Organ container with oxygenation option

Abstract

An organ container insertable into an apparatus for storing organs or tissue and for perfusion and / or transport of organs or tissues includes a bowl configured to hold the organ or tissue and a perfusate bath. The organ container also includes tubing that (i) is connectable to an oxygen source, (ii) includes a plurality of holes through which oxygen can exit the tubing, and (iii) is positioned within the bowl so that the tubing is submerged in the perfusate bath during perfusion or transport. One or more holders can be provided within the bowl to secure the tubing below the surface of the perfusate bath. A connection can be provided within the bowl to disconnect the tubing from an oxygen line connected to the oxygen source, allowing the practitioner to switch between bubble and surface oxygenation. First and second outer lids can be provided to cover the bowl and other components of the apparatus, respectively.

Description

Continuity Information

[0001] This non-provisional patent application claims priority to U.S. Provisional Patent Application No. 62,900,131, filed September 13, 2019, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] The relevant technical field includes organ or tissue perfusion devices capable of maintaining and / or restoring viability of an organ or tissue and preserving an organ or tissue 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.

[0003] The purpose of an organ perfusion machine is to support aerobic metabolism so that the organ remains viable before being used for research, diagnosis, therapy or transplantation. Often, organs need to be stored and / or transported between facilities. The purpose of maintaining and restoring the organ during perfusion is to reduce ischemia and reperfusion injury. Increasing the duration of preservation in a normal or near-normal functional state also provides certain advantages. For example, the organ can be transported over greater distances, increasing the time for examination, treatment and evaluation of the organ.

[0004] Various organ perfusion devices are known. U.S. Patent Nos. 9,357,767, 9,357,766, and 9,723,830, for example, disclose perfusion devices employing disposable perfusion circuits that can preserve organs during perfusion. The circuit includes an organ cradle in which the organ can be placed and a bowl that can serve as a container for a perfusion bath that can be formed around the organ. During perfusion, the bowl can be closed using inner and outer lids, and the bowl can fit within a cooling container, thereby allowing hypothermia for both the perfusion bath and the organ. The contents of these prior patents are incorporated herein by reference in their entirety. Summary of the Invention

[0005] The use of hypothermia during transport and perfusion reduces the oxygen demand and metabolic activity of organs, greatly improving organ preservation, but does not eliminate them. The resulting lack of oxygen can drive organ cells into anaerobic activity, leading to lactate accumulation and mitochondrial uncoupling and depletion of adenosine triphosphate ("ATP") stores, thereby leading to the release of toxic molecules such as radical oxygen species, inflammatory cytokines, and lactate. These toxic molecules and anaerobic mitochondrial activity can increase the production of reactive oxygen molecules, which in turn can lead to deleterious ischemia and reperfusion injury.

[0006] Given that oxygen deficiency drives cells into anaerobic activity and exacerbates ischemia and reperfusion injury, there has been great interest in the benefits associated with increasing oxygen in hypothermic perfused organs, for example, by introducing additional oxygen into the perfusate. U.S. Patent Application Serial No. 13 / 545,514, the entire contents of which are incorporated herein by reference, for example, discloses an oxygen generator or concentrator that produces oxygen, preferably in real time, to oxygenate the perfusate.

[0007] However, prior oxygenation devices and methods suffer from at least two difficulties. The first is the time required to adequately oxygenate the perfusate. Because time is limited during organ transplantation, the oxygenation device must be able to oxygenate the perfusate quickly. Additionally, hospitals and clinics may have acquired or purchased a significant amount of disposables for use during perfusion and may be hesitant to dispose of these potentially expensive disposables to oxygenate the perfusate. Thus, there is also a need for a device with an oxygenation option that works in conjunction with existing equipment and disposables to oxygenate the perfusate.

[0008] Thus, disclosed herein is a device with an oxygenation option that may be for oxygenating a perfusate that is perfused through an organ or tissue, the device may include an inlet configured to receive oxygen from an oxygen source, and may include a tube connected to the inlet, the tube including a plurality of holes that allow the received oxygen to exit the tube.

[0009] In any combination of the above or below features, the oxygenation device may also include an upper portion through which the inlet extends, and may further include a plurality of holders extending below the upper portion to secure tubes below the upper portion.

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

[0011] In any combination of the above or below features, the multiple holders can secure the tube into a loop having a circumference sufficient to encircle the organ or tissue in use, and the majority of the loop can be substantially parallel to an imaginary plane formed by the upper portion.

[0012] In any combination of the above or below features, the oxygenation device may be configured to be attached to an organ perfusion circuit, and a top portion of the oxygenation device may form a lid for a bowl of the organ perfusion circuit, having an inlet extending therefrom and configured to hold an organ or tissue during perfusion.

[0013] In any combination of the above or below features, the tube may be secured under the upper portion such that when the oxygenation device is placed on the bowl, the tube and the multiple holes therein may be immersed in a bath of perfusion fluid in the bowl.

[0014] In any combination of the above or below features, the tubing may be secured in place by a plurality of holders such that when the oxygenation device is placed on the bowl, the tubing does not interfere with an organ cradle that may be positioned within the bowl.

[0015] In any combination of the above or below features, the oxygenation device may further include a hydrophobic vent at the top, the vent configured to limit pressure buildup in the bowl when the oxygenation device is placed over the bowl and oxygen flows into the perfusion solution from the multiple holes in the tube.

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

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

[0018] In any combination of the above or below features, each pair of the plurality of groups may be spaced apart by 34.79 mm of the tube, and an average diameter of the plurality of holes may be between 0.10 mm and 0.18 mm.

[0019] Also disclosed herein is a method of using a device with an oxygenation option according to any of the above features, which may include: placing the oxygenation device on a bowl of an organ perfusion circuit such that the tubing and its bores are submerged in a bath of perfusate in the bowl; connecting an inlet of the oxygenation device to an oxygen source; and supplying oxygen from the oxygen source through the inlet and through the bores of the tubing to the perfusate bath to increase the oxygen concentration of the perfusate that constitutes the bath.

[0020] The method may also include the step of supplying oxygen from an oxygen source at a flow rate of about 10 liters per minute for at least 10 minutes.

[0021] This may further include removing the bowl lid prior to the loading step, where the loading step may then involve replacing the bowl lid with the oxygenation device.

[0022] The method may further comprise the step of discontinuing the supply of oxygen from the oxygen source and thereafter placing the organ or tissue in the bowl of the organ perfusion circuit.

[0023] Alternatively, oxygen can be supplied while the organ or tissue is perfused with an organ perfusion circuit.

[0024] However, while a separate device with an oxygenation option has advantages, a clinician may prefer to have the oxygenation structure mounted within the bowl of the organ container itself, which may reduce the number of disposables a hospital or clinician must have on hand, among other advantages, such as the ability to close an overlay over the bowl of the organ container while oxygen is being delivered, particularly during liver perfusion.

[0025] Further disclosed herein is an organ container configured to store an organ or tissue and to be inserted into an apparatus for perfusion and / or transport of the organ or tissue. The organ container may include a bowl configured to hold the organ or tissue and a perfusion fluid bath, and may also include a tube that is (i) connectable to a source of oxygen, (ii) includes a plurality of holes through which oxygen can exit the tube, and (iii) is positioned within the bowl for immersion in the perfusion fluid bath present during perfusion or transport of the organ or tissue.

[0026] In any combination of the above or below features, the organ container may also include at least one holder within the bowl for securing tubing below the surface of the perfusion solution bath.

[0027] In any combination of the above or below features, the at least one holder may be a plurality of holders, each of the plurality of holders (i) extending from an upper edge of the bowl toward a bottom of the bowl, (ii) descending along an inner wall of the bowl, and (iii) including a hole through which a tube passes.

[0028] In any combination of the above or below features, the at least one holder may secure the tube in a loop that encircles the organ or tissue in use.

[0029] In any combination of the above or below features, the organ container may also include a connection within the bowl that may be configured to connect and disconnect oxygen lines and tubing extending outside the bowl.

[0030] In any combination of the above or below features, the connection may be connected to a tube by a T-joint with another tube.

[0031] In any combination of the above or below features, the connection part may be a Luer lock joint.

[0032] In any combination of the above or below features, the holes in the tube may be arranged in a plurality of spaced apart groups along the length of the tube.

[0033] In any combination of the above or below features, the group may include a plurality of holes spaced around the circumference of the tube.

[0034] In any combination of the above or below features, each pair of the plurality of groups may be spaced apart by about 34.79 mm of the tube, and an average diameter of each of the plurality of holes may be between 0.10 mm and 0.18 mm.

[0035] And, in any combination of the above or below features, the oxygenation device may further include a hydrophobic vent in each lid of the bowl, the vents in use limiting pressure buildup within the bowl.

[0036] Also disclosed is an apparatus for perfusion and / or transport of an organ or tissue, which may include the organ container described above and may include an oxygen line configured to deliver oxygen from an oxygen source to the tube, a first end of the oxygen line may be within the bowl of the organ container and a second end of the oxygen line may be outside the bowl.

[0037] In any combination of the above or below features, the device may further include a first overcap configured to cover the bowl when closed, and a second overcap adjacent to the first overcap and configured to cover other components of the device when closed. Even when the first overcap is closed, the second end of the oxygen line may be exposed.

[0038] In any combination of the above or below features, the apparatus may further comprise an antibacterial filter at the second end of the oxygen line.

[0039] Also disclosed herein is a method for oxygenating perfusion fluid being perfused through an organ or tissue. The method may include the steps of introducing perfusion fluid into a bowl of the organ container to form a perfusion fluid bath in which tubing inside the bowl is immersed. The method may also include the steps of connecting the tubing to an oxygen source and supplying oxygen from the oxygen source through holes in the tubing into the perfusion fluid bath to increase the oxygen concentration of the perfusion fluid that constitutes the bath.

[0040] The method may further include providing oxygen from an oxygen source at a flow rate of about 10 liters per minute for at least 10 minutes.

[0041] And the method may further include the steps of disconnecting the tubing from the oxygen by a connection in the bowl such that oxygen is supplied to the space in the bowl above the surface of the perfusion solution bath, reducing the flow rate of supplied oxygen, introducing the organ or tissue into the bowl of the organ container, and perfusing the organ or tissue with perfusion solution while oxygen is supplied to the space in the bowl and above the surface of the perfusion solution bath.

[0042] These and other aspects of the present disclosure will be explained with reference to the accompanying drawings and the following detailed description. [Brief description of the drawings]

[0043] [Figure 1] FIG. 1 is a cross-sectional view of an organ perfusion device according to one or more embodiments of the present disclosure. [Diagram 2] FIG. 2 is a cross-sectional view of the combined cooling vessel, bowl and cradle of the organ perfusion apparatus of FIG. [Diagram 3] FIG. 1 is a top perspective view of a device with an oxygenation option in accordance with one or more embodiments of the present disclosure. [Figure 4] FIG. 4 is a bottom perspective view of the oxygenation device of FIG. [Diagram 5] FIG. 4 is a top view of the oxygenation device of FIG. 3. [Figure 6] FIG. 4 is a bottom view of the oxygenation device of FIG. 3. [Figure 7] FIG. 4 is a side view of the oxygenation device of FIG. 3. [Figure 8] FIG. 4 is another side view of the oxygenation device of FIG. 3. [Figure 9] FIG. 9 is an enlarged view of a portion IX of the tube shown in FIG. [Figure 10] 10 is a cross-sectional view of the tube taken along line XX in FIG. 9. [Figure 11] FIG. 4 illustrates a process for using the oxygenation device of FIG. 3. [Figure 12] FIG. 4 is a cross-sectional view of the oxygenation device of FIG. 3 mounted on the bowl of an organ perfusion circuit. [Figure 13]FIG. 13 is a top view of a bowl of an organ container in accordance with one or more embodiments of the present disclosure. [Figure 14] FIG. 14 is a top view of an organ perfusion device configured to receive the organ container of FIG. [Figure 15] FIG. 15 is another top view of the organ perfusion device of FIG. [Figure 16] FIG. 14 illustrates a process for using the organ container of FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] 1 and 2 show an exemplary organ perfusion device 10. The organ may preferably be a liver, kidney, heart, lung, or intestine, but may be any human or animal, natural or artificial, healthy, damaged, or diseased organ or tissue. The device 10 may include an organ container including an outer cover 20, 22, and a bowl 30 (see FIG. 2) upon which the organ may be placed. The bowl 30 may hold a removable cradle 60, which may preferably include a surface 60a upon which the organ may rest when in the device 10. The bowl 30 and / or cradle 60 may preferably be configured to accommodate a perfusion bath of perfusion fluid, such as VASOSOL®, around the organ.

[0045] Preferably, bowl 30 may be placed within an insulated cooling vessel 50 which may contain a cooling material such as ice, ice water, brine, etc. Cooling vessel 50 may be permanently or removably attached to apparatus 10 or may be an integral monolithic part of apparatus 10. Thus, in use, as shown in FIG. 2, an organ may be placed within cradle 60, which may be placed within bowl 30, and bowl 30 may be placed within coolant vessel 50. The arrangement of cooling vessel 50, bowl 30 and cradle 60 preferably provides a configuration which provides cooling to the organ without the contents of cooling vessel 50 contacting the organ or cradle 60. Although cooling vessel 50 is described herein as containing ice or ice water, any suitable cooling medium may be used.

[0046] As further shown in FIG. 2, the upper surface of the bowl 30 may be provided with an inner lid 66 and an outer lid 67. The inner lid 66 may be sized to be in close proximity to the peripheral upper surface of the cradle 60 to help maintain stability of the organ during mechanical bumps and shocks during transport. More specifically, the inner lid 66 may have a downwardly projecting extension 66a configured to conform to the peripheral shape of the peripheral projection 60b of the cradle 60 and contact the peripheral projection 60b to help hold the cradle 60 in place. The lids 66 and 67 may form a substantially liquid-tight seal with the bowl 30 to prevent contamination. The lids 66 and 67 may also provide a redundant air-tight seal in the event that the seal by either the lid 66 or 67 fails. Both the inner lid 66 and the outer lid 67 may preferably include air vents, e.g., porous hydrophobic membranes, to allow gas movement to maintain pressure equilibrium.

[0047] Preferably, all components of device 10 that come into contact with perfusion fluid and / or the organ are disposable and / or easily replaceable. These components may include bowl 30, organ cradle 60, and lids 66 and 67, which may form part of a disposable organ perfusion circuit. In use, this disposable organ perfusion circuit may be loaded into the non-disposable portion of device 10, and the organ may be loaded onto organ cradle 60 in bowl 30. Due to the presence of cooling reservoir 50, both the organ and the perfusion fluid bath in bowl 30 are exposed to hypothermia. Perfusion fluid may then be circulated through the disposable perfusion circuit and the organ.

[0048] 3 and 4 show a device 100 with an oxygenation option according to one or more aspects of the present disclosure. The device 100 may be designed to increase the oxygen concentration of the perfusate bath in the bowl 30 in conjunction with the perfusion apparatus 10. The device 100 may generally be comprised of a body 110 and an oxygenation component 150. The body 110 may include a top portion 120 including radially inner and outer portions 122 and 124, as shown in FIG. 5. The body 110 may also include a bottom portion 130 projecting downwardly from the top portion 120, as shown in FIG. 6. The body 110 may be formed, for example, from a clear polycarbonate plastic resin.

[0049] The top 120 may be sized to match the bowl 30, as may the inner lid 66. More specifically, a lower edge 126 (see FIG. 4) of the radially outer portion 124 of the top 120 may be sized to be received by the recess 36 (see FIG. 2) in the upper surface of the bowl 30, thereby allowing the oxygenation device 100 to constitute a lid for that bowl in place of the inner lid 66. A latch (not shown) on the bowl 30 may be used to secure the oxygenation device 100 in place relative to the bowl 30. As shown in FIGS. 7 and 8, the top 120 may be substantially planar. That is, the surfaces of at least one of the radially inner and outer portions 122 and 124 may be slightly inclined, but the overall shape of the top 120 forms an imaginary plane that projects into the page in FIGS. 7 and 8. For example, the outer portion 124 may be flat, while the inner portion 122 may be outwardly convex. Also, a vent 128 may be provided within the top 120 (see FIGS. 5 and 6). Similar to the air vents in lids 66 and 67, vent 128 may include a porous hydrophobic membrane that allows gas transfer to maintain pressure equilibrium. More specifically, the membrane of vent 128 may be an acrylic copolymer that has been treated to render it hydrophobic and oleophobic, and the membrane may be attached and bonded to a non-woven nylon substrate. The membrane itself may have an average porosity of 0.45 microns, repel and resist oil, water, and organic solvents, and be non-wetting to most low surface tension liquids. This is in contrast to, for example, hydrophilic membranes, which tend to mix with and be wet by such liquids. An adhesive is applied around the periphery of vent 128 to secure vent 128 to the remainder of top 120, thereby ensuring that vent 128 remains sealingly attached to top 120.

[0050] Bottom 130 may be formed in the space between radially inner and outer portions 122 and 124 of top 120 and may have a substantially triangular shape in cross section. More specifically, a radially outer wall 132 (see FIG. 4 ) of bottom 130 may extend downwardly substantially perpendicular to an imaginary plane of top 120, and a radially inner wall 134 of bottom 130 may extend downwardly from top 120 at an oblique angle relative to outer wall 132. Walls 132 and 134 meet at an apex 136, which ensures that body 110 and bowl 30 can form a substantially fluid-tight seal, thereby preventing contamination. Finally, the bottom 130 (and particularly the apex 136), as well as the downwardly projecting extension 66a of the inner lid 66, may conform to the peripheral shape of the peripheral protrusion 60b of the cradle 60 and thus may likewise be configured to contact that peripheral protrusion to help hold the cradle 60 and the organs thereon in place.

[0051] And, the oxygenation component 150 may include an oxygen inlet 160, a T-fitting 162, a holder 170, and a tube 180, as shown in FIG. 7. The oxygen inlet 160 may be an oxygen barb protruding from a bridge portion 129 (see FIG. 5) connecting the radially inner and outer portions 122 and 124 of the top portion 120. The oxygen inlet 160 may be angled substantially perpendicular to an imaginary plane of the top portion 120 to improve ease of use and reduce the risk of kinking of the tube that supplies oxygen to the inlet. And, a T-fitting 162 may be fluidly connected to the oxygen inlet 160 and formed in a gap 138 formed in the bottom portion 130, below the bridge portion 129.

[0052] The tube 180 may be fluidly connected to the T-joint 162 and may be secured in place by a number of holders 170. As shown in FIG. 8, each of these holders 170 may be secured to the bottom 130 of the body 110 and may include an upper vertical portion 172 that protrudes from the top 120 in a direction substantially perpendicular to an imaginary vertical plane of the top 120. The holders 170 may secure the tube 180 below the bottom 130, and each of the holders 170 may also include an angled portion 174 that is angled outwardly relative to the vertical portion 172. The angled portion 174 may be angled by, for example, 2.5 degrees relative to the vertical portion 172, although other angles are possible. The angled portion 174 of each holder 170 may include a hole through which the tube 180 may pass. As described below, the angling of angled portion 174 relative to vertical portion 172 can help ensure that neither holder 170 nor tube 180 interferes with organ cradle 60, the organs or vasculature thereon, or a cannula that may be placed within bowl 30 during use. The rounded ends of angled portion 174 where the holes are located can also ensure that there is no collision or obstruction with bowl 30 during use.

[0053] The tube 180 may be formed of an aromatic polyether-based polyurethane and may be long enough to surround the bottom 130 and thus the perfused organ when the oxygenation device 100 functions as a lid for the bowl 30. Preferably, the overall length of the tube 180 may be equal to or about 1,054.10 mm, although other lengths are possible. FIG. 9 is an enlarged view of portion IX of the tube 180 shown in FIG. 8, and as shown in this figure, the tube 180 may include multiple groups 182 of holes 184 that may be spaced apart a distance 186 along the length of the tube 180. Preferably, the distance 186 may be equal to or about 34.79 mm, although other distances are possible. Twenty-four groups 182 may be formed in the tube 180, and each group may include five holes 184 evenly spaced around the circumference of the tube 180, as shown in FIG. 10, which shows a cross-section of the tube 180 in one of the groups 182. Thus, the tube 180 may include a total of 120 holes 184. Each of the holes 184 may be formed in the tube 180 by laser ablation. And each hole 184 may have a diameter of 0.10 mm to 0.18 mm, which is within the capabilities of the laser ablation process and has been shown to be sufficiently reproducible. A hollow fiber filter may be used in place of the tube 180 to provide oxygen to the perfusate. A hollow fiber filter may prevent bubbles in the perfusate during the oxygenation process. However, if the perfusate is not whole blood, this potential difference may not be enough to justify the significant increase in cost of a hollow fiber filter compared to the tube 180.

[0054] The above-mentioned arrangement of holes 184, particularly their number and diameter, ensures that the perfusate in the perfusate bath is "bubbly" in a sufficiently short time to saturate with oxygen while maintaining reasonable costs. Preferably, at an oxygen flow rate of, for example, 10 liters per minute, the holes 184 ensure that the perfusate in the bath is saturated within a time frame of 10 to 15 minutes, which is acceptable in most clinics since concurrent surgical procedures may take significantly longer. Other numbers of holes 184 and other sizes of those holes are possible, but various considerations must be taken into account. For example, having more holes 184 of the same diameter can reduce the time required to fully saturate the perfusate. However, since the cost of the tubing 180 is directly proportional to the number of holes 184, increasing the number may increase the cost of the tubing. On the other hand, a substantially smaller number of holes 184 may increase the time required to saturate the perfusate in the bath.

[0055] Other arrangements of holes 184 are possible. They may be arranged, for example, linearly along the length of tube 180. However, the above arrangement of groups 182 helps to ensure that the five holes 184 are spaced around the circumference of tube 180 and that at least most of the holes 184 are located below the surface of the perfusate during use. Evenly spacing groups 182 by distances 186 along the length of tube 182 may also help to ensure that the majority of the perfusate is evenly exposed to oxygen gas, thereby preventing insufficient concentrations in certain areas.

[0056] FIG. 11 illustrates how a device 100 with an oxygenation option can be used with a perfusion apparatus, such as perfusion apparatus 10, to increase the amount of dissolved oxygen in the perfusate that constitutes the perfusate bath. In a first step 210, the oxygenation device 100 can be placed on the bowl 30. This arrangement is shown in cross-section in FIG. 12. As shown in this figure, the lower edge 126 of the oxygenation device 100 can be sized to match the recess 36 on the upper surface of the bowl 30. The holder 170 can also secure the tube 180 and its hole 184 in a position low enough to be immersed in the perfusate bath, a possible reference position of which is shown at 190 in FIG. 12. And also, the angled portion 174 of the holder 170 allows the tube 180 to be positioned outwardly so as not to interfere with the organ cradle 60, the organs or vasculature thereon, or the cannula in the assembled position shown in FIG. 12. The oxygenation device 100 can be secured to the bowl 30 by the latches described above.

[0057] In the next step 220, the oxygenation device 100 can be connected to an external oxygen source. The oxygen source is not particularly limited, except that it is preferable to provide regulated medical grade oxygen. It can be, for example, an oxygen cylinder or a wall valve located in a hospital or clinic. To connect the oxygenation device 100 to the oxygen source, the user(s) 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.

[0058] Following step 220, oxygen may be supplied at step 230. Preferably, oxygen may be supplied from an oxygen source at a flow rate of 10 liters per minute or about 10 liters per minute for at least 10 minutes, more preferably at least 15 minutes, and even more preferably at least 20 minutes. However, other oxygen flow rates are possible. For example, oxygen may be supplied from an oxygen source at a flow rate of 1, 2, or 3 liters per minute. However, this may unacceptably lengthen the period required to fully saturate the perfusate in the perfusate bath. On the other hand, oxygen flow rates up to 20 liters per minute or more are contemplated. However, flow rates above 20 liters per minute may create high back pressure at the connection between tubing 180 and T-fitting 162, which may cause a risk of the perfusate bath not being fully saturated with oxygen due to high pressure leaks. Supplying oxygen at the preferred flow rates for the preferred duration may result in dissolved oxygen levels in the perfusate of 600-800 mmHg, which is believed to be desirable for organ perfusion. Despite the additional oxygen being introduced into bowl 30 via tube 180 and its holes 184, vent 128 allows the atmospheric pressure within bowl 30 and above the perfusate bath to avoid a substantial increase in pressure, by releasing most of the introduced oxygen to the atmosphere. In fact, the increase in atmospheric pressure within bowl 30 may be less than 5 mmHg. When the supply of oxygen is interrupted, vent 128 allows the pressure within bowl 30 to equilibrate with the pressure of the outside atmosphere.

[0059] Once the desired oxygenation level has been reached, the oxygen supply can be discontinued and the oxygenation device 100 can be removed from the bowl 30. The inner lid 66 can then be placed on the bowl 30, preferably as soon as possible, since the oxygenated perfusate is then open to the atmosphere. The organ can then be placed in the bowl 30 and perfused with the oxygenated perfusate. It is also envisaged that once the oxygen supply has been discontinued, there will be some delay in placing the organ in the bowl 30 and initiating perfusion. It will therefore be necessary to re-oxygenate the perfusate after a period of time so that the desired oxygenation level can be maintained. This re-supply is preferably done before removing the oxygenation device 100 from the bowl 30, since once removed from the bowl the sterility of the device may be compromised.

[0060] Thus, the process 200 shown in FIG. 11 provides a means to pre-fill the perfusate with oxygen prior to placement of an organ in the perfusion circuit and subsequent perfusion of the organ. However, various modifications are envisioned. For example, the oxygenation device 100 may not be removed from the bowl 30 upon completion of pre-filling, and thus may function as a bowl lid during perfusion of the organ. The oxygenation device 100 may also continue to oxygenate the perfusate during perfusion and / or transport of the organ. This oxygenation during perfusion may help to maintain elevated oxygen levels in the perfusate during transport. Of course, a portable oxygen source would be beneficial for this modification. Step 210 of the process 200 may also precede steps 205 and 207. In step 205, following priming and cooling of the perfusion circuit, the inner lid 66 of the perfusion circuit may be removed to make room for the oxygenation device 100. Then, in step 207, the perfusion fluid may be decanted into bowl 30 to form a perfusion fluid bath.

[0061] Thus, as described above, device 100 with an oxygenation option provides a mechanism for rapidly oxygenating the perfusate, thereby providing the above-mentioned benefits of oxygen while avoiding the risks associated with delaying the transplant process. It also works in conjunction with existing perfusion circuits, ensuring that clinics or hospitals get the benefits of oxygenation without having to replace these expensive disposables.

[0062] As shown in Figures 3-8, the oxygenation component 150 may constitute part of a separate oxygenation device 100. However, this need not be the case. Instead, and as shown in Figure 13, part or all of the oxygenation component 350 may be integrated with the organ container. For example, a tube 380, which may be identical to any of the tube 180 embodiments described above, may be incorporated inside the bowl 30. This tube 380 may extend generally along the inner wall 32 of the bowl to surround the organ or tissue placed in the bowl. Holders 370 may extend from the rim 34 of the bowl 30 and hold the tube 380 submerged in the perfusion fluid bath within the bowl during perfusion of the organ. These holders 370 generally descend along the inner wall 32 of the bowl 30, and like the holders 170, they may each include a hole through which the tube 380 can pass.

[0063] Also included within bowl 30 may be a T362 fitting that fluidly connects tubing 380 to an oxygen source, and a connection 364 upstream of the T362 fitting that allows the practitioner to switch between bubble and surface oxygenation. More specifically, when oxygen line 390 upstream of connection 364 and downstream tubing 382 are connected at connection 364, input oxygen is delivered to tubing 380, which may be submerged below the surface of the perfusion bath during perfusion of an organ. However, when that connection is disconnected at connection 364, input oxygen is delivered within bowl 30 but above the surface of the perfusion bath. Preferably, connection 364 may be a luer lock connection or a three-way stopcock.

[0064] FIG. 14 shows an oxygen line 390 that may extend from connection 364 to the exterior of bowl 30. Oxygen may be provided from an oxygen source (not shown) at end 392 of oxygen line 390. An antibacterial filter 394 may be attached to oxygen line 390 to filter the input oxygen. For example, as shown in FIG. 14, filter 394 may be attached to end 392 of the line. As shown in FIG. 15, oxygen line 390 may extend away from bowl 30 so that oxygen may be input to line 390 even when overcap 20 is closed.

[0065] 16 shows a method 400 in which a perfusion apparatus, such as perfusion apparatus 10, with an organ container including a bowl 30 having an oxygenation component 350 can be used to increase the amount of dissolved oxygen in the perfusate constituting the perfusate bath. In a first step 410, an oxygen line 390 can be connected to an oxygen source, such as an external oxygen source, via an antibacterial filter 394. Preferably, this connection is made after a volume of Vasosol solution, such as 3 L, has been added to the bowl 30 to form a perfusate bath therein, and both the inner and outer lids 66 and 67 are placed on the bowl 30 to seal it from the outside environment. In a second step 420, oxygen is preferably supplied to the oxygen line 390 at a flow rate of 10 L / min. This input oxygen is supplied to the perfusate bath via the submerged tubing 380, as the oxygen line 390 and tubing 382 are connected via connection 364. This bubble oxygenation may continue for at least 10 minutes, more preferably at least 20 minutes, during which time the clinician may prepare the organ for machine perfusion. Both lids 66, 67 may remain closed during the supply of oxygen by tube 380.

[0066] In step 430, both inner and outer lids 66, 67 can be removed to leave bowl 30 in an open position. After outer lid 67 is opened, a sterile drape can optionally be applied before opening inner lid 66. Once both lids are removed, oxygen line 390 and tubing 382 can be disconnected at connection 364. It may be preferable to also reduce the oxygen input to oxygen line 390 to about 2 L / min, which can then be supplied to the surface of the perfusion bath via open connection 364. An organ can then be introduced into bowl 30 and perfusion of the organ can begin. Inner lid 66 can then be placed over bowl 30 as soon as possible thereafter, and once the perfusion flow rate has stabilized, the sterile drape can be removed and outer lid 67 can also be placed over bowl 30. Preferably, outer lid 20 is closed during this surface oxygenation to help maintain a hypothermic environment for the perfused organ. Surface oxygenation can continue until transportation, step 440, whereupon oxygen line 390 can be disconnected from the external oxygen source and overcap 22 covering end 390 of oxygen line can also be closed. Upon arrival at the transplant center, surface oxygenation can be resumed, step 450. This can be accomplished by opening overcap 22, connecting oxygen line 390 to another oxygen source through antibacterial filter 394, and then providing a reduced flow rate of oxygen, preferably 2 L / min, until transplantation of the organ.

[0067] Moving oxygenation component 350 to bowl 30 in this manner provides various functionality differences as compared to component 150 being part of a separate oxygenation device 100. For example, bubble oxygenation may be achieved without the presence of device 100. Additionally, locating end 392 of oxygen line 390 outside of bowl 30 while including connection 364 within the bowl allows the option of continuing oxygenation during perfusion via an interface between the perfusate bath and the gas.

[0068] What has been described and illustrated herein are embodiments of the present invention with some variations. The terms, descriptions and figures used herein are set forth by way of example only and are not meant to be limiting. Those skilled in the art will recognize that many variations are possible within the spirit and scope of the present invention. For example, adding an external port to the perfusion device 10 for an oxygen line 390 allows for continuous surface oxygenation even when both lids 20, 22 are closed during transport. A compact oxygen generator may also eliminate the need for an external oxygen source.

Claims

1. 1. An apparatus for perfusion and / or transport of an organ or tissue, the apparatus comprising: An organ container for preserving the organ or tissue, a bowl configured to hold the organ or tissue and a perfusion bath; an organ container comprising: (i) a tube connectable to an oxygen source, (ii) comprising a plurality of holes through which oxygen can exit the tube, and (iii) a tube positioned within the bowl so as to be immersed in the perfusion fluid bath present during perfusion or transport of the organ or tissue; an oxygen line configured to deliver oxygen from an oxygen source to the tube, an oxygen line, a first end of the oxygen line within the bowl of the organ container and a second end of the oxygen line outside the bowl; a first outer lid configured to cover the bowl when closed; a second overcap adjacent to the first overcap and configured to cover other components of the device when closed; The apparatus wherein the second end of the oxygen line is exposed even when the first overcap is closed.

2. 10. The apparatus of claim 1, further comprising at least one holder within said bowl for securing said tubing below the surface of said perfusion fluid bath.

3. the at least one holder is a plurality of holders; Each of the plurality of holders comprises: (i) extending from an upper edge of the bowl toward a bottom of the bowl; (ii) moving down along the inner wall of the bowl; and 3. The device of claim 2, further comprising: (iii) a hole through which the tube passes.

4. 3. The device of claim 2, wherein the at least one holder secures the tube in a loop that encircles the organ or tissue in use.

5. further comprising a connector within the bowl; 3. The apparatus of claim 2, wherein the connection is configured to connect and disconnect the oxygen line and the tube that extend outside the bowl.

6. 6. The apparatus of claim 5, wherein the connection is connected to the tube by a T-joint with another tube.

7. The device of claim 5 , wherein the connection is a Luer lock fitting.

8. The device of claim 1 , wherein the holes are arranged in a plurality of groups spaced apart along the length of the tube.

9. 9. The apparatus of claim 8, wherein each of said groups includes a plurality of said holes spaced around a circumference of said tube.

10. each group of the plurality of groups is spaced from another group of the plurality of groups by about 34.79 mm of the tube; 10. The apparatus of claim 9, wherein an average diameter of each of the plurality of holes is between 0.10 mm and 0.18 mm.

11. 10. The apparatus of claim 1, further comprising an antibacterial filter at a second end of the oxygen line.

12. 1. A method of oxygenating a perfusate perfused through an organ or tissue, comprising: introducing the perfusion fluid into the organ container of the apparatus of claim 1 so as to form a perfusion fluid bath in which the tubes inside the bowl are immersed; connecting the tube to a source of oxygen; and supplying oxygen from the oxygen source through holes in the tube into the perfusion bath to increase the oxygen concentration of the perfusion fluid constituting the perfusion bath.

13. 13. The method of claim 12, further comprising the step of supplying oxygen from the oxygen source at a flow rate of about 10 liters per minute for at least 10 minutes.

14. 13. The method of claim 12, disconnecting the tubing from the oxygen source with a connection in the bowl such that oxygen from the oxygen source is delivered to a space in the bowl above the surface of the perfusion solution bath; reducing the flow rate of the oxygen supplied; introducing an organ or tissue into the bowl of the organ container; and perfusing the organ or tissue with the perfusion solution while the oxygen is supplied to the bowl and to the space above the surface of the perfusion solution bath.

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