; and subsequently placing the organ or tissue in the storage tank of the organ perfusion circuit.

14. The method according to claim 10, wherein the oxygen is administered during perfusion of the organ or tissue in the organ perfusion circuit.

Citation Information

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