Electrical Biosensors Research Articles

Development of low noise FET biosensor using graphene and ZnO nanostructures on cost effective substrates for biomolecule detection with enhanced performance

The idea is to develop nanostructure based biosensing platforms as commercial diagnostic tools for early stage non-invasive virus detection to enhance the selectivity from the existing electrical biosensors by introducing additional electrical signatures and correlating electrical characterization data with other proteomics characterization results. The aim of this proposed research is the performance enhancement of available nanobiosensors in terms of sensitivity and selectivity for the early and rapid diagnosis and prognosis of viral infections.

Direct DNA Methylation Profiling with an Electric Biosensor.

DNA methylation is one of the principal epigenetic mechanisms that control gene expression in humans, and its profiling provides critical information about health and disease. Current profiling methods require chemical modification of bases followed by sequencing, which is expensive and time-consuming. Here, we report a direct and rapid determination of DNA methylation using an electric biosensor. The device consists of a DNA-tweezer probe integrated on a graphene field-effect transistor for label-free, highly sensitive, and specific methylation profiling. The device performance was evaluated with a target DNA that harbors a sequence of the methylguanine-DNA methyltransferase, a promoter of glioblastoma multiforme, a lethal brain tumor. The results show that we successfully profiled the methylated and nonmethylated forms at picomolar concentrations. Further, fluorescence kinetics and molecular dynamics simulations revealed that the position of the methylation site(s), their proximity, and accessibility to the toe-hold region of the tweezer probe are the primary determinants of the device performance.

A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy

Cellular dielectric spectroscopy (CDS) is a novel technology enabling pharmacological evaluation of multiple receptor types with a label-free cell-based assay. We evaluated activities of a family of ligand-gated channels, transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels by an electrical impedance-based biosensor (CellKey™ system) using CDS. Measures of both potency (EC50) and efficacy (Emax) of these agonists with CellKey™ were almost identical to those made using the traditional Ca2+ influx assay in TRPV1- or TRPA1-expressing cells, suggesting that CellKey™ is a simpler and easier means of evaluating TRP activities.

Voltammetric DNA Biosensor for Human Papillomavirus (HPV) Strain 18 Detection

This research was developed to focus on the study of the voltammetric DNA biosensor for the detection of HPV strain 18. In this research, electrical DNA biosensor was expected to detect HPV strain 18 more efficiently by using electrical characterization. In this project, device inspection was conducted to make sure the functional of the gold interdigitated electrode (IDE) by using Scanning Electron Microscope (SEM). 3-Aminopropyl Triethoxysilane (APTES) solution was used for the process of surface modification to form the amine group on the surface of the device to facilitate the attachment of the DNA probe. In this project, synthetic DNA sample and DNA from the saliva of several Biosystems Engineering students were used as the target DNA. The current-voltage (I-V) electrical characterization was conducted to detect the presence of HPV strain 18 in both DNA samples. As the results, perfect alignment between the electrodes on the IDE was detected under SEM. Surface modification of the biosensor successfully conducted which is the covalent bond between APTES and DNA probe increase the electrical. Synthetic DNA shows the presence of HPV strain 18 while there was no HPV strain 18 detected in the DNA from saliva samples.

Aptamer-Based Field-Effect Transistor for Detection of Avian Influenza Virus in Chicken Serum.

Early diagnosis of the highly pathogenic H5N1 avian influenza virus (AIV) is significant for preventing and controlling a global pandemic. However, there is no existing electrical biosensor for detecting biomarkers for AIV in clinically relevant samples such as chicken serum. Herein, we report the first use of an aptamer-functionalized field-effect transistor (FET) as a label-free sensor for AIV detection in chicken serum. A DNA aptamer is employed as a sensitive and selective receptor for hemagglutinin (HA) protein, which is a biomarker for AIVs. This aptamer is immobilized on a gold microelectrode that is connected to the gate of a reusable FET transducer. The specific binding of the target protein results in a change in the surface potential, which generates a signal response of the FET transducer. We hypothesize that a conformational change in the DNA aptamer upon specific binding of HA protein may alter the surface potential. The signal of the aptamer-based FET biosensor increased linearly with the increase in the logarithm of HA protein concentration in a dynamic range of 10 pM to 10 nM with a detection limit of 5.9 pM. The selectivity of the biosensor for HA protein was confirmed by employing relevant interfering proteins. The proposed biosensor was successfully applied to the selective detection of HA protein in a chicken serum sample. Owing to its simple and low-cost architecture, portability, and sensitivity, the aptamer-based FET biosensor has potential as a point-of-care diagnosis of H5N1 AIVs in clinical samples.

Development of Voltage Amplifier Electronic Reader for Multiplex Detection of Two Electrode Electrical Biosensors

Amperometric electrical biosensors have small current variations at nano to micro range. There are limited number of electrical based two electrode electronic readers for biosensors are commercial available because of the amplification and noise issues at nano to micro ampere current range. The electronic reader focused on design a voltage amplifier circuit to capture and amplify three different range of current as nano, micro and mili ampere and convert it to detectable voltage range as an output voltage signal. Current input as nano, micro and mili current were flown through 10 K Ω, 10 Ω and 10 m Ω resistors, respectively to convert different current inputs to the similar range in micro voltage. Then, MAX 4238 op-amp IC was used to amplify micro voltage to mili voltage. Arduino Uno circuit was act as the process and control circuit to read the output voltage from the amplifier circuit. Arduino Uno circuit will convert analog signal to digital signal and then the output voltage value is display in the LCD screen. The Proteus 8 Pro software was used to design, simulate and calibrate the amplifier circuit and Arduino Uno circuit. While, Arduino software was used to create a programming code and to upload in Arduino Uno circuit. Start your abstract here.

Amyloid-beta peptide detection via aptamer-functionalized nanowire sensors exploiting single-trap phenomena

New highly sensitive direct methods for the early detection of peptides involved in Alzheimer's disease (AD) are required in order to prolong effective and healthy memory and thinking capabilities and also to stop the factors resulting in AD. In this contribution, we report the successful demonstration of a label-free approach for the detection of amyloid-beta (Aβ) peptides by highly selective aptamers immobilized onto the SiO2 surface of the fabricated sensors. A modified single-stranded deoxyribonucleic acid (ssDNA) aptamer was specially designed and synthesized to detect the target amyloid beta-40 sequence (Aβ-40). Electrolyte–insulator–semiconductor (EIS) structures as well as silicon (Si) nanowire (NW) field-effect transistors (FETs) covered with a thin SiO2 dielectric layer have been successfully functionalized with Aβ-40-specific aptamers and used to detect ultra-low concentrations of the target peptide. The binding of amyloid-beta peptides of different concentrations to the surface of the sensors varied in the range from 0.1 pg/ml to 10 μg/ml resulting in a change of the surface potential was registered by the fabricated devices. Moreover, we show that the single-trap phenomena observed in the novel Si two-layer (TL) NW FET structures with advanced characteristic parameters can be effectively used to increase the sensitivity of nanoscale sensors. The obtained experimental data demonstrate a highly sensitive and reliable detection of ultra-low concentrations of the Aβ-40 peptides. This opens up prospects for the development of real-time electrical biosensors for studying and understanding different stages of AD by utilizing Si TL NW FET structures fabricated on the basis of cost-efficient CMOS-compatible technology.

Gas Biosensor Arrays Based on Single-Stranded DNA-Functionalized Single-Walled Carbon Nanotubes for the Detection of Volatile Organic Compound Biomarkers Released by Huanglongbing Disease-Infected Citrus Trees.

Volatile organic compounds (VOCs) released by plants are closely associated with plant metabolism and can serve as biomarkers for disease diagnosis. Huanglongbing (HLB), also known as citrus greening or yellow shoot disease, is a lethal threat to the multi-billion-dollar citrus industry. Early detection of HLB is vital for removal of susceptible citrus trees and containment of the disease. Gas sensors are applied to monitor the air quality or toxic gases owing to their low-cost fabrication, smooth operation, and possible miniaturization. Here, we report on the development, characterization, and application of electrical biosensor arrays based on single-walled carbon nanotubes (SWNTs) decorated with single-stranded DNA (ssDNA) for the detection of four VOCs—ethylhexanol, linalool, tetradecene, and phenylacetaldehyde—that serve as secondary biomarkers for detection of infected citrus trees during the asymptomatic stage. SWNTs were noncovalently functionalized with ssDNA using π–π interaction between the nucleotide and sidewall of SWNTs. The resulting ssDNA-SWNT hybrid structure and device properties were investigated using Raman spectroscopy, ultraviolet (UV) spectroscopy, and electrical measurements. To monitor changes in the four VOCs, gas biosensor arrays consisting of bare SWNTs before and after being decorated with different ssDNA were employed to determine the different concentrations of the four VOCs. The data was processed using principal component analysis (PCA) and neural net fitting (NNF).

Highly sensitive three-dimensional interdigitated microelectrode biosensors embedded with porosity tunable hydrogel for detecting proteins

This study focused on fabricating a target-specific electrical biosensor with high sensitivity and dynamic range by embedding a hydrogel, that incorporated a much larger number of antibodies in the reaction region of the sensor, allowing all biomolecules except the target molecules to be filtered off. The biosensor is comprised of a three-dimensional interdigitated microelectrode (3D IMEs) with much higher aspect ratios than conventional IMEs and a hydrogel with a 3D mesh structure. The hydrogel increases the number of antibodies in the reaction region of the 3D IMEs by approximately 1,000-fold and enhances the impedance change induced by the specific binding of biomolecules. The hydrogel density is altered according to the target biomolecules. The impedance change by Aβ42 binding was maximized to approximately 12.135 ± 0.903% in the 3D IMEs with a ‘dense’ hydrogel. The change by prostate-specific antigen (PSA) binding was maximized in the 3D IMEs with a ‘loose’ hydrogel. Thus, the dynamic range and sensitivity for detecting Aβ42 were enhanced by a maximum of two orders and by approximately 2.58-fold compared to planar IMEs. These results demonstrate the high performance of the hydrogel-embedded 3D IMEs and its applicability for biological fluid-based diagnosis.

High Sensitive Au Nanoparticles Igzo FET Cancer Sensor Via Real-Time Analysis Micro-Fluid Separation

The bio-sensor technologies to detect cancer cells have been attracted much attention because detecting the presence of a cancer in a human blood at an early stage can extend the human lifetime. To diagnose a cancer in human normal blood cells, electrical biosensors such as carbon nanotube field-effective transistor, AlGaN/GaN HEMT, reduced graphene oxide TFT, Si nanowire FET, PEDOT:PSS conducting paper, and ZnO nano-rods have been intensively studied because they detect and diagnose the type and amount of cancer cell by estimating the electrical charge amount of the cancer cell in the human blood. However, they have not demonstrated for detecting and diagnosing a cancer cell in circulating cancer stem cell (CCSC). In our study, thus, we cultured breast cancer cell (BCC) line, MDA-MB-231, and designed cancer detecting system in which the detection devices are implemented with a separation device to separate the cancer cell from mixed solution of cancer cell line and normal blood by utilizing both size and deformability of cancer cell. In particular, we designed a real time enumeration image analysis tool to acquire morphology data of breast cancer cell line for image-based cell analysis. For detecting the cancer cell via determining the threshold voltage shift (∆Vth) of field effect transistor (FET), an In-Ga-Zn-Oxide (IGZO) based FET implemented with Au nano-particles (NPs) was fabricated. For the experimental process, the 10-μL solution of separated cancer cell lines connected with the cancer-anti-body (CD-44) was dropped on the IGZO FET channel with Au NPs where a linker (8-Mercaptooctanoic acid) was attached on Au NPs. Consequently, we successfully demonstrated the separation of cancer cell from normal blood sample and after dropping cancer cell on the detection device the ∆Vth value was shifted negative direction. Furthermore, we observed the fluorescent staining image of cancer cell separated from normal blood sample. We report the separation and detection system which enables to separate and detect cancer cell. Figure 1

Electrical pulse-induced electrochemical biosensor for hepatitis E virus detection

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. In this work, a pulse-triggered ultrasensitive electrochemical sensor was fabricated using graphene quantum dots and gold-embedded polyaniline nanowires, prepared via an interfacial polymerization and then self-assembly approach. Introducing an external electrical pulse during the virus accumulation step increases the sensitivity towards HEV due to the expanded surface of the virus particle as well as the antibody-conjugated polyaniline chain length, compared to other conventional electrochemical sensors. The sensor was applied to various HEV genotypes, including G1, G3, G7 and ferret HEV obtained from cell culture supernatant and in a series of fecal specimen samples collected from G7 HEV-infected monkey. The sensitivity is similar to that detected by real-time quantitative reverse transcription-polymerase chain (RT-qPCR). These results suggests that the proposed sensor can pave the way for the development of robust, high-performance sensing methodologies for HEV detection.

Membraneless reproducible MoS2 field-effect transistor biosensor for high sensitive and selective detection of FGF21

Fibroblast growth factor 21 (FGF21) serves as an essential biomarker for early detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). It has received a great deal of attention recently in efforts to develop an accurate and effective method for detecting low levels of FGF21 in complex biological settings. Herein, we demonstrate a label-free, simple and high-sensitive field-effect transistor (FET) biosensor for FGF21 detection in a nonaqueous environment, directly utilizing two-dimensional molybdenum disulfide (MoS2) without additional absorption layers. By immobilizing anti-FGF21 on MoS2 surface, this biosensor can achieve the detection of trace FGF21 at less than 10 fg mL−1. High consistency and satisfactory reproducibility were demonstrated through multiple sets of parallel experiments for the MoS2 FETs. Furthermore, the biosensor has great sensitivity to detect the target FGF21 in complex serum samples, which demonstrates its great potential application in disease diagnosis of NAFLD. Overall, this study shows that thin-layered transition-metal dichalcogenides (TMDs) can be used as a potential alternative platform for developing novel electrical biosensors with high sensitivity and selectivity.

Unamplified gene sensing via Cas9 on graphene.

An electrical biosensor that relies on the binding of target nucleic acid sequences to Cas9 immobilized on a graphene field-effect transistor enables the rapid detection of mutations in purified samples without the need for nucleic acid amplification.

Electrical Biosensing at Physiological Ionic Strength Using Graphene Field-Effect Transistor in Femtoliter Microdroplet.

Graphene has strong potential for electrical biosensing owing to its two-dimensional nature and high carrier mobility which transduce the direct contact of a detection target with a graphene channel to a large conductivity change in a graphene field-effect transistor (G-FET). However, the measurable range from the graphene surface is highly restricted by Debye screening, whose characteristic length is less than 1 nm at physiological ionic strength. Here, we demonstrated electrical biosensing utilizing the enzymatic products of the target. We achieved quantitative measurements of a target based on the site-binding model and real-time measurement of the enzyme kinetics in femtoliter microdroplets. The combination of a G-FET and microfluidics, named a "lab-on-a-graphene-FET", detected the enzyme urease with high sensitivity in the zeptomole range in 100 mM sodium phosphate buffer. Also, the lab-on-a-graphene-FET detected the gastric cancer pathogen Helicobacter pylori captured at a distance greater than the Debye screening length from the G-FET.

Amperometric biosensing system directly powered by button cell battery for lactate.

The development of new signal systems for electrical biosensors could provide exciting new opportunities for biomedical analysis, pollutant monitoring, and explosive detection. The signal systems for commercial portable sensors involve the integration of a battery and a circuit conditioning system to power an amperometric biosensor. However, this increases the size and complexity of the entire system. In this study, we develop a simple amperometric biosensor that is directly powered by a button cell battery for the detection of lactate. A two-electrode sensing transducer was printed on cardboard or integrated on a ring. It was directly powered by a button cell battery, and connected to a multimeter for current measurement. This sensor showed a sensitive detection range of 0.04762–9.21429 mM and short measuring time of 2 min. These results show that this system can achieve an excellent sensing performance, and the construction of this new sensing system directly powered by a button cell battery offers a new method for further developing a wide range of miniaturized, flexible, portable, or wearable sensing systems, and these could be used in detecting various analytes that are important in medical diagnosis and environmental monitoring.

Signs of Life

Scientists are trying new ways to push beyond the limits of electrical biosensing, as Chris Edwards explains

COD Removal and Electricity Generation From Domestic Wastewater Using Different Anode Materials in Microbial Fuel Cells

Microbial fuel cells (MFCs) set a new trend of converting chemical energy or bio energy to electricity from wastewater (domestic and industries) at the same time removal of chemical oxygen demand (COD) from the wastewater. Electrical energy generated from microbial fuel cell could be used for small electrical device example biosensors. The main components of MFCs are the anode, and the cathode salt bridge. It contains an anode chamber and a cathode chamber which separate electrodes for the production of electricity, using wastewater in an anaerobic chamber helps grow native microorganisms. Adding substrates increases productivity of the electrons that are moving from the anode chamber to the cathode chamber by help of the salt bridge. Bioreactors based on power generation in MFCs are a new approach to wastewater treatment. Power generation and current is modulated in this system. If it is optimised, MFCs would prove to be new method to offset wastewater treatment plant operating costs.

Graphene nanogap electrodes in electrical biosensing

Graphene nanogap electrodes are reported here for the first time in an electrical biosensor for the detection of biomolecular interactions. Streptavidin-biotin was chosen as a model system for evaluating the sensor’s performance. High-affinity interactions of streptavidin-gold nanoparticles (strep-AuNPs) to the biotin-functionalized nanogap localizes AuNPs, thereby bridging the gap and resulting in changes in device conductance. Biosensing performance was optimized by varying the gap size, AuNP diameter, and streptavidin coverage on AuNPs. The sensitivity and limit of detection (LOD) of streptavidin detection with the optimized parameters were determined to be 0.3 µA/nM and 0.25 pM, respectively. The proposed platform suggests high potential as a portable point-of-use biosensor for the detection of other affinity-based biomolecular interactions, such as antigen-antibody, nucleic acid, or chemo-selective interactions.

Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia

Inadequate blood supply to the intestine can lead to acute mesenteric ischemia (AMI), with a mortality rate ranging from 60% to 90%. This high mortality rate is partially due to late detection and the lack of efficient early diagnostic tests. There is an urgent need for a point-of-care tool for immediate bedside diagnosis. Here we present for the first time a rapid and non-invasive electrochemical biosensor device based on non-faradic impedance spectroscopy to detect intestinal fatty-acid binding protein (I-FABP) as an indication of AMI. The electrochemical biosensors consist of gold interdigitated electrodes that were fabricated using photolithographic techniques on top of silicon dioxide substrates. The electrode surfaces were functionalized with an I-FABP capture antibody (CAnB) to entice the target protein, while gold nanoparticles (GNPs) functionalized with detection antibodies (DAnB-GNPs) were utilized as a novel mechanism to enhance the detection signal. Quantification of the I-FABP concentration in the medium depended on its attachment to CAnB and DAnB-GNPs in a sandwich manner, where the latter boosts the impedance signal through its binding to the I-FABP. This non-invasive non-faradic electric biosensor device demonstrates the potential for bench-to-bedside translation with the goal of decreasing morbidity and mortality from AMI.

Tactile Chemomechanical Transduction Based on an Elastic Microstructured Array to Enhance the Sensitivity of Portable Biosensors

Tactile sensors capable of perceiving biophysical signals such as force, pressure, or strain have attracted extensive interest for versatile applications in electronic skin, noninvasive healthcare, and biomimetic prostheses. Despite these great achievements, they are still incapable of detecting bio/chemical signals that provide even more meaningful and precise health information due to the lack of efficient transduction principles. Herein, a tactile chemomechanical transduction strategy that enables the tactile sensor to perceive bio/chemical signals is proposed. In this methodology, pyramidal tactile sensors are linked with biomarker-induced gas-producing reactions, which transduce biomarker signals to electrical signals in real time. The method is advantageous as it enhances electrical signals by more than tenfold based on a triple-step signal amplification strategy, as compared to traditional electrical biosensors. It also constitutes a portable and general platform capable of quantifying a wide spectrum of targets including carcinoembryonic antigen, interferon-γ, and adenosine. Such tactile chemomechanical transduction would greatly broaden the application of tactile sensors toward bio/chemical signals perception which can be used in ultrasensitive portable biosensors and chemical-responsive chemomechanical systems.