Protein Detection by Counting Molecules.

Clinical Chemistry
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Duffy DC and Walt DR

Clin Chem. 2019 Published May 2019 DOI: 10.1373/clinchem.2018.298653 

Article

Featured Article: Rissin DM, Kan CW, Campbell TG, Stuart SC, Fournier DR, Song L, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 2010;28:595–9.3

Proteins are the functional units of life. Berson et al. opened the field of protein measurements with the development of RIAs in the 1950s (1). In 1971, Engvall and Perlmann reported the ELISA (2) that has since been the staple for protein measurements. In 2010, when our article featured here was published, there were 325 proteins detectable in blood, of which 171 were Food and Drug Administration–approved tests of clinical value (3). Most of these proteins are measured using ELISA. When the human genome was sequenced, it was predicted that there should be nearly 4000 proteins in the human bloodstream (4). Where are the missing proteins? ELISA enabled detection down to picomolar concentrations, but this limit of quantification was insufficient to fully access the human blood proteome. The single-molecule array (Simoa) …