. The objective of this revised Phase I SBIR proposal is to develop a subcellular spatial resolution imaging capability for organic compounds in support of neuroscience research. The proposed imaging capability will be based on modification of an existing """"""""nanoprobe"""""""" instrument that uses Ga+ ion beam sputtering to desorb neutral analyte molecules from biological tissues followed by laser postionization and analysis by time-of- flight mass spectrometry. The goals of the Phase I research were to improve the spatial resolution of the existing instrumentation, test the relative merits of nanosecond vs. femtosecond lasers for postionization, test cryogenic sample preparation procedures for their ability to preserve biological information in a vacuum environment, and demonstrate the feasibility of imaging a neurotransmitter such as dopamine in a biological system. Phase II will involve implementation of cryogenic sample preparation techniques and an optimum laser postionization system on the nanoprobe instrument. The instruments capabilities will then be tested in a series of experiments aimed at elucidating molecular mechanism of exocystosis and the spatial distribution of neurotransmitter release. In Phase III, postionization nanoprobe analyses and instrumentation will be made available to the biomedical, pharmaceutical and other analytical research communities.
