"The proposed research is based on a recent breakthrough in directly observing atomic motions during structural changes and in studying energy redistribution channels in liquid water on the femtosecond time scale. These studies provided the key insights that drove the development of a new laser concept for direct-drive laser ablation. By judicious choice of laser pulse parameters, it is now possible to selectively excite water molecules to act as a propellant to drive molecules into the gas phase faster than any other energy exchange mechanism or growth of nucleation sites to cause shock wave damage or other deleterious effects. With the resulting Picosecond Infrared Laser (PIRL) surgical tool, proof-of-principle studies have shown that it is possible to produce wound sizes at the fundamental limit of a single cell - with virtually no scar tissue formation. More than an order of magnitude reduction in the wound healing zone relative to the conventional scalpel has been achieved with complete healing. Equally important, the laser ablated molecules remain completely intact for determination of the tissue type. This is the first time it has been possible to drive intact proteins into the gas phase, in a matrix independent manner, for ultrasensitive detection using mass spectroscopy. The prospects for advancing both surgery and biodiagnostics to their respective fundamental limits of single cell precision and single molecule detection is within reach. This proposal represents a well coordinated effort involving medical researchers across a broad spectrum of disciplines to fully explore the applications of this new technology, from minimally invasive surgery with molecular signatures for feedback and on the fly guidance to prevent cutting critical structures, to in situ pathology and cancerous tissue identification, to detection of disease at the earliest possible stage from a single drop of body fluids. Such is the promise of this new technology."