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Updated: Jun 14, 2026

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An antibody-based molecular switch for continuous small-molecule biosensing.

Ian A P Thompson1, Jason Saunders1, Liwei Zheng2

  • 1Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.

Science Advances
|September 22, 2023
PubMed
Summary
This summary is machine-generated.

We developed antibody-switches for real-time, sample-free biosensing of small molecules. This modular design enables continuous optical detection of biomarkers like cortisol in biological samples.

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Area of Science:

  • Biomedical Engineering
  • Molecular Biology
  • Analytical Chemistry

Background:

  • Continuous monitoring of small-molecule biomarkers is crucial for diagnostics.
  • Existing biosensing methods often require sample preparation and lack real-time detection capabilities.

Purpose of the Study:

  • To develop a generalizable method for creating antibody-based biosensors capable of continuous, real-time, and sample-preparation-free detection of small-molecule biomarkers.
  • To engineer "antibody-switches" for optical biosensing applications.

Main Methods:

  • Antibodies were engineered into target-responsive "antibody-switches" by linking them to a molecular competitor via a DNA scaffold.
  • Competitive binding of the target analyte induced scaffold switching and fluorescent signal changes.
  • The system was demonstrated for sensing digoxigenin and cortisol in undiluted plasma.
  • Sensitivity modulation was achieved by altering the molecular competitor for cortisol detection.
  • The antibody-switch was integrated with a fiber optic sensor for continuous monitoring.

Main Results:

  • Rapid, sample-preparation-free sensing of digoxigenin and cortisol in undiluted plasma was achieved.
  • The cortisol switch demonstrated tunable sensitivity across a wide concentration range (3.3 nM to 3.3 mM).
  • Continuous sensing of cortisol in buffer and blood with a time resolution under 5 minutes was successfully demonstrated.

Conclusions:

  • The developed antibody-switch platform offers a modular and versatile approach for continuous biosensing.
  • This technology has the potential to enable the development of real-time biosensors for a wide array of small-molecule biomarkers.
  • The method eliminates the need for sample preparation, simplifying biosensing procedures.