Time-Domain Quantum Cascade Laser-Based Vibrational Circular Dichroism Spectroscopy with Linear Dichroism Monitoring

Vibrational circular dichroism (VCD) offers sensitive structural information at the molecular scale by measuring the differential absorption of left- and right circularly polarized light associated with molecular vibrational transitions, enabling determination of configuration and detection of higher-order asymmetry in biomolecules. With the development of high-brightness quantum cascade lasers (QCLs), opportunities have emerged for advancing instrumentation. However, implementing VCD with QCLs introduces complications due to VCD signals being orders of magnitude weaker than classic absorbance as well as laser fluctuations, amplified further by polarization artifacts arising from highly coherent illumination. In this work, we utilize digitally referenced detection (DRD) that performs per-pulse noise reduction, enabling time-domain acquisition of VCD signals from purely circularly polarized pulse pairs that are, in principle, free of polarization artifacts caused by linear dichroism (LD) and linear birefringence (LB). The method is further extended to simultaneously extract LD signals within the same polarization modulation cycle (∼20 μs), allowing real-time monitoring of molecular orientation information without system modifications. Finally, we compare VCD measurements obtained using the DRD-based approach versus conventional lock-in amplifier (LIA) demodulation, showing a 4-fold spectral signal-to-noise ratio (SNR) improvement when normalized to acquisition time and spectral band size. We further validate the artifact detection capabilities with various levels of LDLB effects through polymer films. These advances establish a robust framework for high-SNR, real-time VCD measurements with built-in detection of LDLB effects, paving the way for accurate analysis of complex chiral systems and enabling future applications in solid-state VCD and chirality imaging.