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A Wearable Microfluidic Device for Capture and Quantitative Analysis of Glucose coupled with Skin Electrodermal Activity

A multiparametric, non-invasive, and reagentless sensing strategy for diabetic monitoring is proposed based on a bespoke graphite ink “writable” formulation (including biocompatible binders and modifiers) used as a conductive layer for glucose oxidase immobilisation within an epidermal patch. This enables the encapsulation of heterocyclic quinoid species 1,10-phenanthroline-5,6-dione 1 which acts as a proton and electron acceptor for FADH2 cofactor regeneration. The surface characterisation of the ink layer was achieved via FTIR, thermal analysis (TGA/DSC), and scanning electron microscopy. Voltammetric and pulse techniques establish analytical performance criteria for the mediated device over physiological glucose levels in sweat (10-200 mM 2) at neutral pH levels. Hygroscopic hydrogels (chitosan/poly vinyl alcohol) and nanofibrous mats form overlaid membranes as sweat collection zones, sandwiched beneath a cotton fabric wicking layer for fingertip perspiration harvesting.

The prototype electronic control system involves a customisable Arduino-based potentiostat 3 with off-the-shelf electronic components capable of performing electrochemical measurements, as well as recording temperature and galvanic skin sensor responses (GSR) 4. The addition of electrodermal activity via a GSR sensor detection module and a temperature probe makes for a multiparametric system which responds to electrical activity in the skin due to the variation in moisture levels due to sweating. GSR reflects sweat gland activity and changes in the sympathetic nervous system, as well as the activity of the sweat glands in response to sympathetic nervous stimulation4. Calibration parameters can thus be adjusted dynamically relative to changes in temperature and other measurement variables. Such a system requires small sample volumes (<50 mL), provides rapid time to result <1 min, and is portable and disposable. The integration of allied electronics has the potential to carry out transduction and wireless transmission, enabling smart and remote healthcare.

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Detection of Tetrodotoxins and their Analogues in Pufferfish with a Single-Cell Biosensing Device

Tetrodotoxins (TTXs) are one of the most potent marine neurotoxins known, and pufferfish are their main vector in nature. The toxicity of TTXs relies on the blockage of voltage-gated sodium channels (VGSCs) in neuronal or excitable cells, producing severe gastrointestinal and neurological symptoms that, in some cases, may be fatal. Until now, more than 30 TTX analogues have been described, but little is known about their role in poisoning. In this work, we propose the use of a high-throughput biosensing device for the detection of TTX and its analogues in pufferfish by assessing the electrophysiological activity of Neuro-2a cells exposed to fish extracts. The system showed an IC50 value of 6.4 nM for TTX and, since detection was not affected by the presence of matrix components from different tissues of a TTX-free pufferfish specimen when analysed at 10 mg/mL, an LOD of 0.05 mg TTX equiv./kg was achieved (far below the Japanese regulatory limit of 2 mg TTX equiv./kg). The system was also used to evaluate the toxicity equivalency factors (TEFs) of five TTX analogues purified from the liver of a Lagocephalus sceleratus specimen fished near Crete (Greece). Then, naturally contaminated pufferfish samples were analysed using the single-cell biosensing device and compared with the LC-MS/MS quantifications after applying the TEFs, obtaining excellent correlations. Overall, the biosensing device presented in this work provides a rapid, highly sensitive and reliable toxicological method for the assessment of TTX and its analogues in seafood to protect consumers from TTX poisoning.

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Development of a Fully Integrated Color Detection Biosensor for Agricultural and Biomedical Applications

Colorimetric strips have a wide range of applications in medical and agricultural fields. There are many test kits available for measuring these analytes. These tests kits typically comprise of several activated test strips with a color-matching legend printed on the label of the bottle. The test process typically involves dipping the test strip in the sample, then comparing the changed color of the test strip against the color samples printed on the label and finding the closest match. While this method is good enough for determining the approximate value of the concentration of the analyte, in addition to being prone to human error, it can never provide precise concentration due to the limited number of color samples that can be printed on the label.

Therefore, there is a need to develop a biosensor that can provide a precise measurement of the concentration of the analyte. In this research, we propose the design of a fully integrated and standalone biosensor that can read out a color strip and provide a value in the actual units such as ppm or percentage. Using this biosensor, the user tests the sample by dipping a colorimetric strip in the sample, and finally puts the strip next to the color sensor. The micro-controller reads out the developed color of the strip, determines the concentration of a particular analyte present in the test sample, and displays the concentration in ppm. Since the aim is to design a universal sensor that can be adapted to various applications, therefore, an AI model is being developed and trained for various known concentrations of several analytes. These samples are pre-tested in the lab to fully calibrate the biosensor. Since this biosensor can be fully calibrated in different lighting conditions, human error can be eliminated from the color-matching part of the process.

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Patent Analysis of Innovative Hyaluronic-Acid-based Hydrogel Biosensors

Introduction

Hydrogel-based biosensors show promising potential for various applications, including biomedical applications, disease diagnoses, and detecting and quantifying pharmaceuticals. These biosensors employ different detection principles. Hyaluronic-acid-based hydrogels with specific functional groups have been used as cost-effective, miniature biosensors for chemical and biological detection, with sensitivity dependent on factors such as the temperature, pH, and concentration of analytes. In this analysis based on patents, the advances in the development of hyaluronic-acid-based hydrogel biosensors were addressed.

Resources and Methods

Different patent databases have been used according to different keywords related to the topic “hyaluronic-acid-based hydrogel biosensors”. Patent documents were filtered to include only patent applications and granted patents.

Results

From 2003 to 2023, 50 patent documents were published, including 41 patent applications and 9 granted patents. Many patent documents stem from universities and collaborations between academia and industry, as well as foundations. Furthermore, about 54% of all patent documents come from the United States. Cooperative patent classification showed that the majority of patent documents are indeed involving biosensors for measuring characteristics of blood in vivo (e.g., gas concentration, pH value, etc.). More specifically, that concerns measuring glucose by tissue impedance measurement using enzyme electrodes with immobilized oxidase. Based on relevant patents, to create a biosensor, the process involves providing a solid material with an electrode, placing a hydrogel drop on the electrode, subjecting the material to a partial vacuum, spinning it, and finally heating it.

Conclusions and Outlook

In summary, hyaluronic-acid-based hydrogels have enhanced mechanical properties and can be modified to have electrical conductivity, making them suitable for biosensors. These biosensors offer a new perspective for fabricating efficient biosensing systems with applications in various fields. Despite the potential of HA-based hydrogels for biosensors, there are still challenges to be addressed, including regulatory and commercialization hurdles.

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Investigation of a camera-based contactless pulse oximeter with time-division multiplex lightning on piglets for neonatological applications.
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Objective: The purpose of the study is to create the basis for non-contact monitoring of premature babies in neonatal intensive care units.

Methods: A contactless pulse oximeter is presented which measures the arterial oxygen saturation and heart rate with a monochrome camera and a time division multiplex controlled illumination with three wavelengths (660 nm, 810 nm and 940 nm). The related hardware setup and the signal processing is described in detail. The newly developed technology as prototype was used for the first time on an animal model.

Results: Using the camera system and our new designed algorithm for further analysis, the detection of heartbeat and calculation of the oxygen saturation was evaluated. Under ideal conditions, heartbeat and respiration were separated clearly by flat breathing and only minor intervention. In this case, the saturation can be determined with an mean difference of 0.7%.

Conclusion: The general functionality of the sensor can be guaranteed by the results of the presented experiments under ideal conditions. The results allow a systematic improvement for the further development of contactless vital sign monitoring systems.

Significance: The results presented here are a major step towards the development of an incubator with non-contact sensor systems for use in the neonatal intensive care unit.

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Toward Plantar Pressure Evaluation in Real Time-Based Wearable Audio-Biofeedback

Introduction: Wearable audio-biofeedback (ABF) is emerging to provide real-time feedback to heighten both biomechanical and physiological outcomes. A novel ABF prototype was developed to acquire the signals provided by a pressure-sensitive insole, measure the plantar pressure (PP), and offer biofeedback in real time. This study aimed to investigate the short-term effect of the ABF system on PP and linear acceleration. Methods: The ABF system based on Arduino micro (sample rate 34Hz) was made with 10 force-sensing resistors (FSR402), an MPU-6050 triaxial accelerometer (ACC), and a headset for posture control based on ABF. Also, TRIGNO™ Wireless System assessed postural control using 10 triaxial ACC sensors (27x37x15mm, with a sample rate of 148Hz) placed on the spinous process of C7 and L5, the deltoid tuberosity of the humerus, the midpoint between the anterior superior iliac spine and the upper border of the patella bone, 15 cm above the lateral malleolus, and the anterior midpoint of the head of the III, IV, and V phalangeal metatarsus. Results: Four participants (aged 29±3.92 years) performed standing trials with the ABF system both ON and OFF. A significant improvement in posture control was shown based on PP and linear acceleration with the ABF ON. Higher PP (p<0.001) was detected when the stimulus was ON, particularly in the middle and final right foot of the task. Notably, a significant modification of linear acceleration was observed in most sensors. Participants reported comfort in wearing the ABF device, highlighting its potential for practical use. The linear acceleration of the low-cost ABF system showed similar performance with that of the commercial system. Conclusion: Our findings underscore the potential practical use of the ABF device for enhancing postural proprioception in outpatient clinical and home-based rehabilitation.

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In situ Real-time Monitoring and Simulation of Metabolic Activity in Biofilm of Sulfate-reducing Bacteria
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Sulfate-reducing bacteria (SRB) are a typical, well-studied, and highly corrosive microorganism that is closely associated with the formation of biofilms on metal surfaces. Traditional methods for measuring SRB activity in biofilms are unable to distinguish between the metabolic activity of sessile SRB in the biofilm and planktonic SRB in bulk solution, making it difficult to apply in the field. To address these issues, this thesis presents two types of all-solid ion-selective electrochemical microprobes that were used to construct metabolic activity detection platforms for the continuous, in situ detection of SRB metabolic activity in biofilms by selectively recognizing characteristic metabolic substances. Additionally, the feasibility of the SRB metabolic activity detection performances was verified by two organic fluorescent probes. The metabolic activity of sessile SRB in the biofilm on the surface of an inert material and planktonic SRB in bulk solution were continuously measured, and the test results preliminarily revealed the changes and differences in metabolic activity between SRB cells in the biofilm and free SRB cells. Subsequently, the metabolic activity of sessile SRB in biofilm on the surface of metal material and planktonic SRB in bulk solution were continuously measured, and the results were discussed in this thesis. This study was of great significance for revealing the variation regulation and different characteristics of SRB metabolic activity inside and outside the biofilm, and held significant meaning for the research of SRB biofilms' corrosive mechanisms.

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Ferromagnetic Nanoparticles-modified Immunosensor: A Novel Methodology for Polycyclic Aromatic Hydrocarbons (PAHs) Detection.

Polycyclic aromatic hydrocarbons (PAHs) encompass an extensive group of organic compounds comprised solely of carbon and hydrogen elements. These substances exert a significant influence as contaminants in the environment, bearing notable implications. Given their link to heightened cancer risks in humans, PAHs raise significant human health apprehensions. Consequently, establishing a means to identify these compounds in various substances that humans come into contact with, such as water, soil, and food, is paramount. The European Drinking Water Directive (98/83/EC) prescribes a stringent threshold of 0.01ng/mL for Benzo[a]pyrene (BaP) levels in potable water. Traditional practices for PAH detection in the environment have relied on costly instruments like High-Performance Liquid Chromatography with fluorescence detection (HPLC-fluorescence) and Gas Chromatography-Mass Spectrometry (GC-MS). These methodologies entail substantial expenses, employ significant quantities of hazardous solvents, demand substantial time investments, and lack portability. In this research, an alternative electrochemical approach was introduced, offering distinct advantages over established PAH detection techniques. The method achieved a Limit of Detection (LOD) at 0.01ng/mL and a linear range spanning from 13.7 to 123 ng/mL. This innovative technique also facilitates the automation of steps inherent to immunoassay procedures. Consequently, integration into a portable lab-on-a-chip solution holds promise as a prospective avenue for monitoring water quality. This approach circumvents the need for resource-intensive and inefficient water sample analyses conducted within dedicated laboratories, thus mitigating costs and enhancing efficiency.

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Plant-wearable sensors made on eco-friendly mats for on-site and fast pesticide detection

Sustainable materials for designing eco-friendly wearable sensors are needed to reach the increasing demand for new technologies for agriculture 5.0. Herein, we present the use of biocompatible mats made of poly(lactic acid) (PLA) fibers obtained using the solution-blow spinning technique as a substrate for screen-printed carbon electrode (SPCE) fabrication. The low-cost plant-wearable sensor (<US$ 0.08 per unit) was used to detect carbendazim and diquat pesticides in food and crop samples using differential pulse voltammetry (DPV). The current signals increased linearly from 0.2 to 1.4 µM for carbendazim and diquat. The linear regression of I (A) = 3.42 × 10–8 + 2.85 CCarbendazim (M) and I (A) = -2.95 × 10–8 + 16.55 CDiquat (M) yielded the detection limits of 43 and 57 nM for carbendazim and diquat, respectively. We also compared the analytical performance of a plant-wearable sensor made on a PLA substrate with a petroleum-derived polyethylene terephthalate (PET) substrate reaching a 5-fold and 4-fold increase in the sensitivity of carbendazim and diquat detection. The plant-wearable sensor was used to detect agrochemicals residues in apple and cabbage samples, providing good recovery values between 90 and 110%. Thus, the plant-wearable sensor could be helpful in offering real-time alerts on pesticide residues in fruit and vegetable samples. The eco-friendly sensor was successfully used on the skin of apples and cabbage surfaces for discriminating carbendazim and diquat. All those outcomes show the potential of the eco-friendly mats made of poly(lactic acid) fibers as a substrate for the development of screen-printed electrodes, providing a sustainable technology for non-enzymatic pesticide detection.

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Ultrasensitive Detection of 3-Hydroxy-2-Butanone Biomarker at Low Temperatures Through Trace Au Atom Enhancement in Mesoporous SnO2 Spheres

The development of semiconductor metal oxide gas sensors with high sensitivity and selectivity under low-temperature operating conditions remains a significant challenge. Herein, mesoporous SnO2 spheres loaded with trace Au atoms are designed for the low-temperature detection of 3-hydroxy-2-butanone, a biomarker of Listeria monocytogenes frequently found in food. The designed sensing materials have a large pore size (~5.8 nm), high specific surface area (56.9-63.5 m2/g), and ultra-low Au contents (0.6 wt%). The fabricated gas sensors exhibit an ultra-high response (587.3) toward 2 ppm 3-hydroxy-2-butanone at 50 ºC, which is 183.5 times greater than the sensor based on mesoporous SnO2. The temperature range has been effectively reduced from 100 to 50 °C, while simultaneously achieving an impressive detection limit of only 10 ppb. The sensitivity is as high as 291.5 ppm–1. The gas sensors could be further utilized for discriminating Listeria from other bacterial strains, including E. coli, Salmonella, Thermophilus, and S. aureus. The superior sensing performance can be due to the mesoporous framework with a low gas diffusion resistance, and the highly accessible Au-O-Sn sites with strong interactions toward the target gas. This work provides a reliable and facile method for the synthesis of noble metal single-atom-decorated mesoporous metal oxide spheres, which can be used in various fields, such as chemical sensing, energy, and environmental catalysis. The unique modification of noble metal single atoms on the mesoporous semiconductor metal oxides is an efficient strategy for the fabrication of high-performance gas sensors operated at low temperatures, which is expected to boost the development of high-performance sensors with low energy consumption for applications in environmental monitoring, food safety, smart homes, and intelligent agriculture.

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