Flexible minimally invasive coherent anti-Stokes Raman spectroscopy (CARS) measurement method with tapered optical fiber probe for single-cell application

We proposed and demonstrated a flexible, endoscopic, and minimally invasive coherent anti-Raman Stokes scattering (CARS) measurement method for single-cell application, employing a tapered optical fiber probe. A few-mode fiber (FMF), whose generated four-wave mixing band is out of CARS signals, was selected to fabricate tapered optical fiber probes, deliver CARS excitation pulses, and collect CARS signals. The adiabatic tapered fiber probe with a diameter of 11.61 μm can focus CARS excitation lights without mismatch at the focal point. The measurements for proof-of-concept were made with methanol, ethanol, cyclohexane, and acetone injected into simulated cells. The experimental results show that the tapered optical fiber probe can detect carbon-hydrogen (C–H) bond-rich substances and their concentration. To our best knowledge, this optical fiber probe provides the minimum size among probes for detecting CARS signals. These results pave the way for minimally invasive live-cell detection in the future.