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Protein Dynamics in Living Cells

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Proteome-wide Quantification of Labeling Homogeneity at the Single Molecule Level

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Published on: April 19, 2019

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

Randall Goldsmith¹, Julia Rasch², Anna Clayborn²

¹University of Wisconsin-Madison.

Research Square

|April 10, 2026

Summary

Researchers achieved label-free, single-amino acid detection using fiber-based Fabry-Pérot microcavities (FFPCs). This photonic technology can differentiate amino acids and peptides in solution, paving the way for protein sequencing.

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Published on: August 19, 2013

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.