The objective of the proposed work is the development of a micro-machined cryosurgical instrument that utilizes a mixed-gas Joule-Thomson thermodynamic cycle to produce cryogenic tip temperatures. The device incorporates a micro-scale active valve and a composite recuperative heat exchanger in order to overcome limitations that currently limit cryosurgical instruments. The ultimate goal of this research is to provide surgeons with a cryosurgical probe that has significant advantages in terms of thermal performance, size, flexibility, and cost relative to the current state-of-the-art. The technical developments proposed here will enable MEMS technology, with all of its inherent advantages, to be brought to bear on the problem of cryosurgery. The cryoprobe wilJbe fabricated using conventional micro-fabrication techniques resulting in a low cost device that can be batch fabricated. Instrumentation and heaters to monitor and control the temperature field may be monolithically installed on the probe. The probe structure will be primarily silicon and glass and will therefore be compatible with magnetic resonance imaging, enabling real-time monitoring of cryosurgical procedures. During the R21 Phase of the project we will design and separately fabricate the active valve and recuperative heat exchanger. These components will be tested to demonstrate that they satisfy the requirements of the cryosurgical system. The R21 phase will culminate in a system level test that demonstrates the viability of the thermodynamic cycle and the reliability of the components. The goal of the R33 Phase is to utilize this technology base in order to design, fabricate, and demonstrate an integrated micro-fabricated cryosurgical probe. The demonstration probe will be packaged in a manner that is consistent with clinical usage. The ability of the probe to withstand pressure, thermal, and bending loads that are greater than those anticipated during usage will be demonstrated. The performance of the cryoprobe will be precisely measured in a thermal vacuum environment. Subsequent, in-vivo testing will occur in a gelatin solution and later in excised animal tissue in order to quantify the time and length scales associated with the freeze zone. Control algorithms that will enable automatic implementation of surgical protocols, defined in terms of freeze zone characteristics, will be developed and demonstrated.