Electric fields for warming cryopreserved tissue

Vitrification is enabling successful cryopreservation of progressively larger organs. Heating the whole volume of an organ simultaneously instead of only the surface during recovery from vitrification has been vital to this success. Volumetric warming enables faster and more uniform warming. Faster warming reduces ice crystal growth, ice recrystallization, and toxic effects of cryoprotectants by reducing ice growth time and cryoprotectant exposure time during warming. Nanowarming of intravascular magnetic nanoparticles by alternating magnetic fields, and direct dielectric warming by alternating electric fields, have both been used successfully for volumetric warming of vitrified organs. Dielectric warming predates vitrification, having been studied intermittently in cryobiology since the 1950s. Most early research was empirical, using microwaves at 915 MHz or 2.45 GHz because of wide availability of magnetron generators and microwave ovens. With greater theoretical understanding, interest later grew in frequencies near 400 MHz and lower. Larger energy absorption and smaller wavelengths inside tissue warming from vitrification instead of thawing from freezing made optimum frequencies for vitrification even lower, below 100 MHz for organs more than 10 cm in diameter. Recent dielectric warming research has used 27, 40, and 55 MHz, achieving heating rates of 200 - 700 °C/min. The advantages of dielectric warming not being dependent upon exogenous particles or vascular volume, high energy efficiency, and ability to monitor temperature by impedance behavior during warming, are counterbalanced by the need for organ immersion before vitrification and pre-warming to a uniform starting temperature above the glass transition temperature. With measurements of two electrical properties of a vitrification solution, permittivity and loss factor as function of temperature, detailed theoretical analysis and modeling of dielectric warming is possible. Comparatively little research has been done on dielectric warming at frequencies optimal for vitrification. This review covers the history, theory, equipment types, practical aspects, and future directions of dielectric warming of cryopreserved tissue.