This PDF file contains the front matter associated with SPIE Proceedings Volume 12387, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.

Peripheral arterial disease (PAD) affects an estimated 8.5 million people in the United States. PAD is caused by atherosclerosis, which is a narrowing of the arteries due to plaque build-up. Patients with a severe presentation of the disease often require a surgical intervention to reopen the arteries and restore blood flow to the affected areas. During the intervention, physicians often monitor the progress of the intervention using contrast angiography. The process requires a contrast agent and high radiation doses. Our lab has proposed the use of dynamic vascular optical spectroscopy (DVOS) as a non-invasive, non-iodizing method to track changes in the arteries during an intervention. In this preliminary study, we found that the DVOS signal changes in response to intervention techniques such as balloon inflations and deflations. For our trial subject, we saw on average a 19.5% change in total hemoglobin concentration (HbT) due to injection of a contrast agent prior to balloon inflation and on average a 26.6% change in HbT due to injection of a contrast agent after a sequence of balloon inflations and deflations. The data suggest that DVOS can monitor vascular health and blood perfusion in arteries in real-time during a surgical intervention.

Dopamine, an important neurotransmitter, can play both excitatory as well as inhibitory role in human body by either exciting the receptors on postsynaptic membrane or by inhibiting or suppressing them. It plays crucial roles in the working of renal, central-nervous, hormonal and cardiovascular system. An elevated level of dopamine results in cardio-toxicity that leads to rapid increase in heart rates, hypertension, drug addiction and heart failure. The low level of dopamine, on the other hand, may cause stress, depression, ailments such as schizophrenia, Alzheimer's disease, Parkinson's disease and many more. Thus, monitoring of dopamine measures in body in real time is vital for observing its impact on biological process and mechanism. In this work, a straightforward and efficient sensor model is proposed to detect the presence of dopamine in human body. Etched optical fiber with an overlayer of one of the most promising 2D material-graphene oxide (GO) is used for developing the sensor with the lossy mode resonance (LMR) approach. The sensor probe was analyzed for its performance in terms of stability. The experimental results show that the proposed etched LMR biosensor has immense capacity to sense the presence of dopamine in human and thus have significant application in real time detection and monitoring of dopamine.

We provide a framework for a wireless, low-cost, wearable laser speckle contrast imaging device for early detection of postpartum hemorrhage. The developed device was validated in vitro using optical flow phantoms and in vivo in a swine hemorrhage model.

In this study, we propose to improve driving ability by biofeedback using an RGB camera by monitoring the mental situation of driver. Driving a car or other vehicle while distracted is extremely dangerous. For example, distracted driving may lead to an accident because of the delay in noticing pedestrians. We believe that it is important for drivers to understand and improve their own distractibility in order to prevent accidents. However, it is difficult to estimate whether a driver is distracted or not, and to improve the situation. Therefore, it is expected to build a method for drivers to understand and improve their own attentiveness. Distractibility is known to be related to sympathetic arousal. In this study, we obtained pulse waves from facial video images using an RGB camera and estimated sympathetic nervous system values from the pulse waves. Biofeedback is provided by optical signals in real time. Biofeedback is performed by presenting color using threshold values based on the estimated sympathetic nerve values. To validate the proposed method, we generated a distracted state by subjecting him to a task and compared the results with and without biofeedback. As a result, it is shown that the amount of time spent in the distracted state with biofeedback was reduced compared to that without biofeedback.

Photoplethysmography (PPG) is a non-invasive optical measurement that detects blood volume changes within the tissue from the skin's surface and is traditionally integrated into wearable technology to measure heart rate from the dorsal side of the wrist. The dorsal side of the wrist contains no major arteries, whereas the palmar side has two; the radial and ulnar arteries. To better understand the morphology of a PPG signal acquired along a major artery, this study investigated the change in PPG signals acquired from the distal to proximal locations of these two major arteries within the forearm. A multiwavelength (670nm, 770nm, 810nm, 850nm, 950nm) reflectance-based system was used to analyze the change in PPG morphology with the change in measurement location. Specifically, the sensor was placed into several zones down both arteries in the forearm to evaluate PPG waveform features. As the sensor traversed the arteries, changes in the morphology in each forearm zone were observed. Additionally, by using multiple wavelengths distinct waveforms were acquired from each penetration depth, as both arteries descend deeper away from the surface as you travel distal to proximal.

Photoplethysmography (PPG) sensors, commonly used today in wearable biomedical devices, are an easily deployable low-cost technology to estimate heart rate, heart rate variability, and, when coupled with multiple wavelengths, blood oxygenation. PPG sensors can measure these parameters by measuring volumetric changes in the blood due to light absorption. While the technology is established, its utility is hindered due to several factors, including skin contact pressure. Thus, to advance fitness trackers toward regulated medical devices, confounding factors related to contact pressure and its effect on the PPG wave morphology, intensity, and signal-to-noise ratio (SNR) need to be better understood. Toward that end, this study evaluates the effects of contact pressure between the PPG sensor and the wrist, particularly on the palmar side of the wrist along the radial artery. The amplitude of the AC and DC components of the PPG signal, the perfusion index, and the signal morphology were determined for varying contact pressures utilizing three wavelengths of light, green, red, and infrared (537, 660, and 880 nm, respectively). As pressure was applied and varied, the compression effects on the pulsatile and non-pulsatile components were observed, along with changes in the perfusion index and prominent features of the PPG signal. The results showed significant differences in morphology and intensity, which varied with each PPG wavelength. These varying effects of PPG signal morphology, intensity, and SNR as a function of contact pressure suggest that pressure must be considered with wearable sensing technology and when developing signal analysis methods in order to allow the advancement of fitness trackers toward regulated medical devices.

Finger-based photoplethysmography (PPG) is traditionally acquired using a finger clip form factor on the fingertip. This form factor is not conducive for long-term measurements during regular everyday activities due to its inability to be easily worn while moving outside a clinical setting. However, advancements in finger-based PPG sensors over the last several decades include ring designs at the proximal phalanx of the finger, which are more conducive to being worn during everyday living conditions. The anatomy of this location is more complex relative to the tip as there is a smaller density of blood vessels. Also, the finger's proximal phalanx is comprised of more opaque tissue and bone, which affects the path of the light. In this study, a ring design that included 8 LEDs/PDs each at 45 degrees that included two wavelengths (940 nm: infrared and 655 nm: red) on the proximal phalanx of the finger was studied in terms of their relative placement to each other for detection. Specifically, the system was used to investigate how the pulsatile and DC component amplitudes of the photodiodes varied around the finger in both transmission and reflectance modes as a function of the 8 LEDs/PDs pairs at 45 degrees on the ring. All 64 combinations of LEDs/PDs located at the proximal phalanx of the finger were investigated. The results showed the locations that yielded the strongest amplitude PPG signals.

Observing micro-vessels in conjunctiva could be used not only for diagnosing conjunctival diseases including conjunctivitis and pterygium but also as biomarkers for circulatory diseases. Many research teams have developed compact imaging and auto-analysis systems to simplify the conventional slit lamp as well as enhance the analysis process. The imaging system, previously developed by our research team, corrects eye motion in imaging windows through image registration and template matching. The developed system quantifies blood flow velocity using the sequence of motion-corrected images. This study compares estimated flow velocity and the fluid's actual velocity using the experimental phantom comprising transparent hoses and fluid including beads corresponding to red blood cells. The flow velocities are calculated using the Hagen-Poiseuille equation, and the flow rates generated by the syringe pump. The pump applies three kinds of flow rates to generate flow velocity variations and the estimated velocities are linearly proportional to these variations. In addition, the phantom has a random motion to mimic the fixational eye movements within the range of the healthy subject's angular eye motion. Through these experiments, we verified the previously developed flow velocity measurement system having percent errors under 3% by comparing estimated flow velocities with actual flow velocities. The system's accuracy, especially under conditions without artificial motion, is over 98.5%. These experiments can provide the supporting background for feasibility and accuracy in a further clinical study in conjunctival microcirculation.

Partial thickness burn wounds extend partially through the dermis, leaving many pain receptors intact and making the injuries very painful. Due to the painfulness, quick assessment of the burn depth is important to not delay surgery of the wound if needed. Laser speckle imaging (LSI) of skin blood flow can be helpful in finding severe coagulation zones with impaired blood flow. However, LSI measurements are typically too superficial to properly reach the full depth of adult dermis and cannot resolve the flow in depth. Diffuse correlation spectroscopy (DCS) uses varying source-detector separations to allow differentiation of flow depths but requires time-consuming 2D scanning to form an image of the burn area. We here present a prototype for a hybrid DCS and LSI technique called speckle contrast Diffuse Correlation Tomography (scDCT) with the novel approach of using a laser line as a source. This will allow for fast 1D scanning to perform 3D tomographic imaging, making quantitative estimates of the depth and area of the coagulation zone from burn wounds. Simulations and experimental results from a volumetric flow phantom show promise to differentiate flows at different depths. The aim is to create a system that will provide more quantitative estimates of coagulation depth in partial thickness burn wounds to better estimate when surgery is needed.

We report a single-step, room-temperature, five to ten minute SARS-CoV-2 saliva self-monitoring method that overcomes the limitations of existing approaches through the use of fluorophore-releasing Designer DNA Nanostructures (DDNs) that bind with the multivalent pattern of spike proteins on the exterior intact virions and an inexpensive smartphone-linked, pocket-size fluorimeter, called a “V-Pod” for its resemblance to an Apple AirPod™ headphone case. We characterize the V-Pod fluorimeter performance and the DDN-based assay to demonstrate a clinically relevant detection limit of 10⁴ virus particles/mL for pseudo-typed WT SARS-CoV-2 and 10⁵ virus particles/mL for real pathogenic variants, including Delta, Omicron, and D614g.

A 3D printed (3DP) microfluidic polymerase chain reaction (PCR) device was demonstrated by detecting synthetic SARS-CoV-2 at 106 copies/μL. The microfluidic device was fabricated using stereolithography 3DP and had a reaction volume of ~22 nL. The microdevice showed PCR amplification with 85 base synthetic ssDNA targets and primers designed for a SARS-CoV-2-specific region. The device was 2.5 times faster compared to a qPCR instrument with >60,000 times smaller reagent volume. The 3DP microdevice is a promising technology to significantly reduce the manufacturing costs of microfluidic devices that could be used towards point-of-care applications.

We report an integrated system for rapid sample-to-answer detection of a viral pathogen in a droplet of whole blood comprised of a two-stage microfluidic cartridge for sample processing and nucleic acid amplification, and a clip-on detection instrument that interfaces with the image sensor of a smartphone. The cartridge is designed to release RNA from the Zika virus in whole blood using chemical lysis, followed by mixing with the assay buffer for performing reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) reactions in six parallel microfluidic compartments. The battery-powered instrument heats the compartments from below, while LEDs illuminate from above. Fluorescence generation in the compartments is dynamically monitored by a smartphone camera. We characterize the assay time and detection limits for detecting Zika RNA and gamma-irradiated Zika virus spiked into buffer and whole blood and compare the performance of the same assay when conducted in conventional PCR tubes. Our approach for kinetic monitoring of the fluorescence-generating process in the microfluidic compartments enables spatial analysis of early fluorescent “bloom” events for positive samples. We show that dynamic image analysis reduces the time required to designate an assay as a positive test to 22 minutes, compared to ~30-45 minutes for conventional analysis of the average fluorescent intensity of the entire compartment. We achieve a total sample-to-answer time in the range of 17-32 minutes, while demonstrating a viral RNA detection as low as 2.70×10² copies/ul, and a gamma-irradiated virus of 103 virus particles in a single 12.5 microliter droplet blood sample.

When it comes to diagnostics for various microorganisms, biosensors offer great advantages over conventional analytical techniques. Specifically, they can provide multiple capabilities such as user-friendly operation, real-time analysis, rapid response, high sensitivity and specificity, portability, label-free detection, and cost-effectiveness. As a result, this diagnostic approach possesses suitable features to develop point‐of‐care (POC) diagnostics and monitoring technologies. In this study, for the first time, an optical biosensor chip was developed and analysed using a localised surface plasmon resonance (LSPR) optical biosensing technique to monitor biomolecular interactions between mycolic acid TB antigen and anti-mycobacterium tuberculosis antibody. Mycolic acid was successfully immobilised on a gold-coated biosensor chip and allowed to react with an anti-mycobacterium tuberculosis antibody. To enhance the detection signal from biomolecular binding events, AuNPs were used and successfully bioconjugated with goat anti-rabbit IgG H&L secondary antibody and characterised using ultraviolet-visible (UV-vis) spectroscopy and subsequently introduced on the biosensing layer. Scanning electron microscopy (SEM) and energy-dispersive x-ray (EDX) spectroscopy were used to characterise the biosensing surface. The optimised biosensor chip was analysed using a custom-built biosensing transmission spectroscopy setup to perform LSPR biosensing. From our findings, it was realised that mycolic acid was successfully immobilised on the biosensing surface and made it possible to capture anti-mycobacterium tuberculosis antibodies. The LSPR optical biosensing technique was indeed successful in the detection of anti-mycobacterium tuberculosis antibodies.

Optical detection techniques have been extensively implemented for liquid biosensing and, among all, surface enhanced Raman spectroscopy (SERS) constitutes the one of the most promising analytical method as alternative to current traditional bioassays. With the attempt to develop point-of-impact diagnostic devices, in the present study, advanced and standard manufacturing processes were successfully combined with nanoparticles (NPs) engineering for the development of multifunctional lab-on-chips (LoCs) that integrate SERS sensors for liquid optical probing. As a matter of fact, LoCs allow to handle easily micro- to nanoliters volumes of samples as well as to perform multifunctional analyses on the same restricted volumes while avoiding cross-contaminations. Furthermore, due to the exploitation of 3D printing process, the LoCs design can be rapidly prototyped to highly integrate networks of channels and detection chambers of varied size and shape smartly arranged with respect to the Raman set-up in order to optimize signal delivery and collection. Within the detection chambers, SERS functionality is achieved by the selective interaction of the target analytes with gold NPs with embedded optical fibers positioned at different excitation and collection angles. The resulting SERS-fluidic devices, characterized by different detection configurations, represent highly versatile SERS-fluidic platforms providing high repeatability, high sensitivity and speed of analysis, possibly revolutionizing liquid biopsy by making it costless, on-chip, handy, and easy to use.

Preeclampsia (PE) is a condition that affects women during pregnancy. It is a leading cause of maternal and infant death worldwide and is typically detected in the second trimester or later. Predicting PE at an early stage is one of the most important goals of maternal-fetal medicine. Thus, there is an unmet need for accurate early detection of preeclampsia, ideally at the point-of-care. In a pilot study, microRNA-20a (miR-20a) showed an upregulation in the blood samples of the first trimester of preeclamptic pregnancies when compared to healthy mothers. In this research, a dual capture probe sandwich assay, sensitive to miR-20a, that used surface-enhanced Raman scattering (SERS)-active gold nanoparticles for the signal transduction was developed. The assay was translated to a lateral flow paper fluidic device, for potential low cost and ease of use in low-resource settings. Each paper layer has different pore sizes and features an array of buffers that store nanoparticle conjugates, guide flow, and reduce non-specific binding. Using a handheld Raman reader with a 638 nm excitation laser, reliable SERS detection of miR-20a was shown with resolutions down to 1 nM. Colorimetric detection of these concentrations using the RGB pixels from scanning the test line is also depicted, showing multi-modal detection to potentially enhance specificity for this early epigenetic biomarker.

Sweat biomarker analysis has attracted much interest in applications ranging from sports to wearable healthcare. Among all the sweat biomolecules, abnormal urea levels have been linked to several complications, particularly renal dysfunction. Here, we report the first application of non-enhanced (i.e., spontaneous) Raman spectroscopy for urea sensing in sweat. The proposed method eliminates the need for plasmonic surface fabrication for surface enhancement or bulky ultrashort-pulsed lasers for coherent enhancement. The exploitation of non-enhanced Raman was made possible because the concentration of urea in sweat, due to sweat physiology, is significantly higher with respect to urea concentration in blood. To demonstrate the feasibility of the proposed technique, we first identified the most intense urea Raman band. We then investigated the feasibility of the single-band integration data analysis to predict urea concentration in buffer solution. Single-band data analysis holds great promise for instrument miniaturization and facilitates the effort toward mobile and wearable photonic technologies. Next, we provided firm evidence of the high selectivity of the proposed sensing concept with human sweat in vitro. Finally, we reported successful ex vivo physiological sweat urea monitoring (with artificial eccrine perspiration, the closest mimic to true human eccrine sweat) on a porcine phantom, which mimics human skin, proving the potential of the proposed technique for in situ sweat urea analysis. We recorded an excellent linear calibration for urea concentrations from 0 to 60 mM with R² value of 0.9973, high sensitivity of 3521 count/mM, and low detection and quantification limits of 0.47 and 1.33 mM, respectively.

Severe radiation toxicity can continue years after the completion of radiotherapy for prostate cancer patients. Currently, it is impossible to predict before treatment which patients will experience these long-term side effects. New approaches based on vibrational spectroscopy have advantages over lymphocyte and genomic assays in terms of minimal sample preparation, speed and cost. A high throughput method has been developed to measure Raman spectra from liquid plasma in a cover glass bottomed 96 well plate. However, the Raman spectra can show contributions from glass and water. The current study aims to optimise pre-processing steps to improve classification performance.

Attenuated total reflection (ATR) spectroscopy is a powerful tool for the optical analysis of biomarkers in the mid-infrared spectral range. We study the signal-enhanced ATR spectroscopy of silicon ATR crystals using silicon micropillars etched on the active surface of the silicon crystal, where we use an effective-index approximation for the micropillar layer as the micropillars are much smaller than the optical wavelength. The reflectance, as well as the effective length due to using the micropillars are calculated as a function of wavelength using a model based on the Fresnel equations. The path length is shown to possibly increase by up to 10X due to using these pillars.

Tuberculosis (TB) is one of the world’s largest infectious diseases. It causes high mortality in humans and leads to about three million deaths worldwide annually, hence early detection is crucial, especially in a point-of-care (POC) setting to prevent the spreading of the pathogen by undiagnosed individuals. In the current work, a photonic crystal (PhC)-based optical biosensor chip was developed for diagnosing TB using mycolic acid TB antigen as a biorecognition element to capture anti-mycobacterium tuberculosis antibodies. Mycolic acid was successfully immobilized on the PhC biosensor chip to react with anti- mycobacterium tuberculosis antibody, and the white light-based transmission setup was used for optical biosensing to monitor biomolecular interactions between the antigen and antibody. Gold nanoparticles (AuNPs) before and after bioconjugation with goat anti-rabbit IgG H&L secondary antibody were characterised using ultravioletvisible (UV-vis) spectroscopy. Bioconjugated AuNPs were subsequently bound to the biosensing surface to enhance the detection signal of biomolecular binding events. The biosensing surface was further characterised using atomic force microscopy (AFM). Analysis of biomolecular binding events on the biosensing surface was achieved using a custom-built PhC optical biosensing setup which successfully distinguished between experiment and control samples. From our findings, it was realised for the first time that mycolic acid antigen could be immobilised on a biosensing surface to capture anti-mycobacterium tuberculosis antibodies. From this result, it was concluded that the PhC optical biosensing technique was successful in detecting small refractive index changes on the biosensing surface for the diagnosis of TB. These results pave the way for the development of a photonics-based POC diagnostic device for TB.

An essential part of efficient herd reproduction management is the prompt insemination of fertile cows after successfully noticing bovine heat. Signs of heat demonstrate that an animal is in estrus, ready to be inseminated. An affordable technique for heat detection is photoplethysmography (PPG, pulse oximetry), which can quantify changes in vulvar blood circulation (swelling and erythema). Previously, only experienced operators applied PPG devices. In this study, an inexperienced user clinically tested PPG for heat detection in nine cows. The analysis focused on the signal baseline (DC component), power, and kurtosis between 0.7 and 3 Hz. Compared to the experienced, inexperienced operator's PPG signal variability significantly increased. The green PPG signal baseline's range (a difference between the 25th and 75th percentile) almost tripled. Furthermore, variability in signal power increased between 6.9 and 13.1 times, indicating several operator-introduced oscillations. The results showed that inexperienced PPG operator retrieves more variable PPG signals than professionals, indicating a need for consistent device handling. The potential changes could include a pressure sensor or a clamp, guaranteeing constant pressure between the PPG sensor and the vaginal wall.