Apparatus and method for perfusing an organ or tissue

Abstract

An apparatus for perfusing an organ or tissue includes a perfusion circuit for perfusing the organ or tissue with a liquid perfusate and an oxygenation system for oxygenating the perfusate recirculated through the perfusion circuit. The oxygenation system includes an oxygen circuit for delivering oxygen to the liquid perfusate and an air circuit for delivering ambient air to the liquid perfusate. The air can be pumped through the oxygenation system via an air pump. The air or oxygen can be bubbled through the perfusate to increase the oxygen level in the perfusate. This supplemental oxygen can be beneficial during hypothermic preservation of the organ.

Description

[0001] This application is a divisional application of the invention patent application filed on April 30, 2018, with international application number PCT / US2018 / 030214, Chinese national phase application number 201880027908.8, entitled "Organ transport device with supplemental oxygenation system".

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 491,863, filed on April 28, 2017. Background Technology

[0003] Related technical fields include organ or tissue perfusion devices capable of maintaining and / or restoring the viability of organs or tissues and preserving organs or tissues for diagnostic, therapeutic, storage, and / or transportation purposes. For convenience, unless otherwise stated, the term "organ" as used herein should be understood to mean both organs and / or tissues.

[0004] Organ perfusion devices are designed to mimic the human body's condition, keeping organs viable before they are used for research, diagnosis, treatment, or transplantation. Often, organs need to be stored and / or transported between devices. The goal of maintaining and restoring organs during perfusion is to reduce ischemia and reperfusion injury. Increased storage time in normal or near-normal functional conditions also offers certain advantages, such as allowing organs to be transported over longer distances and increasing the time available for organ testing, treatment, and evaluation.

[0005] When maintaining an organ in near-ideal conditions and physiological states, it is known to provide an oxygenated perfusion fluid to the organ. For example, U.S. Patents 9,357,767, 7,998,725, and 6,673,594 disclose a configuration in which the organ is provided with a perfusion fluid that is oxidized by gaseous oxygen supplied to an oxide film. The entire contents of the aforementioned patents are incorporated herein by reference, and the present invention may be used therein. Summary of the Invention

[0006] Organ transport devices can transport organs, especially over long distances. Organ transport devices may include features of organ perfusion equipment, such as sensors and temperature controllers, as well as box interface features.

[0007] When organs or tissues have been harvested, it may be beneficial to perfuse them with an oxygenated perfusion solution, preferably a liquid perfusion solution. Although the perfusion solution can be pre-oxygenated, it may require more oxygen during perfusion as the organ uses oxygen from the perfusion solution. Therefore, it is desirable to provide a perfusion device that can supply oxygen to the perfusion solution, allowing it to be oxygenated during perfusion.

[0008] This article discloses an infusion device with an oxygenation system that supplies supplemental oxygen or air to the infusion fluid. The oxygenation system includes a medical air pump designed to maintain the oxygen tension of the infusion fluid at physiological levels for 24 hours or longer. The oxygenation system allows the user to connect to an external oxygen source to rapidly increase the oxygen tension of the infusion fluid to physiological or supraphysiological levels, or any desired level, during or at any point in the process of establishing a circuit at the donor site, upon arrival at the transplant hospital, or anywhere along the route. Attached Figure Description

[0009] Figure 1 This is a diagram of an oxygenation system.

[0010] Figure 2 This is a schematic diagram of the circuit used in the oxygenation system. Detailed Implementation

[0011] According to an exemplary embodiment, an apparatus is provided for oxygenating an perfusion fluid by allowing oxygen and / or air to flow into it, and for perfusing an organ with the oxygenated perfusion fluid. The apparatus may include: a perfusion circuit for perfusing an organ or tissue; and an oxygenation system comprising an oxygen supply device configured to supply oxygen to the perfusion fluid, an inlet for receiving oxygen from an external oxygen source, an oxygen line for supplying oxygen from an external oxygen source to the perfusion fluid, and an air pump configured to supply air to the perfusion fluid. The oxygenation system may be embedded in the apparatus.

[0012] Exemplary implementations may include methods for perfusing organs or tissues. This method may include supplying oxygen or air to the perfusion fluid via an oxygenation system to oxygenate the perfusion fluid, and perfusing the organ or tissue with the oxygenated perfusion fluid. The oxygenation system includes an oxygen supply unit or an air pump. The oxygen supply may be, for example, an oxygen cylinder or an external oxygen source. The air pump may, for example, pump air into the perfusion fluid when oxygen is unavailable. The air pump may be autonomous, rechargeable, and reusable. The air pump may be embedded in the perfusion device and designed to maintain the oxygen tension of the perfusion fluid at physiological levels for 24 hours or longer. The user may choose to expel oxygen or air, or alternate between the two. The oxygenation system allows the user to connect an external oxygen source during circuit establishment at the donor site, upon arrival at the transplant hospital, or anywhere in between, to rapidly increase the oxygen tension of the perfusion fluid to supraphysiological levels.

[0013] Exemplary perfusion devices for organs include a box or basin in which an organ can be placed. The organ may preferably be a liver, kidney, heart, lung, or intestine, but can be any human or animal organ or tissue, natural or modified, healthy, injured, or diseased. While the organ is in the device, the box may hold a holder on which the organ is arranged. The box and / or perfusion device may include a filter that can function as a coarse particle filter. The box and / or holder are preferably configured to allow a perfusion bath to form around the organ. The organ box may be configured to provide uninterrupted sterile conditions and effective heat transfer during transport, recovery, analysis, and storage, including during transitions between transport devices, perfusion devices, and organ diagnostic devices and / or other devices.

[0014] The cassette or infusion device may also include temperature sensors located or focused in or near the holder. The cassette or device may include multiple temperature sensors, which can provide redundancy in case of failure and / or provide temperature measurements at multiple locations. Preferably, one or more temperature sensors are infrared temperature sensors. When the organ is arranged in the holder, the one or more temperature sensors are preferably arranged as close to the organ as possible to improve the usability and accuracy of the temperature sensors, which preferably provide measurements of the irrigation fluid temperature that may be related to the organ temperature. Alternatively or additionally, the one or more temperature sensors may be used to directly measure the organ temperature.

[0015] The box or basin is preferably arranged within a recess of an insulated coolant container, which can hold cold materials such as ice, ice water, or brine. The coolant container can be permanently or removably attached to the entire device or a single part of the device. Thus, in use, the organ is arranged in a bracket, the bracket is arranged in a basin or box, and the basin or box is arranged in the coolant container. The coolant container, basin or box, and bracket are preferably constructed to provide cooling for the organ without the contents of the coolant container contacting the organ or bracket. Although the coolant container is described herein as containing ice or ice water, any suitable cooling medium can be used. Ice or ice water may be preferred due to its easy availability, but those skilled in the art will understand that any suitable cooling medium can be used, which can be an active cooling medium (e.g., a thermoelectric cooler or refrigerant circuit) or a passive cooling medium similar to ice or ice water, or a combination thereof. The amount of ice or other cooling medium that can be placed in the coolant container should be determined based on the longest period of cooling to be provided to the organ while it is in the device.

[0016] The support may include components configured to securely restrain an organ in place. These components may include, for example, a user-selectable mesh fastened to the support. The user-selectable mesh holds the organ in place when it is manipulated or moved. For example, the mesh on the support can be used to hold the organ in place before it is placed in a basin or infusion device while manipulating the organ (e.g., trimming blood vessels, attaching cannulas, etc.). Similarly, the organ can be held in place when it is moved into a basin with the support, when the basin is moved into a coolant container, and when the device itself is moved during transport.

[0017] Figure 1 An exemplary oxygenation system is illustrated. The oxygenation system can be embedded in and integrated with the perfusion device of an organ transport device. For example, the oxygenation system can be embedded in the lid of the coolant container or ice bucket of the organ transport device. The oxygenation system includes an oxygen circuit and an air circuit. The user can choose to pump oxygen or air directly from the oxygenation system into the perfusion bath in the box, or can switch between air and oxygen. In some embodiments, the selection to pump air and / or oxygen into the perfusion fluid can be manual, automatic, or programmed. For example, the controller can be pre-programmed to deliver oxygen for a period of time before switching to the air circuit to deliver air into the perfusion fluid. A fitting for delivering oxygen or air from the oxygenation system into the perfusion bath in the box can be immersed in the perfusion bath. In some embodiments, the end of the fitting can be positioned at or near the bottom of the box, or in any other suitable location, such as anywhere within the perfusion bath in the box. The fitting may include means for bubbling oxygen and / or air through the perfusion fluid. For example, the tubing may be perforated to create one or more holes at the ends or anywhere along the tubing immersed in the perfusion bath, allowing oxygen or air to bubble through the perfusion fluid. This bubbling of oxygen or air through the perfusion fluid increases the partial pressure of oxygen. This supplemental oxygen can be beneficial, for example, during the mechanical preservation of donor organs for transplantation. Supplying supplemental oxygen to the organ during mechanical preservation of the organ during hypothermia can lead to better post-transplant patient outcomes.

[0018] like Figure 1As shown, the oxygen circuit includes a port or inlet for connecting to an external oxygen source or oxygen tank. The port may include a Luer connector or any other suitable connector. The oxygen supply to the oxygen port can be regulated by an O2 flow meter. The flow meter may include a needle / seat control valve for precise control of the oxygen flow rate. Oxygen may flow into the oxygenation system via an oxygen inlet, for example, a Luer connection, or via a direct Luer connection to a filter, such as a biofilter, as discussed in more detail below. If the oxygen supply is connected to the oxygen port, once oxygen passes through that port, it can flow downstream through an oxygen check valve and / or a T- or Y-connector to a second port or outlet. A T- or Y-connector can connect the oxygen circuit to an air circuit. Alternatively, the oxygen and air circuits can be separated by separate ports and fittings for delivering oxygen and / or air to the filling fluid. For example, a filter or housing may have two ports for receiving separate fittings for delivering oxygen and air. The oxygenation system may have one or more outlets, which may have one or more Luer lock fittings or any other suitable fittings to provide a secure connection between the oxygenation system and the biofilter, which will be discussed in more detail below.

[0019] In the air circuit, ambient air, such as indoor air, can enter through an air inlet. The air inlet may have a Luer connector or any other suitable connector. The air pump may be configured to allow air to flow from the air inlet to a second port or outlet, and into the filling bath within the housing. Once the air exits the air pump, it can flow downstream through an air check valve and / or a T- or Y-connector to the outlet port. Oxygen and air can travel (flow) when the system cover is open or closed.

[0020] The oxygen and air check valves and filters discussed below prevent contamination problems. For example, oxygen and air check valves prevent contamination problems associated with backflow in gas and / or exhaust lines. For example, the valve can be configured as an anti-backflow valve to prevent backflow. Oxygen and air check valves can be any suitable valve or other device, such as an on / off switch that can be manually or automatically controlled by a controller.

[0021] Once air and / or oxygen flows through the outlet port, it will flow through the fitting into the box and into the infusion fluid. One or more filters, such as a biofilter or any other suitable filter, may be installed between the second port and the box. The filter may be attached to the outer end of the fitting, which is connected to the outlet port on the oxygenation system via, for example, a Luer lock fitting or any other suitable fitting. One or more filters may also be located between the box and the infusion circuit, which will be discussed in more detail below. For example, the filter may be located between the oxygenation system and the box, upstream of the oxygenation system, between the box and the infusion circuit, and / or any other suitable location.

[0022] One or more filters prevent contamination problems. For example, filters can facilitate the entry of clean air and / or oxygen from the oxygenation system into the cartridge and filling fluid, while restricting the passage of dirt, dust, liquids, and other contaminants. The pore size of the filters, such as biofilters or microbial filters, can be selected to prevent the passage of bacteria. For example, filters may have a pore size of 0.22 micrometers to allow only sterile oxygen and / or air into the cartridge.

[0023] The filter may be, for example, a microbiological filter, to ensure the sterility of the oxygen and / or air supplied from the oxygenation system or otherwise prevent its contamination. As will be understood by one of ordinary skill in the art, any suitable device may be provided in place of the filter to ensure the sterility of the oxygen or prevent its contamination. Any device used to ensure the sterility of the oxygen and / or air supply or to prevent its contamination may be a disposable component.

[0024] The fittings through which oxygen and / or air flow after exiting the oxygenation system or filter outlet may have weighted ends to allow the fittings to be submerged in the filling fluid. For example... Figure 1 As shown, the weighted end holds the tube at the bottom of the box. Figure 1 As shown, the pipe fittings can be perforated to allow oxygen and air to bubble through the injection fluid. For example... Figure 1 As shown, small molded bosses can be provided on the inside of the box to precisely position and orient the end of the bubbler. Oxygen levels are increased by bubbling in the perfusion fluid. This supplemental oxygen can be beneficial during the mechanical preservation of organs in hypothermic environments. For example, perfusion of organs intended for transplantation with supplemental oxygen can provide better post-transplant patient outcomes.

[0025] The air pump can be any pump suitable for pumping air in the infusion apparatus. For example, the air pump can be an electromechanical pressure generator, such as a DC air pump. The pump speed can be controlled by a potentiometer, such as a 5-position potentiometer. For example, the pump flow rate can be from about 25 ml / min to about 500 ml / min, from about 50 to about 250 ml / min, from about 100 ml / min to about 200 ml / min, or from about 150 ml / min to about 250 ml / min. The air pump can operate intermittently. The pump can be controlled by a controller, such as a control PCB or any other suitable controller. For example, based on user input, the controller can control the air pump to supply air to the infusion fluid or allow oxygen to be supplied to the infusion fluid via an oxygen circuit.

[0026] This device allows oxygen and / or air to be pumped into the perfusion fluid. For example, oxygen can be pumped into the perfusion fluid during preparation, prior to organ attachment to the device. During preparation, oxygen or air can be pumped into the perfusion fluid for approximately 30 minutes to 3 hours, approximately 1 hour, approximately 2 hours, or any other suitable time. In one embodiment, after pumping oxygen through the perfusion fluid for a period of time, the device can switch to pumping air into the perfusion fluid. Alternatively, after pumping air through the perfusion fluid, the device can switch to pumping oxygen. In another embodiment, after pumping oxygen into the perfusion fluid for a period of time, the available oxygen in the top space of the chamber can be recirculated through the oxygenation system and enter the bubbler, instead of being converted into air. In this embodiment, filters, such as biofilters, can be provided at both the inlet and outlet of the recirculation system to protect the pump from contamination. The user can choose to pump either oxygen or air into the perfusion fluid. In some embodiments, a combination of oxygen and air can be delivered into the perfusion fluid.

[0027] The electronic module can also be installed in the organ transport device. The electronic module can be cooled by ventilated air convection and also by a fan. The electronic module can be positioned separately from the perfusion and oxygenation / air tubing to prevent the perfusion fluid from wetting the electronic module and to avoid adding external heat from the electronic module to the perfusion fluid.

[0028] Although it has been discussed Figure 1 The specific embodiments shown describe an oxygenation system, but any suitable devices, valves, filters, fittings, pumps, and their constructions can be used.

[0029] Figure 2 A schematic diagram of the circuitry for the air pump is shown. The pump can be battery-powered. The battery can be a rechargeable battery, and preferably a fast-rechargeable one. For example, the battery can be a rechargeable lithium-ion, lithium-ion polymer, lead-acid, nickel-cadmium, nickel-metal hydride, or solid-state battery. The battery pack can be selected to allow it to be airborne, as organs are frequently transported by aircraft. The air pump can operate for up to 24 hours or more on a single charge. One or more LED indicators can be provided on the transport equipment of the manifold to indicate when the battery is charged and / or powered. A USB port or micro-USB port can be provided for charging the battery within the oxygenation system. The USB port is preferably waterproof. The USB port can be located on one side of the oxygenation system for easy access. For example, when the oxygenation system is embedded in an organ transport device, the USB port can be located on one side of the transport device or on one side of a component of the transport device, such as the lid of a coolant container or ice bucket.

[0030] The infusion equipment and integrated oxygenation system may include an integrated control panel, including a power on / off switch. The on / off switch is preferably waterproof. The control panel may also display characteristics such as, but not limited to, a charging status indicator, a power status indicator, injection pressure, error or fault conditions, flow rate, flow resistance, injection temperature, bath temperature, pumping time, temperature profiles (maximum and minimum), cap opening or closing, historical logs or graphs, and additional status details and messages, some or all of which may be further transmitted to a remote location for data storage and / or analysis. For example, such as... Figure 2 As shown, charging and power status indicators can be provided, for example, as LEDs. Flow and pressure sensors or transducers can be configured to monitor various organ characteristics, including pump pressure and vascular resistance of the organ, which can be stored in computer memory to allow analysis, for example, of vascular resistance history, and detection of faults in the device, such as elevated pressure.

[0031] The perfusion equipment and oxygenation system are configured to be assembled or fitted within the organ transport device to enable efficient heat transfer. Preferably, the organ transport device includes a compartment for receiving the perfusion equipment and oxygenation system. For example, the organ transport device can rely on conduction to move heat from the container to the coolant contained in the compartment. This heat movement allows the transport device to maintain the desired temperature of the perfusion solution.

[0032] The perfusion fluid discharged from the organ and / or contained in the perfusion bath within the container is pumped out via tubing to circulate through a perfusion circuit, which may include filters, sensors, oxygenators, and bubble traps, as discussed in more detail below. In an exemplary perfusion device, as the perfusion fluid is pumped out of the container, it passes through a filter, such as a coarse particle filter. After passing through the filter, the perfusion fluid flows along a first flow path, which includes suitable fluid conduits, such as flexible or rigid tubing, a pump, a pressure sensor, a second filter, an oxygenator, and a bubble trap, each of which will be discussed below. In combination with one or both of the portal vein flow path and the liver flow path (discussed below), the first flow path may form a recirculating perfusion fluid flow path that supplies perfusion fluid to the organ and then recirculates the perfusion fluid.

[0033] The first filter is preferably a relatively coarse filter (relative to the second filter). Such a coarse filter can be provided to prevent large particles from entering and clogging the fluid paths of the device; these large particles can be, for example, byproducts of organs or byproducts of organs removed from a donor. The first filter can be an integral part of the cartridge, or it can be located at another location in the first flow path downstream of the cartridge. For example, the first filter can also be a component separate from the cartridge or disposed within a fluid conduit.

[0034] The first flow path may also include a pump. This pump can be any pump suitable for perfusion of the combined organ. Examples of suitable pumps include manual pumps, centrifugal pumps, and roller pumps. If a roller pump is included, it may comprise a single channel or flow path (where only one fitting is compressed by the rollers), or it may comprise multiple parallel channels or flow paths (where multiple fittings are compressed by the rollers). If multiple parallel channels or flow paths are included, the rollers may preferably be arranged out of phase or offset, such that the pulses generated by the rollers are out of phase, which can result in a relatively smaller pulsation in the fluid flow exiting the roller pump compared to the case of a single roller. Such a multi-channel roller pump can achieve a constant flow rate or a flow rate with minimal pulsation, which may be advantageous depending on the other components in the flow path and / or the type of organ being perfused.

[0035] The flow path may include a pressure sensor. The pressure sensor is preferably positioned downstream of the pump outlet to monitor and / or control the pressure generated at the pump outlet via a suitable controller. The pressure sensor can provide continuous or periodic pressure monitoring.

[0036] The flow path may include an oxygenator, such as an oxygenator membrane or body, to provide oxygen to the perfusion fluid. Oxygen can be provided, for example, by an oxygen generator or oxygen concentrator, which may be separate from or integrated into the device. For example, the oxygen generator or concentrator may be contained within the device, or it may be an external device that can be connected to the device to supply oxygen to it. Oxygen can be generated by any suitable means, some examples of which include pressure swing adsorption using molecular sieves (e.g., zeolites), by a ceramic oxygen generator (solid-state oxygen pump), or by the splitting of water. Each of the above types of oxygen generators or concentrators may be adapted to be separate from or integrated into the device; however, some devices may be more advantageously adapted to be integrated or separate. For example, an electrochemical oxygen generator may be relatively compact (on the order of several cubic inches including the water reservoir) and is therefore very suitable to be integrated, while a pressure swing adsorption device may be relatively large (due to the size of the adsorbent material container and the need for a pressurized air source, such as a compressor) and is therefore very suitable to be separate.

[0037] The oxygen generator or concentrator preferably produces oxygen in real time to provide oxygenation to the perfusion fluid, but it can also produce and store oxygen for short or long periods, depending on oxygen consumption requirements and the specifications of the technology used to produce oxygen. Depending on the need for oxygenation of the perfusion fluid and / or the type of device used to produce oxygen, the oxygen generator or concentrator can produce oxygen continuously or discontinuously. The equipment may be configured such that, apart from any residual oxygen contained in the piping system or conduits(s) from the outlet of the oxygen generator or concentrator to the oxygenator, there is no oxygen storage device for the oxygen produced from the oxygen generator or concentrator. In other words, preferably, the equipment 10 does not include any structure specifically configured for oxygen storage. The equipment 10 may include devices such as microbial filters to ensure the sterility of the oxygen supplied to the oxygenator or to prevent its contamination. Preferably, such a device is located between the oxygen generator or concentrator and the oxygenator, but it may also be located upstream of the oxygen generator or concentrator or in both locations. Preferably, any device used to ensure the sterility of the oxygen supply or otherwise prevent its contamination is a disposable component. As will be understood by those skilled in the art, any suitable device can be provided in place of a microbial filter to ensure the sterility of oxygen or prevent its contamination.

[0038] The flow path may include an oxygenator, such as an oxygenator membrane or body, to provide oxygen to the filling fluid. Oxygen can be supplied to the oxygenator by any suitable means. Suitable oxygen sources may include pure oxygen or mixed gases, such as air. The gas may be compressed, such as in a high-pressure cylinder, liquefied, such as to be stored in a Dewar flask, or extracted from the surrounding atmosphere. Preferably, oxygen may be provided by an oxygen generator, which may be separate from or integrated into the equipment. Oxygen may be generated by any suitable means, some examples of which include pressure swing adsorption using molecular sieves, by a ceramic oxygen generator (solid-state oxygen pump), or by water splitting.

[0039] The flow path may include a bubble trap. The bubble trap preferably separates bubbles that may be entrained in the perfusion fluid flow and prevents these bubbles from continuing downstream and entering the organ. The bubble trap can also serve as an accumulator to reduce or eliminate pulsations in the perfusion fluid flow. The bubble trap may include an initial or accumulated volume of gas to suppress or eliminate pressure fluctuations in the perfusion fluid.

[0040] The bubble trap may include a vent that allows for the removal of gases during startup or purification processes. This vent may be connected to or be part of a purification flow path (discussed in detail below). During startup, the vent is preferably opened to purge any air or other gases from the injection fluid path. Once the gas has been purged from the injection fluid path, the vent is preferably closed. The vent may be closed manually or automatically via a controller.

[0041] The bubble trap may include a level sensor. During the purification process, a level sensor may optionally be used to determine when purification is complete and / or to determine when the purification process needs to be repeated, which may occur after bubbles have been trapped in the bubble trap. Furthermore, by using the level sensor and vent, the accumulator function of the bubble collector can be adjusted to account for different amplitudes and frequencies of pulsations in the perfusion flow.

[0042] The bubble trap can have any number of outlets, as required for a given application of the perfusion device. For example, three outlets can connect to three different flow paths, which can be particularly suitable for liver perfusion. When perfusing the liver, these three paths preferably include a portal vein path connecting to the portal vein of the liver, a liver path connecting to the hepatic artery of the liver, and a bypass flow path providing a return path to a box or basin. In any fluid path, there may also be a port allowing fluid to enter the perfusion solution. This port is preferably located within the bubble trap. This port may preferably include a Luer-type connector, allowing the user to extract a small sample of the perfusion solution for analysis. The user can also use this port to administer substances to the perfusion solution without opening the box or basin. In some embodiments, more than one oxygenator and / or bubble trap may be provided. For example, an oxygenator and a bubble trap may be provided for each of the portal vein flow path and the liver flow path. This configuration allows for different levels of oxygenation in each of the portal vein flow path and the liver flow path. A single oxygen concentrator or generator can supply oxygen to both the portal vein and hepatic flow paths, or a separate oxygen concentrator or generator can be provided for each flow path. If a single oxygen concentrator or generator supplies oxygen to both flow paths, suitable valves, such as on / off valves and / or pressure regulators, can control the oxygen supply to each flow path to make it different.

[0043] The portal vein flow path and the hepatic flow path can optionally include similar or different components, such as valves; bubble sensors; flow sensors; flow control clamps; and pressure sensors. Each similar component can function in a similar manner, and such components can optionally be structurally and / or functionally identical to reduce manufacturing costs. While any suitable sensor can be used, the flow sensor is preferably an ultrasonic sensor arranged around the tubing. Ultrasonic sensors may be advantageous because, during normal use, such sensors do not come into contact with the perfusion fluid and are therefore not in a sterile path. This implementation of an ultrasonic sensor eliminates the need for replacement and / or cleaning after use.

[0044] The valve can be a pinch valve used to squeeze the tubing and reduce or shut off the flow, but any suitable valve can also be used. Pinch valves may be advantageous because they do not come into contact with the injection fluid during normal use and therefore do not require replacement and / or cleaning after use.

[0045] Preferably, while any suitable sensor can be used, the bubble sensor may preferably be an ultrasonic sensor arranged around the fitting. Similar to pinch valves, ultrasonic sensors may be advantageous because they do not come into contact with the filling fluid during normal use and therefore do not require replacement and / or cleaning after use. Instead, the ultrasonic sensor may be arranged to contact, be adjacent to, or surround the outer surface of the fitting in order to sense bubbles.

[0046] A flow control clip can be used to fine-tune the flow rate in one or both of the portal vein flow path and the hepatic flow path. Preferably, the organ provides self-regulation to control the amount of flow exiting the bubble collector and distributed between the portal vein flow path and the hepatic flow path. In this self-regulating flow, a pressure sensor provides overpressure monitoring. If the pressure delivered to the organ in one or both of the portal vein flow path or the hepatic flow path exceeds a predetermined threshold, the device can automatically stop and / or reduce the flow rate provided by the pump to prevent damage to the organ. Additionally or alternatively, the pressure sensor can be used to generate a warning signal to the user and / or an appropriate controller when the pressure approaches a predetermined threshold.

[0047] After leaving one or both of the portal vein and hepatic pathways, the perfusion fluid flows through the organ and returns to the pelvis to form an organ bath.

[0048] The bypass flow path may include valves and / or sensors, such as oxygen sensors and pH sensors. Preferably, the valve is a pinch valve and may have a similar construction, but any suitable valve may be used. The oxygen sensor and pH sensor can be used to determine the state of the perfusion fluid. Preferably, the bypass flow path is used only during the purification or preparation process, although it may also be used during perfusion; preferably, the bypass flow path is used continuously to monitor the perfusion fluid characteristics in real time.

[0049] The organ perfusion device may also include an accelerometer. Preferably, the accelerometer is a triaxial accelerometer, although multiple uniaxial accelerometers can be used for the same effect. The accelerometer can be used to continuously or periodically monitor and / or record the state of the device. Monitoring may include monitoring for excessive vibration and the device's attitude. By implementing such monitoring, misuse or potential inappropriateness of the device can be detected and recorded.

[0050] The device may include storage compartments for items other than organs. For example, the device may include a document compartment for storing organ-related documents and / or diagrams. Similarly, the device may include one or more sample compartments. For example, the sample compartments may be configured to store fluid and / or tissue samples. The sample compartments may be advantageously arranged near a coolant container to provide cooling, which may be similar to or equivalent to the cooling provided to organs.

[0051] The device may include one or more tamper-proof closures. Tamper-proof closures can be used to warn the user that the device has been opened at an unauthorized time and / or place and / or by an unauthorized person. Evidence of tampering can warn the user to perform additional tests, screenings, etc., before using the organ and / or device.

[0052] Organ transport equipment is preferably portable for carrying organs or tissues from one place to another, and is sized to be carried by one or two people and loaded into a car or small aircraft. The perfusion equipment and integrated oxygenation system are preferably designed to be portable organ transport equipment, for example, with dimensions less than 42 inches long × 18 inches wide × 14 inches high, and a weight less than 90 pounds (lbs), including the weight of the entire loaded system (e.g., transport equipment, disposable components, organ, ice, and 3 liters of perfusion solution).

[0053] The preferred embodiments and some variations of the invention have been described and illustrated herein. The terminology, descriptions, and drawings used herein are set forth by way of illustration only and are not intended to be limiting. Those skilled in the art will recognize that many variations can be made within the spirit and scope of the invention.

Claims

1. An apparatus for perfusing an organ or tissue, comprising: Coolant container, including lid; A box, disposed within the coolant container and configured to hold the organ or tissue and the fluid perfusion solution, the box defining a top space above the fluid perfusion solution; The perfusion circuit is configured to perfuse the organ or tissue with the liquid perfusion solution; The oxygenation system includes: The oxygen inlet is configured to receive oxygen from the oxygen supply unit. An oxygen delivery fitting includes a perforated portion configured to be immersed in the liquid filling fluid, the oxygen delivery fitting being configured to receive oxygen from the oxygen inlet and deliver the oxygen to the liquid filling fluid; Pump; The recirculation flow path is configured to draw oxygen-containing gas from the top space of the box, pass it through the pump, and deliver the oxygen-containing gas to the liquid filling solution through the oxygen delivery fitting; A biofilter is disposed on at least one of the inlet and outlet of the recirculation flow path; and At least one check valve is configured to control the direction of airflow through the oxygenation system. The oxygenation system is configured to introduce oxygen received from the oxygen supply unit, oxygen-containing gas drawn from the top space of the box, or a combination thereof, into the liquid filling solution through the perforated portion of the oxygen delivery pipe.

2. The device as described in claim 1, characterized in that, The oxygenation system is configured to allow oxygen or oxygen-containing gas to bubble through the liquid injection fluid via the perforated portion of the oxygen delivery pipe.

3. The device as described in claim 1, characterized in that, The biofilter has a pore size of 0.22 micrometers.

4. The device as described in claim 1, characterized in that, The oxygenation system is embedded in the cap of the coolant container.

5. The device as described in claim 1, characterized in that, The oxygen delivery fitting has a weighted end that holds the perforated portion of the oxygen delivery fitting at the bottom of the box, and the inner side of the box includes a molded boss that positions and orients the end of the fitting.

6. The device as described in claim 1, characterized in that, The recirculation system includes a biofilter on both its inlet and outlet, and the biofilter is configured to protect the pump from contamination.

7. The device as described in claim 1, characterized in that, It also includes a controller configured to operate the recirculation flow path to deliver the oxygen-containing gas to the liquid filling fluid through the oxygen delivery fitting after oxygen has been supplied from the oxygen supply unit to the liquid filling fluid for a period of time.

8. The device as described in claim 1, characterized in that, It also includes a controller configured to switch between delivering oxygen from the oxygen supply unit to the liquid filling fluid and delivering oxygen-containing gas from the top space of the box to the liquid filling fluid based on user input.

9. The device as described in claim 1, characterized in that, The recirculation flow path fluidly connects the top space of the box to the oxygen delivery fitting.

10. The device as claimed in claim 1, characterized in that, The oxygenation system further includes an airflow connection that fluidly connects the oxygen inlet and the recirculation flow path to the oxygen delivery pipe.

11. A method for perfusing an organ or tissue via the device of claim 1, comprising: The oxygen or oxygen-containing gas is supplied to the liquid perfusion solution via the oxygenation system to oxygenate the liquid perfusion solution; as well as The organ or tissue is perfused with the oxygenated perfusion solution via the perfusion circuit.

12. The method as described in claim 11, characterized in that, The oxygen is bubbled through the liquid injection fluid via the perforated portion of the oxygen delivery fitting.

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