In order to improve the quality of differential cancer diagnostics and metastatic tumor origination using protein and carbohydrate biomarker detection of patient biopsies, BioAnalyte Inc. and collaborators at MGH and JHMI propose to develop laser capture microdissection (LCM) as a sample preparation system for the biomolecular profiling capabilities of MALDI-ToF mass spectrometry. The work will first optimize protocols for collecting cells from mammalian tissue for MALDI-ToF analysis. For differential diagnostics we will analyze several LCM-selected cells from the tumor collection at MGH representing a variety of cancers will be used to determine the MALDI-ToF profiles of transformed and adjoining normal tissue. For identification of a metastatic tumor with its primary, we will make MALDI-ToF MS profiles of LCM-selected cells from metastatic cancers and compare them to profiles of LCM-selected cells in the original tissue. New software about written for general MALDI-ToF chemometric analysis of profiles WII be implemented here to determine fingerprint regions of the mass spectra in each of its applications. Hardware to optimize the coupling of LCM transfer caps to MALDI-ToF ionization sources will be developed.
