High Performance Secondary Ion Mass Spectrometer Upgrade of Advanced Scanning Ion Microprobe

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We propose a biological instrumentation development program aimed at a radical upgrade of the mass discrimination capability and secondary ion detection sensitivity of the University of Chicago high resolution Scanning Ion Microprobe (UC SIM). This is to be accomplished by replacing the existing RF quadrupole mass filter with a high performance magnetic sector mass spectrometer. The design and construction of appropriate transfer optics, and modification to the present secondary ion extraction system, together with high voltage and hardware construction, will be required to implement this goal. The pursuit of fundamental biological studies at a much improved level of performance with this instrument, that has already contributed substantial advances in many areas that benefit from imaging microanalysis, justifies the proposed upgrade. Established biologists from several academic institutions will collaborate with us in exciting applications of the upgraded microprobe, in all cases continuation and amplification of successful pilot experiments already carried out with the UC SIM. These applications will aim at: (a) Director mapping of the distribution of isotope-labelled nucleotides in human chromosomes and evaluation of the nucleotide content of fragile sites. (b) Identification of the mineral phases involved in bone formation and of the mechanism of bone resorption initiated by osteoclasts. This will entail experiments with Ca isotopes as tracers, and the detection and measurement of phosphorus. (c) Localization and kinetics of trace elements in tooth and bone tissues, relative to microstructure. Microstructural study of organs (bone, brain) affected by aluminum. (d) Study of the role of calcium in neuronal ischemia using retinal neurons as model system. These studies will make use of Ca isotopes and isotope-labelled nucleotides as tracers.