Spatially resolved diffuse reflectance spectroscopy endoscopic sensing with custom Si photodetectors

Abstract

Early detection and surveillance of disease progression in epithelial tissue is key to improving long term patient outcomes for colon and esophageal cancers, which account for nearly a quarter of cancer related mortalities worldwide. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a non-invasive optical technique to sense biological changes at the cellular and sub-cellular level that occur when normal tissue becomes diseased, and has the potential to significantly improve the current standard of care for endoscopic gastrointestinal (GI) screening. Herein the design, fabrication, and characterization of the first custom SRDRS device to enable endoscopic SRDRS GI tissue characterization using a custom silicon (Si) thin film multi-pixel endoscopic optical sensor (MEOS) is described. Depeursinge, "In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties," J. Biomed. Opt. 8(3), 495-503 (2003). 11. Z. Ge, K. T. Schomacker, and N. S. Nishioka, "Identification of colonic dysplasia and neoplasia by diffuse reflectance spectroscopy and pattern recognition techniques," Appl. Spectrosc. 52(6), 833-839 (1998 Marcu, "Effects of fiber-optic probe design and probe-to-target distance on diffuse reflectance measurements of turbid media: an experimental and computational study at 337 nm," Appl. Opt. 43(14), 2846-2860 (2004) Opt. Express 8(3), 1512-1524 (2017 Wilke, and N. Ramanujam, "Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins," Opt.

Methods of extraction of optical properties from diffuse reflectance measurements of ex-vivo human colon tissue using thin film silicon photodetector arrays

“…Development and evaluation of MC populated LUT inverse models for the extraction of colon optical properties using the MEOS probe were based on the system in Fig. 1, using initial measured phantom and MC forward modeling studies previously reported [18].…”

“…However, the reliance of conventional DRS systems on optical fibers for reflectance collection limits system performance, limits scalability, and constrains the design options. In contrast, custom thin film silicon (Si) photodetectors (PDs) offer a high performance, scalable, and highly customizable alternative to optical fibers for reflectance collection in tissue DRS applications [14][15][16][17][18]. Si PDs improve performance over optical fibers since they have higher numerical apertures (NAs) and collect light from a larger fraction of the probe surface, they are highly scalable due to Si manufacturing technology, they can be geometrically optimized for specific applications, they can be implemented on a variety of substrates, including flexible or conformal, and they can be implemented in the instrument channel or as an attachment to an endoscope.…”

“…Previous reports on the development of a custom Si thin film multi-pixel endoscopic optical sensor (MEOS) leveraged the advantages of thin film Si PD based SRDRS systems for endoscopic applications such as colonoscopy [18]. A conceptual diagram of the system used to perform measurements with the MEOS is provided in Fig.…”

“…The three Si PDs surround a shared 750 nm diameter illumination aperture, with at increasing mean radii of 450 µm, 540 µm, and 860 µm, for PDs 1, 2, and 3, respectively, and increasing PD widths of 58 µm, 100 µm, and 550 µm, respectively. The geometries of the custom PDs were optimized for measurement of colon tissue, and the MEOS was fabricated using standard Si microfabrication techniques [18]. The tissue (or tissue phantom) measured by the MEOS is interrogated by photons provided by an optical fiber coupled to the backside of the transparent glass substrate.…”

“…Photons pass through the glass substrate and through the circular illumination aperture at the center of the three concentric PDs before sampling the tissue under measurement. Reflectance data is collected with the PDs in direct contact with the tissue and collected photons that have sampled the tissue are converted to electrical signals by the PDs [18]. Each of the three PDs in the MEOS system measure relative diffuse reflectance, as described by Eq.…”