LIVE · Laser-Based Infrared Vibrational Electric-Field Fingerprinting

A biological system’s phenotype and the evolution thereof are mirrored in molecular composition. The complexity of biological samples, however, renders quantitative, multivariate molecular probing challenging, in particular for non-destructive, label-free approaches. Vibrational spectroscopies capture signals from all molecular bonds exchanging energy with an optical excitation, delivering highly-specific optical fingerprints of samples in their native state, to which virtually all molecules contribute. Yet, while infrared (IR) spectroscopies profit from large vibrational cross-sections, technical limitations of IR radiation sources and detection have so far limited their applicability to real-world biomedical settings, in particular in the context of highly absorbing water (ubiquitous in biological samples). The project LIVE aims at harnessing the unparalleled control over light, on the level of individual optical-field oscillations, afforded by femtosecond lasers and nonlinear optics, to overcome current technological limitations and advance IR spectroscopy toward the fundamental limits set by the nature of light and, thus, toward the ultimate sensitivity, specificity and throughput achievable in optical vibrational fingerprinting. To this end, we envisage the development of powerful sources of fewcycle pulses covering the entire IR molecular fingerprint region (500–4000 cm-1) with utmost electric-field waveform stability, and of innovative electric-field sampling techniques capturing nearly all photons emitted by linearly and nonlinearly excited molecular vibrations. The host institution permits immediate validation of these developments for real-world biomedical samples, including, high-throughput vibrational fingerprinting of individual cells in flow cytometry, spectral tissue histopathology and high-resolution, high-sensitivity breath gas monitoring. Thus, LIVE promises direct impact on patients’ health, deeply rooted in basic photonics research.