ReviewThe fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry
Section snippets
Immunoassays are imperfect
Ever since the description of the first immunoassay in the late 1950s (Yalow and Berson, 1960), the use of antibodies to measure the concentration of proteins and small molecules in clinical samples has been changing the face of medicine. The platform for immunoassays has evolved from its initial conception as a competitive radioimmunoassay to enzyme linked immunosorbent assays on plastic surfaces to sandwich liquid phase chemiluminescent immunometric assays using paramagnetic beads on
Could mass spectrometry be the answer?
In the 1980s, scientists at Yale described robust methods for ionizing intact molecules and introducing them into mass analyzers (Whitehouse et al., 1985). These ionization strategies combined with gas-phase fragmentation permitted the de novo identification of peptides and proteins from complex mixtures, thus birthing the field of proteomics. Later advances in electronics and architecture have made modern mass analyzers capable of directly detecting attomoles of analyte. With this level of
Potential pitfalls of LC-MS/MS in the clinical quantification of proteins
However exciting mass spectrometric assays for protein quantification might seem, they will undoubtedly have significant problems of their own. In this section we will highlight recognized issues with mass spectrometric assays, but we must keep in mind that unanticipated problems will also likely surface over time. Indeed, the abovementioned problems with immunoassays were only elucidated after years of clinical use.
Conclusions
Over the past five decades, we have learned that immunoassays can be used to help diagnose human disease. Sadly, we have also learned that immunoassays can hurt patients. It is important for clinicians to remember how immunoassays can give inaccurate results in many clinical situations. It is also important for the community as a whole to look for solutions, which may reside in novel detection technologies like tandem mass spectrometry. And as with all novel technologies, we must be prepared
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