Saving lives, limbs, food, and energy with isochoric cryopreservation

Transporting a human organ from donor to recipient is a race against time. Current methods involve packing the organ in ice and maintaining it just above freezing to prevent damage caused by the formation of ice crystals. At these temperatures, a heart can remain viable outside the body for only four to six hours, while a liver can last eight to 12. Isochoric cryopreservation, a technique invented by Boris Rubinsky, PhD ’81, a professor of bioengineering and mechanical engineering at UC Berkeley, extends this time to days.

COURTESY OF BORIS RUBINSKY

“The fundamentals came from my thermodynamics classes at MIT,” says Rubinsky, who studied under Professor Ernest G. Cravalho—a mentor he credits with shaping his career and in whose honor he established a best paper award in cryobiology.

“Everyone was attempting to cryopreserve organs under natural atmospheric conditions with constant pressure,” explains Rubinsky. “But thermodynamics are completely different in an isochoric system, where volume remains constant and pressure changes.” In such a system, he found, “ice and liquid water can coexist in thermodynamic equilibrium until about –21 °C, leaving 45% of the volume unfrozen at that temperature.” He adds, “If biological matter is sequestered in this unfrozen portion, it can be preserved at subfreezing temperatures without freezing.” 

This groundbreaking technique quickly gained attention from transplant surgeons and the military. “We received grants from DARPA, NASA, NSF, and USDA, among others, reflecting the vast range of potential applications,” says Rubinsky, who notes that isochoric freezing also holds “immense” promise for the food industry: “Replacing conventional freezing with an isochoric freezing process is like removing a million cars from the road—it’s that energy efficient.” He is now collaborating with NASA to design an isochoric chamber for transporting organoids to the space station, with the goal of generating a liver in zero gravity. 

Rubinsky holds more than 130 patents, many of which have been successfully commercialized. One is for the NanoKnife, a tissue ablation technology now widely used to treat prostate cancer, pancreatic cancer, and arrhythmia. NanoKnife is now being advanced by biomedical companies such as Medtronic and Boston Scientific. BioChoric, an isochoric cold storage startup he cofounded in 2023, is already valued at $70 million.  “I develop new technologies, make them available, and then move on,” he says with a laugh. “The fun is in creating, not making money.”