Developing Single-Molecule Augmented Capture (SMAC) to Detect Biomarkers in Human Blood

The ability to accurately identify and characterize individual biomarker proteins in patient blood samples could improve diagnosis of diseases at an earlier stage, when treatment is typically more effective. Current blood tests, including ultra-sensitive assays, depend on ensemble measurements which are hampered by background detection errors1-6. Single-molecule imaging approaches, by contrast, directly inspect individual target protein molecules, potentially offering much greater sensitivity and reliability7. However, the detection limit of single-molecule imaging has thus far been confined to the picomolar (10-12 M) range in cultured cell lysate, and these approaches have not been previously translatable to clinical samples7,8. In Chapter 1, we stated comparison of existing detection methods and the need of a new technology. Then we described Single-Molecule Augmented Capture (SMAC), a single-molecule imaging technique to visualize and quantify individual proteins-of-interest down to the sub-femtomolar (