Field Effect Transistor Biosensor Research Articles

ZnO Nanorod FET Biosensors With Enhanced Sensing Performance: Design Issues for Rational Geometry Selection

ZnO nanorod field effect transistor (FET) biosensors enable ultrasensitive, rapid and label free detection of biomolecules. However, the fabrication of these nanorods without any design guideline results in poor signal to noise ratio, limiting their commercial deployment. The various forces operating within the spacing of the nanorods may prevent complete penetration of the liquid for large aspect ratios and hence mere enhancement of the geometric surface area may not yield the optimum output which indicates the intricacies involved in the design of such sensors. The present work consistently models the analyte and the device regions of the sensor by transforming the understanding of the transduction mechanism of biomolecule capture in nanowire FETs into nanorod FET structure and integrating the spacing dependent liquid penetration depth along with the various temporal fluctuations of the sensor to enhance the signal to noise ratio ( SNR ) and lower the molecule detection limit(MDL). Simulation results, verified experimentally for prostate specific antigen (PSA) shows that the optimal geometry does not correspond to the maximum surface area. Instead it is dependent on the developed surface potentials after receptor immobilization and ligand capture which vary non-monotonically with nanorod radius due to nonlinear dependence of buffer penetration for high aspect ratios. This approach has significantly increased the SNR leading to reliable quantification of PSA in human serum with MDL reduced by almost three orders of magnitude in comparison to recent reports. In summary, this work brings the ZnO nanorod sensors a step closer towards practical application for early diagnosis.

Profound analysis on sensing performance of Nanogap SiGe source DM-TFET biosensor

This present work is an extensive effort to report the key role of indispensable technical challenges in the sensing performance of an embedded nanogap SiGe source dielectric-modulated tunnel field effect transistor (SGS-DM-TFET) biosensor during the conjugation of biological samples for the first time. In order to reach high and brilliant insights into the different design considerations impacting on the sensing performance of the biosensor under the study, two key issues in terms of process-related issue and real-time-related issues covering biomolecules manners in the nanogap cavity of the biosensor have been comprehensively studied through extensive numerical simulation. Investigations in this work revealed that the SGS-DM-TFET biosensor must be truly configured for working in realistic conditions. The obtained results give us a useful guideline for sensing the biomolecules samples in the real conditions including low coverage percentage of biological samples, charge effect, and discrete probe position with the help of SGS-DM-TFET biosensor while keeping the high sensitivity.

Evaluating Insect Odorant Receptor Display Formats for Biosensing Using Graphene Field Effect Transistors

Graphene field effect transistor (GFET) biosensors have been used to evaluate insect odorant receptor (OR) display formats and the effect of the presence of the Orco subunit on in vitro sensing usi...

Split gated silicon nanotube FET for bio‐sensing applications

A split gated silicon nanotube field-effect transistor (FET) biosensor has been proposed for the label free detection of the biomolecules for the first time in literature. The sensitivity of the sensing device has been analysed considering the on current (ION) and the threshold voltage (Vth) variation. Sub-threshold regime has been considered here to detect the charged/neutral biomolecules. Extensive simulations have been done using the SILVACO ATLAS. Sensitivity analysis has been carried out by considering half-filled and full-filled nanogaps with the neutral or charged biomolecules inside the cavity. Significant sensitivity and excellent reduction in short-channel effects has been observed in proposed biosensor.

Analysis of interactions between proteins and small-molecule drugs by a biosensor based on a graphene field-effect transistor

We synthesized large-area single-crystal graphene sheets to use them in biosensors based on field-effect transistors (FET) for quantitative analysis of interaction kinetics and affinity between the imatinib drug and its target protein kinase Abl1. The G-FET biosensor showed an excellent performance and recognized imatinib at as low as 15.5 fM. The biosensor also showed a linear response to the logarithm of imatinib concentration in the 0.1 pM-10 μM range. This graphene-based FET biosensor (G-FET) was also applied to quantify Abl1 Y253 F mutation and Abl1 dependency on Mg2+ to bind to imatinib in real-time. Results demonstrated in this work clearly showed that the novel G-FET biosensors are very promising to analyze interactions between proteins and low molecular weight drugs.

Design and Performance Analysis of Symmetrical and Asymmetrical Triple Gate Dopingless Vertical TFET for Biorecognition

The present paper proposes a dielectric modulation based Triple Gate Doping Less Tunnel Field Effect Transistor (TG-DLTFET) biosensor with a cavity introduced underneath the gate and source metal for symmetrical and asymmetrical device to recognize very small size biomolecules such as Amino Acids (AAs). The proposed n + pocket doped vertical device aims to achieve high sensitivity with lower short channel effects. The placement and width of the n + pocket layer within the source are reformed with the goal of acquiring the higher current switching ratio. The variation in the device’s electrical parameters (surface potential, drain current and sensitivity) corresponding to dielectric constant and charge density reflected the biorecognition process in the biosensor. Additionally, the impact of variations in device geometry (spacer length, cavity length, cavity thickness, and gate misalignment effects) on the drain current and drain current sensitivity of device have also been evaluated and reasoned, respectively. The results reflect that with proper choice of the geometric parameters, the device sensitivity can be attained up to 1010. Thus, the present findings reflected that TG-DLTFET has a better sensing capability as a biosensor, together with a low value of short channel effect and leakage current. The proposed n + pocket doped vertical device has a significant potential to detect varations in AAs and DNA.

Impact of surface defects in electron beam evaporated ZnO thin films on FET biosensing characteristics towards reliable PSA detection

In this work, the impact of surface defects in zinc oxide (ZnO) thin films on the performance of field effect transistor (FET) biosensors has been explored. Here, ZnO thin films have been fabricated using electron beam evaporation with various deposition parameters to tune the surface roughness and defect state density. The films have been deployed for sensing prostate specific antigen (PSA) after anti-PSA antibody immobilization. Interestingly, it has been observed that though the transconductance of the sensors degrade monotonically with increasing defect density, the antibody binding density has a non-monotonic behaviour due to enhanced steric hindrance effect beyond a certain limit of surface roughness. There is a variation of sensitivity by 15 times with different physical properties of ZnO and the optimized sensor has a PSA detection limit of 0.06 fM. Further, the sensor with the best sensitivity retains its performance upto 2 months while a non-optimized sensor with initial PSA detection limit of 0.1 fM has longevity of 4 months. Thus, it can be envisaged that tuning the surface defect state in ZnO FET biosensor is an essential requirement not only to ensure a low detection limit and high sensitivity but also to assure a reliable long term performance.

Direct Detection of Uranyl in Urine by Dissociation from Aptamer-Modified Nanosensor Arrays.

An ever-growing demand for uranium in various industries raises concern for human health of both occupationally exposed personnel and the general population. Toxicological effects related to uranium (natural, enriched, or depleted uranium) intake involve renal, pulmonary, neurological, skeletal, and hepatic damage. Absorbed uranium is filtered by the kidneys and excreted in the urine, thus making uranium detection in urine a primary indication for exposure and body burden assessment. Therefore, the detection of uranium contamination in bio-samples (urine, blood, saliva, etc.,) is of crucial importance in the field of occupational exposure and human health-related applications, as well as in nuclear forensics. However, the direct determination of uranium in bio-samples is challenging because of "ultra-low" concentrations of uranium, inherent matrix complexity, and sample diversity, which pose a great analytical challenge to existing detection methods. Here, we report on the direct, real-time, sensitive, and selective detection of uranyl ions in unprocessed and undiluted urine samples using a uranyl-binding aptamer-modified silicon nanowire-based field-effect transistor (SiNW-FET) biosensor, with a detection limit in the picomolar concentration range. The aptamer-modified SiNW-FET presented in this work enables the simple and sensitive detection of uranyl in urine samples. The experimental approach has a straight-forward implementation to other metals and toxic elements, given the availability of target-specific aptamers. Combining the high surface-to-volume ratio of SiNWs, the high affinity and selectivity of the uranyl-binding aptamer, and the distinctive sensing methodology gives rise to a practical platform, offering simple and straightforward sensing of uranyl levels in urine, suitable for field deployment and point-of-care applications.

Non-Carbon 2D Materials-Based Field-Effect Transistor Biosensors: Recent Advances, Challenges, and Future Perspectives.

In recent years, field-effect transistors (FETs) have been very promising for biosensor applications due to their high sensitivity, real-time applicability, scalability, and prospect of integrating measurement system on a chip. Non-carbon 2D materials, such as transition metal dichalcogenides (TMDCs), hexagonal boron nitride (h-BN), black phosphorus (BP), and metal oxides, are a group of new materials that have a huge potential in FET biosensor applications. In this work, we review the recent advances and remarkable studies of non-carbon 2D materials, in terms of their structures, preparations, properties and FET biosensor applications. We will also discuss the challenges facing non-carbon 2D materials-FET biosensors and their future perspectives.

Reduced graphene oxide-based field effect transistors for the detection of E7 protein of human papillomavirus in saliva.

Several challenging biological sensing concepts have been realized using electrolyte-gated reduced graphene oxide field effect transistors (rGO-FETs). In this work, we demonstrate the interest of rGO-FET for the sensing of human papillomavirus (HPV), one of the most common sexually transmitted viruses and a necessary factor for cervical carcinogenesis. The highly sensitive and selective detection of the HPV-16 E7 protein relies on the attractive semiconducting characteristics of pyrene-modified rGO functionalized with RNA aptamer Sc5-c3. The aptamer-functionalized rGO-FET allows for monitoring the aptamer-HPV-16 E7 protein binding in real time with a detection limit of about 100 pg mL−1 (1.75 nM) for HPV-16 E7 from five blank noise signals (95% confidence level). The feasibility of this method for clinical application in point-of-care technology is evaluated using HPV-16 E7 protein suspended in saliva and demonstrates the successful fabrication of a promising field effect transistor biosensor for HPV diagnosis.Graphical abstract

The Study of HIV-1 Vpr-Membrane and Vpr-hVDAC-1 Interactions by Graphene Field-Effect Transistor Biosensors.

The viral protein R (Vpr) of human immunodeficiency virus 1 (HIV-1) is involved in many cellular processes during the viral life cycle; however, its associated mechanisms remain unclear. Here, we designed an Escherichia coli expression construct to achieve a milligram yield of recombinant Vpr. In addition, we fabricated a graphene field-effect transistor (G-FET) biosensor, with the modification of a supported lipid bilayer (SLB), to study the interaction between Vpr and its interaction partners. The Dirac point of the SLB/G-FET was observed to shift in response to the binding of Vpr to the SLB. By fitting the normalized shift of the Dirac point as a function of Vpr concentration to the Langmuir adsorption isotherm equation, we could extract the dissociation constant (Kd) to quantify the Vpr binding affinity. When the 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG) membrane was used as the SLB, the dissociation constant was determined to be 9.6 ± 2.1 μM. In contrast, only a slight shift of the Dirac point was observed in response to the addition of Vpr when the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane was used as the SLB. Taking advantage of the much weaker binding of Vpr to the DOPC membrane, we prepared a human voltage-dependent anion channel isoform 1 (hVDAC-1)-embedded DOPC membrane as the SLB for the G-FET and used it to determine the dissociation constant to be 5.1 ± 0.9 μM. In summary, using the clinically relevant Vpr protein as an example, we demonstrated that an SLB/G-FET biosensor is a suitable tool for studying the interaction between a membrane-associated protein and its interaction partners.

A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids.

A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body.

Low frequency electrochemical noise in AlGaN/GaN field effect transistor biosensors

Little has been studied on how the electrochemical noise impacts the limit of detection of field effect transistor (FET) biosensors. Herein, we investigate low frequency noise associated with phosphate-buffered saline (PBS) solutions at varying ionic strengths (Ni) under both weak and strong gate biases corresponding to saturation and sub-threshold regimes, respectively, in AlGaN/GaN heterojunction FET biosensors. We show that the electrochemical noise is strongly dependent on the ionic strength and gate biasing conditions. In the saturation regime (low bias), varying the ionic strength (a range of 10−6× PBS to PBS 1 × stock solutions used for testing) has little to no effect on the characteristic frequency exponent β(β=1), indicating a predominately diffusion-based process. Conversely, under higher biases (sub-threshold regime), the β parameter varies from 1 to 2 with ionic strength exhibiting both diffusion and drift characteristics, with a “cut point” at approximately 10−5× PBS (Ni≈9×1014/mL). Under a high bias, once the PBS concentration reaches 10−3×, the behavior is then drift dominant. This indicates that the higher bias likely triggers electrochemical reactions and by extension, faradaic effects at most physiologically relevant ionic strengths. The signal-to-noise ratio (SNR) of the device has an inverse linear relationship with the low frequency current noise. The device exhibits a higher SNR in the sub-threshold regime than in the saturation regime. Specifically, within the saturation regime, an inversely proportional relationship between the SNR and the ionic concentration is observed. The electrochemical noise induced from ionic activities is roughly proportional to Ni−1/2.

Supported and Suspended 2D Material-Based FET Biosensors

Field Effect Transistor (FET)-based electrochemical biosensor is gaining a lot of interest due to its malleability with modern fabrication technology and the ease at which it can be integrated with modern digital electronics. To increase the sensitivity and response time of the FET-based biosensor, many semiconducting materials have been categorized, including 2 dimensional (2D) nanomaterials. These 2D materials are easy to fabricate, increase sensitivity due to the atomic layer, and are flexible for a range of biomolecule detection. Due to the atomic layer of 2D materials each device requires a supporting substrate to fabricate a biosensor. However, uneven morphology of supporting substrate leads to unreliable output from every device due to scattering effect. This review summarizes advances in 2D material-based electrochemical biosensors both in supporting and suspended configurations by using different atomic monolayer, and presents the challenges involved in supporting substrate-based 2D biosensors. In addition, we also point out the advantages of nanomaterials over bulk materials in the biosensor domain.

An Ion-Sensitive Field-Effect Transistor Biosensor Based on SWCNT and Aligned MWCNTs for Detection of ABTS

The perfect combination of biomolecules and nanomaterials is critical to achieve a biosensor with high sensitivity and selectivity. In this study, ion sensitive field effect transistor (ISFET) biosensors were fabricated based on carbon nanotube (CNT) with two different structures as the enzyme immobilization support. Laccase was immobilized over two kinds of CNT including: drop-casted single wall carbon nanotubes (SWCNTs) and forest-like multi-walled carbon nanotubes (MWCNTs) grown via Plasma-Enhanced Chemical Vapor Deposition (PECVD). The immobilization was non-covalent without any coupling agent and direct detection of 2, 2-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) was carried out. Hydrogen and oxygen plasma treatments were performed on both types of devices to assess their effect on the enzyme immobilization. To investigate CNT-laccase interaction, the fourier transform infrared (FTIR)-attenuated total reflection (ATR) analysis was performed before and after the laccase immobilization for pristine and plasma treated CNTs. Results showed that drop-casted SWCNT-based sensor with oxygen treatment has the highest sensitivity as high as 3.66 A. M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> .cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> , limit of detection (LOD) of 3 μM and linear range up to 300 μM .

Fabrication and Characterization of an Aptamer-Based N-type Silicon Nanowire FET Biosensor for VEGF Detection

Cancer detection is an important part of modern medical diagnosis and many strategies based on nanotechnology had been developed in recent years. Of which, silicon nanowire (SiNW) field-effect transistor (FET) biosensor via DNA aptamer capture is considered as an interesting and viable option. Hence, in this report, we had assembled a n-type triple SiNW FET biosensor for the detection of vascular endothelial growth factor (VEGF) via surface functionalized DNA aptamer for a proof-of-concept. The SiNW FET biosensor was fabricated via "top-down" approach and the physical nature of the nanowire assembly was examined via atomic force microscopy (AFM) as well as scanning electron microscopy (SEM). We had subsequently grafted VEGF specific DNA aptamer via conventional EDC/NHS chemistry and later measured the conductance of the nanowires in a four-point probe detector for VEGF detection. We had demonstrated that the detection of VEGF was possible even at a concentration of 2.59 nM which was highly comparable to the other common biosensors for detection of VEGF protein. In addition to being scalable with complementary metal–oxide–semiconductor (CMOS) technology, the findings as demonstrated from our simple SiNW FET biosensor setup had helped to provide better insights towards optimizing the approach for the development of the next generation of miniature biosensors.

Non-enzymatic and highly sensitive lactose detection utilizing graphene field-effect transistors

Field-effect transistor (FET) biosensors based on low-dimensional materials are capable of highly sensitive and specific label-free detection of various analytes. In this work, a FET biosensor based on graphene decorated with gold nanoparticles (Au NPs) was fabricated for lactose detection in a liquid-gate measurement configuration. This graphene device is functionalized with a carbohydrate recognition domain (CRD) of the human galectin-3 (hGal-3) protein to detect the presence of lactose from the donor effect of lectin – glycan affinity binding on the graphene. Although the detection of lactose is important because of its ubiquitous presence in food and for disease related applications (lactose intolerance condition), in this work we exploit the lectin/carbohydrate interaction to develop a device that in principle could specifically detect very low concentrations of any carbohydrate. The biosensor achieved an effective response to lactose concentrations over a dynamic range from 1 fM to 1 pM (10−15 to 10−12 mol L−1) with a detection limit of 200 aM, a significant enhancement over previous electrochemical graphene devices. The FET sensor response is also specific to lactose at aM concentrations, indicating the potential of a combined lectin and graphene FET (G-FET) sensor to detect carbohydrates at high sensitivity and specificity for disease diagnosis.

Surface functionalized β-Bi2O3 nanofibers based flexible, field-effect transistor-biosensor (BioFET) for rapid, label-free detection of serotonin in biological fluids

In this work, we demonstrate a high-performance Field effect transistor-based biosensor (BioFET) on Al functionalized β-Bi2O3 nanofibers for highly selective and rapid detection of serotonin. The β-Bi2O3 nanofibers were synthesized using electrospinning technique and conductivity was tailored by surface functionalization using Al nanoparticles. Interdigitated silver electrodes deposited over the flexible polyimide (PI) substrate acts as contact terminals and dielectric substrate respectively while Al functionalized β-Bi2O3 nanofibers acts as n-type semiconductor channel and a thermally evaporated silver electrode beneath the PI tape as a back-gate terminal. Detailed characterization reveals the formation of β-phase monoclinic, high mobility, 1-D Bi2O3 nanofibers, and Al functionalization was validated using elemental composition studies. The fabricated FET exhibited a transconductance of 5.23 μS and mobility of 64.4 cm2 V−1s−1 with an Ion/ Ioff ratio ∼106. The BioFET exhibited an excellent sensitivity of 51.64 μA/nM towards serotonin over a wide linear detection range of 10 nM- 1 μM and a limit of detection of 0.29 nM. This can be ascribed to the excellent change in surface potential upon interaction of serotonin molecules with the electroactive surface functionalized multidimensional nanoparticle-nanofiber network and the back-gate electrode-based control of the Debye screening length. The fabricated BioFET exhibits excellent sensitivity, stability and reproducibility with a rapid response time of 0.8 s. Excellent selectivity towards serotonin in the presence of interfering analytes like ascorbic acid (AA), uric acid (UA), Glucose, Na+, K+, Dopamine (DA) is observed owing to the formation of selective binding complexes between the aromatic amine and β-Bi2O3. The real-time applicability of the sensor was successfully tested using urine samples as a test matrix thus establishing it as a promising platform for label free detection of biomolecules in point-of care diagnostics.

Tetrameric jacalin as a receptor for field effect transistor biosensor to detect secretory IgA in human sweat

Secretory immunoglobulin A (s-IgA), found in biological fluids, is useful for monitoring condition on mental health to prevent depression. In this study, the non-invasive detection of s-IgA in human sweat was demonstrated using field effect transistor (FET) biosensors modified with a plant lectin, jacalin, as a receptor. The s-IgA molecules were detected with greater sensitivity using the jacalin-immobilized FET biosensors as compared to the sensitivity shown by Fab-immobilized FET biosensors. Jacalin, which is a small lectin tetramer, has four glycan-binding sites and can capture a large number of s-IgA molecules within the charge-detectable region in terms of Debye length. Moreover, the jacalin-immobilized FET biosensor could detect s-IgA at concentrations ranging from 0.1 μg/mL to 100 μg/mL. Additionally, by using a filtration process to eliminate the interference of other components found in human sweat, our FET sensing system could specifically and quantitatively detect s-IgA. Therefore, our results show the utility of this device in monitoring mental stress.

Wafer-Scale Uniform Carbon Nanotube Transistors for Ultrasensitive and Label-Free Detection of Disease Biomarkers.

Carbon nanotube (CNT) field-effect transistor (FET)-based biosensors have shown great potential for ultrasensitive biomarker detection, but challenges remain, which include unsatisfactory sensitivity, difficulty in stable functionalization, incompatibility with scalable fabrication, and nonuniform performance. Here, we describe ultrasensitive, label-free, and stable FET biosensors built on polymer-sorted high-purity semiconducting CNT films with wafer-scale fabrication and high uniformity. With a floating gate (FG) structure using an ultrathin Y2O3 high-κ dielectric layer, the CNT FET biosensors show amplified response and improved sensitivity compared with those sensors without Y2O3, which is attributed to the chemical gate-coupling effect dominating the sensor response. The CNT FG-FETs are modified to selectively detect specific disease biomarkers, namely, DNA sequences and microvesicles, with theoretical record detection limits as low as 60 aM and 6 particles/mL, respectively. Furthermore, the biosensors exhibit highly uniform performance over the 4 in. wafer as well as superior bias stress stability. The FG CNT FET biosensors could be extended as a universal biosensor platform for the ultrasensitive detection of multiple biological molecules and applied in highly integrated and multiplexed all CNT-FET-based sensor architectures.