Rapid Vibrational Circular Dichroism Spectroscopy via Synchronized Photoelastic Modulator-Quantum Cascade Laser Integration.

Accurate and rapid analysis of chirality is crucial for understanding biological processes and molecular interactions, yet traditional vibrational circular dichroism (VCD) techniques are limited by long acquisition times and low throughput. We present a quantum cascade laser (QCL)-based VCD system that integrates a photoelastic modulator (PEM) with pulsed laser sources, using precise temporal synchronization and a novel calibration method based on Welch's power spectral density analysis. This hardware-software integration enables real-time demodulation without the need for conventional lock-in amplifiers and achieves accurate, high-SNR VCD spectra of α-pinene (±) mixtures with high reproducibility. Real-time enantiomeric excess determination is achieved with a 10× improvement in speed and a 5× enhancement in SNR compared to conventional VCD methods. These advancements pave the way for high-throughput and nondestructive chiral analysis, with potential applications in biosensing, structural biology, and pharmaceutical research.