This disclosure is related to methods of preserving biological samples such as organs, and tissue. The present disclosure relates to methods of subzero preservation of biological tissue samples, such as entire organs from mammals, e.g., humans. The present disclosure is based, at least in part, on the discovery that biological tissue samples can be supercooled while minimizing formation of ice crystals by reducing liquid-air interfaces and lowering the melting point of the tissue samples, e.g., organs, or liquid in the tissue samples by use of cryoprotective agents while ensuring uniform distribution of cryoprotective agents throughout the biological sample by using improved perfusion techniques.

The invention provides integrated Organ-on-Chip microphysiological systems representations of living Organs and support structures for such microphysiological systems.

The invention provides, in various embodiments, devices and methods relating to ex-vivo organ care. In certain embodiments, the invention relates to aortic cannulas for use in perfusion systems to return perfusate to the heart or delivering perfusate from the heart while the organ is sustained ex vivo at physiologic or near-physiologic conditions.

The present disclosure includes a system to preserve tissue and associated methods. The system can include a portable oxygen source to provide oxygen and apply a pressure gradient to a flow of the oxygen, an organ preservation system having an inlet to fluidly couple to vasculature of the tissue, and an oxygen line to fluidly couple the portable oxygen source to the organ preservation system at the inlet, wherein the portable oxygen source is to apply the pressure gradient to pump fluid containing the oxygen through the organ preservation system.

In a method of ventilating excised lungs, a ventilation gas is supplied to an airway of a lung and a vacuum is formed around the lung. A quality of the vacuum is varied between a lower level and a higher level to cause the lung to breathe, while the pressure of the ventilation gas supplied to the airway is regulated to maintain a positive airway pressure in the airway of the lung. The vacuum may be cyclically varied between the two vacuum levels. The levels may be maintained substantially constant over a period of time, or one or both of the lower and higher levels may be adjusted during ventilation. The lung may be placed in a sealed chamber, and a vacuum is formed in the chamber around the lung.

The present disclosure relates to devices and methods for increasing the probability of a successful organ donation by decreasing organs' warm ischemia time. Furthermore, the present disclosure relates to increasing the pool of eligible donors, including donors who had prior chest surgeries or prior abdominal surgeries. The present disclosure provides a catheter extending through a cannula, wherein the cannula delivers cold perfusion fluid and the catheter blocks the aorta, forcing the cold perfusion fluid to pass to organs in the donor's abdomen. The present disclosure further provides for advancing the catheter from a retracted position to an extended position, and creating a watertight seal at the cannula to prevent backflow of cold perfusion fluid.

Systems and methods of the invention generally relate to prolonging viability of bodily tissue, especially an organ such as a lung, by adjusting pressure as needed to maintain a constant pressure within the organ even during external pressure fluctuations due, for example, to transportation of the organ in an airplane. Gas passing into and out of the organ may be conditioned to prolong tissue viability.

The disclosure provides, in various embodiments, systems, devices and methods relating to ex-vivo organ care. In certain embodiments, the disclosure relates to maintaining an organ ex-vivo at near-physiologic conditions. The present application describes, for example, a method for using lactate measurement in the arterial and the venous blood lines of the Organ Care System Heart perfusion device to evaluate, for example, the: 1) overall perfusion status of an isolated heart; 2) metabolic status of an isolated heart; and 3) overall vascular patency of an isolated donor heart. This aspect of the present disclosure may use, for example, the property of myocardial cell's unique ability to produce/generate lactate when they are starved for oxygen and metabolize/utilize lactate for energy production when they are well perfused with oxygen.

The disclosure provides, in various embodiments, systems, devices and methods relating to ex-vivo organ care. In certain embodiments, the disclosure relates to maintaining an organ ex-vivo at near physiologic conditions. In certain embodiments, the disclosure relates to placing an ex-vivo heart in a chamber of a portable organ care system; providing, via a pump, a pulsatile flow of a perfusion fluid to the ex-vivo heart; measuring, with a sensor, one or more physiologic characteristics of the ex-vivo heart while the ex-vivo heart is beating; and operating the pump in response to the one or more physiologic characteristics.

A system for maintaining immune separation between an extracorporeal organ and a bioreactor includes an organ chamber holding an extracorporeal organ and a cross-circulation circuit connecting the extracorporeal organ with the bioreactor. The cross-circulation circuit can direct the flow of perfusate therebetween. The bioreactor may include an allogeneic or xenogeneic host organism. for example a swine host. The cross-circulation circuit comprises at least one semipermeable membrane configured to establish an immunologic barrier to maintain separation between the immune responses of the bioreactor and the extracorporeal organ and to maintain physiologic stability of the bioreactor and the extracorporeal organ. The immune-reduced cross-circulation circuit may improve extracorporeal organ viability for research and transplant purposes.