Quantum Cascade Laser–Based Vibrational Circular Dichroism Imaging for Chiral Biosensing

Vibrational circular dichroism (VCD) is an established chiroptical technique that probes molecular handedness via differential IR absorption of left- and right-circularly polarized light. Quantum cascade lasers (QCLs) have revitalized VCD spectroscopy by delivering high-power, narrowband mid-IR sources that, combined with polarization-modulation strategies, have dramatically improved VCD sensitivity and speed-enabling imaging that was not previously attainable. We review the instrumental design of QCL-based VCD imaging and demonstrate its application to spatially resolved chiral biosensing. By mapping VCD signals with micrometer resolution, one can detect and differentiate protein secondary structures, monitor enantiomeric purity in pharmaceutical compounds, and visualize pathological tissue features without labels. We discuss practical challenges, including cell-window birefringence, polarization-sensitive detection, and data processing, and propose optimized configurations for robust imaging. Finally, we outline future directions for QCL-VCD systems and their integration with nonlinear chiroptical techniques, highlighting the potential of QCL-VCD imaging to transform chiral analysis in biological and clinical contexts.