This PDF file contains the front matter associated with SPIE Proceedings Volume 10072 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

Sensitive detection of specific chemicals on site can be extremely powerful in many fields. Owing to its molecular fingerprinting capability, surface-enhanced Raman scattering has been one of the technological contenders. In this paper, we describe the novel use of DNA topological nanostructure on nanoporous gold nanoparticle (NPG-NP) array chip for chemical sensing. NPG-NP features large surface area and high-density plasmonic field enhancement known as “hotspots”. Hence, NPG-NP array chip has found many applications in nanoplasmonic sensor development. This technique can provide novel label-free molecular sensing capability and enables high sensitivity and specificity detection using a portable Raman spectrometer.

Human biomarkers are indicative of the body’s relative state prior to the onset of disease, and sometimes before symptoms present. While blood biomarker detection has achieved considerable success in laboratory settings, its clinical application is lagging and commercial point-of-care devices are rare. A physician’s ability to detect biomarkers such as microRNA-17, a potential epigenetic indicator of preeclampsia in pregnant woman, could enable early diagnosis and preventive intervention as early as the 1st trimester. One detection approach employing DNA-functionalized nanoparticles to detect microRNA-17, in conjunction with surface-enhanced Raman spectroscopy (SERS), has shown promise but is hindered, in part, by the use of large and expensive benchtop Raman microscopes. However, recent strides have been made in developing portable Raman systems for field applications. Characteristics of the SERS assay responsible for strengthening the assay’s plasmonic response were explored, whilst comparing the results from both benchtop and portable Raman systems. The Raman spectra and intensity of three different types of photoactive molecules were compared as potential Raman reporter molecules: chromophores, fluorophores, and highly polarizable small molecules. Furthermore, the plasmonic characteristics governing the formation of SERS colloidal nanoparticle assemblies in response to DNA/miRNA hybridization were investigated. There were significant variations in the SERS enhancement in response to microRNA-17 using our assay depending on the excitation lasers at wavelengths of 532 nm and 785 nm, depending on which of the three different Raman systems were used (benchtop, portable, and handheld), and depending on which of the three different Raman reporters (chromophore, fluorophore, or Raman active molecule) were used. Analysis of data obtained did indicate that signal enhancement was better for the chromophore (MGITC) and Raman active molecule (DTNB) than it was for the fluorophore (TRITC) and that, although it is possible to obtain enhancements when using excitation lasers that do not directly coincide with the optical properties of the Raman reporter molecule, clearly the enhancements are more significant when it reaches to the characteristic wavelengths of those molecules.

Surface enhanced raman scattering (SERS) is known for its high sensitivity toward detection down to single molecule level under optimal conditions using surface plasmon resonance (SPR). To excite the SPR for SERS application, nanostructured noble metal supports such as a nanoparticle have been widely used. However, for excitation of SPR for SERS application using noble metal nanoparticle has several disadvantages such as sophisticated fabrication procedure and low reproducibility of SPR excitation efficiency. To overcome these disadvantages, in this study, plasmonic crystal (PC)-SERS substrate which has a periodic noble metal nanostructure was successfully fabricated rapidly and cost-effectively based on nanoimprint lithography (NIL).

Laser spectroscopy provides the basis of instrumentation developed for the diagnosis of infectious disease, via quantification of organic biomarkers that are produced by associated bacteria. The technology is centred on a multichannel pulsed quantum cascade laser system that allows multiple lasers with different wavelengths to be used simultaneously, each selected to monitor a different diagnostic biomarker. The instrument also utilizes a hollow silica waveguide (HSW) gas cell which has a very high ratio of interaction pathlength to internal volume. This allows sensitive detection of low volume gas species from small volume biological samples. The spectroscopic performance of a range of HSW gas cells with different lengths and bore diameters has been assessed using methane as a test gas and a best-case limit of detection of 0.26 ppm was determined. The response time of this cell was measured as a 1,000 sccm flow of methane passed through it and was found to be 0.75 s. These results are compared with those obtained using a multi-pass Herriot cell. A prototype instrument has been built and approved for clinical trials for detection of lung infection in acute-care patients via analysis of ventilator breath. Demonstration of the instrument for headspace gas analysis is made by monitoring the methane emission from bovine faeces. The manufacture of a hospital-ready device for monitoring biomarkers of infection in the exhaled breath of intensive care ventilator patients is also presented.

Direct ultra-sensitive detection of pathogen biomarkers in blood could provide a universal strategy for diagnosis of bacterial infections, which remain a leading cause of morbidity and mortality in many areas of the world. Many factors complicate diagnosis, including the presence of multiple co-infections in a given patient, and lack of infrastructure in rural settings. In some pediatric patients, such as those in areas with poor resources, an additional challenge exists with low sample volumes due to age and other health factors such as anemia and dehydration. Our team is working on developing novel diagnostic assays, with a waveguide-based biosensor platform, to rapidly and specifically identify pathogen biomarkers from small samples of serum or plasma, allowing for the timely and sensitive diagnosis of infection at the point of care. In addition to the platform, we have developed novel membrane insertion and lipoprotein capture assay methods, to capture lipidated pathogen biomarkers in aqueous blood, by virtue of their interactions with host lipoprotein carriers. Herein, we demonstrate our efforts to adapt the lipoprotein capture assay for the detection of small concentrations of pathogen-secreted lipopolysaccharides in aqueous blood, with the ultimate aim of diagnosing Gram-negative infections effectively.

The last twenty years have seen the increasing demand by physicians of devices able to carry out fast and reliable measurements of chemical and biochemical parameters beside the patient’s bed so as to allow the formulation of a rapid and reliable diagnosis and/or the choice of the most appropriate therapy, avoiding the need for analysis of centralized laboratories. These are the so-called Point of Care Testing (POCT) devices that are becoming essential for the analysis of many diseases, where a quick medical attention is crucial for the patient's life. Optical biosensors and chemosensors can definitely play a fundamental role in this area and the use of optical fibers as optical links can also lead to invasive continuous measurements within the human body. The determination of one single parameter is sometimes sufficient, but it is important to emphasize that it is often necessary to monitor a panel of biomarkers associated to the onset and/or to the development of a definite pathology and, in this context, the optical biochip can play an essential role in the development of POCT equipment. The activity developed at the Institute of Applied Physics in this field in strict collaboration with physicians is described with particular attention to the measurement of bile-containing refluxes in the gastroesophageal apparatus in non- hospitalized patients, to the detection of gastric carbon dioxide in intensive care patients, to the simultaneous measurement of sepsis biomarkers in serum samples and to the measurements of immuno-suppressants in transplanted patients.

A novel therapeutic drug monitoring point of care testing (POCT) optical device for the detection of immunosuppressants in transplanted patients was designed and tested, with the body interface constituted by an intravascular microdialysis catheter (MicroEye®) which provides the dialysate as clinical sample. An optical biochip with 10 microchannels, based on total internal reflection fluorescence (TIRF), enables the frequent measurement of immunosuppressants. Heterogeneous competitive immunoassays for the detection of mycophenolic acid, tacrolimus and cyclosporine A are implemented on the different microchannels, with the derivative of the immunosuppressants immobilised on the bottom part of the micro-channels.

Blood glucose monitoring has been realised by biosensors in combination with micro-dialysis, using either subcutaneously or intravascularly implanted catheters. Another alternative is ex-vivo micro-dialysis of continuously sampled heparinized whole blood available from the patient even under critical care conditions. However, most devices suffer from inaccuracies due to variable recovery rates. Infrared spectrometry has been suggested for analyte quantification, since besides glucose other clinically relevant analytes can be simultaneously determined that are, e.g., important for intensive care patients. Perfusates with acetate and mannitol have been investigated as recovery markers (internal standards). In contrast to the previously used acetate, an almost linear dependency between mannitol loss and glucose recovery was observed for micro-dialysis of glucose spiked aqueous albumin solutions or porcine heparinized whole blood when testing flat membranes within a custom-made micro-dialysator. By this, a straightforward compensation of any dialysis recovery rate variation during patient monitoring is possible. The combination of microdialysis with infrared spectrometry provides a calibration-free assay for accurate continuous glucose monitoring, as reference spectra of dialysate components can be a-priori allocated.

Nowadays, continuous sensing systems are important point-of-care devices for the hospital and personalized patient technology. FTIR-spectrometers have been successfully employed for the development of bed-side systems. In-vivo applications for critically ill patients can be envisaged for analytes and parameters, which are of interest for intensive care such as lactate, urea, pCO₂ and pH. The human body maintains the blood pH around 7.4, but for severe pH level changes acidosis or alkalosis can lead to serious health problems. Three different buffer systems exist based on bicarbonate, phosphate and proteins; for the most important bicarbonate and phosphate systems infrared transmission spectra were recorded. By using the CO₂ and HCO₃ - bands of the bicarbonate spectra, the pH of the harvested biofluid can be predicted using the Henderson-Hasselbalch equation. Furthermore, we studied the solubility of CO₂ in aqueous solutions using gas mixtures of N₂ and CO₂ with known composition within partial pressures of CO₂ as relevant for invivo conditions. Thus, values of pCO₂ up to 150 mm Hg (200 hPa) with distilled water and a Ringer solution, which is an isotonic electrolyte solution used for medical infusion, were measured at 25 °C and 37 °C (normal body temperature).

Cytology tests, whether performed on body fluids, aspirates, or scrapings are commonly used to detect, diagnose, and monitor a wide variety of health conditions. Complete blood counts (CBCs) quantify the number of red and white blood cells in a blood volume, as well as the different types of white blood cells. There is a critical unmet need for an instrument that can perform CBCs at the point of care (POC), and there is currently no product in the US that can perform this test at the bedside. We have developed a system that is capable of tomographic images with sub-cellular resolution with consumer-grade broadband (LED) sources and CMOS detectors suitable for POC implementation of CBC tests. The systems consists of cascaded static Michelson and Sagnac interferometers that map phase (encoding depth) and a transverse spatial dimension onto a two-dimensional output plane. Our approach requires a 5 microliter sample, can be performed in 5 minutes or less, and does not require staining or other processing as it relies on intrinsic contrast. We will show results directly imaging and differentiating unstained blood cells using supercontinuum fiber lasers and LEDs as sources and CMOS cameras as sensors. We will also lay out the follow up steps needed, including image segmentation, analysis and classification, to verify performance and advance toward CBCs that can be performed bedside and do not require CLIA-certified laboratories.

Current flow-based blood counting devices require expensive and centralized medical infrastructure and are not appropriate for field use. In this paper we report a method to count red blood cells, white blood cells as well as platelets through a low-cost and fully-automated blood counting system. The approach consists of using a compact, custom-built microscope with large field-of-view to record bright-field and fluorescence images of samples that are diluted with a single, stable reagent mixture and counted using automatic algorithms. Sample collection is performed manually using a spring loaded lancet, and volume-metering capillary tubes. The capillaries are then dropped into a tube of pre-measured reagents and gently shaken for 10-30 seconds. The sample is loaded into a measurement chamber and placed on a custom 3D printed platform. Sample translation and focusing is fully automated, and a user has only to press a button for the measurement and analysis to commence. Cost of the system is minimized through the use of custom-designed motorized components. We performed a series of comparative experiments by trained and untrained users on blood from adults and children. We compare the performance of our system, as operated by trained and untrained users, to the clinical gold standard using a Bland-Altman analysis, demonstrating good agreement of our system to the clinical standard. The system’s low cost, complete automation, and good field performance indicate that it can be successfully translated for use in low-resource settings where central hematology laboratories are not accessible.

Portable devices have been recognized as the future linkage between end-users and lab-on-a-chip devices. It has a user friendly interface and provides apps to interface headphones, cameras, and communication duct, etc. In particular, the digital resolution of cameras installed in smartphones or pads already has a high imaging resolution with a high number of pixels. This unique feature has triggered researches to integrate optical fixtures with smartphone to provide microscopic imaging capabilities. In this paper, we report our study on developing a portable diagnostic tool based on the imaging system of a smartphone and a digital PCR biochip. A computational algorithm is developed to processing optical images taken from a digital PCR biochip with a smartphone in a black box. Each reaction droplet is recorded in pixels and is analyzed in a sRGB (red, green, and blue) color space. Multistep filtering algorithm and auto-threshold algorithm are adopted to minimize background noise contributed from ccd cameras and rule out false positive droplets, respectively. Finally, a size-filtering method is applied to identify the number of positive droplets to quantify target’s concentration. Statistical analysis is then performed for diagnostic purpose. This process can be integrated in an app and can provide a user friendly interface without professional training.

Recent advances in inkjet-printed optics have created a new class of lens fabrication technique. Lenses with a tunable geometry, magnification, and focal length can be fabricated by dispensing controlled amounts of liquid polymer onto a heated surface. This fabrication technique is highly cost-effective, and can achieve optically smooth surface finish. Dubbed DotLens, a single of which weighs less than 50 mg and occupies a volume less than 50 μL. DotLens can be attached onto any smartphone camera akin to a contact lens, and enable smartphones to obtain image resolution as fine as 1 µm. The surface curvature modifies the optical path of light to the image sensor, and enables the camera to focus as close as 2 mm. This enables microscopic imaging on a smartphone without any additional attachments, and has shown great potential in mobile point-of-care diagnostic systems, particularly for histology of tissue sections and cytology of blood cells. DotLens Smartphone Microscopy represents an innovative approach fundamentally different from other smartphone microscopes. In this paper, we describe the application and performance of DotLens smartphone microscopy in biological and biomedical research. In particular, we show recent results from images collected from pathology tissue slides with cancer features. In addition, we show performance in cytological analysis of blood smear. This tool has empowered Citizen Science investigators to collect microscopic images from various interesting objects.

This paper presents a technology of hybrid integration vertical cavity surface emitting lasers (VCSELs) directly on silicon photonics chip. By controlling the reflow of the solder balls used for electrical and mechanical bonding, the VCSELs were bonded at 10 degree to achieve the optimum angle-of-incidence to the planar grating coupler through vision based flip-chip techniques. The 1 dB discrepancy between optical loss values of flip-chip passive assembly and active alignment confirmed that the general purpose of the flip-chip design concept is achieved. This hybrid approach of integrating a miniaturized light source on chip opens the possibly of highly compact sensor system, which enable future portable and wearable diagnostics devices.

In immunoassay analyzers for in-vitro diagnostics, Xenon flash lamps have been widely used as excitation light sources. Recent advancements in UV LED technology and its advantages over the flash lamps such as smaller footprint, better wall-plug efficiency, narrow emission spectrum, and no significant afterglow, have made them attractive light sources for gated detection systems. In this paper, we report on the implementation of a 340 nm UV LED based time-resolved fluorescence system based on europium chelate as a fluorescent marker. The system performance was tested with the immunoassay based on the cardiac marker, TnI. The same signal-to-noise ratio as for the flash lamp based system was obtained, operating the LED below specified maximum current. The background counts of the system and its main contributors were measured and analyzed. The background of the system of the LED based unit was improved by 39% compared to that of the Xenon flash lamp based unit, due to the LEDs narrower emission spectrum and longer pulse width. Key parameters of the LED system are discussed to further optimize the signal-to-noise ratio and signal-to-background, and hence the sensitivity of the instrument.

The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of fluorescence analysis into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone is one of the steps for development of the device with a view to clinical diagnostics of redox potential. Recording of fluorescence was carried out with spectrometer using UV irradiation source with thin band (max at 287 and 330 nm) as a background radiation. Concentrations of ubiquinone from 0.25 to 2.5 mmol/l in explored samples were used for investigation. Recording data was processed using correlation analysis and differential analytical technique. The fourth derivative spectrum of fluorescence spectrum provided the basis for a multicomponent analysis of the solutions. As a technique in clinical diagnostics fluorescence analysis with processing method including differential spectrophotometry, it is step forward towards redox potential calculation and quality control in pharmacy for better health care.

Imaging photoplethysmography is a technique through which the morphology of the blood volume pulse can be obtained through non-contact video recordings of exposed skin with superficial vasculature. The acceptance of such a convenient modality for use in everyday applications may well depend upon the availability of consumer-grade imagers that facilitate ease-of-adoption. Multiple imagers have been used previously in concept demonstrations, showing improvements in quality of the extracted blood volume pulse signal. However, the use of multi-imager sensors requires synchronization of the frame exposures between the individual imagers, a capability that has only recently been available without creating custom solutions. In this work, we consider the use of multiple, commercially-available, synchronous imagers for use in imaging photoplethysmography. A commercially-available solution for adopting multi-imager synchronization was analyzed for 21 stationary, seated participants while ground-truth physiological signals were simultaneously measured. A total of three imagers were used, facilitating a comparison between fused data from all three imagers versus data from the single, central imager in the array. The within-subjects design included analyses of pulse rate and pulse signal-to-noise ratio. Using the fused data from the triple-imager array, mean absolute error in pulse rate measurement was reduced to 3.8 as compared to 7.4 beats per minute with the single imager. While this represents an overall improvement in the multi-imager case, it is also noted that these errors are substantially higher than those obtained in comparable studies. We further discuss these results and their implications for using readily-available commercial imaging solutions for imaging photoplethysmography applications.

Photoplethysmographic imaging (PPGI) systems are relatively new non-contact biophotonic diffuse reflectance systems able to assess arterial pulsations through transient changes in light-tissue interaction. Many PPGI studies have focused on extracting heart rate from the face or hand. Though PPGI systems can be used for widefield imaging of any anatomical area, whole-body investigations are lacking. Here, using a novel PPGI system, coded hemodynamic imaging (CHI), we explored and analyzed the pulsatility at major arterial locations across the whole body, including the neck (carotid artery), arm/wrist (brachial, radial and ulnar arteries), and leg/feet (popliteal and tibial arteries). CHI was positioned 1.5 m from the participant, and diffuse reactance from a broadband tungsten-halogen illumination was filtered using 850{1000 nm bandpass filter for deep tissue penetration. Images were acquired over a highly varying 24-participant sample (11/13 female/male, age 28.7±12.4 years, BMI 25.5±5.2 kg/m²), and a preliminary case study was performed. B-mode ultrasound images were acquired to validate observations through planar arterial characteristics.

Imaging photoplethysmography uses image sensors to measure changes in light absorption resulting from skin microvascular blood volume pulsations throughout the cardiac cycle. Imaging photoplethysmography has been demonstrated as an effective, non-contact means of assessing pulse rate, pulse rate variability, and respiration rate. Other potential uses include measuring spatial blood perfusion, oxygenation, and flow dynamics. Herein we demonstrate the development of a multispectral testbed for imaging photoplethysmography consisting of 12 monochromatic, 120fps imagers with 50nm, bandpass filters distributed from 400-750nm and contained in a 3D-printed, 4x3 grid housing mounted on a tripod positioned orthogonal to the subject. A co-located dual-CCD RGB/near-infrared imager records conventional RGB and NIR images expanding the spectral window recorded. After image registration, a multispectral image cube of the 13, partially overlapping bands is created. A spectrometer records high (spectral) resolution data from the participant’s right cheek using a collimating lens attached to the measurement fiber. In addition, a spatial array of 5 RGB imagers placed at 0°, ±20° and ±40° positions with respect to the subject is employed for motion and spatial robustness. All imagers are synchronized by a hardware trigger source synchronized with a reference, physiological measurement device recording the subject’s electrocardiography, bilateral fingertip and/or ear lobe photoplethysmography, bilateral galvanic skin response, and respiration signals. The development of the testbed and pilot data is presented. A full-scale evaluation of the spectral components of the imaging photoplethysmographic signal, optimization of iPPG SNR, and spatial perfusion and blood flow dynamics is currently underway.

Imaging photoplethysmography, a method using imagers to record absorption variations caused by microvascular blood volume pulsations, shows promise as a non-contact cardiovascular sensing technology. The first long-range imaging photoplethysmography measurements at distances of 25, 50, and 100 meters from the participant was recently demonstrated. Degraded signal quality was observed with increasing imager-to-subject distances. The degradation in signal quality was hypothesized to be largely attributable to inadequate light return to the image sensor with increasing lens focal length. To test this hypothesis, a follow-up evaluation with 27 participants was conducted outdoors with natural sunlight illumination resulting in ~5-33 times the illumination intensity. Video was recorded from cameras equipped with ultra-telephoto lenses and positioned at distances of 25, 50, 100, and 150 meters. The brighter illumination allowed high-definition video recordings at increased frame rates of 60fps, shorter exposure times, and lower ISO settings, leading to higher quality image formation than the previous indoor evaluation. Results were compared to simultaneous reference measurements from electrocardiography. Compared to the previous indoor study, we observed lower overall error in pulse rate measurement with the same pattern of degradation in signal quality with respect to increasing distance. This effect was corroborated by the signal-to-noise ratio of the blood volume pulse signal which also showed decreasing quality with respect to increasing distance. Finally, a popular chrominance-based method was compared to a blind source separation approach; while comparable in measurement of signal-to-noise ratio, we observed higher overall error in pulse rate measurement using the chrominance method in this data.

Background: After an acute traumatic spinal cord injury (SCI), the spinal cord is subjected to ischemia, hypoxia, and increased hydrostatic pressure which exacerbate further secondary damage and neuronal deficit. The purpose of this pilot study was to explore the use of near infrared spectroscopy (NIRS) for non-invasive and real-time monitoring of these changes within the injured spinal cord in an animal model. NIRS is a non-invasive optical technique that utilizes light in the near infrared spectrum to monitor changes in the concentration of tissue chromophores from which alterations in tissues oxygenation and perfusion can be inferred in real time. Methods: A custom-made miniaturized NIRS sensor was developed to monitor spinal cord hemodynamics and oxygenation noninvasively and in real time simultaneously with invasive, intraparenchymal monitoring in a pig model of SCI. The spinal cord around the T10 injury site was instrumented with intraparenchymal probes inserted directly into the spinal cord to measure oxygen pressure, blood flow, and hydrostatic pressure, and the same region of the spinal cord was monitored with the custom-designed extradural NIRS probe. We investigated how well the extradural NIRS probe detected intraparenchymal changes adjacent to the injury site after alterations in systemic blood pressure, global hypoxia, and traumatic injury generated by a weight-drop contusion. Results: The NIRS sensor successfully identified periods of systemic hypoxia, re-ventilation and changes in spinal cord perfusion and oxygenation during alterations of mean arterial pressure and following spinal cord injury. Conclusion: This pilot study indicates that extradural NIRS monitoring of the spinal cord is feasible as a non-invasive optical method to identify changes in spinal cord hemodynamics and oxygenation in real time. Further development of this technique would allow clinicians to monitor real-time physiologic changes within the injured spinal cord during the acute post-injury period.

In reconstructive surgery, impeded blood flow in microvascular free flaps due to a compromise in arterial or venous patency secondary to blood clots or vessel spasms can rapidly result in flap failures. Thus, the ability to detect changes in microvascular free flaps is critical. In this paper, we report progress on in vivo pre-clinical testing of a compact, multimodal, fiber-based diffuse correlation and reflectance spectroscopy system designed to quantitatively monitor tissue perfusion in a porcine model’s surgically-grafted free flap. We also describe the device’s sensitivity to incremental blood flow changes and discuss the prospects for continuous perfusion monitoring in future clinical translational studies.

The purpose of this study was to test the hypothesis that mobile, wireless near-infrared spectroscopy (NIRS) instruments can be used during standard lung function tests to measure adaptations in respiratory muscle metabolism over weeks to months. In eight varsity soccer players at 0 weeks and after 16 weeks of routine training, commercially available mobile, wireless NIRS instruments were used to measure oxygenation and hemodynamics in the sternocleidomastoid (SCM, accessory inspiration muscle). During maximal expiratory pressure (MEP) and forced vital capacity (FVC) maneuvers we determined peak or antipeak changes relative to baseline in oxygenation and hemodynamics: Δ%Sat (muscle oxygen saturation), ΔtHb (total hemoglobin), ΔO2Hb (oxygenated hemoglobin), and ΔHHb (deoxygenated hemoglobin). Subjects reported that the average training load was ~13.3 h/week during the 16 study weeks, compared to ~10.4 h/week during 12 prior weeks. After 16 weeks of training compared to 0 weeks we found statistically significant increases in SCM Δ%Sat (57.7%), ΔtHb (55.3%), and ΔO2Hb (56.7%) during MEP maneuvers, and in SCM Δ%Sat (64.8%), ΔtHb (29.4%), and ΔO2Hb (51.6%) during FVC maneuvers. Our data provide preliminary evidence that NIRS measurements during standard lung function tests are sufficiently sensitive to detect improvements or declines in respiratory muscle metabolism over periods of weeks to months due to training, disease, and rehabilitation exercise.

Monte Carlo modeling of photon propagation has been used in the examination of particular areas of the body to further enhance the understanding of light propagation through tissue. This work seeks to improve upon the established simulation methods through more accurate representations of the simulated tissues in the wrist as well as the characteristics of the light source. The Monte Carlo simulation program was developed using Matlab. Generation of different tissue domains, such as muscle, vasculature, and bone, was performed in Solidworks, where each domain was saved as a separate .stl file that was read into the program. The light source was altered to give considerations to both viewing angle of the simulated LED as well as the nominal diameter of the source. It is believed that the use of these more accurate models generates results that more closely match those seen in-vivo, and can be used to better guide the design of optical wrist-worn measurement devices.

We employ a physical theory to construct a computational model that accounts for both multiple scattering and absorption of light. The approach does not require a calibration model. Mie theory to describe single particle scattering, which is combined with the diffuse approximation to the radiative transfer equation to provides an analytical prediction of the reflectance. This approach is applied to experimental reflectance measurements on polystyrene particle suspensions with a wide range of particle radii and volume fractions. The method provides good estimates of the suspension properties from a full NIR-vis-UV spectrum.

The pulse oximetry is a non-invasive method to monitor the oxygen saturation and is clinically used for many years. However this technology has some limitations. In case of the presence of dysfunctional hemoglobin derivatives as carboxyhemoglobin (COHb) or methemoglobin (MetHb) the readings of the pulse oximeter are distorted. This erroneous diagnosis of the patient’s status can result in a life threatening situation. This paper will describe a sensor system for noninvasive determination of carboxy- and methemoglobin.

Optical sensing techniques for organic and biological molecules traditionally require the collection of complete, well-defined, vibrational spectra of a sample. The vibrational absorption bands of the spectra are identified, and statistical methods are then utilized to determine the moieties and concentration of target analytes present in a given sample. In this work, we present a new, non-spectroscopic alternative technique to molecular vibrational sensing. This biomimetic method, based on human color vision, uses only three broad, overlapping infrared (IR) optical filters to discriminate between chemicals with similar vibrational absorption bands. Unique detection vectors are defined by the interaction of a given chemical’s absorption bands with the three filter channels. Identification of the analytes present in a sample are then determined based on these detection vectors. We present multiple studies that demonstrate the ability of this approach to clearly discriminate between molecules with similar infrared vibrational absorption bands. We show that this method has the ability to precisely identify specific analytes in the presence of potential interferents with similar infrared absorption bands in the same sample. An optical filter based sensor that operates in the mid-IR using low power components, requiring no spectral scanning has been developed using this technique, and results using this sensor are shown. This method has the potential to lead the development of small, rugged optical sensors for non-invasive diagnostics and sensing of biological fluids.

An oxidative damage in cell structures is a basis of most mechanisms that lead to health diseases and senescence of human body. The presence of antioxidant issues such as redox potential imbalance in human body is a very important question for modern clinical diagnostics. Implementation of multispectral and colour analysis of the human skin into optical diagnostics of such wide distributed in a human body antioxidant as ubiquinone can be one of the steps for development of the device with a view to clinical diagnostics of redox potential or quality control of the cosmetics. The recording of multispectral images of the hand skin with monochromatic camera and a set of coloured filters was provided in the current research. Recording data of the multispectral imaging technique was processed using principal component analysis. Also colour characteristics of the skin before and after the skin treatment with facial mask which contains ubiquinone were calculated. The results of the mask treatment were compared with the treatment using oily ubiquinone solution. Despite the fact that results did not give clear explanation about healthy skin or skin stressed by reactive oxygen species, methods which were described in this research are able to identify how skin surface is changing after the antioxidant treatment. In future it is important to provide biomedical tests during the optical tests of the human skin.

Recently the essential amino acid tryptophan has attracted attention in cancer research, as its metabolism regulates antitumor immune responses and tumor-intrinisic properties. Measurement techniques to determine tryptophan concentrations of aqueous solutions are therefore vastly important for ongoing research in this field. Recently, Terahertz spectroscopy has illustrated its high potential to be utilized for the characterization of bio-crystals and bio-molecules. We have developed a method to detect and quantify tryptophan based on the parallel-plate waveguide (PPWG) technology together with a commercially available terahertz time domain spectroscopy (TDS) system called “T-SPECTRALYZER F” providing a spectral bandwidth from 0.1 THz to 5 THz. As Terahertz waves are strongly absorbed by water, a measurement of aqueous solutions is a challenging task. In our setup, parallel-plate waveguides are used to detect low tryptophan concentrations, in principle, in solution. Drop-casting the solution into the waveguide forms a dry homogeneous film after evaporation of the solvent. A spectroscopic analysis of the transmission spectrum of the waveguide allows for a determination of the tryptophan concentration as the detection limit is drastically improved by the use of waveguides. In order to increase the detection sensitivity of this measurement technique the terahertz setup was encapsulated in a dry air box to reduce water vapor effects. Here we introduce the working mechanism of “TSPECTRALYZER F” and present the spectral evaluation procedures applied. Finally, we show the improvement of the detection sensitivity using a terahertz time-domain spectroscopy system together with PPWG technology.

Point-of-care diagnostics are of interest in the medical, security and food industry, the latter particularly for screening food adulterated for economic gain. Milk adulteration continues to be a major problem worldwide and different methods to detect fraudulent additives have been investigated for over a century. Laboratory based methods are limited in their application to point-of-collection diagnosis and also require expensive instrumentation, chemicals and skilled technicians. This has encouraged exploration of spectroscopic methods as more rapid and inexpensive alternatives. Raman spectroscopy has excellent potential for screening of milk because of the rich complexity inherent in its signals. The rapid advances in photonic technologies and fabrication methods are enabling increasingly sensitive portable mini-Raman systems to be placed on the market that are both affordable and feasible for both point-of-care and point-of-collection applications. We have developed a powerful spectroscopic method for rapidly screening liquid milk for sucrose and four nitrogen-rich adulterants (dicyandiamide (DCD), ammonium sulphate, melamine, urea), using a combined system: a small, portable Raman spectrometer with focusing fibre optic probe and optimized reflective focusing wells, simply fabricated in aluminium. The reliable sample presentation of this system enabled high reproducibility of 8% RSD (residual standard deviation) within four minutes. Limit of detection intervals for PLS calibrations ranged between 140 - 520 ppm for the four N-rich compounds and between 0.7 - 3.6 % for sucrose. The portability of the system and reliability and reproducibility of this technique opens opportunities for general, reagentless adulteration screening of biological fluids as well as milk, at point-of-collection.

Based on its integrated camera, new optical attachment, and inherent computing power, we propose an instrument design and validation that can potentially provide an objective and accurate method to determine surface meat color change and myoglobin redox forms using a smartphone-based spectrometer. System is designed to be used as a reflection spectrometer which mimics the conventional spectrometry commonly used for meat color assessment. We utilize a 3D printing technique to make an optical cradle which holds all of the optical components for light collection, collimation, dispersion, and a suitable chamber. A light, which reflects a sample, enters a pinhole and is subsequently collimated by a convex lens. A diffraction grating spreads the wavelength over the camera’s pixels to display a high resolution of spectrum. Pixel values in the smartphone image are translated to calibrate the wavelength values through three laser pointers which have different wavelength; 405, 532, 650 nm. Using an in-house app, the camera images are converted into a spectrum in the visible wavelength range based on the exterior light source. A controlled experiment simulating the refrigeration and shelving of the meat has been conducted and the results showed the capability to accurately measure the color change in quantitative and spectroscopic manner. We expect that this technology can be adapted to any smartphone and used to conduct a field-deployable color spectrum assay as a more practical application tool for various food sectors.

In this paper we present a fiber-based low-coherence self-mixing interferometer exploiting a single-arm approach to measure the flow in a pipe. The main advantages of the proposed system are the flexibility offered by fiber-connected optical head, a greater ease of alignment, the rejection of “common-mode” vibrations, and greater stability. Thanks to the use of a low-coherence source, the proposed system investigates the velocity of the scattering particles owing only in a fixed and well defined region located close to the duct wall itself. The reported experimental results demonstrate that in laminar flow regime the developed system is able to determine the flow and it is quite robust to variation in the scatterers concentration. Increasing the scatterers concentration of about 24 times, the sensitivity S has reduced of less than 30%.

It is essential to monitor tissue perfusion during and after reconstructive surgery, as restricted blood flow can result in graft failures. Current clinical procedures are insufficient to monitor tissue perfusion, as they are intermittent and often subjective. To address this unmet clinical need, a compact, low-cost, multimodal diffuse correlation spectroscopy and diffuse reflectance spectroscopy system was developed. We verified system performance via tissue phantoms and experimental protocols for rigorous bench testing. Quantitative data analysis methods were employed and tested to enable the extraction of tissue perfusion parameters. This design verification study assures data integrity in future in vivo studies.