This proposal is for a new Q-TRAP 4000 LC-MS/MS system, both to enhance the existing capabilities of our mass spectrometry resources and eventually to replace the aging QuattroLC that is currently in use. The current mass spectrometry resources are located at the Central Instrument Facility (CIF), the Pharmacology Core of the Karmanos Cancer Institute (KCI), and the Proteomics Core of Wayne State University. Of these, only the CIF and Pharmacology Core offer LC-MS/MS capability. One of the major areas of the participating faculty's research involves identification and/or quantitation of small molecules such as, lipid mediators of inflammation, anticancer natural products from dietary ingredients, etc. The other major area of interest is the signal transduction pertaining to cancer. The research projects currently utilize the existing mass spectrometry resources distributed among three core facilities on campus. While the Time of Flight (TOF) instruments available at CIF and Proteomics Core are used for the protein identification work, the triple quadrupole instruments at CIF and Pharmacology Core are used for structure identification and LC-MS quantitation. Of these, the LC-MS of Pharmacology Core is primarily used by KCI researchers for drug metabolism, pharmacokinetics, and clinical trials. The QuattroLC at the CIF is the primary resource for small molecule analysis by the investigators participating in this proposal. While this instrument is still functional and heavily used by these investigators for small molecule quantitation and peptide sequencing work, its sensitivity in the nanomolar range is inadequate for the analysis and identification of biomarkers. Moreover, this instrument is more than seven years old and is frequently in need of service. Many of the projects that will be served by the proposed Q-TRAP LC- MS/MS system require detection limits in the fmol range as well as fast MRM scan capability for the identification and quantification of biomarkers of inflammation and cancer. Additionally, the proteomics capability of the new system along with the Nanospray ion source, would be immensely valuable for the research projects in peptide sequencing to identify chemically cross linked domains of interacting proteins. Research projects of the faculty participating in this proposal are continuously funded by NIH, some for more than two decades, and the Q-TRAP 4000 LC-MS/MS system would be an indispensable resource for their continued success. Additionally, this instrument will catalyze the setup of a much needed Lipidomics core facility at Wayne State University.
The type of LC-MS/MS system requested is used for the measurement of small molecule analytes present at extremely low concentrations in biological samples. These include biomarkers of inflammation, cancer, and related diseases. Identification of novel biomarkers and validation of known biomarkers of diseases that facilitate early detection, diagnosis, and treatment is the primary purpose of this instrument.
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