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Attaching Biological Probes to Silica Optical Biosensors Using Silane Coupling Agents
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The Origin of Single-Molecule Sensitivity in Label-Free Solution-Phase Optical Microcavity Detection.

Carlos Andres Saavedra Salazar1, Daniel Sole-Barber1, Sushu Wan1

  • 1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.

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This study reveals how Fiber Fabry-Perot microcavities (FFPCs) achieve ultra-sensitive detection of single biomolecules. By operating FFPCs in an unstable state, minute molecular movements cause amplified signals, enabling label-free analysis.

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Area of Science:

  • Optics and Photonics
  • Biophysics
  • Analytical Chemistry

Background:

  • Fiber Fabry-Perot microcavities (FFPCs) enhance light-matter interactions.
  • Photothermal nonlinearities and Pound-Drever-Hall frequency locking are key to sensitive detection.

Purpose of the Study:

  • To elucidate the quantitative mechanism behind single-molecule sensitivity in FFPCs.
  • To achieve quantitative agreement between experimental observations and theoretical models.

Main Methods:

  • Utilizing a combination of experimental techniques and computational simulations.
  • Operating FFPCs in an unstable regime to exploit photothermal nonlinearities.
  • Employing Pound-Drever-Hall frequency locking for precise control.

Main Results:

  • Demonstrated a mechanism where rapid shifts between photothermal equilibria amplify responses to molecular perturbations.
  • Identified a 'molecular velocity filter window' for selective and amplified detection.
  • Achieved quantitative agreement between the model and experimental data.

Conclusions:

  • The developed model quantitatively explains single-molecule detection sensitivity.
  • The FFPC system can detect resonance fluctuations smaller than the microcavity line width.
  • The model provides a predictive tool for exploring single-molecule hydrodynamic behavior detection.