New spin coated multilayer lactate biosensor for acidosis monitoring in continuous flow assisted with an electrochemical pH probe.

A LOx-based electrochemical biosensor for high-level lactate determination was developed. For the construction of the biosensor, chitosan and Nafion layers were integrated by using a spin coating procedure, leading to less porous surfaces in comparison with those recorded after a drop casting procedure. The analytical performance of the resulting biosensor for lactate determination was evaluated in batch and flow regime, displaying satisfactory results in both modes ranging from 0.5 to 20 mM concentration range for assessing the lactic acidosis. Finally, the lactate levels in raw serum samples were estimated using the biosensor developed and verified with a blood gas analyzer. Based on these results, the biosensor developed is promising for its use in healthcare environment, after its proper miniaturization. A pH probe based on common polyaniline-based electrochemical sensor was also developed to assist the biosensor for the lactic acidosis monitoring, leading to excellent results in stock solutions ranging from 6.0 to 8.0 mM and raw plasma samples. The results were confirmed by using two different approaches, blood gas analyzer and pH-meter. Consequently, the lactic acidosis monitoring could be achieved in continuous flow regime using both (bio)sensors.

Characterizing the Sensing Response of Carbon Nanocomposite-Based Wearable Sensors on Elbow Joint Using an End Point Robot and Virtual Reality.

Physical therapy is often essential for complete recovery after injury. However, a significant population of patients fail to adhere to prescribed exercise regimens. Lack of motivation and inconsistent in-person visits to physical therapy are major contributing factors to suboptimal exercise adherence, slowing the recovery process. With the advancement of virtual reality (VR), researchers have developed remote virtual rehabilitation systems with sensors such as inertial measurement units. A functional garment with an integrated wearable sensor can also be used for real-time sensory feedback in VR-based therapeutic exercise and offers affordable remote rehabilitation to patients. Sensors integrated into wearable garments offer the potential for a quantitative range of motion measurements during VR rehabilitation. In this research, we developed and validated a carbon nanocomposite-coated knit fabric-based sensor worn on a compression sleeve that can be integrated with upper-extremity virtual rehabilitation systems. The sensor was created by coating a commercially available weft knitted fabric consisting of polyester, nylon, and elastane fibers. A thin carbon nanotube composite coating applied to the fibers makes the fabric electrically conductive and functions as a piezoresistive sensor. The nanocomposite sensor, which is soft to the touch and breathable, demonstrated high sensitivity to stretching deformations, with an average gauge factor of ~35 in the warp direction of the fabric sensor. Multiple tests are performed with a Kinarm end point robot to validate the sensor for repeatable response with a change in elbow joint angle. A task was also created in a VR environment and replicated by the Kinarm. The wearable sensor can measure the change in elbow angle with more than 90% accuracy while performing these tasks, and the sensor shows a proportional resistance change with varying joint angles while performing different exercises. The potential use of wearable sensors in at-home virtual therapy/exercise was demonstrated using a Meta Quest 2 VR system with a virtual exercise program to show the potential for at-home measurements.

Biomimetic Neuromorphic Sensory System via Electrolyte Gated Transistors.

Biomimetic neuromorphic sensing systems, inspired by the structure and function of biological neural networks, represent a major advancement in the field of sensing technology and artificial intelligence. This review paper focuses on the development and application of electrolyte gated transistors (EGTs) as the core components (synapses and neuros) of these neuromorphic systems. EGTs offer unique advantages, including low operating voltage, high transconductance, and biocompatibility, making them ideal for integrating with sensors, interfacing with biological tissues, and mimicking neural processes. Major advances in the use of EGTs for neuromorphic sensory applications such as tactile sensors, visual neuromorphic systems, chemical neuromorphic systems, and multimode neuromorphic systems are carefully discussed. Furthermore, the challenges and future directions of the field are explored, highlighting the potential of EGT-based biomimetic systems to revolutionize neuromorphic prosthetics, robotics, and human-machine interfaces. Through a comprehensive analysis of the latest research, this review is intended to provide a detailed understanding of the current status and future prospects of biomimetic neuromorphic sensory systems via EGT sensing and integrated technologies.

A Low-Cost Handheld Centrifugal Microfluidic System for Multiplexed Visual Detection Based on Isothermal Amplification.

A low-cost, handheld centrifugal microfluidic system for multiplexed visual detection based on recombinase polymerase amplification (RPA) was developed. A concise centrifugal microfluidic chip featuring four reaction units was developed to run multiplexed RPA amplification in parallel. Additionally, a significantly shrunk-size and cost-effective handheld companion device was developed, incorporating heating, optical, rotation, and sensing modules, to perform multiplexed amplification and visual detection. After one-time sample loading, the metered sample was equally distributed into four separate reactors with high-speed centrifugation. Non-contact heating was adopted for isothermal amplification. A tiny DC motor on top of the chip was used to drive steel beads inside reactors for active mixing. Another small DC motor, which was controlled by an elaborate locking strategy based on magnetic sensing, was adopted for centrifugation and positioning. Visual fluorescence detection was optimized from different sides, including material, surface properties, excitation light, and optical filters. With fluorescence intensity-based visual detection, the detection results could be directly observed through the eyes or with a smartphone. As a proof of concept, the handheld device could detect multiple targets, e.g., different genes of African swine fever virus (ASFV) with the comparable LOD (limit of detection) of 75 copies/test compared to the tube-based RPA.

The Tunable Parameters of Graphene-Based Biosensors.

Graphene-based surface plasmon resonance (SPR) biosensors have emerged as a promising technology for the highly sensitive and accurate detection of biomolecules. This study presents a comprehensive theoretical analysis of graphene-based SPR biosensors, focusing on configurations with single and bimetallic metallic layers. In this study, we investigated the impact of various metallic substrates, including gold and silver, and the number of graphene layers on key performance metrics: sensitivity of detection, detection accuracy, and quality factor. Our findings reveal that configurations with graphene first supported on gold exhibit superior performance, with sensitivity of detection enhancements up to 30% for ten graphene layers. In contrast, silver-supported configurations, while demonstrating high sensitivity, face challenges in maintaining detection accuracy. Additionally, reducing the thickness of metallic layers by 30% optimizes light coupling and enhances sensor performance. These insights highlight the significant potential of graphene-based SPR biosensors in achieving high sensitivity of detection and reliability, paving the way for their application in diverse biosensing technologies. Our findings pretend to motivate future research focusing on optimizing metallic layer thickness, improving the stability of silver-supported configurations, and experimentally validating the theoretical findings to further advance the development of high-performance SPR biosensors.

Gas Chromatography-Sensor System Aids Diagnosis of Inflammatory Bowel Disease, and Separates Crohn's from Ulcerative Colitis, in Children.

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn's disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD. VOC profiles can be rapidly determined using a gas chromatography-sensor device (OdoReader©). In an inception-cohort of children presenting with suspected IBD, we directly compared the diagnostic fidelity of faecal calprotectin (FCP, a non-specific protein marker of intestinal inflammation) with OdoReader© VOC profiles of children subsequently diagnosed with IBD with matched controls diagnosed with other gastrointestinal conditions. The OdoReader© was 82% (95% confidence interval 75-89%) sensitive and 71% (61-80%) specific but did not outperform FCP (sensitivity 93% (77-99%) and specificity 86% (67-96%); 250 µg/g FCP cut off) in the diagnosis of IBD from other gastrointestinal conditions when validated in a separate sample from the same cohort. However, unlike FCP and better than other similar technologies, the OdoReader© could distinguish paediatric CD from UC (up to 88% (82-93%) sensitivity and 80% (71-89%) specificity in the validation set) and justifies further validation in larger studies. A non-invasive test based on VOCs could help streamline and limit invasive investigations in children.

Taste Sensor Assessment of Bitterness in Medicines: Overview and Recent Topics.

In recent decades, taste sensors have been increasingly utilized to assess the taste of oral medicines, particularly focusing on bitterness, a major obstacle to patient acceptance and adherence. This objective and safe method holds promise for enhancing the development of patient-friendly medicines in pharmaceutical companies. This review article introduces its application in measuring the intensity of bitterness in medicine, confirming the achievement of taste masking, distinguishing taste differences between branded and generic medicines, and identifying substances to suppress bitterness in target medicines. Another application of the sensor is to predict a significant increase in bitterness when medicine is taken with certain foods/beverages or concomitant medication. Additionally, to verify the sensor's predictability, a significant correlation has been demonstrated between the output of a bitter-sensitive sensor designed for drug bitterness (BT0) and the bitterness responses of the human taste receptor hT2R14 from BitterDB (huji.ac.il). As a recent advancement, a novel taste sensor equipped with lipid/polymer membranes modified by 3-Br-2,6-dihydroxybenzoic acid (2,6-DHBA), based on the concept of allostery, is introduced. This sensor successfully predicts the bitterness of non-charged pharmaceuticals with xanthine skeletons, such as caffeine or related compounds. Finally, the future prospects of taste sensors are discussed.

Seizing the Hidden Assassin: Current Detection Strategies for Staphylococcus aureus and Methicillin-Resistant S. aureus.

Staphylococcus aureus (S. aureus) is a kind of pathogenic bacteria which can lead to food poisoning, hospital, and community infections. S. aureus and methicillin-resistant S. aureus (MRSA) have become headaches for public health worldwide. Therefore, strengthening the detection of S. aureus and MRSA is a critical step to prevent and control its spread and infection. This review summarized multiple detection methods (electrochemical, optical, and other biosensors) for sensitive and efficient detection of nonresistant and resistant S. aureus. First, we have introduced the principle and methods of detection platform for S. aureus and MRSA. We also contrasted various detection strategies. Finally, the current situation and prospect of S. aureus and MRSA detection in the future are explored in depth, and its development direction of detection methods is also predicted. In this review, we found that although biosensors have shown tremendous brilliance in the field of monitoring, they are currently in the experimental stage. It can be certain that we are very close to entering the commercialization stage. The point-of care testing available to nonprofessionals will become a new direction. We firmly believe that the monitoring system will be more perfect and stable and public life will be healthier and safer.

Microfluidic finger-actuated mixer for ultrasensitive electrochemical measurements of protein biomarkers for point-of-care testing.

Current diagnostic tests for high sensitivity detection of protein biomarkers involve long incubation times or require bulky/expensive instrumentation, hindering their use for point-of-care testing. Here, we report a microfluidic electrochemical immunosensor that employs a unique finger-actuated mixer for rapid, ultrasensitive measurements of protein biomarkers. Mixing was implemented during the incubation steps, which accelerated biomolecular transport and promoted immunocomplex formation, leading to enhanced analytical sensitivity and a shortened detection time. Electrochemical measurements were performed using a handheld diagnostic device consisting of a smartphone and miniature potentiostat. Proof of principle was demonstrated by using this platform for quantitative measurements of C-X-C motif chemokine ligand 9 (CXCL9), a serological biomarker for autoimmune and inflammatory diseases, which could be detected in human plasma at concentrations as low as 4.7 pg mL-1 in <25 min. The ability to rapidly detect protein biomarkers with high sensitivity in a point-of-care format makes this device a promising tool for diagnostic testing, particularly in resource-limited settings.

Simple bioelectrical microsensor: oocyte quality prediction via membrane electrophysiological characterization.

Oocyte selection is a crucial step of assisted reproductive treatment. The most common approach relies on the embryologist experience which is inevitably prone to human error. One potential approach could be the use of an electrical-based approach as an ameliorative alternative. Here, we developed a simple electrical microsensor to characterize mouse oocytes. The sensor is designed similarly to embryo culture dishes and is familiar to embryologists. Different microelectrode models were simulated for oocyte cells and a more sensitive model was determined. The final microsensor was fabricated. A differential measuring technique was proposed based on the cell presence/absence. We predicted oocyte quality by using three electrical characteristics, oocyte radii, and zona thicknesses, and also these predictions were compared with an embryologist evaluation. The evaluation of the oocyte membrane capacitance, as an electrophysiological characteristic, was found to be a more reliable method for predicting oocytes with fertilization and blastocyst formation success competence. It achieved 94% and 58% prediction accuracies, respectively, surpassing other methods and yielding lower errors. This groundbreaking research represents the first of its kind in this field and we hope that this will be a step towards improving the accuracy of the treatment.

Early detection of hypo/hyperglycemia using a microneedle electrode array-based biosensor for glucose ultrasensitive monitoring in interstitial fluid.

Diabetes is a common chronic metabolic disease with a wide range of clinical symptoms and consequences and one of the main causes of death. For the management of diabetes, painless and continuous interstitial fluid (ISF) glucose monitoring is ideal. Here, we demonstrate continuous diabetes monitoring using an integrated microneedle (MN) biosensor with an emergency alert system. MNs are a novel technique in the field of biomedical engineering because of their ability to analyze bioinformation with minimal invasion. In this work we developed a poly(methyl methacrylate) (PMMA) based MN glucose sensor. The device was produced by the 3D printing technique, microfabrication, electrodeposition, and enzyme immobilization step. The in vitro test for the glucose MN sensor showed a linear range from 1.5 to 14 mM with a sensitivity of 1.51 µA mM-1, limit of detection (LOD) of 0.35 mM and good selectivity. Highly repeatable sensing is observed with good reproducibility. The interference-free detection of glucose in the presence of physiologically relevant concentrations of ascorbic acid, uric acid, and mannose is demonstrated, along with the operational stability of the array. After resolving the biofouling consequences linked to on-body sensing, this MN platform would be appealing for minimally invasive electrochemical glucose monitoring. An alert is sent to confidants via email or SMS when the values are abnormal. The application is also able to display the recorded values in the form of a graph to help determine the state of health of the user over a period of time. It can be concluded that continuous monitoring and an emergency alert system are important for keeping an eye on diabetic patients and can send alert in case of an abnormal situation of the patient.

Near-infrared-triggered plasmonic regulation and cardiomyocyte-based biosensing system for in vitro bradyarrhythmia treatment.

Bradyarrhythmia, a life-threatening cardiovascular disease, is an increasing burden for the healthcare system. Currently, surgery, implanted device, and drug are introduced to treat the bradyarrhythmia in clinical practice. However, these conventional therapeutic strategies suffer from the invasive surgery, power supply, or drug side effect, respectively, hence developing the alternative therapeutic strategy is necessarily imperative. Here, a convenient and effective strategy to treat the bradyarrhythmia is proposed using near-infrared-triggered Au nanorod (NR) based plasmonic photothermal effect (PPE). Moreover, electrophysiology of cardiomyocytes is dynamically monitored by the integrated biosensing-regulating system during and after the treatment. Cardiomyocyte-based bradyarrhythmia recover rhythmic for a long time by regulating plasmonic photothermal effect. Furthermore, the regulatory mechanism is qualitatively investigated to verify the significant thermal stimulation in the recovery process. This study establishes a reliable platform for long-term recording and evaluation of mild photothermal therapy for bradyarrhythmia in vitro, offering an efficient and non-invasive strategy for the potential clinical applications.

Iodide based electrochemical gold quantification method for lateral flow assays.

The lateral flow assay (LFA) is an ideal technology for at-home medical diagnostic tests due to its ease of use, cost-effectiveness, and rapid results. Despite these advantages, only few LFAs, such as the pregnancy and COVID-19 tests, have been translated from the laboratory to the homes of patients. To date, the medical applicability of LFAs is limited by the fact that they only provide yes/no answers unless combined with optical readers that are too expensive for at-home applications. Furthermore, LFAs are unable to compete with the state-of-the-art technologies in centralized laboratories in terms of detection limits. To address those shortcomings, we have developed an electrochemical readout procedure to enable quantitative and sensitive LFAs. This technique is based on a voltage-triggered in-situ dissolution of gold nanoparticles, the conventional label used to visualize target-specific signals on the test line in LFAs. Following the dissolution, the amount of gold is measured by electroplating onto an electrode and subsequent electrochemical quantification of the deposited gold. The measured current has a low noise, which achieves superior detection limits compared to optical techniques where background light scattering is limiting the readout performance. In addition, the hardware for the readout was developed to demonstrate translatability towards low-cost electronics.

One-base-mismatch CRISPR-based transistors for single nucleotide resolution assay.

An effective strategy for accurately detecting single nucleotide variants (SNVs) is of great significance for genetic research and diagnostics. However, strict amplification conditions, complex experimental instruments, and specialized personnel are required to obtain a satisfactory tradeoff between sensitivity and selectivity for SNV discrimination. In this study, we present a CRISPR-based transistor biosensor for the rapid and highly selective detection of SNVs in viral RNA. By introducing a synthetic mismatch in the crRNA, the CRISPR-Cas13a protein can be engineered to capture the target SNV RNA directly on the surface of the graphene channel. This process induces a fast electrical signal response in the transistor, obviating the need for amplification or reporter molecules. The biosensor exhibits a detection limit for target RNA as low as 5 copies in 100 µL, which is comparable to that of real-time quantitative polymerase chain reaction (PCR). Its operational range spans from 10 to 5 × 105 copy mL-1 in artificial saliva solution. This capability enables the biosensor to discriminate between wild-type and SNV RNA within 15 min. By introducing 10 µL of swab samples during clinical testing, the biosensor provides specific detection of respiratory viruses in 19 oropharyngeal specimens, including influenza A, influenza B, and variants of SARS-CoV-2. This study emphasizes the CRISPR-transistor technique as a highly accurate and sensitive approach for field-deployable nucleic acid screening or diagnostics.

A wearable microneedle patch incorporating reversible FRET-based hydrogel sensors for continuous glucose monitoring.

Continuous glucose monitors are crucial for diabetes management, but invasive sampling, signal drift and frequent calibrations restrict their widespread usage. Microneedle sensors are emerging as a minimally-invasive platform for real-time monitoring of clinical parameters in interstitial fluid. Herein, a painless and flexible microneedle sensing patch is constructed by a mechanically-strong microneedle base and a thin layer of fluorescent hydrogel sensor for on-site, accurate, and continuous glucose monitoring. The Förster resonance energy transfer (FRET)-based hydrogel sensors are fabricated by facile photopolymerizations of acryloylated FRET pairs and glucose-specific phenylboronic acid. The optimized hydrogel sensor enables quantification of glucose with reversibility, high selectivity, and signal stability against photobleaching. Poly (ethylene glycol diacrylate)-co-polyacrylamide hydrogel is utilized as the microneedle base, facilitating effective skin piercing and biofluid extraction. The integrated microneedle sensor patch displays a sensitivity of 0.029 mM-1 in the (patho)physiological range, a low detection limit of 0.193 mM, and a response time of 7.7 min in human serum. Hypoglycemia, euglycemia and hyperglycemia are continuously monitored over 6 h simulated meal and rest activities in a porcine skin model. This microneedle sensor with high transdermal analytical performance offers a powerful tool for continuous diabetes monitoring at point-of-care settings.

Rapid and sensitive detection of heart-type fatty acid binding protein using aggregation-induced emission nanoparticles on digital microfluidics workstation.

Early and rapid diagnostic of acute myocardial infarction (AMI) during its developing stage is crucial due to its high fatality rate. Heart-type fatty acid binding protein (h-FABP) is an ideal biomarker for the quantitative diagnosis of AMI, surpassing traditional markers such as myoglobin, creatine phosphokinase-MB, and troponin in terms of sensitivity, specificity, and prognostic value. To obtain diagnostic and prognostic information, a precise and fully quantitative measurement of h-FABP is essential, typically achieved through an immunosorbent assay like the enzyme-linked immunosorbent assay. Nevertheless, this method has several limitations, including extended detection time, complex assay procedures, the necessity for skilled technicians, and challenges in implementing automated detection. This research introduces a novel biosensor, utilizing aggregation-induced emission nanoparticles (AIENPs) and integrated with a digital microfluidic (DMF) workstation, designed for the sensitive, rapid, and automated detection of h-FABP in low-volume serum samples. AIENPs and magnetic beads in nanoscale were served as the capture particles and the fluorescent probe, which were linked covalently to anti-h-FABP antibodies respectively. The approach was based on a sandwich immunoassay and performed on a fully automated DMF workstation with assay time by 15 min. We demonstrated the determination of h-FABP in serum samples with detection limit of 0.14 ng/mL using this biosensor under optimal condition. Furthermore, excellent correlations (R2 = 0.9536, n = 50) were obtained between utilizing this biosensor and commercialized ELISA kits in clinical serum detecting. These results demonstrate that our flexible and reliable biosensor is suitable for direct integration into clinical diagnostics, and it is expected to be promising diagnostic tool for early detection and screening tests as well as prognosis evaluation for AMI patients.

Assessing the performance of a robust multiparametric wearable patch integrating silicon-based sensors for real-time continuous monitoring of sweat biomarkers.

The development of wearable devices for sweat analysis has experienced significant growth in the last two decades, being the main focus the monitoring of athletes health during workouts. One of the main challenges of these approaches has been to attain the continuous monitoring of sweat for time periods over 1 h. This is the main challenge addressed in this work by designing an analytical platform that combines the high performance of potentiometric sensors and a fluidic structure made of a plastic fabric into a multiplexed wearable device. The platform comprises Ion-Sensitive Field-Effect Transistors (ISFETs) manufactured on silicon, a tailor-made solid-state reference electrode, and a temperature sensor integrated into a patch-like polymeric substrate, together with the component that easily collects and drives samples under continuous capillary flow to the sensor areas. ISFET sensors for measuring pH, sodium, and potassium ions were fully characterized in artificial sweat solutions, providing reproducible and stable responses. Then, the real-time and continuous monitoring of the biomarkers in sweat with the wearable platform was assessed by comparing the ISFETs responses recorded during an 85-min continuous exercise session with the concentration values measured using commercial Ion-Selective Electrodes (ISEs) in samples collected at certain times during the session. The developed sensing platform enables the continuous monitoring of biomarkers and facilitates the study of the effects of various real working conditions, such as cycling power and skin temperature, on the target biomarker concentration levels.

Spatial-resolved and self-calibrated 3D-printed photoelectrochemical biosensor engineered by multifunctional CeO2/CdS heterostructure for immunoassay.

A spatial-resolved and self-calibrated photoelectrochemical (PEC) biosensor has been fabricated by a multifunctional CeO2/CdS heterostructure, achieving portable and sensitive detection of carcinoembryonic antigen (CEA) using a homemade 3D printing device. The CeO2/CdS heterostructure with matched band structure is prepared to construct the dual-photoelectrodes to improve the PEC response of CeO2. In particular, as the photoactive nanomaterial, the CeO2 also plays the role of peroxidase mimetic nanozymes. Therefore, the catalytic performance of CeO2 with different morphologies (e.g., nano-cubes, nano-rods and nano-octahedra) have been studied, and CeO2 nano-cubes (c-CeO2) achieve the optimal catalytic activity. Upon introducing CEA, the sandwich-type immunocomplex is formed in the microplate using GOx-AuNPs-labeled second antibody as detection antibody. As a result, H2O2 can be produced from the catalytic oxidization of glucose substrate by GOx, which is further catalyzed by CeO2 to form •OH, thus in situ etching CdS and decreasing the photocurrents. The self-calibration is achieved by the dual-channel photoelectrodes on the homemade 3D printing device to obtain the photocurrents ratio, thus effectively normalizing the fluctuations of external factors to enhance the accuracy. This integrated biosensor with a detection limit as low as 0.057 ng mL-1 provides a promising way for ultrasensitive immunoassay in clinic application in complex environments.

Spontaneous aggregation-enhanced electrochemiluminescence via galvanic strategy.

Researchers unremittingly strive to develop innovative luminophores to enhance intrinsic electrochemiluminescence (ECL) performance. However, the potential to harness facile strategies, such as manipulating the physical properties of luminophores while retaining functional chemical properties to fabricate cost-effective ECL complexes, remains underexplored. Herein, we reported a novel and efficient one-step galvanic technique to actualize aggregation-enhanced ECL (AEECL) of ruthenium complexes. It marked the first instance of the galvanic process being employed to synthesize aggregate luminophores through electrostatic attraction. The ECL intensity and efficiency of the prepared ruthenium complexes with AEECL properties surpassed traditional ruthenium complexes by 8.9 and 13.6 times, respectively, outperforming most reported luminophores. Remarkably, the target luminophore exhibited high stability across varied scan rates and temperatures. Furthermore, a binder-free and carbon paper-based AEECL analytical device for lidocaine detection was fabricated, achieving a satisfactory detection limit (0.34 nM) and selectivity. The convenient modulation strategy of aggregate structure, along with the transformative leap from insufficient ECL to AEECL, bring forth a new revenue in aggregate science. This research also promises a universally applicable and versatile protocol for future biological analysis and bioimaging applications.