Patent Description:
It is an objective of organ perfusion apparatuses to support aerobic metabolism such that the organ remains viable before being used for research, diagnosis, treatment, or transplantation. Often the organ must 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.

Various organ perfusion apparatuses are known. <CIT>; <CIT>; and <CIT> disclose, for example, a perfusion apparatus that employs a disposable perfusion circuit within which the organ may be stored during perfusion. This circuit comprises a basin that may serve as a receptacle for an organ cradle on which the organ may be placed and for a perfusate bath that may be formed around the organ. Inner and outer lids may be used to close the basin during perfusion, and the basin may fit within a coolant container so that both the perfusate bath and the organ are brought to hypothermic temperatures. <CIT> discloses an oxygenator device.

<CIT> discloses an organ transporter with supplemental oxygenation system, wherein the latter may be embedded in the lid of the coolant container. A submerged tube for delivering the oxygen from the oxygenation system to the perfusate bath in the organ cassette may include holes that allow the oxygen to be bubbled through the perfusate. The oxygenation system includes an inlet port for connecting an external oxygen source, and an outlet port for connection to the submerged tube via a biofilter outside the cassette. <CIT> discloses an in-vitro animal organ perfusion device; <CIT> discloses an organ preservation system.

Although the use of hypothermic temperatures during transportation and perfusion greatly improves organ preservation by decreasing oxygen demands and metabolic activity of the organ, it does not completely eliminate them. A corresponding lack of oxygen can drive the cells of the organ to anaerobic activity, which causes a buildup of lactate and mitochondrial uncoupling and depleted adenosine triphosphate ("ATP") stores, and thereby leads to the release of toxic molecules such as radical oxygen species, inflammatory cytokines, and lactate. These toxic molecules and anaerobic mitochondrial activity increase the production of reactive oxygen molecules, which may in turn lead to adverse ischemia and reperfusion injury.

Given that a lack of oxygen drives the cells to anaerobic activity and worsens ischemia and reperfusion injury, there has been great interest in the benefits associated with increasing oxygen to a hypothermic perfused organ by, say, introducing additional oxygen into the perfusate solution. <CIT> discloses an oxygen generator or concentrator that preferably produces oxygen in real time to provide oxygenation to the perfusate, for example.

However, there are at least two difficulties associated with prior oxygenation devices and methods. The first is the amount of time required to adequately oxygenate the perfusate solution. Time during organ transplantation is at a premium, so an oxygenator device should be able to rapidly oxygenate the perfusate solution. Further, hospitals and clinics may have also acquired or purchased a substantial amount of disposables to be used during perfusion, and may be hesitant to discard these likely expensive disposables to oxygenate the perfusate solution. There is thus also a need for a device with an oxygenation option that works with existing equipment and disposables to oxygenate the perfusate solution.

Disclosed herein is a device with an oxygenation option for oxygenating a perfusate solution to be perfused through an organ or tissue. This device comprises an inlet configured to receive oxygen from an oxygen supply, and it also comprises tubing connected to the inlet, the tubing including a plurality of holes by which the received oxygen may exit the tubing.

In combination with any of the above or below features, the oxygenation device may also comprise a top portion from which the inlet extends, and it may further include a plurality of holders extending below the top portion so as to secure the tubing below the top portion.

In combination with any 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 tubing may be secured by the angled portions of the plurality of holders.

In combination with any of the above or below features, the plurality of holders may secure the tubing in a loop having a circumference sufficient to encircle the organ or tissue in use, and a majority of this loop may be substantially parallel to a virtual plane formed by the top portion.

In combination with any 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, from which the inlet extends, may constitute a lid for a basin of the organ perfusion circuit that is configured to hold the organ or tissue during perfusion.

In combination with any of the above or below features, the tubing may be fixed below the top portion so that, when the oxygenation device is placed on the basin, the tubing and the plurality of holes therein may be submerged in a bath of the perfusate solution in the basin.

In combination with any of the above or below features, the tubing may be secured in position by a plurality of holders so that, when the oxygenation device is placed on the basin, the tubing does not interfere with an organ cradle locatable within the basin.

In combination with any of the above or below features, the oxygenation device may further comprise a hydrophobic vent in the top portion, the vent being configured to limit pressure increase within the basin when the oxygenation device is placed on the basin and oxygen flows from the plurality of holes in the tubing to the perfusate solution.

In combination with any of the above or below features, the holes may be arranged in a plurality of groupings spaced apart along a length of the tubing.

In combination with any of the above or below features, each of the groupings may comprise a plurality of the holes spaced apart around a circumference of the tubing.

In combination with any of the above or below features, each pair of the plurality of groupings may be spaced apart by <NUM> of the tubing, and an average diameter of the plurality of holes may be between <NUM> and <NUM>.

Also disclosed herein is a method of using the device with an oxygenation option in accordance with any of the above features. This method may include placing the oxygenation device on a basin of an organ perfusion circuit so that the tubing and the holes therein are submerged within a bath of the perfusate solution within the basin; connecting the inlet of the oxygenation device to an oxygen supply; and administering oxygen from the oxygen supply, through the inlet, through the holes in the tubing, and into the perfusate bath so as to increase oxygen concentration of the perfusate solution constituting the bath.

The method may also include a step of administering the oxygen from the oxygen source at a rate of about <NUM> liters per minute for at least <NUM> minutes.

It may further include, prior to the placing step, removing a lid of the basin. The placing step may thus replace the lid of the basin with the oxygenation device.

The method may yet further include steps of discontinuing administration of the oxygen from the oxygen supply, and then placing the organ or tissue in the basin of the organ perfusion circuit.

The oxygen may alternatively be administered while the organ or tissue is being perfused in the organ perfusion circuit.

But although a separate device with an oxygenation option has its benefits, a clinician may instead prefer that the oxygenation structures be located within the basin of the organ container itself. Among other advantages like the ability to close an outer lid on top of the basin of the organ container during oxygen administration and especially the ability to provide oxygen during liver perfusion, this could reduce the number of disposables that a hospital or clinician must maintain on hand.

In accordance with a first aspect of the invention, there is disclosed an apparatus for at least one of perfusion and transport of an organ or tissue as defined in claim <NUM>. The apparatus comprises an organ container for storing the organ or tissue and configured to be inserted into the apparatus. The organ container includes a basin configured to hold the organ or tissue and a perfusate bath, and it also includes tubing that (i) is connectable to a source of oxygen, (ii) includes a plurality of holes by which the oxygen may exit the tubing, and (iii) is located within the basin so as to be submerged within the perfusate bath present during the perfusion or transport of the organ or tissue.

In combination with any of the above or below features, the organ container may also include at least one holder within the basin to secure the tubing below a surface of the perfusate bath.

In combination with any of the above or below features, the at least one holder may be a plurality of the holders, and each of the plurality of holders may: (i) extend toward a bottom of the basin from an upper rim of the basin; (ii) descend along an internal wall of the basin; and (iii) include a hole through which the tubing passes.

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

In combination with any of the above or below features, the organ container may also include a connector within the basin, and the connector may be configured to connect and disconnect the tubing with an oxygen line that extends outside of the basin.

In combination with any of the above or below features, the connector may be connected to the tubing by another tubing and a T-fitting.

In combination with any of the above or below features, the connector may be a Luer Lock fitting.

In combination with any of the above or below features, the holes of the tubing may be arranged in a plurality of groupings spaced apart along a length of the tubing.

In combination with any of the above or below features, the groupings may comprise a plurality of the holes spaced apart around a circumference of the tubing.

In combination with any of the above or below features, each pair of the plurality of groupings may be spaced apart by about <NUM> of the tubing, and an average diameter of each of the plurality of holes may be between <NUM> and <NUM>.

And in combination with any of the above or below features, the oxygenation device may further include a hydrophobic vent in each lid of the basin, the vent in use limiting pressure increase within the basin.

The apparatus includes an oxygen line configured to convey oxygen from a source of oxygen to the tubing. A first end of the oxygen line is within the basin of the organ container, and a second end of the oxygen line is outside the basin.

The apparatus further includes a first external lid configured to cover the basin when closed and a second external lid, adjacent the first external lid, and configured to cover other components of the apparatus when closed. The second end of the oxygen line is exposed even when the first external lid is closed.

In combination with any of the above or below features, the apparatus may further include an anti-bacterial filter at the second end of the oxygen line.

In accordance with a second aspect of the invention, there is disclosed a method of oxygenating a perfusate solution to be perfused through an organ or tissue as defined in claim <NUM>. This method includes a step of introducing the perfusate solution into the organ container discussed above so as to form in the basin of the organ container a perfusate bath within which the tubing inside the basin is submerged. The method also includes steps of connecting the tubing to a source of oxygen and administering oxygen from the source, through the holes in the tubing, and into the perfusate bath so as to increase oxygen concentration of perfusate solution constituting the bath.

The method may further include a step of administering the oxygen from the oxygen source at a rate of about <NUM> liters per minute for at least <NUM> minutes.

The method further includes the steps of: disconnecting the tubing from the oxygen by way of a connector within the basin so that the oxygen is administered in a space within the basin above a surface of the perfusate bath; reducing a flow rate of the administered oxygen; introducing an organ or tissue into the basin of the organ container; and perfusing the organ or tissue with the perfusate solution while the oxygen is being administered in the space within the basin and above the surface of the perfusate bath.

These and other aspects of the present disclosure will be described with reference to the attached drawings and following detailed description.

<FIG> and <FIG> show an exemplary perfusion apparatus <NUM> for an organ. The organ may preferably be a liver, kidney, heart, lung, or intestine, but it may be any human or animal, natural or engineered, healthy, injured, or diseased organ or tissue. The apparatus <NUM> may include outer lids <NUM>, <NUM> and an organ container including a basin <NUM> (see <FIG>) in which the organ may be placed. The basin <NUM> may hold a removable cradle <NUM>, which may preferably include a surface 60a on which the organ may be disposed when the organ is in the apparatus <NUM>. The basin <NUM> and/or the cradle <NUM> may preferably be configured to allow a perfusate bath of perfusate solution such as VASOSOL® to be contained around the organ.

The basin <NUM> may preferably be disposed within an insulating coolant container <NUM> that may contain cold materials such as ice, ice water, brine, or the like. Coolant container <NUM> may be permanently or removably attached to, or an integral, monolithic part of, apparatus <NUM>. Thus, in use, the organ may be disposed within the cradle <NUM>, which may be disposed within the basin <NUM>, which may be disposed within the coolant container <NUM>, as shown in <FIG>. The arrangement of the coolant container <NUM>, basin <NUM>, and cradle <NUM> preferably provides a configuration that provides cooling for the organ without the contents of coolant container <NUM> contacting the organ or the cradle <NUM>. Although the coolant container <NUM> is described herein as containing ice or ice water, any suitable cooling medium can be used.

As further shown in <FIG>, an inner lid <NUM> and an outer lid <NUM> may be provided on an upper surface of the basin <NUM>. The inner lid <NUM> may be sized to come into close proximity to the perimeter top surface of the cradle <NUM> to help maintain stability of the organ in the event of mechanical impact and shock during transport. More specifically, the inner lid <NUM> may have a downwardly protruding extension 66a that matches a circumferential shape of a peripheral ridge 60b of the cradle <NUM> and is configured to contact the peripheral ridge 60b and help hold the cradle <NUM> in position. The lids <NUM> and <NUM> may create a substantially fluid-tight seal with the basin <NUM>, and they can prevent contamination. The lids <NUM> and <NUM> may also provide for a redundant airtight seal should the seal from either lid <NUM> or <NUM> fail. Both the inner lid <NUM> and the outer lid <NUM> may preferably contain an air vent, e.g., a porous hydrophobic membrane, that allows for gas transfer in order to maintain pressure equilibrium.

Preferably, all components of the apparatus <NUM> that come into contact with perfusate solution and/or the organ are disposable and/or easily replaced. These components may include the basin <NUM>, the organ cradle <NUM>, and the lids <NUM> and <NUM>, which may constitute parts of a disposable organ perfusion circuit. In use, this disposable organ perfusion circuit may be placed within the non-disposable portion of the apparatus <NUM>, and the organ may be placed on the organ cradle <NUM> within the basin <NUM>. Because of the presence of the coolant container <NUM>, both the organ and the perfusate bath within the basin <NUM> are subjected to hypothermic temperatures. The perfusate solution may then be circulated through the disposable perfusion circuit and the organ.

<FIG> and <FIG> show a device with an oxygenation option <NUM> in accordance with one or more aspects of the present disclosure. The device <NUM> may be designed to work with the perfusion apparatus <NUM> to increase the oxygen concentration of the perfusate bath within the basin <NUM>. This device <NUM> may generally be constituted by a main body <NUM> and oxygenation components <NUM>. The main body <NUM> may in turn include a top portion <NUM> including, as shown in <FIG>, radially inner and outer portions <NUM> and <NUM>. The main body <NUM> may also include, as shown in <FIG>, a bottom portion <NUM> projecting downward from the top portion <NUM>. The main body <NUM> may be formed, for example, from clear polycarbonate plastic resin.

The top portion <NUM> may be, like the inner lid <NUM>, sized to correspond to the basin <NUM>. More specifically, a lower lip <NUM> (see <FIG>) of the radially outer portion <NUM> of the top portion <NUM> may be sized so as to be received by an indentation <NUM> (see <FIG>) in an upper surface of the basin <NUM> and thereby allow the oxygenation device <NUM> to constitute a lid for that basin in place of the inner lid <NUM>. Latches (not shown) on the basin <NUM> may be used to lock the oxygenation device <NUM> in place relative to the basin <NUM>. As shown in <FIG> and <FIG>, the top portion <NUM> may be substantially planar. That is, although the surface of at least one of the radially inner and outer portions <NUM> and <NUM> may be slightly inclined, the overall shape of the top portion <NUM> forms a virtual plane projecting into the pages of <FIG> and <FIG>. For example, the outer portion <NUM> may be flat, whereas the inner portion <NUM> may be convex outward. Also provided within the top portion <NUM> may be a vent <NUM> (see <FIG> and <FIG>). Like the air vents of the lids <NUM> and <NUM>, the vent <NUM> may include a porous hydrophobic membrane, which allows for gas transfer in order to maintain pressure equilibrium. More specifically, the membrane of the vent <NUM> may be an acrylic copolymer 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 <NUM> microns, and it may repel and be resistant to oil, water, and organic solvents and be non-wettable by most low-surface-tension liquids. This stands in contrast to, say, a hydrophilic membrane that has a tendency to mix with or be wettable by such liquids. Around the perimeter of the vent <NUM> may be provided an adhesive to secure the vent <NUM> to the remainder of the top portion <NUM> and thereby ensure that it remains attached thereto with a tight seal.

The bottom portion <NUM> may be formed in the space between the radially inner and outer portions <NUM> and <NUM> of the top portion <NUM>, and it may have a substantially triangular shape in cross-section. More specifically, a radially outer wall <NUM> (see <FIG>) of the bottom portion <NUM> may extend downward substantially perpendicular to the virtual plane of the top portion <NUM>, and a radially inner wall <NUM> of the bottom portion <NUM> may extend downward from the top portion <NUM> at an angle inclined relative to the outer wall <NUM>. The walls <NUM> and <NUM> may meet at a vertex <NUM>, thereby ensuring that the main body <NUM> is able to create a substantially fluid-tight seal with the basin <NUM> and thereby prevent contamination. Finally, the bottom portion <NUM> (and particularly the vertex <NUM>) may, like the downwardly protruding extension 66a of the inner lid <NUM>, also match the circumferential shape of the peripheral ridge 60b of the cradle <NUM>, and it may thus likewise be configured to contact that peripheral ridge and help hold the cradle <NUM> and any organ thereon in position.

The oxygenation components <NUM> may in turn include, as shown in <FIG>, an oxygen inlet <NUM>, a T-fitting <NUM>, holders <NUM>, and tubing <NUM>. The oxygen inlet <NUM> may be an oxygen barb projecting from a bridge portion <NUM> (see <FIG>) that connects the radially inner and outer portions <NUM> and <NUM> of the top portion <NUM>. The oxygen inlet <NUM> may be angled substantially perpendicular to the virtual plane of the top portion <NUM> to facilitate ease of use and to reduce the risk of kinking of the tube delivering oxygen to the inlet. The T-fitting <NUM> may in turn be fluidly connected to the oxygen inlet <NUM>, and it may be formed below the bridge portion <NUM> in a gap <NUM> formed in the bottom portion <NUM>.

The tubing <NUM> may be fluidly connected to the T-fitting <NUM>, and it may be secured in position by the plurality of holders <NUM>. As shown in <FIG>, each of these holders <NUM> may include an upper, vertical portion <NUM> secured to the bottom portion <NUM> of the main body <NUM> and projecting from the top portion <NUM> in a direction substantially perpendicular to the virtual vertical plane of the top portion <NUM>. The holders <NUM> may secure the tubing <NUM> below the bottom portion <NUM>, and each of the holders <NUM> may also include an angled portion <NUM> that is angled outward relative to the vertical portion <NUM>. The angled portion <NUM> may be angled relative to the vertical portion <NUM> by, say, <NUM> degrees, although other angles are possible. The angled portion <NUM> of each of the holders <NUM> may include a hole through which the tubing <NUM> may pass. As discussed below, angling the angled portions <NUM> relative to the vertical portions <NUM> may help ensure that neither the holders <NUM> nor the tubing <NUM> interferes in use with the organ cradle <NUM>, any organ or vasculature thereon, or cannula that may be disposed within the basin <NUM>. The rounded ends of the angled portions <NUM>, at which the holes are located, may also ensure that there is no crashing or interference with the basin <NUM> during use.

The tubing <NUM> may be formed of aromatic polyether-based polyurethane, and it may be of sufficient length to encircle the bottom portion <NUM> and thus to encircle a perfused organ when the oxygenation device <NUM> serves as the lid for the basin <NUM>. Preferably, the total length of the tubing <NUM> may be equal to or about <NUM>,<NUM>, although other lengths are possible. <FIG> shows an enlarged view of the portion IX of the tubing <NUM> shown in <FIG>, and as shown in this Figure, the tubing <NUM> may include a plurality of groupings <NUM> of holes <NUM> that may be spaced apart along the length of the tubing <NUM> by a distance <NUM>. Preferably, the distance <NUM> may be equal to or about <NUM>, although other distances are possible. <NUM> groupings <NUM> may be formed in the tubing <NUM>, and as shown in <FIG>, which shows a cross-section of the tubing <NUM> at one of the groupings <NUM>, each grouping may include <NUM> holes <NUM> equally spaced around the circumference of the tubing <NUM>. The tubing <NUM> may thus include a total of <NUM> holes <NUM>. Each of the holes <NUM> may be formed in the tubing <NUM> by way of laser ablation. And each hole <NUM> may have a diameter of <NUM> to <NUM>, which has been shown to be well within the capability of the laser ablation process and repeatable. Instead of the tubing <NUM>, hollow fiber filters may be used to provide oxygen to the perfusate solution. Hollow fiber filters may prevent bubbling of the perfusate solution during the oxygenation process. But if the perfusate solution is not whole blood, this potential difference may be insufficient to justify the substantial increase in cost of hollow fiber filters relative to the tubing <NUM>.

The above-described arrangement of the holes <NUM>, and particularly their number and diameter, achieves a sufficiently short time to "bubble" and therefore saturate the perfusate solution of the perfusate bath with oxygen while maintaining a suitable cost. Preferably, at an oxygen flow rate of, say, <NUM> liters per minute, the holes <NUM> ensure that the perfusate solution of the bath will be saturated within a timeframe of <NUM>-<NUM> minutes, which is acceptable for most clinics as surgical procedures taking place concurrently may take substantially longer. Other numbers of holes <NUM> and other sizes of those holes are possible; however, various considerations should be taken into account. More holes <NUM> of the same diameter, for example, may reduce the time required to fully saturate the perfusate solution. But cost of the tubing <NUM> is directly proportional to the number of holes <NUM>, so increasing their number may result in increased cost of the tubing. Substantially less holes <NUM>, on the other hand, may unsatisfactorily increase the time required to saturate the perfusate solution of the bath.

Other arrangements of the holes <NUM> are also possible. They could be positioned linearly along the length of the tubing <NUM>, for example. However, the above-described arrangement with the groupings <NUM>, in which five holes <NUM> are spaced around the circumference of the tubing <NUM>, helps ensure that at least most of the holes <NUM> are placed below the surface of the perfusate in use. Equally spacing the groupings <NUM> by the distance <NUM> across the length of the tubing <NUM> may also help ensure that most of the perfusate solution is evenly exposed to oxygen gas, thereby preventing one region from being underconcentrated.

<FIG> shows a method by which the device with an oxygenation option <NUM> may be used with a perfusion apparatus, e.g., the perfusion apparatus <NUM>, to increase the dissolved oxygen content in the perfusate solution constituting a perfusate bath. In a first step <NUM>, the oxygenation device <NUM> may be placed on the basin <NUM>. This arrangement is shown by cross-section in <FIG>. As shown in this Figure, the lower lip <NUM> of the oxygenation device <NUM> may be sized so as to correspond to the depression <NUM> in the top surface of the basin <NUM>. The holders <NUM> may also secure the tubing <NUM> and the holes <NUM> therein low enough within the basin <NUM> to be submerged within the perfusate bath, a possible level of which is shown by <NUM> in <FIG>. And also by virtue of the angled portions <NUM> of the holders <NUM>, the tubing <NUM> may be located outside so as not to interfere with the organ cradle <NUM>, any organ or vasculature thereon, or any cannula in the assembled position shown in <FIG>. The oxygenation device <NUM> may be secured to the basin <NUM> by way of the aforementioned latches.

In a next step <NUM> the oxygenation device <NUM> may be connected to an external oxygen source. Other than preferably providing regulated, medical-grade oxygen, the oxygen source is not particularly limited. It may be, for example, an oxygen cylinder or a wall valve in a hospital or clinic setting. To connect the oxygenation device <NUM> and the oxygen source, a user or users of the device <NUM> may attach one end of an extension tube to the oxygen inlet <NUM> and another end of that tube to the oxygen source.

Following step <NUM>, oxygen may be administered in a step <NUM>. Preferably, oxygen may be administered from the oxygen source at a rate at or about <NUM> liters per minute for at least <NUM> minutes, more preferably for at least <NUM> minutes, and even more preferably for at least <NUM> minutes. Other rates of oxygen flow are possible, however. For example, the oxygen could be administered from the oxygen source at a rate of <NUM>, <NUM>, or <NUM> liters per minute. But this may unacceptably lengthen the period of time required to fully saturate the perfusate solution of the perfusate bath. On the other hand, oxygen flow rates up to <NUM> liters per minute or more are conceived. However, flow rates greater than <NUM> liters per minute may create a risk of high back pressure on the connections between the tubing <NUM> and the T-fitting <NUM>, which could prevent the perfusate bath from being fully saturated with oxygen due to leaks caused by the high pressure. Administering oxygen at the above preferred rate for the preferred duration may result in dissolved oxygen levels within the perfusate solution of <NUM>-<NUM> mmHg, which is believed to be desirable for perfusion of the organ. Despite the additional oxygen introduced into the basin <NUM> by way of the tubing <NUM> and the holes <NUM> therein, the vent <NUM> may prevent substantial increases in pressure of the atmosphere within the basin <NUM> and above the perfusate bath by venting most of the introduced oxygen to atmosphere. Indeed, the increase in atmosphere pressure within the basin <NUM> may be less than <NUM> mmHg. Once administration of oxygen is discontinued, the pressure within the basin <NUM> may equilibrate to that of the external atmosphere due to the vent <NUM>.

Once desirable oxygenation levels have been reached, the oxygen administration may be discontinued and the oxygenation device <NUM> may be removed from the basin <NUM>. Because the oxygenated perfusate is then open to atmosphere, the inner lid <NUM> may then preferably be placed on the basin <NUM> as soon as possible. The organ may then be placed within the basin <NUM> and perfused with the oxygenated perfusate solution. It is also conceivable that, once the administration of oxygen has been discontinued, there may be some delay in placing the organ within the basin <NUM> and beginning perfusion. It may therefore be necessary to oxygenate the perfusate solution again after a period of time so that the desirable oxygenation level can be maintained. Preferably this re-administration occurs prior to removal of the oxygenation device <NUM> from the basin <NUM>, as the device's sterility may become compromised once removed from the basin.

The process <NUM> shown in <FIG> thus provides a means by which to precharge with oxygen a perfusate solution prior to placement of an organ within the perfusion circuit and subsequent perfusion of that organ. However, various modifications are envisioned. For example, the oxygenation device <NUM> may not be removed from the basin <NUM> once pre-charging is complete, and it could thus serve as the lid of the basin during perfusion of the organ. The oxygenation device <NUM> could also continue to oxygenate the perfusate during perfusion and/or transport of the organ. This oxygenation during perfusion could help maintain elevated oxygen levels in the perfusate throughout transport. Of course, a portable oxygen source would likely be beneficial for this modification. The step <NUM> of the process <NUM> may also be preceded by steps <NUM> and <NUM>. In step <NUM>, following priming and cooling of the perfusion circuit, the inner lid <NUM> of the perfusion circuit may be removed to make space for the oxygenation device <NUM>. And in step <NUM>, the perfusate solution may be decanted into the basin <NUM> so as to form the perfusate bath.

As explained above, the device with an oxygenation option <NUM> thus provides a mechanism by which to rapidly oxygenate a perfusate solution, thereby providing the above-described benefits of oxygen while avoiding the hazards associated with delays in the transplantation process. It also works with existing perfusion circuits, ensuring that these costly disposables need not be replaced by a clinic or hospital to obtain the benefits of oxygenation.

As shown in <FIG>, the oxygenation components <NUM> may constitute part of a separate oxygenation device <NUM>. But this need not be the case. Instead, and as shown in <FIG>, some or all of oxygenation components <NUM> may be integrated with the organ container. For example, tubing <NUM>, which may be identical to any of the embodiments of the tubing <NUM> discussed previously, may be incorporated inside the basin <NUM>. This tubing <NUM> may run generally along an internal wall <NUM> of the basin so as to encircle an organ or tissue placed within the basin. Holders <NUM> may extend from a rim <NUM> of the basin <NUM> and hold the tubing <NUM> so that it is submerged within a perfusate bath in the basin during perfusion of the organ. These holders <NUM> may generally descend along the internal wall <NUM> of the basin <NUM>, and like the holders <NUM>, they may each include a hole through which the tubing <NUM> may pass.

Also included within the basin <NUM> may be a T-fitting <NUM>, which fluidly connects the tubing <NUM> to an oxygen source, and a connector <NUM>, upstream of the T-fitting <NUM>, that enables a practitioner to switch between bubble and surface oxygenation. More specifically, when upstream, oxygen line <NUM> and tubing <NUM> downstream of the connector <NUM> are connected at the connector <NUM>, input oxygen is routed to the tubing <NUM>, which may be submerged below the surface of the perfusate bath during perfusion of the organ. But when that connection is severed at the connector <NUM>, the input oxygen is administered within the basin <NUM> but above the surface of the perfusate bath. Preferably, the connector <NUM> may be a Luer Lock connector or <NUM>-way stopcock.

<FIG> shows the oxygen line <NUM>, which may extend from the connector <NUM> and outside of the basin <NUM>. At an end <NUM> of the oxygen line <NUM>, oxygen may be supplied from an oxygen source (not shown). And an anti-bacterial filter <NUM> for filtering the input oxygen may be attached to the oxygen line <NUM>. For example, and as shown in <FIG>, this filter <NUM> may be attached to the end <NUM> of the line. And as shown in <FIG>, by virtue of the oxygen line <NUM> extending away from the basin <NUM>, oxygen may still be input to that line <NUM> with the outer lid <NUM> closed.

<FIG> shows a method <NUM> by which a perfusion apparatus, e.g., the perfusion apparatus <NUM>, equipped with an organ container including a basin <NUM> having the oxygenation components <NUM> may be used to increase the dissolved oxygen content in the perfusate solution constituting a perfusate bath. In a first step <NUM>, the oxygen line <NUM> may be connected to an oxygen source, e.g., an external oxygen source, by way of the anti-bacterial filter <NUM>. Preferably, this connection occurs after an amount, e.g., <NUM>, of Vasosol solution has been added to the basin <NUM> so as to form the perfusate bath therein and both inner lid <NUM> and outer lid <NUM> are placed on the basin <NUM> so as to seal it from the external environment. In a second step <NUM>, oxygen is administered to the oxygen line <NUM> at a rate of preferably <NUM>/min. Because the oxygen line <NUM> and the tubing <NUM> are connected by way of the connector <NUM>, this input oxygen is supplied to the perfusate bath by way of the submerged tubing <NUM>. This bubble oxygenation may continue for at least <NUM> minutes, and more preferably for at least <NUM> minutes, during which time the clinician may be preparing the organ for machine perfusion. Both lids <NUM>, <NUM> may remain closed during the administration of oxygen by way of the tubing <NUM>.

In step <NUM>, both inner and outer lids <NUM>, <NUM> may be removed so as to open the basin <NUM>. A sterile drape may optionally be applied after opening the outer lid <NUM> and before opening the inner lid <NUM>. Once both lids are removed, the oxygen line <NUM> and the tubing <NUM> may be disconnected at the connector <NUM>. Oxygen input to the oxygen line <NUM> may also be reduced, preferably to at or about <NUM>/min, and this reduced oxygen may then be administered to the surface of the perfusate bath by way of the open connector <NUM>. The organ may then be introduced into the basin <NUM> and perfusion of that organ may begin. The inner lid <NUM> may then be placed on the basin <NUM> as soon as possible thereafter, and once perfusion flows have stabilized, the sterile drape may be removed and the outer lid <NUM> also placed on the basin <NUM>. Preferably, the outer lid <NUM> is closed during this surface oxygenation so as to help maintain a hypothermic environment for the perfused organ. Surface oxygenation may continue until a transport step <NUM>, in which the oxygen line <NUM> may be disconnected from the external oxygen source and the outer lid <NUM>, which covers the end <NUM> of the oxygen line, may also be closed. Upon arrival at a transplant center, surface oxygenation may be resumed at step <NUM>. This may be accomplished by opening outer lid <NUM>, connecting the oxygen line <NUM> to another oxygen source by way of the anti-bacterial filter <NUM>, and then administering oxygen at a reduced flow rate, preferably <NUM>/min, until implantation of the organ.

Moving oxygenation components <NUM> into the basin <NUM> thus provides various differences in functionality relative to the components <NUM> constituting part of a separate oxygenation device <NUM>. For example, bubble oxygenation may be achieved without the presence of the device <NUM>. Further, placing the end <NUM> of the oxygen line <NUM> outside the basin <NUM> while including the connector <NUM> in that basin enables the option to continue oxygenation during perfusion by way of the interface between the perfusion bath and the gas above.

Claim 1:
An apparatus (<NUM>) for at least one of perfusion and transport of an organ or tissue, the apparatus (<NUM>) comprising:
an organ container for storing the organ or tissue, the organ container being configured to be inserted into the apparatus (<NUM>) and comprising:
a basin (<NUM>) configured to hold the organ or tissue and a perfusate bath; and
tubing (<NUM>) that (i) is connectable to a source of oxygen, (ii) includes a plurality of holes (<NUM>) by which the oxygen may exit the tubing (<NUM>), and (iii) is located within the basin (<NUM>) so as to be submerged within the perfusate bath present during the perfusion or transport of the organ or tissue; and
an oxygen line (<NUM>) configured to convey oxygen from a source of oxygen to the tubing (<NUM>), a first end of the oxygen line (<NUM>) being within the basin (<NUM>) of the organ container and a second end of the oxygen line (<NUM>) being outside the basin (<NUM>), the apparatus (<NUM>) further comprising:
a first external lid (<NUM>) configured to cover the basin (<NUM>) when closed; and
a second external lid (<NUM>), adjacent the first external lid (<NUM>), and configured to cover other components of the apparatus (<NUM>) when closed,
wherein the oxygen line (<NUM>) is able to convey oxygen from the oxygen source to the tubing (<NUM>) when the first external lid (<NUM>) is closed, and wherein the second end of the oxygen line (<NUM>) is exposed even when the first external lid (<NUM>) is closed.