Mass tag-based mass spectrometric immunoassay and its bioanalysis applications

The sensitive and accurate determination of macromolecular biomarkers is in high demand for clinical diagnosis. Mass spectrometric immunoassay (MSIA) combines the advantages of immunoassay with mass spectrometry (MS) detection, which offers excellent specificity and sensitivity in bioanalysis and attracts more and more research attentions. Compared with the direct MS analysis, mass tag-based MSIA overcomes the limitation of the low ionization efficiency of biomacromolecules through the transformation of detection signal from biomacromolecule to the mass tag, and provides the possibility of highly sensitive detection. In this review, the comprehensive and essential developments of MSIA are summarized and categorized from the perspective of mass tags and their bioanalytical applications. The mass tags are introduced in three categories: inorganic molecules, organic molecules, and biomolecules and the applications of mass tag-based MSIA in bioanalysis are systematically reviewed. Finally, challenges of mass tag-based MSIA are summarized and the perspectives are proposed for their further developments and bioanalytical applications.