Key mass spectrometry techniques used in clinical biomarker research

Abstract

Mass spectrometry has been playing an increasingly important role in various aspects of biomarker research, ranging from discovery of novel biomarkers to quantitative measurement of known biomarkers for clinical applications. Following a brief overview of multiple reaction monitoring (MRM)-based LC/MS approach, the gold standard for quantitative mass spectrometry, this chapter provides an overview of several emerging mass spectrometry techniques benefit from recent advances in mass spectrometry instrumentation and related technologies. These new techniques enable researchers to develop sensitive, specific, robust, and higher throughput biomarker assays for novel clinical applications. Multiple reaction monitoring cubed (MRM3) technique is capable of measuring analytes in complex matrices without extensive sample pretreatment. High-pressure, high-resolution separations with intelligent selection and multiplexing (PRISM) technique greatly increase the efficiency of complex sample analysis in a highly automatic fashion. High-resolution mass spectrometry (HRMS) enables the extraction of analyte information from complicated matrices with minimal efforts in method development. Parallel reaction monitoring (PRM) offers an enhanced MRM approach with better tolerance to background interference and the potential of achieving better detection limits. Microfluidic LC/MS utilizes low-flow LC to boost sensitivity tremendously and enables the detection of extremely low-abundance analytes. Stable isotope dilution mass spectrometry (SID-MS) enables accurate measurement of protein and peptide in biological matrices. These new technologies have changed the landscape of MS usage in clinical biomarker field and will continue to bring positive impact as more advanced tools become available.