A sedentary lifestyle is one of the leading risk factors for developing obesity, increasing the risk of cardiovascular disease. In this work, we developed a novel approach to tracking glucose and cortisol to observe the dynamic relationship between the target biomarkers due to physical activity, nutrition, and the circadian cycle, via a machine learning-assisted wearable sweat-based electrochemical sensor. The machine learning approach helps to provide real-time biomarker value and a basis for actionable insight. Through this observational study, we illustrate the real-world performance of our sensing platform by examining the glucose and cortisol levels in passive sweat (<1 μL/min) of 4 healthy participants over 3 weeks for approximately 24–30 h twice a week. The ensemble learning model reached an R2 of 0.96 with an RMSE of 0.4. This novel glucose and cortisol tracking paradigm establishes the foundation for future research, including lifestyle choices’ effect on target biomarkers of metabolic disorders.

Micro RNAs (miRNAs) are 19–23 nucleotides-long non-coding RNA which have been identified as important biomarkers for many diseases, including cancers. Here, we report an ultrasensitive, highly specific, label-free, and without nucleic acid amplification (NAA) detection of miRNAs using paper-based single-walled carbon nanotubes (SWNTs) field-effect transistor (FET) biosensors. The strategy involved a two-step protocol starting with direct hybridization of the target miRNA with a specific RNA probe immobilized on SWNTs networks deposited on the paper substrate to generate the first response, followed by the recognition of the resulting RNA/miRNA duplexes with the Carnation Italian ringspot virus p19 protein (p19) in a size-dependent manner, giving the second electrical response that magnified the biosensor sensitivity. As a demonstration, we detected the miRNA-122a, a promising biomarker for the diagnosis of early-stage hepatocellular carcinoma (HCC) in various sample matrices, including phosphate buffers, human serum, and synthetic saliva. We achieved the lowest detection of 0.1 aM and a wide dynamic range of 0.1 aM–1 fM, that demonstrated its potential for rapid, facile, low-cost, and point-of-care detection of miRNAs for early cancer diagnosis.

Herein, we developed a novel method for identifying protein-small molecule interactions (PSMIs) based on the switching of DNA polymerase activity. This strategy employs the small molecule-linked DNA probe (SMP) that could bind to and disrupt the DNA polymerase aptamer probe (DAP) capable of inhibiting DNA polymerase activity. Without the binding of the target protein, the SMP is readily degraded by the applied exonuclease I (exo I), preventing its binding to the DAP. The DAP then freely inhibits the polymerase activity through its specific binding to the polymerase. In the presence of the target protein, however, the binding between the target protein and the small molecule protects the SMP against the exo I-catalyzed degradation. The intact SMP now binds to the DAP and disrupts its active aptameric structure, preventing the DAP from inhibiting the polymerase activity. The uninhibited DNA polymerase catalyzes the primer extension reaction in conjugation with the TaqMan probe (TP), leading to a significant fluorescence enhancement. Taking advantage of this elaborate design principle, we successfully identified the two model PSMIs, streptavidin/biotin (SA/BTN) and anti-digoxigenin/digoxigenin (ADIG/DIG), as low as 4.01 nM and 6.72 nM, respectively, with excellent specificity. We further validated its practical applicability by reliably identifying the SA/BTN interaction in heterogeneous human serum specimens.

The detection of Circulating Tumor Cells (CTCs) is of profound importance for cancer diagnosis and monitoring in diseased patients. In the presented work, an aptasensor for CTC detection was developed using AS1411 aptamer specific for nucleolin on cancer cells’ surface as receptor on Gold NanoParticles (GNPs) decorated U-bent optical fiber. The aptamer binds to target upon folding into a parallel G-quadruplex structure, and therefore, components of folding and running buffer were optimized to 50 mM tris buffer and 100 mM KCl with and without 5 mM Mg+2 based on Circular Dichroism spectroscopy (CD) and bright field microscopy respectively. Further, the binding of aptamer and MCF-7 cells to GNP coated U-bent fiber were validated by fluorescence microscopy. The aptasensor showed significantly higher absorbance for 104 cancer cells (retinoblastoma, meningioma, breast, cervical, and colon cancer cells) as compared to non-cancer cells (MCF-10A and WBCs) with a t-test p-value of 0.0012. On an optical bench, aptasensor was able to detect as low as 500 cells/mL. To develop a portable and small CTC detection system, aptasensor was integrated with a hand-held opto-electronic device μSens (custom developed in our lab) and was able to detect 50 cells/mL. This is the first time a portable sensing system based on U-bent optical fiber was tested for sensing cancer cells. The ability to detect diverse types of cancer cells by AS1411 aptamer is promising and paves the way for the detection of circulating tumor cells in blood samples, with relative ease and low cost.

This review aims to systematize data on the construction and applications of bacterial lux-biosensors in various fields ranging from investigation of gene regulation and regulatory networks to the new probiotics' search and ecotoxicological research. The typical technical solutions and devices required for diverse tasks applying lux-biosensors are reviewed. Aspects of the application of lux-biosensors in fundamental researches, such as the study of oxidative stress, heat shock, DNA-damaging, pro- and antioxidant activities, are also considered. This technology allows rapid screening of the biological activities of newly synthesized compounds, which could be applied as components for fuels, household chemicals, and drugs. Works related to the ecological state assessment on water resources are also described. The use of lux-biosensor complexes based on different organisms, including both gram-positive and gram-negative bacteria, makes toxicological investigations more comprehensive. Bacterial lux-biosensors based on Escherichia coli can be used as a model for evaluation of the effect of certain substances on the transmembrane potential in mitochondria, albeit with extrapolation to a certain extent. Another aspect that draws our interest is that biosensors are able to help predict some systemic properties of probiotics. In the future, it's quite promising to see more applications of lux-biosensors for environmental control, microbial-microbial interaction assessment, antioxidant action mechanism studies and toxicological studies in the development of new drugs.

Therapeutic drug monitoring (TDM) of methotrexate (MTX), an anticancer drug, is critical since MTX therapy can lead to severe adverse effects if not monitored to ensure clearance. Discriminating and quantifying MTX among its metabolites is challenging, time consuming, and not universally available. Therefore, we propose a surface-enhanced Raman scattering (SERS) based method as a rapid and easy-to-use alternative to complex standard methods. We implemented a solid phase extraction (SPE) process in a syringe filter holder (μ-SPE-SFH), suitable for the extraction of MTX and compatible with nanopillar assisted separation (NPAS) and SERS-based detection. All of the parameters related to the extraction, desorption, and NPAS procedure were investigated and optimized. The SERS spectra from maps were analyzed with partial least squares as regression (PLSR) and as a discrimination analysis (PLS-DA) to enable, for the first time with SERS, the identification and quantification of MTX in the presence of its metabolites (7-hydroxy-methotrexate (7-OH MTX) and 2,4-diamino-N(10)-methylpteroic acid (DAMPA)). PLSR facilitated MTX quantification in patient samples in the presence of drugs that could be co-administered during MTX therapy. We found the detection limit to be 0.15 μM while the limit of quantification was 0.55 μM. In addition, for the PLSR, the accuracy, precision, analytical sensitivity, and inverse of analytical sensitivity were 0.66 μM, 0.5 μM, 10.5 μM−1, and 0.1 μM respectively. Furthermore, when quantifying MTX from patient samples, we found a good agreement between calculated MTX concentration with the developed method and reference assay, showing the potential of the sensor in clinical application.

We describe an enzymatic fuel cell (EFC) that can electrooxidize glucose completely. The EFC contains the hybrid Ni@Pt-CNT/OxOx bioanode, composed of a bimetallic composite catalyst (Ni@Pt-CNT) and the enzyme oxalate oxidase (OxOx), which can cleave carbon-carbon bonds. Ni@Pt-CNT/OxOx displayed 3-fold higher catalytic activity in the presence than in the absence of glucose (1.3 and 0.4 mA cm−2, respectively), indicating that Ni@Pt-CNT and OxOx acted synergistically. Electrochemical impedance spectroscopy showed that Ni@Pt-CNT/OxOx had higher charge transfer resistance and double layer capacitance than Ni@Pt-CNT. Long-term bulk electrolysis (18 h) revealed that the EFC operating with Ni@Pt-CNT/OxOx presented better current density and stability than the electrochemical cell operating with Ni@Pt-CNT, so deep glucose electrooxidation generated energy. The glucose oxidation products detected by HPLC-UV/RID confirmed that glucose was fully electrooxidized, and that 24 electrons were harvested from it. The hybrid Ni@Pt-CNT/OxOx bioanode developed herein could be used in cascade reactions, to provide an EFC with promising application in self-powered electronic devices.

COVID-19, a highly contagious viral infection caused by the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV-2), has turned out to be a viral pandemic then ravaged many countries worldwide. In the recent years, point-of-care (POC) biosensors combined with state-of-the-art bioreceptors, and transducing systems enabled the development of novel diagnostic tools for rapid and reliable detection of biomarkers associated with SARS-CoV-2. The present review thoroughly summarises and discusses various biosensing strategies developed for probing SARS-CoV-2 molecular architectures (viral genome, S Protein, M protein, E protein, N protein and non-structural proteins) and antibodies as a potential diagnostic tool for COVID-19. This review discusses the various structural components of SARS-CoV-2, their binding regions and the bioreceptors used for recognizing the structural components. The various types of clinical specimens investigated for rapid and POC detection of SARS-CoV-2 is also highlighted. The importance of nanotechnology and artificial intelligence (AI) approaches in improving the biosensor performance for real-time and reagent-free monitoring the biomarkers of SARS-CoV-2 is also summarized. This review also encompasses existing practical challenges and prospects for developing new POC biosensors for clinical monitoring of COVID-19.

Geobacter sulfurreducens is an essential microorganism in biogeochemical cycles. It is used biotechnologically in bioremediation and electricity production. The importance of G. sulfurreducens lies in its capacity to contact extracellular electron acceptors, including several electrode materials. Taking advantage of the versatility of G. sulfurreducens to grow on different surfaces, it is possible to design and synthesize new electrodes that can expand and improve the applications of these bacteria. In this work, we performed multidisciplinary research studies to demonstrate an innovative application of this well-known microbial system. The interaction between fluorine-doped tin oxide (FTO) and ordinary glass with G. sulfurreducens was enhanced by modifying the surface with Fe2O3 films. As confocal laser microscopy analyses revealed, the enhancement promoted biofilm development, whose parameters were significantly better than the bare support-electrodes. Furthermore, we provided evidence that G. sulfurreducens interacted with and dissolved the Fe2O3 film during incubation. Then, when we added sodium acetate to the system, the microbial metabolism was activated and decreased the electrochemical response of this compound. We benefited from that behavior to develop a voltammetric-based robust biosensor that could measure sodium acetate at high concentrations with an acceptable linear interval, from 10 to 110 mM, with LOD = 5.9 ± mM and LOQ = 18.1 ± 1.5 mM.

This work presents the first integration of antibodies into one of the electrodes of a passive direct methanol fuel cell (DMFC) to create an autonomous immunosensor for cancer antigen 15–3 (CA15-3). The anode of the fuel cell was first made of carbon cloth with carbon black, platinum and ruthenium nanoparticles and then modified with anti-CA15-3, while the cathode was made of carbon cloth with carbon black and platinum nanoparticles. This hybrid DMFC (hDMFC), which works as an immunosensor, was fed with dilute methanol to generate a concentration-dependent current.The hDMFC device was calibrated in different media (buffer and serum), by incubating increasing concentrations of CA15-3 standard solutions, ranging from 47 to 750 U/mL. The linear response ranged from 188 to 563 U/mL, and the limit of detection (LoD) was 39.8 U/mL. The selectivity of the biosensor was also evaluated with competing cancer biomarkers, such as carcinoembryonic antigen (CEA), and cancer antigen 125 (CA-125), as well as with other compounds normally present in blood plasma (ascorbic acid, glucose, uric acid and urea), adjusted to the normal range of concentrations in serum. The results obtained indicate good selectivity of the immunosensor in the fuel cell.In general, the immunosensor showed a good response considering its integration into a passive DMFC. It is a good sensor for point-of-care (PoC) diagnosis because it has a good performance in human serum and, most importantly, it pursues electrical autonomy.

A facile synthesis method involving a one-step solvothermal method is demonstrated in producing fluorescent nitrogen-doped carbon dots (N-CDs) by employing biomass waste (Jengkol peels) and ethylenediamine as a source for carbon and nitrogen. The synthesized N-CDs are spherical nanoparticles with an average size of 4.495 nm, exhibit solubility in water, emit bluish-green fluorescence and a high quantum yield of up to 42%. By using UV–Visible, FTIR, XPS, HR-TEM and Photoluminescence analysis, the as-prepared N-CDs were verified. We demonstrate that nitrogen doping increases fluorescence emission intensity to its radiative recombination of the π − π∗ transitions at CC and n − π∗ at CO or CN. an optimized excitation at 370 nm, the N-CDs exhibited strong PL emission at 522 nm. Under optimized conditions, N-CDs can be used to detect Hg2+ ions based on quenched fluorescence phenomenon. The result reveals excellent selectivity and sensitivity to Hg2+ ions with a detection range of 0.5 μM–4.5 μM. The resulting N-CDs may be used for detecting Hg2+ ions in cosmetics and tap water.

This study presents a sensitive and selective aptasensor for the detection of trace amounts of MAMP. The aptasensing principle relies on modifying the planar screen-printed carbon electrode (SPCE) with the synthesized nanostructures of N-doped hollow carbon spheres (N-HCSs) and silver nanocubes (AgNCs). The nanocomposite has presented high active surface area and more electron transfer ability than bare SPCE surface. Furthermore, AgNCs in the nanocomposite acts as a linker to load high amounts of aptamer (Apt) biocaptures on the modified SPCE surface. By MAMP incubation on the embedded interface sensing, Apt arm wrapped around MAMP and the more space barrier induced on the surface and reduced the electrochemical signal of ferro/ferri cyanide as the anion redox probe. The aptasensor affinity toward MAMP led to a wide linear dynamic range (LDR) value from 1.00 pM to 50.00 mM with a low limit of detection (LOD) value of 3.33 × 10−4 pM compared to other electrochemical sensors with no significant interference from other common species. The aptasensor efficiency for MAMP measurement was satisfactory evaluated in some spiked and non-spiked serum, urine and saliva samples from a healthy and addicted person for MAMP. These acceptable results may promise the reliability of the proposed methodology for routine MAMP tests, especially saliva monitoring as the non-invasive analysis. The sensitivity and selectivity of the aptasensor, which is a bonus to accurate and valid discrimination of MAMP, holds great promise to provide technical support for routine analysis of real-world clinical samples.

At present, many single-cell electrical parameter measurement techniques have exhibit broad application prospects, but there are still some limitations such as complex single-cell operation and time-consuming measurement. This paper proposed a microflow cytometer chip with multiple electro-rotation units for measuring the electrical properties of single cells. The microdevice leverages three serial electro-rotation units to rapidly obtain rotation speeds under different signal frequencies. According to the rotation results, the electrical parameters (membrane permittivity and cytoplasmic conductivity) are estimated by using Maxwell's mixture equation fitting and neural network fitting methods respectively. We demonstrated the measurement advantages of combining microflow and electro-rotation techniques. Experimental results show that the cytometer measurement method greatly improves the throughput of single-cell characterization with a guaranteed error of less than 0.8%. The microdevice provides a microfluidic platform capable of characterizing the electrical properties of cells and the possibility of combining with neural networks.

The conjugation of antibodies onto the solid surface in a well-oriented manner has a profound impact on the sensitivity and limit of detection of an immunoassay. The chosen method of immobilisation significantly influences the interaction between antibodies and antigens on the sensing surface. Optimal antigen capture capacity is achieved when the Fab fragments of the antibodies are properly oriented away from the surface. However, conventional approaches, such as physisorption and covalent conjugation, often lead to random immobilisation, which can ultimately result in the loss of antibody functional activity. To address these challenges, linker-mediated immunoassay (LMI) has been developed to precisely control the orientation of antibody. This review, thereby, presents the fundamental principles of oriented antibody immobilisation and highlights various target sites for controlled conjugation. Additionally, this review thoroughly discusses several linker-mediated immobilisation strategies based on different noncovalent interactions, including Fc binding proteins-mediated immobilisation, DNA-directed immobilisation, biotin-streptavidin-mediated immobilisation and Fc binding peptides-mediated immobilisation, accentuating their respective strengths and limitations. Hence, this review adds more to our understanding of the state-of-the-art of LMI technology, with a particular focus on the oriented immobilisation of full-length antibodies and its potential for future applications.

Lactose concentration is a key parameter for assessing the quality of raw and processed milk and identifying abnormal milk. Current methods for lactose determination are laborious, time-consuming and oftentimes require skilled lab workers, expensive equipment, and special reagents. In this study, an optical biosensor system based on nanosized titanium dioxide (TiO2) is presented for routine measurement of lactose in milk without sample preparation. TiO2 was obtained via sol-gel synthesis and characterized using dynamic light scattering, microelectrophoresis, X-ray diffraction, transmission electron microscopy, and nitrogen adsorption-desorption analysis. The system, whose colorimetric response was based on the chromogen-free TiO2-based detection of hydrogen peroxide (H2O2), used β-galactosidase and/or glucose oxidase as the biorecognition elements. The selectivity and sensitivity of the biosensors for lactose and glucose was investigated by diffuse reflectance spectroscopy using standard aqueous lactose and glucose solutions and whole milk samples. The results showed that the proposed biosensors had high optical signal reproducibility (RSD = 5–6%), high sensitivity (LOD = 0.005 wt%), and high selectivity. The linear dynamic ranges of lactose and glucose detection were from 0.005 wt% to 0.100 wt%, and the optimal response time of the biosensor was 25 min. The listed features and advantages of label-free detection make the biosensor attractive for simple, inexpensive, sensitive, and selective determination of lactose in milk.

As unsafe food production poses global health threats, especially in developing countries, food safety detection always significantly impacts all fields of the food industry, such as production, processing, transportation, storage, and consumption. Many classical food safety detecting methods have been widely used to provide accurate, sensitive, and reliable analytical characteristics, while they rely on clean laboratories, bulky setups, trained personnel, and long-time detection. Because of those conditions, they are not suitable for on-site food safety detecting applications. To solve this problem, various food safety detecting approaches relying on field-portable devices and field-operable techniques have been designed and successfully used, indicating that they are potentially ideal solutions for on-site applications. This review summarizes the progress on on-site food safety detecting approaches and applications for various risk factors, including bacteria, parasites, viruses, toxins, pesticide and veterinary drug residues, illegal food additives, restricted food ingredients, and heavy metals. It outlines recent advances in field-portable devices and field-operable techniques that provide conditions for on-site food safety detection. Recommended on-site food safety detecting approaches for different food safety risk factors are comprehensively suggested considering detecting feasibility, accuracy, and speed. These approaches reveal an attractive and promising route for future practical food safety detecting applications with the merits of portable devices, simple user-friendly operation, and rapid on-site detection. This review further addresses current challenges, and finally discusses future trends and strategies that could be employed in on-site food safety detection.

Recent advances in flexible sensors and wireless electronics have driven the development of lightweight and ergonomic wearable sensing gloves. Such gloves can be employed in mixed reality (MR) environments to give haptic capabilities during interactions with various objects. However, no prior study shows a quantitative measurement of physical user interactions of object manipulation in MR. Here, we report an MR-integrated soft bioelectronic system on a glove for quantifying the changes in the user's pinching tasks. We use nanomanufacturing techniques to fabricate flexible sensors, wireless circuits, and stretchable interconnectors seamlessly integrated with a wearable glove. The wearable biosensing glove with an integrated capacitive pressure sensor evaluates how users interact directly and indirectly interact with objects. The direct mode describes a user's direct touching and manipulating objects in MR. In contrast, in the indirect mode, objects are located far away and touched via a narrow light beam. The virtual object measurement parameters include mass, movement latency, dynamic friction coefficient, angular drag coefficient, and linear drag coefficient. The experimental results with human subjects show positive, linear relationships between pinching force and dynamic friction coefficient and mass parameters during the direct manipulation mode. Collectively, the MR-enabled wearable biosensing glove system offers unique advantages in detecting physical interactions and sensory feedback for various rehabilitation applications and MR human-machine interfaces.

Magnetoresistance-based biosensors utilize changes in electrical resistance upon varying magnetic fields to measure biological molecules or events involved with magnetic tags. However, electrical resistance fluctuates with temperature. To decouple unwanted temperature-dependent signals from the signal of interest, various methods have been proposed to correct signals from magnetoresistance-based biosensors. Yet, there is still a need for a temperature correction method capable of instantaneously correcting signals from all sensors in an array, as multiple biomarkers need to be detected simultaneously with a group of sensors in a central laboratory or point-of-care setting. Here we report a giant magnetoresistive biosensor system that enables real-time temperature correction for individual sensors using temperature correction coefficients obtained through a temperature sweep generated by an integrated temperature modulator. The algorithm with individual temperature correction coefficients obviously outperformed that using the average temperature correction coefficient. Further, temperature regulation did not eliminate temperature-dependent signals completely. To demonstrate that the method can be used in biomedical applications where large temperature variations are involved, binding kinetics experiments and melting curve analysis were conducted with the temperature correction method. The method successfully removed all temperature-dependent artifacts and thus produced more precise kinetic parameters and melting temperatures of DNA hybrids.

The COVID-19 pandemic has presented a significant challenge to the world's public health and led to over 6.9 million deaths reported to date. A rapid, sensitive, and cost-effective point-of-care virus detection device is essential for the control and surveillance of the contagious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. The study presented here aimed to demonstrate a solid-phase isothermal recombinase polymerase amplification coupled CRISPR-based (spRPA-CRISPR) assay for on-chip multiplexed, sensitive and visual COVID-19 DNA detection. The assay targets the SARS-CoV-2 structure protein encoded genomes and can simultaneously detect two specific genes without cross-interaction. The amplified target sequences were immobilized on the one-pot device surface and detected using the mixed Cas12a-crRNA collateral cleavage of reporter-released fluorescent signal when specific genes were recognized. The endpoint signal can be directly visualized for rapid detection of COVID-19. The system was tested with samples of a broad range of concentrations (20 to 2 × 104 copies) and showed analytical sensitivity down to 20 copies per microliter. Furthermore, a low-cost blue LED flashlight (∼$12) was used to provide a visible SARS-CoV-2 detection signal of the spRPA-CRISPR assay which could be purchased online easily. Thus, our platform provides a sensitive and easy-to-read multiplexed gene detection method that can specifically identify low concentration genes.

Cancer remains the most lethal disease in today's scientific and technological age, claiming the lives of thousands of people every day. In many cases, cancer can be cured with our present technology interventions when it is detected at an early stage. State-of-the-art diagnostic devices are one of the viable strategies to combat cancer. Among various methods, optical and photoelectrochemical biosensors are the most popular for detecting cancer. This review article has focused on different optical analysis techniques and photoelectrochemical techniques for the early diagnosis of cancer via the detection of several cancer biomarkers. Optical analysis techniques involve the use of light properties such as resonance, interference, luminescence, scattering, etc. To detect analytes with high sensitivity and specificity making the techniques desirable over the traditional techniques. The photoelectrochemical technique which uses light-activating photoresponsive materials has also gained popularity lately due to its low cost, high sensitivity, and specificity. These techniques can be used to identify specific biomarkers that are associated with cancer, enabling early detection and diagnosis. Furthermore, the role of nanomaterials in designing the biosensor was taken into consideration for this study. Nanomaterials-based biosensors can detect very low concentrations of biomarkers, which is crucial for early cancer diagnosis. Additionally, the performance limitations of optical and photoelectrochemical nanobiosensors have been analyzed. Given the huge number of articles published in recent years, studies published only in the last five years have been reviewed.