Noncontact Fiber Optic Probe for Clinical Applications of Raman Spectroscopy

Clinical applications of Raman spectroscopy (RS) typically rely on fiber optic probes that directly interface with the tissue site. These devices are designed with small diameters, enabling them to navigate narrow body cavities and seamlessly integrate into routine medical instruments. However, the performance of conventional RS fiber probes suffers during noncontact operation due to decreased collection efficiency and a larger laser spot size that restricts spatial precision. To address these limitations, a novel RS probe design is presented here that can efficiently collect both fingerprint (FP) and high-wavenumber (HW) regions of the Raman spectrum at an offset from the target tissue using a miniature lens at the probe tip. The development process began with stochastic light propagation simulations that served as a foundation for the device's expected performance improvements compared to a standard RS probe design, which were then experimentally verified. Lenses were fabricated from various materials, including fused silica, quartz, sapphire, and calcium fluoride, to assess the impact of aberrant lens emissions on the analysis of tissue Raman features within the FP and HW spectral regions. Signal quality metrics are reported from in vivo tissue using each type of lens, demonstrating that crystalline lenses best preserve the weak Raman signal generated by tissues during dual-region RS analysis. Still, the ideal lens type will ultimately depend on material characteristics and which spectral region is required for tissue interrogation. This device demonstrated a 90% increase in signal intensity and a four-fold improvement in spatial selectivity compared to a conventional RS probe during noncontact operation. Finally, one embodiment of the noncontact probe is described to showcase a clinically compatible prototype, which incorporates a widefield camera module for positioning guidance during in vivo use.