Optofluidic FRET Lasers and Their Applications in Novel Photonic Devices and Biochemical Sensing

Abstract

Incorporating fluorescence resonance energy transfer (FRET) into a laser cavity can increase the sensitivity of FRET-based biochemical sensors due to the nonlinear dependence of the lasing output on the FRET parameters. Here, we carry out a comprehensive theoretical analysis of optofluidic FRET lasers based on a Fabry–Perot microcavity using a rate equation model. We compare conceptually distinct cases of donor and acceptor molecules diffusing freely in a bulk solution versus molecules connected by a fixed-length linker and show that the latter arrangement is especially well suited for sensing of low-concentration analytes. By comparing FRET lasing-based sensors with conventional FRET sensors, we show that for optimal pump fluence and FRET-pair concentration, FRET lasing can lead to more than 100-fold enhancement in detection sensitivities of conformational changes in the Forster radius range. We also show that for optimal experimental conditions, donor and acceptor emission intensities become over 20-fold more sensitive to FRET-pair concentration changes in the presence of FRET lasing. We study the dependence of the sensitivity enhancement on the cavity Q-factor. We show that the highest enhancements can be obtained for Q-factors between $10^4\text{--}10^6$ , and enhancement values decrease for Q-factors above $10^6$ due to the radiative energy transfer in the cavity.