Electrolyte-gated Graphene Field-effect Transistors Research Articles

Modelling and Optimization of the Differential Surface Capacitance in Electrolyte-Gated Graphene Field-Effect Transistors

Graphene field-effect transistors (GFETs) are a promising avenue for the detection of biomarkers, allowing to envision improvements in diagnostic approaches for different types of cancer and other diseases. To enable such applications, the detection metrics of the devices must be optimized, including their sensitivity, selectivity, and stability. In particular, the capacitance of the device is one of the key determinants of the sensitivity of the electrical current of graphene to nearby changes in electrical potentials. In this presentation, we present our approach to optimize the surface capacitance of electrolyte-gated GFETs, by investigating theoretically and/or experimentally the effect of specific design parameters, including the graphene area, the removal of the backgate, and the passivation of electrodes. On the theoretical side, a mathematical representation of the device capacitance was established as an equivalent circuit of capacitors modelling for the quantum capacitance of graphene, the backgate capacitance, and the capacitance of electrical double layers in the electrolyte. On the experimental side, microchips of GFET arrays were assembled using microfabrication techniques on two types of substrates: a standard Si++/SiO2 wafer in which the doped silicon layer is used as a backgate, and a pure non-conducting borosilicate glass wafer in comparison. The capacitance of the devices was then measured using a custom parallel electrical prober by stepping the applied voltage in the solution and analyzing the resulting current response through a standard RC direct current model. We will present our analyses by comparing the relative impact of electrode passivation, backgate usage, and graphene area on the capacitance of devices. These results will enable a rational design of GFET devices with improved sensitivity for their use in applications such as biological, chemical, and gas sensing.

Graphene-based materials and their applications in electrolyte-gated transistors for sensing

Graphene is a two-dimensional material with remarkable physicochemical characteristics. In particular, graphene is highly sensitive to its electronic and electrostatic environment. For these reasons, among various applications of graphene, its use as a sensitive material in field-effect transistors (FETs) is widely studied, especially for biodetection purposes. So, this review aims to introduce the reader to the state of the art of graphene-based materials for their applications in electrolyte-gated graphene field-effect transistors (EGGFETs) for biosensing applications. Among numerous ways to produce graphene-based materials for such devices, some of the most important, widely used methods are presented herein. After that, the working principle of graphene-based FETs is discussed and the various ways to tune graphene's electronic properties are presented. The fabrication methods are discussed, with an emphasis on inkjet printing which allows printing of EGGFETs from aqueous graphene oxide inks, providing that it is subsequently reduced to adjust the mobility of charge carriers and the doping state. Finally, some of the recent works concerning the use of FETs in biosensing applications are reviewed.

An Electrolyte-Gated Graphene Field-Effect Transistor for Detection of Gadolinium(III) in Aqueous Media

In this work, an electrolyte-gated graphene field-effect transistor is developed for Gd3+ ion detection in water. The source and drain electrodes of the transistor are fabricated by photolithography on polyimide, while the graphene channel is obtained by inkjet-printing a graphene oxide ink subsequently electro-reduced to give reduced graphene oxide. The Gd3+-selective ligand DOTA is functionalized by an alkyne linker to be grafted by click chemistry on a gold electrode without losing its affinity for Gd3+. The synthesis route is fully described, and the ligand, the linker and the functionalized surface are characterized by electrochemical analysis and spectroscopy. The as functionalized electrode is used as gate in the graphene transistor so to modulate the source-drain current as a function of its potential, which is itself modulated by the concentration of Gd3+captured on the gate surface. The obtained sensor is able to quantify Gd3+ even in a sample containing several other potentially interfering ions such as Ni2+, Ca2+, Na+ and In3+. The quantification range is from 1 pM to 10 mM, with a sensitivity of 20 mV dec-1 expected for a trivalent ion. This paves the way for Gd3+ quantification in hospital or industrial wastewater.

A sprayed graphene transistor platform for rapid and low-cost chemical sensing.

We demonstrate a novel and versatile sensing platform, based on electrolyte-gated graphene field-effect transistors, for easy, low-cost and scalable production of chemical sensor test strips. The Lab-on-PCB platform is enabled by low-boiling, low-surface-tension sprayable graphene ink deposited on a substrate manufactured using a commercial printed circuit board process. We demonstrate the versatility of the platform by sensing pH and Na+ concentrations in an aqueous solution, achieving a sensitivity of 143 ± 4 μA per pH and 131 ± 5 μA per log10Na+, respectively, in line with state-of-the-art graphene chemical sensing performance.

Electrolyte-Gated Graphene Field Effect Transistor-Based Ca2+ Detection Aided by Machine Learning.

Flexible electrolyte-gated graphene field effect transistors (Eg-GFETs) are widely developed as sensors because of fast response, versatility and low-cost. However, their sensitivities and responding ranges are often altered by different gate voltages. These bias-voltage-induced uncertainties are an obstacle in the development of Eg-GFETs. To shield from this risk, a machine-learning-algorithm-based LgGFETs' data analyzing method is studied in this work by using Ca2+ detection as a proof-of-concept. For the as-prepared Eg-GFET-Ca2+ sensors, their transfer and output features are first measured. Then, eight regression models are trained with the use of different machine learning algorithms, including linear regression, support vector machine, decision tree and random forest, etc. Then, the optimized model is obtained with the random-forest-method-treated transfer curves. Finally, the proposed method is applied to determine Ca2+ concentration in a calibration-free way, and it is found that the relation between the estimated and real Ca2+ concentrations is close-to y = x. Accordingly, we think the proposed method may not only provide an accurate result but also simplify the traditional calibration step in using Eg-GFET sensors.

Optimizing PMMA solutions to suppress contamination in the transfer of CVD graphene for batch production

Mass production and commercial adoption of graphene-based devices are held back by a few crucial technical challenges related to quality control. In the case of graphene produced by chemical vapor deposition, the transfer process represents a delicate step that can compromise device performance and reliability, thus hindering industrial production. In this context, the impact of poly(methyl methacrylate) (PMMA), the most common support material for transferring graphene from the Cu substrate to any target surface, can be decisive in obtaining reproducible sample batches. Although effective in mechanically supporting graphene during the transfer, PMMA solutions needs to be efficiently designed, deposited, and post-treated to serve their purpose while minimizing potential contaminations. Here, we prepared and tested PMMA solutions with different average molecular weight (AMW) and weight concentration in anisole, to be deposited by spin coating. Optical microscopy and Raman spectroscopy showed that the amount of PMMA residues on transferred graphene is proportional to the AMW and concentration in the solvent. At the same time, the mechanical strength of the PMMA layer is proportional to the AMW. These tests served to design an optimized PMMA solution made of a mixture of 550,000 (550k) and 15,000 (15k) AMW PMMA in anisole at 3% concentration. In this design, PMMA-550k provided suitable mechanical strength against breakage during the transfer cycles, while PMMA-15k promoted depolymerization, which allowed for a complete removal of PMMA residues without the need for any post-treatment. An XPS analysis confirmed the cleanness of the optimized process. We validated the impact of the optimized PMMA solution on the mass fabrication of arrays of electrolyte-gated graphene field-effect transistors operating as biosensors. On average, the transistor channel resistance decreased from 1860 to 690 Ω when using the optimized PMMA. Even more importantly, the vast majority of these resistance values are distributed within a narrow range (only ca. 300 Ω wide), in evident contrast with the scattered values obtained in non-optimized devices (about 30% of which showed values above 1 MΩ). These results prove that the optimized PMMA solution unlock the production of reproducible electronic devices at the batch scale, which is the key to industrial production.

Experimental comparison of direct and indirect aptamer-based biochemical functionalization of electrolyte-gated graphene field-effect transistors for biosensing applications

Aptamer-based electrolyte-gated graphene field-effect transistor (EGFET) biosensors have gained considerable attention because of their rapidity and accuracy in terms of quantification of a wide range of biomarkers. Functionalization of the graphene channel of EGFETs with aptamer biorecognition elements (BREs) is a crucial step in fabrication of EGFET aptasensors. This paper presents a comprehensive comparison of commonly used biochemical functionalization approaches applied for preparation of sensing films in EGFET aptasensors, namely indirect and direct immobilization of BREs. This study is the first of its kind to experimentally compare the two BREs immobilization approaches in terms of their effects on the carrier mobility of the monolayer graphene channel and their suitability for sensing applications. Both approaches can preserve and even improve the carrier mobility of bare graphene channel and hence the sensitivity of the EGFET; however, the direct BREs immobilization method was selected to develop an aptameric EGFET biosensor as this method enables simpler and more efficient preparation of the graphene-based aptameric sensing film. The utility of the prepared EGFET aptasensor is demonstrated through detection of tumor necrosis factor-α (TNF-α), an important inflammatory biomarker. The direct BREs immobilization approach is applied to develop an EGFET aptasensor to measure TNF-α in a detection range from 10 pg/ml to 10 ng/ml, representative of its physiological level in human sweat, as a non-invasively accessible biofluid. The outstanding sensing performance of the developed TNF-α EGFET aptasensor based on direct BREs immobilization can pave the way for development of graphene biosensors.

Wet-Chemical Noncovalent Functionalization of CVD Graphene: Molecular Doping and Its Effect on Electrolyte-Gated Graphene Field-Effect Transistor Characteristics

Wet-Chemical Noncovalent Functionalization of CVD Graphene: Molecular Doping and Its Effect on Electrolyte-Gated Graphene Field-Effect Transistor Characteristics

Development and Functionalization of Electrolyte-Gated Graphene Field-Effect Transistor for Biomarker Detection.

In the current study, graphene and its derivatives have been investigated and used for many applications, including electronics, sensing, energy storage, and photocatalysis. Synthesis and fabrication of high quality, good uniformity, and low defects graphene are critical for high-performance and highly sensitive devices. Among many synthesis methods, chemical vapor deposition (CVD), considered a leading approach to manufacture graphene, can control the number of graphene layers and yield high-quality graphene. CVD graphene needs to be transferred from the metal substrates on which it is grown ontoinsulating substrates for practical applications. However, separation and transferring of graphene onto new substrates are challenging for a uniform layer without damaging or affecting graphene's structures and properties. Additionally, electrolyte-gated graphene field-effect transistor (EGGFET) has been demonstrated for its wide applications in various biomolecular detections because of its high sensitivity and standard device configuration. In this article, poly (methyl methacrylate) (PMMA)-assisted graphene transferring approach, fabrication of graphene field-effect transistor (GFET), and biomarker immunoglobulin G (IgG) detection are demonstrated. Raman spectroscopy and atomic force microscopy were applied to characterize the transferred graphene. The method is shown to be a practical approach for transferring clean and residue-free graphene while preserving the underlying graphene lattice onto an insulating substrate for electronics or biosensing applications.

Development and Functionalization of Electrolyte-Gated Graphene Field-Effect Transistor for Biomarker Detection

Development and Functionalization of Electrolyte-Gated Graphene Field-Effect Transistor for Biomarker Detection

Dielectric‐Modulated Biosensing with Ultrahigh‐Frequency‐Operated Graphene Field‐Effect Transistors

Owing to their excellent electrical properties and chemical stability, graphene field-effect transistors (Gr-FET) are extensively studied for biosensing applications. However, hinging on surface interactions of charged biomolecules, the sensitivity of Gr-FET is hampered by ionic screening under physiological conditions with high salt concentrations up to frequencies as high as MHz. Here, an electrolyte-gated Gr-FET in reflectometry mode at ultrahigh frequencies (UHF, around 2GHz), where the ionic screening is fully cancelled and the dielectric sensitivity of the device allows the Gr-FET to directly function in high-salt solutions, is configured. Strikingly, by simultaneous characterization using electrolyte gating and UHF reflectometry, the developed graphene biosensors offer unprecedented capability for real-time monitoring of dielectric-specified biomolecular/cell interactions/activities, with superior limit of detection compared to that of previously reported nanoscale high-frequency sensors. These achievements highlight the unique potential of ultrahigh-frequency operation for unblocking the true potential of graphene biosensors for point-of-care diagnostic.

Origins of Leakage Currents on Electrolyte-Gated Graphene Field-Effect Transistors

Graphene field-effect transistors are widely used for development of biosensors. However, certain fundamental questions about details of their functioning are not fully understood yet. One of these questions is the presence of gate (leakage) currents in the electrolyte-gated configuration. Here, we report our observations considering causes of this phenomena on chemical vapor deposition (CVD) grown graphene. We observed that gate currents reflect currents that occur on the transistor surface similarly to a working electrode - counter electrode pair currents in an electrochemical cell. Gate currents are capacitive when the graphene channel is doped by holes and Faradaic when it is doped by electrons in field-effect measurements. The Faradaic current is attributed to a reduction of oxygen dissolved in the aqueous solution and its magnitude increases with each measurement. We employed cyclic voltammetry with a redox probe Fc(MeOH)2 to characterize changes of the graphene structure that are responsible for this activation. Collectively, our results reveal that through the course of catalytic oxygen reduction on the transistor's surface more defects appear.

A Sensitivity-Enhanced Electrolyte-Gated Graphene Field-Effect Transistor Biosensor by Acoustic Tweezers.

Low-abundance biomolecule detection is very crucial in many biological and medical applications. In this paper, we present a novel electrolyte-gated graphene field-effect transistor (EGFET) biosensor consisting of acoustic tweezers to increase the sensitivity. The acoustic tweezers are based on a high-frequency bulk acoustic resonator with thousands of MHz, which has excellent ability to concentrate nanoparticles. The operating principle of the acoustic tweezers to concentrate biomolecules is analyzed and verified by experiments. After the actuation of acoustic tweezers for 10 min, the IgG molecules are accumulated onto the graphene. The sensitivities of the EGFET biosensor with accumulation and without accumulation are compared. As a result, the sensitivity of the graphene-based biosensor is remarkably increased using SMR as the biomolecule concentrator. Since the device has advantages such as miniaturized size, low reagent consumption, high sensitivity, and rapid detection, we expect it to be readily applied to many biological and medical applications.

The role of graphene patterning in field-effect transistor sensors to detect the tau protein for Alzheimer's disease: Simplifying the immobilization process and improving the performance of graphene-based immunosensors

We report the improvement in the sensing performance of electrolyte-gated graphene field-effect transistor (FET) sensors capable of detecting tau protein through a simplified, linker-free, anti-tau antibody immobilization process. For most of the graphene-based immunosensor, linkers, such as pyrenebutanoic acid, succinimidyl ester (PSE) must be used to the graphene surface, while the other side of linkers serves to capture the antibodies that can specifically interact with the target biomarker. In this study, graphene was patterned into eight different types and linker-free patterned graphene FET sensors were fabricated to verify their detection performance. The linker-free antibody immobilization to patterned graphene exhibited that the antibody was immobilized to the edge defect and had a doping-like behaviors on graphene. As the tau protein concentration in the electrolyte increased from 10 fg/ml to 1 ng/ml, the performances, charge neutral point shift and current change rate of the patterned graphene sensors without linkers were enhanced 2–3 times compared to a pristine graphene sensor with the PSE linker. Moreover, tau protein in the plasma of five Alzheimer's disease patients was measured using a linker-free patterned graphene sensor. It shows a 3–4 times higher current change rate than that of pristine graphene sensor with the PSE linker. Since the antibody is immobilized directly without a linker, a patterned graphene sensor without a linker can operate more sensitively in higher ionic concentration electrolyte.

Inkjet-Printed Graphene Sensors for the Bedside Detection of Tear Film pH.

PurposeTo determine whether an inexpensive, graphene thin-film electronic pH sensor could be used to measure tear film pH.MethodsThe pH-sensitive electrolyte-gated graphene field-effect transistors (EG-GFETs) were fabricated by patterning graphene ink and ultraviolet-cured dielectric onto 125 µm–thick polyimide substrate using a nanomaterials inkjet printer. A flow-cell was used to exchange test solutions and record current flow through the EG-GFET. Laboratory reference pH test solutions were used to calibrate the sensor. Contrived tears with lipids were pH buffered using HCL (1 M) or NAOH (1 M) to produce tear solutions ranging in pH from 2.0 to 9.5. A laboratory-reference pH meter was used to verify the pH of each solution. Dirac curves that demonstrate pH-dependent changes in current flow through the EG-GFET were measured for each test solution, using dual sourcemeters.ResultsGraphene EG-GFET devices were highly sensitive to changes in artificial tear-film pH. The Dirac voltage was defined as the gate voltage at which minimum source drain current was measured. The relationship between Dirac voltage and tear film pH was highly linear with a slope of 17.2 mV per pH unit over the range of solutions tested, from pH 2.0 to pH 9.5 (r2 = 0.977).ConclusionsGraphene field-effect transistors accurately measure tear film pH and may be useful in the emergency management of ocular adnexal exposure to acids or bases.Translational RelevanceThin-film graphene sensors are low cost and can rapidly map tear-film pH at multiple sites on the ocular surface and within the conjunctival fornices, avoiding subjective, colorimetric test-paper methods.

Self-Assembled Pyrene Stacks and Peptide Monolayers Tune the Electronic Properties of Functionalized Electrolyte-Gated Graphene Field-Effect Transistors.

Aromatic molecules such as pyrenes are a unique class of building units for graphene functionalization, forming highly ordered π-π stacks while peptides provide more complex, biocompatible linkers. Understanding the adsorption and stacking behavior of these molecules and their influence on material properties is an essential step in enabling highly repeatable 2D material-based applications, such as biosensors, gas sensors, and solar cells. In this work, we characterize pyrene and peptide self-assembly on graphene substrates using fluorescence microscopy, atomic force microscopy and electrolyte-gated field-effect measurements supported by quantum mechanical calculations. We find distinct binding and assembly modes for pyrenes versus peptides with corresponding distinct electronic signatures in their characteristic charge neutrality point and field-effect slope responses. Our data demonstrates that pyrene- and peptide-based self-assembly platforms can be highly beneficial for precisely customizing graphene electronic properties for desired device technologies such as transport-based biosensing graphene field-effect transistors.

Sensitive detection of lung cancer biomarkers using an aptameric graphene-based nanosensor with enhanced stability.

We present an electrolyte-gated graphene field effect transistor (GFET) nanosensor using aptamer for rapid, highly sensitive and specific detection of a lung cancer biomarker interleukin-6 (IL-6) with enhanced stability. The negatively charged aptamer folds into a compact secondary conformation upon binding with IL-6, thus altering the carrier concentration of graphene and yielding a detectable change in the drain-source current Ids. Aptamer has smaller size than other receptors (e.g. antibodies), making it possible to bring the charged IL-6 more closely to the graphene surface upon affinity binding, thereby enhancing the sensitivity of the detection. Thanks to the higher stability of aptamer over antibodies, which degrade easily with increasing storage time, consistent sensing performance was obtained by our nanosensor over extended-time (>24h) storage at 25°C. Additionally, due to the GFET-enabled rapid transduction of the affinity recognition to IL-6, detection of IL-6 can be achieved in several minutes (<10min). Experimental results indicate that this nanosensor can rapidly and specifically respond to the change in IL-6 levels with high consistency after extended-time storage and a detection limit (DL) down to 139 fM. Therefore, our nanosensor holds great potential for lung cancer diagnosis at its early stage.

Attomolar Label-Free Detection of DNA Hybridization with Electrolyte-Gated Graphene Field-Effect Transistors.

In this work, we develop a field-effect transistor with a two-dimensional channel made of a single graphene layer to achieve label-free detection of DNA hybridization down to attomolar concentration, while being able to discriminate a single nucleotide polymorphism (SNP). The SNP-level target specificity is achieved by immobilization of probe DNA on the graphene surface through a pyrene-derivative heterobifunctional linker. Biorecognition events result in a positive gate voltage shift of the graphene charge neutrality point. The graphene transistor biosensor displays a sensitivity of 24 mV/dec with a detection limit of 25 aM: the lowest target DNA concentration for which the sensor can discriminate between a perfect-match target sequence and SNP-containing one.

Matrix Effect Study and Immunoassay Detection Using Electrolyte-Gated Graphene Biosensor.

Significant progress has been made on the development of electrolyte-gated graphene field effect transistor (EGGFET) biosensors over the last decade, yet they are still in the stage of proof-of-concept. In this work, we studied the electrolyte matrix effects, including its composition, pH and ionic strength, and demonstrate that variations in electrolyte matrices have a significant impact on the Fermi level of the graphene channel and the sensitivity of the EGGFET biosensors. This is attributed to the polarization-induced interaction between the electrolyte and the graphene at the interface which can lead to considerable modulation of the Fermi level of the graphene channel. As a result, the response of the EGGFET biosensors is susceptible to the matrix effect which might lead to high uncertainty or even false results. Then, an EGGFET immunoassay is presented which aims to allow good regulation of the matrix effect. The multichannel design allows in-situ calibration with negative control, as well as statistical validation of the measurement results. Its performance is demonstrated by the detection of human immunoglobulin G (IgG) from serum. The detection range is estimated to be around 2–50 nM with a coefficient of variation (CV) of less than 20% and the recovery rate for IgG detection is around 85–95%. Compared with traditional immunoassay techniques, the EGGFET immunoassay is label-free and ready to be integrated with microfluidics sensor platforms, suggesting its great prospect for point-of-care applications.

Frequency Response of Graphene Electrolyte-Gated Field-Effect Transistors.

This work develops the first frequency-dependent small-signal model for graphene electrolyte-gated field-effect transistors (EGFETs). Graphene EGFETs are microfabricated to measure intrinsic voltage gain, frequency response, and to develop a frequency-dependent small-signal model. The transfer function of the graphene EGFET small-signal model is found to contain a unique pole due to a resistive element, which stems from electrolyte gating. Intrinsic voltage gain, cutoff frequency, and transition frequency for the microfabricated graphene EGFETs are approximately 3.1 V/V, 1.9 kHz, and 6.9 kHz, respectively. This work marks a critical step in the development of high-speed chemical and biological sensors using graphene EGFETs.