Monitoring optogenetic stimulation of light-sensitive stem cells using a twin-core fiber-based Mach-Zehnder interferometer

Abstract

The application of optical fibers in optogenetics is rapidly expanding due to their compactness, cost-effectiveness, sensitivity, and accuracy. This paper introduces a twin-core optical fiber (TCF) sensor employing a Mach-Zehnder interferometer (MZI) to monitor the optogenetic response of opsin-expressing human dental pulp stem cells (hDPSCs) based on refractive index (RI) measuring. In order to improve the RI sensitivity of the sensor, an in-fiber Mach-Zeander modulator formed using TCF optics segments can detect changes in the RI in the surrounding medium, and in order to improve the RI sensitivity of the sensor, it is proposed to etch one side of the TCF cladding. The RI sensitivity of the sensor was obtained 233.62 nm/RIU in the range of 1.33–1.4 RIU and 870.01 nm/RIU in the range of 1.4–1.43 RIU, R² = 0.99. simulation results show that in terms of sensor sensitivity and spectral response, there is a good agreement between the theoretical and experimental results, indicating that the TCF-MZI sensor can perform optical neural recording. In vitro experiments monitored wavelength changes in opsin-expressing and non-opsin-expressing in human dental pulp stem cells (hDPSCs) during optogenetic stimulation with 473 nm pulsed illumination. The results revealed that optical stimulation of ChR2 opsin-expressing hDPSCs leads to active the light sensitive ion channel and changing the effective RI of the surrounding medium. The neural activity is driven by changes in intracellular and extracellular ion concentrations, which lead to alterations in the RI of the cell medium RI variations detectable by the sensor. The novel sensor structure demonstrated its ability to detect RI changes in the cell medium during optogenetic stimulation and fiber optic sensors can be a good candidate for optical recording of the neural activity. Beyond these in vivo applications, label free fiber optic biosensors-based IR measurement can be used for all optical multifunctional probe in stimulation, recording, and sensing of neuroscience applications.