Systems and methods for tissue maintenance, assessment, maturation and repair - Patents.com

Abstract

A system and method for tissue perfusion to assess, maintain, mature, or repair tissue. The system of the present teachings includes a tissue enclosure having a fluid reservoir. A pump, valves, and controller move perfusion fluid through the tissue. The system includes features to assist in monitoring the health of the tissue, and a removable tray to facilitate movement of the tissue from an origin to the tissue enclosure. The system moves perfusion fluid to and through the tissue to provide nutrients to the tissue. The system includes an output flow rate / volume sensor, at least one infusion pump, disposable and durable components, and a suite of sensors.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a non-provisional patent application claiming priority to earlier filed U.S. Provisional Patent Application No. 63 / 269,205, filed March 17, 2022, the contents of which are incorporated herein by reference.

[0002] The present disclosure relates to the maintenance, assessment, maturation and repair of tissue for transplant recipients. [Background technology]

[0003] In 2020, approximately 39,000 transplants of all types of tissues were performed in the United States. Someone is added to the transplant waiting list every 9 minutes. There are numerous types of different tissues available from organ donors. Tissues, including organs, that are considered for transplantation include, but are not limited to, kidney, pancreas, liver, heart, lung, stomach, intestine, composite allografts, thymus, uterus, skin, bone, tendon, middle ear, cartilage, heart valve, trachea, nerve, vein, hand, foot, arm, adrenal tissue, fetal thymus, cornea, and composite graft tissue. In terms of specific organs, in 2020 in the United States, there were 12,141 people on the liver transplant waiting list, but only 8,906 transplants were performed. There were 14,489 people waiting for pancreas, heart, lung, and intestine transplants. In addition, there were 91,834 people on the transplant list waiting for a kidney transplant, but only around 20,000 kidney transplants were performed.

[0004] Regarding kidneys, in 2020, over 700,000 patients per year in the United States and an estimated 2 million patients worldwide suffered from end-stage renal disease (ESRD). Furthermore, the incidence of COVID-19 among ESRD patients increased during the first months of the pandemic, resulting in an estimated 6,953 to 10,316 cases. The primary treatments for ESRD are dialysis and kidney transplantation. In the United States, the overwhelming proportion of ESRD patients undergoes dialysis, with only a small proportion surviving transplants. In general, dialysis patients have a shorter life expectancy and a lower quality of life than patients who have undergone kidney transplantation. The majority of transplanted kidneys are from deceased donors, and many of these available kidneys are discarded. Deceased donor kidneys present several challenges, including a higher rate of delayed graft function (DGF) after transplantation, a relatively longer ischemic time during kidney recovery, a higher degree of cold-induced injury, and a lower long-term graft survival rate.

[0005] When harvesting tissue for transplantation, the supporting tissue, which provides the necessary life support for the tissue and provides the necessary connective tissue during transplantation, is cut in a manner that leaves as much of the supporting tissue intact as possible. During storage and transplantation, support means are often connected, detached, and reconnected to the supporting tissue to facilitate the supply of life-sustaining nutrients to the tissue to be transplanted. During such connection, detachment, and reconnection, incremental portions of the supporting tissue are often cut or altered, thereby reducing the supporting tissue available for subsequent attachment during transplantation.

[0006] Although logistically effective, cold storage of tissue for transport can be injurious to the tissue, and assessing tissue integrity can be a challenge, especially when the tissue is cold and not metabolically active. Cold storage cycles (warm-cold-warm) can result in a chain reaction of oxygen deprivation, which can result in ischemic injury. Early effects of such injury can include delayed graft function, which may have long-term effects on renal function.

[0007] Current tissue screening methods may be imperfect and may not provide a direct measure of tissue health. If tissue is deemed to be potentially marginal, tissue screening systems are biased toward discard. As a result, a large proportion of donated tissue is discarded annually (21% or 5,051 kidneys in the United States in 2020 alone). Studies have found that a significant proportion of these discards could have resulted in favorable patient outcomes if transplanted. To reduce discard rates, thorough quantitative ex vivo assessment of tissue is crucial. Ex vivo tissue assessment can eliminate the dependency on donor scoring and provide a real-time measure of tissue health, which can ease the mindset of risk-averse physicians. Other future options may include immunomodulatory drugs that can alleviate donor matching issues, gene therapy to treat tissue in vivo, tissue engineering, and tissue transplantation.

[0008] Further options include normothermic / subnormothermic perfusion, which has a high probability of extending preservation time, allows real-time tissue diagnosis, and significantly reduces cold-induced injury. Extended preservation time increases the likelihood of finding a recipient for the tissue. Preservation techniques such as ex vivo normothermic machine perfusion (NMP) can be used to assess tissue quality prior to transplantation before committing the recipient to surgery. Normothermic or subnormothermic perfusion results in metabolically active tissue, which can allow assessment of renal function via direct measures and through validation of laboratory analysis of tissue, perfusate, and urine samples. Summary of the Invention [Problem to be solved by the invention]

[0009] What is needed is a system that provides a releasable interface with tissue that allows the tissue to flow with nutrients necessary to maintain its vitality prior to transplantation while preserving supporting tissue so that it can interface with the recipient's tissue during transplantation. What is needed is a system that allows medical personnel to observe, sample, or otherwise collect data about metabolically active tissue to aid in assessing the health and viability of the tissue. Such a system would be capable of sensing a full range of properties, including, but not limited to, glucose and pH. A normal tissue maintenance and assessment system would provide medical personnel with a quantitative assessment of tissue health and allow for reconditioning of the tissue to optimize its performance prior to transplantation, and could allow for ex vivo treatment of the tissue, such as, but not limited to, drug therapy and gene therapy. What is further needed is a system that achieves low hemolysis and maintains the desired properties of the tissue. What is needed is a normothermic / subnormothermic tissue perfusion device with on-board sensors to simulate the body's blood circulation and monitor the tissue, respectively. [Means for solving the problem]

[0010] According to some configurations, the present teachings can include systems and methods for tissue perfusion to maintain or repair tissue. Among other features, the systems of the present teachings include a tissue enclosure having a fluid reservoir. Pumps, valves, and controllers can move perfusion fluid through the tissue. The systems can include features to assist in monitoring tissue health, and removable trays to facilitate movement of the tissue from an origin to the tissue enclosure. The systems of the present teachings are generally configured to perfuse and provide nutrients for transplant tissue, such as, but not limited to, human tissue. Other features of the systems of the present teachings include, but are not limited to, urine flow rate sensors, nutrient pumps, disposable and durable components, and non-invasive sensors.

[0011] The system of the present teachings can include at least one controller or processor that enables the valves and pumps to perfuse fluid through tissue, such as, for example, but not limited to, human tissue. The at least one controller / processor can be, for example, but not limited to, a general-purpose processor that manages multiple tasks, a custom processor configured to manage a specific task, a proportional and integral controller, a differential controller, a programmable logic controller, a distributed control system, a programmable automation controller, a microcontroller, a microprocessor, an embedded processor, or supervisory control and data acquisition software. The controller / processor can receive data from sensors located throughout the system and other forms of data input, among other things, and can adjust the pumps and valves according to the data. For example, the controller / processor can receive usable user input, recipe input, and / or default settings along with values ​​of sensor data to adjust flow parameters of the perfusion fluid. In some configurations, the controller / processor can access a default perfusion method for a particular type of tissue. The default method can be provided with a standard set of instructions known to normally elicit a desired result for the tissue. The default method can be dynamically changed when sensor data indicates that the standard instructions cannot achieve the desired result. User input can also result in changes to the default method.

[0012] In addition to controlling perfusion fluid flow, the controller / processor can issue commands to pumps and valves to regulate the delivery of infusion fluid / nutrients to the tissue. In some configurations, infusion fluid / nutrients can be pumped into the perfusion fluid in a fluid reservoir in fluid communication with the tissue. When a sensor indicates the need for perfusion fluid modification, the contents of possible infusion fluid / nutrients options can be pumped into the fluid reservoir. The system of the present teachings can include a pumping cassette that can deliver infusion fluid / nutrients at possible variable rates specific to a particular tissue and specific to the tissue's current condition under direction from the controller / processor. The controller can perform processing associated with a particular set of sensors. In some configurations, the controller can automatically determine which sensors are available in a particular system and execute processes associated with the identified sensors.

[0013] The system of the present teachings can include a pump subsystem that can enable perfusion of the tissue and recirculation of the perfusate. The pump subsystem can pump perfusate, e.g., blood and other additives, through the tissue. The blood can include, e.g., whole blood or diluted / modified / altered blood compositions. In some configurations, the pump subsystem can enable a flow rate of perfusate at a rate of up to 600 ml / min at a mean arterial pressure of 20-120 mmHg. The flow can optionally be pulsatile, with the pulsatile flow rate and rate being adjustable. As an example, for cold or damaged tissue, lower arterial pressures and flow rates may be required. As tissue function improves, the arterial pressure and flow rate can be adjusted to accommodate the changed conditions. Both pulsatile flow or flow rates controlled by physiological parameters can be accommodated by the pump of the present teachings. In some configurations, a direct-acting pneumatic pump can be used in series to provide a continuous flow of perfusate. Direct-acting pneumatic pumps contain active inlet and outlet valves, thus allowing a high level of control over the flow rate within the perfusate flow circuit. For example, the kidney can tolerate flow rates of 200-600 mL / min. One goal of pump selection is to reduce hemolysis. Direct-acting pneumatic pumps can allow for minimal hemolysis and flow metering for wet materials as discussed herein. The pumping cycle of the direct-acting pneumatic pump can be modified to match the physiological pulsatile duty cycle.

[0014] In some configurations, when suction is used to fill the pumping system of the pumping cassette, a variable pressure scheme for negative (gauge) air pressure is used. The overall goal is to minimize the amount of suction pressure required, since it is well known that minimizing suction minimizes shearing of blood cells in the perfusate and avoids hemolysis. To this end, the minimum necessary fill pressure is identified to ensure that the end of the fill stroke for one chamber aligns (plus a small buffer time) with the end of the delivery stroke of the other chamber. The process includes, but is not limited to, the following steps: (1) While filling the chamber, monitor the pressure in the chamber itself and in the regulated negative tank (negative pressure source). Record the time when these pressures equalize (to within ±5 mmHg). This equalization occurs when the chamber membrane stops moving, thus marking the actual end of the fill stroke. (2) Record the time when the chamber was disconnected from the regulated negative tank. This is based on a time offset from the start of the fill stroke, which is the planned end of the stroke. (3) Calculate the time difference between these two times when preparing for the next stroke. (4) If the actual end of the fill stroke occurred before the calculated end of the fill stroke by a preselected amount of time, such as, but not limited to, more than 200 ms, the suction pressure was higher than necessary. In this case, the suction pressure is reduced, such as, but not limited to, by 1 mmHg to a minimum of -40 mmHg gauge pressure. (5) If the actual end of the fill stroke occurred too close to the planned end of the fill stroke, such as, but not limited to, less than 50 ms, or did not occur at all, the relative pressure difference was not high enough to completely fill the chamber. In this case, the suction pressure is increased, such as, but not limited to, by 1 mmHg to a maximum of -140 mmHg. (6) If the fill and delivery timing is shortened when preparing for the next stroke (i.e., the time from the start of the fill stroke to the planned end of the fill stroke is shortened), the suction pressure is pre-increased to ensure that the next fill stroke is completed on time.For example, if the fill time is shortened by more than 50 ms, the fill pressure is increased by 5 mmHg (up to a maximum of -140 mmHg). (7) To ensure that the two pumping systems remain in cycle, a check within this process step is performed on one of the two chambers to prevent timing mismatch or pressure oscillations. In one embodiment, a visual sensor is used to detect the location of the stroke. Since blood has an IR or visual response, the visual sensor detects the thickness of blood in front of the membrane to determine where the membrane is on the stroke.

[0015] In some configurations, the pump is direct acting, where compressed air (or vacuum) is used to push / pull the membrane against the fluid. A set of valves controls the movement of the membrane coupled with one or more pumping systems. In some configurations, there are two pumping systems. One fills and one delivers at the beginning of each stroke. A new stroke is not completed until the sequence is complete. Partial strokes are possible, for example, to reduce hemolysis. In some configurations, sensors, including but not limited to visual, infrared, or ultrasonic sensors, are used to identify the position of the membrane inside the chamber to control the delivery volume and ensure short strokes. The pump controls the nominal pressure in the pumping system by throttling the supply valve. In pump pressure control mode, the fill / delivery nominal pumping system pressure can be adjusted. The higher the relative pressure (or vacuum), the faster the fill or delivery time will result. The pump can provide a smooth and consistent flow or it may provide a pulsatile flow. In some configurations, the system can include multiple controllers, such as a valve controller, a pumping system controller, and a pump controller.

[0016] The role of the perfusion loop is to replicate basic biological functions that would otherwise occur in the body. These functions include oxygenation, carbon dioxide control, heat control, and nutrient delivery. Oxygenation and carbon dioxide control are accomplished through the use of a membrane oxygenator. A heat exchanger is used to maintain the desired perfusate temperature. The perfusion fluid leaves the tissue, is passed through an oxygenator, is passed through a heat exchanger, and then returns to the tissue. Nutrients are provided in the perfusion solution and can be added manually or through the use of an automated infusion pump. The power generated by the tissue flows out of the tissue and is available for sampling through a sterile sample port. The power can be directed back into the perfusion loop or discarded. The power flow rate and volume are measured and stored by the system. If recirculating the power proves to be a challenge, the system can be modified to collect the power or potentially pass it through a dialysis loop.

[0017] The perfusion loop essentially acts like a maintenance loop for the system, agitating the fluid reservoir to allow for filling or draining of the fluid reservoir and recirculation of fluid from the fluid reservoir. This loop can include an infusion pump so that the infusion fluid can be delivered, diluted, and mixed in the perfusion fluid instead of passing directly into the tissue. Some or all of the infusion pumps can be part of the perfusion loop. In some configurations, the system includes a bypass valve that can be opened during priming if an air bubble is detected. To introduce new perfusion fluid components or drain the system, the system includes at least one valve associated with the infusion path. In some configurations, one pinch valve can be associated with the incoming perfusion fluid while another pinch valve can be associated with the drain path. In one embodiment, a pneumatic valve can be used. Other types of valves are contemplated in the present teachings. The perfusion fluid pump can also drain the tissue enclosure.

[0018] The system includes means for monitoring, for example, the tissue, the perfusate, and the output of the tissue. Data collected during monitoring can be used to adjust, for example, the tissue environment and the perfusate characteristics. Any type and number of sensors can be used for monitoring, and the controller can be programmed to automatically or manually respond to detected conditions. In some configurations, concentrations of nutrients provided, dissolved oxygen and carbon dioxide in the perfusate, hemoglobin oxygen saturation levels, perfusion pumping rate, glucose and lactate concentrations in the perfusate, temperature, and / or pH are monitored through sensors strategically positioned within the perfusion loop. The system includes sensors both inside and outside the fluid path to enable proper perfusion and collect data for assessment of the tissue, as well as sterile sample ports for removing output and perfusate fluids with a sterile syringe. In one embodiment, the system includes pressure sensors on the tubing exiting the pump and exiting the heat exchanger. In one embodiment, the system includes a membrane between the heat exchanger channel and the thermal control plate includes a pressure sensor. In one embodiment, the system includes a flow sensor and / or a drip sensor to measure the output collected from the cannulated tissue. The system can optionally include a first of the at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate before it enters the tissue and a second of the at least one oxygen saturation sensor that monitors the oxygen saturation of the perfusate leaving the perfusate reservoir. The system can optionally include a first of the at least one dissolved oxygen sensor that monitors dissolved oxygen in the perfusate leaving the perfusate reservoir and a second of the at least one dissolved oxygen sensor that monitors dissolved oxygen in the perfusate before it enters the tissue.

[0019] The system may optionally include at least one pH sensor for monitoring the pH of the perfusate leaving the fluid reservoir, and at least one means for measuring oxygen levels. One possible means is to use a dissolved oxygen sensor for monitoring the dissolved oxygen of the perfusate in the fluid reservoir, and a second of the at least one dissolved oxygen sensor for monitoring the dissolved oxygen of the perfusate before it enters the tissue. Another possible means is to measure hemoglobin saturation when red blood cells are present in the perfusate, or when oxygen is greater than 100% saturated during perfusion and dissolved oxygen needs to be measured to calculate the total oxygen level. The system may optionally include a first of at least one pressure sensor for monitoring the pressure of the perfusate before it enters the gas management subsystem, and a second of at least one pressure sensor for monitoring the pressure of the perfusate before it enters the tissue. The system may optionally include a glucose sensor and a lactate sensor for monitoring glucose and lactate. In one embodiment, the properties of the circulating perfusate are determined by sensors embedded in the fluid path. In some configurations, dissolved oxygen, pH, temperature and oxygen saturation, among other properties, are measured as the perfusion fluid circulates. Sensors, which can include low-cost, single-use spot sensors, can be selected based on the tissue being perfused.

[0020] The tissue enclosure provides a barrier against contamination of the tissue when maintained. In one embodiment, the tissue enclosure includes three main parts, a fluid reservoir, a tissue platform, and a hood, all operatively coupled to form an isolated environment for the tissue. The geometry of the tissue enclosure includes a connector for receiving the tissue platform, a connector and seal for receiving the hood, a reservoir for containing fluid, a space above the fluid in which the tissue platform is placed, and a fluid ramp for receiving at least a portion of the tissue output and directing the output toward the fluid reservoir. A temperature control mechanism is positioned near the tissue enclosure. In an exemplary configuration, the temperature control mechanism is positioned below the tissue enclosure and is fluidly coupled to the tissue enclosure.

[0021] In some configurations, the tissue enclosure is a disposable component configured to be securely coupled to and decoupled from the set of durable components described herein. In one embodiment, one possible secure means for coupling the tissue enclosure to the durable components is an interaction between features on the tissue enclosure that operably couple with a durable hinge component. In one embodiment, the hinge component includes a pin that travels through a groove and rotates at least one cam. When rotated, the at least one cam exerts pressure against the tissue enclosure feature to drive the tissue enclosure to the heat exchanger in secure contact with the thermal control plate. The tissue enclosure coupling / decoupling means is augmented by a locking mechanism described herein that couples the disposable components of the perfusion pumping assembly with a durable interface to the pneumatic assembly.

[0022] In one embodiment, the fluid reservoir contains, for example, but not limited to, output products from the tissue, venous output from the tissue, and possibly nutrients and medicines. The types and amounts of components in the fluid are not limited to additives as listed herein, but rather include components appropriate for the type of tissue being maintained. The fluid reservoir resides below the tissue platform, such that the tissue is in the space above the fluid reservoir. Perfusion fluid is pumped from the fluid reservoir and its properties and temperature are regulated and monitored before being pumped into the tissue.

[0023] The tissue platform includes a means for a stable connection between the platform and the tissue enclosure. In one aspect, the connection has self-mating features, snap features, such as annular, torsion and cantilever snap locks, latch features, hook features, mating detents, interlocking features, press fits, interference fits and bolt fastenings. In one aspect, the connection can be multi-purpose, if necessary, and provide electrical and / or data interfaces via plugs or jacks. In an exemplary configuration, the tissue platform includes female position alignment features. The tissue platform also includes at least one handle for retracting the platform from the tissue enclosure. The at least one handle can include a pull handle without features, a pull handle with ergonomic features such as a grip, a recessed folding pull handle, an offset pull handle, a utility handle, a recessed handle, an edge pull, an extension handle. In an exemplary embodiment, the at least one handle includes a fixed pull handle with ergonomic features. At least one handle can be affixed to the tissue platform or can be attached to the tissue platform prior to retraction or placement of the tissue platform. Multiple handles can be affixed to the side of the tissue platform, or to the center of the tissue platform, or within the body of the tissue platform.

[0024] The tissue platform can optionally be divided into multiple areas of the platform floor. One area can be configured to accommodate tissue. The tissue itself can be positioned on the platform floor where the tissue can be intubated or otherwise operably coupled to the irrigation tube. In some configurations, the tissue is secured to the platform by, for example, straps, tie-downs, belts or cords secured in recesses on the rim of the tissue platform. A portion of the floor can be configured to manage tubing or perhaps wiring. Tube management can include, but is not limited to, weld mount clamps, rail clamps, magnetic clamps, snap-in clamps, multi-line clamps, connectable clamps, telescoping clamps, adhesive-backed clamps, lock-close strut mount clamps, stand-off clamps, low-profile clamps and loop clamps. In an exemplary configuration, tubes and cables are routed through merlons positioned on the floor of the tissue platform spaced apart, for example depending on the expected size of the tubes and cables. Other tube and cable attachment points allow the tubes and cables to be elevated above the platform floor. In an exemplary configuration, one or more standoff features are configured with tube holders, such as curved finger-like protrusions. In an exemplary configuration, tubing and cables are routed along the sides of the tissue platform between crenellated edges to allow for tube / cable routing between the tissue platform and other components of the tissue maintenance system. The crenellations can be spaced apart depending on the desired or expected tube / cable size. If desired, multiple tubes / cables can be accommodated in the space between the crenellations. The tubing or wiring is routed to exit the tissue platform, for example, but not limited to, duct tubing, routing tubing, routing panels, or channeling. The tubing is coupled with a connector that allows for connection to additional tubing within the tissue enclosure.On-board coupling between the tissue and perfusion tubing or other required system connections allows the tissue to be prepared for management with a system that is remote from the tissue enclosure and convenient to the location of the tissue, thereby reducing the amount of manual manipulation that the tissue must endure.

[0025] In one aspect, the platform floor is configured to contain fluids, such as output products from the tissue and venous fluids. The floor can include drainage means to allow tissue fluids to exit the platform floor without stagnation around the tissue. In an exemplary configuration, the floor is sloped toward a drain cavity in the floor. The drain cavity allows tissue fluids to flow from the tissue to a fluid reservoir below the platform. In one aspect, the tissue enclosure is configured to channel fluids from the platform so that the fluids enter the tissue reservoir in a controlled manner. In an exemplary configuration, the tissue enclosure includes a ramp that ensures that the fluid enters the fluid reservoir at a constant angle.

[0026] Other platform configurations are contemplated by the present teachings. The platform removable from the fluid reservoir can be the only part of the system that may be specific to a certain tissue type, but multiple platforms are contemplated for use for multiple tissue types. The platforms described herein used for the kidney illustrate the features of a particular platform. The present disclosure is not limited to accommodate renal platforms, nor is it limited to the geometry of the renal platform.

[0027] In one embodiment, the tissue enclosure includes a hood that includes a durable / disposable barrier and houses at least one sensor. The barrier and gasket fitted to the tissue enclosure protect the tissue on the tissue platform from external environmental conditions. The barrier allows manual and automated observation of the tissue on the tissue platform and is securely attached to the rim of the tissue enclosure to completely protect the tissue while still providing an option for viewing. Observation includes providing images of the tissue that can aid the user in assessing the tissue. For example, the tissue can be measured, the color of the tissue can be observed, for example to detect hemoglobin sufficient perfusion or bacterial infection, and the size / shape of the tissue over time can be determined, for example to detect tissue edema development. If the tissue is performing a particular physiological function, the user and / or controller can observe the function of the tissue over time.

[0028] In one aspect, the barrier is associated with an anti-fog means to reduce condensation and aid in tissue visibility through a window in the barrier. The window can occupy the entire barrier or simply a portion of the barrier. In an exemplary configuration, the anti-fog means includes a heating wire that is assembled adjacent to the barrier or threads through the entire barrier material. Typically, fogging occurs in cooler environments, which may necessitate insulating the tissue enclosure and thermal control features to allow tissue viewing among other reasons. Anti-fog materials such as polypropylene can cause moisture buildup to bead up. Anti-fog coatings on, for example, glass and plastic surfaces can be used as well, including but not limited to, polyvinyl alcohol molecules, surfactants such as detergents, hydrophilic coatings such as polymers and hydrogels. A non-fog window allows for standardized imaging, optical measurements, and the use of advanced imaging such as thermal imaging, infrared imaging, and hyperspectral imaging. Through a non-fog window, the user can view the appearance of the tissue without destroying the sterile barrier. Thermal management of the tissue enclosure walls has the added benefit of promoting moisture retention outside of the tissue itself, preventing the tissue from drying out and eliminating the need for additional moisture control such as placing moist gauze on the tissue. Additionally, the effect of thermal management on moisture reduces hemolysis by preventing gradients through the removal of pure water and reintroducing pure water as condensation droplets drip back into the perfusate.

[0029] Manual observation can include viewing the tissue through a transparent barrier. In some configurations, the barrier may be opaque and manual observation may not be possible. The hood can house sensors that can enable assisted automatic observation. The sensors can include, but are not limited to, image sensors such as CCDs, optical sensors, x-ray devices, and ultrasound devices, among others. In an exemplary configuration, the hood houses a camera mounting device and a camera. Data collected by the sensor can be provided to, for example, a controller, and / or a local display, and / or a handheld / wireless device. The data can be stored and tracked, and automated analysis can be performed on the collected image data, for example to automatically determine the state of the tissue over time. In one embodiment, an image sensor is mounted either on the outside or inside of the barrier, while other types of sensors whose data provide context to the image data are mounted inside the hood. Such sensors can include non-contact or contact sensors and can measure, but are not limited to, temperature, pressure, pH, oxygen, carbon dioxide, and glucose data. Sensor data can be collected wirelessly or by a wired connection between the sensor and the connector. In one embodiment, the sensor includes a camera with associated lighting. In one embodiment, the camera may be disposable. The sensor data provides tissue appearance data in real time. The user can use these data to inspect the tissue for key areas of interest, such as, but not limited to, color, edema, hypoxia, bleeding, and leakage. In one embodiment, the sensor data may be recorded and evaluated over time to assess changes. Sensor detectable clues to edema include tissue size increase over time. Sensor detectable clues to poor perfusion include tissue color change and bleeding / leaking. Sensor detectable clues to renal dysfunction include, for example, seizures. Sensor detectable clues to ureteral problems include, for example, lack of ureteral motion. Areas of concern are based on tissue type and other factors.

[0030] The system of the present teachings pumps perfusion fluid in a closed loop through the tissue. In one embodiment, the system includes one or more fluid pumps to achieve perfusion. Types of perfusion pumps include, but are not limited to, axial pumps, peristaltic pumps, diaphragm pumps, pumping cassettes, roller pumps, centrifugal pumps, pulsatile pumps, and non-occlusive roller pumps. Pumps that can enable perfusion of the system of the present teachings can deliver physiological blood flow against high resistance without damaging the blood, provide accurate and easily monitorable flow rates, create no turbulence or stagnation, and can be manually operable in the event of a power failure. In some configurations, an extracorporeal membrane oxygenation (ECMO) type device is used to perfuse and oxygenate the blood in the system. In some configurations, the oxygenation device uses a silicone membrane contactor. The perfusion fluid is pumped through multiple possible correction stations and past multiple sensors before entering the tissue. In an exemplary configuration, a pumping cassette can move the perfusion fluid from a fluid reservoir into the oxygenator upon instruction of a controller. An exemplary cassette pump is described in U.S. Pat. No. 9,999,717, issued June 19, 2018, entitled "System and Method for Detecting Vascular Access Disconnection."

[0031] In one embodiment, a pumping cassette is used having a first side containing a number of valve wells and a second side having a fluid bus. In one embodiment, each side is covered with a flexible membrane and includes a control surface having a number of valve well control stations actuatable in relation to the flexible membrane covering the first side of the cassette to open and close the valve wells when the cassette is mated against the control surface. In one embodiment, the pumping cassette includes two chambers. The use of the chambers may be alternated to generate continuous flow or timed to generate pulsatile flow. A pressure distribution assembly may be included having positive and negative pressure sources and a number of pneumatic valves. The controller is configured to selectively activate the number of pneumatic valves to apply pressure against the valve well control stations in a valve pumping sequence until a volume is displaced from the source through the fluid bus of the pumping cassette to a destination within a target volume range. The flow rate and pressure of the perfusion pump as it pumps the perfusion fluid through the system are adjusted such that the flow rate and pressure of the perfusion fluid going into the tissue is adjusted. The resistance of tissue may change over time, for example with changes to physiology. The pressure of the pumped irrigation fluid may need to change over time to accommodate the needs of the tissue. Overpressurization of the fluid lines can cause lysis.

[0032] Mechanical causes of cell damage include, for example, mechanical trauma, extreme temperatures, sudden pressure changes, radiation, and electricity. One possible form of mechanical trauma can be indirectly caused by the perfusion fluid pump. To avoid this form of mechanical trauma, the system of the present teachings includes a flow sensor to measure the flow rate and at least one pressure sensor to measure the perfusion fluid pressure. The flow rate and pressure of the perfusion fluid pumped through the system are adjusted to a desired amount. Pressure management in the system of the present teachings includes establishing a desired pressure and applying that pressure to the pneumatic side of the pumping cassette. The flow rate, as determined by a flow meter in the perfusion path, is integrated over time to determine the volume of fluid perfused over a fixed amount of time. Since the volume of the pumping system on the fluid side of the pumping cassette is known and the volume of fluid over a preselected amount of time is known, the controller switches chambers when the volume of fluid in the pumping system reaches a preselected level. This form of control can, for example, avoid mechanical trauma to cells in the perfusate because the perfusate is not pressed against the bottom of the pumping system by the membrane, thus limiting hemolysis. For example, the controller can switch the pumping chamber when the chamber is 95% full. The pressure required to reach the desired fluid pressure at the inlet to the tissue is the desired air pressure. The desired air pressure can, at least in part, explicitly control the mechanical cause of cell damage to ensure that cell damage in the perfusate is limited to a desired level. In one embodiment, a flow meter monitors the instantaneous flow rate and integrates the volume. As the control loop operates, the pump ensures that the membrane for the direct-acting pump does not lyse red blood cells.

[0033] The flow meter is used to adjust the pressure on the tissue as the thermal profile of the tissue changes. For example, as the tissue warms, its blood vessels dilate, reducing fluid resistance and the allowable perfusion fluid flow rate through the tissue at a given pressure generally increases. In one embodiment, the tissue surface temperature is used to adjust the pumping pressure of the perfusion fluid. The resistance of the tissue to perfusion is a function of the volume and pressure of the fluid being perfused over a preselected amount of time. Renal resistance is defined as the pressure divided by the flow rate. When the flow is laminar, the nominal magnitude of renal resistance is (L / D 4 ), where L is the average blood vessel length through the kidney and D is the average vasculature diameter within the kidney, which is a function of temperature and kidney health. Renal resistance is directly proportional to the ratio of pressure on the perfusate to flow volume. In an exemplary configuration, pressure is automatically adjusted based on tissue surface temperature or calculated resistance.

[0034] The tissue receives perfusion fluid in its cannulated orifice and generates an output through another cannulated orifice of the tissue. For example, if the tissue is a kidney, at least one of the outputs is urine. At least one output from the tissue is routed from the tissue for monitoring of the output before the output is routed back to a fluid reservoir or routed to a waste area. To enable monitoring of the output, the system includes an output flow device including a collector container and a sensor, as well as a means for managing the accumulation of the collection device. The container can be of any shape and can include, for example, graduated fill marks. When selecting the shape and size of the container, the convenience of assembly of the container in relation to the platform and the output metric can be considered. The container includes at least one sensor that indicates to the controller the level of the output in the container. In some configurations, the container is coupled with multiple sensors, at least one at a desired output high level and at least one at a desired output low level. When the output reaches the high level sensor, the controller instructs the valve to open and release the output. When the output reaches the low level sensor, the controller instructs the valve to close and again retain the fluid in the container. In an exemplary configuration, the level sensor includes an ultrasonic sensor. In one embodiment, the level sensor includes at least one visual sensor that determines the level of the fluid by locating a float within the fluid. The present teachings contemplate multiple high and low levels to allow for different types of measurements. The valve is selected from the group consisting of, but not limited to, ball valves, butterfly valves, check valves, gate valves, knife gate valves, spherical valves, needle valves, pinch valves, and plug valves. In an exemplary configuration, the valve is a pinch valve. In one embodiment, the valve is a pneumatic valve. In some configurations, the output flow container is configured to allow for visual inspection of the output. For example, the output passes through a transparent or partially transparent container. The container can be completely opaque except for a window, or it can be substantially transparent or some layout in between.

[0035] Other methods for evaluating the tissue output over time are contemplated by the present teachings. Output monitoring can be manual, automatic, real-time, and through post-processing. Sensor types include, but are not limited to, visual sensors, such as cameras, IR, x-ray, temperature, pressure, chemical, ultrasonic, humidity, color, and light sensors. Real-time manual monitoring can be enabled by a transparent collector through which the output can flow and be collected. In an exemplary configuration, the transparent collector includes graduated markings associated with the desired accuracy of the collected volume. In one embodiment, the collector is opaque to electromagnetic radiation to protect the output from degradation due to exposure. If the collector is opaque, sensors in addition to the fill sensor are assembled inside and outside the collector to enable manual and automatic monitoring. Sensor data can include, for example, the amount of output, the characteristics of the output, and the elapsed output collection time. The sensor data can be transmitted wirelessly or wired to a controller, display, or a handheld device that can be monitored manually. The controller receives data associated with the output and performs real-time automated monitoring, which may include analysis of sensor data collected while the output is collected and flowing. The controller can modify at least some of the system's characteristics based on the analysis, if necessary. The controller can control off-line automated monitoring by collecting samples, subjecting them to tests, perhaps of longer duration than the real-time tests, and recording the data or using the information to manage controllable characteristics of the system. In an exemplary configuration, the tissue is the kidney and the output is urine output. Urine output from the kidney can be measured and compared to an expected amount to assess kidney function. The color of the urine output can be observed / measured, and urine can be tested for, for example, acidity, particle concentration, protein, sugar, ketones, bilirubin, signs of infection, and blood. Possible sensors include optical sensors to measure urine color. For example, free hemoglobin in urine, blood, or osmolality in urine can be optically detected. For example, some of these tests can be performed in real time, and the amount of nutrients can be modified, or the amount of carbon dioxide can be adjusted to move the kidney to a healthy state.Some testing can be done through post-processing and perhaps the results can be used to manage kidney perfusion. In one embodiment, the output container is transparent and includes a reservoir that allows the user to visually monitor the flow rate, color and opacity of the output in real time. A sample of the output can be removed and tested offline and / or the output returned to the perfusate reservoir.

[0036] In some configurations, the output flow device is configured with a sample means. The output can be sampled as it enters or leaves the container. The sample can be tested in real time or offline. The output can be directed by tubing and valves to a sample container, or back into a perfusate reservoir below the tissue platform, or elsewhere. The controller directs the routing valves to open or close depending on the desired destination of the output or, for example, the amount of output to be sampled, among other options. In some configurations, a single three-way valve is used to contain the output, route the output to a sample container, or route the output into a perfusate reservoir below the platform. In some configurations, the output can be passively driven by a combination of tissue forces to move the output from the tissue into the output flow device and gravity to move the output from the container for further processing. The output container is positioned above the perfusate reservoir and below the tissue platform so that gravity plays a role. In some configurations, the output is pumped from the tissue or output reservoir into a flow meter, e.g., pumped from the container to be sampled or to join other tissue perfusate. A portion of the output can be routed to a sample collector to allow for offline manual monitoring. The output flow device container output tubing can be branched. One branch of the branched tubing can go through a valve controlled by the controller and back to the perfusate reservoir. The other branch can go to a sample container. The controller manages which branch is taken by controlling the valves at the branch. The sample can also be subjected to chemical and / or biological analysis, e.g., that can be visually inspected or manually inspected. In an exemplary renal process, a urine sample is collected and disposed of at the beginning of the perfusion, e.g., to remove urine containing inflammatory markers. In one embodiment, all collected during the first 50 mL or 1.5 hour collection time is discarded. Monitoring can lead to changes.For example, if a user observes that the output is not the expected color or quantity, the user can manually make changes to the currently running perfusion path or can instruct the system to automatically make a series of changes. For example, if the urine is observed to be red, then there is either blood or free hemoglobin in the urine. The system can automatically stop urine recirculation and begin infusion of remedial measures such as nutrients and medicines to the kidney. If cloudy urine is detected, the system can automatically issue an alarm to alert the user since this observation may indicate a bacterial infection. In the system of the present teachings, the output color can be observed by a transparent output container, and the output quantity can be observed by an output measurement system of the present teachings. Similarly, if a user observes that the perfusion fluid characteristics are insufficient for proper tissue preservation, the user can override the default instructions and take action to modify the characteristics. In some configurations, the user can start the perfusion process and manually control the entire process. In some configurations, the user starts manual control after the system has performed a certain number of steps. In some configurations, the automated operation may be so sophisticated that no user input is required, or perhaps not until the end of the perfusion cycle, perhaps as determined, for example, from tissue characteristics or the amount of time elapsed. Renal indicative characteristics may be determined, for example, from examination of creatinine clearance, fractional excretion of creatinine, and fractional excretion of sodium present in the urine. Pool et al., Prolonged ex-vivo normothermic kidney perfusion: The impact of perfusate composition,. PLoS ONE 16(5):e0251595, https: / / doi.org / 10.1371 / journal.pone.0251595, May 18, 2021, p.4(Pool)

[0037] The system of the present teachings provides nutrients and medicines to the tissue when needed, for example. The controller controls the device to access various infusion materials depending on the needs of the tissue. The nutrients and medicines can include, but are not limited to, water, lipids, amino acids, glucose, vitamins, hormones, antibiotics, chemotherapy drugs, vasodilators, vasoconstrictors, diuretics, antidiuretics, antihemorrhagic drugs, and insulin. In one embodiment, the kidney characteristics are controlled by adjusting the infusion material, monitoring the results of the infusion on the kidney characteristics, and then adjusting the infusion rate based on the results. The nutrients are provided by an infusion pump, which is a device that delivers the nutrients and medicines in controlled amounts. The pump is configured either automatically or manually to provide a particular nutrient at a particular flow rate. An automatic infusion configuration occurs when the system of the present teachings determines what type of tissue is being processed and automatically sets the nutrients and medicines. A manual infusion configuration occurs when the system accesses or the user provides setup parameters such as the components, delivery rate, and delivery time of the nutrients and / or medicines. In either case, the controller determines an alert when there is a potential or actual failure of the pump or a potential or actual drug interaction, among other types of alerts. In an exemplary configuration, the nutrients and medications are pumped into a fluid reservoir by an infusion pump, several possibilities of which are described herein. In an exemplary configuration, a pumping cassette pumps the nutrients and medications to the tissue, directly into the arterial line or into the reservoir. In one embodiment, the pumping cassette is sized to accommodate the requirements for delivering the nutrients and medications. For example, the pumping cassette includes a single chamber that pumps a preselected amount of fluid at a consistent rate, such as 10 ml / hour. In one embodiment, sensors measure the consumption rate of the nutrients / medicines, and these sensor data are used to control the infusion of these components. For example, a glucose sensor measures how much glucose is in the perfusate exiting the tissue, and the measurement is used to adjust the amount of glucose infused based on the metabolic rate of the tissue.The nutrient pump of the present teachings is configured to pump from an intravenous bag at a rate of 1-20 mL / hr, eliminating the need for an IV pump. In one embodiment, the nutrient pump is a sterile, disposable device that can be integrated with the pneumatic system of the present teachings. In one embodiment, the nutrient pump performs closed-loop glucose control.

[0038] In some configurations, a low bolus, high precision infusion pump is used to allow for clinical infusion of vasodilators or insulin formulations. In some configurations, multiple infusion pumps are used to allow for infusion of multiple different substances, possibly simultaneously. In some configurations, the pump reservoir is 3 mL and the pump infuses into the perfusate reservoir, corresponding to infusion rates of 0.5-300.0 μL / hr and infusion volumes of 0.5-250.0 μL.

[0039] In some configurations, where the tissue is a kidney, the replacement components can include, for example and without limitation, a plurality of infusion solutions. The infusion solutions can include, but are not limited to, an isotonic crystalloid / dextran solution, and a buffer solution. The isotonic crystalloid / dextran solution can include an isotonic crystalloid along with 0.026 g / mL of dextran, a complex polysaccharide derived from the condensation of glucose. During replacement, the system includes means for maintaining a target glucose range of 100-150 mg / dL and a basal flow rate of 10 mL every 15 minutes. These targets, if met, deliver 25 g of dextran and 960 mL of perfusate replacement per day. The time between doses is adjustable to achieve the targets. Insulin can be added depending on the sensed glucose reading. The buffer solution is used to adjust the pH of the perfusate. The target pH can include a range of 6.9-7.9. In some configurations, the system includes means for flushing the kidney with a high flow, low potassium preservation solution. In some configurations, the system includes means for perfusing the kidney and monitoring renal characteristics to determine whether the infusion is maintaining renal viability. Possible renal nutrients may include, for example, but are not limited to, albumin, saline, adenine, glucose and mannitol, creatinine, MgSO4, calcium gluconate, insulin, and dexamethasone.

[0040] The system of the present teachings includes a means for thermal control of the perfusate and the tissue itself. In some configurations, maintaining the tissue at a desired temperature includes selecting a temperature regulation option that meets weight, power and size requirements. Possible options include, but are not limited to, thermodynamic heat engines, phase change, and thermoelectric systems. In some configurations, the heat load is 10-20 W to maintain a 20° C. temperature difference between the environment and the tissue, or less if the tissue is maintained at a subnormothermic temperature. For heat loads on the higher side of the 10-20 W range, a thermodynamic heat engine can be selected. For systems where a battery, if present, may be of significant size, a thermoelectric system can be selected because it is scalable. If the tissue enclosure must be placed in a closed environment, a phase change material system can be used because it can store and release heat generated and consumed inside the closed environment. Maintaining the tissue 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.

[0041] In some configurations, the temperature of the perfusion fluid is controlled through a heat exchanger. The heat exchanger can optionally include a thermal energy source, a surface having at least one channel for holding the perfusion fluid, a membrane covering the surface and conducting thermal energy from the heat source through the membrane to the perfusion fluid, and a heat transfer plate between the membrane and the heat source. The at least one channel can include a serpentine flow path resting on the thermally conductive and reflective membrane. In some configurations, the heat transfer plate includes cartridge elements for active control of the temperature of the perfusion fluid. The system includes a temperature sensor that senses the temperature of the perfusion fluid as it enters and exits the serpentine fluid path. The active control of temperature can maintain a temperature within a range of, for example, 3°-42° C. required for perfusion of the tissue. The number and size of the cartridge elements are based at least on the characteristics required to maintain a uniform distribution across the serpentine path. The size of the thermal control plate is determined by, for example, but not limited to, the number and size of the cartridges and the volume and geometry of the tissue reservoir. The width of the serpentine channel is based on the need to maintain adequate surface area inside the channel, avoid stagnation, avoid substantial pressure loss, and maintain uniform heat transfer. The geometry of the serpentine channel can be important to prevent stagnation and prevent turbulence.

[0042] The system may optionally include a first of at least one thermal sensor that monitors the perfusate temperature before the perfusate 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.

[0043] The heat exchanger can optionally include a plate having a first side etched with the fluid pathway and a second opposing side positioned against the tissue reservoir, 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 the thermal energy source.

[0044] The system of the present teachings includes a gas management subsystem that adjusts gas saturation in the perfusate. The gas management subsystem can optionally include at least one oxygenator that supplies oxygen and manages carbon dioxide levels to the perfusate, and at least one gas supply device that provides at least one gas to the perfusate. The at least one gas can optionally include oxygen, nitrogen, and carbon dioxide. Before the perfusate enters the oxygenator from the perfusion pump, the pressure exerted by the perfusate exiting the pump is measured. The controller adjusts the pressure of the perfusion pump based on the measured pressure information and the needs of the tissue. The oxygenator adjusts the gas levels in the perfusate as the pump moves the perfusate through the oxygenator. For example, based on the measured pH, dissolved oxygen, and blood oxygen saturation levels, the controller creates a gas mixture that can adjust properties such as pH and dissolved oxygen in the perfusate. The controller interfaces with a mass flow controller, for example, to direct the gas mixture to flow through the oxygenator. In an exemplary configuration, air is removed from the perfusate by an in-line air trap, where air bubbles are suspended on the top surface of the incoming perfusate and the fluid exits through a non-air section of the air trap.

[0045] Methods of the present teachings can include, without limitation, assembling tissue onto a tissue platform and positioning it for perfusion. The method can include coupling an orifice of the tissue to a preselected location on the platform through tubing, connectors, etc. For example, if the platform is configured for a kidney, the platform can include a connector and tubing for transporting perfusate into the kidney and another connector and tubing for transporting urine out of the kidney. The method can include directing the venous output into a perfusion reservoir. The vein can be cannulated and directed to a fluid reservoir by tubing, or it can simply exit the kidney and transition through a cavity in the platform to the perfusion fluid reservoir. In an exemplary configuration, the artery and ureter can be cannulated and the cannulation tubing can be passed through a protrusion on the platform that can prevent the tubing from moving on its way to the platform orifice and connector.

[0046] The method can include coupling the platform connector to a perfusion system and securing the platform in place above the perfusion fluid in a perfusion fluid reservoir. The perfusion fluid reservoir can include a space for the perfusion fluid below the platform. Output from tissue mounted on the platform can flow into this fluid. For example, if the tissue is a kidney, the output is venous perfusion fluid and urine.

[0047] The method may include measuring the output from the tissue. The perfusion fluid pumped into the tissue artery may pass through the tissue and exit, at least in part, through the tissue vein and into a perfusion fluid reservoir. The method may include recirculating the perfusion fluid from the perfusion fluid reservoir back to the tissue artery. The perfusion fluid may include, but is not limited to, oxygen carriers, such as, but not limited to, perfluorocarbons, hemoglobin-based perfusion fluids, and annelid hemoglobin-based perfusion fluids. Hemoglobin-based oxygen carriers may include infusible oxygen-carrying perfusion fluids prepared from purified human or animal hemoglobin. The perfusion fluid may include a combination of electrolytes, carbohydrates, vitamins, proteins, prescription drugs, and pH buffers. The method may include monitoring and adjusting the temperature of the perfusion fluid prior to pumping the perfusion fluid into the tissue. In some configurations, the temperature may be adjusted to room temperature. In some configurations, the temperature may be adjusted to body temperature. In some configurations, the temperature may be adjusted to a range of 3-42°C. Normal tissue handling procedures within the system and through the methods of the present teachings protect tissue from extreme temperatures over extended periods of time. When maintaining tissue at hypothermic levels, target temperatures include the range of 3-10° C. When maintaining tissue at subnormothermic levels, target temperatures include the range of 18.5-25.5° C. When maintaining tissue at normothermic levels, target temperatures include the range of 32-42° C.

[0048] The method may include pumping air through an oxygen concentrator device to provide oxygen to the perfusate. A mass flow controller (MFC) establishes a steady gas flow by controlling mass flow and pressure for air pressure pump control and for providing the gas mixture to the perfusate. In one embodiment, oxygen is controlled to maintain a desired hemoglobin oxygen saturation or oxygen partial pressure. In one embodiment, carbon dioxide is controlled to maintain a desired carbon dioxide partial pressure or pH. In one embodiment, nitrogen is controlled for equilibration. In one embodiment, the target ranges for dissolved oxygen include 74-160 mmHg in the artery and 30-40 mmHg in the vein. In one embodiment, the target ranges for dissolved oxygen include 74-500 mmHg in the artery and 30-500 mmHg in the vein. In one embodiment, the system can aid in tissue repair as needed at levels up to 760 mmHg. In one embodiment, the target ranges for both arterial and venous dissolved oxygen include 300-500 mmHg if no additional oxygen is available or to ensure that extra oxygen is available. The target range for dissolved carbon dioxide includes 35-45 mmHg. The method can include replenishing fluids, electrolytes, nutrients, and other biological compounds necessary to maintain tissue health. In some configurations, an infusion pump is used to provide replenishing fluid into the perfusate reservoir at a flow rate of 1-20 mL / min. In one embodiment, urine is collected from the kidney, urine conductivity is monitored, conductivity is correlated to electrolyte composition, and replenishing fluid is delivered via two nutrient pumps. In one embodiment, various electrolytes are measured in the urine, each requiring specific adjustments. The method can include monitoring tissue vitality, for example, but not limited to, through monitoring tissue resistance changes (pressure / flow), oxygen consumption, and pH status. Monitoring tissue properties provides an indication of tissue health.

[0049] The system of the present teachings includes a combination of disposable and durable materials. For example, the oxygenation means is disposable along with the heat exchanger, while the thermal energy source is durable. At least one perfusion pump is disposable, while at least one pump interface coupling the at least one disposable pump to the pneumatic system is durable. At least one infusion pump is disposable. The pneumatic system 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. The durable components can include at least one sensor that provides sensor data for monitoring the tissue, and at least one controller that receives and processes the sensor data. The disposable components can include a spot sensor, tubing, a cassette pump, a tissue container, and an oxygenator.

[0050] The foregoing features of the present disclosure will be more readily understood by reference to the following description taken in conjunction with the accompanying drawings, in which: [Brief description of the drawings]

[0051] [Figure 1A] FIG. 1A is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 1B] FIG. 1B is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 1C] FIG. 1C is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 1D] FIG. 1D is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 1E] FIG. 1E is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 1F] FIG. 1F is a schematic block diagram of a system of the present teachings for maintaining and assessing tissue. [Figure 2A] FIG. 2A is a schematic perspective view of one configuration of the system of the present teachings. [Figure 2B] FIG. 2B is a schematic elevation view of one configuration of the system of the present teachings. [Figure 2C] FIG. 2C is a schematic elevation view of one configuration of the system of the present teachings. [Figure 2D] FIG. 2D is a schematic perspective view of one configuration of the system of the present teachings. [Figure 2E] FIG. 2E is a schematic side view of one configuration of the system of the present teachings. [Figure 2F] FIG. 2F is a schematic side view of one configuration of the system of the present teachings. [Figure 2G] FIG. 2G is a schematic side view of one configuration of the system of the present teachings. [Figure 2H] FIG. 2H is a schematic top view of one configuration of the system of the present teachings. [Figure 2I] FIG. 2H is a schematic bottom view of one configuration of the system of the present teachings. [Figure 3A] FIG. 3A is a schematic perspective view of the durability components of the configuration depicted in FIG. 2A. [Figure 3B] FIG. 3B is a schematic perspective view of a durability component of the configuration depicted in FIG. 2A. [Figure 3C] FIG. 3C is a schematic perspective view of a durability component of the configuration depicted in FIG. 2A. [Figure 3D] FIG. 3D is a schematic block diagram of a sensor system configuration for monitoring power output of the present teachings. [Figure 4A] FIG. 4A is a schematic perspective view of the disposable components of the configuration depicted in FIG. 2A. [Figure 4B] FIG. 4B is a schematic perspective view of the disposable components of the configuration depicted in FIG. 2A. [Figure 4C] FIG. 4C is a schematic perspective view of the disposable components of the configuration depicted in FIG. 2A. [Figure 5A] FIG. 5A is a schematic perspective view of the disposable portion of the infusion pump of the configuration depicted in FIG. 2A. [Figure 5B] FIG. 5B is a schematic perspective view of the disposable portion of the infusion pump of the configuration depicted in FIG. 2A. [Figure 5C] FIG. 5C is a schematic perspective view of the disposable portion of the infusion pump of the configuration depicted in FIG. 2A. [Figure 5D] FIG. 5D is a schematic perspective view of a disposable portion of an infusion pump of the configuration depicted in FIG. 2A. [Figure 5E] FIG. 5E is a schematic perspective view of the disposable portion of the infusion pump of the configuration depicted in FIG. 2A. [Figure 6] FIG. 6 is a schematic perspective view of a pneumatic assembly that controls pumping of the arrangement depicted in FIG. 2A. [Figure 7] FIG. 7 is a schematic top-down view of a pneumatic assembly of the configuration depicted in FIG. 2A. [Figure 8] FIG. 8 is a schematic diagram of the electronics layout of the configuration depicted in FIG. 2A. [Figure 9A] FIG. 9A is a schematic perspective view of a container hood and barrier heating assembly of the configuration depicted in FIG. 2A. [Figure 9B] FIG. 9B is a schematic perspective view of a container hood and barrier heating assembly of the configuration depicted in FIG. 2A. [Figure 9C] FIG. 9C is a schematic side view of a container hood and barrier heating assembly of the configuration depicted in FIG. 2A. [Figure 10A] FIG. 10A is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10B] FIG. 10B is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10C] FIG. 10C is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10D] FIG. 10D is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10E] FIG. 10E is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10F] FIG. 10F is a schematic perspective view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 10G] FIG. 10G is a schematic elevational view of a tissue container assembly and mounting mechanism of the configuration depicted in FIG. 2A. [Figure 10H] FIG. 10H is a schematic elevational view of a tissue container assembly and mounting mechanism of the configuration depicted in FIG. 2A. [Figure 10I] FIG. 10I is a schematic elevational view of a tissue container assembly and mounting mechanism of the configuration depicted in FIG. 2A. [Figure 10J] FIG. 10J is a schematic elevational view of a tissue container assembly and mounting mechanism of the configuration depicted in FIG. 2A. [Figure 10K] FIG. 10K is a schematic top view of a tissue container assembly and assembly mechanism of the configuration depicted in FIG. 2A. [Figure 11A] FIG. 11A is a schematic perspective view of a tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 11B] FIG. 11B is a schematic perspective view of a tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 11C] FIG. 11C is a schematic perspective view of a tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 11D] FIG. 11D is a schematic perspective view of a tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 11E] FIG. 11E is a schematic perspective view of a tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 11F] FIG. 11F is a schematic top view of the tissue container tank thermal regulation assembly of the configuration depicted in FIG. 2A. [Figure 12] FIG. 12 is a perspective view of a tissue strap of the configuration depicted in FIG. 2A. [Figure 13A]FIG. 13A is a schematic perspective view of a second embodiment of a tissue container tank assembly of the configuration depicted in FIG. 2A. [Figure 13B] FIG. 13B is a schematic perspective view of a second embodiment of a tissue container tank assembly of the configuration depicted in FIG. 2A. [Figure 13C] FIG. 13C is a schematic exploded view of a second embodiment of a tissue container tank assembly of the configuration depicted in FIG. 2A. [Figure 14A] FIG. 14A is a schematic perspective view of a second embodiment of a tissue container assembly in the configuration depicted in FIG. 2A. [Figure 14B] FIG. 14B is a schematic perspective view of a second embodiment of a tissue container assembly in the configuration depicted in FIG. 2A. [Figure 14C] FIG. 14C is a schematic exploded view of a second embodiment of a tissue container assembly in the configuration depicted in FIG. 2A. [Figure 15] FIG. 15 is a perspective view of a second embodiment of the hood assembly of the configuration depicted in FIG. 2A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0052] A system of the present teachings for maintaining, assessing, maturing and repairing tissue is described in detail herein. In particular, the systems and methods of the present teachings are configured to enable real-time assessment of tissue and use this assessment to continuously maintain tissue health. The system of the present teachings includes, but is not limited to, a disposable component set and a durable component set. The disposable components include, but are not limited to, a tissue container assembly that holds tissue and a reservoir of perfusate, a perfusion pump assembly that pumps perfusate through the tissue, tubing that connects the tissue container with the perfusion pump assembly, a tissue gas regulating device that maintains a myriad of properties of the perfusate, and sensors that provide data about the tissue necessary to maintain the tissue. The disposable components may also include at least one infusion pump assembly that provides nutrients and medicines to the tissue, and a power monitoring, measuring and sampling assembly that receives output from the tissue, assesses the output in real-time and possibly offline, and returns the output to the tissue container perfusate reservoir. Durable components include, but are not limited to, a tank monitor assembly that protects the tissue from environmental contamination and allows for visual and sensory recording of the tissue, a thermal regulation assembly that maintains the temperature of the perfusate, a pneumatic assembly that drives the perfusion pump assembly to circulate the perfusate, and power, data and control electronics that power the components of the system and sequence events in the system based at least on the sensor data.

[0053] 1A-1E, various configurations of the system of the present teachings are illustrated in block diagram form. All exemplary configurations include a durable and a disposable assembly. The present teachings contemplate additional configurations beyond those depicted herein. The drawings in FIGS. 1A-1E are for illustrative purposes only. In one embodiment, a system 100 of the present teachings (FIG. 1A) includes a durable assembly 115A (FIG. 1A) and a disposable assembly 113 (FIGS. 1A-1D). The disposable assembly 113 (FIGS. 1A-1D) includes a container or tank that houses the tissue to be maintained and assessed. The container is operably coupled to the durable assembly 115A (FIG. 1A) while protecting the enclosed tissue and fluids that nourish and medicate the tissue from environmental contamination. Durable assembly 115A (FIG. 1A) includes tank monitor 119 (FIGS. 1A-1D), electronics 111 (FIGS. 1A-1D), thermal regulation assembly 107 (FIGS. 1A-1D), and pneumatic assembly 105 (FIGS. 1A-1D). Tank monitor 119 (FIGS. 1A-1D) includes at least one sensor capable of capturing and retaining data about tissue placed in disposable assembly 113. Tank monitor 119 (FIGS. 1A-1D) includes, for example, a transparent barrier that can protect tissue from environmental contamination while simultaneously allowing immediate inspection of the tissue. The barrier can be completely transparent to all frequencies or completely transparent to some frequencies and opaque to other frequencies. A portion of the barrier can be opaque while other portions can be transparent. Inspection can be performed manually, manually enabled by a sensor, partially automated via a sensor enabled by a controller, or fully automated. The sensors can include, but are not limited to, cameras and x-rays, and remote probes that monitor, for example, temperature, humidity, light, pressure, flow rate, air quality, and air differential pressure. The electronics 111 (FIGS. 1A-1D) includes a controller that manages various activities related to the sensors, such as the collection, display, analysis, and storage of data from the sensors.Thermal regulation assembly 107 (FIGS. 1A-1D) maintains a desired temperature within disposable assembly 113 (FIGS. 1A-1D) and provides thermal regulation for the perfusion fluid used to nourish and medicate the tissue without thermal regulation assembly 107 contacting the tissue. Movement of perfusion fluid, nutrients and medications to and through the tissue is enabled by pneumatic assembly 105 (FIGS. 1A-1D) which drives at least one disposable pump. The present teachings contemplate other methods for driving the pump. Pumps in the systems of the present teachings have delivery requirements. These requirements dictate the desired characteristics of any device that drives the pump. In one aspect, the pneumatic valve assembly is capable of delivering the required quantity without causing damage to the fluid traversed.

[0054] 1B, an exemplary system 200 includes a durability assembly 115B that includes a tank thermal conditioning assembly 109. In such a configuration, the tank thermal conditioning assembly 109 insulates the tank and provides thermal control for the tank. The purpose of the assembly is to substantially prevent condensation from adhering to the tank. Condensation on the tank can affect tissue monitoring and may be indicative of a condensation / evaporation cycle that can remove moisture from the tissue or completely dry out the tissue surface, affecting tissue viability. Tank insulation can reduce condensation, and thermal control can also reduce condensation.

[0055] 1C, an exemplary system 150 includes a user interface 101 and an output monitor 103. In such a configuration, sensor data collected by sensors in the durable assembly 115C and the disposable assembly 113 can be made available to a user through the user interface 101. Possible user interface options include wired and wireless devices, devices with and without visual, audio and tactile interfaces, and / or combinations of interfaces. For example, a computer monitor can display a readout of the sensor data collected about the tissue and can be coupled with a keyboard where the user can request the type of data and / or control the sequencing of events occurring about the tissue. The user interface can be used to override or extend all or part of any automatic behavior the system takes to maintain the tissue. Changes in the tissue over time can be depicted graphically, either by a table of tissue characteristics over time, a graphical depiction of such data, photographs and / or videos of the tissue at various checkpoints and continuously, audio reports of the tissue and / or a tactile readout of the status. The data may be analyzed and recorded, and the user and / or can retrieve the analyzed data. The output monitor 103 allows for collecting the output from the tissue, measuring it, inspecting it, and routing it based on automatic and / or manual selection. The output monitor 103 includes a vial or collection bag into which the tissue output is routed, for example, by tubing intubated into the tissue orifice, e.g., the ureter if the tissue is a kidney. Other types of routing of the output are also contemplated by the present teachings. In either case, the tissue enclosure is properly sealed from environmental contamination even as the output travels from inside the enclosure to a collection point outside the enclosure. Connectors providing environmental isolation and a closed circulation path maintain the desired protection from contaminants. The output travels to a collection point at which the output can be measured, assessed, and released.The collection point can allow for assessments ranging from manual visual inspection to fully automated multi-sensor assessments and including all types of testing and assessments in between. For example, if the collection point is configured as a transparent or translucent container, the user can visually view the urine if the tissue is a kidney and manually adjust parameters that can return the urine to a healthy appearance. In a similar manner, the sensor can automatically deliver data about the urine to the controller, which can automatically adjust parameters that affect the health of the kidney. In one embodiment, the collection point includes at least one inflow fluid path that captures output from the tissue into the collection point. In one embodiment, the collection point includes a means for detecting a volume of the output. When a preselected amount of output has been collected, this amount is measured and released through at least one outflow fluid path. In one embodiment, the means for detecting the volume includes at least one level sensor coupled with at least one valve controlled by the controller. In one embodiment, the controller receives a signal when the level sensor detects that fluid has reached a preselected level in the collection device. In one embodiment, the controller activates the sensor to inspect the collected output. Upon completion of the test, the controller opens at least one valve to emit the output. The controller discontinues the emission by closing the valve when the level sensor detects that the fluid has reached a preselected level in the collection device. Other means for measuring the level of the output are also contemplated by the present teachings. The output can be emitted to at least one reservoir. In one embodiment, the output can be emitted to a reservoir selected by the controller. In one embodiment, a single path of the output can be routed through a multi-path connector. In one embodiment, one path can route fluid into a tissue container to merge with a reservoir of perfusion fluid. In one embodiment, one path can route fluid to a waste reservoir, which can be removed and deposited in an appropriate receptacle.In one embodiment, one pathway can route fluid into a sample reservoir, which can be removed and assessed offline. Other output pathways are also contemplated by the present teachings.

[0056] 1D, the durable assembly 115C of the exemplary system 250 can include a disposable initiator 108. In one embodiment, the disposable assembly 113 can be fully decoupled from the durable assembly 115C by (1) aligning a complementary joint, such as between the durable pneumatic assembly 105 and the disposable pump controlled by the pneumatic assembly 105, and (2) engaging a mechanism that allows for a secure coupling between the disposable and durable assemblies. In one embodiment, the mechanism includes at least one tapered locking shaft that is coupled with at least one disposable locking carriage. The locking carriage locks the disposable assembly 113 in place by sliding across the locking shaft until it passes a spring plunger. To decouple the disposable assembly 113 from the durable assembly 115C, the spring plunger is released. Other means of coupling the durable and disposable assemblies are also contemplated by the present teachings.

[0057] 1E, the disposable assembly 113A includes components that directly contact the tissue and / or perfusion fluid, and / or nutrients and / or medications. These components can include, but are not limited to, a tissue container, pumps that allow the flow of perfusion fluid, medications, and nutrients, tubing, sensors, and sample collection / assessment containers. In one embodiment, the disposable assembly 113A includes a disposable subassembly 303, a drip assembly 305, a perfusion pump assembly 307, a tissue container assembly 309, tubing 311, an output assembly 313, a sensor 315, and a sample collection device 317. In one embodiment, the pneumatic drip assembly 305 drives the perfusion pump assembly 307 to deliver medications and nutrients to the perfusion fluid. In one embodiment, nutrients can be delivered by one pneumatic drip pump, while medications can be delivered by another pneumatic drip pump. In one embodiment, the pneumatic drip pumps are controlled by a controller. In one embodiment, medications and / or nutrients can be delivered by independent remotely operated pumps that are not tied to the pneumatic system. The choice of pump depends on the desired delivery rate and other factors associated with the product being delivered. In one embodiment, the infusion pump can include a cassette pump designed to deliver the infusion material according to the desired flow rate and pressure. The perfusion pump assembly 307 includes at least one perfusion pump. In one embodiment, the perfusion pump enables the flow of perfusion fluid to and through the tissue. In one embodiment, the perfusion pump can include one or more cassette pumps. Other types of pumps are also contemplated by the present teachings. In one embodiment, the tissue container assembly 309 includes a removable tissue platform that isolates the tissue from a reservoir of perfusion fluid. In one embodiment, the removable tissue platform allows for coupling of the tissue to input and output fluid paths. The tissue platform allows for initial intubation of the tissue, since intubation can be performed away from the perfusion system, after which the tissue and platform are taken into the perfusion system and simply plugged in.The tissue platform allows for the tissue to be positioned and secured with a removable fitting. In this way, the tissue platform fitting can simply be uncoupled from the tissue container without the need to untubulate when the tissue is ready to be removed for transplantation. The tissue container assembly 309 includes a sample port and various disposable sensors. The tissue container assembly 309 includes a perfusate reservoir. In one embodiment, the reservoir is refilled with output from the tissue, nutrients and medicines. Refilling is based on the volume of discarded output, if any. Tubing 311 connects the various parts of the disposable assembly 113A to each other through tubing and appropriate connectors to form a closed loop and avoid environmental contamination. The output assembly 313 includes at least one vial for holding the output as it is measured and evaluated as described herein. The vial can be transparent for visual evaluation of the output. The disposable sensor 315 can include a sensor in contact with the tissue and / or the perfusate. The sampler 317 receives the output from the tissue and makes the output available for online or offline sampling. The disposable subassembly 303 includes components such as, but not limited to, an oxygenator, a hood mount, and tissue straps. The oxygenator provides oxygen to the perfusate. The hood mount provides a surface for an environmental barrier to be mated with the tissue container. The tissue straps maintain the position of the tissue on the tissue platform.

[0058] 1F, the flow and data / control / electrical connections of an exemplary configuration of a system of the present teachings are shown. In one embodiment, a controller 279 controls the sequencing of events that move perfusion fluid, medications and nutrients from one point to another. Starting from a perfusion fluid reservoir 284, perfusion fluid flows into and through a perfusion pump 275, where the pressure of the perfusion fluid is measured in-line by a pump pressure sensor 273 before the perfusion fluid enters an oxygenator 271. The oxygenated perfusion fluid flows into a heat exchanger 285, where the temperature of the perfusion fluid is adjusted to a desired level and then assessed by an in-line sensor 291. Air bubbles are removed by an air trap 293, and the in-line flow rate is measured by a flow meter 295. The oxygenated, bubble-free and thermally conditioned perfusion fluid is pumped through a connector to which the tissue is attached and into the tissue in a tissue holder 283. The tissue processes the perfusion fluid by producing an output. A portion of the output exits the tissue through an orifice in the tissue itself, such as a ureter in a kidney, and some fluid becomes available based on the process. The output that exits the tissue through the tissue orifice is pumped to the output assembly as described herein. In one embodiment, the other output fluid follows a fluid ramp into the reservoir 284. The fluid ramp allows for a soft landing of the output fluid in the reservoir 284 to avoid damage to the contents of the perfusion fluid. The loop continues with the perfusion fluid pumped into the perfusion pump 275. In one embodiment, the controller 279 tracks the output that is not returned to the tank 284. The pumping action of the drip pump 299 allows for equal amounts of perfusion fluid and nutrients / medications 297 to be added to the reservoir 284. In one embodiment, the system includes a number of different types of drip pumps, some specific for delivery of medicines and some specific for delivery of nutrients. In one embodiment, the controller 279 receives data from the sensor 287 and activates the thermal regulation 289 based on the data. In one embodiment, the controller 279 receives data from the sensors 291, the air trap 293 and the flow meter 295 and adjusts the properties, flow rate and possibly flow volume based on this data.In one embodiment, an operator can perform manual inspection of data from the sensors and can adjust, for example, but not limited to, medications, nutrients, temperature, flow rate, oxygenation, and flow volume in the perfusion fluid to maintain tissue viability. The sensors collect data such as, but not limited to, glucose, dissolved oxygen, temperature, pH, and oxygen saturation.

[0059] 2A-2I, various views of an exemplary configuration system 20024 of the system of the present teachings are shown. System 20024 includes assemblies and components such as durable enclosure assembly 20034 (FIG. 2A), lid housing 30177, thermal regulation assembly 20035 (FIG. 2A), disposable assembly 20028 (FIG. 2A), and pneumatic infusion pump assembly 20026, which are described in detail herein. Other components include sensor cover 30181 (FIG. 2B), sensor mount 30180 (FIG. 2B), durable system shell 30169 (FIG. 2B), enclosure plate 30147 (FIG. 2B), locking carriage front 30187 (FIG. 2B), cassette pump component 31107 (FIG. 2B), and output flow chamber 30128 (FIG. 2B). Most of the components are surrounded by an enclosure plate, for example enclosure plate 30147, which forms the tissue durable system shell 30169. The shell 30169 and lid housing 30177 combine to enclose most of the system's components. The durable assembly 20034 and disposable assembly 20028 are coupled together by the interaction of a locking shaft (not shown in FIGS. 2A and 2B) and a locking carriage 30187 with a spring 139 (FIG. 2B). The locking carriage 30187 (FIG. 2B) couples the durable assembly 20034 (FIG. 2A) and the disposable assembly 20028 (FIG. 2A) when in the position shown in FIG. 2B, i.e., seated to the left in the cavity 140 (FIG. 2B). In this position, the locking carriage 30187 (FIG. 2B) is held in place by the extended spring 139 (FIG. 2B). Contracting the spring 139 (FIG. 2B) releases the locking carriage 30187 (FIG. 2B) and advances it to the right within the cavity 140 (FIG. 2B), releasing the coupling between the durable assembly 20034 (FIG. 2A) and the disposable assembly 20028 (FIG. 2A).

[0060] 2A-2I, the sensor cover 30181 (FIG. 2B) and sensor mount 30180 (FIG. 2B) provide a mounting and protective location for a sensor that can monitor the health of the tissue within the tissue container. For example, a camera can be used to continuously monitor the visual aspects of the tissue. Other sensors can monitor the tissue as well, all providing data to the controller. In order for the visual sensor to properly view the tissue, there must be transparency to one or more desired frequencies within the barrier between the durable components (mount and sensor) and the tissue. Additionally, over time, reasons that may cause the barrier to cloud are addressed within the system to ensure the barrier remains clear. For example, condensation may inhibit transparency. In one embodiment, to address the issue of condensation, a heating element can be placed within the barrier to reduce condensation. Other methods of addressing condensation include chemical treatment and insulation.

[0061] 2A-2I, an output flow chamber 30128 receives the output from the tissue in the tissue container. In one embodiment, a t-connector into which the output flows can be used to control the flow and hold the output in the flow chamber 30128. In one embodiment, pinch valves 30085A and 30085B can be closed to hold the output. In either case, the output is held in the chamber 30128 until the level sensor 30049A reports that the desired output level has been reached. This signals the opening of either or both of the t-connector and / or one or more pinch valves. In the illustrated system, once the pinch valve 30085A opens, the output flows into the waste reservoir 131. In this case, the controller can signal that a replenishment of the fluid in the amount measured in the chamber 30128 may be required. When the pinch valve 30085B is open, the output flows back to the tissue container reservoir (not shown in FIGS. 2A and 2B), forming a closed loop that may never require replenishment of perfusate. When the level sensor 30049B reports that the output has reached a preselected level, the output release is complete and the pinch valve is closed. Although two variations for the output flow are shown, the system of the present teachings contemplates more or less variations. As shown in FIG. 2B, the output exits the tissue container through a tubing connector. Inside the tissue container, the tissue is positioned in a tissue holder that allows for the orifice of the tissue to be cannulated with a fluid connector, as described herein. For example, once the kidney is positioned on the tissue holder, the ureter can be cannulated using tubing with a fluid connector.

[0062] 2A-2I, an exemplary user interface device is shown in the form of a display 129. The display 129 may be an output-only device or an input / output device, perhaps a touch screen. The display 129 may be wired or wireless. Other forms of user interfaces, such as, but not limited to, handheld devices, laptop computers, desktop computers, etc., may allow for remote monitoring and operation.

[0063] 2A-2I, for example, medications and nutrients can be infused into the perfusion fluid by at least one infusion pump assembly 20026. As shown in FIG. 2B, the infused fluid enters the tissue container above the level of the reservoir. The perfusion fluid exits the reservoir near the bottom of the tissue container. The controller sequences the events that occur with the infusion pumps, thus delivering the nutrients and medications in a timely manner. In one embodiment, the pump 21055pi delivers the infusion fluid at a rate and volume different from that characteristic of the infusion pump 20026. In one embodiment, some or all of the infusion pumps can be controlled separately from each other and from the controller-managed pumps, perhaps allowing for asynchronous operation with the controller-managed pumps. Advantages of such a configuration include manual override of medication delivery.

[0064] 3A-3B, there are shown components of the durable assembly 20034 on the exterior (FIG. 3A) and interior (FIG. 3B) of the shell 30169 (FIG. 3A). Enclosure plates 30144, 30145, 30146 and 30148 form part of the surrounding shell 30169 as discussed herein, on which are mounted accessory fixtures such as hooks 133 and USB hub mount / monitor mount 143. The shell 30169 includes a cavity 355 that captures a disposable tissue container 30076 (FIG. 3B). The tissue container 30076 (FIG. 3B) is held in place by the container shell 30184 and container locking mechanisms 30171 (FIG. 3A) and 30172 (FIG. 3A). Shown in this configuration is an output level sensor mounting spacer 30189 onto which the level sensors 30049A and 30049B (FIG. 2B) are mounted. The spacer 30189 is constructed to space the level sensors to accommodate the desired level trigger. The spacer 30189 can include an adjustable mounting location for the level sensor 40035, allowing for adjustment of the output volume measurement without the need for tools. The durable components can include a pinch valve 40037 mounted with a pinch valve mount 30085 (FIG. 3B). The infusion pump mount 30056 (FIG. 3A) provides a suitable slide-in mounting option for the infusion pump 21055pi (FIG. 2B). A variety of mounting geometries, pump sizes and shapes, and mount numbers are contemplated by the present teachings. A gas fitting 30134 allows gas to flow through the mass flow controller into the oxygenator 40005 (FIG. 2B). A pump 31107 (FIG. 2B) couples to the pump bracket 30004, which provides an interface between the pneumatic system and the pump 31107 (FIG. 2B).

[0065] 3C, the locking carriage 30187, spring 139 and locking shaft 30185 (FIG. 3B) as shown in FIG. 3C enable a secure coupling between the pump 31107 (FIG. 2B) and the pump bracket 30004 (FIG. 3B). Specifically, when the spring 139 is in the depressed position as shown, the locking carriage 30187 presses against the shaft spring 359, forcing the locking carriage 30187 towards the locking shaft guide 30186 and pressing against the shaft spring 359. In this configuration, the disposable and durable components are securely engaged to form an environmental barrier that protects the durable components from perfusion fluid leakage while allowing the disposable and durable components to interact between the disposable assembly 20028 (FIG. 2A) and the durable assembly 20034 (FIG. 2A). Specifically, the locking shaft 30185 is mounted within a locking shaft clamp 363 (FIG. 4B) that is part of the disposable assembly 20028 (FIG. 2A), while the shaft guide 30186 is assembled onto the durable assembly 20034 (FIG. 2A). When the spring 139 is withdrawn, as illustrated by arrow 138, the locking carriage 30187 is forced by the shaft spring 359, as shown by arrow 136, away from the locking shaft guide 30186. At this point, the durable and disposable assemblies are released from one another. This feature can be used to easily replace the disposable components once tissue assessment and maintenance is completed for a particular tissue.

[0066] 3D, one possible method for measuring the power level in the output container 30051, among many others contemplated by the present teachings, includes a visual sensor 375 that reports the height of a float 379 related to an average power level 377. Shown in FIG. 3D are two different power levels, each of which can trigger the activity of the input and output valves and measurements of the output characteristics.

[0067] 4A-4B, a disposable assembly 20028 is shown. The disposable assembly 20028 includes a front component subassembly 20029, including, but not limited to, a tissue container 20023, a drip assembly 20041, and a perfusion subassembly, and an output monitor assembly 20040. Connecting these parts to form a closed fluid loop is tubing. In one embodiment, perfusion fluid is moved through the closed loop by at least one perfusion pump, while nutrients and medications are infused into the perfusion fluid by at least one infusion pump. In one embodiment, a single type of pump is used for both perfusion and infusion. In one embodiment, perfusion fluid is moved by at least one first type of cassette pump, and medications and nutrients are infused by at least one second type of cassette pump. In one embodiment, medications are infused by a first infusion pump, while nutrients are infused by a second infusion pump. In one embodiment, the operation of the at least one perfusion pump and the at least one infusion pump is controlled by a controller. In one embodiment, the operation of the at least one perfusion pump is controlled by a first controller and the operation of the at least one infusion pump is controlled by a second controller. In one embodiment, the operation of the first at least one infusion pump is controlled by a first controller and the operation of the second at least one infusion pump is controlled by a second controller. In one embodiment, the first controller and / or the second controller can be implemented by an application that is remote to the system of the present teachings. In one embodiment, for example, tubing 40093 can couple additional pumps to the tissue container 20023 to deliver infusion fluid. In one embodiment, depending on the characteristics of the output, the output monitor 20040 can deliver the tissue output to the drain bag 131 and / or the tissue container 20023.

[0068] 4C, the flow of fluid in the exemplary configuration is illustrated by the arrows in FIG. 4C. Starting from fluid in a reservoir (not shown) in the tissue container 30076, the perfusion fluid exits the tissue container 30076 in tubing associated with arrow 207, enters the perfusion pump 20005, and is pumped through / out of the perfusion pump 20005 in the direction of arrows 367 / 369 / 365. The perfusion fluid proceeds past sensors in the direction of arrow 195, past pressure sensor 30126 and possibly other sensors, into the oxygenator 40058 in the direction of arrow 197, and into the heat exchange area 371 (FIG. 11B) in the direction of arrow 203. The perfusion fluid exits the heat exchange area 371 (FIG. 11B) in the direction of arrow 187, passes through a sensor such as a pressure sensor in the direction of arrow 191, and enters the bubble trap 30088. The perfusion fluid exits the bubble trap 30088 in the direction of arrow 193, passes through the tube guides 179 and 181, passes through the durable flow meter 141 (FIG. 3A), in the direction of arrow 189, and through the connector 183 into the cannulated tissue. Fluid associated with the function of the tissue drains into the reservoir, and closed-loop perfusion fluid movement continues. If desired, output from the cannulated orifice of the tissue can flow from the tissue in the direction of arrow 373 into the output monitor 30051. For example, depending on the condition of the output, the fluid in the output monitor 30051 can proceed in the direction of arrow 201 to the drain bag 131 (FIG. 4A) or back to the reservoir in the direction of arrow 205. A vent line T-connected to the line connecting the output monitor 30051 and the tissue container 30076 includes a sterile filter that vents to atmosphere. In one embodiment, one end of the vent line is connected to the tissue container and the other end is connected to a pump that is used to establish a slightly negative pressure inside the tissue container, just below atmospheric pressure. In one embodiment, pressure in the tissue container that is slightly lower than venous pressure mimics an interstitial pressure that is slightly negative relative to venous pressure, promoting integrity within the vein and preventing kinking and collapsing of the vein. Other flow paths are contemplated by exemplary configurations of the present teachings. Alternative flow paths can be initiated "manually" or automatically.In one embodiment, a user interface may display possible flow paths and allow the user to select a flow path. In one embodiment, a controller may access the recipe and / or user selected flow paths and open and close valves associated with the pneumatic assembly to move perfusate and / or infused materials in a path, possibly different than the path depicted. Technology associated with the perfusion pump 20005 is described in U.S. Patent No. 9,999,717, filed June 19, 2018, to DEKA Products Limited Partnership, entitled "System and Method for Detecting Disconnection of Vascular Access," which is incorporated herein by reference in its entirety. To provide pulsatile flow, a pause is allowed between delivery to the first and second pump chambers to allow pressure to drop to a desired magnitude. The delivery volume is adjusted to the target desired beats per minute rate. In one embodiment, the chamber pressure valve may be closed before the fluid valve to emulate a sawtooth law.

[0069] 5A-5E, a first type of infusion pump configuration is shown. The depicted infusion pump follows the same process as perfusion pump 20005 (FIG. 4B), but unlike perfusion pump 20005, only requires a single chamber to deliver intermittent boluses. Infusion pump 20026 includes an infusion pump cover 30111, an infusion pump intermediate base 30110, an infusion pump pneumatic cover 30109, and a gasket 31110 adapted to prevent leakage between pump intermediate base 30110 and pneumatic cover 30109. The technology associated with the second type of infusion pump 21055pi (FIG. 2B) is described in U.S. Patent Application Publication No. 2021 / 0393870 to DEKA Products Limited Partnership, entitled "Infusion Pump Assembly," published Dec. 23, 2021, and incorporated herein by reference in its entirety.

[0070] 6, an exemplary configuration of the pneumatic pumping assembly 20036 is shown. An air supply tank 30099pl supplies compressed or low pressure air in the accumulation tank manifold block 30009, which supplies compressed or vacuum air to the regulator manifold block 30008. For each supply tank 30099pl, there is one array of valves 40000 / valve controls 50002 / pressure sensors 50003 / H-chamber pneumatic manifold block 30011 / H-valve pneumatic manifold block 30010, and one array for the manifold block 30008. The manifold blocks are surrounded by a pumping manifold end cap 30003 and assembled on a pneumatic base plate 30151. The pneumatic assembly is connected to an electronic control board via electronic connections provided by a breakout board 40049. A pneumatic pumping assembly 20036 drives the pumping cassette of the exemplary configuration, and the controller selects which valves on the pumping cassette to activate based on any or all of user input, recipe values, and sensor input. A pneumatic pump 40034 provides compressed air within the system. A vacuum pump provides low pressure air within the system.

[0071] 7, a top view of several durable components is shown. A mass flow controller 217 establishes a steady gas flow by controlling the mass flow rate for pneumatic pump control and to supply the gas mixture to the perfusate. Any mass flow controller having the desired accuracy, control range, repeatability, and response time can be used. Portions of mounting and framing components are shown that allow the exemplary configuration to fit into a relatively small footprint while incorporating both durable and disposable aspects, such as mounting guide rails 30152, tissue container locking base 30171 / 30172, pinch valve mount 30085, output level sensor mounting spacer 30189, tissue container surrounding shell 30184, pneumatic infusion pump durable arm 30163, infusion pump mount 30056, USB hub 215, I2C expansion board, and flow meter 141. Other durable components include, for example, pinch valve 40037 configured to control fluid flow based on controller commands. The display in the exemplary configuration is mounted and oriented according to the mounting plate 211, the display monitor ball base 137 and the socket arm 135. The enclosure lid can be raised and lowered with the aid of a hinged lid support 213.

[0072] 8, an exemplary configuration of electronics assembly 20025 is shown. Exemplary electronics include power supply 219, power and relay board 50006, interface board 50005, and processor development board 40053. Other circuit boards not shown are one or more CPUs and one or more network interfaces. Optionally, a GPU may also be included.

[0073] 9A-9C, a durable lid assembly 20038 (FIG. 9A) is shown. The durable lid assembly 20038 (FIG. 9A) is provided over a tissue container to allow for visual and other monitoring of the tissue. The assembly 20038 (FIG. 9A) includes a sensor cover 30181 (FIG. 9A), a sensor mount 30180 (FIG. 9A), a hood handle 30178 (FIG. 9A), and a hood housing 30177 (FIG. 9A). A sensor, such as a camera 40059 (FIG. 9A), is mounted on the sensor mount 30180 (FIG. 9A) and is protected from the environment by the sensor cover 30181 (FIG. 9A) and the hood housing 30177 (FIG. 9A). Other types of sensors, such as sensors that detect properties of the underlying tissue, can be mounted on the sensor mount 30180 (FIG. 9A). A transparent, translucent, or opaque environmental barrier separates the sensor from the underlying tissue. In one embodiment, the barrier is transparent to all or selected electromagnetic frequencies, or is transparent in a preselected window and opaque in other areas of the barrier, or is entirely opaque to all or certain frequencies. For vision-dependent sensors such as cameras, an exemplary configuration includes a heating assembly 20039 (FIG. 9B) to reduce condensation and maintain a clear view of the tissue. The heating assembly 20039 (FIG. 9B) includes a heating top surface 30182 (FIG. 9B) to protect the heating element 40080 (FIG. 9B), a thermal dowel 40081 (FIG. 9B) positioned to guide the heating element 40080 (FIG. 9B), and a thermal terminal 40082 (FIG. 9B) to connect the heating element 40080 (FIG. 9B) to a power source.

[0074] 10A-10E, there is shown a tissue container assembly 20023. The tissue container assembly 20023 includes an environmental enclosure, a tissue container, and disposables for perfusate thermal control. The tissue container 30076 is covered by a lid 30108, where a gasket 30168 provides an environmental seal between the tissue container 30076 and the lid 30108. Placed inside the tissue container 30076 is a tissue holder 30129 (FIGS. 10A and 10E). The tissue holder 30129 (FIG. 10E) is a removable platform on which tissue can be placed and intubated if necessary. After the tissue is positioned on the removable platform, the tissue and platform are placed inside the tissue container 30076 and remain in a sealed environment until the maintenance and assessment process is completed, for example, until the tissue is implanted. Each tissue platform 30129 (FIG. 10E) is configured for a group of tissue types or one specific tissue type, with cavities and cannulation opportunities positioned according to the physiology of the tissue type. The exemplary tissue holder 30129 (FIG. 10E) is configured to accommodate at least a kidney. Other tissue types can be accommodated as well. The cannula assembly 40077-1 / 40077-2 (FIG. 10C / D), when coupled with tissue, directs perfusion fluid from outside the tissue container through the connectors 227 / 229 (FIG. 10A) and tubing into the tissue and directs tissue output from the tissue to outside the tissue container, forming at least one closed circulation loop. The connectors can include, for example, barbed and luer connectors. A tissue placement mat 30137 (FIG. 10A) and tissue retention gasket 30136 (FIG. 10A) hold the tissue in place on the tissue holder 30129 (FIG. 10E). Beneath the tissue holder 30129, and therefore the tissue, is a perfusate reservoir as described herein with respect to perfusate flow. In one embodiment, a heat exchanger 335 (FIG. 10B) is integrated with the tissue container. In one embodiment, the heat exchanger sheet 231 (FIG. 10D) and the heat exchanger 335 (FIG. 10D) are separate components. The combination is used in conjunction with a thermal plate assembly 20035 (FIG. 11C) to regulate the thermal profile of the perfusate in the circulation loop.Inside the tissue container 30076 (FIG. 10A) is an output ramp 345 (FIG. 10B) that provides gentle deposition of fluid from the tissue into the perfusate tank.

[0075] 10F-10K, one implementation of components that together securely lock a disposable tissue container within a durable mount is shown. Now referring to FIG. 10F, swinging the door 30184 of the shell surrounding the container from an open position (not shown) to a closed position (FIG. 10F) secures the tissue container 30076 within the durable enclosure and places the tissue container 30076 in thermal communication with the heating plate assembly 20035. The durable container locking mechanism base 30171 / 30172 (FIGS. 10G / H) is formed to receive the geometry of the base of the tissue container 30076 (FIG. 10I). In one embodiment, the base 30171 / 30172 (FIGS. 10G / H) and the base of the tissue container 30076 can be jointly formed into any geometry. In one embodiment, the base 30171 / 30172 is formed as a single component. In one embodiment, the base 30171 / 30172 (FIG. 10G / H) includes separate components to accommodate different sizes and shapes of tissue containers. In one embodiment, the tissue container 30076 includes rails 381 / 383 (FIG. 10I) that engage guides 385 (FIG. 10G) on the container locking camshaft 30173 (FIG. 10H) that engage container locking torsion pivot 30175 (FIG. 10H). To set up the system configuration of the present teachings, the rails 381 / 383 (FIG. 10I) are engaged with the guides 385 (FIG. 10G) and the tissue container 30076 (FIG. 10I) is moved onto the heating plate assembly 20035 (FIG. 10F) to a predetermined position inside the durable enclosure. Once the tissue container 30076 (FIG. 10I) is fully in place, the shell door 30184 (FIG. 10J / K) is moved from an open position (not shown) to a position where the shell door 30184 (FIG. 10J / K) is flush with the tissue container 30076 (FIG. 10I) and the other components of the arrangement. As the shell door 30184 (FIG. 10J / K) moves from the open position to the closed position, the pins 391 / 393 (FIG. 10H) engage the pin runs 387 / 389 (FIG. 10K) causing rotation of the locking camshafts 30173 (FIG. 10H) (one on each of the container locking mechanism bases 30171 / 30172 (FIG. 10H)).The rotation exerts a force on the rails 381 / 383 (FIG. 10I), thus securing the tissue container 30076 (FIG. 10I) firmly in thermal coupling with the heating plate assembly 20035 (FIG. 10F). The tissue container 30076 (FIG. 10I) is locked in place when the shell door 30184 (FIG. 10F) is closed by the locking torsion pivot 30175 (FIG. 10H). Upon opening the shell door 30184 (FIG. 10F), the cam shaft 30173 (FIG. 10H) is rotated in the opposite direction, unlocking the torsion pivot 30175 (FIG. 10H) and releasing the tissue container 30076 (FIG. 10I). The tissue container 30076 (FIG. 10I) is, in some configurations, a disposable component, removed and replaced once tissue maintenance is completed.

[0076] 11A-11F, a disposable tissue container 30076 is shown in association with a durable thermal conditioning assembly 20035 and a heating plate mounting bracket 30135 (FIG. 11D). The thermal conditioning assembly 20035 includes a cartridge heater 40062 (FIG. 11B) located inside the thermal conditioning plate 30132 (FIG. 11B) for measuring temperature and controlling the thermal conditioning plate 30132 (FIG. 11B), as well as an oximeter breakout 263 (FIG. 11C), an oximeter 40011 (FIG. 11D), an oximeter mount 245 (FIG. 11D), a sensor retainer 259 (FIG. 11C), a fiber optic connector 265 (FIG. 11C), a temperature sensor mount 243 (FIG. 11D), and an IR temperature sensor 40055 (FIG. 11C). An O-ring 241 (FIG. 11D) seals the durable heat plate assembly 20035 (FIG. 11C) from environmental ingress.

[0077] 12, the tissue strap 30136 includes arms configured to accommodate various tissue sizes. After the tissue is positioned, the tissue strap 30136 is placed over the tissue and the arms are held in place by slots on the tissue platform that secure the tissue strap 30136.

[0078] 13A-13C, a second exemplary configuration of disposable and durable components of a tissue container is shown. The second configuration includes a tank thermal regulation assembly 20037 (FIG. 13B) that includes insulation 30143 and thermal regulation elements 30140 / 30141 / 30142 around a tissue container 30076 for the purpose of achieving thermal and moisture control of the tissue. Shown is a tissue holder 30077 and tissue 30136.

[0079] 14A-14C, a third exemplary configuration of disposable and durable components of the tissue container is shown. The third configuration includes a tank thermal control panel 237 (FIG. 14B), a tank thermal control overmold 235 (FIG. 14B), and a tank thermal control insulation 239 (FIG. 14B), one surrounding the other and all surrounding the tissue container 30076. The tissue platform includes merlons 339 (FIG. 14C) and tube guides 349 (FIG. 14A) and crenellations 337 (FIG. 14C), which are used to advance the intubation tubing from the tissue to the connectors that provide a fluid path from the exterior and interior of the tissue container 30076 to the tissue and an external destination, respectively. Fluid can flow into the reservoir of the tissue container 30076 through cavity 343 (FIG. 14C).

[0080] 15, a second configuration of the tissue container hood 20027 is shown. In this configuration, an illumination device is taken into account. Light blocking plates 30121 / 30122 and light box 30124 manage the illumination of the tissue. Additionally, window heat regulation 30119 and window heat regulation top 30120 manage condensation on the disposable tissue container lid 30108 (FIG. 10A) to maintain a clear view of the tissue for the sensor 40059.

[0081] Those skilled in the art can devise various variations and modifications without departing from the present disclosure. Therefore, the present disclosure is intended to cover all such variations, modifications and differences. Moreover, although some exemplary configurations of the present disclosure have been shown in the drawings and / or discussed herein, the present disclosure is not intended to be limited thereto, and the present disclosure has as broad a scope as the art will permit, and the specification is intended to be read accordingly. Thus, the above description should not be considered limiting, but merely illustrative of a particular configuration. Moreover, those skilled in the art will envision other modifications that fall within the scope and spirit of the claims appended hereto. Other elements, steps, methods and techniques that are insubstantial different from those described above and / or in the appended claims are also intended to fall within the scope of the present disclosure.

[0082] The drawings are presented only to demonstrate some embodiments of the present disclosure, and the drawings described are merely exemplary and non-limiting. In the drawings, for illustrative purposes, the size of some elements may be exaggerated and not drawn to a particular scale. Moreover, elements shown in the drawings having the same number may be identical or similar elements, depending on the context.

[0083] When the term "comprising" is used in the present specification and claims, it does not exclude other elements or steps. When an indefinite or definite article, such as "a", "an" or "the", is used when referring to a singular noun, this includes a plurality of that noun, unless something is specifically stated otherwise. 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.

[0084] Moreover, terms such as "first," "second," "third," and the like, whether used herein or in the claims, are provided to distinguish between similar elements and not necessarily to describe an order or chronology. It should be understood that terms so used are interchangeable under appropriate circumstances (unless otherwise expressly disclosed) and that the disclosure described herein is capable of operating in orders and / or arrangements other than those described or illustrated herein.

Claims

1. In a supportive platform to sustain the organization: a tissue container for containing the tissue; at least one perfusion loop operably coupled to perfuse the tissue; a support assembly that engages the tissue enclosure and the at least one perfusion loop to drive the perfusion loop and control perfusion of the tissue; Including, The tissue container comprises: a wall forming an enclosure; a tissue platform within the enclosure for receiving and supporting the tissue; a fluid reservoir within the enclosure for containing and storing a fluid associated with perfusion of the tissue; It further includes The support platform further comprising a void between at least one of the fluid reservoirs and the tissue platform.

2. The support platform of claim 1 , wherein at least one of the tissue container, the at least one perfusion loop, and the support assembly is disposable.

3. The support platform of claim 1 , wherein at least one of the tissue container, the at least one perfusion loop, and the support assembly is reusable.

4. The support platform of claim 1 , wherein the tissue container and the at least one perfusion loop are disposable.

5. The support platform of claim 1 , wherein the support assembly is reusable.

6. The tissue platform comprises: Multiple surfaces, The support platform of claim 1 further comprising:

7. The support platform of claim 1 , wherein the perfusion loop is in fluid communication with the fluid reservoir.

8. The support platform of claim 7 , wherein the perfusion loop is operably coupled to an artery of the tissue.

9. The support platform of claim 8 , wherein the perfusion loop circulates fluid from the fluid reservoir into the arteries to perfuse the tissue, and the fluid exits the veins of the tissue and returns to the fluid reservoir.

10. at least one enclosure connector configured to operably couple the tissue platform to the fluid reservoir; at least one perfusion connector configured to operably couple the tissue with a perfusion loop, the perfusion loop providing perfusion of the tissue; at least one output connector configured to operably couple the tissue with an output fluid route, the output fluid route accommodating output from the tissue; The support platform of claim 1 further comprising:

11. The support platform of claim 10 , wherein the at least one enclosure connector, the at least one perfusion connector, and the at least one output connector comprise disposable materials.

12. The support platform of claim 10, wherein at least one of the tissue platform, the at least one enclosure connector, the at least one perfusion connector, and the at least one output connector comprises a geometry adapted for a particular tissue.

13. a wiring and / or tubing management structure within the tissue container for supporting wiring and / or tubing away from the tissue; The support platform of claim 1 further comprising:

14. The support platform of claim 13 , wherein the wiring and / or piping management structures are selected from the group consisting of merlons, standoff features, crenellated edges, clamps, cutouts, and combinations thereof.

15. a tissue enclosure hood covering a tissue container, the tissue enclosure hood configured, together with a connector and a seal, to operably couple at least one of the tissue enclosure hoods to the tissue container to protect the tissue from environmental contamination; The support platform of claim 1 further comprising:

16. 5. The tissue enclosure hood comprising: at least one sensor configured to collect sensor data about the tissue; at least one mounting device configured to position the at least one sensor within a preselected range from the tissue; 16. The support platform of claim 15, further comprising:

17. The support platform of claim 16 , wherein the at least one sensor comprises a wired sensor.

18. The support platform of claim 16 , wherein the at least one sensor comprises a wireless sensor.

19. The support platform of claim 16 , wherein the at least one sensor mount is configured to mount the at least one sensor outside the tissue container.

20. The support platform of claim 16 , wherein the at least one sensor mount is configured to mount the at least one sensor inside the tissue container.

21. 17. The support platform of claim 16, wherein the at least one sensor provides sensor data to at least one controller, the at least one controller configured to drive a display, the display configured to present the sensor data.

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