Browsing by Author "Jokerst, Nan M"

Data acquisition and diagnostics for chemical and biological analytes are critical to medicine, security, and the environment. Miniaturized and portable sensing systems are especially important for medical and environmental diagnostics and monitoring applications. Chip scale integrated planar photonic sensing systems that can combine optical, electrical and fluidic functions are especially attractive to address sensing applications, because of their high sensitivity, compactness, high surface specificity after surface customization, and easy patterning for reagents. The purpose of this dissertation research is to make progress toward a chip scale integrated sensing system that realizes a high functionality optical system integration with a digital microfluidics platform for medical diagnostics and environmental monitoring.

This thesis describes the details of the design, fabrication, experimental measurement, and theoretical modeling of chip scale optical sensing systems integrated with electrowetting-on-dielectric digital microfluidic systems. Heterogeneous integration, a technology that integrates multiple optical thin film semiconductor devices onto arbitrary host substrates, has been utilized for this thesis. Three different integrated sensing systems were explored and realized. First, an integrated optical sensor based upon the heterogeneous integration of an InGaAs thin film photodetector with a digital microfluidic system was demonstrated. This integrated sensing system detected the chemiluminescent signals generated by a pyrogallol droplet solution mixed with H2O2 delivered by the digital microfluidic system.

Second, polymer microresonator sensors were explored. Polymer microresonators are useful components for chip scale integrated sensing because they can be integrated in a planar format using standard semiconductor manufacturing technologies. Therefore, as a second step, chip scale optical microdisk/ring sensors integrated with digital microfluidic systems were fabricated and measured. . The response of the microdisk and microring sensing systems to the change index of refraction, due to the glucose solutions in different concentrations presented by the digital microfluidic to the resonator surface, were measured to be 95 nm/RIU and 87nm/RIU, respectively. This is a first step toward chip-scale, low power, fully portable integrated sensing systems.

Third, a chip scale sensing system, which is composed of a planar integrated optical microdisk resonator and a thin film InGaAs photodetector, integrated with a digital microfluidic system, was fabricated and experimentally characterized. The measured sensitivity of this sensing system was 69 nm/RIU. Estimates of the resonant spectrum for the fabricated systems show good agreement with the theoretical calculations. These three systems yielded results that have led to a better understanding of the design and operation of chip scale optical sensing systems integrated with microfluidics.

Diffuse reflectance spectroscopy (DRS) is a simple, yet powerful technique that has the potential to offer practical, non-invasive, and cost effective information for op- tical diagnostics and therapeutics guidance. Any progress towards moving DRS systems from their current laboratory settings to clinical settings, field settings and ambitiously to home settings, is a significant contribution to society in terms of reducing ever growing healthcare expenditures of an aging society. Additionally, im- proving on the existing mathematical models used to analyze DRS signals; in terms of speed, robustness, accuracy, and capability in accounting for larger feature space dimensionality (i.e. extraction of more tissue-relevant information) is equally im- portant for real-time diagnosis in the desired settings and to enable use of DRS in as many biomedical applications (e.g. skin cancer diagnosis, diabetics care, tissue oxygenation monitoring) as possible. Improving the reflectance signal complexity and density through novel DRS instrumentation, would facilitate development of the desired models or put the existing ones built on simulations in practical use; which otherwise could not go beyond being a theoretical demonstration.

DRS studies tissue morphology and composition through quantification of one or more (ideally all of them) of the tissue- and wavelength-specific optical properties: absorption coefficient (μa), reduced scattering coefficient (μ1s), scattering anisotropy (g), tissue thickness, and scattering phase function details (e.g. higher order moments of the scattering phase function). DRS involves sampling of diffusely reflected photons which experience multiple scattering and absorption as they travel within the tissue, at the tissue surface. Spatially resolved diffuse reflectance spectroscopy (SRDRS) is a subset of general DRS technique, which involves sampling of diffuse reflectance signals at multiple distances to an illumination source. SRDRS provides additional spatial information about the photon path; yielding depth-resolved tissue information critical to layered tissue analysis and early cancer diagnostics. Exist- ing SRDRS systems use fiber optic probes, which are limited in accommodation of large number and high-density collection fibers (i.e. yielding more and dense spa- tially resolved diffuse reflectance (SRDR) measurement data) due to difficulty of fiber multiplexing. The circular shape of the fibers restricts the implementable probe ge- ometries and reduces the fill factor for a given source to detector (i.e. collection fiber) separation (SDS); resulting in reduced light collection efficiency. The finite fiber nu- merical aperture (NA) reduces the light collection efficiency well as; and prevents selective interrogation of superficial tissues where most cancers emerge. Addition- ally, SRDR systems using fiber optic probes for photon collection, require one or more photodetectors (i.e. a cooled CCD); which are often expensive components of the systems.

This thesis deals with development of an innovative silicon SRDRS probe, which partially addresses the challenge of realizing high measurement density, miniaturized, and inexpensive SRDRS systems. The probe is fabricated by conventional, flexible and inexpensive silicon fabrication technology, which demonstrates the feasibility of developing SRDRS probes in any desired geometry and complexity. Although this approach is simple and straightforward, it has been overlooked by the DRS community due to availability of the conventional fiber optic probe technology. This new probe accommodates large number and high density of detectors; and it is in the form of a concentric semi-annular photodiode (PD) array (CMPA) with a central illumination aperture. This is the first multiple source-detector spacing Si SRDRS probe reported to date, and the most densely packed SRDRS probe reported to date for all types of SRDRS systems. The closely spaced and densely packed detectors enable higher density SRDR measurements compared to fiber-based SRDR probes, and the higher PD NA compared to that of fibers results in a higher SNR increasing light collection efficiency. The higher NA of the PDs and the presence of PDs positioned at very short distances from the illumination aperture center enable superficial tissue analysis as well as depth analysis.

The visible wavelength range has proven to be a useful spectral window for observing biophotonic events such as absorption in materials (oxy-hemoglobin and deoxy-hemoglobin), light scattering in biological tissue, and biochemical and fluorescence reactions. Diffuse reflectance spectroscopy (DRS) is a technique that utilizes the diffuse reflectance spectra from turbid media (e.g. biological tissue) to quantify the optical properties (e.g. absorption and scattering) of those media. DRS in the visible wavelength range can be utilized to optically differentiate between healthy and cancerous tissue, and thus has applications in intra-operative tumor margin assessment.

The footprint of conventional DRS systems used for intra-operative tissue margin assessment prohibits their widespread use inside the surgical suite, where space is at a premium. Conventional quantitative DRS imaging systems utilize unwieldy fiber probes, cooled CCD cameras, and imaging spectrographs for imaging tissue margins. These system components not only increase system size, limiting their use inside the surgical suite, but also limit imaging resolution, imaging speed, and increase overall system cost.

Silicon is an attractive candidate for the development of compact, customized photodetector elements for biophotonic imaging applications such as intra-operative tumor margin assessment using DRS. This thesis deals with the design and development of a customized DRS imaging probe composed of custom silicon imaging arrays for intra-operative breast tumor margin assessment. The first generation of the customized imaging probe consisted of a 4x4 array of annular epitaxial Si pn junction photodiodes (PDs) with a measured responsivity of 0.28 A/W - 0.37 A/W for λ= 470 nm - 600 nm, and a measured dark current density of 1.456 nA/cm2 - 4.48 nA/cm2. The imaging array was used to detect diffuse reflectance when placed in direct contact with tissue. A quartz light delivery tube coupled to a xenon lamp was optimized to deliver light to the tissue through the holes of the annular imaging array across a 256 mm2 imaging area. The pixel-to-pixel spacing in the imaging array was 4.5 mm, the highest resolution reported to date for a multi-pixel DRS probe. This resolution was limited by pixel-to-pixel optical crosstalk, which was theoretically calculated and experimentally characterized, to validate the theoretical model for future designs. This first generation probe was successfully tested on diffuse reflectance standards, tissue-mimicking phantoms, animal tissue, and human breast tissue, and yielded an SNR of 30 dB - 55 dB on all measured specimens.

The next generation of the customized imaging probe consisted of a 4x4 array of annular thin-film Si pn junction PDs heterogeneously bonded to a transparent Pyrex substrate, to enable integration with a guided wave light delivery system. The 4x4 thin-film PD array design and development was prototyped using a 1x2 thin-film PD array heterogeneously bonded to a Pyrex substrate. The responsivity and dark current of the thin-film PDs in the 1x2 array were measured to be 0.19 A/W - 0.34 A/W for λ= 470 nm - 600 nm and 0.63 nA/cm2, respectively. The process for the 1x2 thin-film PD array was scaled to fabricate a 4x4 array of thin-film PDs for DRS, and the 4x4 array was optically and electrically characterized. These heterogeneously bonded thin-film single crystal Si PDs have the highest uncooled responsivity to dark current density ratio (greater than 0.30 - 0.54 cm2/nW for λ= 470 nm - 600 nm) reported to date, to the best of our knowledge. The 1x2 array of thin-film PDs were also heterogeneously bonded to a flexible substrate without any degradation in PD optical and electrical characteristics, opening the door towards conformal tissue imaging.

Locally energized particles that are powered by external fields (e.g., electrical, magnetic, optical, chemical, and thermal gradients) have formed the basis of emerging classes of reconfigurable active matter. The ability to rationally design such particles in a way to enable robust control of their assembly and reconfiguration can ultimately help this promising area to realize its full potential. Herein, we introduce a class of engineered semiconductor active microparticles that can be designed with exceptional specificity (e.g., in size, shape, electric and magnetic polarizability, and field rectification) by leveraging standard electronic fabrication tools. These particles draw energy from applied external fields and actively propel, repel, rotate, and perform on-demand sequential assembly and disassembly. We show that a number of electric field-based effects such as electrohydrodynamic (EHD) flows, induced-charge electroosmosis, induced-charge electrophoresis, and dielectrophoresis can selectively power this suite of particles. We also show that a number of magnetic field-based effects such as magnetohydrodynamic (MHD) flows and magnetophoresis can induce additional functionalities to similarly designed particles. The result is the ability to achieve customized locomotion, interactions, reversible assembly, and synchronous rotational torque on demand that could enable advanced applications such as artificial muscles, remotely powered microsensors, optical switches, and reconfigurable computational systems.

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.

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.

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.

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).

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.

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.

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.

Advances in the development of miniaturized, autonomous general-purpose sensing systems for applications such as medical diagnostics, biological and chemical analysis, and point-of-care testing have driven the emergence of lab-on a-chip (LOC) systems, which integrate sample preparation and sensing. To realize LOC systems, enabling technologies are needed to carry out sample preparation and manipulation at the chip-scale, and sensing technologies that can be integrated with the chip-scale fluidic sample preparation platform.

The integration of sample preparation and sensing is key to LOC systems. Electrowetting-on-dielectric (EWD) fluidic technology enables digital droplet manipulation at the chip-scale with standard microfabrication manufacturing techniques, with the advantages of non-bulky systems, low cost and portability [1]. EWD system have been integrated with optical, mechanical and electrochemical sensing mechanisms to realize a miniaturized LOC [2]–[4].Fluorescence sensing is one of the most widely used types of analyte sensing for biochemical targets due to its high sensitivity and specificity [2]. Intensity-based fluorescence sensing provides fast, localized detection that can be correlated to the concentration of the test analyte, thus providing quantitative detection information. Most current microfluidic LOC systems that utilize fluorescent sensing use large external microscopes or bulky filters and lenses for extracting the quantitative information, thus compromising on the portability and cost-effectiveness. The realization of optical fluorescence sensing integrated directly into microfluidic-based LOC systems can enable the systems to become more self-contained, portable, and potentially low cost.

Fluorescence sensing is an effective method of identifying target species, and the integration of fluorescence sensing into a programmable digital microfluidic platform is the goal of the thesis work described herein. Silicon photodetectors (PDs) are an excellent choice for optical sensing due to their high responsivity at visible wavelengths, which corresponds to the emission wavelengths of many fluorophores. Additionally, using Si PDs enables the use of standard microfabrication processes that can be scaled for mass manufacturing. Furthermore, using thin film Si photodetectors provides the ability to be bonded to a chosen substrate for further system integration in small spaces where conventional photodetectors will not fit, without significantly altering the spatial configuration of the region where the sensing occurs.

This dissertation presents the design and fabrication of annular, thin film Si photodetectors heterogeneously bonded to a pyrex substrate for fluorescence sensing, with a longer-term goal of integration into an EWD to realize a LOC system. Herein we design, fabricate, and test the performance of PD fluorescence sensors with thin film Si PD testing, followed by PD integration into an EWD microfluidic system. This system is simple and low cost, because it does not utilize filters to block the optical pump beam selectively from the PD, but rather, uses a novel optical design to suppress the fluorescence pump signal with the bottom plate of the microfluidic system, so that the signal to noise ratio (SNR) of the fluorescence signal to the pump signal is high. This device has the potential to be applied as a miniature, non-invasive, multi-target sensor.

[Figure 1: Cross-section schematic of the integrated thin film Si fluorescence sensor with a bottom plate designed for integration with an EWD system. PD thickness not drawn to scale.]

The target EWD system for integration with the fluorescence sensor has a top plate and a bottom plate, with the thin film Si PD integrated onto the top plate. The PD sensor is a thin film annular silicon PD bonded to the pyrex top plate, as shown in Figure 1, which can also serve as a ground electrode for the microfluidic platform. The optical pump signal, delivered herein through an optical fiber, is coupled to the droplet under test (containing the fluorophore) through the pyrex, through a thin metallization on the pyrex to minimize stray light, and then through the aperture in the photodetector. Light delivery can also be carried out using an integrated optical (LED or laser) source with or without an optical waveguide. The droplet is sandwiched between the top plate and the bottom plate. Fluorophore concentrations ranging from 0.3 μM to 20 μM were tested with different bottom plate substrates and herein, we discuss high SNR detection for droplet sizes as low as 10 μL over a time period of microseconds. Next, the integration of the fluorescence sensor with a digital microfluidic system is discussed. Finally, the performance of the sensor is evaluated, followed by conclusions and thoughts for future work.

The optical characteristics of tissue can give insight into the health status of that tissue. Tissue health is indicated by tissue properties such as chromophore concentrations (including hemoglobin, iron, glucose and cytochrome oxidase) as well as by the type of cells (cancerous vs normal) present in the tissue. Diffuse reflectance spectroscopy (DRS) is a non-invasive optical interrogation technique for the quantification of tissue properties and the classification of tissue. DRS systems are generally composed of two parts, the sensing system and the data processing used for tissue/sample analysis. Systems and analysis techniques can both range widely depending on the application. Moreover, the classification accuracy of both can suffer in low signal-to-noise ratio (SNR) settings.

This thesis combines a high density multipixel Si photodetector (PD) probe, Monte Carlo (MC) simulations, and partial least squares regression (PLSR) analysis to enable the extraction of optical properties and the classification of samples in low SNR settings. The development and characterization of a DRS multipixel Si PD sensor array is presented. A multipixel Si PD sensor array is used herein to measure homogenous liquid tissue-mimicking phantoms. This data was then used to develop a PLSR algorithm to directly predict, for the first time, the optical coefficients of a tissue-mimicking phantom in a leave-one-out approach. The Si PD array was also used to conduct DRS measurements of 2-layer and 3-layer solid phantoms that were modeled using MC simulations to analyze the depth sensitivity of the multipixel Si PD array. This depth sensitivity analysis contributes to the DRS field by examining the difference in DRS signals between homogeneous and heterogenous samples using a multipixel Si PD probe, demonstrating, for the first time, that low contrast buried layers surrounding by homogenous media can be detected.

Integrated sensing systems are designed to address a variety of problems, including clinical diagnosis, water quality testing, and air quality testing. The growing prevalence of tropical diseases in the developing world, such as malaria, trypanosomiasis (sleeping sickness), and tuberculosis, provides a clear and present impetus for portable, low cost diagnostics both to improve treatment outcomes and to prevent the development of drug resistance in a population. The increasing scarcity of available clean, fresh water, especially noticeable in the developing world, also presents a motivation for low-cost water quality diagnostic tools to prevent exposure of people to contaminated water supplies and to monitor those water supplies to effectively mitigate their contamination. In the developed world, the impact of second-hand cigarette smoke is receiving increased attention, and measuring its effects on public health have become a priority. The `point-of-need' technologies required to address these sensing problems cannot achieve a widespread and effective level of use unless low-cost, small form-factor, portable sensing devices can be realized. Optical sensors based on low cost polymer materials have the potential to address the aforementioned `point-of-need' sensing problems by leveraging low-cost materials and fabrication processes. For portable clinical diagnostics and water quality testing in particular, on-chip sample preparation is a necessity. Electrowetting-on-dielectric (EWD) technology is an enabling technology for chip-scale sample preparation, due to its very low power consumption compared to other microfluidics technologies and the ability to move fluids without bulky external pumps. Potentially, these technologies could be combined into a cell phone sized portable sensing device.

Towards the goal of developing a portable diagnostic device using EWD microfluidics with an embedded polymer microresonator sensor, this thesis describes a viable fabrication process for the system and explores the design trade-offs of such a system. The main design challenges for this system are optimization of the sensor's limit-of-detection, minimization of the insertion loss of the optical system, and maintaining the ability to actuate droplets onto and off of the sensor embedded in the microfluidic system. The polymer microresonator sensor was designed to optimize the limit-of-detection (LOD) using SU-8 polymer as the bus waveguide and microresonator material and SiO2 as the substrate cladding material. The fabrication process and methodology were explored with test devices using a tunable laser system working around a wavelength of 1550 nm using glucose solutions as a refractive index standard. This sensor design was then utilized to embed the sensor and bus waveguides into an EWD top plate in order to minimize the impact of the sensor integration on microfluidic operations. Finally, the performance of the embedded sensor embedded was evaluated in the same manner and compared to the performance of the sensor without the microfluidic system.

The primary result of this research was the successful demonstration of a high performance polymer microresonator sensor embedded in the top plate of an electrowetting microfluidic device. The embedded sensor had the highest reported figure-of-merit for any microresonator integrated with electrowetting microfluidics. The embedded microresonator sensor was also the first fully-embedded microresonator in an EWD system. Because the sensor was embedded in the top plate, full functionality of the EWD system was maintained, including the ability to move droplets onto and off of the sensor and to address the sensor with single droplets. Furthermore, the highest figure-of-merit for an SU-8 microresonator sensor yet reported at a probe wavelength of 1550 nm was measured on a test device fabricated with the embedded sensor structure described herein. Optimization of the sensor sensitivity utilized recently developed waveguide sensor design theory, which accurately predicted the measured sensitivity of the sensors. Altogether, the results show that embedding of a microresonator sensor in an EWD microfluidics system is a viable approach to develop a portable diagnostic system with the high efficiency sample preparation capability provided by EWD microfluidics and the versatile sensing capability of the microresonator sensor.

Patient outcomes for colon and esophageal cancers depend on early detection and surveillance of the progression of dysplasia (abnormal cellular growth indicative of pre-cancer) and malignancy (cancer) in the epithelium of these organs. The present standard of care for detection and surveillance of these diseases is to inspect the surface of the colon and esophagus searching for high-risk tissue using white light endoscopy (WLE), which provides imaging of the organ surface. While WLE is effective for the detection of some high-risk tissues such as colon polyps, other types of high-risk tissue, such as flat dysplasia, may not be visually observable to the physician by WLE. The limited efficacy of WLE results in reduced adenoma detection rates, unnecessary resection of healthy tissues, incomplete resection of high-risk tissues, and necessitates random sampling of esophageal or colon regions known to be at elevated risk for flat dysplasia, such as in cases of Barrett’s esophagus or inflammatory bowel disease. Patient outcomes for colon and esophageal cancer can be improved if the capabilities of WLE can be augmented to readily detect the microstructural and biochemical characteristics of these diseases in tissues during endoscopy.

Diffuse reflectance spectroscopy (DRS) is a label free optical technique that can be used to sense the morphological and biochemical changes that occur when normal colon or esophageal tissue becomes pre-cancerous or cancerous, and DRS has the potential to be used to augment the performance of traditional WLE. However, the reliance of conventional DRS systems on optical fibers for reflectance collection limits system performance, limits scalability, and constrains the design options.

Custom thin film silicon (Si) photodetectors (PDs) offer a high performance, scalable, and highly customizable alternative to optical fibers for reflectance photon collection in tissue DRS applications. Si PDs improve performance over optical fibers since they have superior numerical apertures (NAs) and collect light from a larger fraction of the probe surface; they are highly scalable due to Si processing technology; they can be geometrically optimized for specific applications; and they can be implemented on a variety of substrates, including flexible or conformal, and can be implemented as an attachment to an endoscope. And arrays of Si PDs can be used perform spatially resolved DRS (SRDRS), which adds depth sensitivity to DRS by simultaneously measuring the tissue reflectance at multiple illumination-collection distances.

This dissertation describes the design, fabrication, optoelectronic characterization, phantom studies with reduced scattering coefficient (μ_s^' (λ)) and absorption coefficient (μ_a (λ)) extraction, and preliminary clinical testing on ex-vivo human colon tissue of the first Si thin film multi-pixel SRDRS array optimized for a specific tissue measurement application. The illumination-collection geometry of the Si PD based SRDRS sensor array described herein was designed using Monte Carlo simulation to maximize performance when characterizing human colon tissue. The design was then implemented using 10 μm thick crystalline Si PD arrays heterogeneously integrated onto a transparent substrate and packaged for phantom and clinical ex-vivo human tissue testing. The performance of the fabricated sensors was initially evaluated on synthetic liquid tissue phantoms, with comparisons of the experimentally measured diffuse reflectance from these phantoms compared to Monte Carlo simulated diffuse reflectance, yielding a mean discrepancy of 8.4% over the 450 to 650 nm wavelength range.

To enable extraction of tissue optical properties from measured tissue diffuse reflectance, two inverse DRS methods were developed which relied on look-up tables of Monte Carlo simulated diffuse reflectance. One method extracts spectrally constrained values of μ_s^' (λ) and μ_a (λ) from measurements of diffuse reflectance independently for each PD in the SRDRS sensor. A second model uses the radial dependence of the PDs in the SRDRS sensor to both spatially and spectrally constrain the extracted values of μ_s^' (λ) and μ_a (λ). The average percent error between expected (known) and extracted μ_s^' (λ) and μ_a (λ) values of eight liquid phantoms used to evaluate the inverse models was 13.25% and 31.42%, respectively, for the first inverse method, and 6.38% and 8.38%, respectively, for the second, for diffuse reflectance measurements spanning the 450 nm to 750 nm wavelength range. These results indicate that use of three PDs in the SRDRS sensor can reduce the error for tissue optical property extraction.

Further assessment of the Si PD array performance and tissue compatibility was conducted on ex-vivo porcine esophageal tissue, and an experimental set-up to enable clinical measurements of resected human colon tissue samples was developed in collaboration with physicians in the Duke University Medical Center: Dr. N. Lynn Ferguson, MD, Assistant Professor of Pathology in the Duke University Department of Pathology, Dr. Katherine Garman, MD, Associate Professor of Medicine in the Duke University Department of Medicine, and Dr. Deborah Fisher, MD, Associate Professor of Medicine in the Duke University Department of Medicine.

SRDRS measurements on excised normal and tumorous human colon tissue were performed with a prototype thin film Si PD based SRDRS probe, and the absorption and reduced scattering optical properties of the tissue were extracted. The extracted optical properties are comparable to previously reported values optical properties for similar tissue and indicate that the prototype system is able to extract similar tissue information as other more expensive and less scalable tissue spectroscopic systems.

The thin film Si PD based SRDRS probe and experimental work presented herein contributes to the field of Si PD based tissue DRS by being the first demonstration of a thin-film Si PD based DRS or SRDRS system in direct contact with human and animal tissues. The development, experimental validation, and demonstrated application to analysis of SRDRS measurements of human colon tissue, of a method for tissue optical property extraction described herein is the first inverse method to demonstrate an improvement of optical property extraction in a Si PD based system by utilizing the spatial dependence of reflectance, compared to a single PD based extraction method. The novel inverse model extraction method presented herein, which utilizes multiple Monte Carlo populated LUTs of diffuse reflectance to spatially and spectrally constrain extracted optical properties, is a contribution to the field of tissue optical property extraction from SRDRS measurements. Finally, the report of μ_s^' (λ) and μ_a (λ) properties for unfrozen ex-vivo human colon tissue adds to the sparsely reported data of this type in the literature, contributing to the general field of biophotonics.

The integration of planar on-chip light sources is a bottleneck in the implementation of portable planar chip-scale photonic integrated sensing systems, integrated optical interconnects, and optical signal processing systems on platforms such as Silicon (Si) and Si-CMOS integrated circuits. A III/V on-chip laser source integrated onto Si needs to use standard semiconductor fabrication techniques, operate at low power, and enable efficient coupling to other devices on the Si platform.

In this thesis, thin film strain compensated InGaAs/GaAs single quantum well (SQW) separate confinement heterostructure (SCH) edge emitting lasers (EELs) have been implemented with patterning on both sides of the thin film laser under either growth or host substrate support, with the devices metal/metal bonded to Si and SiO₂/Si substrates. Gain and index guided lasers in various configurations fabricated using standard semiconductor manufacturing processes were simulated, fabricated, and experimentally characterized. Low threshold current densities in the range of 250 A/cm2 were achieved. These are the lowest threshold current densities achieved for thin film single quantum well (SQW) lasers integrated on Si reported to date, and also the lowest reported, for thin film lasers operating in the 980 nm wavelength window.

These thin film EELs were also integrated with photolithographically patterned polymer (SU-8) waveguides on the same SiO₂/Si substrate. Coupling of the laser and waveguide was compared for the cases where an air gap existed between the thin film laser and the waveguide, and in which one facet of the thin film laser was embedded in the waveguide. The laser to waveguide coupling was improved by embedding the laser facet into the waveguide, and eliminating the air gap between the laser and the waveguide. Although the Fresnel reflectivity of the embedded facet was reduced by embedding the facet in the polymer waveguide, leading to a 27.2% increase in threshold current density for 800 &mum long lasers, the slope efficiency of the L-I curves was higher due to preferential power output from the front (now lower reflectivity) facet. In spite of this reduced mirror reflectivity, threshold current densities of 260 A/cm2 were achieved for 1000 &mum long lasers. This passively aligned structure eliminates the need for precise placement and tight tolerances typically found in end-fire coupling configurations on separate substrates.