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Intrinsic Kinetic Control Enables Scalable and Ultrasensitive Single-Molecule Sensing.

Zhencai Xu1, Qiang Zeng2, Zhuoyin Liu3

  • 1College of Life Science, Qingdao University, Qingdao, Shandong 266071, China.

ACS Sensors
|October 9, 2025
PubMed
Summary
This summary is machine-generated.

A new dynamic single-molecule sensing (DSMS) platform uses optimized nanoparticle size and buffer conditions for ultrasensitive biomarker detection. This approach achieves femtomolar sensitivity for thrombin and HIV-1 p24 antigen without probe modification.

Keywords:
biomarker detectiondynamic single-molecule sensingintrinsic kinetic modelingionic strength engineeringnanoparticle size optimization

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Area of Science:

  • Biophysics
  • Nanotechnology
  • Biomarker Detection

Background:

  • Dynamic single-molecule sensing (DSMS) offers high sensitivity for molecular interactions.
  • Current DSMS platforms face limitations in simplicity and scalability due to probe redesign or external force modulation.
  • Optimizing intrinsic parameters is crucial for advancing DSMS technology.

Purpose of the Study:

  • To develop an intrinsically regulated DSMS platform for ultrasensitive biomarker detection.
  • To overcome the limitations of existing DSMS systems by optimizing nanoparticle size and buffer ionic strength.
  • To establish a scalable and robust sensing strategy for clinical diagnostics.

Main Methods:

  • Developed a theoretical model for kinetic regimes in DSMS.
  • Empirically optimized a DSMS system using average binding dwell time and total binding events.
  • Utilized 150 nm polystyrene nanoparticles and 150 mM NaCl buffer conditions.

Main Results:

  • Achieved femtomolar detection limits for thrombin (213.9 fM) and HIV-1 p24 antigen (4.3 fM).
  • Demonstrated excellent specificity in diluted serum using dwell-time filtering.
  • Validated the platform's robustness in complex biological matrices.

Conclusions:

  • The engineered DSMS platform enables efficient single-molecule sensing without probe modification or external actuation.
  • This strategy offers a scalable solution for high-performance biomarker detection.
  • The findings pave the way for advanced clinical diagnostics and point-of-care applications.