Design of Pyrrole-Based Gate-Controlled Molecular Junctions Optimized for Single-Molecule Aflatoxin B1 Detection.

Food contamination by aflatoxins is an urgent global issue due to its high level of toxicity and the difficulties in limiting the diffusion. Unfortunately, current detection techniques, which mainly use biosensing, prevent the pervasive monitoring of aflatoxins throughout the agri-food chain. In this work, we investigate, through ab initio atomistic calculations, a pyrrole-based Molecular Field Effect Transistor (MolFET) as a single-molecule sensor for the amperometric detection of aflatoxins. In particular, we theoretically explain the gate-tuned current modulation from a chemical-physical perspective, and we support our insights through simulations. In addition, this work demonstrates that, for the case under consideration, the use of a suitable gate voltage permits a considerable enhancement in the sensor performance. The gating effect raises the current modulation due to aflatoxin from 100% to more than 103÷104%. In particular, the current is diminished by two orders of magnitude from the µA range to the nA range due to the presence of aflatoxin B1. Our work motivates future research efforts in miniaturized FET electrical detection for future pervasive electrical measurement of aflatoxins.

Enhanced Enzymatically Amplified Metallization on Nanostructured Surfaces for Multiplexed Point-of-Care Electrical Detection of COVID-19 Biomarkers.

Inexpensive yet sensitive and specific biomarker detection is a critical bottleneck in diagnostics, monitoring, and surveillance of infectious diseases such as COVID-19. Multiplexed detection of several biomarkers can achieve wider diagnostic applicability, accuracy, and ease-of-use, while reducing cost. Current biomarker detection methods often use enzyme-linked immunosorbent assays (ELISA) with optical detection which offers high sensitivity and specificity. However, this is complex, expensive, and limited to detecting only a single analyte at a time. Here, it is found that biomarker-bound enzyme-labeled probes act synergistically with nanostructured catalytic surfaces and can be used to selectively reduce a soluble silver substrate to generate highly dense and conductive, localized surface silver metallization on microelectrode arrays. This enables a sensitive and quantitative, simple, direct electronic readout of biomarker binding without the use of any intermediate optics. Furthermore, the localized and dry-phase stable nature of the metallization enables multiplexed electronic measurement of several biomarkers from a single drop (<10 µL) of sample on a microchip.This method is applied for the multiplexed point-of-care (POC) quantitative detection of multiple COVID-19 antigen-specific antibodies. Combining a simple microchip and an inexpensive, cellphone-interfaced, portable reader, the detection and discrimination of biomarkers of prior infection versus vaccination is demonstrated.

Review of the use of nanodevices to detect single molecules.

The development of methodologies to identify single molecules and/or to detect/monitor molecular behavior at the single-molecule level is one of the important research topics in chemistry and biology. In this review, we summarized the state-of-the-art of single molecule measurement methods and its latest applications using nanodevices integrated with molecular-size functional nanostructures, nanopores, nanogaps, and nanofluidic channels, which detect differences in chemical species, presence or absence of translational modifications, changes in steric structure, and changes in interactions between molecules. Besides these fundamental analytical achievements of molecular identification abilities, the latest applications include the single-molecule electrical sequencing, disease diagnosis, viral testing, single-molecule drug screening, and environmental monitoring. Finally, we added some discussion on the current status of single-molecule measurement as a method and technology to solve the problems to expand the future application needs of single-molecule measurement.

Advances in multiplex electrical and optical detection of biomarkers using microfluidic devices.

Microfluidic devices can provide a versatile, cost-effective platform for disease diagnostics and risk assessment by quantifying biomarkers. In particular, simultaneous testing of several biomarkers can be powerful. Here, we critically review work from the previous 4 years up to February 2021 on developing microfluidic devices for multiplexed detection of biomarkers from samples. We focus on two principal approaches: electrical and optical detection methods that can distinguish and quantify biomarkers. Both electrical and spectroscopic multiplexed detection strategies are being employed to reach limits of detection below clinical sample levels. Some of the most promising strategies for point-of-care assays involve inexpensive materials such as paper-based microfluidic devices, or portable and accessible detectors such as smartphones. This review does not comprehensively cover all multiplexed microfluidic biomarker studies, but rather provides a critical evaluation of key work and suggests promising prospects for future advancement in this field. Electrical and optical multiplexing are powerful approaches for microfluidic biomarker analysis.

Luminescent Silicon Nanowires as Novel Sensor for Environmental Air Quality Control.

Air quality monitoring is an increasingly debated topic nowadays. The increasing spillage of waste products released into the environment has contributed to the increase in air pollution. Consequently, the production of increasingly performing devices in air monitoring is increasingly in demand. In this scenario, the attention dedicated to workplace safety monitoring has led to the developing and improving of new sensors. Despite technological advancements, sensors based on nanostructured materials are difficult to introduce into the manufacturing flow due to the high costs of the processes and the approaches that are incompatible with the microelectronics industry. The synthesis of a low-cost ultra-thin silicon nanowires (Si NWs)-based sensor is here reported, which allows us the detection of various dangerous gases such as acetone, ethanol, and the ammonia test as a proof of concept in a nitrogen-based mixture. A modified metal-assisted chemical etching (MACE) approach enables to obtain ultra-thin Si NWs by a cost-effective, rapid and industrially compatible process that exhibit an intense light emission at room temperature. All these gases are common substances that we find not only in research or industrial laboratories, but also in our daily life and can pose a serious danger to health, even at small concentrations of a few ppm. The exploitation of the Si NWs optical and electrical properties for the detection of low concentrations of these gases through their photoluminescence and resistance changes will be shown in a nitrogen-based gas mixture. These sensing platforms give fast and reversible responses with both optical and electrical transductions. These high performances and the scalable synthesis of Si NWs could pave the way for market-competitive sensors for ambient air quality monitoring.

A machine learning approach for accurate and real-time DNA sequence identification.

BACKGROUND: The all-electronic Single Molecule Break Junction (SMBJ) method is an emerging alternative to traditional polymerase chain reaction (PCR) techniques for genetic sequencing and identification. Existing work indicates that the current spectra recorded from SMBJ experimentations contain unique signatures to identify known sequences from a dataset. However, the spectra are typically extremely noisy due to the stochastic and complex interactions between the substrate, sample, environment, and the measuring system, necessitating hundreds or thousands of experimentations to obtain reliable and accurate results. RESULTS: This article presents a DNA sequence identification system based on the current spectra of ten short strand sequences, including a pair that differs by a single mismatch. By employing a gradient boosted tree classifier model trained on conductance histograms, we demonstrate that extremely high accuracy, ranging from approximately 96 % for molecules differing by a single mismatch to 99.5 % otherwise, is possible. Further, such accuracy metrics are achievable in near real-time with just twenty or thirty SMBJ measurements instead of hundreds or thousands. We also demonstrate that a tandem classifier architecture, where the first stage is a multiclass classifier and the second stage is a binary classifier, can be employed to boost the single mismatched pair's identification accuracy to 99.5 %. CONCLUSIONS: A monolithic classifier, or more generally, a multistage classifier with model specific parameters that depend on experimental current spectra can be used to successfully identify DNA strands.

Titanium dioxide-mediated resistive nanobiosensor for E. coli O157:H7.

A titanium dioxide nanoparticle (TiO2 NP)-mediated resistive biosensor is described for the determination of DNA fragments of Escherichia coli O157:H7 (E. coli O157:H7). The sol-gel method was used to synthesize the TiO2 NP, and microlithography was applied to fabricate the interdigitated sensor electrodes. Conventional E. coli DNA detections are facing difficulties in long-preparation-and-detection-time (more than 3 days). Hence, electronic biosensor was introduced by measuring the current-voltage (I-V) DNA probe without amplification of DNA fragments. The detection scheme is based on the interaction between the electron flow on the sensor and the introduction of negative charges from DNA probe and target DNA. The biosensor has a sensitivity of 1.67 × 1013 Ω/M and a wide analytical range. The limit detection is down to 1 × 10-11 M of DNA. The sensor possesses outstanding repeatability and reproducibility and is cabable to detect DNA within 15 min in a minute-volume sample (1 µL). Graphical abstract Fig. (a) Graphical illustration of electronic biosensor set up and (b) relationship between limit of detection (LOD) and the unaffected poultry samples on E. coli O157:H7.

A Miniature Aerosol Sensor for Detecting Polydisperse Airborne Ultrafine Particles.

Counting and sizing of polydisperse airborne nanoparticles have attracted most attentions owing to increasing widespread presence of airborne engineered nanoparticles or ultrafine particles. Here we report a miniature aerosol sensor to detect particle size distribution of polydisperse ultrafine particles based on ion diffusion charging and electrical detection. The aerosol sensor comprises a couple of planar electrodes printed on two circuit boards assembled in parallel, where charging, precipitation and measurement sections are integrated into one chip, which can detect aerosol particle size in of 30-500 nm, number concentration in range of 5 × 10²-107 /cm³. The average relative errors of the measured aerosol number concentration and the particle size are estimated to be 12.2% and 13.5% respectively. A novel measurement scheme is proposed to actualize a real-time detection of polydisperse particles by successively modulating the measurement voltage and deducing the particle size distribution through a smart data fusion algorithm. The effectiveness of the aerosol sensor is experimentally demonstrated via measurements of polystyrene latex (PSL) aerosol and nucleic acid aerosol, as well as sodium chloride aerosol particles.

Digital Sort-Enabled Counting Allows Absolute Electrical Quantification of Target Nucleic Acid.

Quantitative nucleic acid amplification tests are of great importance for diagnostics, but current approaches require complex and costly optical setups that limit their nonlaboratory applications. Herein we describe the implementation of a microfluidics platform that can perform binary DNA-amplification-activated droplet sorting. The digital sort-enabled counting (DISCO) platform enables label-free absolute quantification of the nucleic acid. This is achieved by provoking a pH change in droplets through a loop-mediated isothermal amplification (LAMP) reaction, followed by using sorting by interfacial tension (SIFT) to direct positive and negative droplets to different outlets. With the use of on-chip electrodes at both outlets, we demonstrate that the digital electrical counting of target DNA and RNA can be realized. DISCO is a promising approach for realizing sensitive nucleic acid quantification in point-of-care settings.

Direct-Current Electrical Detection of Surface-Acoustic-Wave-Driven Ferromagnetic Resonance.

Surface acoustic waves (SAW) provide a promising platform to study spin-phonon coupling, which can be achieved by SAW-driven ferromagnetic resonance (FMR) for efficient acoustic manipulation of spin. Although the magneto-elastic effective field model has achieved great success in describing SAW-driven FMR, the magnitude of the effective field acting on the magnetization induced by SAW still remains hard to access. Here, by integrating ferromagnetic stripes with SAW devices, direct-current detection for SAW-driven FMR based on electrical rectification is reported. By analyzing FMR rectified voltage, the effective fields are straightforwardly characterized and extracted, which exhibits the advantages of better integration compatibility and lower cost than traditional methods such as vector-network analyzer-based techniques. A large nonreciprocal rectified voltage is obtained, which is attributed to the coexistence of in-plane and out-of-plane effective fields. The effective fields can be modulated by controlling the longitudinal and shear strains within the films to achieve almost 100% nonreciprocity ratio, demonstrating the potential for electrical switches. Besides its fundamental significance, this finding provides a unique opportunity for a designable spin acousto-electronic device and its convenient signal readout.

Fabrication of Silicon Nanowire Sensors for Highly Sensitive pH and DNA Hybridization Detection.

A highly sensitive silicon nanowire (SiNW)-based sensor device was developed using electron beam lithography integrated with complementary metal oxide semiconductor (CMOS) technology. The top-down fabrication approach enables the rapid fabrication of device miniaturization with uniform and strictly controlled geometric and surface properties. This study demonstrates that SiNW devices are well-aligned with different widths and numbers for pH sensing. The device consists of a single nanowire with 60 nm width, exhibiting an ideal pH responsivity (18.26 × 106 Ω/pH), with a good linear relation between the electrical response and a pH level range of 4-10. The optimized SiNW device is employed to detect specific single-stranded deoxyribonucleic acid (ssDNA) molecules. To use the sensing area, the sensor surface was chemically modified using (3-aminopropyl) triethoxysilane and glutaraldehyde, yielding covalently linked nanowire ssDNA adducts. Detection of hybridized DNA works by detecting the changes in the electrical current of the ssDNA-functionalized SiNW sensor, interacting with the targeted ssDNA in a label-free way. The developed biosensor shows selectivity for the complementary target ssDNA with linear detection ranging from 1.0 × 10-12 M to 1.0 × 10-7 M and an attained detection limit of 4.131 × 10-13 M. This indicates that the use of SiNW devices is a promising approach for the applications of ion detection and biomolecules sensing and could serve as a novel biosensor for future biomedical diagnosis.

Silicon nanowires-based biosensors for the electrical detection of Escherichia coli.

One of the main challenges in terms of public health concerns the prevention of bacterial contamination using rapid, highly sensitive and specific detection techniques. The development of highly sensitive bacterial sensors for Escherichia coli detection based on networks of silicon nanowires has been carried out in this work. The interest of these nano-objects takes advantage in a large contact surface allowing potentially important interactions with bacteria. Their presence induces a change in electrical interaction through the silicon nanowires array and is the basis for the development of silicon nanowires based electrical resistances acting as bacteria sensors. High specificity of these sensors is ensured by chemical functionalization of the nanowires allowing the binding of specific antibodies targeting the lipopolysaccharide (anti-LPS) of E. coli, but not S. aureus. The sensor displays a sensitivity of 83 µA per decade of CFU/mL due to the nanometric dimensions of the nanowires. The electrical measurements ensure the detection of various E. coli concentrations down to 102 CFU/mL. This SiNW biosensor device demonstrated its potential as an alternative tool for real-time bacterial detection as miniaturizable and low-cost integrated electronic sensor compatible with the classical silicon technology.

A microfluidic platform for electrical detection of DNA hybridization.

Current methods used for detection of DNA hybridization involve the use of DNA microarrays which require overnight incubation times along with bulky and expensive fluorescent scanners. Here, we demonstrate electrical detection of DNA hybridization in an oligonucleotide functionalized microfluidic channel. We use microchannels functionalized with DNA probes integrated with electrodes for measuring conductance across the channel. As beads conjugated with the target DNA passing through the channel are captured on the surface, we are able to electrically detect changes in resistance due to bead capture. Our assay can be completed in less than an hour using less than a microliter of reagent, and has the potential for extensive multiplexing. Such a device can be useful as a handheld platform in a clinical setting where one would need to rapidly genotype a small number of genes rapidly.

Ten Years Progress of Electrical Detection of Heavy Metal Ions (HMIs) Using Various Field-Effect Transistor (FET) Nanosensors: A Review.

Heavy metal pollution remains a major concern for the public today, in line with the growing population and global industrialization. Heavy metal ion (HMI) is a threat to human and environmental safety, even at low concentrations, thus rapid and continuous HMI monitoring is essential. Among the sensors available for HMI detection, the field-effect transistor (FET) sensor demonstrates promising potential for fast and real-time detection. The aim of this review is to provide a condensed overview of the contribution of certain semiconductor substrates in the development of chemical and biosensor FETs for HMI detection in the past decade. A brief introduction of the FET sensor along with its construction and configuration is presented in the first part of this review. Subsequently, the FET sensor deployment issue and FET intrinsic limitation screening effect are also discussed, and the solutions to overcome these shortcomings are summarized. Later, we summarize the strategies for HMIs' electrical detection, mechanisms, and sensing performance on nanomaterial semiconductor FET transducers, including silicon, carbon nanotubes, graphene, AlGaN/GaN, transition metal dichalcogenides (TMD), black phosphorus, organic and inorganic semiconductor. Finally, concerns and suggestions regarding detection in the real samples using FET sensors are highlighted in the conclusion.

Recent advances in nanomaterial-modified electrical platforms for the detection of dopamine in living cells.

Dopamine is a key neurotransmitter that plays essential roles in the central nervous system, including motor control, motivation, arousal, and reward. Thus, abnormal levels of dopamine directly cause several neurological diseases, including depressive disorders, addiction, and Parkinson's disease (PD). To develop a new technology to treat such diseases and disorders, especially PD, which is currently incurable, dopamine release from living cells intended for transplantation or drug screening must be precisely monitored and assessed. Owing to the advantages of miniaturisation and rapid detection, numerous electrical techniques have been reported, mostly in combination with various nanomaterials possessing specific nanoscale geometries. This review highlights recent advances in electrical biosensors for dopamine detection, with a particular focus on the use of various nanomaterials (e.g., carbon-based materials, hybrid gold nanostructures, metal oxides, and conductive polymers) on electrode surfaces to improve both sensor performance and biocompatibility. We conclude that this review will accelerate the development of electrical biosensors intended for the precise detection of metabolite release from living cells, which will ultimately lead to advances in therapeutic materials and techniques to cure various neurodegenerative disorders.

Alternative screening method for analyzing the water samples through an electrical microfluidics chip with classical microbiological assay comparison of P. aeruginosa.

Pseudomonas aeruginosa is a pathogenic bacterium in fresh water supplies that creates a risk for public health. Microbiological analysis of drinking water samples is time consuming and requires qualified personnel. Here we offer a screening system for rapid analysis of spring water that has the potential to be turned into a point-of-need system by means of simple mechanism. The test, which takes 1 h to complete, electrically interrogates the particles through a microfluidic chip suspended in the water sample. We tested the platform using water samples with micro beads and water samples spiked with P. aeruginosa at various concentrations. The mono disperse micro beads were used to evaluate the performance of the system. The results were verified by the gold standard membrane filtration method, which yielded a positive test result only for the P. aeruginosa spiked samples. Detection of 0-11 k bacteria in 30 µL samples was successfully completed in 1 h and compared with a conventional microbiological method. The presented method is a good candidate for a rapid, on-site, screening test that can result in a significant reduction in cost and analysis time compared to microbiological analyses routinely used in practice.

Tunable Magnetic Vortex Dynamics in Ion-Implanted Permalloy Disks.

Nanoscale, low-phase-noise, tunable transmitter-receiver links are key for enabling the progress of wireless communication. We demonstrate that vortex-based spin-torque nano-oscillators, which are intrinsically low-noise devices because of their topologically protected magnetic structure, can achieve frequency tunability when submitted to local ion implantation. In the experiments presented here, the gyrotropic mode is excited with spin-polarized alternating currents and anisotropic magnetoresistance measurements yield discrete frequencies from a single device. Indeed, chromium-implanted regions of permalloy disks exhibit different saturation magnetization than neighboring, non-irradiated areas, and thus different resonance frequency, corresponding to the specific area where the core is gyrating. Our study proves that such devices can be fabricated without the need for further lithographical steps, suggesting ion irradiation can be a viable and cost-effective fabrication method for densely packed networks of oscillators.

Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs.

The rapid increase in antibiotic resistant pathogenic bacteria has become a global threat, which besides the development of new drugs, requires rapid, cheap, scalable, and accurate diagnostics. Label free biosensors relying on electrochemical, mechanical, and mass based detection of whole bacterial cells have attempted to meet these requirements. However, the trade-off between selectivity and sensitivity of such sensors remains a key challenge. In particular, point-of-care diagnostics that are able to reduce and/or prevent unneeded antibiotic prescriptions require highly specific probes with sensitive and accurate transducers that can be miniaturized and multiplexed, and that are easy to operate and cheap. Towards achieving this goal, we present a number of advances in the use of graphene field effect transistors (G-FET) including the first use of peptide probes to electrically detect antibiotic resistant bacteria in a highly specific manner. In addition, we dramatically reduce the needed concentration for detection by employing dielectrophoresis for the first time in a G-FET, allowing us to monitor changes in the Dirac point due to individual bacterial cells. Specifically, we realized rapid binding of bacterial cells to a G-FET by electrical field guiding to the device to realize an overall 3 orders of magnitude decrease in cell-concentration enabling a single-cell detection limit, and 9-fold reduction in needed time to 5 min. Utilizing our new biosensor and procedures, we demonstrate the first selective, electrical detection of the pathogenic bacterial species Staphylococcus aureus and antibiotic resistant Acinetobacter baumannii on a single platform.

"Development and application of analytical detection techniques for droplet-based microfluidics"-A review.

Droplet-based microfluidics has emerged as a powerful platform for high-throughput and low-volume analysis and screening. At present, droplet-based microfluidics is transitioning from the proof-of-concept stage to real-world applications. During this process, analytical detection techniques play indispensable roles for successfully implementing droplet-based chemical or biological assays. In this review, we provide an overview of recent developments in analytical techniques for droplet analysis and elucidate the advantages and limitations of each technique. We cover the majority of technology categories, including optical detection, electrical detection, mass spectrometry, and nuclear magnetic resonance spectroscopy. Additionally, we highlight new research areas that have been enabled by these technical advances. Finally, we provide perspectives on both future technological directions and potential enabling applications.

Recent Advances in AIV Biosensors Composed of Nanobio Hybrid Material.

Since the beginning of the 2000s, globalization has accelerated because of the development of transportation systems that allow for human and material exchanges throughout the world. However, this globalization has brought with it the rise of various pathogenic viral agents, such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus, and Dengue virus. In particular, avian influenza virus (AIV) is highly infectious and causes economic, health, ethnical, and social problems to human beings, which has necessitated the development of an ultrasensitive and selective rapid-detection system of AIV. To prevent the damage associated with the spread of AIV, early detection and adequate treatment of AIV is key. There are traditional techniques that have been used to detect AIV in chickens, ducks, humans, and other living organisms. However, the development of a technique that allows for the more rapid diagnosis of AIV is still necessary. To achieve this goal, the present article reviews the use of an AIV biosensor employing nanobio hybrid materials to enhance the sensitivity and selectivity of the technique while also reducing the detection time and high-throughput process time. This review mainly focused on four techniques: the electrochemical detection system, electrical detection method, optical detection methods based on localized surface plasmon resonance, and fluorescence.