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Opto-acoustic sensor for protein conformational fingerprinting beyond concentration degeneracy: analytical modelling
Optics Express
|August 14, 2026
Summary
This study introduces a novel dual-observable sensor for precise protein analysis. It combines spectroscopy and acoustic force to create a unique conformational fingerprint, achieving over 99% accuracy in protein discrimination.
Area of Science:
- Biophysics
- Analytical Chemistry
- Spectroscopy
Background:
- Existing biosensors struggle to differentiate protein concentration from conformation.
- Accurate protein characterization is crucial for diagnostics and drug development.
Purpose of the Study:
- To develop a novel biosensing platform that resolves concentration-conformation degeneracy.
- To create a label-free method for quantitative protein sensing.
Main Methods:
- Combining whispering-gallery-mode lasing spectroscopy with acoustic radiation force modulation in microdroplets.
- Utilizing time-resolved protein concentration and recovery rates to form a 2D conformational fingerprint.
- Employing Monte Carlo analysis and Support Vector Machine (SVM) classification for data interpretation.
Main Results:
- The dual-observable sensor successfully distinguishes protein concentration from conformational states.
- Protein concentration dynamics are governed by acoustic contrast, while recovery reflects hydrodynamic radius.
- Conformational states were discriminated with over 99% accuracy.
Conclusions:
- The proposed platform offers a novel, label-free approach for quantitative protein sensing.
- This method overcomes limitations of existing biosensors by providing a unique conformational fingerprint.
- The technology has potential applications in diagnostics and biochemical analysis.
