Abstract: The first atomic view of strongly driven phase transitions (Siwick et al, Science 2003) illustrated the mechanism to control nucleation growth to nm scales (nucleation as small as 10 molecules). To take advantage of this new insight, a laser concept was developed based on a seeded Optical Parametric Amplifier and microchip laser technology to provide a compact robust source engineered to excite the OH stretch of water in biological tissue for use in laser surgery. The pulses must be shorter than the time for nucleation growth but longer than peak power limitations to dielectric breakdown. The pulses are deliberately made to be in the picosecond domain to avoid peak power conditions leading to multiphoton ionization and potential long term health risk issues related to all ionizing radiation effects. This feature distinguishes this approach from femtosecond laser applications. The laser ablation process is driven within resonant 1-photon transitions in which the strong localization of the laser energy is provided by the extremely strong absorption of water in the 3 micron range. The strong absorption of water provides intrinsic confinement of the ablation process to the micron dimensions of a single cell in the longitudinal direction with lateral confinement defined by the laser focus conditions. Lasers currently in clinical use involve either massive tissue damage due to shock wave and thermal transport resulting in burning and tissue necrosis or is highly ionizing. The Picosecond InfraRed (PIRL) scalpel readily cuts all tissues types and most importantly, the damage to surrounding tissue is negligible, with no discernable scar tissue formation – and stronger tensile strength than scar tissue. The long held promise of the laser for achieving the fundamental (cell) limit to surgery has now been realized. In the process, it was also discovered that entire proteins, even protein complexes, are ejected into the gas phase intact. This observation has been rationalized on the basis that the whole process of vibrational excitation and coupling to translational motion driving ablation occurs faster than even collisional exchange of the excited water with the constituent proteins and the ensuing ablation occurs on time scales much faster than thermal fragmentation of the protein signatures. This new laser ablation mechanism referred to as Desorption by Impulsive Vibrational Excitation (DIVE) provides a new means for in situ spatial mapping with mass spectroscopy in which very detailed molecular fingerprints of different tissue types can be retrieved, as a “frozen snapshot” of the proteome, with cancer margins delineated. On the fly, molecular level pathology during surgery is now well within reach.
Equally important, by exploiting the technology developed for ultrabright electron sources for lighting up atomic motions, it is possible to push mass spectroscopy by several orders of magnitude to true single molecule detection limits for the earliest possible disease detection. The basic concepts for the laser ablation process, as well as applications for mass spectroscopy as feedback in laser surgery, and towards fundamental limits in spatial mapping and biodiagnostics, will be discussed.
Free Lunch will be provided!