Biosensors

Rapid, sensitive, selective and portable virus detection is in high demand globally. However, differentiating non-infectious viral particles from intact/infectious viruses is still a rarely satisfied sensing requirement. Using the negative space within monolayers of polystyrene (PS) spheres deposited directly on gold electrodes, we fabricated tuneable nanochannels decorated with target-selective bioreceptors that facilitate the size-selective detection of intact viruses. Detection occurred through selective nanochannel blockage of diffusion of a redox probe, [Fe(CN)₆]^3/4−, allowing a quantifiable change in the oxidation current before and after analyte binding to the bioreceptor immobilised on the spheres. Our model system involved partial surface passivation of the mono-assembled PS spheres, by silica glancing angle deposition, to confine bioreceptor immobilisation specifically to the channels and improve particle detection sensitivity. Virus detection was first optimised and modelled with biotinylated gold nanoparticles, recognised by streptavidin immobilised on the PS layer, reaching a low limit of detection of 37 particles/mL. Intact, label-free virus detection was demonstrated using MS2 bacteriophage (~23–28 nm), a marker of microbiological contamination, showing an excellent limit of detection of ~1.0 pfu/mL. Tuneable nanochannel geometries constructed directly on sensing electrodes offer label-free, sensitive, and cost-efficient point-of-care biosensing platforms that could be applied for a wide range of viruses. Full article

Pulse wave velocity (PWV) measured at a specific artery location is called local PWV, which provides the elastic characteristics of arteries and indicates the degree of arterial stiffness. However, the large and cumbersome ultrasound probes require an appropriate sensor position and pressure maintenance, introducing usability constraints. In this paper, we developed a light (0.5 g) and thin (400 $\mathsf{\mu }$m) flexible ultrasound array by encapsulating 1–3 composite piezoelectric transducers with a silicone elastomer. It can capture the distension waveforms of four arterial positions with a spacing of 10 mm and calculate the local PWV by multi-point fitting. This is illustrated by in vivo experiments, where the local PWV value of five normal subjects ranged from 3.07 to 4.82 m/s, in agreement with earlier studies. The beat-to-beat coefficient of variation (CV) is 12.0% ± 3.5%, showing high reliability. High reproducibility is shown by the results of two groups of independent measurements of three subjects (the error between the mean values is less than 0.3 m/s). These properties of the developed flexible ultrasound array enable the bandage-like application of local PWV monitoring to skin surfaces. Full article

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments. Full article

Aptamers are a particular class of functional recognition ligands with high specificity and affinity to their targets. As the candidate recognition layer of biosensors, aptamers can be used to sense biomolecules. Aptasensors, aptamer-based biosensors, have been demonstrated to be specific, sensitive, and cost-effective. Furthermore, smartphone-based devices have shown their advantages in binding to aptasensors for point-of-care testing (POCT), which offers an immediate or spontaneous responding time for biological testing. This review describes smartphone-based aptasensors to detect various targets such as metal ions, nucleic acids, proteins, and cells. Additionally, the focus is also on aptasensors-related technologies and configurations. Full article

This work is aimed at the development of new heterostructures based on cobalt phthalocyanines (CoPc) and gold nanoparticles (AuNPs), and the evaluation of the prospects of their use to determine low concentrations of ammonia and nitric oxide. For this purpose, CoPc films were decorated with AuNPs by gas-phase methods (MOCVD and PVD) and drop-casting (DC), and their chemiresistive sensor response to low concentrations of NO (10–50 ppb) and NH₃ (1–10 ppm) was investigated. A comparative analysis of the characteristics of heterostructures depending on the preparation methods was carried out. The composition, structure, and morphology of the resulting hybrid films were studied by X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission (ICP-AES) spectroscopy, as well as electron microscopy methods to discuss the effect of these parameters on the sensor response of hybrid films to ammonia and nitric oxide. It was shown that regardless of the fabrication method, the response of Au/CoPc heterostructures to NH₃ and NO gases increased with an increase in the concentration of gold. The sensor response of Au/CoPc heterostructures to NH₃ increased 2–3.3 times compared to CoPc film, whereas in the case of NO it increased up to 16 times. The detection limits of the Au/CoPc heterostructure with a gold content of ca. 2.1 µg/cm² for NH₃ and NO were 0.1 ppm and 4 ppb, respectively. It was shown that Au/CoPc heterostructures can be used for the detection of NH₃ in a gas mixture simulating exhaled air (N₂—74%, O₂—16%, H₂O—6%, CO₂—4%). Full article

Fetal electrocardiography (ECG) monitoring during pregnancy can provide crucial information for assessing the fetus’s health status and making timely decisions. This paper proposes a portable ECG monitoring system to record the abdominal ECG (AECG) of the pregnant woman, comprising both maternal ECG (MECG) and fetal ECG (FECG), which could be applied to fetal heart rate (FHR) monitoring at the home setting. The ECG monitoring system is based on data acquisition circuits, data transmission module, and signal analysis platform, which consists of low input-referred noise, high input impedance, and high resolution. The combination of the adaptive dual threshold (ADT) and the independent component analysis (ICA) algorithm is employed to extract the FECG from the AECG signals. To validate the performance of the proposed system, AECG is recorded and analyzed of pregnant women in three different postures (supine, seated, and standing). The result shows that the proposed system can record the AECG in different postures with good signal quality and high accuracy in fetal ECG and heart rate information. Sensitivity (Se), positive predictive accuracy (PPV), accuracy (ACC), and their harmonic mean (F1) are utilized as the metrics to evaluate the performance of the fetal QRS (fQRS) complexes extraction. The average Se, PPV, ACC, and F1 score are 99.62%, 97.90%, 97.40%, and 98.66% for the fQRS complexes extraction,, respectively. This paper shows the proposed system has a promising application in fetal health monitoring. Full article

Software tools that are able to simulate the functionality or interactions of an enzyme biosensor with Metal Oxide Semiconductor (MOS), or any Field Effect Transistor (FET) as transducer, represent a gap in the market. Bio-devices, or Enzyme-FET, cannot be simulated by Atlas or equivalent software. This paper resolves this issue for the enzymatic block coupled with FETs’ role within biosensors. The first block has the concentration of biological analyte as the input signal and concentration of ions from the enzymatic reaction as the output signal. The modeling begins from the Michaelis–Menten formalism and analyzes the time dependence of the product concentrations that become the input signal for the next FET block. Comparisons within experimental data are provided. The analytical model proposed in this paper represents a general analytical tool in the design stage for enzymatic transistors used in clinical practices. Full article

The development of precise and efficient diagnostic tools enables early treatment and proper isolation of infected individuals, hence limiting the spread of coronavirus disease 2019 (COVID-19). The standard diagnostic tests used by healthcare workers to diagnose severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have some limitations, including longer detection time, the need for qualified individuals, and the use of sophisticated bench-top equipment, which limit their use for rapid SARS-CoV-2 assessment. Advances in sensor technology have renewed the interest in electrochemical biosensors miniaturization, which provide improved diagnostic qualities such as rapid response, simplicity of operation, portability, and readiness for on-site screening of infection. This review gives a condensed overview of the current electrochemical sensing platform strategies for SARS-CoV-2 detection in clinical samples. The fundamentals of fabricating electrochemical biosensors, such as the chosen electrode materials, electrochemical transducing techniques, and sensitive biorecognition molecules, are thoroughly discussed in this paper. Furthermore, we summarised electrochemical biosensors detection strategies and their analytical performance on diverse clinical samples, including saliva, blood, and nasopharyngeal swab. Finally, we address the employment of miniaturized electrochemical biosensors integrated with microfluidic technology in viral electrochemical biosensors, emphasizing its potential for on-site diagnostics applications. Full article

Metallic nanoparticles potentially have wide practical applications in various fields of science and industry. In biosensorics, they usually act as catalysts or nanozymes (NZs) and as mediators of electron transfer. We describe here the development of amperometric biosensors (ABSs) based on purified oxidases, synthesized nanoparticles of CuCe (nCuCe), and micro/nanoporous gold (pAu), which were electro-deposited on a graphite electrode (GE). As an effective peroxidase (PO)-like NZ, nCuCe was used here as a hydrogen-peroxide-sensing platform in ABSs that were based on glucose oxidase, alcohol oxidase, methylamine oxidase, and L-arginine oxidase. At the same time, nCuCe is an electroactive mediator and has been used in laccase-based ABSs. As a result, the ABSs we constructed and characterized were based on glucose, methanol, methyl amine, L-arginine, and catechol, respectively. The developed nCuCe-based ABSs exhibited improved analytical characteristics in comparison with the corresponding PO-based ABSs. Additionally, the presence of pAu, with its extremely advanced chemo-sensing surface layer, was shown to significantly increase the sensitivities of all constructed ABSs. As an example, the bioelectrodes containing laccase/GE, laccase/nCuCe/GE, and laccase/nCuCe/pAu/GE exhibited sensitivities to catechol at 2300, 5055, and 9280 A·M⁻¹·m⁻², respectively. We demonstrate here that pAu is an effective carrier of electroactive nanomaterials coupled with oxidases, which may be promising in biosensors. Full article

Terahertz (THz)-detection technology has been proven to be an effective and rapid non-destructive detection approach in biomedicine, quality control, and safety inspection, among other applications. However, the sensitivity of such a detection method is limited due to the insufficient power of the terahertz source and the low content, or ambiguous characteristics, of the analytes to be measured. Metamaterial (MM) is an artificial structure in which periodic sub-wavelength units are arranged in a regular manner, resulting in extraordinary characteristics beyond those possessed by natural materials. It is an effective method to improve the ability of terahertz spectroscopy detection by utilizing the metamaterial as a sensor. In this paper, a dual-band, high-sensitivity THz MM sensor based on the split metal stacking ring resonator (SMSRR) is proposed. The appliance exhibited two resonances at 0.97 and 2.88 THz in the range of 0.1 to 3 THz, realizing multi-point matching between the resonance frequency and the characteristic frequency of the analytes, which was able to improve the reliability and detection sensitivity of the system. The proposed sensor has good sensing performance at both resonant frequencies and can achieve highest sensitivities of 304 GHz/RIU and 912 GHz/RIU with an appropriate thickness of the analyte. Meanwhile, the advantage of multi-point matching of the proposed sensor has been validated by distinguishing four edible oils based on their different refractive indices and demonstrating that the characteristics obtained in different resonant frequency bands are consistent. This work serves as a foundation for future research on band extension and multi-point feature matching in terahertz detection, potentially paving the way for the development of high-sensitivity THz MM sensors. Full article

Microorganisms are omnipresent and inseparable from our life. Many of them are beneficial to humans, while some are not. Importantly, foods and beverages are susceptible to microbial contamination, with their toxins causing illnesses and even death in some cases. Therefore, monitoring and detecting harmful microorganisms are critical to ensuring human health and safety. For several decades, many methods have been developed to detect and monitor microorganisms and their toxicants. Conventionally, nucleic acid analysis and antibody-based analysis were used to detect pathogens. Additionally, diverse chromatographic methods were employed to detect toxins based on their chemical and structural properties. However, conventional techniques have several disadvantages concerning analysis time, sensitivity, and expense. With the advances in biotechnology, new approaches to detect pathogens and toxins have been reported to compensate for the disadvantages of conventional analysis from different research fields, including electrochemistry, nanotechnology, and molecular biology. Among them, we focused on the recent studies of transcription factor (TF)-based biosensors to detect microorganisms and discuss their perspectives and applications. Additionally, the other biosensors for detecting microorganisms reported in recent studies were also introduced in this review. Full article

In this paper, we present ARMIA: a sensorized arm wearable that includes a combination of inertial and sEMG sensors to interact with serious games in telerehabilitation setups. This device reduces the cost of robotic assistance technologies to be affordable for end-users at home and at rehabilitation centers. Hardware and acquisition software specifications are described together with potential applications of ARMIA in real-life rehabilitation scenarios. A detailed comparison with similar medical technologies is provided, with a specific focus on wearable devices and virtual and augmented reality approaches. The potential advantages of the proposed device are also described showing that ARMIA could provide similar, if not better, the effectivity of physical therapy as well as giving the possibility of home-based rehabilitation. Full article

One of the most effective ways to detect and measure antibiotics is to detect their biomarkers. The best biomarker for the control and detection of oxytetracycline (OTC) is the OTC-specific aptamer. In this study, a novel, rapid, and label-free aptamer-based electrochemical biosensor (electrochemical aptasensor) was designed for OTC determination based on a newly synthesized nanocomposite including multi-walled carbon nanotubes (MWCNTs), gold nanoparticles (AuNPs), reduced graphene oxide (rGO), and chitosan (CS), as well as nanosheets to modify a glassy carbon electrode, which extremely enhanced electrical conductivity and increased the electrode surface to bind well with the amine-terminated OTC-specific aptamer through self-assembly. The (MWCNTs-AuNPs/CS-AuNPs/rGO-AuNPs) nanocomposite modified electrode was synthesized using a layer- by-layer modification method which had the highest efficiency for better aptamer stabilization. Differential pulse voltammetry (DPV), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) techniques were used to investigate and evaluate the electrochemical properties and importance of the synthesized nanocomposite in different steps. The designed aptasensor was very sensitive for measuring the OTC content of milk samples, and the results were compared with those of our previously published paper. Based on the calibration curve, the detection limit was 30.0 pM, and the linear range was 1.00–540 nM for OTC. The repeatability and reproducibility of the aptasensor were obtained for 10.0 nM of OTC with a relative standard deviation (RSD%) of 2.39% and 4.01%, respectively, which were not affected by the coexistence of similar derivatives. The measurement in real samples with the recovery range of 93.5% to 98.76% shows that this aptasensor with a low detection limit and wide linear range can be a good tool for detecting OTC. Full article

Diabetes is a health disorder that necessitates constant blood glucose monitoring. The industry is always interested in creating novel glucose sensor devices because of the great demand for low-cost, quick, and precise means of monitoring blood glucose levels. Electrochemical glucose sensors, among others, have been developed and are now frequently used in clinical research. Nonetheless, despite the substantial obstacles, these electrochemical glucose sensors face numerous challenges. Because of their excellent stability, vast surface area, and low cost, various types of 2D materials have been employed to produce enzymatic and nonenzymatic glucose sensing applications. This review article looks at both enzymatic and nonenzymatic glucose sensors made from 2D materials. On the other hand, we concentrated on discussing the complexities of many significant papers addressing the construction of sensors and the usage of prepared sensors so that readers might grasp the concepts underlying such devices and related detection strategies. We also discuss several tuning approaches for improving electrochemical glucose sensor performance, as well as current breakthroughs and future plans in wearable and flexible electrochemical glucose sensors based on 2D materials as well as photoelectrochemical sensors. Full article

COVID-19 continues to spread and has been declared a global emergency. Individuals with current or past infection should be identified as soon as possible to prevent the spread of disease. Surface-enhanced Raman spectroscopy (SERS) is an analytical technique that has the potential to be used to detect viruses at the site of therapy. In this context, SERS is an exciting technique because it provides a fingerprint for any material. It has been used with many COVID-19 virus subtypes, including Deltacron and Omicron, a novel coronavirus. Moreover, flexible SERS substrates, due to their unique advantages of sensitivity and flexibility, have recently attracted growing research interest in real-world applications such as medicine. Reviewing the latest flexible SERS-substrate developments is crucial for the further development of quality detection platforms. This article discusses the ultra-responsive detection methods used by flexible SERS substrate. Multiplex assays that combine ultra-responsive detection methods with their unique biomarkers and/or biomarkers for secondary diseases triggered by the development of infection are critical, according to this study. In addition, we discuss how flexible SERS-substrate-based ultrasensitive detection methods could transform disease diagnosis, control, and surveillance in the future. This study is believed to help researchers design and manufacture flexible SERS substrates with higher performance and lower cost, and ultimately better understand practical applications. Full article

Mental stress is on the rise as one of the major health problems in modern society. It is important to detect and manage mental stress to prevent various diseases caused by stress and to maintain a healthy life. The purpose of this paper is to present new heart rate variability (HRV) features based on empirical mode decomposition and to detect acute mental stress through short-term HRV (5 min) and ultra-short-term HRV (under 5 min) analysis. HRV signals were acquired from 74 young police officers using acute stressors, including the Trier Social Stress Test and horror movie viewing, and a total of 26 features, including the proposed IMF energy features and general HRV features, were extracted. A support vector machine (SVM) classification model is used to classify the stress and non-stress states through leave-one-subject-out cross-validation. The classification accuracies of short-term HRV and ultra-short-term HRV analysis are 86.5% and 90.5%, respectively. In the results of ultra-short-term HRV analysis using various time lengths, we suggest the optimal duration to detect mental stress, which can be applied to wearable devices or healthcare systems. Full article

Electrochemical nano-biosensor systems are popular in the industrial field, along with evaluations of medical, agricultural, environmental and sports analysis, because they can simultaneously perform qualitative and quantitative analyses with high sensitivity. However, real-time detection using an electrochemical nano-biosensor is greatly affected by the surrounding environment with the performance of the electron transport materials. Therefore, many researchers are trying to find good factors for real-time detection. In this work, it was found that a composite composed of graphite oxide/cobalt/chitosan had strong stability and electron transfer capability and was applied to a bioelectrochemical nano-biosensor with high sensitivity and stability. As a mediator-modified electrode, the GO/Co/chitosan composite was electrically deposited onto an Au film electrode by covalent boding, while glucose oxidase as a receptor was immobilized on the end of the GO/Co/chitosan composite. It was confirmed that the electron transfer ability of the GO/Co/chitosan composite was excellent, as shown with power density analysis. In addition, the real-time detection of D-glucose could be successfully performed by the developed nano-biosensor with a high range of detected concentrations from 1.0 to 15.0 mM. Furthermore, the slope value composed of the current, per the concentration of D-glucose as a detection response, was significantly maintained even after 14 days. Full article

This paper aims to propose a new photoacoustic/ultrasound endoscopic imaging reconstruction algorithm based on the approximate Gaussian acoustic field which significantly improves the resolution and signal-to-noise ratio (SNR) of the out-of-focus region. We demonstrated the method by numerical calculations and investigated the applicability of the algorithm in a chicken breast phantom. The validation was finally performed by the rabbit rectal endoscopy experiment. Simulation results show that the lateral resolution of the target point in the out-of-focus region can be well optimized with this new algorithm. Phantom experimental results show that the lateral resolution of the indocyanine green (ICG) tube in the photoacoustic image is reduced from 3.975 mm to 1.857 mm by using our new algorithm, which is a 52.3% improvement. Ultrasound images also show a significant improvement in lateral resolution. The results of the rabbit rectal endoscopy experiment prove that the algorithm we proposed is capable of providing higher-quality photoacoustic/ultrasound images. In conclusion, the algorithm enables fast acoustic resolution photoacoustic/ ultrasonic dynamic focusing and effectively improves the imaging quality of the system, which has significant guidance for the design of acoustic resolution photoacoustic/ultrasound endoscopy systems. Full article

Wound healing is a complex biological phenomenon, having different but overlapping stages to obtained complete re-epithelization. The aim of the current study was to develop a dendrimer-based hydrogel bandage, to ameliorate full-thickness wounds. Hesperidin, a bioflavonoid found in vegetables and citrus fruits, is used for treatment of wounds; however, its therapeutic use is limited, due to poor water solubility and poor bioavailability. This issue was overcome by incorporating hesperidin in the inner core of a dendrimer. Hence, a dendrimer-based hydrogel bandage was prepared, and the wound healing activity was determined. A hemolysis study indicated that the hesperidin-loaded dendrimer was biocompatible and can be used for wound healing. The therapeutic efficacy of the prepared formulation was evaluated on a full-thickness wound, using an animal model. H&E staining of the control group showed degenerated neutrophils and eosinophils, while 10% of the formulation showed wound closure, formation of the epidermal layer, and remodeling. The MT staining of the 10% formulation showed better collagen synthesis compared to the control group. In vivo results showed that the preparation had better wound contraction activity compared to the control group; after 14 days, the control group had 79 ± 1.41, while the 10% of formulation had 98.9 ± 0.42. In a nutshell, Hsp-P-Hyd 10% showed the best overall performance in amelioration of full-thickness wounds. Full article