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Updated: Aug 1, 2025

Monitoring Conformational Dynamics of Single Unmodified Proteins using Plasmonic Nanotweezers
Published on: March 21, 2025
Photonic-Plasmonic Coupling Enhanced Fluorescence Enabling Digital-Resolution Ultrasensitive Protein Detection
Priyash Barya1,2, Yanyu Xiong1,3, Skye Shepherd3,4
1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
This study introduces a novel method combining plasmonic and photonic modes to significantly amplify fluorophore signals, enabling detection of single molecules. This breakthrough enhances sensitivity in bioassays, improving diagnostic capabilities for diseases like cancer and sepsis.
Area of Science:
- Biophotonics
- Nanotechnology
- Biomedical Diagnostics
Background:
- Fluorophore-based assays are crucial in life sciences but often limited by weak emission intensity.
- High signal-to-noise ratios typically require numerous labeled molecules for detection.
Purpose of the Study:
- To develop a method for significantly boosting fluorophore emission intensity.
- To enable sensitive detection and digital counting of individual target molecules.
Main Methods:
- Synergistic coupling of plasmonic nanoparticle (PF) and photonic crystal (PC) modes.
- Optimally matching PF and PC resonant modes with fluorescent dye spectra.
- Characterizing a sandwich immunoassay for human interleukin-6.
Main Results:
- Achieved a 52-fold improvement in signal intensity by matching plasmonic and photonic modes.
- Enabled observation and digital counting of individual PFs, representing single target molecules.
- Demonstrated a limit of detection of 10 fg mL⁻¹ in buffer and 100 fg mL⁻¹ in human plasma.
Conclusions:
- The plasmonic-photonic coupling method dramatically enhances fluorophore signal intensity.
- This technique allows for single-molecule detection, significantly improving assay sensitivity.
- The method shows promise for advanced diagnostics, particularly for biomarkers like interleukin-6.
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