Nanowire Field-effect Transistor Biosensors Research Articles

A Calibration Strategy for Silicon Nanowire Field-Effect Transistor Biosensors and Its Application in Ultra-Sensitive, Label-Free Biosensing.

The silicon nanowire field-effect transistor (SiNW FET) has been developed for over two decades as an ultrasensitive, label-free biosensor for biodetection. However, inconsistencies in manufacturing and surface functionalization at the nanoscale have led to poor sensor-to-sensor consistency in performance. Despite extensive efforts to address this issue through process improvements and calibration methods, the outcomes have not been satisfactory. Herein, based on the strong correlation between the saturation response of SiNW FET biosensors and both their feature size and surface functionalization, we propose a calibration strategy that combines the sensing principles of SiNW FET with the Langmuir-Freundlich model. By normalizing the response of the SiNW FET biosensors (ΔI/I0) with their saturation response (ΔI/I0)max, this strategy fundamentally overcomes the issues mentioned above. It has enabled label-free detection of nucleic acids, proteins, and exosomes within 5 min, achieving detection limits as low as attomoles and demonstrating a significant reduction in the coefficient of variation. Notably, the nucleic acid test results exhibit a strong correlation with the ultraviolet-visible (UV-vis) spectrophotometer measurements, with a correlation coefficient reaching 0.933. The proposed saturation response calibration strategy exhibits good universality and practicability in biological detection applications, providing theoretical and experimental support for the transition of mass-manufactured nanosensors from theoretical research to practical application.

Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.

Polyethylene Glycol Functionalized Silicon Nanowire Field-Effect Transistor Biosensor for Glucose Detection.

Accurate monitoring of blood glucose levels is crucial for the diagnosis of diabetes patients. In this paper, we proposed a simple "mixed-catalyzer layer" modified silicon nanowire field-effect transistor biosensor that enabled direct detection of glucose with low-charge in high ionic strength solutions. A stable screening system was established to overcome Debye screening effect by forming a porous biopolymer layer with polyethylene glycol (PEG) modified on the surface of SiNW. The experimental results show that when the optimal ratio (APTMS:silane-PEG = 2:1) modified the surface of silicon nanowires, glucose oxidase can detect glucose in the concentration range of 10 nM to 10 mM. The sensitivity of the biosensor is calculated to be 0.47 μAcm-2mM-1, its fast response time not exceeding 8 s, and the detection limit is up to 10 nM. This glucose sensor has the advantages of high sensitivity, strong specificity and fast real-time response. Therefore, it has a potential clinical application prospect in disease diagnosis.

Silicon Nanowires Length and Numbers Dependence on Sensitivity of the Field-Effect Transistor Sensor for Hepatitis B Virus Surface Antigen Detection.

Silicon nanowire field effect transistor (NWFET) sensors have been demonstrated to have high sensitivity, are label free, and offer specific detection. This study explored the effect of nanowire dimensions on sensors’ sensitivity. We used sidewall spacer etching to fabricate polycrystalline silicon NWFET sensors. This method does not require expensive nanoscale exposure systems and reduces fabrication costs. We designed transistor sensors with nanowires of various lengths and numbers. Hepatitis B surface antigen (HBsAg) was used as the sensing target to explore the relationships of nanowire length and number with biomolecule detection. The experimental results revealed that the sensor with a 3 µm nanowire exhibited high sensitivity in detecting low concentrations of HBsAg. However, the sensor reached saturation when the biomolecule concentration exceeded 800 fg/mL. Sensors with 1.6 and 5 µm nanowires exhibited favorable linear sensing ranges at concentrations from 800 ag/mL to 800 pg/mL. The results regarding the number of nanowires revealed that the use of few nanowires in transistor sensors increases sensitivity. The results demonstrate the effects of nanowire dimensions on the silicon NWFET biosensors.

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.

A new biosensor detection system to overcome the Debye screening effect: dialysis-silicon nanowire field effect transistor.

Background: A silicon nanowire field effect transistor biosensor has four advantages in the detection of small biomolecules. It is mark-free, immediately responsive, highly sensitive, and specific. However, because of environments with a high salt concentration, the Debye screening effect has been a major issue in biological detection.Objective: To overcome Debye screening effect, realize the clinical application of silicon nanowire field effect transistor and verify its specificity and sensitivity.Materials and methods: The test solution was desalted by miniature blood dialyzer, and then the tumor markers were detected by silicon nanowire field effect transistor.Results: Tumor markers in serum were detected successfully and their sensitivity and specificity were verified.Conclusion: This method was found to effectively promote the development of semiconductor materials in biological solution detection.

The impact of the modified Poisson–Boltzmann model on protein bound to a lipid coated silicon nanowire field effect transistor biosensor in an electrolyte environment

ABSTRACTThe aim of this work was to analyse the electrostatic potential profile, various effects of electrolyte concentrations, and the influences of surface charge on a protein bound to a lipid coated Silicon nanowire field effect transistor (Si-NW FET) biosensor by implementing the modified Poisson–Boltzmann (MPB) model. In this work, we modelled a lipid monolayer-coated Si-NW FET for the sensing of proteins, which consisted of variable amounts of aspartic acid. The electrostatic potential profile, protein charge distributions, the response to various electrolyte concentration, and the impacts of various surface charge were studied by implementing the MPB model with the Si-NW FET biosensor. Additionally, a comparison between the use of the MPB and the Poisson–Boltzmann model in studying the effects of various surface charges was carried out. Taken together, it was found that the MPB model showed a higher resolution in studying the Si-NW FET biosensor model when higher concentrations and surface charges were administered.

Ultrasensitive nanowire-based detection of HCVcoreAg in the serum using a microwave generator

The detection of a hepatitis C protein marker – core antigen of hepatitis C virus (HCVcoreAg) with a nanowire field-effect transistor biosensor, coupled with a microwave generator, has been studied.

Hepatocellular Carcinoma Diagnosis by Detecting α-Fucosidase with a Silicon Nanowire Field-Effect Transistor Biosensor

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal cancers. However, traditional clinical imaging modalities cannot detect small tumors and are not suitable for the early stage diagnosis of hepatic cancer. In this study, we applied silicon nanowire field-effect transistors (SiNW-FETs) as a biosensor to detect α-fucosidase (AFU), which is a biomarker of high sensitivity and specificity for the HCC diagnosis. Fuconojirimycin (FNJ) is an inhibitor of AFU with very high binding affinity to AFU. By modifying the FNJs of optimized receptor length and number density on SiNW-FET (referred to as FNJ/SiNW-FET), this biosensing device can detect AFU to a very low concentration level with the detection limit of ∼1.3 pM. With the merits of high sensitivity, target specificity, and label-free detection, this FNJ/SiNW-FET can be developed as a powerful biosensor to detect AFU for the early HCC diagnosis.

Charge and dielectric effects of biomolecules on electrical characteristics of nanowire FET biosensors

The sensing mechanism of nanowire field effect transistor (NWFET) biosensors is investigated by taking into consideration both the charge and dielectric effects of biomolecules. The dielectric effect of the biomolecules is dominantly reflected in the linear regime, whereas the charge property is manifested in the subthreshold regime. The findings are supported by bio-experiments and numerical simulations. This study provides a rudimentary means of understanding interactions between biomolecules and NWFET biosensors.

Nanotechnology for the diagnosis and treatment of diseases.

Nanotechnology for the diagnosis and treatment of diseases.

Semiconductor Electronic Label-Free Assay for Predictive Toxicology.

While animal experimentations have spearheaded numerous breakthroughs in biomedicine, they also have spawned many logistical concerns in providing toxicity screening for copious new materials. Their prioritization is premised on performing cellular-level screening in vitro. Among the screening assays, secretomic assay with high sensitivity, analytical throughput, and simplicity is of prime importance. Here, we build on the over 3-decade-long progress on transistor biosensing and develop the holistic assay platform and procedure called semiconductor electronic label-free assay (SELFA). We demonstrate that SELFA, which incorporates an amplifying nanowire field-effect transistor biosensor, is able to offer superior sensitivity, similar selectivity, and shorter turnaround time compared to standard enzyme-linked immunosorbent assay (ELISA). We deploy SELFA secretomics to predict the inflammatory potential of eleven engineered nanomaterials in vitro, and validate the results with confocal microscopy in vitro and confirmatory animal experiment in vivo. This work provides a foundation for high-sensitivity label-free assay utility in predictive toxicology.

A comparison between bipolar transistor and nanowire field effect transistor biosensors

Important performance metrics, such as sensitivity and signal to noise ratio (SNR) of bipolar transistor based biosensors, are compared to those for nanowire field effect transistor (FET) sensors. The sensor consists of a heterojunction bipolar transistor (HBT) with silicon germanium base connected to a sensing surface in contact with the solution. The measured sensitivity is ≥2 times and SNR is >20 times higher in comparison to those for nanowire FET sensors. More importantly, the HBT biosensor sensitivity is constant over the sensing range of ∼5 decades and depends only on the temperature. In comparison, the nanowire FET sensor sensitivity varies in a complex manner over the sensing range and exhibits significant fabrication induced sensor to sensor variations. Consequently, HBT sensors would require minimal calibration for quantitative sensing studies. Furthermore, the bipolar transistor SNR is not only significantly higher but is also constant over the sensing range. In comparison, the nanowire FET sensor SNR varies with the peak value confined over a narrow sensing range. Hence, HBT sensor has <20 times lower detection limit that remains constant over the sensing range. In summary, HBT sensors are demonstrated to have superior performance metrics and are better suited for quantitative studies. Lastly, these HBT sensors also provide simultaneous temperature measurement.

(Invited) Planar Field Effect Transistor Biosensors: Toward Single Molecular Detection and Clinical Applications

Field effect transistor (FET) based biosensors that can translate directly specific bindings between receptors and target analytes to electrical signals have attracted considerable interests for label free, rapid, low-cost detection of biomolecules. However, it is challenging to detect biomarkers at low concentrations in physiological buffers with high ionic strengths due to the small Debye length. FET biosensors on a planar configuration are highly preferable because of the process compatibility with microelectronic manufacturing. III-nitride semiconductor materials have been considered as a promising candidate for biosensing applications due to their unique properties, such as chemical inertness, non-toxicity, and excellent thermal stability. In particular, III-nitrides FETs are ion-impermeable and highly stable in electrolytes, making them ideal for detection at ultralow concentrations in fluids with high ionic strengths. Here we present a recessed gate planar AlGaN/GaN heterojunction FET (HFET) for biodetection. The gate area of the AlGaN/GaN HFET was recessed by inductively coupled plasma (ICP) etching to shift the threshold voltage to near zero volt regime for sensitivity enhancement. As such, the device works at the subthreshold regime. The biosensing measurement was performed on a non-bias gate setting to eliminate the noise and electrochemical activities from the gate electrode. The signal-to-noise ratio of these recessed AlGaN/GaN FET biosensors is two orders of magnitude higher than that of the Si nanowire FET biosensors previously reported. Detection of streptavidin at concentration of 16 aM in PBS physiological buffer has been demonstrated. To the best of our knowledge, this is the highest sensitivity ever reported on a field effect-based biosensor in physiological buffer. These devices have demonstrated their potential in biochemical and clinical applications. We have successfully detected MIG (monokine induced by interferon gamma, an indicator of transplant rejection in patients when detected at a concentration level above nano Molar) in clinical samples. Utilizing of ion impermeable semiconductors like GaN opens up opportunities of FET-based biosensors for direct detection of biomarkers in physiological fluids at low concentrations for early disease diagnosis with excellent manufacturing compatibility.

Real-Time and Label-Free Detection of the Prostate-Specific Antigen in Human Serum by a Polycrystalline Silicon Nanowire Field-Effect Transistor Biosensor

In this research, we used a polycrystalline silicon nanowire field-effect transistor (poly-Si NWFET) as a biosensor that employs the sidewall spacer technique instead of an expensive electron beam lithography method. When compared with commercial semiconductor processes, the sidewall spacer technique has the advantages of simplicity and low cost. In this study, we employed a novel poly-Si NWFET device for real-time, label-free, and ultrahigh-sensitivity detection of prostate-specific antigen (PSA) in human serum. Since serum proteome is very complex containing high levels of salts and other interfering compounds, we hereby developed a standard operating procedure for real-sample pretreatment to keep a proper pH value and ionic strength of the desalted serum and also utilized Tween 20 to serve as the passivation agent by surface modification on the NWFET to reduce nonspecific binding for medical diagnostic applications. We first modified 3-aminopropyltriethoxysilane on the surface of a poly-Si nanowire device followed by glutaraldehyde functionalization, and the PSA antibodies were immobilized on the aldehyde terminal. While PSA was prepared in the buffers to maintain an appropriate pH value and ionic strength, the results indicated that the sensor could detect trace PSA at less than 5 fg/mL in a microfluidic channel. The novel poly-Si NWFET is developed as a diagnostic platform for monitoring prostate cancer and predicting the risk of early biochemical relapse.

Enhanced Sensing of Nucleic Acids with Silicon Nanowire Field Effect Transistor Biosensors

Silicon nanowire (SiNW) field effect transistors (FETs) have emerged as powerful sensors for ultrasensitive, direct electrical readout, and label-free biological/chemical detection. The sensing mechanism of SiNW-FET can be understood in terms of the change in charge density at the SiNW surface after hybridization. So far, there have been limited systematic studies on fundamental factors related to device sensitivity to further make clear the overall effect on sensing sensitivity. Here, we present an analytical result for our triangle cross-section wire for predicting the sensitivity of nanowire surface-charge sensors. It was confirmed through sensing experiments that the back-gated SiNW-FET sensor had the highest percentage current response in the subthreshold regime and the sensor performance could be optimized in low buffer ionic strength and at moderate probe concentration. The optimized SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of target DNA with a detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism discrimination. In our work, enhanced sensing of biological species by optimization of operating parameters and fundamental understanding for SiNW FET detection limit was obtained.

Fabrication of Silicon Nanowire Field-Effect Transistor Biosensor by CMOS Compatible Top-Down Approach with Descum Process

Fabrication of Silicon Nanowire Field-Effect Transistor Biosensor by CMOS Compatible Top-Down Approach with Descum Process