System and method for organ maintenance and transport

Abstract

To provide a system and a method that enable a circulating perfusate at normothermic or subnormothermic temperatures for maintaining an organ and transporting the organ from a donor to a recipient.SOLUTION: A system (100) includes a circulation system that provides oxygenated perfusate to an organ (135) and enables continuous monitoring of the perfusate moving through the organ. A tank (123) can provide an inlet that can accept selected infusible materials, and an outlet that can enable sampling and waste removal. The system can continually monitor a solution bath in which the organ is bathed, and the system can manage the composition of the gas in the tank. A direct acting pneumatic pump can be used to enable minimal hemolysis. The system can include disposable portions and durable portions.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This utility patent application claims the benefit of U.S. Provisional Patent Application No. 62 / 979,144 (Attorney Docket No. AA195), filed February 20, 2020, and entitled "System and Method for Kidney Transport." [Background technology]

[0002] The present disclosure relates to the maintenance of harvested organs for transplant recipients. Many types of organs are harvested from organ donors, the most common being kidneys. In 2018, end-stage renal disease (ESRD) affected more than 700,000 patients annually in the United States and an estimated 2 million patients worldwide. The primary treatments for ESRD are dialysis and kidney transplants. In the United States, the overwhelming majority of people with ESRD receive dialysis, with only a small proportion living with a transplant. Patients receiving dialysis generally have a shorter life expectancy and poorer quality of life than those receiving kidney transplants. Patients undergoing dialysis treatment who could alternatively seek a transplant must queue for more than five times the number of available donor kidneys. While most transplanted kidneys are from deceased donors, many available kidneys must be discarded. Deceased donor kidneys have several challenges: (1) a high rate of delayed graft function (DGF), a higher susceptibility to cold-induced injury, and a lower long-term graft survival rate. While logistically effective, cold storage of organs for transport can damage organs, and assessing organ health can be difficult, especially when the organ is cold and not metabolically active. The result of cold storage cycles (high-low-high temperature) can be a chain reaction of O2 deprivation, which can cause ischemic injury. The initial effects of such injury can include delayed organ transplant function, and long-term effects on kidney function can exist. Current kidney screening methods can be flawed and cannot provide a direct measure of kidney health. When kidneys are deemed to be of marginal potential, kidney assessment systems are biased toward discarding. As a result, a large number of donated organs (3,500 in the United States alone) are discarded each year. Studies have found that a significant proportion of these discards could have been transplanted with favorable outcomes for the resulting patient. Thorough quantitative ex vivo assessment of organs is important to reduce discard rates. Ex vivo organ assessment can eliminate reliance on donor scoring and provide a real-time measurement of kidney health, which can alleviate the concerns of risk-averse physicians.Other future options include immunomodulatory drugs, which may reduce donor matching issues, gene therapy for in vivo kidney treatment, kidney tissue engineering, and tissue transplantation. Yet further options include normothermic / subnormothermic perfusion, which likely extends preservation time, allows real-time organ diagnostics, and eliminates cold-induced injury. Preservation techniques such as ex vivo normothermic machine perfusion (NMP) can be used to resuscitate and assess kidney quality before transplantation and have been used to restore discarded kidneys before the recipient undergoes surgery. Normothermic or subnormothermic perfusion results in a metabolically active kidney, which allows for assessment.

[0003] What is needed is a system designed to reduce the number of discarded organs. What is needed is a system that can maintain a preselected oxygen level in the circulating perfusate during transport from donor to transplant recipient, potentially, and / or constantly monitor the organ and dynamically adjust the desired oxygen level. The system must be designed to provide the organ with the nutrients necessary to maintain its vitality, even during transport that may last, for example, 24 hours. The system must be designed to sense a sufficient range of properties, such as, but not limited to, glucose and pH, to help medical personnel determine whether the organ is viable. A successful organ transport system may provide medical personnel with a quantitative measure of organ health, enable organ reconditioning to optimize its performance prior to transplantation, limit acute injury to the organ that may occur during organ transport, and enable ex vivo treatment of the organ, such as, but not limited to, pharmacological and gene therapy. What is further needed is a system that achieves low hemolysis and maintains the desired properties of the organ. What is needed is a normothermic / subnormothermic organ perfusion device with on-board sensors for assessing kidney health in real time. Summary of the Invention [Means for solving the problem]

[0004] According to some configurations, the present teachings include systems and methods for normothermic kidney perfusion. Normothermic perfusion can extend preservation time, enable real-time kidney diagnostics, and eliminate cold-induced injury. In the systems of the present teachings, the kidney can be perfused in a tank that can be configured to be portable or stationary.

[0005] The portable tank can be self-contained, disconnected from wall power and supporting equipment, and configured to operate without external power for relatively long durations, for example, but not limited to, 24 hours. Infusate can be provided in the tank, and the kidney can be immersed in fluid exiting the kidney's renal vein as it is perfused, potentially among other components. Perfusion and infusion can include a repeatable and successful process managed by a controller receiving feedback from sensors installed in-line, for example, but not limited to, in the perfusion circuit and in the solution bath. The present systems and methods can increase the number of successful kidney transplants, improve patient health, and enable advances in kidney transplant clinical techniques. Systems and methods for kidney perfusion can provide surgeons with quantitative measurements of kidney health, enable kidney reconditioning prior to transplantation to optimize kidney performance after transplant, limit acute kidney injury that can occur during kidney transport, and enable ex vivo treatment of the kidney, for example, but not limited to, pharmacological and gene therapy. The present systems and methods can allow marginal kidneys to be repaired and qualified as potential transplant candidates. The present systems and methods can allow for quantification of kidney health.

[0006] The method of the present teachings can include, but is not limited to, placing the kidney in a tank. The tank can trap air and prevent recirculating air bubbles. The tank can allow volume to change within the tank, which can limit exposure of the kidney to vacuum pressure from the perfusion system and allow circulation through the kidney. The method can include connecting the renal artery to the perfusion system and connecting the ureter to a drain line. Perfusion fluid pumped into the renal artery can at least partially escape through the renal vein and flow into the tank. The perfusion system can provide a near-physiological pressure, for example, 90 mmHg. In some configurations, pressures of up to 200 mmHg and flow rates of up to 500 mL / min can be accommodated in the method of the present teachings. The perfusion fluid can be recirculated from the tank back into the renal artery. The perfusion fluid can include, but is not limited to, oxygen carriers, such as, but not limited to, perfluorocarbons, hemoglobin-based fluids, and marine worm hemoglobin-based fluids. Hemoglobin-based oxygen carriers can include infusible oxygen-carrying fluids prepared from purified human or animal hemoglobin. Marine worm hemoglobin-based fluids can add density and viscosity to the perfusion fluid. The perfusion fluid can include a combination of electrolytes, sugars, vitamins, and pH buffers. The method can include monitoring and adjusting the temperature of the perfusion fluid prior to pumping the perfusion fluid into the kidney. In some configurations, the temperature can be adjusted to room temperature. In some configurations, the temperature can be adjusted to body temperature. In some configurations, the temperature can be adjusted to a range of 3 to 42°C. Normal kidney handling procedures in the system and throughout the method of the present teachings can protect the kidney from extreme temperatures over extended periods of time. When maintaining the kidney at a hypothermic level, the target temperature can include a range of 3 to 10°C. When maintaining the kidney at a subnormothermic level, the target temperature can include a range of 18.5 to 25.5°C. When maintaining the kidney at a normothermic level, the target temperature can include a range of 32 to 42°C.

[0007] The method can include pumping air through an oxygenator capable of extracting oxygen from the air and supplying oxygen to the perfusate. Target ranges for dissolved oxygen can include 74-100 mmHg in the artery and 30-40 mmHg in the vein. The oxygenated perfusate can allow CO2 generated within the kidney to escape. Target ranges for CO2 can include 23-29 mmol / L. The method can include replenishing fluid, salts, nutrients, and other biological compounds necessary to maintain renal health. In some configurations, an infusion pump can be used to provide fluid replenishment into the solution reservoir 125 at a flow rate of 1-20 mL / min. The method can include monitoring renal vitality, for example, but not limited to, through monitoring renal resistance changes (pressure / flow), oxygen consumption, and pH status. Monitoring renal characteristics can provide an indication of renal health.

[0008] In some configurations, the supplemental source may include, for example, but not limited to, a single infusion solution of Plasmalyte with 0.026 g / mL dextran, a complex polysaccharide derived from the condensation of glucose. During supplementation, the method may include maintaining a target glucose range of 170-180 mg / dL and a basal flow rate of 10 mL every 15 minutes. If these targets are met, 25 g of dextran / day and 960 mL of perfusate supplementation may be delivered. The method may include adjusting the time between administrations to achieve the targets. Insulin may be added depending on the sensed glucose reading.

[0009] In some configurations, the supplemental ingredients may include, for example, but not limited to, two infusion solutions. The infusion solutions may include, but are not limited to, a Plasmalyte / dextran solution and a buffer solution. The Plasmalyte / glucose solution may include Plasmalyte with 0.026 g / mL dextran. The buffer may be used to adjust the pH of the perfusate. The target pH may be in the range of 6.9 to 7.9. In some configurations, the method may include flushing the kidney with a high-flow, low-potassium conservation solution. In some configurations, the method may include reperfusing the kidney and monitoring kidney characteristics to determine whether the infusion maintains renal viability.

[0010] In some configurations, maintaining the kidney at a desired temperature can include selecting a temperature regulation option that meets weight, heat load, and size requirements. Possible options include, but are not limited to, Carnot, phase change, and thermoelectric systems. In some configurations, the heat load is 10-20 W to maintain a 20° temperature difference between the environment and the kidney, and less if the kidney is maintained at sub-normothermic temperatures. For heat loads on the higher end of the 10-20 W range, a Carnot system can be selected. For systems where battery size may be important, thermoelectric systems can be selected because they can be scaled. When a kidney enclosure is to be placed within the enclosed area, phase change material systems can be selected because they do not require heat transfer to or from the surrounding environment. Maintaining the kidney at a desired temperature can include selecting an appropriate insulation material. In some configurations, vacuum panels, aerogel, and / or closed-cell rigid insulation systems can be selected.

[0011] In other configurations, the system of the present teachings can include a pump subsystem that can enable organ perfusion, perfusate recirculation, and possibly infusion. The pump subsystem can pump perfusate, e.g., blood, through the organ. The blood can include, for example, whole blood or packed red blood cells. In some configurations, the pump subsystem can enable perfusate flow at a rate of up to 500 ml / min at a pressure of 20-120 mmHg. The flow can optionally be pulsatile, and the rate can be adjustable. As an example, a low flow rate may be required for an injured kidney. As renal function improves, the flow rate can be adjusted to accommodate changed conditions. Both pulsatile flow or flow rates controlled by physiological parameters can be accommodated by the pump of the present teachings. Pump types can include centrifugal pumps and direct-acting pneumatic pumps. Centrifugal pumps can enable portability and maintenance of physiological conditions. Direct-acting pneumatic pumps can be used in conjunction to provide a more continuous flow of blood. Direct-acting pneumatic pumps can include active inlet and outlet valves, allowing for a high degree of control of flow within the blood flow circuit. For example, the kidney can tolerate flow rates of 200–500 mL / min. Adjusting the flow rate can accommodate any inherent device variations, such as during start-up. One goal of pump selection is to reduce hemolysis. Direct-acting pneumatic pumps can enable flow metering with minimal hemolysis and wetted materials. Modifying the pumping cycle of a direct-acting pneumatic pump to match the physiological pulsatile pressure duty cycle is a feasible option.

[0012] In some configurations, the pump is direct-acting, and compressed air (or vacuum) is used to push / pull a membrane against the fluid. A set of valves controls where the pumping pods are connected, allowing filling from the inlet and pushing to the outlet. In some configurations, there are two pumping pods. One fills and one delivers at the beginning of each stroke. A new stroke is not completed until that sequence is complete. Partial strokes are possible, for example, to mitigate hemolysis. The pump controls the nominal pressure in the pumping pod by throttling the supply valve. The result is a sawtooth pressure instead of a time graph. In pump pressure control mode, the fill / delivery nominal pumping pod pressure can be adjusted. Higher pressure (or vacuum) will result in faster filling or delivery times. The pump can provide smooth / consistent flow and pulsatile flow. In some configurations, the system can include multiple controllers, such as a valve controller, a pumping chamber controller, and a pump controller. The system of the present teachings is capable of exchanging a large portion of the perfusion fluid volume while maintaining perfusion.

[0013] The role of the perfusion loop is to provide basic biological functions that would otherwise occur in the body. These include oxygenation, nutrient delivery, and carbon dioxide removal. Oxygenation and carbon dioxide removal are achieved through the use of a steady-state membrane oxygenator. Perfusion fluid leaves the kidney, passes through an oxygenator, and is then pumped back into the kidney. Nutrients are provided in the perfusion solution and can be added manually or through the use of an infusion solution. Urine produced by the kidney flows out the ureter and will be available for sampling through a sterile sample port. The urine is then directed back into the perfusion loop. Urine flow rate and volume are measured and stored by the system. In cases where recirculating urine proves difficult, the system can be modified so that urine is collected or potentially passed through a dialysis loop.

[0014] The recirculation loop acts like a maintenance loop for the system, allowing the kidney reservoir to fill or drain and recirculate fluid from the reservoir, essentially agitating the reservoir. This loop can include an infusion pump so that infusate can be delivered, diluted, and mixed into the perfusion fluid instead of being passed directly into the kidney. Some or all of the infusion pumps can be part of the perfusion loop. In some configurations, the system can include a bypass valve that can be opened during priming when an air bubble is detected. To introduce new blood or drain the system, the system can include at least one pinch valve associated with the infusion path. In some configurations, a pinch valve can be associated with the inflow perfusion fluid, while another pinch valve can be associated with the drain path. The perfusion fluid pump can also drain tissue inclusions.

[0015] The flow rate and pressure of the perfusion pump as it pumps blood into the oxygenator can be adjusted, as can the flow rate and pressure going into the kidney. The kidney's resistance changes over time as it achieves better health, and the pressure of the pumped perfusion fluid needs to adapt to the kidney's needs. Over-pressurizing the fluid lines can cause lysis.

[0016] Blood perfusion pumps can include, but are not limited to, roller, centrifugal, pulsatile, and non-occlusive roller. Pumps that can enable perfusion in the system of the present teachings can deliver physiological blood flow against high resistance without damaging the blood, provide precise and easily monitored flow, do not create any turbulence or stagnation, and can be manually operable in the event of a power outage. In some configurations, an extracorporeal membrane oxygenation (ECMO)-type device with a silicone membrane contactor can be used to perfuse and oxygenate the blood in the system.

[0017] In some configurations, a low-bolus, high-accuracy infusion pump can be used to allow for clinical infusion of prescription vasodilators or insulin, etc. In some configurations, multiple infusion pumps can be used to allow multiple different substances to be infused, potentially simultaneously. In some configurations, the pump reservoir is 3 mL, and the pump can accommodate infusion rates of 0.5 to 300.0 μL / hour and infusion volumes of 0.5 to 250.0 μL, infused into a recirculation loop that is fed into the organ enclosure.

[0018] The system can include sensors to enable proper perfusion and collect data for renal assessment. The system can include sterile sample ports for removing urine and perfusate fluid using a sterile syringe. The system of the present teachings includes sensors outside the fluid path as well as sensors within the fluid path. The system can include pressure sensors on the tubing exiting the tissue enclosure and exiting the heat exchanger. A membrane between the heat exchange channel and the thermal control pad can include a pressure sensor. The membrane can be, for example, a rubber material. The system can include an air trap where air bubbles float on top of the entering perfusate, and fluid can exit through a non-air section of the air trap. The system can include a flow / droplet sensor to measure urine collected from a cannulated urethra.

[0019] The system of the present teachings controls the temperature of the perfusate through a heat exchanger. The heat exchanger includes a serpentine flow path resting on a thermally conductive and reflective membrane. In some configurations, the thermal control plate includes cartridge elements for active control of the temperature of the perfusate. The system includes a temperature sensor that senses the temperature of the perfusate as it enters and exits the serpentine path. Active temperature control can maintain the 37°C temperature required for kidney perfusion. The number and size of cartridge elements are based at least on the characteristics required to maintain uniform distribution across the serpentine path. The size of the thermal control plate is dictated by the number and size of the cartridges. The width of the serpentine channel is based on the need to maintain adequate surface area inside the channel, avoid stagnation, avoid extreme pressure, and maintain uniform heat transfer. The geometry of the serpentine channel can be important to prevent stagnation. In some configurations, the camera can be scaled to view a macroscopic view of the organ, potentially through a window within the tissue enclosure. In some configurations, the camera can take time-lapse photos, snapshots, and videos.

[0020] A system of the present teachings for enabling sustained normothermic or subnormothermic perfusion of an organ with a perfusate includes, but is not limited to, a tissue enclosure having a platform and a fluid reservoir, where the platform has a height, the fluid reservoir has a fluid level below the height, and the organ can be positioned on the platform. The system can include a gas management subsystem that adjusts gas saturation in the perfusate, a thermal management subsystem that adjusts the temperature of the perfusate according to a preselected threshold, the preselected threshold being normothermic or subnormothermic, and a perfusion subsystem that circulates the perfusate through the organ, the gas management system, and the thermal management subsystem, where the perfusate enables sustained normothermic or subnormothermic conditions for the organ. The system can optionally include a power management subsystem that measures output from the organ, a gas trap that removes gas from the perfusate, a sensor subsystem that monitors properties of the perfusate and / or the fluid reservoir, and an infusion subsystem that introduces additives into the perfusate and / or the fluid reservoir. The infusion subsystem can optionally include at least one perfusion pump. The perfusion subsystem can optionally include at least one perfusion pump that enables low hemolysis. The gas management subsystem can optionally include at least one oxygenator that supplies oxygen to the perfusion solution and manages carbon dioxide levels, and at least one gas supply device that provides at least one gas to the perfusion solution. The at least one gas can optionally include oxygen, nitrogen, and carbon dioxide. The thermal management subsystem can optionally include a heat exchanger. The heat exchanger can optionally include a source of thermal energy, a surface having at least one channel that holds the perfusion solution, a membrane covering the surface and conducting thermal energy from the source through the membrane to the perfusion solution, and a heat transfer plate between the membrane and the source.

[0021] The system may optionally include a first of at least one thermal sensor that monitors the perfusate temperature of the perfusate before it enters the thermal management subsystem, a second of at least one thermal sensor that monitors the perfusate temperature of the perfusate after it exits the thermal management subsystem, and a third of at least one thermal sensor that monitors the perfusate temperature of the perfusate in the fluid reservoir. The system may optionally include a first of at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate before it enters the organ and a second of at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate leaving the fluid reservoir. The system may optionally include at least one pH sensor that monitors the pH of the perfusate in the fluid reservoir and at least one dissolved oxygen sensor that monitors the dissolved oxygen of the perfusate in the fluid reservoir. The system can optionally include a first of at least one pressure sensor that monitors the pressure of the perfusion fluid before it enters the gas management subsystem and a second of at least one pressure sensor that monitors the pressure of the perfusion fluid before it enters the organ.

[0022] A system of the present teachings for enabling sustained normothermic or sub-normothermic perfusion of an organ with a perfusate may include, but is not limited to, a tissue enclosure having a fluid reservoir, the tissue enclosure holding the organ, a gas management subsystem regulating gas saturation in the perfusate, a thermal management subsystem regulating the temperature of the perfusate according to a preselected threshold, the preselected threshold being normothermic or sub-normothermic, a perfusion subsystem circulating perfusate through the organ, the gas management subsystem, and the thermal management subsystem, the perfusion subsystem enabling sustained normothermic or sub-normothermic conditions for the organ, a pneumatic subsystem driving the perfusion subsystem to pump the perfusion fluid, and a control subsystem controlling the pneumatic subsystem, the thermal management subsystem, and the gas management subsystem. The system may optionally include a power management subsystem measuring power output from the organ, a gas trap removing gases from the perfusate, and a sensor subsystem monitoring properties of the perfusate, the sensor subsystem collecting sensor data. The system can optionally include a data processor that receives the sensor data and provides the sensor data to a control subsystem, where the control subsystem controls the thermal management subsystem based at least on the sensor data, a data processor that receives the sensor data, where the data processor provides the sensor data to the control subsystem, where the control subsystem controls the pneumatic subsystem based at least on the sensor data, The system can optionally include a data processor that receives the sensor data, where the data processor provides the sensor data to the control subsystem, where the control subsystem controls the gas management subsystem based at least on the sensor data, and an infusion subsystem that introduces an additive into the perfusion solution.

[0023] The gas management system can optionally include a disposable oxygenator. The thermal management subsystem can optionally include a disposable heat exchanger, a disposable thermally conductive membrane, and a durable thermal energy source. The perfusion subsystem can optionally include at least one disposable pump that pumps perfusate through the organ and at least one durable pump interface that couples the at least one disposable pump to the pneumatic subsystem. The pneumatic subsystem can optionally include at least one durable valve, at least one durable chamber, at least one durable pressure source, and at least one durable vacuum source.

[0024] A system of the present teachings for enabling sustained normothermic or subnormothermic perfusion of an organ with perfusate can include a disposable portion including, but not limited to, disposable components and tubing connecting the disposable components together to form a circulation loop enabling circulation of perfusate through the organ, a durable portion including a pneumatic system for driving the circulation of the perfusate, a thermal energy source for supplying thermal energy to the perfusate to maintain the circulating perfusate at a normothermic or subnormothermic temperature, and a control system for controlling the pneumatic system and the thermal energy source. The disposable portion can optionally include a heat exchanger for transferring heat from the thermal energy source to the perfusate. The heat exchanger can optionally include a plate having a first side etched with a fluid pathway and a second opposing side, the second opposing side being positioned against a tissue enclosure housing the organ, and a thermally conductive membrane having a first membrane side covering the first side, the thermally conductive membrane having a second opposing membrane side positioned against a thermal energy source. The disposable part can optionally include an oxygenator that provides oxygen to the perfusate, at least one pump that pumps the perfusate through the organ, the pneumatic system driving the at least one pump, at least one pump that infuses a substance into the perfusate, at least one power management system that measures power output from the organ, and a gas trap that removes gases from the perfusate. The durable portion can optionally include at least one sensor that provides sensor data and monitors the organ, and at least one data processor that receives and processes the sensor data, wherein the at least one data processor provides the processed sensor data to a control system that controls the pneumatic system and the thermal energy source based at least on the processed sensor data. The present invention provides, for example, the following. (Item 1) 1. A system for enabling sustained normothermic or subnormothermic perfusion of a kidney, comprising: a tank for storing the kidney, the tank preventing recirculation of gas bubbles, the tank limiting exposure of the kidney to vacuum pressure, the tank holding a solution bath, the solution bath surrounding the kidney; a perfusion system operatively coupled to at least one orifice of the kidney, the perfusion system circulating a perfusion fluid through the kidney, the perfusion system allowing for monitoring and regulation of the perfusion fluid as it circulates; a temperature control system for maintaining the bath and the perfusion solution at a desired temperature, the temperature control system including thermal insulation; a carrying case that holds the reservoir, the perfusion system, and the temperature management system, the carrying case enabling transportation of the kidney; A system comprising: (Item 2) 2. The system of claim 1, wherein the perfusion system comprises a perfusion pump that pumps a perfusion solution at the desired temperature through the kidney. (Item 3) Item 10. The system of item 1, further comprising an oxygenator that supplies oxygen to the perfusate and allows carbon dioxide to escape from the kidney. (Item 4) Item 10. The system of item 1, further comprising an infusion pump that pumps a selected solution into the tank. (Item 5) Item 10. The system of item 1, further comprising an infusion pump that pumps a selected solution into the kidney. (Item 6) Item 10. The system of item 1, further comprising at least one sensor that collects at least one perfusate characteristic of the perfusate and at least one renal characteristic of the kidney. (Item 7) Item 10. The system of item 1, further comprising a sample / waste container for collecting urine, the urine being indicative of at least one renal characteristic of the kidney. (Item 8) 1. A method for enabling sustained normothermic perfusion of a kidney, the kidney including a ureter and a renal artery, the kidney being contained in a tank, the kidney being transported from a donor to a recipient, the method comprising: pumping perfusion fluid into the renal artery, the kidney being surrounded by a reservoir of solution filling the reservoir; monitoring perfusate characteristics of the perfusate while the kidney is being transported; adjusting the perfusate characteristics while the kidney is being transported based on the monitoring; A method comprising: (Item 9) 9. The method of claim 8, further comprising maintaining the perfusion fluid at a preselected temperature while the kidney is being transported. (Item 10) sampling urine from the ureter; Discarding the sampled urine. Item 9. The method of item 8, further comprising: (Item 11) monitoring a bath characteristic of the bath; controlling a selector valve and an infusion pump to draw a selected solution into the solution reservoir based on the solution reservoir characteristics; controlling a temperature control system based on the bath characteristics; Item 9. The method of item 8, further comprising: (Item 12) 9. The method of claim 8, further comprising oxygenating the perfusate while the kidney is being transported. (Item 13) 1. A system for enabling sustained normothermic or subnormothermic perfusion of an organ with a perfusion fluid, said system comprising: a tissue enclosure having a platform and a fluid reservoir, the platform having a height, the fluid reservoir having a fluid level, the fluid level being lower than the height, and the organ being positioned on the platform; a gas management subsystem that adjusts gas saturation in the perfusate; a thermal management subsystem that adjusts the temperature of the perfusion fluid according to a preselected threshold, the preselected threshold being normothermic or subnormothermic; a perfusion subsystem that circulates a perfusion fluid through the organ, the gas management system, and the thermal management subsystem, the perfusion fluid enabling sustained normothermic or subnormothermic conditions for the organ; A system comprising: (Item 14) Item 14. The system of item 13, further comprising a power management subsystem that measures power output from the organ. (Item 15) Item 14. The system of item 13, further comprising a gas trap that removes gases from the perfusion solution. (Item 16) 14. The system of claim 13, further comprising a sensor subsystem that monitors characteristics of the perfusion fluid. (Item 17) Item 14. The system of item 13, further comprising a sensor subsystem that monitors a characteristic of the fluid reservoir. (Item 18) 14. The system of claim 13, further comprising an injection subsystem that introduces an additive into the perfusion solution. (Item 19) Item 14. The system of item 13, further comprising an injection subsystem that introduces an additive into the fluid reservoir. (Item 20) 14. The system of claim 13, further comprising an infusion subsystem including at least one perfusion pump. (Item 21) 14. The system of claim 13, wherein the perfusion subsystem comprises at least one perfusion pump, the perfusion pump enabling low hemolysis. (Item 22) 14. The system of claim 13, wherein the gas management subsystem comprises at least one oxygenator, the at least one oxygenator providing oxygen to the perfusate and managing carbon dioxide levels. (Item 23) 14. The system of claim 13, wherein the gas management subsystem comprises at least one gas supply device, the at least one gas supply device providing at least one gas to the perfusion solution. (Item 24) 24. The system of claim 23, wherein the at least one gas comprises oxygen. (Item 25) 24. The system of claim 23, wherein the at least one gas comprises nitrogen. (Item 26) 24. The system of claim 23, wherein the at least one gas comprises carbon dioxide. (Item 27) Item 14. The system of item 13, wherein the thermal management subsystem comprises a heat exchanger. (Item 28) The heat exchanger comprises: A source of thermal energy, a surface having at least one channel, the at least one channel holding the perfusion fluid; and a membrane covering the surface, the membrane conducting thermal energy from the source through the membrane to the perfusion fluid; Item 28. The system of item 27, comprising: (Item 29) Item 29. The system of item 28, wherein the heat exchanger further comprises a heat transfer plate between the membrane and the source. (Item 30) a first of at least one thermal sensor that monitors a perfusate temperature of the perfusate before the perfusate enters the thermal management subsystem; a second of the at least one thermal sensor that monitors a perfusate temperature of the perfusate after the perfusate exits the thermal management subsystem; a third one of the at least one thermal sensor for monitoring a perfusion fluid temperature of the perfusion fluid in the fluid reservoir; Item 14. The system of item 13, further comprising: (Item 31) a first of at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate before the perfusate enters the organ; a second of the at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate leaving the fluid reservoir; Item 14. The system of item 13, further comprising: (Item 32) at least one pH sensor that monitors the pH of the perfusion fluid in the fluid reservoir; at least one dissolved oxygen sensor that monitors the dissolved oxygen of the perfusate in the fluid reservoir; Item 14. The system of item 13, further comprising: (Item 33) a first of at least one pressure sensor that monitors the pressure of the perfusion fluid before it enters the gas management subsystem; a second one of the at least one pressure sensor that monitors the pressure of the perfusion fluid before the perfusion fluid enters the organ; Item 14. The system of item 13, further comprising: (Item 34) 1. A system for enabling sustained normothermic or subnormothermic perfusion of an organ with a perfusion fluid, said system comprising: a tissue enclosure having a fluid reservoir, the tissue enclosure holding the organ; a gas management subsystem that adjusts gas saturation in the perfusate; a thermal management subsystem that adjusts the temperature of the perfusion fluid according to a preselected threshold, the preselected threshold being normothermic or subnormothermic; a perfusion subsystem that circulates a perfusion fluid through the organ, the gas management subsystem, and the thermal management subsystem, the perfusion fluid enabling sustained normothermic or subnormothermic conditions for the organ; a pneumatic subsystem that drives the perfusion subsystem to pump the perfusion fluid; a control subsystem for controlling the pneumatic subsystem, the thermal management subsystem, and the gas management subsystem; A system comprising: (Item 35) 35. The system of claim 34, further comprising a power management subsystem that measures power output from the organ. (Item 36) 35. The system of claim 34, further comprising a gas trap that removes gases from the perfusate. (Item 37) 35. The system of claim 34, further comprising a sensor subsystem that monitors a characteristic of the perfusion fluid, the sensor subsystem collecting sensor data. (Item 38) 38. The system of claim 37, further comprising a data processor that receives the sensor data, the data processor providing the sensor data to the control subsystem, and the control subsystem controlling the thermal management subsystem based at least on the sensor data. (Item 39) 38. The system of claim 37, further comprising a data processor that receives the sensor data, the data processor providing the sensor data to the control subsystem, and the control subsystem controlling the pneumatic subsystem based at least on the sensor data. (Item 40) 38. The system of claim 37, further comprising a data processor that receives the sensor data, the data processor providing the sensor data to the control subsystem, and the control subsystem controlling the gas management subsystem based at least on the sensor data. (Item 41) 35. The system of claim 34, further comprising an injection subsystem that introduces an additive into the perfusion solution. (Item 42) 35. The system of claim 34, wherein the gas management system comprises a disposable oxygenator. (Item 43) the thermal management subsystem: a disposable heat exchanger; a disposable thermally conductive film; Durable thermal energy source Item 35. The system of item 34, comprising: (Item 44) The perfusion subsystem includes: at least one disposable pump for pumping the perfusion fluid through the organ; at least one durable pump interface coupling the at least one disposable pump with the pneumatic subsystem; Item 35. The system of item 34, comprising: (Item 45) The pneumatic subsystem includes: at least one durable valve; at least one durability chamber; at least one durable pressure source; At least one durable vacuum source; Item 35. The system of item 34, comprising: (Item 46) 1. A system for enabling sustained normothermic or subnormothermic perfusion of an organ with a perfusion fluid, said system comprising: a disposable portion including disposable components and tubing that connects the disposable components together and forms a circulation loop, the circulation loop allowing circulation of the perfusion fluid through the organ; a durable portion including a pneumatic system for driving the circulation of the perfusion fluid, a thermal energy source for supplying thermal energy to the circulating perfusion fluid to maintain the perfusion fluid at a normothermic or subnormothermic temperature, and a control system for controlling the pneumatic system and the thermal energy source; A system comprising: (Item 47) Item 47. The system of item 46, wherein the disposable portion comprises a heat exchanger that transfers heat from the thermal energy source to the irrigation fluid. (Item 48) The heat exchanger comprises: a plate having a first side etched with a fluid pathway and a second opposing side, the second opposing side positioned against a tissue enclosure, the tissue enclosure containing the organ; a thermally conductive film having a first film side covering the first side, the thermally conductive film having a second opposing film side positioned relative to the thermal energy source; Item 48. The system of item 47, comprising: (Item 49) Item 47. The system of item 46, wherein the disposable portion comprises an oxygenator that provides oxygen to the perfusate. (Item 50) Item 47. The system of item 46, wherein the disposable portion comprises at least one pump that pumps the perfusion fluid through the organ, and the pneumatic system drives the at least one pump. (Item 51) Item 47. The system of item 46, wherein the disposable portion comprises at least one pump that injects a substance into the perfusion solution. (Item 52) Item 47. The system of item 46, wherein the disposable portion comprises at least one power management system that measures power output from the organ. (Item 53) The durable portion is at least one sensor providing sensor data, the at least one sensor monitoring the organ; at least one data processor that receives and processes the sensor data, the at least one data processor providing the processed sensor data to the control system, the control system controlling the pneumatic system and the thermal energy source based at least on the processed sensor data; Item 47. The system of item 46, comprising: (Item 54) Item 47. The system of item 46, wherein the disposable portion comprises a gas trap that removes gases from the perfusion solution. [Brief explanation of the drawings]

[0025] The foregoing features of the present disclosure will be more readily understood by reference to the following description considered in conjunction with the accompanying drawings, in which:

[0026] [Figure 1] FIG. 1 is a schematic block diagram of a system of the present teachings.

[0027] [Figure 2] FIG. 2 is a pictorial representation of a first configuration of the system of the present teachings.

[0028] [Figure 2A] FIG. 2A is a pictorial representation of a second configuration of the system of the present teachings.

[0029] [Figure 2B] FIG. 2B is a pictorial representation of a third configuration of the system of the present teachings.

[0030] [Figure 2C] FIG. 2C is a pictorial representation of a fourth configuration of the system of the present teachings.

[0031] [Figure 2D]FIG. 2D is a pictorial representation of a fifth configuration of the system of the present teachings.

[0032] [Figure 2E] FIG. 2E is a pictorial representation of a sixth configuration of the system of the present teachings.

[0033] [Figure 3] 3A-3C are graphical illustrations of the results of operation of the systems and methods of the present teachings.

[0034] [Figure 4A] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings. [Figure 4B] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings. [Figure 4C] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings. [Figure 4D] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings. [Figure 4E] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings. [Figure 4F] 4A-4F are schematic block diagrams of the architecture of the system of the present teachings.

[0035] [Figure 4G] 4G-4H are schematic block diagrams of specific implementations of the system architecture of the present teachings. [Figure 4H] 4G-4H are schematic block diagrams of specific implementations of the system architecture of the present teachings.

[0036] [Figure 5A] 5A-5B are perspective views of components of a first implementation of a system of the present teachings. [Figure 5B] 5A-5B are perspective views of components of a first implementation of a system of the present teachings.

[0037] [Figure 6A] 6A-6B are perspective views of a durable enclosure assembly of a first implementation of the system of the present teachings. [Figure 6B] 6A-6B are perspective views of a durable enclosure assembly of a first implementation of the system of the present teachings.

[0038] [Figure 6D] 6D-6H are perspective views of valve and pump views of a first implementation of the system of the present teachings. [Figure 6E] 6D-6H are perspective views of valve and pump views of a first implementation of the system of the present teachings. [Figure 6F] 6D-6H are perspective views of valve and pump views of a first implementation of the system of the present teachings. [Figure 6G] 6D-6H are perspective views of valve and pump views of a first implementation of the system of the present teachings. [Figure 6H] 6D-6H are perspective views of valve and pump views of a first implementation of the system of the present teachings.

[0039] [Figure 6I] FIG. 6I is a perspective view of a perfusion pump of a first implementation of the system of the present teachings.

[0040] [Figure 6J] 6J-6K are perspective views of a manifold system of a first implementation of the system of the present teachings. [Figure 6K] 6J-6K are perspective views of a manifold system of a first implementation of the system of the present teachings.

[0041] [Figure 7A] 7A-7C are perspective views of a disposable interface enclosure assembly of a first implementation of the system of the present teachings. [Figure 7B] 7A-7C are perspective views of a disposable interface enclosure assembly of a first implementation of the system of the present teachings. [Figure 7C] 7A-7C are perspective views of a disposable interface enclosure assembly of a first implementation of the system of the present teachings.

[0042] [Figure 8A] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8B] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8C] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8D] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8E] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8F-1] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8F-2] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8G] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8H] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings. [Figure 8I] 8A-I are perspective views of a disposable assembly of a first implementation of the system of the present teachings.

[0043] [Figure 9A] 9A-9C are perspective views of an electronics assembly of a first implementation of the system of the present teachings. [Figure 9B] 9A-9C are perspective views of an electronics assembly of a first implementation of the system of the present teachings. [Figure 9C]9A-9C are perspective views of an electronics assembly of a first implementation of the system of the present teachings.

[0044] [Figure 10A] 10A-10C are perspective views of a second implementation of the system of the present teachings. [Figure 10B] 10A-10C are perspective views of a second implementation of the system of the present teachings. [Figure 10C] 10A-10C are perspective views of a second implementation of the system of the present teachings.

[0045] [Figure 11] FIG. 11 is a schematic diagram of fluid flow in a second implementation of the system of the present teachings.

[0046] [Figure 12] FIG. 12 is a schematic diagram of the configuration of the pneumatic subsystem of the present teachings. DETAILED DESCRIPTION OF THE INVENTION

[0047] Detailed Description A system of the present teachings for providing normothermic kidney transport with thermal control can include a tank enclosure for storing the kidney and a circulation system. The tank enclosure and circulation system can be thermally controlled. In some configurations, the tank can be insulated. The circulation system can provide oxygenated perfusate to the kidney and can allow for continuous monitoring of the perfusate moving through the kidney. The tank can provide an inlet that can receive a selected infusate and an outlet that can allow sampling and waste removal. The system can constantly monitor a solution bath in which the kidney is immersed, and the system can manage the composition of gases in the tank.

[0048] 1 , system 100 can include, but is not limited to, tank 123, oxygen source 157, sample / waste container 131, infusible solution 103, circulation monitor sensor 148, tank monitor sensor 104, temperature management subsystem 101, pump 129 / 113, and controller 102. Tank 123 can be sized to accommodate kidney 135 to be transplanted, solution bath 125 in which kidney 135 can be immersed, and gas 163 above solution bath 125. In some configurations, tank 123 can be constructed with transparent sides to allow visual monitoring of kidney 135. Oxygen source 157 can provide dissolved oxygen to the perfusate in circulation route 126.

[0049] 2 , system 100A provides a first configuration of system 100. In system 100A, renal artery 141 can receive perfusate through circulation route 126 into kidney 135, which can process the perfusate and discharge the treated perfusate through renal vein 139 and ureter 137. Renal vein 139 can provide the treated perfusate to solution reservoir 125. Perfusion pump 129 can pump perfusate from solution reservoir 125 to circulation route 126. The pressure applied by perfusion pump 129 can be monitored by controller 102 as it receives data from pressure gauge 117. Controller 102 can adjust the pressure on the perfusate in circulation route 126 to a desired pressure based at least on the data collected by pressure gauge 117.

[0050] Continuing with reference to FIG. 2 , circulation route 126 can allow movement of perfusate into kidney 135, through kidney 123, and from tank 123 past circulation monitor sensor 148 and temperature management 101 back into tank 123 and kidney 135. Perfusion pump 129 can pump perfusate through kidney 135 to simulate what would normally occur in the body. The perfusate can provide oxygen to kidney 135, remove CO2, remove waste products, and provide a chemical buffer, creating near-physiologically correct chemical conditions for kidney 135. Perfusate entering kidney 135 can be held at a controlled pressure to ensure kidney 135 is subjected to both a desired total pressure and / or a desired chemical gradient. An upper limit on pressure can be set by physiological boundaries; for example, excessive pressure can result in barotrauma to the kidney, or if pressure exceeds 30-40 mmHg, temperature can become hypothermic and edema can occur. The selection of the type of perfusion pump 129 can be based on the type of perfusate. Possible perfusate solutions and ingredients include, but are not limited to, blood or packed red blood cells, conventional organ storage solutions such as, but not limited to, KPS-1, HTK, and UW, plasma substitutes such as, but not limited to, Plasmalyte, Ringer's solution, and Stelfundin, pH buffers, amino acids, cell culture media such as, but not limited to, DMEM and growth factors, sugars, electrolytes, pharmaceuticals such as, but not limited to, heparin, vasodilators, antibiotics, and antifungals, hemoglobin extracts such as, but not limited to, HbO2 therapeutic agents and hemarina, perfluorocarbon oxygen carriers such as, but not limited to, perfluorodecalin, and vasodilators. Some solutions (such as blood-based solutions) can require low shear conditions to minimize hemolysis. In addition, the mechanical properties of the perfusate, such as density and viscosity, can dictate pump requirements.

[0051] Continuing with reference to FIG. 2 , because physiological pressure is not constant, the geometry of the perfusion pump 129 and / or the process by which it is controlled can be adjusted to create a pressure profile that approximates physiological conditions. For example, the size and shape of a direct-acting pumping chamber can be customized, the occlusion of a peristaltic pump can be varied by modifying the radial position of the rollers, a blend of dual pump heads and pump stroke timing can be used, the timing of the pump stroke can be varied, and the size of the pumping chamber can be changed. Types of perfusion pumps can include, but are not limited to, peristaltic, rotary vane, rotary piston, and direct-acting pneumatic pumps. The latter can be useful when low-shear conditions are required.

[0052] Continuing with reference to FIG. 2 , the tank monitor sensor 104 ( FIG. 1 ) can monitor the characteristics of the solution bath 125 and enable the addition of solution 103 to adjust the characteristics of the solution bath 125. For example, but not limited to, sensors such as tank level 105, tank thermistor 107, pH 109, and dissolved oxygen 111 can monitor the solution bath 125. The controller 102 can adjust the characteristics of the solution bath 125 based at least on the sensed data. The vitality of the kidney 135 can be monitored by a kidney sensor 108 ( FIG. 1 ), which can test urine in the sample / waste container 131. The controller 102 can receive data from the kidney sensor 108, the circulation monitor sensor 148, and the tank monitor sensor 104 and can evaluate whether to modify the characteristics of the solution bath 125 to maintain the desired vitality of the kidney 135. The controller 102 can report the actual status of the kidney 135.

[0053] Continuing with reference to FIG. 2 , the perfusate can be subjected to oxygenation and temperature control as it travels along the circulation route 126. The role of the oxygenator is to act similarly to how the lungs would function in the body, supplying oxygen and removing CO2 from the recirculating perfusion fluid. An air compressor 159 can work in conjunction with the oxygenator 158 in a manner that can mimic the interaction between the diaphragm and lungs of the human body by drawing fresh air into the system. Portable systems can include a portable air compressor. Non-portable systems can be connected to an indoor oxygen source and potentially do not have any need for the oxygenator 158 or air compressor 159. Air entering the system can be filtered to remove particulates, bacteria / mold, and toxic fumes, such as, but not limited to, paint fumes and automobile exhaust. Filters can include, but are not limited to, particulate filters, sterilizing filters, and activated carbon filters. In some configurations, the oxygenator 158 can extract oxygen from air provided by an air compressor 159 and can provide oxygen to the circulating perfusate when the controller 102 discovers from sensor data collected from the dissolved oxygen sensor 151 that the circulating perfusate is measuring below a desired dissolved oxygen level. In some configurations, the air compressor 159 can provide air to the oxygenator 158 through an air pressure line 161. The oxygenator 158 can vent waste air 155 when needed. Types of oxygenators that can meet the needs of the systems and methods of the present teachings can include silicone membrane oxygenators, bubbler-type systems, and “airlift” oxygenation loops. Extracorporeal membrane oxygenation therapy can be used to circulate the perfusate through the kidney 135. In an airlift oxygenation loop, air is introduced through a sparger at the bottom of the fluid column, and the air bubbles displace the fluid, pushing it up, which then pours into tank 123 and recirculates back into the column out outlet port 164, thus creating an independent oxygenation loop.In some configurations, the airlift can be integrated with the tank 123 and the bubble resonance time of the column can be increased, for example, but not limited to, by making the bubble size smaller and inducing a longer flow path.

[0054] Continuing with reference to FIG. 2 , in some configurations, air can be prevented from entering the kidney 135. Air bubbles within the kidney 135 can impede flow, which in turn can limit the performance of physiological tasks, such as, but not limited to, oxygen delivery or CO2 removal. An air trap can prevent air from entering the kidney 135. The air trap can be embodied in various physical forms and can be a passive or active component. In some configurations, the air trap can include a tank with an inlet that is not in series with the outlet from the tank, allowing air bubbles to rise to the top of the tank. In some configurations, a venturi or centrifugal force can be used to draw air bubbles out of the solution, or a degassing chamber can create undesirable turbulence or other conditions for entrapped air bubbles to remain in the perfusate. Air bubble detectors, such as, but not limited to, optical and ultrasonic sensors, can detect air bubbles in the perfusate. The controller 102, through control of the valve 143, can redirect the perfusate to bypass the kidney 135 until the bubble trap collects the entrapped air bubbles. The use of the bubble trap can reduce or eliminate the need to prime the system.

[0055] Continuing with reference to FIG. 2 , the infusion pump 113 can pump infusion solution 103 into the reservoir 123 when adjustment of the solution reservoir 125 is necessary. The infusion solution 103 can allow for fluid, electrolyte, and / or nutrient replenishment, such as, but not limited to, administration of correction solutions such as glucose, insulin, buffer solutions, antibiotics, vasodilators, or other medications. The switching valve 115 can allow the infusion pump 113 to administer multiple infusion solutions. Together, the infusion pump 113 and the switching valve 115 can administer metered amounts of the infusion solution 103 into the reservoir 123. Providing the infusion solution 103 directly into the holding reservoir 123 can allow the infusion solution 103 to mix with the solution reservoir 125 and diffuse into the solution reservoir 125 prior to being circulated into the kidney 135. Diffusion can allow for administration of a relatively higher concentration of infusion solution 103 than could be administered directly into the kidney 135. Alternatively, the infusion solution 103 can be delivered directly to the kidney 135 through the tubing 118. If response time is a factor, the infusion solution 103 can be pumped to the kidney 135 through the opening valve 134 and the tubing 118. In some configurations, the infusion solution 103 can be premixed and stored in a sterile container. In some configurations, the controller 102 can be configured to deliver the infusion solution 103 in a preselected dose at a preselected time interval. For example, a medication can be delivered on a preselected schedule. In some configurations, the controller 102 can be configured to deliver a bolus to bring various components to desired levels. For example, a glucose bolus can be delivered to bring glucose to a desired level. Table I illustrates possible infusion schedules. [Table 1]

[0056] Continuing with FIG. 2, the accuracy of the injection pump 113 can vary depending on the amount of dilution relied upon to manage concentration and whether the system is portable. The diverter valve 115 can be embodied in a variety of ways, such as a rotary diverter valve powered by a stepper or servo motor, a series of line and occlusion valves, and a spool occlusion valve. In some configurations, the disposable line can pass by a spool roller, which can be rotated by a motor that can roll and occlude various lines based on its position. In some configurations, a cleaning chemical can be injected to clean the system.

[0057] 2, the controller 102 can set the selector valve 115 to provide at least one desired infusion solution 103 to the solution reservoir 125. Properties of the solution reservoir 125 can be sensed and adjusted by the controller 102 and the infusion solution 103. The properties of the solution reservoir 125 can include tank level, temperature, pH, and dissolved oxygen.

[0058] Continuing with reference to FIG. 2 , the level of the reservoir 123 can be sensed by the reservoir level sensor 105 and regulated by the controller 102 by adding infusion solution 103 and draining excess solution reservoir 125 through drain port 163. The reservoir 123 can hold the kidney 135 and a majority of the perfusion fluid required for perfusion. The perfusion fluid can surround the kidney 135, provide chemical homogeneity, and provide mechanical support for the kidney 135. The reservoir 123 can accommodate mixing of the infusion solution 103 and the solution reservoir 125. The reservoir 123 can include a compliant feature to prevent the perfusion pump 129 from exposing the kidney 135 to a vacuum. In some configurations, the compliant feature can include a sterile vent cap for venting the reservoir 123. The sterile vent cap can maintain the pressure within the reservoir 123 near ambient pressure. Additionally, a sterile vent cap can allow for priming of the system, as air trapped within the reservoir 123 can escape as fluid is pushed in. The presence of air 163 above the solution reservoir 125 can provide compliance, as the air 163 can compress and expand as needed. In some configurations, the reservoir 123 can be sterile and disposable, and can be made from, for example, but not limited to, molded plastic, stainless steel, glass, or flexible plastic. The reservoir 123 can accommodate connections such as, for example, but not limited to, perfusion lines, urine / sample ports, and infusion inputs. In some configurations, such as, for example, but not limited to, portable configurations, the reservoir 123 can include means for protecting the kidney 135 from encountering the walls of the reservoir 123.

[0059] Continuing with reference to FIG. 2 , in some configurations, the temperature can be adjusted to the needs of the kidney 135, with emphasis on the sub-normothermic and normothermic regions to provide a hypothermic to normothermic range. In some configurations, the tank 163 includes insulation 144 surrounding the tank 123, which can minimize the amount of energy required to heat / cool the solution bath 125. In some configurations, the insulation 144 can include, but is not limited to, vacuum panels and aerogel. In some configurations, heating / cooling can be applied directly to the perfusate line via a hot / cold plate or to the walls of the tank 123. In some configurations, an additional cooling loop can include a heat exchanger. In some configurations, heating can be provided by a resistive heater, and cooling can be provided by a Peltier device. In some configurations, a phase change material, such as, but not limited to, ice and wax, can act as a cold sink, and a heating element can be used to equilibrate the temperature. In some configurations, a phase change material can be used in a reservoir, for example, but not limited to, around the perfusion fluid line and / or around tank 123, and a resistive heater can be used to "charge" the phase change material, causing it to melt and keep the system warm. In some configurations, the heater can melt the phase change material when the system is cooled below the temperature at which the phase change material freezes.

[0060] Continuing with reference to FIG. 2 , sensors can provide diagnostic data about the kidney 135 to assess the vitality of the kidney 135 and enable active control in the system to maintain biological conditions. In some configurations, the controller 102 can assess characteristics of the circulating perfusate to determine if the circulating perfusate requires adjustment and can actively control the infusate to implement any desired adjustments. Characteristics can be determined from sensor data from sensors such as, for example, but not limited to, a glucose sensor 149 and a pH sensor 153. Adjustments can be made to the perfusate by adjusting the solution 103 added to the solution reservoir 125. A thermistor 147 can measure the temperature of the circulating perfusate, and the temperature management system 101 can adjust the temperature of the circulating perfusate to a desired value. Sensors can include, but are not limited to, pressure, temperature, dissolved oxygen, oximeter, pH, glucose / lactate, conductivity, tank level, and perfusate flow sensor or pump metering. In some configurations, differential measurements can be taken, for example, without limitation, before and after the perfusate encounters the kidney 135. Differential oxygen levels can be used to calculate oxygen consumption. Differential pressure levels can be used, for example, without limitation, to detect blockages. In some configurations, a hydrogel sensor and / or hydrogel spot and an optical source / receiver can be included in the system. The optical source can generate light that can interact with the spot, and the emitted wavelengths can be received by the optical sensor. Various wavelengths can be emitted by adjusting a monochromatic filter or by configuring a bank of LEDs to provide specific wavelengths. In some configurations, a conductivity sensor can provide an indirect measurement of the salt concentration of the perfusate. The conductivity sensor can include a three-electrode system, where the polarity is reversed between two points at a predetermined frequency, and the voltage along the circuit can be checked, although offset, at the same frequency. The conductivity sensor can limit the data processing required.Timing for the conductivity sensor can be achieved via a microcontroller or FPGA. The selection between sensors can be based, at least in part, on whether sensing is being done in conjunction with a disposable portion.

[0061] 2 , an optional component of the system, waste / sample container 131, may be compliant to minimize the overall weight of the component prior to filling and may allow a urine sample to be collected that may be used for renal diagnostics. When kidney 135 is functioning, urine is secreted into sample / waste container 131 through ureter 137. The volume and contents of sample / waste container 131 may be tested to determine if kidney 135 is functioning properly. In some configurations, level sensor 133 may detect the amount of urine in sample / waste container 131.

[0062] 2A, the temperature management system 101 can include a hot zone 1151 and a cold zone 1153. The multiple insulated compartments can include various temperature management solutions, such as, but not limited to, resistive heating and / or hot / cold packs. The temperature management system 101 can include valve-directed flow through the hot zone 1151 or the cold zone 1153, depending on the desired temperature.

[0063] Referring now to FIG. 2B, the thermal management system 101 can include thermoelectric technology such as, for example, but not limited to, Peltier technology 1155, where reverse polarity can be used to achieve a heating / cooling effect.

[0064] 2C, the temperature management system 101 can include heat exchanger technology 1157 having a reversible heat pump 1159. The heat pump 1159 can be reversed to achieve a heating / cooling effect. In some configurations, the flow rate of the perfusate can be varied to manage heat transfer.

[0065] 2D, the temperature management system 101 can include a series dual heat exchanger technology having a resistive heat exchanger 1163 and a cooling exchanger 1165. The resistive heat exchanger 1163 allows for a reduction in the amount of heat added. The cooling circuit 1161 allows for a reduction in the amount of cooling that needs to be delivered by the cooling exchanger 1165.

[0066] 2E, the thermal management system 101 may include a phase change material 1167 surrounding the tank 123. In some configurations, no active thermal control may be necessary.

[0067] Referring now to Figures 3-3C, the systems and methods of the present teachings can perfuse a kidney at a preselected pressure, at room temperature, while adjusting other parameters in the reservoir. These parameters can include both in-line (pre-renal) and tank sensors for dissolved oxygen and pH, along with tank and ambient temperature sensors. An in-line tube feeds into the reservoir, to which the cannulated kidney can be attached. The system then draws perfusate from the reservoir itself into the in-line tube; the renal vein is not cannulated / isolated. The system can include a membrane contactor that can oxygenate the deoxygenated perfusion fluid to atmospheric equilibrium levels. In some configurations, the perfusate can include Custodiol-HTK, a solution designed for ex vivo use. The solution can be supplemented with 4.5 g / L of glucose to meet the metabolic needs of the active kidney. Prior to use, the solution can be filtered, for example, but not limited to, using a sterile filter. The method of the present teachings can include cannulating the renal artery and ureter if a urine sample is desired. The method can include pumping perfusion fluid through the kidney to remove potential contaminants from the kidney. The method can include pumping a cleaning solution through the system and rinsing the system with, for example, but not limited to, sterile DI water until a desired pH is reached. The method can include attaching a cannula to in-line tubing, priming the cannula through bypass tubing 119 and bypass valve 143, closing bypass valve 143, and beginning perfusion of the kidney 135. The perfusion pressure can be set manually, can include a default value, or can be dynamically determined. The method can include perfusing the kidney for a preselected amount of time, for example, but not limited to, 24 hours. The method can include periodically checking glucose levels.

[0068] Continuing with reference to Figures 3A-3C, results from performing the methods described herein include renal resistance over time. Renal resistance, as shown in Figure 3A, can be considered an indicator of renal health. Low resistance and no increase over time is a desired outcome. Dissolved oxygen values, as shown in Figure 3B, for both the series sensor and the tank sensor can indicate the level of oxygen consumption within the kidney. pH values, as shown in Figure 3C, can indicate renal health and cell viability. In particular, acidification indicates a healthy kidney.

[0069] 4A-4G, a system of the present teachings for normothermic and subnormothermic organ perfusion can include disposable and durable components. This can reduce the operating costs of the system and reduce contamination from one organ perfusion cycle to another. The term normothermic is used herein to refer to temperatures between 32°C and 38°C, the term subnormothermic is used herein to refer to temperatures within the range of 20°C to 32°C, and the term hypothermic can refer to temperatures within the range of 4°C to 19°C. The disposable components can include pumps for enabling any of organ perfusion, fluid recirculation, and infusion. The disposable components can also include thermal control components such as a heat exchanger and a tissue enclosure for holding the organ. In all configurations, all fluid-contacting components are considered disposable. In some configurations, the disposable components can include the organ enclosure, oxygenator, tubing, cannula, manifold, pump cassette, reservoir, heat exchanger, and internally mounted sensors. The durable portion can include interface components, electronics, pneumatics, and controls for coupling the disposable components to other parts of the system. Durability components can also include non-invasive sensors and thermal control elements. In some configurations, for example, an imaging sensor can record real-time information about the organ. For example, images / videos can record changes in color and size of the organ. Color can indicate the quality of perfusion through the organ, and size can indicate edema of the organ. In some configurations, the organ enclosure can include a defroster window that can maintain a fog-free surface through which imaging capture can occur.

[0070] 4A , an exemplary system 500A can provide normothermic or subnormothermic maintenance of an organ 1029. The system 500A can include, but is not limited to, a perfusion system 1001, a gas management 1025, a thermal management 1013, a power management 527, pneumatics 505, a data processor 503, and a controller 501. The system 500A can include a tissue enclosure 1005, which can take any shape and size depending on the type of tissue contained therein. For example, the tissue enclosure 1005 can include, for example, four sides and a lid. In some configurations, the sides and lid can be transparent for viewing the enclosed tissue. In some configurations, any of the surfaces forming the tissue enclosure 1005 can include anti-fog features. One such feature can include an anti-fog patch, which can include an embedded wire. An electric current can be passed through the embedded wires to heat the anti-fogging patch, which can then make the underlying surface of the tissue enclosure 1005 transparent by preventing water vapor from condensing or allowing it to evaporate. The tissue enclosure 1005 can include a gas vent and filter 1004. The gas vent and filter 1004 can fix the exit pressure from the organ 1029. The system can include a sample port 502 (FIG. 4A). Other ports can be added as needed. The organ 1029 can rest within the bioreactor 1005, possibly on a platform 1018 or any suitable support means. The bioreactor 1005 can be shaped and sized for a specific type of organ or can include features that are common to several organ types. The bioreactor 1005 can include various interfaces to allow fluid input and output. To the extent possible, system 500A can enable the circulation of perfusion fluid drawn from fluid reservoir 1027 to mimic in vivo flow through organ 1029.The control system 501 can activate and monitor the pneumatic system 505 and the data processor 503 according to preselected, default, user-defined, dynamically determined, or other criteria. The control system 501 can instruct the pneumatic system 505 to control the flow rate and pressure of the circulating perfusion fluid. The perfusion system 1001 can include a perfusion pump. The perfusion pump can include features such as those described in U.S. Patent No. 8,273,049, issued September 25, 2012, entitled "Pumping Cassette." Additionally, the pressure profile can be adjusted. The filling and delivery pressures of the pumping cassette can be independently adjusted to manage the flow rate by feathering / toggling any of the valves controlling the pumping cassette to achieve the desired pressure. An exemplary valve arrangement is shown in FIG. 12. Of particular importance is that the perfusion pump has the ability to adjust the flow rate and pressure entering the organ 1029. As resistance in the organ 1029 changes, the perfusion pump should include the ability to vary pumping pressure and flow rate to adapt to the changed resistance. The perfusion pump should also enable low hemolysis. The data processor 503 can receive and store data from any monitoring components in the system 500A and provide those data to the control system 501. To properly mimic in vivo behavior, the dissolved gas concentration and temperature of the perfusion fluid can be maintained at levels that can be preselected, manually initiated, or dynamically determined, for example. In some configurations, the perfusion system 1001 can pump perfusion fluid through the gas management system 1025 and thermal management system 1013, through the air trap 1009, and through the arterial cannula 1033 into the organ 1029, through the organ 1029, out the waste exit cannula 1031, and back into the fluid reservoir 1027. At the same time, the perfusion system 1001 can draw perfusion fluid from the fluid reservoir 1027 to continue the circulation process. The gas in the perfusion fluid can be regulated as the perfusion system 1001 pumps the perfusion fluid to the gas management system 1025.The gas management system 1025 can regulate depleted gas as the perfusate progresses through the organ 1029. The perfusate temperature can be maintained within a preselected temperature range by the thermal management system 513. Gas bubbles can be removed from the perfusate by any available inline method. In some configurations, a gas trap 1009 provides space for gas bubbles to float to the top of the enclosure, allowing the liquid perfusate to flow into the organ 1029 through an arterial cannula 1033, for example. Perfusate exiting the organ 1029 via a vein can ultimately be directed to a fluid reservoir 1027 or other component (not shown) for managing the circulated perfusate. In some configurations, the venous output can flow directly into the perfusion system 1001, creating a closed-loop circulation and potentially reducing hemolysis. For some types of organs, flowing the output into a fluid reservoir 1027 can create an environment that can resemble the human body as closely as possible. In some configurations, the output can be sent to a waste treatment system, and a replacement solution can be infused into the system at a flow rate matching the output flow rate. In some configurations, the exiting perfusate, i.e., the output, can be measured. In some configurations, the output management 527 can measure the flow rate, for example, over a preselected amount of time. Measurement of other types of waste can be accommodated by the system 500A. The fluid reservoir 1027 can thus allow complete circulation of the perfusate through the organ 1029. In some configurations, a filter can be placed between the fluid reservoir 1027 and the perfusion system 1001. The filter can capture particulates, such as tissue chunks or contamination, so that they are not pumped into the organ. In some configurations, the filter can include a 20-30 micron screen. In some configurations, the bioreactor 1005 can be moved from one environment to another, specifically from a relatively cryogenic environment to a normothermic environment as described herein.

[0071] 4B , in some configurations, the system 500B can be used to add substances to the fluid reservoir 1027 using an infusion system 507. The infusion system 507 can allow one or more additives, such as, but not limited to, glucose, insulin, hormones, vasodilators, and pharmaceuticals, to be infused into the perfusion fluid, for example, when the perfusion fluid is determined to have a deficiency and / or imbalance, or on a regular dosing schedule. The control system 501 can instruct the pneumatic system 505 to drive the infusion system 507, possibly in response to sensor data. For example, vascular resistance can be measured, and when the resistance is deemed to be outside a preselected or user-defined or dynamically determined threshold, the response can be the introduction of a vasodilator. Glucose can be measured, and when the glucose is deemed to be outside a preselected or user-defined or dynamically determined threshold, the response can be the introduction of glucose or insulin. Multiple substances can be added simultaneously. The infusion system 507 can use a pump with features such as, but not limited to, those described in U.S. Patent Application No. 8,613,724, issued December 24, 2013, entitled "Infusion Pump Assembly." In some configurations, the infusion system 507 can allow for the infusion of a substance directly into the bioreactor 1005. In some configurations, the infusion system 507 can allow for the infusion of a substance into tubing that fluidly interconnects parts of the system of the present teachings. For example, when infusing a compound with a relatively short half-life, such as 5-10 minutes, injecting the compound directly into the arterial supply can ensure that the compound has not reached its half-life by the time it arrives in the organ.

[0072] Referring now to FIG. 4C , in system 500C, sensors can be used to monitor the circulating perfusate. Characteristics that can be monitored include, but are not limited to, perfusate flow rate, creatinine concentration, sodium concentration, fluid level in bioreactor 1005, temperature, pH, dissolved oxygen concentration, Hb saturation, conductivity, and gas. Pump pressure can be monitored by pump pressure sensor 1037. Pump pressure sensor 1037 can determine the in-line pressure of the perfusate flowing through the tubing connecting perfusion pump 1001 and gas management 1025. In some configurations, pump pressure sensor 1037 can be durable, while the in-line connector coupling pump pressure sensor 1037 to the tubing can be disposable. In some configurations, the sensor can also be disposable. Pump pressure sensor 1037 can provide the sensed pressure to data processor 503. Control system 501 can use that data to automatically trigger an increase or decrease in pressure applied by perfusion system 1001. The pressure can also be adjusted manually, or based on a time schedule, a recipe, or other factors in addition to or instead of the pressure detected by the pressure sensor 1037. Pressure changes can be required when the organ's resistance changes, for example, when the organ's health status changes. Pressure sensors can be positioned throughout the circulation loop of the system 500C. For example, a perfusate pressure sensor 1011 can monitor the pressure of the fluid leaving the thermal management system 513. This information can be useful for monitoring the perfusate pressure at critical entry points into the organ 1029. Perfusate pressure above a preselected range can damage the organ 1029, while too low a perfusate pressure can cause improper nutrient flow and waste removal through the organ 1029. In some configurations, the pressure sensor 1011 can be durable, while the serial connector giving the sensor access to the sensed pressure can be disposable. Other sensors can also measure various parameters depending on the needs of the tissue held within the bioreactor 1005.For example, an optical clearance sensor can use a series of LEDs to detect absorption changes at different wavelengths to provide creatinine / BUN measurements of blood and organ output. In some configurations, the optical clearance sensor can be a non-contact sensor located within the tubing and output system. Together, the sensors can measure, for example, creatinine clearance.

[0073] 4C , glucose sensor 1036 can monitor glucose and possibly lactose levels in the perfusion fluid pumped from fluid reservoir 1027. In some configurations, glucose sensor 1036 can include a durable PCB coupled with a disposable serial glucose sensor. Control system 501 can use the glucose data collected by glucose sensor 1036 and provided to data processor 503 to automatically trigger one or more of infusion pumps 1003 to add glucose and / or other substances to the circulating perfusion fluid. Glucose data can be monitored manually, and glucose and / or other substances can be added manually to the perfusion fluid.

[0074] Referring now to FIG. 4D , the system 500D can include a pinch valve 1039 as an output measurement means. In some configurations, the output management 527 can measure the waste flow rate for a preselected amount of time, and the pinch valve 1039 can hold the output for the same period of time. The amount of output and its flow rate can be measured, and the pinch valve 1039 can be opened after the time has elapsed to release the output into the fluid reservoir 1027. In some configurations, a sample port can allow sampling of the output, for example, for experimental work. In some configurations, a level sensor can be used to measure the amount of output. In some configurations, the accumulated output can be held in a transparent enclosure that can be used for optical inspection of the output, either manually or automatically. For example, the color of the kidney output can indicate blood in the urine, or cloudy urine can indicate possible kidney health issues. In some configurations, an optical clearance sensor can enable automated measurement of creatinine and blood urinary nitrogen concentrations using a series of LEDs and photodetectors.

[0075] Referring now to FIG. 4E, in system 500E, sensors can be advantageously installed to thoroughly monitor the circulating perfusion fluid and trigger adjustments as necessary. The sensors in this system can provide diagnostic information that can assist medical professionals in assessing organ quality. Diagnostic information can include, but is not limited to, vascular resistance as a function of arterial flow and arterial pressure, oxygen consumption, glucose consumption, power production, physical appearance, glomerular clearance, and fractional sodium excretion. Fractional sodium excretion can be calculated as a function of output flow rate, blood and output sodium concentrations, and glomerular clearance. Sodium concentration can be measured by various means and can be measured from anywhere in the system. In some configurations, sodium concentration can be measured in the recirculation line and in the output loop, and the difference between the two measurements can be calculated. Although not explicitly shown, all sensors can provide sensor data to data processor 503. Data processor 503 can perform, for example, sensor data filtering, sensor data fusion, and sensor data monitoring, and provide information to control system 501. The control system 501 can control the actions of the sensors themselves, as well as the actions of other components of the system 500E, according to the received sensor data. In the system 500E, a glucose sensor 1036 and a pump pressure sensor 1037 can be positioned to collect sensor data about the perfusate flowing from the perfusion system 1001 to the gas management system 1025. Measuring glucose at this point in the circulation cycle can provide advantages over other placement possibilities, if applicable, depending on the type of organ and stage of organ repair within the bioreactor 1005. For example, an optical level sensor can be positioned at a preselected height within the output reservoir and can trigger the release of the output into the fluid reservoir when the output reaches the preselected height.

[0076] 4E , the system 500E can include a thermal sensor 1124 that senses the temperature of the perfusion fluid as it enters the thermal management system 513. The thermal sensor 1124, in some configurations, can include a durable IR sensor coupled to disposable tubing through which the perfusion fluid travels. The system 500E can include a thermal sensor 1014 that can measure the temperature of the perfusion fluid as it exits the thermal management system 513. The temperature of the perfusion fluid can be determined by the temperature sensor 1014 as the perfusion fluid exits the heat exchange means 1013. Monitoring the temperature before and after progression of the thermal management system 513 can indicate to the control system 501 that a change in thermal management may be necessary depending on a preselected thermal target, a manually entered thermal target, and / or possibly a dynamically determined thermal target based on the status of the organ 1029 and / or other sensor data. The system 500E can include additional thermal monitoring by a thermal sensor 1044 positioned to monitor the temperature of the perfusate as it leaves the fluid reservoir 1027. Such a reading can indicate the level of thermal change between when the perfusate enters the organ 1029 and when the perfusate completes its circulatory path en route to the perfusion system 1001. The thermal change can trigger adjustments in the environment of the bioreactor 1005 that can, for example, allow for minimizing thermal fluctuations over time. In some configurations, the temperature sensors described herein can include external infrared (IR) sensors and can be durable, while the tubing to which the sensor is attached can be disposable.

[0077] Continuing with reference to FIG. 4E , the system 500E can include a durable oxygen saturation sensor 1046 that can measure venous oxygen saturation. Abnormalities in venous oxygen saturation can indicate that the metabolic needs of the organ 1029 are not being met. The system 500E can include an oxygen saturation sensor 1026 that can measure oxygen saturation before the perfusate enters the organ 1029 through the arterial cannula 1033. Abnormalities in the oxygen saturation of the perfusate entering the organ 1029 can indicate the need for supplemental oxygen. The gas management system 1025 can supply such oxygen to the perfusate. In some configurations, the oxygen saturation sensor 1026 can be a durable item, while the tubing through which oxygen saturation is measured can be disposable. In some configurations, the system of the present teachings can respond to high / low oxygen saturation by altering the supply of oxygen to the gas management 1025. In some configurations, the system of the present teachings can respond to high / low pH values ​​by altering the supply of carbon dioxide flowing to the gas management 1025.

[0078] Continuing with reference to FIG. 4E, the system 500E can include a gas sensor 1034 that can detect gas in the perfusate before it enters the organ 1029. In sufficient quantities, gas in the perfusate can cause serious complications to the organ 1029. Information from the gas sensor 1034 can be provided to the data processor 503, which can inform the control system 501 about possible mitigation strategies, potentially depending at least on, for example, but not limited to, preselected, dynamically determined, or manually entered acceptable gas thresholds. The gas sensor 1034 can include an ultrasound housing that can be durable, while the tubing through which the perfusate is probed can be disposable. The gas sensor 1034 can be used for automatic system priming. The organ can be bypassed or not be part of the circulation loop at all until the gas sensor 1034 no longer detects any gas. System 500E can include a pump flow sensor 1032 that can measure pump flow pressure and flow rate as perfusion fluid enters organ 1029. Data from this sensor can be used to adjust pneumatic system 505, which can ultimately regulate the pressure in perfusion system 1001. Pump flow sensor 1032 can include an ultrasound housing that can be durable, while the tubing through which perfusion fluid is probed can be disposable. Under normal circumstances (i.e., no triggers are set off by sensor data), perfusion fluid can enter arterial cannula 1033 and then enter organ 1029.

[0079] Continuing with reference to FIG. 4E, the system 500E can include sensors within the fluid reservoir 1027. Exemplary sensors include, but are not limited to, a dissolved oxygen sensor 1022 and a pH sensor 1024. The dissolved oxygen sensor 1022 can monitor the oxygen concentration in the perfusate. The gas management system 1025 can be directed by the control system 501 to adjust the amount of oxygen added to the perfusate based on sensor data from at least the dissolved oxygen sensor 1022. In some configurations, the dissolved oxygen sensor 1022 can include a disposable component and a durable component. The disposable component can include a spot sensor, which may optionally be self-adhesive. The durable component can include sensor-specific electronics and wiring. The wiring can optionally include a fiber optic cable. The pH sensor 1024 can monitor the pH of the perfusate. When the perfusate deviates from its normal acid / base balance, adjustments are possible through various well-known means, depending, for example, on the type of organ being repaired. Types of adjustments can include, but are not limited to, adding buffer compounds and / or modifying carbon dioxide input to the gas management 1025 and / or injecting buffer solutions. In some configurations, the pH sensor 1024 can include a disposable component and a durable component. The disposable component can include a spot sensor, which may optionally be self-adhesive. The durable component can include sensor-specific electronics and wiring. The wiring can optionally include fiber optic cable.

[0080] 4F, system 500F can include components of systems 500D (FIG. 4D) and 500E (FIG. 4E), specifically, the sensors described with respect to system 500E and the output measuring means described with respect to system 500D. Indeed, any combination of components and other additional components is contemplated by the systems of the present teachings. Sensor placement can depend on the needs of the tissue being maintained and / or repaired.

[0081] 4G and 4H, exemplary system 1000A can provide an implementation of any of the configurations of systems 500A-500F as applied to an organ such as kidney 2029. The perfusion system of system 1000A can include, but is not limited to, perfusion pump 2001, which can enable circulation of perfusion fluid to mimic, to the extent possible, in vivo flow from a perfusion fluid source through kidney 2029. In some configurations, pulsatile pumping of perfusion fluid is possible at a rate that can mimic physiological rhythms. The timing of pump strokes can be adjusted to achieve such pulsatile flow. In some configurations, PWM of a valve providing air pressure to the pumping pod of perfusion pump 1001 can create a pressure profile in the air pressure that can create a desired fluid pressure on the fluid side of perfusion pump 1001. The perfusate pumped from the fluid reservoir 1027 can be subjected to temperature and oxygen saturation testing, for example, but not limited to, by a temperature sensor 1014 and an oxygen saturation sensor 1016, respectively, as discussed herein. Gas management in the system 1000A can include an oxygenator 1035. The terminology does not limit gas regulation in the systems of the present teachings to oxygen alone. Possible oxygenation devices can include, but are not limited to, an extracorporeal membrane oxygenation (ECMO) device and a microporous hollow fiber oxygenator. In some configurations, oxygen and other gases can be supplied to the oxygenator 1035, for example, by a supply canister, an oxygen concentrator, or any other oxygen separation or concentration method. Exemplary gases that can be delivered to the oxygenator 1035 include, but are not limited to, one or more of oxygen 1019, nitrogen 1021, and carbon dioxide 1023. Other types of gases are also contemplated and can be accommodated by the systems of the present teachings. Before the perfusate is pumped from the perfusion pump 2001 to the oxygenator 1035, the perfusate can be tested for various properties. For example, a glucose sensor 1036 can monitor the glucose level of the perfusate and trigger adjustments to the perfusate during the circulation cycle.

[0082] 4G and 4H , following oxygenation, the perfusion fluid can undergo thermal regulation by a thermal management system. In some configurations, the thermal management system of system 1000A can include, for example, but not limited to, a heat exchanger 1013, a heat transfer plate 1015, and a heat generator 1017. In some configurations, the heat exchanger 1013 can rest on the heat transfer plate 1015, which can rest on the heat generator 1017. The heat generator 1017 can provide an amount of thermal energy to the heat exchanger 1013 through the heat transfer plate 1015. The amount of thermal energy can be determined by a control system, which can rely on sensor data to adjust the thermal energy available to the perfusion fluid, for example. Alternatively, for example, thermal regulation can occur on a preset timetable, or manual adjustments can be made. The heat exchange means 1013 can include, but is not limited to, a system in which fluid within the heat exchange means 1013 can be diffused across the extent of the heat transfer plate 1015 without physically contacting the heat transfer plate 1015. The heat exchange means 1013 can include a membrane that can geometrically couple the heat transfer plate 1015 to the heat exchange means 1013, thereby providing thermal insulation and efficient energy transfer. In some configurations, the membrane can be 0.01 inches thick and constructed from a material that expands when pressure is applied. In some configurations, the membrane can be laser welded to create a flow path. The heat exchange means 1013 can include a fluid pathway of any shape covered by the membrane, and the fluid pathway can have at least one fluid channel. The length of the fluid pathway can dictate the size of the heat transfer plate 1015. The width and depth of the channels that make up the fluid pathway can be based on the desired surface interface area (through the membrane) between the perfusion fluid and the heat transfer plate 1015 and the desired uniformity of heat transfer. The membrane can comprise a conformal material such as, but not limited to, a polymer, e.g., rubber, plastic, fiber, adhesive, and coating, any material that has conformal and insulating properties. In some configurations, the membrane can function as a pressure sensor. On one side of the membrane is flowing perfusion fluid, and on the other side is a thermally conductive heat transfer plate 1015.Separating the perfusion fluid from the heat transfer plate 1015 and the heat generator 1017 can allow the number of disposable components in the thermal management means to be limited to the heat exchange means 1013. In some configurations, the heat transfer plate 1015 can be constructed from a thermally conductive material, such as, but not limited to, aluminum. Thus, thermal energy from the heat generator 1017 can be transferred to the heat transfer plate 1015, which can transfer the thermal energy through the conformal membrane to the perfusion fluid flowing in the fluid channels. In some configurations, the heat generator 1017 can include cavities for thermal cartridges, such as, but not limited to, the OMEGA™ Cartridge Heater CSS-03130 / 120V. The size of the cartridges, the number of cartridges, and other characteristics of the cartridges can be determined based on the need for uniform heating in the perfusion fluid flowing across the heat generator 1017, and therefore across the heat transfer plate 1015, and ultimately through the heat exchange means 1013. Other heat exchanger systems are also contemplated by the system of the present teachings. For example, a thermoelectric device such as, but not limited to, a LAIRD™ Thermal Systems Hot Plate (Model Number SH10 125 05 L1) can provide both heating and cooling to the perfusate. Temperature can be measured by temperature sensor 1012 (FIG. 4H) before the perfusate enters the heat exchanger and by temperature sensor 1014 (FIG. 4H) after the perfusate exits the heat exchanger.

[0083] Continuing with reference to FIGS. 4G and 4H, gas can be removed from the perfusate by any available method. In some configurations, an air trap 1009 provides space for gas bubbles to float to the top of the enclosure, allowing the liquid perfusate to flow into the kidney 2029. Other gas capture and removal systems are also envisioned. Under normal circumstances (i.e., no triggers are turned off by sensor data), perfusate can enter the arterial cannula 1033 and then the kidney 2029. As a result of the kidney 2029's filtering task, fluid exits the ureter through the ureteral cannula 1031. The perfusate exiting the kidney 2029 will eventually be directed to the fluid reservoir 1027. In some configurations, the exiting perfusate, i.e., output, can be measured. The flow sensor 1007 can accumulate the output from the ureter 1031 over a period of time using a pinch valve 1039. After an accumulation time has elapsed, the amount of output is known and a pinch valve 1039 can release the output into the fluid reservoir 1027. In some configurations, the output can be extracted through a syringe port. The output can be tested in the field or at another location.

[0084] 5A and 5B, an exemplary system 20000 of the present teachings can implement, for example, any of systems 500A-500F and systems 1000A and 1000B. Exemplary system 20000 can include, but is not limited to, electronics assembly 20010, durable enclosure assembly 20006, disposable interface enclosure assembly 20007, and disposable assembly 20008. Other configurations of the components of the system are also contemplated and described herein. Electronics assembly 20010 can include, for example, but is not limited to, components that can power and enable sensor data processing and control of any one or all of the system components, such as, but not limited to, sensors, thermal management 513 (FIG. 4F), gas management 1025 (FIG. 4F), insufflation system 507 (FIG. 4F), and pneumatics 505 (FIG. 4F). The durable enclosure assembly 20006 can include, for example, but is not limited to, a pneumatic valve system, an air reservoir, and perfusion, and possibly an infusion pump durable interface. The disposable interface enclosure assembly 20007 can include, but is not limited to, a mounting platform for the disposable assembly 20008, including the tissue enclosure, thermal management system, oxygenator, perfusion pump, sensors, and tubing connecting all disposable components and enabling fluid circulation. Gas from the gas management system 1025 (FIG. 4F) can be supplied to the tissue enclosure 30019 (FIG. 8A) or another location through gas outlet 40085.

[0085] 6A-6B, 8C, and 8D, durable enclosure assembly 20006 can include assemblies such as, but not limited to, pneumatic pumping assembly 20004, pumping bracket assembly 20003, and pumping manifold assembly 20002. Durable enclosure assembly 20006 can include an enclosure that provides protection for the assemblies. The enclosure can include, for example, pumping bracket mount side plate 30017 (FIG. 6A), pumping bracket mount top plate 30018 (FIG. 8D), pumping bracket mount plate 30015 (FIG. 5B), and durable side injection plate 30034 (FIG. 8D). Enclosure internal and external mounting and connector features may be required for specific configurations. Commercially available electrical component tie-down straps 40073 (FIG. 8D) for tying down equipment such as an oxygenator to the enclosure are examples of external mounting features of configurations of the present teachings. The oxygenator may further rest on oxygenator mount 30047 (FIG. 8C). Pinch valve 40014 (FIG. 6B), used to redirect flow for filling and draining within durable enclosure assembly 20006, may be held in place by bracket 40074 (FIG. 6A) and may be attached to durable enclosure assembly 20006 by angle bracket 40075 (FIG. 6A). The system of the present teachings may further include pinch valve 40037 (FIG. 6B), used to redirect flow for filling and draining within durable enclosure assembly 20006. Pinch valve 40037 (FIG. 6B) may be held in place by bracket 40076 (FIG. 6B), which may be attached to durable enclosure assembly 20006 by angle bracket 40077 (FIG. 6B). Gas pump 40002 (FIG. 6B), mounted by gas pump mount 40004 (FIG. 6B), can pump gas filtered by pump filter 40033 (FIG. 6B) into oxygenator 40047 (FIG. 8C). Level sensor 40035 (FIG. 6B) can verify the fluid level within tissue enclosure 30019 (FIG. 8B).

[0086] 6D-6H, pneumatic pumping assembly 20004, which is held in place at least partially within enclosure 20006 by pump bracket mount bottom plate 30013 (FIG. 6A) and pump bracket mount support plate 30016 (FIG. 6H), can be attached to pump bracket mount top plate 30018 (FIG. 8D) by standoffs. Assembly 20004 can include, for example, but not limited to, air reservoir tank 30099 (FIG. 6D) that can hold available air for the positive pressure required for the pneumatic process, and vacuum pump 40032 (FIG. 6D) for providing vacuum air pressure. The air reservoir tank can be coupled to pumping manifold assembly 20002 (FIG. 6K) to provide the air necessary to enable pneumatic operation. Pump mounting plate 30046 (FIG. 6F) can provide a mounting surface for main controller board and power switching board 40017 (FIG. 6G) on one side and air pump 40034 (FIG. 6G) on the other side, which is held in place on pump mounting plate 30046 by air pump mount 40003. Air pump 40034 (FIG. 6G) can be operably coupled to pump filter 40033 (FIG. 6B) to provide filtration of the incoming air. Enabling coupling of the components in assembly 20004 are connector 40070 (FIG. 6H), connector 40068 (FIG. 6H), and connector 40069 (FIG. 6H).

[0087] 6I, the pumping bracket assembly 20003 can include, for example, without limitation, a pumping bracket 30004 and a pumping bracket latch 30005, which can surround a mounting plate 30033 (FIG. 6H). The pumping bracket 30004 can be configured to geometrically conform to a disposable pumping cassette, which can be retained within the pumping bracket 30004 and released after use by a pumping bracket ejector 30006, which can have, for example, a dowel pin 40064 as its axis of movement. Pumping can be enabled by positive and negative pressure delivered by a pneumatic system of the present teachings. A pumping manifold pneumatic tubing interface 30007 can receive a hose barb 40065 and a hose barb non-valved insert 40067, which can enable tubing between the pneumatic system and the controls of the disposable cassette. Negative and positive pressure can be delivered through tubing that pumps or removes air through tubing that traverses the hose barb 40065 and the non-valved insert 40067 .

[0088] Referring now to Figures 6J and 6K, the pumping manifold assembly 20002 can include two of the manifolds 40000 (Figure 6K) for applying regulated pressure to the chambers of the pumping cassette 20005 and two of the manifolds 40000 (Figure 6K) for supplying a set (higher) pressure to the valves of the pumping cassette 20005. The chambers are filled with either gas or fluid, and the valves direct the flow. The fifth manifold is a regulator. Each of the manifolds 40000 (Figure 6K) is connected to a control circuit board 50002 (Figure 6J). The five manifolds are sandwiched between pumping manifold end plates 30003 (Figure 6J). A gas reservoir 30099 (Figure 6D) can be mounted to the accumulation tank manifold block 30009 (Figure 6J) at a fitting location 40062 (Figure 6J). Accumulator tank manifold block 30009 (FIG. 6J) mates with regulator manifold block 30008 (FIG. 6J) and can therefore control the positive air pressure to the pumping cassette through fitting 40061. Accumulator tank manifold block 30009 can include a muffler 40063 that can vent pressurized air to the atmosphere.

[0089] 7A-7C, the disposable interface enclosure assembly 20007 can include, but is not limited to, a disposable interface back plate top 30023 (FIG. 7A) that can be part of a partial enclosure that can be joined by a hinge 40071 (FIG. 7A) and surrounded on three sides by a disposable interface skirt plate 30020 (FIG. 7A). The enclosure can be raised to expose the electronics assembly 20010 (FIG. 9A). The disposable interface front plate top 30021 (FIG. 7A) can provide a mounting location for an air bubble sensor mount 30053 (FIG. 7C), which can hold an air bubble sensor (not shown). An oximeter sensor mount 30054 (FIG. 7A) can also be mounted on the disposable interface front plate top 30021 (FIG. 7A), and an oximeter sensor cover 30055 (FIG. 7A) can be coupled to the oximeter sensor mount 30054 (FIG. 7A) to retain the tubing and sensor. A sensor such as an oximeter 40011 (FIG. 7C) can be mounted to the oximeter sensor mount 30054 (FIG. 7A) through the use of, for example, an oximeter mounting clamp 40072 (FIG. 7C). The disposable interface front plate top 30021 (FIG. 7A) can be mounted on the disposable interface front plate bottom 30022 (FIG. 7A) and can be elevated from the disposable interface front plate bottom 30022 (FIG. 7A) by the disposable interface skirt plate 30020 (FIG. 7A). The disposable interface front plate top 30021 (FIG. 7A) can be elevated to allow room for a thermal management component, for example, a heating plate 30031 (FIG. 7B). A tissue enclosure matching base 30037 (FIG. 7C) can be mounted on top of the thermal management component. A substrate mount 30028 (FIG. 7B) can be mounted between the disposable interface front plate top 30021 (FIG. 7A) and the disposable interface front plate bottom 30022 (FIG. 7A), surrounding the substrate 40006 (FIG. 7B).The level sensor housing 40049 (FIG. 7C) can rest against the tissue enclosure matching base 30037 (FIG. 7C) and can provide mounting for a liquid level switch 40031 (FIG. 7A) that can sense the level of fluid within a tissue enclosure that can be mounted within the tissue enclosure matching base 30037 (FIG. 7C). The fixation shaft 30044 (FIG. 7C) can allow for fastening of the tissue enclosure matching base 30037 (FIG. 7C) to a heat exchanger on the tissue enclosure.

[0090] 8A-8F, the disposable assembly 20008 can include a tissue enclosure 30019 (FIG. 8A), which can hold an organ, such as, but not limited to, a kidney, that is in the process of being repaired or maintained. Perfusion fluid, a circulating fluid, can enter and exit the tissue enclosure 30019. For example, if the tissue is a kidney, the perfusion fluid can enter the tissue enclosure through one of several entry tube / connector combinations and be tubed directly to the arterial orifice of the kidney. As the perfusion fluid exits the kidney, it can be routed to a sensor that can detect, for example, the amount of fluid that has exited the kidney and possibly other characteristics of the waste product. Alternatively, the output can be discarded and / or tested. Thermal energy may need to be added to the system to maintain the tissue at sub-normothermic or normothermic levels. Perfusion pump 20005 (FIG. 8C) can pump perfusion fluid through tubing 40090 (FIG. 8C) and volume control valve 40084 (FIG. 8C) to oxygenator 40047 (FIG. 8C). Infusion pump 20005-1 (FIG. 8C) can infuse substances into tissue inclusions 30019. Substances such as glucose can be added to adjust the perfusion fluid if it is found to be lacking. Gas management can be performed by a gas management system, shown herein as oxygenator 40047 (FIG. 8C), when a controller provides a selected gas to the gas management system, for example, through a volume control valve. The oxygenated perfusion fluid can continue its circulation path through thermal management 30032. Thermal changes induced by thermal management 30032 (FIG. 8F) can be carried out by heat exchanger membrane 30050 (FIG. 8F) to maintain a desired temperature within tissue enclosure 30019 (FIG. 8F). Thermally managed, oxygenated perfusate can be circulated past pressure sensor 40008 (FIG. 8C), through connector 40083 (FIG. 8A) and an air bubble sensor, and into tissue enclosure 30019 (FIG. 8F) to an arterial opening within the tissue.Waste water from the tissue can exit the tissue enclosure 30019 (FIG. 8F), enter the flow chamber 30051 (FIG. 8C) for measurement, and flow back into a fluid reservoir within the tissue enclosure 30019 (FIG. 8F). Perfusate is pumped from the fluid chamber, past, for example, but not limited to, a glucose and / or oxygen saturation and / or temperature sensor 40007, and back to the perfusate pump 20005 (FIG. 8E) to continue circulating. In some configurations, additives such as glucose can be pumped into the fluid reservoir by a separate pumping system. Sensors, for example, but not limited to, a thermistor, pH sensor, and DO sensor, can be positioned within the fluid reservoir to monitor the properties of the perfusate and the health of the tissue. Additionally, sensors can be positioned within and outside the thermal management 30032 (FIG. 8F) to ensure that the temperature of the thermal management 30032 does not exceed a preselected, user-entered, or dynamically determined threshold.

[0091] 8G-8I, thermal management of the present teachings can include circulating perfusion fluid through a heat exchanger before pumping the perfusion fluid into the tissue. The perfusion fluid can be circulated across the area of ​​the heat exchanger 30032 in, for example, but not limited to, a serpentine path 1201 (FIG. 8I). Other types of paths, for example, but not limited to, twisting, undulating, or curving, are also possible. The desired path should achieve uniform temperature management of the perfusion fluid entering the tissue, as well as within the fluid reservoir 1211 (FIG. 8H) and the tissue enclosure 30019 (FIG. 8G). The perfusion fluid can enter at opening 1205 (FIG. 8I), for example, through conduit 1203 (FIG. 8I). Perfusion fluid can travel the length of pathway 1201 (FIG. 8I) and exit heat exchanger 30032 at opening 1207 (FIG. 8I) through connector 40098 (FIG. 8H). Perfusion fluid can travel through tubing 40090 and enter tissue enclosure 30019 through connector 40082 (FIG. 8H). A tissue connection tube (not shown) can enable tissue perfusion. Waste fluid can exit tissue enclosure 30019, for example, through connector 40086 (FIG. 8G) or connector 1213 (FIG. 8G). Configurations with multiple exit pathways are envisioned as described herein, but are not limited to the configurations described herein. Pathway 1201 can be covered by a membrane to retain perfusion fluid while allowing heat transfer to and from a source of thermal energy. Perfusion fluid exiting through connector 40086 (FIG. 8G) can travel back to the perfusion pump to continue the circulation loop as described herein.

[0092] 9A-9C, electronics assembly 20010 can include, but is not limited to, an electronics base plate 30035 (FIG. 9A) on which multiple USB hubs 40019 (FIG. 9A) are mounted. The USB hubs 40019 (FIG. 9A) can be stabilized relative to USB hub mounts 30039 (FIG. 9B). Standoffs 40059 (FIG. 9A) can elevate electronics top plate 30036 (FIG. 9A) to create room for a main board 40015 (FIG. 9A) mounted to electronics top plate 30036 (FIG. 9A). Also mounted on electronics base plate 30035 (FIG. 9A) are, among other components, multiple power relays 40025 (FIG. 9C) and a power switching board 40017 (FIG. 9C). The power plug mount 30041 (FIG. 9C) can include, but is not limited to, a power entry module 40039 (FIG. 9C), a USB entry module 40038 (FIG. 9C), and a power port 40040 (FIG. 9C) mounted therein, and can include feet that can be used for connection to the housing of the durable enclosure assembly 20006 (FIG. 6A). An electronics rear panel board 30042 (FIG. 9B) is mounted to a corner of the electronics base board 30035 (FIG. 9A) for connection to the housing of the durable enclosure assembly 20006 (FIG. 6A). An electrochemical impedance spectroscopy potentiostat 40024 (FIG. 9B) is mounted on the backside of the electronics top board 30036 (FIG. 9A) from the main board 40015 (FIG. 9A). Also mounted on the electronics base plate 30035 (FIG. 9A) is a module mount 30038 (FIG. 9B), which may include multiple slots for mounting electro-optical module DO sensors. A solid-state AC relay can be mounted on a standoff mounted to the electronics base plate 30035 (FIG. 9A). Other configurations of the components described herein and other components, for example, other types of sensors, can be accommodated by the architecture of the present teachings. The description herein is intended to illustrate one possible way to lay out the possible components of the present system.

[0093] 10A-10C, in another configuration, the system of the present teachings can include three major assemblies: electronics assembly 20013, durable enclosure assembly 20015, and a disposable assembly (not shown). Differences between configuration 20000 (FIG. 5A) and configuration 20012 (FIG. 10A) include, but are not limited to, the electronics and disposable interface enclosure assemblies being combined in configuration 20012 (FIG. 10A), the removal of infusion pump 20005-1 (FIG. 8C), the number of manifolds being different between the two configurations, and the infusion pump mounting area 30056 (FIG. 10B) and flow sensor 40051 (FIG. 10B) being mounted near tissue enclosure mounting area 30032 in configuration 20012 (FIG. 10A). The combination of these changes can reduce the footprint and cost to operate the system. Exemplary systems 20000 (FIG. 5A) and 20012 (FIG. 10A) can be configured to match physiological levels of parameters such as, but not limited to, perfusate pressure, perfusate flow rate, oxygenation, temperature, pH, waste generation, glucose consumption, lactate production, hemolysis, blood sodium concentration, waste sodium concentration, waste creatinine concentration, and blood conductivity.

[0094] Continuing with reference to FIGS. 10A-10C, the durable enclosure assembly can include, but is not limited to, a durable enclosure top plate 30069 (FIG. 10A), a durable enclosure left side plate 30080 (FIG. 10A), a durable enclosure back plate 30070 (FIG. 10A), and a durable enclosure front plate 30079 (FIG. 10C). The durable enclosure can also include, for example, a front skirt plate 30087 (FIG. 10B), a sensor mounting feature 30090 (FIG. 10B), and a flow controller 40052 (FIG. 10B). Connectors can include USB and power. The USB can be attached to a plug mount 30065 (FIG. 10B), and power can be enabled by a power distribution block 40036 (FIG. 10B). An electronics top plate 30081 (FIG. 10B) and an electronics base plate 30082 (FIG. 10B) can sandwich the electronics to allow for mounting. The disposable and durable components can be separated from each other in a variety of ways, including, but not limited to, a disposable interface front plate 30083 (FIG. 10B). The disposable tissue enclosure 30019 (FIG. 8A) can interface with the durable component through a tissue enclosure matching base 30086 (FIG. 10B).

[0095] 11 , an exemplary circulation path for configuration 20012 (FIG. 10A) is shown. Perfusion fluid leaving the fluid reservoir within the tissue enclosure 30019 through connector 40086 can proceed through tubing 1231 to pump 31107. All tubing described herein can include preselected outer and inner diameters. For example, the outer diameter can be 3 / 8 inch and the inner diameter can be 1 / 4 inch, or the inner diameter for output transport can be 1 / 8 inch and the outer diameter can be 1 / 4 inch. It should be understood that the length and diameter of the tubing are exemplary only and will depend on the desired characteristics of the system. The characteristics of one type of pump 31107 are described herein. Pumps with characteristics such as maintaining low hemolysis and other features described herein can be used. Pump 31107 can pump perfusate through tubing 1221 to pressure sensor 40008, which is accessed by connector 73316-1 and includes sample port 80213-1. Tubing 1223 can transport the perfusate to gas management system 40047. Gas management system 40047 can adjust the level of gas in the perfusate, e.g., oxygen saturation, as needed. Perfusate can exit from gas management 40047 through tubing 1227 or through tubing 1233, through connector 40081, through connector 40098-1 onto tubing 1225 to thermal management system 30032. Thermal management system 30032 can be mounted below tissue enclosure 30019, without being limited to being so. After the perfusate traverses fluid pathway 30032-1 within thermal management system 30032, which may be, but is not limited to, a heat exchange system, the perfusate can exit through connector 40098-2, through tubing 1239, and to disposable pressure sensor 40008. Connectors 40103 and 73316-2 can be used to couple pressure sensor 40008 and sample port 80213-2 with the perfusate. The perfusate can then traverse tubing 1241 to gas trap 30088. Gas trap 30088 can remove any gases in the oxygenated perfusate before the perfusate is introduced into the tissue within tissue enclosure 30019.After gas is removed from the perfusate, the perfusate can traverse connector 73316-3 and sample port 80213-3, which can be used to sample the perfusate before it enters tissue enclosure 30019 and the organ. The perfusate can proceed toward tissue enclosure 30019, through tubing 1243, through connector 40097 and fitting 40091, to tubing that enters a cannulated artery in the tissue. Waste can exit the tissue through the waste cannula, through tubing and fitting 40092, and connector 40097 mated to tubing 1235. Tubing 1235 can enter output cap 30051 through connector 40095-1 and then onto output body 30052 for measurement. Connector 88213 and sample port 80213-4 can allow sampling of the output, which may be waste from the organ. The output can be directed through tubing 1237, through connectors 40093-40096 and 40078, and back into a fluid reservoir within the tissue enclosure 30019. The output cap 30051 can be vented through connector 40095-2, and the vented material can travel back into the tissue enclosure 30019 through tubing 1229. The circulation loop is completed. In some configurations, a heat exchanger is in direct contact with the tissue enclosure to ensure energy efficiency and capture of possible waste heat, an important feature for those systems that operate on battery power.

[0096] Referring now to FIG. 12, valves can be associated with the pumping cassette to control the filling and delivery of the pump chambers and, therefore, the flow of perfusate. In the configuration shown in FIG. 12, two valve banks and regulators can separately manage filling and delivery. Positive and negative lines can apply positive pressure or create a vacuum, forcing the cassette membrane to move and the cassette contents to be pumped. A controller can open and close the valves according to the valves to allow the desired flow rate and pressure.

[0097] Various alternatives and modifications can be devised by those skilled in the art without departing from the present disclosure. Accordingly, the present disclosure is intended to embrace all such alternatives, modifications, and variations. Additionally, while several exemplary configurations of the present disclosure have been shown in the drawings and / or discussed herein, the disclosure is not intended to be limited thereto, as the disclosure is as broad as the art will permit, and the specification is intended to be read in a similar manner. Therefore, the above description should not be construed as limiting, but merely as an illustration of a particular configuration. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto. Other elements, steps, methods, and techniques that differ insubstantially from those described above and / or in the appended claims are also intended to be within the scope of the present disclosure.

[0098] The drawings are presented only to demonstrate certain embodiments of the present disclosure. Also, the drawings described are illustrative only and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn to particular scale for illustrative purposes. Additionally, elements shown in drawings with the same number may be the same or similar elements, depending on the context.

[0099] When the term "comprising" is used in the present description and claims, it does not exclude other elements or steps. Where an indefinite or definite article, such as "a," "an," or "the," is used when referring to a singular noun, this includes the plural of that noun unless something else is specifically stated. Thus, the term "comprising" should not be interpreted as being limited to the items listed thereafter; it does not exclude other elements or steps, and therefore the scope of the expression "a device comprising items A and B" should not be limited to a device consisting of only components A and B.

[0100] Additionally, the terms "first," "second," "third," and the like, whether used in the description or claims, are provided to distinguish between similar elements and not necessarily to describe a sequential or chronological order. It is to be understood that terms so used are synonymous under appropriate circumstances (unless expressly disclosed otherwise), and that the exemplary configurations of the disclosure described herein are capable of operation in other sequences and / or arrangements than those described or illustrated herein.

Claims

[Claim 1] The invention described herein.

Images