Field Effect Transistor-based Biosensor Research Articles

Recent progress on field-effect transistor-based biosensors: device perspective

Over the last few decades, field-effect transistor (FET)-based biosensors have demonstrated great potential across various industries, including medical, food, agriculture, environmental, and military sectors. These biosensors leverage the electrical properties of transistors to detect a wide range of biomolecules, such as proteins, DNA, and antibodies. This article presents a comprehensive review of advancements in the architectures of FET-based biosensors aiming to enhance device performance in terms of sensitivity, detection time, and selectivity. The review encompasses an overview of emerging FET-based biosensors and useful guidelines to reach the best device dimensions, favorable design, and realization of FET-based biosensors. Consequently, it furnishes researchers with a detailed perspective on design considerations and applications for future generations of FET-based biosensors. Finally, this article proposes intriguing avenues for further research on the topology of FET-based biosensors.

Ultrafast and highly sensitive detection of SARS-CoV-2 spike protein by field-effect transistor graphene-based biosensors

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etiological agent for the coronavirus disease 2019 (COVID-19), has resulted in over 775 million global infections. Early diagnosis remains pivotal for effective epidemiological surveillance despite the availability of vaccines. Antigen-based assays are advantageous for early COVID-19 detection due to their simplicity, cost-effectiveness, and suitability for point-of-care testing (PoCT). This study introduces a graphene field-effect transistor-based biosensor designed for high sensitivity and rapid response to the SARS-CoV-2 spike protein. By functionalizing graphene with monoclonal antibodies and applying short-duration gate voltage pulses, we achieve selective detection of the viral spike protein in human serum within 100 µs and at concentrations as low as 1 fg ml−1, equivalent to 8 antigen molecules per µl of blood. Furthermore, the biosensor estimates spike protein concentrations in serum from COVID-19 patients. Our platform demonstrates potential for next-generation PoCT antigen assays, promising fast and sensitive diagnostics for COVID-19 and other infectious diseases.

Ultrasensitive graphene field-effect transistor biosensor for rapidly detecting miRNA-208a

MicroRNA-208a (miR208a) is a cardiac-specific miRNA and can provide an earlier prediction for AMI onset than currently used cardiac biomarkers. Graphene field-effect transistor (GFET) biosensor, as the promising candidate for next-generation biosensor, has been demonstrated for real-time detection of a variety of bioactive molecules with ultrasensitivity from nM to fM level. Currently, research on GFET sensors mostly focuses on the properties of the devices themselves, rather than aiming for ultra-sensitive detection based on biochemical substances. In this study, we developed a liquid-gated graphene field-effect transistor-based biosensor for detection of miR208a and designed a portable device to adapt with it for a fast readout of the electronic response, achieving a detection range of 0.01-1 pM, detection limit of 5.3 fM and detection time of 40minutes. Our work provides a reliable strategy to rapidly and ultrasensitively quantifying miRNA-208a, which also holds great potential to be extended in a wide range of applications of other disease markers and lead to powerful tools for healthcare.

Ion-Sensitive Field-Effect Transistor-Based Biosensors: The Sources of Gates and Their Sensitive Layers—A Review

Ion-Sensitive Field-Effect Transistor-Based Biosensors: The Sources of Gates and Their Sensitive Layers—A Review

Functionalized-Graphene Field Effect Transistor-Based Biosensor for Ultrasensitive and Label-Free Detection of β-Galactosidase Produced by Escherichia coli.

The detection of β-galactosidase (β-gal) activity produced by Escherichia coli (E. coli) can quickly analyze the pollution degree of seawater bodies in bathing and fishing grounds to avoid large-scale outbreaks of water pollution. Here, a functionalized biosensor based on graphene-based field effect transistor (GFET) modified with heat-denatured casein was developed for the ultrasensitive and label-free detection of the β-gal produced by E. coli in real water samples. The heat-denatured casein coated on the graphene surface, as a probe linker and blocker, plays an important role in fabricating GEFT biosensor. The GFET biosensor response to the β-gal produced by E. coli has a wide concentration dynamic range spanning nine orders of magnitude, in a concentration range of 1 fg·mL-1-100 ng·mL-1, with a limit of detection (LOD) 0.187 fg·mL-1 (1.61 aM). In addition to its attomole sensitivity, the GFET biosensor selectively recognized the β-gal in the water sample and showed good selectivity. Importantly, the detection process of the β-gal produced by E. coli can be completed by a straightforward one-step specific immune recognition reaction. These results demonstrated the usefulness of the approach, meeting environmental monitoring requirements for future use.

Dopamine-Regulated Plasticity in MoO3 Synaptic Transistors.

Field-effect transistor-based biosensors have gained increasing interest due to their reactive surface to external stimuli and the adaptive feedback required for advanced sensing platforms in biohybrid neural interfaces. However, complex probing methods for surface functionalization remain a challenge that limits the industrial implementation of such devices. Herein, a simple, label-free biosensor based on molybdenum oxide (MoO3) with dopamine-regulated plasticity is demonstrated. Dopamine oxidation facilitated locally at the channel surface initiates a charge transfer mechanism between the molecule and the oxide, altering the channel conductance and successfully emulating the tunable synaptic weight by neurotransmitter activity. The oxygen level of the channel is shown to heavily affect the device's electrochemical properties, shifting from a nonreactive metallic characteristic to highly responsive semiconducting behavior. Controllable responsivity is achieved by optimizing the channel's dimension, which allows the devices to operate in wide ranges of dopamine concentration, from 100 nM to sub-mM levels, with excellent selectivity compared with K+, Na+, and Ca2+.

Monitoring the Effects Brought By a Drug on Myocardial Cells Using Field Effect Transistor (FET) Based Sensing Platform

: Ion channels are the membrane proteins that modulate the active flow of ions between cellular environment. These therapeutic targets are expressed in every active cell and can be used as important targets for cellular changes. The ion channels play an important role in different physiological processes including blood regulation, cell proliferation, nerve relaxation, etc. Various cardiac and neurological diseases have been reported to be related to ion channel regulation. They are brought through by the ion channel mutations. Several techniques are currently deployed for monitoring drug effectiveness of ion channels. Among these techniques, patch clamp technology is considered as a golden standard for monitoring the ion channel function. Unfortunately, the conventional patch clamp technologies are not enough to be employed in the early stages of drug discovery. Similarly, serval fluorescence detection methods and combination technologies have been developed for calcium ion channel detection. These assays are not suitable for large scale detection due to less selectivity and sensitivity.At present, field-effect transistor-based biosensors (BioFETs) have been widely employed in various applications due to their non-invasive detection, and high sensitivity. In this work, we adopted an extended gated EDL-FET platform for rapid drug screening on myocardial cell lines (H9c2). The drug effectiveness was studied by tested nifedipine on myocardial cells which were mounted over an EDL-FET platform. Two different surface conditions were studied using Ca2+ treatment and the capability the of EDL-FET sensor as a drug screening platform was discussed.Surface functionalization and Measurements An extended gate chip was used as the sensor array. Before probe immobilization, the sensor electrode was treated with oxygen plasma. Cell attachment over the sensor platform was facilitated using a glycoprotein- Fibronectin. Traut’s reagent was used to modify fibronectin to initiate the covalent attachment to the sensor surface. Optical images and electrical readings were taken to ensure proper functionalization of the fibronectin-attached surface before the cells were seeded over it. Myocardial cells (H9c2 cells), removed from their culture media, were incubated over the functionalized electrodes for ~2 hours following which, electrical measurements were taken to establish a baseline reading using the BioFET device. Different concentrations of nifedipine [0 to 50 μM] and calcium ions [18 μM to 1.8 mM] were used to make testing solutions, which were used for monitoring various changes occurring on the ion channels of the myocardial cells. Figure 1

Acinetobacter Baumannii Detection Using A Bio-FET Device: Towards Healthcare Infection Management

Acinetobacter is a group of bacteria commonly found in the environment, like in soil and water. While there are many types, the most common cause of infections is Acinetobacter baumannii, which accounts for most Acinetobacter infections in humans.Acinetobacter baumannii could result in infections in the blood, urinary tract, in wounds of the body or lungs. Traditionally, medical technicians in hospital use the sample from patients (like stool, urine, or sputum) to streak on a plate or do bacteria culture test. It takes too much time and patients cannot wait so long. Therefore, it is vital that a new diagnostic technique can be used to detect Acinetobacter baumannii much faster than the traditional methods.The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) is a fast and promising diagnostic technique because it is highly sensitive, quickly response, and high selective to the target analyte. Besides, a portable device could help the medical personnel detect the bacteria and treat the patients as early as possible. Here, we used a portable BioFET device from STARX co. (Model II) to detect the complementary Deoxyribonucleic acid (DNA) of Acinetobacter Baumannii via a specific DNA probe we designed. We utilized the portable device to examine the specificity and selectivity in various conditions, such as urine and blood. Thus, the results showed that the system with the portable device could give the hospital personnel a tool to control healthcare associated infection caused by Acinetobacter baumannii. Figure 1

Acinetobacter Baumannii Detection Using A Bio-FET Device: Towards Healthcare Infection Management

This study highlights the need for a fast and sensitive diagnostic technique for detecting Acinetobacter baumannii, a common cause of healthcare infections. The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) is a promising tool that can detect the bacteria quickly and with high sensitivity. Using a portable BioFET device, we designed a specific DNA probe to detect the complementary DNA of Acinetobacter baumannii, which was conjugated with red fluorescence Cy3 to compare sensitivity between bioFET and fluorescent system. The results showed that the device can detect much lower concentration of cDNA than the fluorescent system, indicating its potential as a tool for detecting healthcare-associated infections caused by Acinetobacter baumannii. Thus, the use of portable BioFET devices could improve patient outcomes and reduce the risk of hospital-acquired infections.

Rapid Escherichia coli Cloned DNA Detection in Serum Using an Electrical Double Layer-Gated Field-Effect Transistor-Based DNA Sensor.

In this study, a rapid diagnosis platform was developed for the detection of Escherichia coli O157:H7. An electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) as a point-of-care testing device is demonstrated with its high sensitivity, portability, high selectivity, quick response, and ease of use. The specially designed ssDNA probe was immobilized on the extended gate electrode to bind the target complementary DNA segment of E. coli, resulting in a sharp drain current change within minutes. The limit of detection for target DNA is validated to a concentration of 1 fM in buffer solution and serum. Meanwhile, the results of a Kelvin probe force microscope were shown to have reduced surface potential of the DNA immobilized sensors before and after the cDNA detection, which is consistent with the decreased drain current of the BioFET. A 1.2 kb E. coli duplex DNA synthesized in plasmid was sonicated and detected in serum samples with the sensor array. Gel electrophoresis was used to confirm the efficiency of sonication by elucidating the length of DNA. Those results show that the EDL-gated BioFET system is a promising platform for rapid identification of pathogens for future clinical needs.

Discovery of a Peptide Nucleic Acid (PNA) aptamer for cardiac troponin I: Substituting DNA with neutral PNA maintains picomolar affinity and improves performances for electronic sensing with graphene field-effect transistors (gFET)

DNA-based aptamers are widely employed as bioreceptors, owing to their tuneable affinity and specificity towards their targets. The use of peptide nucleic acids (PNAs) has instead proven challenging for this purpose, due to the absence of selection methods for the independent discovery of suitable receptors and due to the difficult mimicry of established DNA-based ones. Despite that PNAs exceed homologous DNA or RNA in terms of complementary base pairing, they can fail to reproduce alternative modes of binding because of their different structural features. The remarkable stability and charge distribution of PNAs could be beneficial to produce sensing bioreceptors, especially in the development of electronic devices such as field-effect transistor-based (FET) biosensors. We hereby report for the first time a high-affinity PNA aptamer for cardiac Troponin I (cTnI), a biomarker of acute myocardial infarction, able to interact with this specific protein in the picomolar range. The PNA aptamer was immobilized onto a graphene-based FET (gFET) transducer, and its ability in the direct detection of cTnI was compared with that of a DNA-based one of the same sequence. Similar dissociation constants were recorded for both receptors in 0.01 × PBS, as well as comparable detection limits of 6.0 ± 1.0 pg mL-1 (PNA aptamer) and 3.3 ± 0.7 pg mL-1 (DNA aptamer). Apart from the non-trivial demonstration that a PNA can behave as an aptamer, the tested receptor proved to be more consistent upon working in more complex biological matrices.

Carbon dots-functionalized extended gate organic field effect transistor-based biosensors for low abundance proteins.

Organic field effect transistors have emerged as promising platforms for biosensing applications. However, the challenge lies in optimizing functionalization strategies for the sensing interface, enabling the simultaneous detection of low abundance proteins while maintaining device performance. Here, we designed a carbon dots-functionalized extended gate organic field effect transistor. Leveraging the advantages of facile synthesis, tunable modification, small particle size, and cost-effectiveness of carbon dots, we implemented their integration onto the electrode surface. Through harnessing the covalent interactions of functional groups on the surface of carbon dots, we achieved effective immobilization of low abundance proteins without compromising device performance. Consequently, this biosensor exhibits a remarkably low limit of detection of 2.7 pg mL-1 and demonstrates high selectivity for the carcinoembryonic antigen. These findings highlight the superior capabilities of carbon dots in enhancing biosensor performance and emphasize their potential for early cancer detection.

Carbon nanotube based biologically modified field effect transistors (CNT-BioFETs): A research review

In recent years, CNT-BioFETs have attracted great attention because they have been found as ideal biosensor with high selectivity, real-time response and have capability of label free detection. In this article, we present a brief overview of the CNT Field-Effect Transistor-based Biosensors, its working principle and its different types such as ENFET, ImmunoFET, DNA FET and Cell-based FET. The working principle of an n-channel CNT ISFET, the basic block of the BioFET is also discussed in brief. The use of CNT as a conducting channel is evaluated in a few examples of CNT BioFET structures with a detailed view onto its few properties including sensitivity, linear working range and limit of detection. Recent technological advances in the realm of CNT BioFET such as flexible and wearable biosensors are also examined. Keeping in view the above insight, a future prospective is provided later on how to improve the device performance whilst maintaining device miniaturization which is essential in the present More-than-Moore technology-driven world.

A DPP-DTT Field-Effect Transistor-Based Biosensor for Detecting Interleukin-6

The development of a simple, direct, and reliable approach for the rapid, specific, and sensitive determination of a protein could open up significant opportunities for the diagnosis of medical diseases. Poly[2,5-(2-octyldodecyl)-3,6-diketopyrrolopyrrole-alt-5,5-(2,5-di(thien-2-yl)thieno [3,2-b]thiophene)] (DPP-DTT) is a novel polymeric semiconducting material that can be easily fabricated into a transistor device with simple procedures. Interleukin-6 (IL-6) is a typical proinflammatory cytokine and an antiinflammatory myokine. Here, we demonstrate the first time the biosensing measurement of an antibody-immobilized DPP-DTT-based transistor for the specific detection of IL-6. The sensor shows a relatively sensitive detection range of 2.5 to 50 ng/ml. A dry sensing method is used as the detection procedure that results in a reliable sensing signal. We anticipate the results could open up significant opportunities for biosensing of proteins, and advance related diagnosis of biomarkers in diseases.

Biosensor as a novel alternative approach for early diagnosis of monkeypox virus.

Biosensor as a novel alternative approach for early diagnosis of monkeypox virus.

Glucose sensing by field-effect transistors based on interfacial hydrogelation of self-assembled peptide

Interfacial hydrogelation of peptides gated on the semiconductor channel has yet to be explored in surface chemistry and field-effect transistor-based biosensors (bio-FETs). This work reports the first example of peptidic hydrogel gated bio-FET by surface assisted self-assembly for label-free and real-time monitoring of the glucose with low limit of detection, excellent sensitivity, and good stability in mouse serum. The boric acid-containing peptide forms a hydrogel layer on the surface of In2O3, which interacts with glucose reversibly and generates boronate anions to influence the semiconductor's conductivity. The results also indicate the superiority of hydrogel gated bio-FET for real-time monitoring of glucose in complex environments and serve as a wearable device. This work illustrates a simple and fundamental strategy for integrating peptidic hydrogel with bio-FET for the real-time detection of analytes.

Sensitivity Assessment of Electrically Doped Cavity on Source Junctionless Tunnel Field-Effect Transistor-Based Biosensor

The tunnel field-effect transistor (TFET) has emerged as a promising device for biosensing applications due to band-to-band tunneling (BTBT) operation mechanism and a steep subthreshold swing. In this paper, an electrically doped cavity on source junctionless tunnel field-effect transistor (ED-CS-JLTFET)-based biosensor is proposed for label-free detection of biomolecules. In the proposed model, the electrically doped concept is enabled to reduce fabrication complexity and cost. In order to create a nano-cavity at the source region, some portion of the dielectric oxide of the polarity gate terminal is etched away. To perceive the presence of biomolecules, two important properties of biomolecules, such as dielectric constant and charge density, are incorporated throughout the simulation. The sensing performance of the proposed ED-CS-JLTFET-based biosensor has been analyzed in terms of transfer characteristics, threshold voltage and subthreshold swing. In addition, the sensitivity of the proposed biosensor has also been analyzed with respect to different fill factors (FFs), varying nano-cavity dimension and work-function of the control gate. It is found from the simulated results that the proposed ED-CS-JLTFET-based biosensor offers higher current sensitivities with neutral, positively charged and negatively charged biomolecules of [Formula: see text] (at k [Formula: see text]), [Formula: see text] (at [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]) and [Formula: see text] (at k [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]), respectively.

Earlier detection of SARS-CoV-2 infection by blood RNA signature microfluidics assay.

Earlier detection of SARS-CoV-2 infection by blood RNA signature microfluidics assay.

Detection of the O6-Carboxymethylguanine DNA Adduct in Colorectal Cancer Using a Graphene Field-Effect Transistor-Based Biosensors

Detection of the O6-Carboxymethylguanine DNA Adduct in Colorectal Cancer Using a Graphene Field-Effect Transistor-Based Biosensors

Field-Effect Transistor-Based Biosensors for Environmental and Agricultural Monitoring.

The precise monitoring of environmental contaminants and agricultural plant stress factors, respectively responsible for damages to our ecosystems and crop losses, has nowadays become a topic of uttermost importance. This is also highlighted by the recent introduction of the so-called “Sustainable Development Goals” of the United Nations, which aim at reducing pollutants while implementing more sustainable food production practices, leading to a reduced impact on all ecosystems. In this context, the standard methods currently used in these fields represent a sub-optimal solution, being expensive, laboratory-based techniques, and typically requiring trained personnel with high expertise. Recent advances in both biotechnology and material science have led to the emergence of new sensing (and biosensing) technologies, enabling low-cost, precise, and real-time detection. An especially interesting category of biosensors is represented by field-effect transistor-based biosensors (bio-FETs), which enable the possibility of performing in situ, continuous, selective, and sensitive measurements of a wide palette of different parameters of interest. Furthermore, bio-FETs offer the possibility of being fabricated using innovative and sustainable materials, employing various device configurations, each customized for a specific application. In the specific field of environmental and agricultural monitoring, the exploitation of these devices is particularly attractive as it paves the way to early detection and intervention strategies useful to limit, or even completely avoid negative outcomes (such as diseases to animals or ecosystems losses). This review focuses exactly on bio-FETs for environmental and agricultural monitoring, highlighting the recent and most relevant studies. First, bio-FET technology is introduced, followed by a detailed description of the the most commonly employed configurations, the available device fabrication techniques, as well as the specific materials and recognition elements. Then, examples of studies employing bio-FETs for environmental and agricultural monitoring are presented, highlighting in detail advantages and disadvantages of available examples. Finally, in the discussion, the major challenges to be overcome (e.g., short device lifetime, small sensitivity and selectivity in complex media) are critically presented. Despite the current limitations and challenges, this review clearly shows that bio-FETs are extremely promising for new and disruptive innovations in these areas and others.