2D-Bio-FETs for sensitive detection of cardiovascular diseases.

The biosensing industry has seen exponential growth in the past decade. Impact of biosensors in the current scenario cannot be overlooked. Cardiovascular diseases (CvDs) have been recognized as one of the major causes for millions of deaths globally. This mortality can be minimized by early and accurate detection/diagnosis of CvDs with the help of biosensing devices. This also presents a global market opportunity for the development of biosensors for CvDs. A vast variety of biosensing methods and devices have been developed for this problem. Most of commercially available platforms for CvD detection rely on optical (fluorometric and colorimetric analysis) techniques using serum biomarkers since optical testing is the gold standard in medical diagnosis. Field effect transistors-based biosensors, termed as Bio-FETs, are the upcoming devices for blood or serum analyte detection due to excellent sensitivity, low operational voltage, handheld device structure and simple chip-based operation. Further, the discovery of two dimensional (2D) materials and their integration with conventional FETs has improved the overvoltage problem, sensitivity and strict operating conditions as compared to conventional FETs. Graphene-FETs based biosensing devices have been proven as promising candidates due to their attractive properties. Despite the severe threat of CvDs which has further increased in post-covid era, the Bio-FET sensor studies in literature are still rare. In this review, we aim to provide a comprehensive view of all the multidisciplinary concepts related to 2D-BioFETs for CvDs. A critical review of the different platforms has been covered with detailed discussions of related studies to provide a clear concept and present status of 2D-BioFETs based CvD biosensors.

Label-Free and Ultrasensitive Detection of Cartilage Acidic Protein 1 in Osteoarthritis Using a Single-Walled Carbon Nanotube Field-Effect Transistor Biosensor.

Osteoarthritis (OA), a prevalent degenerative joint disease, significantly affects the well-being of afflicted individuals and compromises the standard functionality of human joints. The emerging biomarker, Cartilage acidic protein 1 (CRTAC1), intricately associates with OA initiation and serves as a prognostic indicator for the trajectory toward joint replacement. However, existing diagnostic methods for CRTAC1 are hampered by the limited abundance, thus restricting the precision and specificity. Herein, a novel approach utilizing a single-walled carbon nanotube field-effect transistor (SWCNTs FET) biosensor is reported for the direct label-free detection of CRTAC1. High-purity semiconducting carbon nanotube films, functionalized with antibodies of CRTAC1, provide excellent electrical and sensing properties. The SWCNTs FET biosensor exhibits high sensitivity, notable reproducibility, and a wide linear detection range (1 fg/mL to 100 ng/mL) for CRTAC1 with a theoretical limit of detection (LOD) of 0.2 fg/mL. Moreover, the SWCNTs FET biosensor is capable of directly detecting human serum samples, showing excellent sensing performance in differentiating clinical samples from OA patients and healthy populations. Comparative analysis with traditional enzyme-linked immunosorbent assay (ELISA) reveals that the proposed biosensor demonstrates faster detection speeds, higher sensitivity/accuracy, and lower errors, indicating high potential for the early OA diagnosis. Furthermore, the SWCNTs FET biosensor has good scalability for the combined diagnosis and measurement of multiple disease markers, thereby significantly expanding the application of SWCNTs FETs in biosensing and clinical diagnostics.

Healing Function for Abraded Fingerprint Ridges in Tactile Texture Sensors.

Tactile texture sensors are designed to evaluate the sensations felt when a human touches an object. Prior studies have demonstrated the necessity for these sensors to have compliant ridges on their surfaces that mimic human fingerprints. These features enable the simulation of contact phenomena, especially friction and vibration, between human fingertips and objects, enhancing the tactile sensation evaluation. However, the ridges on tactile sensors are susceptible to abrasion damage from repeated use. To date, the healing function of abraded ridges has not been proposed, and its effectiveness needs to be demonstrated. In this study, we investigated whether the signal detection capabilities of a sensor with abraded epidermal ridges could be restored by healing the ridges using polyvinyl chloride plastisol as the sensor material. We developed a prototype tactile sensor with an embedded strain gauge, which was used to repeatedly scan roughness specimens. After more than 1000 measurements, we observed significant deterioration in the sensor's output signal level. The ridges were then reshaped using a mold with a heating function, allowing the sensor to partially regain its original signal levels. This method shows potential for extending the operational lifespan of tactile texture sensors with compliant ridges.

Nucleic Acid Target Sensing Using a Vibrating Sharp-Tip Capillary and Digital Droplet Loop-Mediated Isothermal Amplification (ddLAMP).

Nucleic acid tests are key tools for the detection and diagnosis of many diseases. In many cases, the amplification of the nucleic acids is required to reach a detectable level. To make nucleic acid amplification tests more accessible to a point-of-care (POC) setting, isothermal amplification can be performed with a simple heating source. Although these tests are being performed in bulk reactions, the quantification is not as accurate as it would be with digital amplification. Here, we introduce the use of the vibrating sharp-tip capillary for a simple and portable system for tunable on-demand droplet generation. Because of the large range of droplet sizes possible and the tunability of the vibrating sharp-tip capillary, a high dynamic range (~2 to 6000 copies/µL) digital droplet loop-mediated isothermal amplification (ddLAMP) system has been developed. It was also noted that by changing the type of capillary on the vibrating sharp-tip capillary, the same mechanism can be used for simple and portable DNA fragmentation. With the incorporation of these elements, the present work paves the way for achieving digital nucleic acid tests in a POC setting with limited resources.

Anti-IgG Doped Melanin Nanoparticles Functionalized Quartz Tuning Fork Immunosensors for Immunoglobulin G Detection: In Vitro and In Silico Study.

The quartz tuning fork (QTF) is a promising instrument for biosensor applications due to its advanced properties such as high sensitivity to physical quantities, cost-effectiveness, frequency stability, and high-quality factor. Nevertheless, the fork's small size and difficulty in modifying the prongs' surfaces limit its wide use in experimental research. Our study presents the development of a QTF immunosensor composed of three active layers: biocompatible natural melanin nanoparticles (MNPs), glutaraldehyde (GLU), and anti-IgG layers, for the detection of immunoglobulin G (IgG). Frequency shifts of QTFs after MNP functionalization, GLU activation, and anti-IgG immobilization were measured with an Asensis QTF F-master device. Using QTF immunosensors that had been modified under optimum conditions, the performance of QTF immunosensors for IgG detection was evaluated. Accordingly, a finite element method (FEM)-based model was produced using the COMSOL Multiphysics software program (COMSOL License No. 2102058) to simulate the effect of deposited layers on the QTF resonance frequency. The experimental results, which demonstrated shifts in frequency with each layer during QTF surface functionalization, corroborated the simulation model predictions. A modelling error of 0.05% was observed for the MNP-functionalized QTF biosensor compared to experimental findings. This study validated a simulation model that demonstrates the advantages of a simulation-based approach to optimize QTF biosensors, thereby reducing the need for extensive laboratory work.

Bio-Skin-Inspired Flexible Pressure Sensor Based on Carbonized Cotton Fabric for Human Activity Monitoring.

With the development of technology, people's demand for pressure sensors with high sensitivity and a wide working range is increasing. An effective way to achieve this goal is simulating human skin. Herein, we propose a facile, low-cost, and reproducible method for preparing a skin-like multi-layer flexible pressure sensor (MFPS) device with high sensitivity (5.51 kPa-1 from 0 to 30 kPa) and wide working pressure range (0-200 kPa) by assembling carbonized fabrics and micro-wrinkle-structured Ag@rGO electrodes layer by layer. In addition, the highly imitated skin structure also provides the device with an extremely short response time (60/90 ms) and stable durability (over 3000 cycles). Importantly, we integrated multiple sensor devices into gloves to monitor finger movements and behaviors. In summary, the skin-like MFPS device has significant potential for real-time monitoring of human activities in the field of flexible wearable electronics and human-machine interaction.

All-MXene electronic tongue for neurotransmitters detection.

Neurotransmitters (NTs) are molecules produced by neurons that act as the body's chemical messengers. Their abnormal levels in the human system have been associated with many disorders and neurodegenerative diseases, which makes the monitoring of NTs fundamentally important. Specifically for clinical analysis and understanding of brain behavior, simultaneous detection of NTs at low levels quickly and reliably is imperative for disease prevention and early diagnosis. However, the methods currently employed are usually invasive or inappropriate for multiple NTs detection. Herein, we developed a MXene-based impedimetric electronic tongue (e-tongue) for sensitive NT monitoring, using Nb2C, Nb4C3, Mo2C, and Mo2Ti2C3 MXenes as sensing units of the e-tongue, and Principal Component Analysis (PCA) as the data treatment method. The high specific surface area, distinct electrical properties, and chemical stability of the MXenes gave rise to high sensitivity and good reproducibility of the sensor array toward NT detection. Specifically, the e-tongue detected and differentiated multiple NTs (acetylcholine, dopamine, glycine, glutamate, histamine, and tyrosine) at concentrations as low as 1 nmol L-1 and quantified NTs present in a mixture. Besides, analyses performed with interferents and actual samples confirmed the system's potential to be used in clinical diagnostics. The results demonstrate that the MXene-based e-tongue is a suitable, rapid, and simple method for NT monitoring with high accuracy and sensitivity.

Signal amplification strategies in photoelectrochemical sensing of carcinoembryonic antigen.

Early detection of cancer markers is critical for cancer diagnosis and cancer therapy since these markers may indicate cancer risk, incidence, and disease prognosis. Carcinoembryonic antigen (CEA) is a type of non-specific and broad-spectrum cancer biomarker commonly utilized for early cancer diagnosis. Moreover, it serves as an essential tool to assess the efficacy of cancer treatment and monitor tumor recurrence as well as metastasis, thus garnering significant attention for precise and sensitive CEA detection. In recent years, photoelectrochemical (PEC) techniques have emerged as prominent methods in CEA detection due to the advantages of PEC, such as simple equipment requirements, cost-effectiveness, high sensitivity, low interference from background signals, and easy of instrument miniaturization. Different signal amplification methods have been reported in PEC sensors for CEA analysis. Based on these, this article reviews PEC sensors based on various signal amplification strategies for detection of CEA during the last five years. The advantages and drawbacks of these sensors were discussed, as well as future challenges.

Laser-assembled conductive 3D nanozyme film-based nitrocellulose sensor for real-time detection of H2O2 released from cancer cells.

In this work, a nanostructured conductive film possessing nanozyme features was straightforwardly produced via laser-assembling and integrated into complete nitrocellulose sensors; the cellulosic substrate allows to host live cells, while the nanostructured film nanozyme activity ensures the enzyme-free real-time detection of hydrogen peroxide (H2O2) released by the sames. In detail, a highly exfoliated reduced graphene oxide 3D film decorated with naked platinum nanocubes was produced using a CO2-laser plotter via the simultaneous reduction and patterning of graphene oxide and platinum cations; the nanostructured film was integrated into a nitrocellulose substrate and the complete sensor was manufactured using an affordable semi-automatic printing approach. The linear range for the direct H2O2 determination was 0.5-80 µM (R2 = 0.9943), with a limit of detection of 0.2 µM. Live cell measurements were achieved by placing the sensor in the culture medium, ensuring their adhesion on the sensors' surface; two cell lines were used as non-tumorigenic (Vero cells) and tumorigenic (SKBR3 cells) models, respectively. Real-time detection of H2O2 released by cells upon stimulation with phorbol ester was carried out; the nitrocellulose sensor returned on-site and real-time quantitative information on the H2O2 released proving useful sensitivity and selectivity, allowing to distinguish tumorigenic cells. The proposed strategy allows low-cost in-series semi-automatic production of paper-based point-of-care devices using simple benchtop instrumentation, paving the way for the easy and affordable monitoring of the cytopathology state of cancer cells.

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.

The Future of Nanotechnology-Driven Electrochemical and Electrical Point-of-Care Devices and Diagnostic Tests.

Point-of-care (POC) devices have become rising stars in the biosensing field, aiming at prognosis and diagnosis of diseases with a positive impact on the patient but also on healthcare and social care systems. Putting the patient at the center of interest requires the implementation of noninvasive technologies for collecting biofluids and the development of wearable platforms with integrated artificial intelligence-based tools for improved analytical accuracy and wireless readout technologies. Many electrical and electrochemical transducer technologies have been proposed for POC-based sensing, but several necessitate further development before being widely deployable. This review focuses on recent innovations in electrochemical and electrical biosensors and their growth opportunities for nanotechnology-driven multidisciplinary approaches. With a focus on analytical aspects to pave the way for future electrical/electrochemical diagnostics tests, current limitations and drawbacks as well as directions for future developments are highlighted.

Early diagnosis of autoimmune diseases through electrochemical biosensing using a modified plastic chip electrode.

Detecting chronic autoimmune disorders (ADs) early reduces the risk of morbidity, disability, and mortality and offers the possibility of significant therapeutic action in a timely manner. Developing low-cost, reliable, and sensitive sensors for ADs can ensure the efficient utilization of healthcare resources at earlier stages. Here, we report on the development of an electrochemical biosensor for sensing CXCL10, a chemokine protein that serves as a biomarker for autoimmune diseases. A self-assembly strategy is used for the immobilization of biorecognition elements on a plastic chip electrode (PCE). A homemade PCE offers a versatile and cost-effective scaffold for sensing applications. Gold nanoparticles were electrochemically deposited on the electrode via the reduction of gold ions on the PCE galvanostatically. The CXCL10 antibody and recognition elements were immobilized on the gold-deposited PCE. The attachment of recognition molecules was confirmed by energy-dispersive scanning electron microscopy, atomic force microscopy, infrared spectroscopy, and electrochemical techniques. Electrochemical impedance spectroscopy (EIS) was used for the detection of CXCL10 within a concentration range spanning from pico- to micro-molar levels. The sensor exhibited remarkable linearity in both buffer and plasma solutions, with a limit of detection (LOD) of up to 0.72 pg mL-1.