Tandem mass spectrometry (MS/MS) will be utilized to develop methods of improved specificity, sensitivity and speed to obtain structural and analytical information from larger molecules of biomedical importance. Instrumentation development will primarily involve the Fourier-transform mass spectrometer, exploiting its potentialities for high resolution MS/MS and high sensitivity for multichannel recording of full spectra, and investigating methods for efficient ion trapping. Methods studied for pulsed ionization of large molecules, especially those to produce multiply charged ions, will include SIMS with greater than or equal to 25 keV Cs+ (or larger) ions, UV laser desorption, and Cf-252 plasma desorption. Methods studied for dissociation of MS-I separated ions will include CAD at surfaces, UV photodissociation, and neutralization of one charge on a multiply charged ion. Advantages of MS/MS/MS for mixtures of peptides and other large molecules will be explored, possibly with two different ion dissociation methods. Fundamental research will continue on unimolecular ion dissociations, especially of multiply-charged and negative ions.
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