Two-photon fluorescence correlation spectroscopy through a dual-clad optical fiber
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Updated: Jul 2, 2026

Dual-Color Fluorescence Cross-Correlation Spectroscopy to Study Protein-Protein Interaction and Protein Dynamics in Live Cells
Published on: December 11, 2021
Yu-Chung Chang1, Jing Yong Ye, Thommey Thomas
1Center for Ultrafast Optical Science, University of Michigan, 2200 Bonisteel Blvd., Ann Arbor, MI 48109-2099, USA. ycchang@umich.edu
Abstract:
We report on the utilization of a dual-clad optical fiber for two-photon excited fluorescence correlation spectroscopy (FCS). High excitation efficiency is obtained by sending prechirped ultrafast pulses through the single-mode core of the fiber, while the fluorescence collection efficiency is enhanced because of the larger numerical aperture of the inner cladding. We show that the utilization of a dual-clad fiber is critical for ultrasensitive two-photon fluorescence detection. Our system has the ability to detect fluorescent nanospheres as small as 12 nm in radius. Quantum dots of radius 7 nm are also measured and show excellent signal to noise ratio. The particle sizes obtained from the fiber FCS system were confirmed by measurements using a commercial dynamic light scattering (DLS) system.
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