Protein detection in blood with single-molecule imaging

Chih Ping Mao, Shih Chin Wang, Yu Pin Su, Ssu Hsueh Tseng, Liangmei He, Annie A. Wu, Richard B.S. Roden, Jie Xiao, Chien Fu Hung

Research output: Contribution to journalArticlepeer-review


The ability to characterize individual biomarker protein molecules in patient blood samples could enable diagnosis of diseases at an earlier stage, when treatment is typically more effective. Single-molecule imaging offers a promising approach to accomplish this goal. However, thus far, single-molecule imaging methods have not been translated into the clinical setting. The detection limit of these methods has been confined to the picomolar (10-12 M) range, several orders of magnitude higher than the circulating concentrations of biomarker proteins present in many diseases. Here, we describe single-molecule augmented capture (SMAC), a single-molecule imaging technique to quantify and characterize individual protein molecules of interest down to the subfemtomolar (<10-15 M) range. We demonstrate SMAC in a variety of applications with human blood samples, including the analysis of disease-associated secreted proteins, membrane proteins, and rare intracellular proteins. SMAC opens the door to the application of single-molecule imaging in noninvasive disease profiling.

Original languageEnglish (US)
Article numbereabg6522
JournalScience Advances
Issue number33
StatePublished - Aug 2021

ASJC Scopus subject areas

  • General


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