Date of Completion

11-24-2015

Embargo Period

11-24-2015

Keywords

proteomics, mass spectrometry, biomarker, derivatization

Major Advisor

Dr. Xudong Yao

Associate Advisor

Dr. Christian Brueckner

Associate Advisor

Dr. Alfredo Angeles-Boza

Associate Advisor

Dr. Jie He

Associate Advisor

Dr. Fatma Selampinar

Field of Study

Chemistry

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

The development of disease protein biomarkers and their use in clinical research have great applications in the diagnosis, prognosis, and treatment of complex diseases. Mass spectrometry methods for protein biomarker quantitation have recently gained importance in the early stages of the biomarker pipeline, but their application in the validation phase is limited by their low sample throughput. The technology of ultrathroughput mass spectrometry (uMS) transforms the intrinsic quantitation capability of MS analyte multiplexing to sample multiplexing. Herein, the novel MS-based bioanalytical platform utilized decoupled use of isotopic quantitation reference standard and non-isotopic mass coding reagents to enable one-experiment quantitation of a target protein biomarker candidate in multiple non-depleted serum samples. Screened repository of signal-enhancing peptidyl reagents enabled N-in-1 analyses for a cost-effective, high sample throughput strategy for protein biomarker validation applications. The signal enhancement and sample multiplexing capability of the derivatization technique were then further investigated within proteomic profiling and derived towards a global quantitative approach.

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