Graphene Field Effect Transistor Sensor Research Articles

Characterizing the Interactions of DNA Oligomers with Graphene Field-Effect Transistors

Introduction: Graphene field-effect transistors (G-FETs) constitute an emerging platform for biosensing applications. Indeed, graphene is an ideal material for the detection of biomolecules: every atom of its monolayer structure is in contact with its environment, resulting in an electrical conductivity that is highly responsive to local electrostatic fluctuations from adjacent molecules. For genomic applications, most detection methods use DNA probe sequences bound to the graphene surface, in order to capture a specific target DNA sequence and detect the corresponding change in the electrical response of the sensor1 - 2. However, the effect of interactions between DNA and graphene on the electrical conductance is still not fully understood. Here, we investigate specifically the adsorption of short DNA oligomers on graphene field-effect transistors, in order to model and control the effect of such interactions in biosensing applications with G-FETs. Methods and Results: First, we fabricated G-FET sensors as follow3: Using photolithography techniques, an array of source and drain electrodes were patterned in gold on a Si wafer with a SiO2 insulator layer, as well as a common on-chip gate electrode in platinum. High-quality monolayer CVD-grown graphene was transferred onto the substrate and then etched to create 6 x 4 µm ribbons between each source-drain pair. Transfer curves (Isd vs. Vg) performed in saline buffer solution revealed a conductance minimum at the charge neutrality point of the graphene. Devices were then exposed to solutions of DNA, consisting in 22-single-stranded nucleotides (ssDNA) or double-stranded nucleotides (dsDNA) DNA oligomers diluted in 0,01X PBS buffer. Selected G-FET devices were exposed to different ssDNA concentrations during 15 min, followed by washing steps with 0,01X PBS. Electrical curves were recorded before, during and after each DNA exposure. In this presentation, we will present results showing that ssDNA exposure causes a left-shift of the charge neutrality point above a concentration threshold, and that this shift is proportional to ssDNA concentration. In addition, non-covalent adsorption of ssDNA on graphene appears to be reversible upon washing. Finally, we will discuss differences between the adsorption of dsDNA and ssDNA. Conclusion and Relevance: Our results suggest that unspecific DNA adsorption on graphene can lead to a G-FET response, which needs to be modeled, compensated and /or passivated in biosensing experiments, especially in order to achieve low detection limits for target sequences in complex biological media.

State-space modeling for dynamic response of graphene FET biosensors

Graphene field effect transistor (G-FET) biosensors exhibit high sensitivity owing to their high electron/hole mobilities and unique 2D nature. However, a baseline drift is observed in their response in aqueous environment, making it difficult to analyze their response against target molecules. Here, we present a computational approach to build state-space models (SSMs) for the time-series data of a G-FET biosensor; the approach helps separate the response against target molecules from the baseline drift. The charge neutral point of the G-FET sensor was continuously measured while sensing target molecules. The obtained time-series data were modeled using the proposed SSMs. The model parameters were estimated through Markov chain Monte Carlo methods. The SSMs were evaluated using the widely-applicable Bayesian information criterion. The SSMs well fitted the time-series data of the G-FET biosensor, and the sensor response to target molecules was extracted from the baseline-drift data.

Cytochrome C-decorated graphene field-effect transistor for highly sensitive hydrogen peroxide detection

High-level in vivo reactive oxygen species (ROS) can damage many biomolecules via oxidative stress and play vital roles in the pathogenesis of several bodily disorders. Therefore, fast and sensitive monitoring strategies for trace ROS, such as hydrogen peroxide (H2O2), are of great significance. Herein, we present a highly sensitive field-effect transistor (FET) sensor based on single-layer graphene for trace hydrogen peroxide (H2O2) detection. Graphene and cytochrome c (Cyt c) were employed as the conductive substrate material and biomolecular receptor for H2O2 detection, respectively. High-efficiency charge transfer can be achieved by reliable electrical contact across the Cyt c/underlying graphene interface. The Cyt c/graphene FET platform exhibited hole-transport behavior with high conductivity and high sensitivity toward H2O2 with a detection limit of 100fM and rapid response time (<1s). Moreover, our sensor platform was able to specifically discriminate H2O2 from a series of interfering substances, such as dopamine, ascorbic acid, glucose, uric acid and glutamate. This result, therefore, demonstrates that the proposed Cyt c/single-layer graphene FET sensor could facilitate the high-efficiency charge transfer between the redox center of the Cyt c/graphene interface, indicating a promising application in future trace H2O2 or free radical biosensors.

Solution-gated graphene field effect transistor for TP53 DNA sensor with coplanar electrode array

This study presents a solution-gated graphene field effect transistor (GFET) for a TP53 DNA sensor using a unique coplanar electrode array integrated with a microfluidic chip. The integrated microfluidic channel controls the exact amount of solution to be delivered. The cancer-related gene, TP53, was applied over the graphene active layers to monitor the sensing performance of the solution-gated GFET. After immobilization of the probe DNA, we hybridized the target DNA with different concentrations (10 μM–1 nM) onto each electrode array. The limit of the detection value obtained herein was 1 nM. To validate the selectivity, when the noncomplementary and one-mismatched DNA molecules were injected into the microchannel, the Dirac point shift values were not significant. The shift of the Dirac point occurs owing to the doping effect caused by the negative charges of the DNA over the graphene surface. When the measurements were reproduced in eight other electrode pairs in the array structure, the transfer curves presented similar Dirac point values, i.e., approximately ±1 mV, indicating the stability of the device. The developed solution-gated GFET sensor provides a reliable measurement of the electrical characteristics and a multiplex detection for cancer diagnostics using a large area of the graphene platform.

Selective detection of water pollutants using a differential aptamer-based graphene biosensor

Graphene field-effect transistor (GFET) sensors are an attractive analytical tool for the detection of water pollutants. Unfortunately, this application has been hindered by the sensitivity of such sensors to nonspecific disturbances caused by variations of environmental conditions. Incorporation of differential designs is a logical choice to address this issue, but this has been difficult for GFET sensors due to the impact of fabrication processes and material properties. This paper presents a differential GFET affinity sensor for the selective detection of water pollutants in the presence of nonspecific disturbances. This differential design allows for minimization of the effects of variations of environmental conditions on the measurement accuracy. In addition, to mitigate the impact of the fabrication process and material property variations, we introduce a compensation scheme for the individual sensing units of the sensor, so that such variations are accounted for in the compensation-based differential sensing method. We test the use of this differential sensor for the selective detection of the water pollutant 17β-estradiol in buffer and tap water. Consistent detection results can be obtained with and without interferences of pH variations, and in tap water where unknown interferences are present. These results demonstrate that the differential graphene affinity sensor is capable of effectively mitigating the effects of nonspecific interferences to enable selective water pollutant detection for water quality monitoring.

Highly Enantioselective Graphene-Based Chemical Sensors Prepared by Chiral Noncovalent Functionalization.

As a basic characteristic of the natural environment and living matter, chirality has been used in various scientific and technological fields. Chiral discrimination is of particular interest owing to its importance in catalysis, organic synthesis, biomedicine, and pharmaceutics. However, it is still very challenging to effectively and selectively sense and separate different enantiomers. Here, enantio-differentiating chemosensor systems have been developed through spontaneous chiral functionalization of the surface of graphene field-effect transistors (GFETs). GFET sensors functionalized using noncovalent interactions between graphene and a newly synthesized chiral-functionalized pyrene material, Boc-l-Phe-Pyrene, exhibit highly enantioselective detection of natural acryclic monoterpenoid enantiomers, that is, ( R)-(+)- and ( S)-(-)-β-citronellol. On the basis of a computational study, the origin of enantio-differentiation is assigned to the discriminable charge transfer from ( R)-(+)- or ( S)-(-)-β-citronellol into graphene with a significant difference in binding strength depending on surface morphology. The chemosensor system developed herein has great potential to be applied in miniaturized and rapid enantioselective sensing with high sensitivity and selectivity.

Detection of Sub-fM DNA with Target Recycling and Self-Assembly Amplification on Graphene Field-Effect Biosensors.

All-electronic DNA biosensors based on graphene field-effect transistors (GFETs) offer the prospect of simple and cost-effective diagnostics. For GFET sensors based on complementary probe DNA, the sensitivity is limited by the binding affinity of the target oligonucleotide, in the nM range for 20 mer targets. We report a ∼20 000× improvement in sensitivity through the use of engineered hairpin probe DNA that allows for target recycling and hybridization chain reaction. This enables detection of 21 mer target DNA at sub-fM concentration and provides superior specificity against single-base mismatched oligomers. The work is based on a scalable fabrication process for biosensor arrays that is suitable for multiplexed detection. This approach overcomes the binding-affinity-dependent sensitivity of nucleic acid biosensors and offers a pathway toward multiplexed and label-free nucleic acid testing with high accuracy and selectivity.

Design and manufacture of TNT explosives detector sensors based on GFET

PurposeSmart sensors based on graphene field effect transistor (GFET) and biological receptors are regarded as a promising nanomaterial that could be the basis for future generation of low-power, faster, selective real-time monitoring of target analytes and smaller electronics. So, the purpose of this paper is to provide details of sensors based on selective nanocoatings by combining trinitrotoluene (TNT) receptors (Trp-His-Trp) bound to conjugated polydiacetylene polymers on a graphene channel in GFET for detecting explosives TNT.Design/methodology/approachFollowing an introduction, this paper describes the way of manufacturing of the GFET sensor by using investigation methods for transferring graphene sheet from Cu foil to target substrates, which is functionalized by the TNT peptide receptors, to offer a system which has the capability of answering the presence of related target molecules (TNT). Finally, brief conclusions are drawn.FindingsIn a word, shortly after graphene discovery, it has been explored with a variety of methods gradually. Because of its exceptional electrical properties (e.g. extremely high carrier mobility and capacity), electrochemical properties such as high electron transfer rate and structural properties, graphene has already showed great potential and success in chemical and biological sensing fields. Therefore, the authors used a biological receptor with a field effect transistor (FET) based on graphene to fabricate sensor for achieving high sensitivity and selectivity that can detect explosive substances such as TNT. The transport property changed compared to that of the FET made by intrinsic graphene, that is, the Dirac point position moved from positive Vg to negative Vg, indicating the transition of graphene from p-type to n-type after annealing in TNT, and the results show the bipolar property change of GFET with the TNT concentration and the possibility to develop a robust, easy-to-use and low-cost TNT detection method for performing a sensitive, reliable and semi-quantitative detection in a wide detection range.Originality/valueIn this timeframe of history, TNT is a common explosive used in both military and industrial settings. Its convenient handling properties and explosive strength make it a common choice in military operations and bioterrorism. TNT and other conventional explosives are the mainstays of terrorist bombs and the anti-personnel mines that kill or injure more than 15,000 people annually in war-torn countries. In large, open-air environments, such as airports, train stations and minefields, concentrations of these explosives can be vanishingly small – a few parts of TNT, for instance, per trillion parts of air. That can make it impossible for conventional bomb and mine detectors to detect the explosives and save lives. So, in this paper, the authors report a potential solution with design and manufacture of a GFET sensor based on a biological receptor for real-time detection of TNT explosives specifically.

Graphene Surface Acoustic Wave Sensor for Simultaneous Detection of Charge and Mass.

We have combined a graphene field-effect transistor (GFET) and a surface acoustic wave (SAW) sensor on a LiTaO3 substrate to create a graphene surface acoustic wave (GSAW) sensor. When a SAW propagates in graphene, an acoustoelectric current (IA) flows between two attached electrodes. This current has unique electrical characteristics, having both positive and negative peak values with respect to the electrolyte-gate voltage (VEg) in solution. We found that IA is controlled by VEg and the amplitude of the SAW. It was also confirmed that the GSAW sensor detects changes of electrical charge in solution like conventional GFET sensors. Furthermore, the detection of amino-group-modified microbeads was performed by employing a GSAW sensor in a phthalate buffer solution at pH 4.1. The hole current peak shifted to the lower left in the IA-VEg characteristics. The left shift was caused by charge detection by the GFET and can be explained by an increase of amino groups that have positive charges at pH 4.1. In contrast, the downward shift is thought to be due to a reduction in the amplitude of the propagating SAW because of an increase in the mass loading of microbeads. This mass loading was detected by the SAW sensor. Thus, we have demonstrated that the GSAW sensor is a transducer capable of the simultaneous detection of charge and mass, which indicates that it is an attractive platform for highly sensitive and multifunctional solution sensing.

Label-Free Sensors Based on Graphene Field-Effect Transistors for the Detection of Human Chorionic Gonadotropin Cancer Risk Biomarker.

We report on the development of label-free chemical vapour deposition (CVD) graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO2 substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalised with a linker molecule to an immobile anti-hCG antibody on the surface of graphene. The binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show that annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s and Parkinson’s) and cardiovascular disorders.

All-Electrical Graphene DNA Sensor Array.

Electrical sensing of biomolecules has been an important pursuit due to the label-free operation and chip-scale construct such sensing modality can enable. In particular, electrical biomolecular sensors based on nanomaterials such as semiconductor nanowires, carbon nanotubes, and graphene have demonstrated high sensitivity, which in the case of nanowires and carbon nanotubes can surpass typical optical detection sensitivity. Among these nanomaterials, graphene is well suited for a practical candidate for implementing a large-scale array of biomolecular sensors, as its two-dimensional morphology is readily compatible with industry standard top-down fabrication techniques. In our recent work published in 2014 Nature Communications, we demonstrated these benefits by creating DNA sensor arrays from chemical vapor deposition (CVD) graphene. The present chapter, which is a review of this recent work, outlines procedures demonstrating the use of individual graphene sites of the array in dual roles--electrophoretic electrodes for site specific probe DNA immobilization and field effect transistor (FET) sensors for detection of target DNA hybridization. The 100fM detection sensitivity achieved in 7 out of 8 graphene FET sensors in the array combined with the alternative use of the graphene channels as electrophoretic electrodes for probe deposition represent steps toward creating an all-electrical multiplexed DNA array.

Graphene field-effect transistor application for flow sensing

Microflow sensors offer great potential for applications in microfluidics and lab-on-a-chip systems. However, thermal-based sensors, which are commonly used in modern flow sensing technology, are mainly made of materials with positive temperature coefficients (PTC) and suffer from a self-heating effect and slow response time. Therefore, the design of novel devices and careful selection of materials are required to improve the overall flow sensor performance. In this work we propose graphene field-effect transistor (GFET) to be used as microflow sensor. Temperature distribution in graphene channel was simulated and the analysis of heat convection was performed to establish the relation between the fluidic flow velocity and the temperature gradient. It was shown that the negative temperature coefficient (NTC) of graphene could enable the self-protection of the device and should minimize sensing error from currentinduced heating. It was also argued that the planar design of the GFET sensor makes it suitable for the real application due to supposed mechanical stability of such a construction.

Specific detection of biomolecules in physiological solutions using graphene transistor biosensors

Nanomaterial-based field-effect transistor (FET) sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although direct measurements in high-ionic-strength physiological solutions remain challenging due to the Debye screening effect. Recently, we demonstrated a general strategy to overcome this challenge by incorporating a biomolecule-permeable polymer layer on the surface of silicon nanowire FET sensors. The permeable polymer layer can increase the effective screening length immediately adjacent to the device surface and thereby enable real-time detection of biomolecules in high-ionic-strength solutions. Here, we describe studies demonstrating both the generality of this concept and application to specific protein detection using graphene FET sensors. Concentration-dependent measurements made with polyethylene glycol (PEG)-modified graphene devices exhibited real-time reversible detection of prostate specific antigen (PSA) from 1 to 1,000 nM in 100 mM phosphate buffer. In addition, comodification of graphene devices with PEG and DNA aptamers yielded specific irreversible binding and detection of PSA in pH 7.4 1x PBS solutions, whereas control experiments with proteins that do not bind to the aptamer showed smaller reversible signals. In addition, the active aptamer receptor of the modified graphene devices could be regenerated to yield multiuse selective PSA sensing under physiological conditions. The current work presents an important concept toward the application of nanomaterial-based FET sensors for biochemical sensing in physiological environments and thus could lead to powerful tools for basic research and healthcare.

Inkjet Printed Flexible Biosensor Based on Graphene Field Effect Transistor

In this paper, we present a graphene field effect transistor (FET) fabricated on a flexible Kapton substrate using 3-D inkjet printing for use as a biosensor to detect infectious organisms. Inkjet printing process of graphene film is described with sheet resistance as low as 110 $\Omega $ /sq. To suppress background noises, the biosensors are based on intensity changes of the ac signal as a function of the biological agents’ concentration. Using the foodborne pathogen, Norovirus, as a proof-of-concept disease target, the value of S12 (i.e., the voltage gain from source to drain) at 10 GHz generates a linear response from 0.07 to 3.70 dB when the concentration of Norovirus protein increases from 0.1 to 100 $\mu \text{g}$ /ml. While further studies are needed to improve surface functionalization and sensitivity, the current study establishes a linear response over three orders of magnitude indicating that the flexible graphene FET sensor has a wide dynamic range for detection of biological targets that could ultimately be applied for detection of a variety of disease-causing pathogens.