<p>The optical properties of biological tissue provide quantitative information about the physiological structure and chemical composition of a tissue sample. The investigation of tissue optical properties through Diffuse Reflectance Spectroscopy (DRS) is a rapid, non-invasive technique with extensive applications in healthcare diagnostics and therapeutics. Breast conservation surgery, a clinical practice performed for nearly 15,000 patients annually, requires accurate diagnosis of the tissue margin, the healthy layer of tissue surrounding the excised tumor. This margin assessment has traditionally been performed via post-operative pathology through one of multiple time-intensive processes that are performed after the surgery is completed. However, the margin assessment can also be rapidly performed by DRS, leading towards pathological evaluations concurrent with the excision surgery. </p><p>Presently, DRS probe designs are limited to laboratory settings. They include illumination and collection optical fibers, spectrometers, and CCD detectors, which all add to the complexity, cost, and size of a diagnostic system. Recently, DRS probes have been designed with Silicon photodetectors (Si PDs), including detector arrays that enable simultaneous DRS imaging of multiple tissue sites. The Si PDs reduce probe system complexity by replacing the cumbersome fiber-based collection probes and CCD detectors. </p><p>However, these monolithic Si PD probes are rigid and flat. When imaging non-planar tissue samples, a rigid probe may experience reduced accuracy from uneven tissue pressure and loss of contact with the tissue surface. A physically flexible DRS probe can improve sensing accuracy by conforming to a tissue surface with arbitrary curvature.</p><p>This thesis presents the design, fabrication, and test of flexible DRS Si PD probes constructed with thin film single crystalline silicon heterogeneously bonded to a flexible polymer substrate. The PDs have dark currents and responsivities comparable to high performance standard thickness Si PDs. The responsivity and zero bias dark current of the flexible PDs were evaluated while flat and while curved up to a 10 mm radius of curvature, with measured variations in responsivity (±0.61%) and dark current (±3 pA).</p><p>The flexible DRS probe was evaluated on benign and malignant breast tissue representative liquid phantoms. DRS measurements were performed with the flexible DRS probe on both liquid phantoms over a wavelength range of 470 – 600 nm at five radii of curvature: flat, 50 mm, 25 mm, 15 mm, and 10 mm. The optical contrast between the benign and malignant phantom DRS measurements ranged from 4.0-13.6% across all measured wavelengths for the flat test case and 5.9-15.5% while curved. For both phantoms at all wavelengths, the DRS signal increased in response to increasing curvature. The increase in reflectance signal ranged from 4.8-12.3% when the liquid phantom curvature was brought from flat to a 10 mm radius of curvature. The experimental results were then compared to theoretical reflectance values generated through a forward Monte Carlo model. The mean error between experiment and theory was 2.33% for the benign phantom and 1.23% for the malignant phantom. </p><p>Pixel-to-pixel crosstalk, the portion of diffusely reflected light that enters the tissue near one PD but is detected at a different PD, was also evaluated using the same test setup as for the DRS signal. The crosstalk signal also increases due to curvature, with an increase of 33.2-40.0% across all measured wavelengths for the benign phantom. The experimental crosstalk signal for the benign phantom was compared to a forward Monte Carlo model with mean error of 4.85%. The crosstalk could not be measured on the malignant phantom due to lower reflected light levels that were below the noise floor of the PD. </p><p>The flexible Si PD probe presented herein shows promising results for optical tissue analysis and feature extraction on both flat and curved tissue surfaces. This flexible probe technology facilitates conformal tissue DRS imaging, potentially in a clinical diagnostic device.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/13431 |
| Date | January 2016 |
| Creators | Miller, David Michael |
| Contributors | Jokerst, Nan M |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
Page generated in 0.0013 seconds