Picosecond Infrared Laser Ablation Mass Spectrometry for Rapid Characterization of Biological Tissues

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My overall research program aims to develop needs driven' enabling sensing' technologies to address unmet needs in the biomedical domain. This proposal describes engineering developments of a laser-based sensing molecular analysis platform capable of characterizing organic matter in a few seconds of laser interrogation and analysis time. The platform will include a wide array of applications in the areas of forensic and food science to rapid pathology, the latter being the focus of proposed validation herein as it addresses a clear unmet need. Sensing is achieved with Mass Spectrometry (MS) that can deliver a molecular complexity profile of the sample which, in combination with a library of complexity profiles, can be identified unambiguously and rapidly with MS. Ablative laser systems capable of desorptive extraction, to the gas phase, of sample molecular content are currently used in a number of MS based molecular analysis platforms. This proposal explores the utility of a specialized, pulsed mid-infrared (IR) laser system that harbours the most optimal conversion of the impulsively deposited vibrational energy to molecular libration. For water-rich samples such as biological tissues, molecular desorption with a Picosecond InfraRed Laser (PIRL) is a highly efficient process due to the strong coupling between libration and vibrational modes of water on this timescale. The bulk of the impulsive energy deposited into the vibrational mode of tissue water molecules is converted into desorption, liberating water and tissue constituent molecules, ejecting them to the gas phase. The process takes place faster than heat transfer from superheated water molecules to the surrounding sample molecules, leaving them intact. This proposal describes engineering, development and the integration of a hand held PIRL-MS probe for the specific purpose of rapid molecular fingerprinting of biological tissues and accelerated decision making; a probe that delivers rapidly information regarding tissue type, tissue chemistry, metabolic state, disease state such tumor type, subtype and disease site margins, based on real time analysis of laser liberated tissue chemical content. Relevant engineering principles will be leveraged to develop an optimized collection and ionization interface, further augmented with statistical analysis methods, and integration with tracking and positioning technologies towards a hand-held molecular profiling tool. Coupling the output of the statistical analysis with 3D positioning systems allows spatially encoded mass spectrometry results (i.e. classifiers) to visualize pathology through an augmented reality display platform. The bundled solution comprising the laser, MS analyzer, molecular fingerprint library, statistical analysis platform and navigation display for spatially encoded MS results will be validated using real world samples.