Dynamic single-molecule sensing by actively tuning binding kinetics for ultrasensitive biomarker detection

Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2120379119. doi: 10.1073/pnas.2120379119. Epub 2022 Mar 1.

Abstract

SignificanceThe detection of low-abundance molecular biomarkers is key to the liquid-biopsy-based disease diagnosis. Existing methods are limited by the affinity and specificity of recognition probes and the mass transportation of analyte molecules onto the sensor surfaces, resulting in insufficient sensitivity and long assay time. This work establishes a rapid and ultrasensitive approach by actively tuning binding kinetics and accelerating the mass transportation via nanoparticle micromanipulations. This is significant because it permits extremely sensitive measurements within clinically acceptable assay time. It is incubation-free, washing-free, and compatible with low- and high-affinity probes.

Keywords: biosensors; immunoassay; microRNA; single molecule; ultrasensitive.

MeSH terms

  • Binding Sites
  • Biomarkers / metabolism
  • Kinetics
  • Limit of Detection
  • Single Molecule Imaging / methods*
  • Thermodynamics

Substances

  • Biomarkers