Label-Free Optical Differentiation of Single Diffusing Amino Acids at Picomolar Concentrations

Area of Science:

• Photonics
• Biotechnology
• Analytical Chemistry

Background:

• Label-free detection methods offer valuable molecular insights.
• High-finesse microcavities enhance light-matter interactions for sensitive measurements.

Purpose of the Study:

• To achieve label-free detection of single amino acids using fiber-based Fabry-Pérot microcavities (FFPCs).
• To demonstrate the differentiation capabilities of FFPCs for various amino acids and small peptides in solution.
• To assess the potential of FFPCs for protein sequencing applications.

Main Methods:

• Utilizing locked high-finesse fiber-based Fabry-Pérot microcavities (FFPCs) to amplify light-matter interactions.
• Varying FFPC sensitivity to differentiate molecules at the single-molecule level.
• Analyzing signal bursts in FFPC transmission for molecular detection events.

Main Results:

• Achieved label-free detection down to the single-amino acid level, including glycine.
• Successfully differentiated subsets of amino acids and small peptides (e.g., peptide vs. tryptophan, tryptophan vs. histidine).
• Demonstrated detection in solution at picomolar (pM) concentrations.

Conclusions:

• FFPCs enable highly sensitive and differentiating label-free detection of single amino acids and peptides.
• The observed neuron-like signal bursts correlate with optical and thermal parameter coupling.
• FFPCs represent a promising photonic technology for advancing single-molecule protein sequencing.