Development and characterization of a disposable submillimeter fiber optic Raman needle probe for enhancing real-time in vivo deep tissue and biofluids Raman measurements

We report on the development and characterization of disposable submillimeter fiber optic Raman needle probe for enhancing real-time in vivo tissue and biofluids Raman measurements. The submillimeter Raman probe is designed and fabricated using an aluminum-coated multimode fiber tapered with a semispherical lens, resulting in the coaxial laser excitation/Raman collection configuration for maximizing tissue and biofluid Raman measurements. We demonstrate that, with the use of the Raman needle probe associated with the structured background subtraction algorithms developed, high quality tissue Raman spectra covering both the fingerprint (FP) (800−1800 cm⁻¹) and high-wavenumber (HW) (2800−3300 cm⁻¹) regions can be acquired within subseconds from different tissue types (e.g., skin, muscle, fat, cartilage, liver, and brain) and biofluids (e.g., blood, urine). By advancing the Raman needle probe into the murine brain tissue model, high quality depth-resolved deep tissue Raman spectra can also be acquired rapidly. This work shows that the submillimeter fiberoptic Raman needle probe is capable of achieving real-time collection of deep tissue and biofluids FP/HW Raman spectra with high signal to noise ratios. This opens a new avenue with dual functioning of Raman optical biopsy and fine needle aspiration biopsy for enhancing in vivo deep tissue and biofluids diagnosis and characterization in different organs.