Mass Spectrometry Immunoassays

  • Mass spectrometry immunoassays (MSIAs) are powerful analytical techniques that combine the high specificity of immunoaffinity capture with the precision and sensitivity of mass spectrometry (MS) for the detection and quantification of target biomolecules. This hybrid approach enables the selective enrichment of low-abundance proteins or peptides from complex biological matrices such as blood, urine, or tissue extracts, followed by their accurate identification and measurement using mass spectrometric analysis.
  • The process typically begins with the use of antibodies that are specific to the target analyte. These antibodies are immobilized on solid supports—such as magnetic beads, pipette tips, or columns—and used to selectively bind and isolate the target molecule from the sample. After washing away unbound components, the captured proteins or peptides are eluted and introduced into a mass spectrometer, usually after enzymatic digestion if proteins are analyzed. The resulting mass spectra provide detailed molecular information, including mass-to-charge ratios, sequence data, and post-translational modifications.
  • MSIAs offer several advantages over traditional immunoassays like ELISA. While ELISAs rely on optical detection and can suffer from cross-reactivity and limited dynamic range, MSIAs provide higher specificity through mass-based detection and can distinguish between closely related isoforms, splice variants, or modified forms of proteins. Moreover, MSIAs can be multiplexed, allowing simultaneous analysis of multiple targets in a single run without the need for multiple antibodies or labels.
  • Applications of mass spectrometry immunoassays are growing in clinical diagnostics, biomarker discovery, pharmacokinetics, and proteomics research. They are particularly valuable in cases where absolute quantification, isoform differentiation, or validation of biomarkers is required. As mass spectrometry technology continues to evolve—becoming faster, more sensitive, and more accessible—MSIAs are poised to play an increasingly important role in precision medicine and personalized healthcare.
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