Development of Time-Resolved Diffuse Optical Systems Using SPAD Detectors and an Efficient Image Reconstruction Algorithm

Time-Resolved diffuse optics is a powerful and safe technique to quantify the optical properties (OP) for highly scattering media such as biological tissues. The OP values are correlated with the compositions of the measured objects, especially for the tissue chromophores such as hemoglobin. The OP are mainly the absorption and the reduced scattering coefficients that can be quantified for highly scattering media using Time-Resolved Diffuse Optical Spectroscopy (TR-DOS) systems. The OP can be retrieved using Time-Resolved Diffuse Optical Imaging (TR-DOI) systems to reconstruct the distribution of the OP in measured media. Therefore, TR-DOS and TR-DOI can be used for functional monitoring of brain and muscles, and to diagnose some diseases such as detection and localization for breast cancer and blood clot. In general, TR-DOI systems are non-invasive, reliable, and have a high temporal resolution. TR-DOI systems have been known for their complexity, bulkiness, and costly equipment such as light sources (picosecond pulsed laser) and detectors (single photon counters). Also, TR-DOI systems acquire a large amount of data and suffer from the computational cost of the image reconstruction process. These limitations hinder the usage of TR-DOI for widespread potential applications such as clinical measurements. The goals of this research project are to investigate approaches to eliminate two main limitations of TR-DOI systems. First, building TR-DOS systems using custom-designed free-running (FR) and time-gated (TG) SPAD detectors that are fabricated in low-cost standard CMOS technology instead of the costly photon counting and timing detectors. The FR-TR-DOS prototype has demonstrated comparable performance (for homogeneous objects measurements) with the reported TR-DOS prototypes that use commercial and expensive detectors. The TG-TR-DOS prototype has acquired raw data with a low level of noise and high dynamic range that enable this prototype to measure multilayered objects such as human heads. Second, building and evaluating TR-DOI prototype that uses a computationally efficient algorithm to reconstruct high quality 3D tomographic images by analyzing a small part of the acquired data. This work indicates the possibility to exploit the recent advances in the technologies of silicon detectors, and computation to build low-cost, compact, portable TR-DOI systems. These systems can expand the applications of TR-DOI and TR-DOS into several fields such as oncology, and neurology.ThesisDoctor of Philosophy (PhD

Characterization of a Time-Resolved Diffuse Optical Spectroscopy Prototype Using Low-Cost, Compact Single Photon Avalanche Detectors for Tissue Optics Applications

Time-resolved diffuse optical spectroscopy (TR-DOS) is an increasingly used method to determine the optical properties of diffusive media, particularly for medical applications including functional brain, breast and muscle measurements. For medical imaging applications, important features of new generation TR-DOS systems are low-cost, small size and efficient inverse modeling. To address the issues of low-cost, compact size and high integration capabilities, we have developed free-running (FR) single-photon avalanche diodes (SPADs) using 130 nm silicon complementary metal-oxide-semiconductor (CMOS) technology and used it in a TR-DOS prototype. This prototype was validated using assessments from two known protocols for evaluating TR-DOS systems for tissue optics applications. Following the basic instrumental performance protocol, our prototype had sub-nanosecond total instrument response function and low differential non-linearity of a few percent. Also, using light with optical power lower than the maximum permissible exposure for human skin, this prototype can acquire raw data in reflectance geometry for phantoms with optical properties similar to human tissues. Following the MEDPHOT protocol, the absolute values of the optical properties for several homogeneous phantoms were retrieved with good accuracy and linearity using a best-fitting model based on the Levenberg-Marquardt method. Overall, the results of this study show that our silicon CMOS-based SPAD detectors can be used to build a multichannel TR-DOS prototype. Also, real-time functional monitoring of human tissue such as muscles, breasts and newborn heads will be possible by integrating this detector with a time-to-digital converter (TDC)

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system

Enhancing responsivity of silicon PIN photodiodes at 1064 nm via light trapping and geometry optimization: a simulation study

Nd:YAG laser light detection at 1064 nm is widely used in applications requiring high-performance photodiodes to measure low light intensities. This study investigates the impact of light trapping and geometric variations on the responsivity of silicon-based PIN photodiodes at 1064 nm. Simulations using Ansys Lumerical FDTD and CHARGE reveal several key findings. Without diffuse reflectors, the responsivity of the photodiodes aligns with theoretical and literature values of approximately 0.4–0.45 A/W. When rear-side diffuse reflectors are used, larger photodiode dimensions result in higher responsivity, with a peak of 0.58 A/W for photodiodes with a 400 µm thickness. Our simulations suggest that combining light trapping with optimized geometries or side reflectors could surpass the current responsivity ceiling of ∼0.57 A/W, offering a pathway to exceed this limit without sacrificing electrical performance. Also, light trapping reduces the required thickness of Si PIN photodiodes for achieving specific responsivity at 1064 nm. For instance, 100 µm thick photodiodes with diffuse reflectors exhibit a responsivity of approximately 0.31 A/W, compared to 0.28 A/W in 400 µm thick photodiodes without reflectors. However, the enhancement from light trapping diminishes as photodiode thickness increases. Optimal photodiode dimensions for balanced performance are suggested to be a thickness of 200–300 μm and an area of 0.6–2.5 mm2. Experimental validation is recommended to assess texturing-related effects, such as increased dark current or recombination

Characterization of a Time-Resolved Diffuse Optical Spectroscopy Prototype Using Low-Cost, Compact Single Photon Avalanche Detectors for Tissue Optics Applications

Time-resolved diffuse optical spectroscopy (TR-DOS) is an increasingly used method to determine the optical properties of diffusive media, particularly for medical applications including functional brain, breast and muscle measurements. For medical imaging applications, important features of new generation TR-DOS systems are low-cost, small size and efficient inverse modeling. To address the issues of low-cost, compact size and high integration capabilities, we have developed free-running (FR) single-photon avalanche diodes (SPADs) using 130 nm silicon complementary metal-oxide-semiconductor (CMOS) technology and used it in a TR-DOS prototype. This prototype was validated using assessments from two known protocols for evaluating TR-DOS systems for tissue optics applications. Following the basic instrumental performance protocol, our prototype had sub-nanosecond total instrument response function and low differential non-linearity of a few percent. Also, using light with optical power lower than the maximum permissible exposure for human skin, this prototype can acquire raw data in reflectance geometry for phantoms with optical properties similar to human tissues. Following the MEDPHOT protocol, the absolute values of the optical properties for several homogeneous phantoms were retrieved with good accuracy and linearity using a best-fitting model based on the Levenberg-Marquardt method. Overall, the results of this study show that our silicon CMOS-based SPAD detectors can be used to build a multichannel TR-DOS prototype. Also, real-time functional monitoring of human tissue such as muscles, breasts and newborn heads will be possible by integrating this detector with a time-to-digital converter (TDC)

Effects of Process Parameters on Pulsed Laser Micromachining for Glass-Based Microfluidic Devices

Glass-based microfluidic devices are essential for applications such as diagnostics and drug discovery, which utilize their optical clarity and chemical stability. This review systematically analyzes pulsed laser micromachining as a transformative technique for fabricating glass-based microfluidic devices, addressing the limitations of conventional methods. By examining three pulse regimes—long (≥nanosecond), short (picosecond), and ultrashort (femtosecond)—this study evaluates how laser parameters (fluence, scanning speed, pulse duration, repetition rate, wavelength) and glass properties influence ablation efficiency and quality. A higher fluence improves the material ablation efficiency across all the regimes but poses risks of thermal damage or plasma shielding in ultrashort pulses. Optimizing the scanning speed balances the depth and the surface quality, with slower speeds enhancing the channel depth but requiring heat accumulation mitigation. Shorter pulses (femtosecond regime) achieve greater precision (feature resolution) and minimal heat-affected zones through nonlinear absorption, while long pulses enable rapid deep-channel fabrication but with increased thermal stress. Elevating the repetition rate improves the material ablation rates but reduces the surface quality. The influence of wavelength on efficiency and quality varies across the three pulse regimes. Material selection is critical to outcomes and potential applications: fused silica demonstrates a superior surface quality due to low thermal expansion, while soda–lime glass provides cost-effective prototyping. The review emphasizes the advantages of laser micromachining and the benefits of a wide range of applications. Future directions should focus on optimizing the process parameters to improve the efficiency and quality of the produced devices at a lower cost to expand their uses in biomedical, environmental, and quantum applications

Recent Progress in PDMS-Based Microfluidics Toward Integrated Organ-on-a-Chip Biosensors and Personalized Medicine

The organ-on-a-chip (OoC) technology holds significant promise for biosensors and personalized medicine by enabling the creation of miniature, patient-specific models of human organs. This review studies the recent advancements in the application of polydimethylsiloxane (PDMS) microfluidics for OoC purposes. It underscores the main fabrication technologies of PDMS microfluidic systems, such as photolithography, injection molding, hot embossing, and 3D printing. The review also highlights the crucial role of integrated biosensors within OoC platforms. These electrochemical, electrical, and optical sensors, integrated within the microfluidic environment, provide valuable insights into cellular behavior and drug response. Furthermore, the review explores the exciting potential of PDMS-based OoC technology for personalized medicine. OoC devices can forecast drug effectiveness and tailor therapeutic strategies for patients by incorporating patient-derived cells and replicating individual physiological variations, helping the healing process and accelerating recovery. This personalized approach can revolutionize healthcare by offering more precise and efficient treatment options. Understanding OoC fabrication and its applications in biosensors and personalized medicine can play a pivotal role in future implementations of multifunctional OoC biosensors

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system