Next generation design, development, and evaluation of cryoprobes for minimally invasive surgery and solid cancer therapeutics: in silico and computational studies.

Cryosurgery is a widely regarded minimally invasive surgery for treatment of various types of cancers. It involves destruction of cancer cells within a limited spatial domain by exposing them to very low temperatures while minimizing injury to surrounding peripheral healthy tissues. Surprisingly, despite increasing demands for cryosurgery, there has been limited innovation in the design of cryoprobes, particularly in solid tumors (e.g., breast, prostate, and lung cancers). For advances in cancer therapeutics, integrative biology research can illuminate the mechanistic interface between a surgical cryoprobe and its tissue site of action. Here, we describe the design and development of three novel low pressure liquid nitrogen (LN2) cryoprobes with different physical dimensions and the parameters that determine their effectiveness experimentally, using water and bio-gel as the phase changing mediums. Smaller diameter low pressure probes produced lesser cryogenic injury. Vapor Separator is found to be an effective means (particularly for smaller diameter probes) to remove the vapor lock in the LN2 low pressure cryoprobes and also to reduce the precooling time. The low pressure LN2 cryoprobes produced lower probe temperatures and consequently larger and faster iceball growth for low cooling loads. Additionally, a numerical code was written in MATLAB based on the Enthalpy method to simulate the bio-heat transfer in a cryosurgical process. The numerical code is validated by analytical solution, laboratory experiments, and data from an in vivo cryosurgery. The developed numerical code is presented herein to illustrate that LN2 cryoprobes capable of producing lower probe temperatures produce more efficient cryosurgical operation by reducing the buffer zone and duration of surgery.This is the first report, to the best of our knowledge, on design of the next generation of LN2 surgical cryoprobes. These new surgical cryoprobes offer potentials for future preclinical and clinical testing in solid cancers.