Electrical Biosensors Research Articles

Silicon Nanowire Biosensors for Diabetes Mellitus Monitoring

The main goal of this research is the development of a label-free biosensor for the detection of diabetes mellitus (DM) using the target molecule retinol-binding protein 4 (RBP4). The enzyme-linked immunosorbent assay (ELISA) approach, currently used to detect DM, is time-consuming and difficult. As a result, label-free biosensors are being considered as an alternative. In this research, silicon nanowires (SiNWs) were selected as the transducer for this biosensor due to their low cost, real-time analysis capability, high sensitivity, and low detection limit. The SiNWs were created using conventional lithography, reactive ion etching (RIE), and physical vapor deposition (PVD), and then dripped with a gold nanoparticle solution to create gold-decorated SiNWs. The surface of the gold-decorated SiNWs was functionalized using 3-aminothiophenol and glutaraldehyde solutions before being immobilized with DM RBP4 antibodies and targets. The electrical characterization of the gold nanoparticle decorated SiNWs biosensor revealed good performance in DM detection. The pH tests confirmed that the SiNWs acted as a transducer, with current proportional to the DM RBP4 concentration. The estimated limit of detection (LOD) and sensitivity for detecting DM RBP4 binding were 0.076 fg/mL and 8.92 nA(g/mL)-1, respectively. This gold nanoparticle decorated SiNWs biosensor performed better than other methods and enabled efficient, accurate, and direct detection of DM. The SiNWs could be used as a distinctive electrical protein biosensor for biological diagnostic purposes. In conclusion, gold nanoparticle deposition offers effective label-free, direct, and high-accuracy DM detection, outperforming previous approaches. Thus, these SiNWs serve as novel electrical protein biosensors for future biological diagnostic applications.

Computational simulation of Casson hybrid nanofluid flow with Rosseland approximation and uneven heat source/sink

This article candidly presents the magnetohydrodynamics Casson hybrid nanofluid flow over a stretching surface. In the present study, we added a nonuniform heat source or sink and non-linear thermal radiation. We considered Al2O3 and copper nanoparticles to have antibacterial and antiviral properties without any harmful impacts and used water as the host fluid. We simplified the governing flow equations by using suitable self-similarity variables, which are used to convert PDEs to ODEs. The mathematical equations are numerically solved by using the bvp5c technique in the MATLAB software. Additionally, with higher values of the magnetic field and Casson fluid parameters the velocity profile decreased. The temperature profile is enhanced by increasing the magnetic field and thermal radiation parameters. Increasing the Casson fluid and radiation parameters enhances the skin friction and Nusselt number profiles. Alumina nanoparticles find applications in cosmetic fillers, polishing materials, catalyst carriers, analytical reagents. Copper nanoparticles have high electrical conductivity, which has many uses in electrical circuits and biosensors.

Design and optimization of refractive index biosensor for MDA-MB-231 and MCF-7 breast cancer biomarker detection

Breast cancer is the leading malignancy in women and the 2nd widespread cancer globally. Earlier identification of breast cancer can improve treatment outcomes and prevent metastasis beyond the breast. Traditional screening tests are not sensitive enough for early diagnosis and have extended detection periods. Recent studies have explored diversified Breast cancer biosensor techniques, including optical, electrical, electrochemical, and mechanical biosensors. This paper nominates a circlet with a large plus sign refraction indices biosensor for the evaluation of two distinct breast cancer cells namely, MDA-MB-231 and MCF-7. The supreme sensitivity has been viewed as 1714.28 nm/RIU for the MDA-MB-231 and 1714.28 nm/RIU for the MCF-7. The supreme quality factor (QF) value for UC1(usual cell of MDA-MB-231) is 10.52, for CC1(cancer cell of MDA-MB-231) is 11.94, for UC2 (usual cell of MCF-7) is 10.64, and for CC2 (cancer cell of MCF-7) is 12.09. The minimal detection value (DL) for UC1 is 0.1573, CC1 is 0.1360, UC2 is 0.1554, and CC2 is 0.1341. This nominated sensor has the potential to sense breast tumor biomarkers.

Succinimide-Functionalized Reduced Graphene Oxide Nanosheets: A High-throughput Resistive Sensing Platform for Age-Related Macular Degeneration Biomarker Determination Using Human Tears.

Age-related macular degeneration (AMD) is a well-recognized affliction among the elderly, causing vision impairment ranging from blurred vision to complete blindness. This underscores the critical need for accurate, precise, and early detection methods. Herein, we developed a noninvasive, label-free electrical biosensor, constructed on an economical printed circuit board (PCB) substrate, designed specifically for the precise quantification of AMD biomarker: complement component III (C3). The hydrothermally reduced graphene oxide (rGO) was deposited between gold-interdigitated microelectrodes, forming a conductive channel. The fabricated C3 biosensor exhibits a low detection limit of 0.4342 ng/mL and an impressive sensitivity of 9.238 ((ΔR/R)/ng.mL-1)/cm2 with a regression coefficient of 0.9815 calibrated within the clinical C3 range of 10-30 ng/mL. This excellent performance is ascribed to the synergistic effects of 1-pyrenebutanoic acid succinimidyl ester (PBASE) linker and conducting properties of rGO as they generate large active sites for higher anti-C3 antibody immobilization, thereby enhancing sensitivity and specificity. Furthermore, the performance of this proposed C3 sensor chip was validated with enzyme-linked immunosorbent assay (ELISA) using five human tear samples exhibiting an outstanding correlation of a regression value of 0.9774. The unparalleled merits of this newly crafted C3 biosensor transcend those of preceding platforms, boasting superior accuracy and precision in quantifying C3 levels in human tears, accelerated operational speed with results attainable within a mere 15 min, cost-effectiveness, and excellent sensitivity.

Metal-based nanowires in electrical biosensing

Metal-based nanowires in electrical biosensing

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.

A recommendation for the use of electrical biosensing technology in neonatology.

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice.

Surface Functionalized Titanium Nitride Electrode for CMOS Compatible Bioelectronic Devices.

The development of bioelectronic devices is heading toward high throughput and high resolution. Yet, most electrode materials utilized in electrical biosensing are not compatible with the manufacturing techniques of semiconductor chips, which somehow hinders the integration and miniaturization of these devices. Titanium nitride (TiN) is a durable and economical material that is widely used in CMOS-based integrated circuits, bioelectronic systems, electrocatalytic systems, etc. Considering different application scenarios, new and efficient methods are required to functionalize TiN surface. In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salt 4-(2-hydroxyethyl)benzenediazonium was presented. Cyclic voltammetry (CV) procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i. e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical property, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characterization techniques, such as CV, atomic force microscopy (AFM), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS), etc., thereby confirming the successful grafting of hydroxyl groups onto the TiN surface. The experiments on DNA synthesis aimed to explore the potential of modified TiN electrode as a novel platform for DNA data storage applications and the corresponding proof-of-principle was accomplished by the process of coupling Cy3-phosphoramidite. Finally, the experiments were successfully reproduced on the randomly selected sites of the modified TiN microarray chips demonstrating the potential of technical protocol to extend applications in future bioelectronic devices, such as bio-sensing, high-throughput DNA synthesis, and molecular manipulation.

A Qualitative Study of Defects with Enhanced Transport Properties of Graphene Exfoliated from Gum Arabic by Rapid Sonication Method

Graphene‐like materials are utilized to make electrical devices, thermal sensors, biosensors, and energy storage batteries. Herein, an efficient and cost‐effective approach is demonstrated by modulating the sonication time duration for producing a few layers of graphene using the emulsification qualities of low‐cost and environmentally friendly gum Arabic. By implementing the modified approach, the production time for graphene synthesis is significantly reduced to a short duration as compared to preliminarily reported methodologies. XRD, field‐emission scanning electron microscopy, and Raman spectroscopic results of graphene samples are presented in order to study the nature of defects. The flakes are thin enough (20 nm) to seem semitransparent under the FESEM. From the combination of both I2D/IG and FWHM (2D), a predominant formation of 3–7 graphene layers is observed. It is identified that mainly foreign adatom defects are present, with a density of ≈1010 cm−2, which results in an increasing Hall carrier concentration (≈2 × 1023 m−3) and mobility (≈27 800 cm2 Vs−1). Furthermore, graphene has a higher electrical conductivity of ≈550 S cm−1, which is far better than previously reported. This research opens the way for the mass manufacturing of simple, green, and cost‐effective graphene with better quality and physical attributes.

Sensor system for analysis of biofilm sensitivity to ampicillin

The resistance of biofilms to antibiotics is a key factor that makes bacterial infections unsusceptible to antimicrobial therapy. The results of classical tests of cell sensitivity to antibiotics cannot be used to predict therapeutic success in infections associated with biofilm formation. We describe a simple and rapid method for the real-time evaluation of bacterial biofilm sensitivity to antibiotics, with Pseudomonas putida and ampicillin as examples. The method uses an electric biosensor to detect the difference between changes in the biofilm electric polarizability, thereby evaluating antibiotic sensitivity. The electric signals showed that P. putida biofilms were susceptible to ampicillin and that at high antibiotic concentrations, the biofilms differed markedly in their susceptibility (dose-dependent effect). The sensor also detected differences between biofilms before and after ampicillin treatment. The electric-signal changes enabled us to describe the physical picture of the processes occurring in bacterial biofilms in the presence of ampicillin. The approach used in this study is promising for evaluating the activity of various compounds against biofilms, because it permits a conclusion about the antibiotic sensitivity of biofilm bacteria to be made in real time and in a short period (analysis time, not longer than 20 min). An added strong point is that analysis can be done directly in liquid, without preliminary sample preparation.Key points• Sensor system to analyze biofilm antimicrobial susceptibility is described.• The signal change depended on the ampicillin concentration (dose-dependent effect).• The sensor allows real-time determination of the antibiofilm effect of ampicillin.

Perspectives on systematic optimization of ultrasensitive biosensors through experimental design.

Biosensors have demonstrated versatility across numerous applications; however, their systematic optimization remains a primary obstacle, limiting their widespread adoption as dependable point-of-care tests. Experimental design, a powerful chemometric tool, offers a solution by effectively guiding the development and optimization of ultrasensitive biosensors. This perspective review provides an overview of recent applications of experimental design in the deployment of optical and electrical ultrasensitive biosensors. Various experimental designs, including full factorial, central composite, and mixture designs, are examined as systematic methodologies for optimizing biosensor fabrication, accounting for both individual variable effects and their interactions. Illustrative examples showcasing the optimization of optical and electronic biosensors through design of experiments are presented and critically analyzed. Finally, the future prospects of experimental design in the biosensor community are outlined, highlighting its potential to expedite development and bolster the performance of biosensing devices for point-of-care diagnostics, thereby facilitating their sustainable and reliable integration.

A rapid field-ready electrical biosensor consisting of bismuthine-derived Au island decorated BiOCl nanosheets for Raphidiopsis raciborskii detection in freshwater.

Cyanobacteria play an essential role in nutrient cycling in aquatic ecosystems. However, certain species adversely affect the environment and human health by causing harmful cyanobacterial algal blooms (cyanoHABs) and producing cyanotoxins. To address this issue, continuous cyanoHAB monitoring has been considered; however, a gold standard has not yet been established. In this study, we aimed to develop a dual DNA-targeting capacitive-type biosensor for rapid field-ready monitoring of Raphidiopsis raciborskii, a causative species of cyanoHAB. To enhance the sensing signal, a plate-like Au-BiOCl nanocomposite was synthesized using a spontaneous carbonation process without additional additives. The alternating-current electrothermal flow (ACEF) technique was applied to enable rapid DNA and probe binding within 10 min. The limits of detection (LODs) for R. raciborskii RubisCO large subunit (rbcL) and RNA polymerase beta subunit (rpoB) genes diluted in deionized (DI) water were 4.89 × 10-17 and 3.89 × 10-17 M, respectively. Furthermore, the LODs of R. raciborskii rbcl and rpoB diluted in freshwater containing HAB were 2.55 × 10-16 and 3.84 × 10-16 M, respectively, demonstrating the field-ready applicability of the device. The fabricated cyanobacterial DNA-sensing platform enabled powerful species-specific detection using a small sample volume and low target concentration without a nucleic acid amplification step, dramatically reducing the detection time. This study has considerable implications for detecting HABs, early warning systems, and species-specific environmental monitoring technology.

Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials.

Bioelectronic devices are designed to translate biological information into electrical signals and vice versa, thereby bridging the gap between the living biological world and electronic systems. Among different types of bioelectronics devices, wearable and implantable biosensors are particularly important as they offer access to the physiological and biochemical activities of tissues and organs, which is significant in diagnosing and researching various medical conditions. Organic conducting and semiconducting materials, including conducting polymers (CPs) and graphene and carbon nanotubes (CNTs), are some of the most promising candidates for wearable and implantable biosensors. Their unique electrical, electrochemical, and mechanical properties bring new possibilities to bioelectronics that could not be realized by utilizing metals- or silicon-based analogues. The use of organic- and carbon-based conductors in the development of wearable and implantable biosensors has emerged as a rapidly growing research field, with remarkable progress being made in recent years. The use of such materials addresses the issue of mismatched properties between biological tissues and electronic devices, as well as the improvement in the accuracy and fidelity of the transferred information. In this review, we highlight the most recent advances in this field and provide insights into organic and carbon-based (semi)conducting materials' properties and relate these to their applications in wearable/implantable biosensors. We also provide a perspective on the promising potential and exciting future developments of wearable/implantable biosensors.

Direct Writing of Aligned Carbon Nanotubes across a Trench.

Aligned and suspended carbon nanotubes can outperform randomly oriented networks in electronic biosensing and thin-film electronics. However, carbon nanotubes tend to bundle and form random networks. Here, we show that carbon nanotubes spontaneously align in an ammonium deoxycholate surfactant gel even under low shear forces, allowing direct writing and printing of nanotubes into electrically conducting wires and aligned thin layers across trenches. To demonstrate its application potential, we directly printed arrays of disposable electrical biosensors, which show femtomolar sensitivity in the detection of DNA and SARS-CoV-2 RNA.

Liquid‐Gated Graphene Field‐Effect Transistors for Biosensing on Lipid Monolayers

This study presents a comprehensive fabrication process for high‐quality graphene field‐effect transistors (GFETs) and their characterization. It is demonstrated that the suggested cost‐efficient method of fabrication utilizing the direct‐laser writing (DLW) system is reliable and ensures lower contact resistance between graphene and metal compared to other works. This improvement results in minimal signal loss and distortion, providing significant benefits to the overall performance of the GFETs. The fabricated devices are functionalized with a lipid monolayer containing tris‐nitrilotriacetic acid fused to the lipids for the binding of histidine‐tagged proteins. Monomeric enhanced green fluorescent protein (GFP) is used as a model protein to explore the current–voltage characteristics response of the liquid‐gated GFETs. The results demonstrate that the devices are well suited for the electrical biosensing of proteins in physiological buffer conditions, paving the way for label‐free detection of protein–protein interactions at membranes.

Device-Physics Realization of ZnO-MWCNT Nanostructure-Based Field-Effect Biosensor for Ultrasensitive Simultaneous Genomic Detection of Foodborne Pathogens.

The complex and versatile interactions among the wide variety of the nanostructures and the target analytes have primarily limited the detailed investigation of the transduction mechanism of nanomaterial-assisted electrical signal-based biosensors despite their high sensitivity, low-cost, portability, and ease of deployment. Hence, no common ground is formed detailing the principle of operation, demanding a strong need for systematic examination instead of hit and trial. Therefore, a maiden mechanistic investigation has been carried out in this paper for a field-effect-based biosensor device relying on the energy band diagram and the surface potential profile. To demonstrate the experimental evidence and appreciate the importance of food safety, three hazardous foodborne pathogens (Proteus mirabilis, Escherichia coli, and Clostridium botulinum) have been detected herein. The biosensor device, built on a hydrothermally synthesized zinc oxide and MWCNT (ZnO-MWCNT) composite nanostructure, simultaneously incorporates three fairly specific ss-DNA probes. Furthermore, the unmet challenge of biosensor device variability is addressed through the optimum selection of operating voltage of the device via a unique "voltage-selection-algorithm". We believe that the rigorous experimentation and the insightful device-physics realization demonstrated in this work will pave the way for a future decisive biosensor platform.

Wafer-Scale Graphene Field-Effect Transistor Biosensor Arrays with Monolithic CMOS Readout.

The reliability of analysis is becoming increasingly important as point-of-care diagnostics are transitioning from single-analyte detection toward multiplexed multianalyte detection. Multianalyte detection benefits greatly from complementary metal-oxide semiconductor (CMOS) integrated sensing solutions, offering miniaturized multiplexed sensing arrays with integrated readout electronics and extremely large sensor counts. The development of CMOS back end of line integration compatible graphene field-effect transistor (GFET)-based biosensing has been rapid during the past few years, in terms of both the fabrication scale-up and functionalization toward biorecognition from real sample matrices. The next steps in industrialization relate to improving reliability and require increased statistics. Regarding functionalization toward truly quantitative sensors, on-chip bioassays with improved statistics require sensor arrays with reduced variability in functionalization. Such multiplexed bioassays, whether based on graphene or on other sensitive nanomaterials, are among the most promising technologies for label-free electrical biosensing. As an important step toward that, we report wafer-scale fabrication of CMOS-integrated GFET arrays with high yield and uniformity, designed especially for biosensing applications. We demonstrate the operation of the sensing platform array with 512 GFETs in simultaneous detection for the sodium chloride concentration series. This platform offers a truly statistical approach on GFET-based biosensing and further to quantitative and multianalyte sensing. The reported techniques can also be applied to other fields relying on functionalized GFETs, such as gas or chemical sensing or infrared imaging.

A single-molecule RNA electrical biosensor for COVID-19

The COVID-19 pandemic shows a critical need for rapid, inexpensive, and ultrasensitive early detection methods based on biomarker analysis to reduce mortality rates by containing the spread of epidemics. This can be achieved through the electrical detection of nucleic acids at the single-molecule level. In particular, the scanning tunneling microscopic-assisted break junction (STM-BJ) method can be utilized to detect individual nucleic acid molecules with high specificity and sensitivity in liquid samples. Here, we demonstrate single-molecule electrical detection of RNA coronavirus biomarkers, including those of SARS-CoV-2 as well as those of different variants and subvariants. Our target sequences include a conserved sequence in the human coronavirus family, a conserved target specific for the SARS-CoV-2 family, and specific targets at the variant and subvariant levels. Our results demonstrate that it is possible to distinguish between different variants of the COVID-19 virus using electrical conductance signals, as recently suggested by theoretical approaches. Our results pave the way for future miniaturized single-molecule electrical biosensors that could be game changers for infectious diseases and other public health applications.

Electrical detection of RNA cancer biomarkers at the single-molecule level

Cancer is a significant healthcare issue, and early screening methods based on biomarker analysis in liquid biopsies are promising avenues to reduce mortality rates. Electrical detection of nucleic acids at the single molecule level could enable these applications. We examine the electrical detection of RNA cancer biomarkers (KRAS mutants G12C and G12V) as a single-molecule proof-of-concept electrical biosensor for cancer screening applications. We show that the electrical conductance is highly sensitive to the sequence, allowing discrimination of the mutants from a wild-type KRAS sequence differing in just one base. In addition to this high specificity, our results also show that these biosensors are sensitive down to an individual molecule with a high signal-to-noise ratio. These results pave the way for future miniaturized single-molecule electrical biosensors that could be groundbreaking for cancer screening and other applications.

Rapid electrical biosensor consisting of DNA aptamer/carbon nanonetwork on microelectrode array for cardiac troponin I in human serum

Rapid detection of cardiac biomarkers is important for the early diagnosis of acute myocardial infarction (AMI). Currently, cardiac troponin I (cTnI) is the standard biomarker for precise diagnosis of AMI. It is essential for rapid diagnosis of AMI patient. Herein, we presented the rapid electrical biosensor composed of a carbon nanotube network (CNN) and DNA aptamer on a microelectrode array to detect cTnI in human serum sample. The island-shaped Au microgap electrodes array was used to provide a high signal-to-noise ratio response and maximize detection sensitivity. In addition, an alternating current electrothermal flow (ACEF) method was introduced to improve the affinity between the DNA aptamer and the target molecule, and cTnI was detected within 10 min using this method. The current change was analyzed using pulse measurement for 100 μs, and the integrated current method was proposed to improve the performance of the sensor platform. This biosensor can detect cTnI in a wide linear range from 1 pM to 100 nM in 10 % human serum. The limit of detection is 6.59 fM, indicating high selectivity. Thus, the proposed electrical biosensor platform may facilitate rapid and early detection of AMI in the future.