Label-Free Optical Sensing and Medical Grade Resins: An Advanced Approach to Investigate Cell-Material Interaction and Biocompatibility.

The Corning Epic® label-free (ELF) system is an innovative technology widely used in drug discovery, immunotherapy, G-protein-associated studies, and biocompatibility tests. Here, we challenge the use of ELF to further investigate the biocompatibility of resins used in manufacturing of blood filters, a category of medical devices representing life-saving therapies for the increasing number of patients with kidney failure. The biocompatibility assays were carried out by developing a cell model aimed at mimicking the clinical use of the blood filters and complementing the existing cytotoxicity assay requested by ISO10993-5. Experiments were performed by putting fibroblasts in both direct contact with two types of selected resins, and indirect contact by means of homemade customized well inserts that were precisely designed and developed for this technology. For both types of contact, fibroblasts were cultured in medium and human plasma. ELF tests confirmed the biocompatibility of both resins, highlighting a statistically significant different biological behavior of a polyaromatic resin compared to control and ion-exchanged resin, when materials were in indirect contact and soaking with plasma. Overall, the ELF test is able to mimic clinical scenarios and represents a promising approach to investigate biocompatibility, showing peculiar biological behaviors and suggesting the activation of specific intracellular pathways.

Novel bioprinted 3D model to human fibrosis investigation.

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFß), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α - smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFß stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFß stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis.

Driver Drowsiness Detection: A Machine Learning Approach on Skin Conductance.

The majority of car accidents worldwide are caused by drowsy drivers. Therefore, it is important to be able to detect when a driver is starting to feel drowsy in order to warn them before a serious accident occurs. Sometimes, drivers are not aware of their own drowsiness, but changes in their body signals can indicate that they are getting tired. Previous studies have used large and intrusive sensor systems that can be worn by the driver or placed in the vehicle to collect information about the driver's physical status from a variety of signals that are either physiological or vehicle-related. This study focuses on the use of a single wrist device that is comfortable for the driver to wear and appropriate signal processing to detect drowsiness by analyzing only the physiological skin conductance (SC) signal. To determine whether the driver is drowsy, the study tests three ensemble algorithms and finds that the Boosting algorithm is the most effective in detecting drowsiness with an accuracy of 89.4%. The results of this study show that it is possible to identify when a driver is drowsy using only signals from the skin on the wrist, and this encourages further research to develop a real-time warning system for early detection of drowsiness.

A transimpedance preamplifier using a feedforward approach for robust rejection of DC photogenerated currents.

The preamplifier proposed in this paper is designed to extract weak variable photogenerated signals from a high-level continuous background ensuring low noise and high transimpedance gain. An efficient cancellation of the DC component directly at the photodetector output, exploiting a feedforward approach, allows us to properly amplify the variable signal components of interest avoiding saturation of the preamplifier. Furthermore, the large transimpedance gain allows for minimizing the effects of the noise introduced by the following stages on the signal processing chain. In the paper, we present the proposed approach and a possible circuit realization with a signal AC/DC ratio as small as 1/1000 ensuring low noise, high gain, and a considerable bandwidth. The realized preamplifier offers a Noise Equivalent Power NEP ≃ 1.12 nW, an in-band transimpedance gain of 4.4 MΩ, and a wide bandwidth from about 1 Hz up to 100 kHz, making it suitable for use in several applications both in biomedical and industrial fields.

An IoT Measurement System Based on LoRaWAN for Additive Manufacturing.

The Industrial Internet of Things (IIoT) paradigm represents a significant leap forward for sensor networks, potentially enabling wide-area and innovative measurement systems. In this scenario, smart sensors might be equipped with novel low-power and long range communication technologies to realize a so-called low-power wide-area network (LPWAN). One of the most popular representative cases is the LoRaWAN (Long Range WAN) network, where nodes are based on the widespread LoRa physical layer, generally optimized to minimize energy consumption, while guaranteeing long-range coverage and low-cost deployment. Additive manufacturing is a further pillar of the IIoT paradigm, and advanced measurement capabilities may be required to monitor significant parameters during the production of artifacts, as well as to evaluate environmental indicators in the deployment site. To this end, this study addresses some specific LoRa-based smart sensors embedded within artifacts during the early stage of the production phase, as well as their behavior once they have been deployed in the final location. An experimental evaluation was carried out considering two different LoRa end-nodes, namely, the Microchip RN2483 LoRa Mote and the Tinovi PM-IO-5-SM LoRaWAN IO Module. The final goal of this research was to assess the effectiveness of the LoRa-based sensor network design, both in terms of suitability for the aforementioned application and, specifically, in terms of energy consumption and long-range operation capabilities. Energy optimization, battery life prediction, and connectivity range evaluation are key aspects in this application context, since, once the sensors are embedded into artifacts, they will no longer be accessible.

A Comprehensive Review on Time Sensitive Networks with a Special Focus on Its Applicability to Industrial Smart and Distributed Measurement Systems.

The groundbreaking transformations triggered by the Industry 4.0 paradigm have dramatically reshaped the requirements for control and communication systems within the factory systems of the future. The aforementioned technological revolution strongly affects industrial smart and distributed measurement systems as well, pointing to ever more integrated and intelligent equipment devoted to derive accurate measurements. Moreover, as factory automation uses ever wider and complex smart distributed measurement systems, the well-known Internet of Things (IoT) paradigm finds its viability also in the industrial context, namely Industrial IoT (IIoT). In this context, communication networks and protocols play a key role, directly impacting on the measurement accuracy, causality, reliability and safety. The requirements coming both from Industry 4.0 and the IIoT, such as the coexistence of time-sensitive and best effort traffic, the need for enhanced horizontal and vertical integration, and interoperability between Information Technology (IT) and Operational Technology (OT), fostered the development of enhanced communication subsystems. Indeed, established technologies, such as Ethernet and Wi-Fi, widespread in the consumer and office fields, are intrinsically non-deterministic and unable to support critical traffic. In the last years, the IEEE 802.1 Working Group defined an extensive set of standards, comprehensively known as Time Sensitive Networking (TSN), aiming at reshaping the Ethernet standard to support for time-, mission- and safety-critical traffic. In this paper, a comprehensive overview of the TSN Working Group standardization activity is provided, while contextualizing TSN within the complex existing industrial technological panorama, particularly focusing on industrial distributed measurement systems. In particular, this paper has to be considered a technical review of the most important features of TSN, while underlining its applicability to the measurement field. Furthermore, the adoption of TSN within the Wi-Fi technology is addressed in the last part of the survey, since wireless communication represents an appealing opportunity in the industrial measurement context. In this respect, a test case is presented, to point out the need for wirelessly connected sensors networks. In particular, by reviewing some literature contributions it has been possible to show how wireless technologies offer the flexibility necessary to support advanced mobile IIoT applications.

Vision-Based Eye Image Classification for Ophthalmic Measurement Systems.

The accuracy and the overall performances of ophthalmic instrumentation, where specific analysis of eye images is involved, can be negatively influenced by invalid or incorrect frames acquired during everyday measurements of unaware or non-collaborative human patients and non-technical operators. Therefore, in this paper, we investigate and compare the adoption of several vision-based classification algorithms belonging to different fields, i.e., Machine Learning, Deep Learning, and Expert Systems, in order to improve the performance of an ophthalmic instrument designed for the Pupillary Light Reflex measurement. To test the implemented solutions, we collected and publicly released PopEYE as one of the first datasets consisting of 15 k eye images belonging to 22 different subjects acquired through the aforementioned specialized ophthalmic device. Finally, we discuss the experimental results in terms of classification accuracy of the eye status, as well as computational load analysis, since the proposed solution is designed to be implemented in embedded boards, which have limited hardware resources in computational power and memory size.

Assessing Biocompatibility of Face Mask Materials during COVID-19 Pandemic by a Rapid Multi-Assays Strategy.

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.

Testing Surgical Face Masks in an Emergency Context: The Experience of Italian Laboratories during the COVID-19 Pandemic Crisis.

The first wave of the COVID-19 pandemic brought about a broader use of masks by both professionals and the general population. This resulted in a severe worldwide shortage of devices and the need to increase import and activate production of safe and effective surgical masks at the national level. In order to support the demand for testing surgical masks in the Italian context, Universities provided their contribution by setting up laboratories for testing mask performance before releasing products into the national market. This paper reports the effort of seven Italian university laboratories who set up facilities for testing face masks during the emergency period of the COVID-19 pandemic. Measurement set-ups were built, adapting the methods specified in the EN 14683:2019+AC. Data on differential pressure (DP) and bacterial filtration efficiency (BFE) of 120 masks, including different materials and designs, were collected over three months. More than 60% of the masks satisfied requirements for DP and BFE set by the standard. Masks made of nonwoven polypropylene with at least three layers (spunbonded-meltblown-spunbonded) showed the best results, ensuring both good breathability and high filtration efficiency. The majority of the masks created with alternative materials and designs did not comply with both standard requirements, resulting in suitability only as community masks. The effective partnering between universities and industries to meet a public need in an emergency context represented a fruitful example of the so-called university "third-mission".

Anterior Chamber Angle Assessment Techniques: A Review.

Assessment of the anterior chamber angle (ACA) is an essential part of the ophthalmological examination. It is intrinsically related to the diagnosis and treatment of glaucoma and has a role in its prevention. Although slit-lamp gonioscopy is considered the gold-standard technique for ACA evaluation, its poor reproducibility and the long learning curve are well-known shortcomings. Several new imaging techniques for angle evaluation have been developed in the recent years. However, whether these instruments may replace or not gonioscopy in everyday clinical practice remains unclear. This review summarizes the last findings in ACA evaluation, focusing on new instruments and their application to the clinical practice. Special attention will be given to the comparison between these new techniques and traditional slit-lamp gonioscopy. Whereas ultrasound biomicroscopy and anterior segment optical coherence tomography provide quantitative measurements of the anterior segment's structures, new gonio-photographic systems allow for a qualitative assessment of angle findings, similarly to gonioscopy. Recently developed deep learning algorithms provide an automated classification of angle images, aiding physicians in taking faster and more efficient decisions. Despite new imaging techniques made analysis of the ACA more objective and practical, the ideal method for ACA evaluation has still to be determined.

In vivo real time non invasive monitoring of brain penetration of chemicals with near-infrared spectroscopy: Concomitant PK/PD analysis.

BACKGROUND: Near-infrared spectroscopy (NIRS) is a non-invasive technique that monitors changes in oxygenation of haemoglobin. The absorption spectra of near-infrared light differ for the oxygenation-deoxygenation states of haemoglobin (oxygenate (HbO2) and deoxygenate (Hb), respectively) so that these two states can be directly monitored. COMPARISON WITH EXISTING METHOD(S): Different methodologies report different basal values of HbO2 and Hb absolute concentrations in brain. Here, we attempt to calculate basal HbO2 levels in rat CNS via evaluation of the influence of exogenous oxygen or exogenous carbon dioxide on the NIRS parameters measured in vivo. NEW METHOD: Furthermore the possibility that changes of haemoglobin oxygenation in rat brain as measured by NIRS might be a useful index of brain penetration of chemical entities has been investigated. Different compounds from different chemical classes were selected on the basis of parallel ex vivo and in vivo pharmacokinetic (PK/PD) studies of brain penetration and overall pharmacokinetic profile. RESULTS: It appeared that NIRS might contribute to assess brain penetration of chemical entities, i.e. significant changes in NIRS signals could be related to brain exposure, conversely the lack of significant changes in relevant NIRS parameters could be indicative of low brain exposure. CONCLUSIONS: This work is proposing a further innovation on NIRS preclinical applications i.e. a "chemical" NIRS [chNIRS] approach for determining penetration of drugs in animal brain. Therefore, chNIRS could became a non invasive methodology for studies on neurobiological processes and psychiatric diseases in preclinical but also a translational strategy from preclinical to clinical investigations.

An in vitro model of a system of electrical potential compensation in extracorporeal circulation.

OBJECTIVES: Extracorporeal circulation (ECC) in patients undergoing cardiac surgery induces systemic immune-inflammatory reaction that results in increased postoperative morbidity. Many factors are responsible for the adverse response after ECC. The present in vitro study aimed to investigate electric charges (ECs) generated during ECC, to set a device compensating the ECs, and checking its effect on red blood cells (RBC). MATERIALS AND METHODS: The electrical signals of blood in ECC were collected by a custom developed low-noise electronic circuit, processed by a digital oscilloscope (DSO) and a dynamic signal analyzer (DSA). The compensation of ECs was performed using a compensation device, injecting a nulling charge into the blood circuit. The compensation effect of the ECs on RBCs was evaluated by scanning electron microscope (SEM). RESULTS: The electrical analysis performed using both the DSO and the DSA confirmed the EC formation during ECC. The notable electric signals recorded in standard ECC circuits substantially nulled once the compensation device was used, thus confirming efficient EC compensation. After two hours of ECC, the SEM non-blended test on human RBC samples highlighted morphological changes in acanthocytes of the normal biconcave-shaped RBC. CONCLUSIONS: The outcomes confirm the development of parasitic ECs during ECC and that a suppressor system may decrease the potential damage of ECs. Nevertheless, further studies are ongoing in order to investigate the complex mechanisms related to lymphocytes and platelet morphological and physiological chances during triboelectric charges in ECC.

In vivo diffuse correlation spectroscopy investigation of the ocular fundus.

Diffuse correlation spectroscopy (DCS) measurements in vivo recorded from rabbits' ocular fundus are presented. Despite the complexity of these ocular tissues, we provide a clear and simple demonstration of the DCS abilities to analyze variations in physiological quantities of clinical interest. Indeed, the reported experimental activities demonstrate that DCS can reveal both choroidal-flow and temperature variations and detect nano- and micro-aggregates in ocular fundus circulation. Such abilities can be of great interest both in fundamental research and practical clinical applications. The proposed measuring system can be useful in: (a) monitoring choroidal blood flow variations, (b) determining the end-point for photo-dynamic therapy and transpupillary thermo therapy and, (c) managing the dye injection and determining an end-point for dye-enhanced photothrombosis. Moreover, it could allow both diagnoses when the presence of nano- and micro-aggregates is related to specific diseases and verifying the effects of nanoparticle injection in nanomedicine. Even though the reported results demonstrate the applicability of DCS to investigate ocular fundus, a detailed and accurate investigation of the limits of detection is beyond the scope of this article.

Does pupil dilation influence subfoveal choroidal laser Doppler flowmetry?

PURPOSE: The aim of this study was to assess (i) whether pupil dilation with tropicamide influences subfoveal choroidal blood flow, as assessed by continuous laser Doppler flowmetry (LDF) and (ii) if this is the case, whether the effect is due to a haemodynamic response of the drug-induced dilation. METHODS: Following the instillation of one drop of 1% tropicamide in one eye of 18 healthy, nonsmoking volunteers (age 20-25 years), the subfoveal choroidal LDF parameters (Vel, Vol and ChBF) were recorded during 30 min, at 3-min intervals under two paradigms: through an artificial pupil (4 mm diameter) placed in front of the cornea (P1) and without this artificial pupil (P2). RESULTS: Tropicamide increased the pupil diameter from 3.3 ± 0.4 mm (mean ± SD) to 8.3 ± .4 mm. Full dilation was reached at ~24 min. During this period of time, linear regression analysis demonstrated that none of the LDF parameters varied significantly (p > 0.05), either under P1 or P2. Based on a group of 12 subjects, the smallest (%) change in the mean value of ChBF (ChBFm ) that would be detectable (sensitivity of the method, S) was found to be 2% for P1 and 6% for P2. The average coefficient of variation of ChBFm based on eight measurements during dilation was greater for P2 than for P1 by a factor of approximately 2. CONCLUSION: Tropicamide had no significant influence on the subfoveal choroidal LDF parameters measured by continuous LDF during pupil dilation. Furthermore, pupil dilation did not affect ChBFm by more than the calculated minimum percentage change of 6% detectable with our method.

Development of a sensor system for the determination of sanitary quality of grapes.

n instrument for the automatic quantification of glycerol in grapes has been developed. We verify here that this analyte can be used as a benchmark of a serious disease affecting the grapevines, namely Botrytis cinerea. The core of the instrument is an amperometric biosensor consisting of a disposable screen printed electrode, generating the analytical signal thanks to a bi-enzymatic process involving glycerol dehydrogenase and diaphorase. The full automation of the analysis is realised by three micropumps and a microprocessor under control of a personal computer. The pumps allow the correct and constant dilution of the grape juice with a buffer solution also containing [Fe(CN)6]3- redox mediator and the injection of NAD+ cofactor when the baseline signal reaches a steady state; the instrument leads to automated reading of the analytical signal and the consequent data treatment. Although the analytical method is based on an amperometric technique that, owing to heavy matrix effects, usually requires an internal calibration, the analyses indicate that a unique external calibration is suitable for giving accurate responses for any grapes, both white and black ones.

Continuous haematic pH monitoring in extracorporeal circulation using a disposable florescence sensing element.

During extracorporeal circulation (ECC), blood is periodically sampled and analyzed to maintain the blood-gas status of the patient within acceptable limits. This protocol has well-known drawbacks that may be overcome by continuous monitoring. We present the characterization of a new pH sensor for continuous monitoring in ECC. This monitoring device includes a disposable fluorescence-sensing element directly in contact with the blood, whose fluorescence intensity is strictly related to the pH of the blood. In vitro experiments show no significant difference between the blood gas analyzer values and the sensor readings; after proper calibration, it gives a correlation of R>0.9887, and measuring errors were lower than the 3% of the pH range of interest (RoI) with respect to a commercial blood gas analyzer. This performance has been confirmed also by simulating a moderate ipothermia condition, i.e., blood temperature 32°C, frequently used in cardiac surgery. In ex vivo experiments, performed with animal models, the sensor is continuously operated in an extracorporeal undiluted blood stream for a maximum of 11 h. It gives a correlation of R>0.9431, and a measuring error lower than the 3% of the pH RoI with respect to laboratory techniques.

Disposable fluorescence optical pH sensor for near neutral solutions.

The design, development and performance evaluation of a fluorescence-based pH sensor for on-line measurements is presented. The pKa of the sensing element has been calculated to be 7.9, thus the sensor is suitable for measurement of near neutral solutions. The sensor consists of a low-cost disposable polymer sensing probe, in contact with the solution under test, interrogated by an optoelectronic transduction system. The pH sensitive dye is based on fluorescein O-methacrylate, which has been covalently linked to a hydrogel matrix, realized through the use of HEMA (2-hydroxyethyl methacrylate), HDDA (1,6-hexanediol diacrylate) and PEGDA (polyethylene glycol diacrylate). The optical interrogation setup, together with the electronics, has been developed to acquire and process the fluorescence signal. The sensor works over a pH range between 6.5 and 9.0. In the range between 7.0 and 8.0, the sensor shows a linear behavior with a maximum linearity error of 5%. Thanks to the good performance of the sensing element and transduction system, the short term drift of the reading (measured over 40 min) is lower than 0.15%. The measuring system also exhibits good performance in terms of response time and reproducibility.

Construction and evaluation of a disposable pH sensor based on a large core plastic optical fiber.

The fabrication and characterization of a disposable optical fiber sensor for the detection of pH in the range 5-8 are described. The sensing element is a drop of sol-gel hybrid material containing phenol red and deposited onto the tip of a large core plastic optical fiber. This fiber is also exploited for the optical interrogation. This probe can be used as a disposable part of a measuring system. The dynamic range and temporal response of the sensor are here investigated.

A simple readout electronics for automatic power controlled self-mixing laser diode systems.

The paper describes a simple electronic circuit to drive a laser diode for self-mixing interferometry. The network integrates a stable commercial automatic power controller and a current mirror based readout of the interferometric signal. The first prototype version of the circuit has been realized and characterized. The system allows easily performing precise interferometric measurements with no thermostatic circuitry to stabilize the laser diode temperature and an automatic control gain network to compensate emitted optical power fluctuations. To achieve this result, in the paper a specific calibration procedure to be performed is described.

Optical and electrical recording of neural activity evoked by graded contrast visual stimulus.

BACKGROUND: Brain activity has been investigated by several methods with different principles, notably optical ones. Each method may offer information on distinct physiological or pathological aspects of brain function. The ideal instrument to measure brain activity should include complementary techniques and integrate the resultant information. As a "low cost" approach towards this objective, we combined the well-grounded electroencephalography technique with the newer near infrared spectroscopy methods to investigate human visual function. METHODS: The article describes an embedded instrumentation combining a continuous-wave near-infrared spectroscopy system and an electroencephalography system to simultaneously monitor functional hemodynamics and electrical activity. Near infrared spectroscopy (NIRS) signal depends on the light absorption spectra of haemoglobin and measures the blood volume and blood oxygenation regulation supporting the neural activity. The NIRS and visual evoked potential (VEP) are concurrently acquired during steady state visual stimulation, at 8 Hz, with a b/w "windmill" pattern, in nine human subjects. The pattern contrast is varied (1%, 10%, 100%) according to a stimulation protocol. RESULTS: In this study, we present the measuring system; the results consist in concurrent recordings of hemodynamic changes and evoked potential responses emerging from different contrast levels of a patterned stimulus. The concentration of [HbO2] increases and [HHb] decreases after the onset of the stimulus. Their variation shows a clear relationship with the contrast value: large contrast produce huge difference in concentration, while low contrast provokes small concentration difference. This behaviour is similar to the already known relationship between VEP response amplitude and contrast. CONCLUSION: The simultaneous recording and analysis of NIRS and VEP signals in humans during visual stimulation with a b/w pattern at variable contrast, demonstrates a strong linear correlation between hemodynamic changes and evoked potential amplitude. Furthermore both responses present a logarithmic profile with stimulus contrast.