Reduced Graphene Oxide Field-effect Transistor Research Articles

Amine and Thiol Cofunctionalized Reduced Graphene Oxide Field-Effect Transistor for the Selective Detection of Formaldehyde

Amine and Thiol Cofunctionalized Reduced Graphene Oxide Field-Effect Transistor for the Selective Detection of Formaldehyde

Integrated FET sensing microsystem for specific detection of pancreatic cancer exosomal miRNA10b

Tumor-derived exosome (TD-Ex) serves as a crucial early diagnostic biomarker of pancreatic cancer (PC). However, accurate identification of TD-Ex from PC is still a challenging work. In this paper, a detection microsystem that integrates magnetic separation and FET biosensor is developed, which is capable of selectively separating TD-Ex of PC from the plasma and detecting exosomal miRNA10b in a sensitive and specific manner. The magnetic beads were functionalized with dual antibody (GPC-1 antibody and EpCAM antibody), enabling selective recognition and capture of PC-derived exosomes. On the other hand, a peptide nucleic acid (PNA)- functionalized reduced graphene oxide field-effect transistor (RGO FET) biosensor was subsequently utilized to detect the exosomal miRNA10b, which is highly expressed in PC- derived exosomes. This system could achieve a low detection limit down to 78 fM, and selectively identify miRNA10b from single-base mismatched miRNA. In addition, 40 clinical plasma samples were tested with this microsystem, and the results indicate that it could effectively distinguish PC patients from healthy individuals. The assay combines specific capture and enrichment of PC-derived exosomes with sensitive and selective detection of exosomal miRNA, showing its potential to be used as an effective scheme for PC early diagnosis.

Ultrasensitive detection of exosomal miRNA with PMO-graphene quantum dots-functionalized field-effect transistor biosensor

SummaryCompared with the conventional DNA probe immobilization on the planar surface, nanoparticles-based DNA probes enable more RNA molecules to be anchored to the sensor surface, thereby improving the detection sensitivity. In this work, we report phosphorodiamidate morpholino oligomers (PMO)-graphene quantum dots (GQDs)-functionalized reduced graphene oxide (RGO) field effect transistor (FET) biosensors for ultrasensitive detection of exosomal microRNAs. After the RGO FET sensor was fabricated, polylysine (PLL) film was deposited onto the RGO surface. GQDs-PMO hybrid was prepared and covalently bound to PLL surface, enabling detection of exosomal microRNAs (miRNAs). The method achieved a detection limit as low as 85 aM and high specificity. Furthermore, the FET sensor was able to detect exosomal miRNAs in plasma samples and distinguish breast cancer samples from healthy samples. Compared with other methods, we use GQDs to further improve the sensitivity of FET, making it a potential tool for early diagnosis of breast cancer.

Design and Development of Graphene FET Biosensor for the Detection of SARS-CoV-2

The most affected disease in recent years is Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) that is notable as COVID-19. It has been started as a disease in one place and arisen as a pandemic throughout the world. A serious health problem is developed in the lungs due to the effect of this coronavirus. Sometimes it may result in death as a consequence of extensive alveolar damage and progressive respiratory failure. Hence, early detection and appropriate diagnosis of corona virus in patient’s body is very essential to save the lives of affected patients This work evolves a Silicon (Si) based label-free electrical device i.e. the reduced graphene oxide field-effect transistor (rGO FET) for SARS-CoV-2 detection. Firstly rGO FET functionalized with SARS-CoV-2 monoclonal antibodies (mAbs). Then the rGO FET characteristic response is observed to detect the antibody-antigen reaction of SARS-CoV-2 with different molar ranges. The developed GFET shows better performance towards the drain current and limit-of-detection (LoD) up to 2E-18 M. Therefore, we believe that an intense response was observed than the earlier developed devices and signifies impressive capability for subsequent implementation in point-of-care (PoC) diagnostic tests.

Hybrid Modeling and Sensitivity Analysis on Reduced Graphene Oxide Field-Effect Transistor

The reduced graphene oxide (RGO) field-effect transistor (FET) has been developed and applied in various areas. However, the effective modeling and sensitivity analysis on RGO FET is still a very challenging problem due to the randomness of bandgap and density of states (DOS) in RGO. In this paper, we propose to solve the RGO FET modeling problem by integrating the data-driven thinking and the graphene FET model to develop a hybrid model. The proposed model takes advantages of the similarities between graphene and RGO to generalize the existing graphene FET model, and employs RGO FET drain-current data to characterize the specificity of the model. The basic idea in the proposed model is to modify the graphene DOS to approximate the RGO DOS so that the charge density, mobility and other parameters can be achieved through the approximated RGO DOS. We validate the model accuracy with the RGO FET based sensors that detect chemical concentrations in the aqueous environment. The RGO FET sensitivity analysis is also demonstrated to provide guidance for RGO FET application and manufacturing.

Amplified Methanol Sensitivity in Reduced Graphene Oxide FET Using Appropriate Gate Electrostatic

The current study concerns a technique to amplify the gas sensitivity of reduced graphene oxide (rGO)-field-effect transistor (FET) sensor for the detection of very low concentration gaseous species. rGO channel exhibits tunable carrier density with ambipolar transport in FET structure by the change of electrostatic potential through the gate terminal. At low carrier density of channel, the exchange of carriers due to surface adsorption and desorption is significant that eventually enhances the sensitivity of the rGO-FET sensor at a typical gate voltage ( ${V}_{GS}$ ). The back-gated rGO-FET sensor was fabricated on ${p}$ -Si substrate with 90-nm-thick SiO2 layer. The defects, disorders, and morphology of single-layer (major) rGO were characterized with the spectroscopic and microscopic study. The modulation of ambient sensitivity of rGO film was tested in the exposure of different ambient like dry air, argon, oxygen, and a test vapor methanol. 1.95% methanol (at 150 ppm) sensitivity at ${V}_{GS}= 0$ V was amplified up to 127.93% at ${V}_{GS}= 5$ V and 82.38% at ${V}_{GS}= 13$ V where the temperature and drain-to-source voltage ( ${V}_{DS}$ ) were 100 °C and 1.4 mV, respectively.

Multiplexed femtomolar detection of Alzheimer's disease biomarkers in biofluids using a reduced graphene oxide field-effect transistor

Alzheimer's disease (AD) is a neurodegenerative disease that accounts for 70% of all dementia. Early stage diagnosis of AD is essential as there is no certain treatment after the lesion has progressed in the late stage. Nevertheless, there are still limitations of early diagnosis of AD using neuroimaging and psychological memory assessments. Here, we demonstrate ultrasensitive and multiplexed detection of pivotal AD biomarkers (Aβ1-42 and t-Tau) in biofluids using a reduced graphene oxide field-effect transistor (gFET). The proposed approach provides a wide logarithmically linear range of detection from 10−1–105 pg mL−1 and a femtomolar-level limit of detection in biofluids (human plasma and artificial cerebrospinal fluid) as well as phosphate-buffered saline (PBS). Furthermore, as these core biomarkers have different surface charges in physiological conditions based on the isoelectric point (pI), we achieved a distinctive output signal for each biomarker. The gFET biosensor platform presented in this paper has great potential and can be used for early diagnosis of AD in clinical practice as well as accurate analysis based on the surface charge of the analytes.

(Invited) Graphene-Based Field Effect Transistor Biosensor for Electrical and Label-Free Quantification of Exosomes

Exosomes are small membrane-bound nanovesicles with a size of 50-150 nm, which contain many functional biomolecules, such as nucleic acids and proteins. Due to their high homology with parental generation, they are of great significance in clinical diagnosis. At present, the quantitative detection of low-concentration of cancer-derived exosomes present in biofluids is still a great challenge. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on reduced graphene oxide (RGO) field effect transistor (FET) biosensor. The RGO FET biosensor modified with specific antibody CD63 in the sensing area was fabricated, which was used for electrical and label-free quantification of exosomes. The method achieved a low limit of detection down to 33 particles/µL, which was lower than that of many other available methods. In addition, the FET biosensor was employed to detect exosomes in clinical serum samples, showing significant differences in detecting healthy people and prostate cancer (PCa) patients. Different from other technologies, this study provides a unique technology capable of directly quantifying exosomes without labeling, indicating its potential as a tool for early diagnosis of cancer.

Electrical and Label-Free Quantification of Exosomes with a Reduced Graphene Oxide Field Effect Transistor Biosensor.

Exosomes are small membrane-bound nanovesicles with a size of 50-150 nm which contain many functional biomolecules, such as nucleic acids and proteins. Due to their high homology with parental generation, they are of great significance in clinical diagnosis. At present, the quantitative detection of low concentrations of cancer-derived exosomes present in biofluids is still a great challenge. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a reduced graphene oxide (RGO) field effect transistor (FET) biosensor. An RGO FET biosensor modified with specific antibody CD63 in the sensing area was fabricated and was used for electrical and label-free quantification of exosomes. The method achieved a low limit of detection down to 33 particles/μL, which is lower than that of many other available methods. In addition, the FET biosensor was employed to detect exosomes in clinical serum samples, showing significant differences in detecting healthy people and prostate cancer (PCa) patients. Different from other technologies, this study provides a unique technology capable of directly quantifying exosomes without labeling, indicating its potential as a tool for early diagnosis of cancer.

Air‐Stable Symmetric Ambipolar Field‐Effect Transistors Based on Reduced Graphene Oxide‐OTS Self‐Assembled Monolayer Heterostructure

AbstractGraphene has attracted great interest in the past decade due to its unique band structure and physical properties such as quantum electronic transport, extremely high mobility, high elasticity and optical properties. Graphene is generally obtained by mechanical exfoliation, epitaxial growth, chemical vapor deposition and chemical synthesis approaches, wherein the reduction of graphene oxide (GO) is a practical approach to synthesize large‐scale graphene. Via reduction, highly conductive reduced graphene oxide (RGO) can be obtained, which has electrical and optical properties analogous to those of graphene. However, Field‐effect transistors (FETs) based RGO typically exhibit p‐type in ambient rather than the ambipolar behavior of intrinsic graphene, due to the doping effect induced by substrate and the air. Meanwhile, large hysteresis accompanies with the p‐type transistor. Here, a self‐assembled monolayer (SAM) of octadecyltrichlorosilane (OTS)‐RGO heterostructure is developed, in which RGO is sandwiched between OTS SAMs. The heterostructure passivates the RGO device and eliminates the doping of graphene from the surroundings. The obtained RGO FETs exhibit air‐stable symmetric ambipolar behavior with Dirac point at 0 V gate voltage and negligible hysteresis. This approach will also be applicable to pristine graphene and other two‐dimensional materials to obtain the intrinsic properties under ambient conditions, thereby promoting the research and applications of two‐dimensional materials.

Microvesicle detection by a reduced graphene oxide field-effect transistor biosensor based on a membrane biotinylation strategy.

Unlike other extracellular vesicle (EV) subtypes such as exosomes, the lack of well-defined universal markers on the surface of microvesicles (MVs) has led to difficulty in the detection of the entire MV population. To design a universal MV detection method, we reported highly sensitive electrical detection of MVs using a reduced graphene oxide (RGO)-based field-effect transistor (FET) biosensor by the introduction of a membrane biotinylation strategy in this work. Biotinylated MVs (B-MVs) were obtained by supplying the culture medium with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)-2000] (DSPE-PEG-biotin) while cultivating the cells. Excellent biotinylation efficiency of MVs (92.6%) was then realized. A streptavidin (SA) probe was subsequently modified onto the channel surface of the as-fabricated RGO-based FET device, which was capable of specifically recognizing B-MVs due to the high affinity between SA and biotin in a 1 : 4 recognition format. The results showed that the RGO-based FET biosensor could detect B-MVs in a wide range from 105 particles per mL to 109 particles per mL with a low detection limit down to 20 particles per μL, which was the lowest value compared with other previously reported results. This platform also allowed distinguishing B-MVs from other unbiotinylated EV types such as MVs and exosomes, exhibiting excellent specificity. Moreover, this FET biosensor demonstrated the capability of detecting B-MVs derived from different cell lines including cancer cells and normal cells, indicating its versatility and potential applications in the biomedical field.

The Effect of Aptamer Concetration towards Reduced Graphene Oxide-Field Effect Transistor Surface Channel for Biosensor Application

Aptamer are artificially produce bioreceptor that has been developed to bind with various target biomolecules such as ion, cells, protein and small molecules. In this research, an aptamer concentration of 0.5 nM, 1 nM, 5 nM, 10 nM, and 50 nM were immobilized on reduced graphene oxide (rGO) integrated with field effect transistor (FET) respectively to study the effect of aptamer concentration toward rGO surface for stable biosensing platform. The 0.5 nM concentration of aptamer shows the highest current result of 84.3 µA at 1 V applied through the source and drain. After immobilized with aminated aptamer, the conductivity shows significant reduction due to the formation of amide bond on rGO surface between aminated aptamer and carboxyl group on rGO. The electrical performance of FET integrated with rGO shows stable electrical performance suitable to be used in the biosensing application.

Pulse-Driven Capacitive Lead Ion Detection with Reduced Graphene Oxide Field-Effect Transistor Integrated with an Analyzing Device for Rapid Water Quality Monitoring.

Rapid and real-time detection of heavy metals in water with a portable microsystem is a growing demand in the field of environmental monitoring, food safety, and future cyber-physical infrastructure. Here, we report a novel ultrasensitive pulse-driven capacitance-based lead ion sensor using self-assembled graphene oxide (GO) monolayer deposition strategy to recognize the heavy metal ions in water. The overall field-effect transistor (FET) structure consists of a thermally reduced graphene oxide (rGO) channel with a thin layer of Al2O3 passivation as a top gate combined with sputtered gold nanoparticles that link with the glutathione (GSH) probe to attract Pb2+ ions in water. Using a preprogrammed microcontroller, chemo-capacitance based detection of lead ions has been demonstrated with this FET sensor. With a rapid response (∼1-2 s) and negligible signal drift, a limit of detection (LOD) < 1 ppb and excellent selectivity (with a sensitivity to lead ions 1 order of magnitude higher than that of interfering ions) can be achieved for Pb2+ measurements. The overall assay time (∼10 s) for background water stabilization followed by lead ion testing and calculation is much shorter than common FET resistance/current measurements (∼minutes) and other conventional methods, such as optical and inductively coupled plasma methods (∼hours). An approximate linear operational range (5-20 ppb) around 15 ppb (the maximum contaminant limit by US Environmental Protection Agency (EPA) for lead in drinking water) makes it especially suitable for drinking water quality monitoring. The validity of the pulse method is confirmed by quantifying Pb2+ in various real water samples such as tap, lake, and river water with an accuracy ∼75%. This capacitance measurement strategy is promising and can be readily extended to various FET-based sensor devices for other targets.

Fine discrimination of volatile compounds by graphene-immobilized odorant-binding proteins

We describe the fabrication and performance of a biosensor for odorants, using wildtype and engineered mutants of the Italian honeybee (Apis mellifera ligustica) odorant binding protein 14 (OBP14), immobilized onto a reduced graphene oxide field-effect transistor (rGO-FET). The binding properties of the protein when immobilized on the biosensor are similar to those measured in solution, thus providing a method for measuring affinities to small molecules as an alternative to the current fluorescence assay. Out of the 14 chemicals tested, the best ligands for wildtype OBP14 were eugenol, homovanillic acid and related compounds sharing a phenol-methoxy backbone. Other chemicals, including methyl eugenol, showed affinities to OBP14 100–1000 times lower. We have also tested two mutants of OBP14. The first, bearing a HisTag at its N-terminus for better orientation on the sensor surface, showed only minor differences in its binding properties for chemicals when compared to the wildtype. The second contained an additional disulfide bond between helices α3 and α6, thus reducing the dynamics of OBP14 and leading to a higher affinity for eugenol. These data also demonstrate that it is feasible to produce biosensors with desired ligand specificities by introducing selected mutations into the structure of OBPs or other active proteins.

Enzyme-polyelectrolyte multilayer assemblies on reduced graphene oxide field-effect transistors for biosensing applications

We present the construction of layer-by-layer (LbL) assemblies of polyethylenimine and urease onto reduced-graphene-oxide based field-effect transistors (rGO FETs) for the detection of urea. This versatile biosensor platform simultaneously exploits the pH dependency of liquid-gated graphene-based transistors and the change in the local pH produced by the catalyzed hydrolysis of urea. The use of an interdigitated microchannel resulted in transistors displaying low noise, high pH sensitivity (20.3µA/pH) and transconductance values up to 800 µS. The modification of rGO FETs with a weak polyelectrolyte improved the pH response because of its transducing properties by electrostatic gating effects. In the presence of urea, the urease-modified rGO FETs showed a shift in the Dirac point due to the change in the local pH close to the graphene surface. Markedly, these devices operated at very low voltages (less than 500mV) and were able to monitor urea in the range of 1–1000µm, with a limit of detection (LOD) down to 1µm, fast response and good long-term stability. The urea-response of the transistors was enhanced by increasing the number of bilayers due to the increment of the enzyme surface coverage onto the channel. Moreover, quantification of the heavy metal Cu2+(with a LOD down to 10nM) was performed in aqueous solution by taking advantage of the urease specific inhibition.

Characterization of reduced graphene oxide field-effect transistor and its application to biosensor

We confirmed the specific detection of immunoglobulin E (IgE) using an aptamer-immobilized reduced graphene oxide (rGO) field effect transistor (FET). The detection limit and dynamic range were estimated to be 8.1 ng/ml and 104, respectively. These characteristics are comparable with these of current fluorescent markers. Although the mobility of rGO-FET was around 6 cm2 V−1 s−1, which is two to three orders lower than that of mechanically exfoliated pristine graphene FET, its sensitivity to IgE was only one order lower than that of pristine graphene FET.

Reduced graphene oxide field-effect transistor with indium tin oxide extended gate for proton sensing

In this study, the reduced graphene oxide field-effect transistor (rGO FET) with indium tin oxide (ITO) extended gate electrode was demonstrated as a transducer for proton sensing application. In this structure, the proton sensing area of the ITO extended gate electrode is isolated from the active area of the rGO FET. The proton sensing properties based on the rGO FET transducer were analyzed. The rGO FET device with encapsulation by a tetratetracontane (TTC) layer showed good stability in electrolytic solutions. The device showed an ambipolar behavior with shifts in Dirac point as the pH of the electrolyte is varied. The pH sensitivity based on the Dirac point shift as a sensing parameter was about 43–50 mV/pH for a wide range of pH values from 2 to 12. The ITO extended gate rGO FET may be considered a potential transducer for sensing of H+ in electrolytes. Its sensing area can be modified further for various ions sensing applications.

Ultrasensitive Label-Free Detection of PNA–DNA Hybridization by Reduced Graphene Oxide Field-Effect Transistor Biosensor

A reduced graphene oxide (R-GO)-based field-effect transistor (FET) biosensor used for ultrasensitive label-free detection of DNA via peptide nucleic acid (PNA)-DNA hybridization is reported. In this work, R-GO was prepared by reduction of GO with hydrazine, and the FET biosensor was fabricated by drop-casting the R-GO suspension onto the sensor surface. PNA instead of DNA as the capture probe was employed, and DNA detection was performed through PNA-DNA hybridization by the R-GO FET biosensor. The detection limit as low as 100 fM was achieved, which is 1 order of magnitude lower than that of the previously reported graphene FET DNA biosensor based on DNA-DNA hybridization. Moreover, the R-GO FET biosensor was able to distinguish the complementary DNA from one-base mismatched DNA and noncomplementary DNA. Interestingly, the fabricated DNA biosensor was found to have a regeneration capability. The developed R-GO FET DNA biosensor shows ultrasensitivity and high specificity, indicating its potential applications in disease diagnostics as a point-of-care tool.

Detection of Protein by Reduced Graphene Oxide Field-Effect Transistor

ABSTRACTWe confirmed a specific detection of immunoglobulin E(IgE) by using an aptamer immobilized reduced graphene oxide(rGo) field effect transistor(FET). A detection limit and dynamic range were estimated 8.1 ng/ml and 10000 respectively. These characteristics are comparable with current fluorescent markers. Although a mobility of rGo FET was around 5 cm2/V.sec, and this is two to three orders lower than mechanically exfoliated pristine graphene FET, a sensitivity of it was only one order lower than using pristine graphene.

Micropatterned reduced graphene oxide based field-effect transistor for real-time virus detection

Graphene, a new class of two-dimensional (2D) carbon crystal structure, holds a train of remarkable properties due to its fast electron transport, high chemical stability and strong mechanical strength. Herein, we report a real-time, rapid and sensitive biosensor for pathogenic rotavirus detection based on the micropatterned reduced graphene oxide field-effect transistor (MRGO-FET) which displays p-type behavior. Single layered and large sized GO sheets greater than 50μm were prepared by a modified Hummers method, and through the photolithography and reduction process, an MRGO-FET was generated. After integration into a polydimethylsiloxane microfluidic channel, specific rotavirus antibodies have been covalently anchored to the graphene surface on which 1-pyrenebutyric acid N-hydroxysuccinimide ester was pre-adsorbed through π–π interaction. Injection of a rotavirus sample whose concentration ranged from 10 to 105pfu/mL led to a quick decrease in the source-drain current and then a gradual saturation. The lowest detection limit for rotavirus was determined as 102pfu which is superior to the conventional ELISA method.