Non-contact optical spectroscopy for tumor-sensitive diffuse reflectance and fluorescence measurements on murine subcutaneous tissue models: Monte Carlo modeling and experimental validations.

Fiber-optic probes are commonly used in biomedical optical spectroscopy platforms for light delivery and collection. At the same time, it was reported that the inconsistent probe-sample contact could induce significant distortions in measured optical signals, which consequently cause large analysis errors. To address this challenge, non-contact optical spectroscopy has been explored for tissue characterizations. However, existing non-contact optical spectroscopy platforms primarily focused on diffuse reflectance measurements and may still use a fiber probe in which the probe was imaged onto the tissue surface using a lens, which serves as a non-contact probe for the measurements. Here, we report a fiber-probe-free, dark-field-based, non-contact optical spectroscopy for both diffuse reflectance and fluorescence measurements on turbid medium and tissues. To optimize the system design, we developed a novel Monte Carlo method to simulate such a non-contact setup for both diffuse reflectance and fluorescence measurements on murine subcutaneous tissue models with a spherical tumor-like target. We performed Monte Carlo simulations to identify the most tumor-sensitive configurations, from which we found that both the depth of the light focal point in tissue and the lens numerical aperture would dramatically affect the system's tumor detection sensitivity. We then conducted tissue-mimicking phantom studies to solidify these findings. Our reported Monte Carlo technique can be a useful computational tool for designing non-contact optical spectroscopy systems. Our non-contact optical setup and experimental findings will potentially offer a new approach for sensitive optical monitoring of tumor physiology in biological models using a non-contact optical spectroscopy platform to advance cancer research.