Back

A practical guide to time-resolved fluorescence microscopy and spectroscopy

Clark, B. S.; Silvernail, I.; Gordon, K.; Castaneda, J. F.; Morgan, A. N.; Rolband, L. A.; LeBlanc, S. J.

2024-03-29 biophysics
10.1101/2024.01.25.577300 bioRxiv
Show abstract

Time-correlated single photon counting (TCSPC) coupled with confocal microscopy is a versatile biophysical tool that enables real-time monitoring of biomolecular dynamics across many timescales. With TCSPC, Fluorescence correlation spectroscopy (FCS) and pulsed interleaved excitation-Forster resonance energy transfer (PIE-FRET) are collected simultaneously on diffusing molecules to extract diffusion characteristics and proximity information. This article is a guide to calibrating FCS and PIE-FRET measurements with several biological samples including liposomes, streptavidin-coated quantum dots, proteins, and nucleic acids for reliable determination of diffusion coefficients and FRET efficiency. The FRET efficiency results are also compared to surface-attached single molecules using fluorescence lifetime imaging microscopy (FLIM-FRET). Combining the methods is a powerful approach to revealing mechanistic details of biological processes and pathways.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.