Graphene field effect transistor (GFET)-based biosensors have gained significant interest due to their superior stability and higher electron mobility. This article discusses the design, applications, and limits of GFET-based biosensors.
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Introduction to GFTEs in Biosensors
A field effect transistor (FET) is a carrier device with three terminals: source, drain, and gate. In FETs, an electric field can be applied at the terminal of the gate, modifying the conductive property of the channel between the drain and the source.1
Graphene was discovered in 2004. It is a two-dimensional (2D) carbon material with a six-circular honeycomb lattice framework. Its unique characteristics, including excellent electrical and thermal conductivity, high electron mobility, large surface area, biocompatibility, and electrochemical inertness, make it an ideal biosensor nanosheet.1,2
Principles of GFET-Based Biosensors
FET-based biosensors work by attaching a bio-sensitive probe to the target analyte, which releases charged ions, enabling the sensor to detect biological materials.3 This alters the carriers within the channel material, affecting electrical properties such as source-drain currents, which are translated into electrical impulses for detection.3
In GFETs, graphene serves as the channel in the FET structure. GFETs can be top-gated or back-gated based on the gate fabrication scheme. The target analyte immobilizes on the graphene surface, modifying its conductivity, which is then measured at the output.4
Graphene's high conductivity allows for very short response times, aiding in rapid detection of the target analyte.4
GFET Biosensors: Design, Fabrication, and Sensing Mechanisms
FET sensors have three primary structural components: source, drain, and bottom or top gate. Biometric elements can be modified on the surface of the graphene channel to detect biological substances.1
Developing high-quality graphene is crucial. Common preparation processes include redox, chemical vapor deposition (CVD), and mechanical stripping.5
There are two main approaches to fabricating GFET biosensors: attaching biological receptors to the graphene surface or placing the biological receptor inside the gate dielectric layer's fabricated cavity.5
In the first fabrication method, biological receptors are attached to the graphene surface to detect targets by mutual forces. Charge transfer modifies the conductivity following specific binding, transforming metabolic changes into detectable electrical signals.
Due to graphene's electrical inertness, surface modifications such as fixed nanoparticle pre-treatment, electrostatic adsorption, and π-π interactions are used to enhance sensitivity.1,6
In the second method, biological molecules with specific dielectric constants are included in the fabricated cavity, altering the dielectric gate capacitance and causing a threshold voltage shift. This current change indicates the presence of the target moiety.1,5
Applications, Recent Developments, and Research Trends
Current research focuses on developing biosensors with rapid detection times, high sensitivity, and minimal sample volume requirements.3 GFET biosensors are popular in medical applications for their selectivity, sensitivity, rapid analysis, low cost, compactness, and integration.3
Immunoassay Based on Single Biosensor
The two primary diagnostic techniques for COVID-19 are viral nucleic acid testing and serology; however, neither method meets the need for speed and accuracy in diagnostic detection.3
Seo et al. reported the use of a graphene sheet as the sensing region combined with a spiked antibody against severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) to detect the virus in clinical specimens using a FET biosensor. This method successfully identified the 100 fg/mL SARS-CoV-2 spike protein within the clinical transport media.7
G-FET-Based Nucleic Acid Sensors
Ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and microRNA (miRNA) are examples of nucleic acids that are important for human physiology and, consequently, for a wide range of disorders. Prior research has indicated a strong correlation between miRNAs and several illnesses, including cancer.8,9
Let7g is a miRNA believed to be involved in tumor suppression. In 2014, Xu et al. successfully developed a G-FET selective for let7g.8,9
Integrated into Array for Multiplexing
According to current research trends, FET sensors may also be applied in human biomimetic sensory systems.3
Ahn et al. created GFET-based dual biological electronic tongues (DBTs) that simultaneously detect umami and sweet tastes.10 This innovation opens new avenues for replicating complex human biomimetic systems and highlights the potential of GFET-based biosensors.
Integrated with Microfluidics for LAB–on–CHIP (LOC)
LOC technology has facilitated the design of handheld, compact medical diagnostic test systems. Combining microfluidic devices with GFET biosensors in LOC presents a promising approach.3
Hajian et al. developed a CRISPR-Chip by modifying the graphene surface with the CRISPR-Cas9 complex. This device holds the potential to advance digital genomics by rapidly, efficiently, and selectively identifying target sequences of the CRISPR-Cas9 gene.10
Challenges and Limitations
The fabrication of GFET biosensors presents several challenges. Although highly sensitive, they also respond to non-targets such as proteins and ions, complicating clinical data analysis.8
Reagents like bovine serum albumin (BSA), polyethylene glycol (PEGs), and surfactants are often used to block the graphene surface, reducing hydrophobic interactions and preventing non-specific binding.11
Additionally, residues from materials used in production, such as poly(methylmethacrylate), pose further limitations. Despite various cleaning techniques, including annealing in a hydrogen atmosphere, no method fully removes these contaminants.11
Future Prospects and Potential Applications
Over the past decade, significant scientific effort has been dedicated to developing GFET-based biosensors. Prototyping proof-of-concept devices is crucial for advancing GFET development, requiring in situ testing of analytes instead of buffered solutions.8
While short-chain nucleotide-based biosensors are being created, future efforts should focus on long-chain nucleotides or entire genes for clinical applicability.8
Further studies on the nano-bio interfaces in GFET sensors are needed. A comprehensive analysis of stability and real-time detection is essential to commercialize GFET biosensors, ensuring long-term stability and high performance for clinical use.8
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References and Further Reading
1. Liang, Q-H., et al. (2023). The Application of Graphene Field-Effect Transistor Biosensors in COVID-19 Detection Technology: A Review. Sensors. doi.org/10.3390/S23218764
2. Sreejith, S, et al. (2023). A comprehensive review on graphene FET bio-sensors and their emerging application in DNA/RNA sensing & rapid COVID-19 detection. Measurement. doi.org/10.1016/j.measurement.2022.112202
3. Hao, R, et al. (2023). Recent Advances in Field Effect Transistor Biosensors: Designing Strategies and Applications for Sensitive Assay. Biosens. doi.org/10.3390/BIOS13040426
4. Sengupta, J., Hussain, CM. (2021). Graphene-based field-effect transistor biosensors for the rapid detection and analysis of viruses: A perspective in view of COVID-19. Carbon Trends. doi.og/10.1016/j.cartre.2020.100011
5. Thriveni, G., Ghosh, K. (2022). Advancement and Challenges of Biosensing Using Field Effect Transistors. Biosens. doi.org/10.3390/bios12080647
6. Gao, J., et al. (2022). Graphene oxide-graphene Van der Waals heterostructure transistor biosensor for SARS-CoV-2 protein detection. Talanta. doi.org/10.1016/j.talanta.2021.123197
7. Seo, G, et al. (2020). Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor. ACS Nano. doi.org/10.1021/acsnano.0c02823/asset/images/large/nn0c02823_0006.jpeg
8. Forsyth, R. (2017). Graphene Field Effect Transistors for Biomedical Applications: Current Status and Future Prospects. Diagnostics. doi.org/10.3390/diagnostics7030045
9. Xu, G., et al. Electrophoretic and field-effect graphene for all-electrical DNA array technology. Nat Commun. doi.org/10.1038/ncomms5866
10. Ahn, SR., et al. Duplex Bioelectronic Tongue for Sensing Umami and Sweet Tastes Based on Human Taste Receptor Nanovesicles. ACS Nano. doi.org/10.1021/acsnano.6b02547
11. Ono, T. (2024). Challenges for Field-Effect-Transistor-Based Graphene Biosensors. Mater. doi.org/10.3390/ma17020333
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