Graphene Field-effect Transistor Biosensor Based on Avidin-Biotin Interaction

学位記番号：理工博甲7

Interfacial Design of Field Effect Transistor Biosensor for Protein Determination

制度:新 ; 報告番号:甲3318号 ; 学位の種類:博士(工学) ; 授与年月日:2011/3/15 ; 早大学位記番号:新562

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 Road Map toward Field-Effect Transistor Biosensor Technology for Early Stage Cancer Detection

Field effect transistor (FET)-based nanoelectronic biosensor devices provide a viable route for specific and sensitive detection of cancer biomarkers, which can be used for early stage cancer detection, monitoring the progress of the disease, and evaluating the effectiveness of therapies. On the road to implementation of FET-based devices in cancer diagnostics, several key issues need to be addressed: sensitivity, selectivity, operational conditions, anti-interference, reusability, reproducibility, disposability, large-scale production, and economic viability. To address these well-known issues, significant research efforts have been made recently. An overview of these efforts is provided here, highlighting the approaches and strategies presently engaged at each developmental stage, from the design and fabrication of devices to performance evaluation and data analysis. Specifically, this review discusses the multistep fabrication of FETs, choice of bioreceptors for relevant biomarkers, operational conditions, measurement configuration, and outlines strategies to improve the sensing performance and reach the level required for clinical applications. Finally, this review outlines the expected progress to the future generation of FET-based diagnostic devices and discusses their potential for detection of cancer biomarkers as well as biomarkers of other noncommunicable and communicable diseases

A high aspect ratio Fin-Ion Sensitive Field Effect Transistor: compromises towards better electrochemical bio-sensing

The development of next generation medicines demand more sensitive and reliable label free sensing able to cope with increasing needs of multiplexing and shorter times to results. Field effect transistor-based biosensors emerge as one of the main possible technologies to cover the existing gap. The general trend for the sensors has been miniaturisation with the expectation of improving sensitivity and response time, but presenting issues with reproducibility and noise level. Here we propose a Fin-Field Effect Transistor (FinFET) with a high heigth to width aspect ratio for electrochemical biosensing solving the issue of nanosensors in terms of reproducibility and noise, while keeping the fast response time. We fabricated different devices and characterised their performance with their response to the pH changes that fitted to a Nernst-Poisson model. The experimental data were compared with simulations of devices with different aspect ratio, stablishing an advantage in total signal and linearity for the FinFETs with higher aspect ratio. In addition, these FinFETs promise the optimisation of reliability and efficiency in terms of limits of detection, for which the interplay of the size and geometry of the sensor with the diffusion of the analytes plays a pivotal role.Comment: Article submitted to Nano Letter

Recent progress on fabrication of zinc oxide nanorod-based field effect transistor biosensors

Zinc oxide is a unique n-type semiconducting material, owing to wide bandgap of ~3.37 eV, non-toxic, bio-safe and biocompatible with high isoelectric point of ~9.5, make it as promising biomaterial to be utilized as sensing matrix in biosensor applications. In addition, ZnO that possess high electron affinity provide a good conduction pathway for the electrons hence result in significant electrical signal change upon detection to target biomolecules. Moreover, high surface area of ZnO nanorod enhance immobilization of enzymes, hence, increase the device performance. Field effect transistor (FET)-based biosensor offer simplicity in handling and label-free, has also become research topic among researchers for novel biosensor development. This review aims to explore the preparation of ZnO nanorod using hydrothermal method and investigate the fabrication of ZnO nanorod-based FET biosensor. Thus, contribute to enhance understanding towards biosensor development for health monitoring, especially based on FETs structure devices

Graphene-based field-effect transistor biosensors for the rapid detection and analysis of viruses: A perspective in view of COVID-19

Current situation of COVID-19 demands a rapid, reliable, cost-effective, facile detection strategy to break the transmission chain and biosensor has emerged as a feasible solution for this purpose. Introduction of nanomaterials has undoubtedly improved the performance of biosensor and the addition of graphene enhanced the sensing ability to a peerless level. Amongst different graphene-based biosensing schemes, graphene field-effect transistor marked its unique presence owing to its ability of ultrasensitive and low-noise detection thereby facilitating instantaneous measurements even in the presence of small amounts of analytes. Recently, graphene field-effect transistor type biosensor is even successfully employed in rapid detection of SARS-CoV-2 and this triggers the interest of the scientific community in reviewing the current developments in graphene field-effect transistor. Subsequently, in this article, the recent progress in graphene field-effect transistor type biosensors for the detection of the virus is reviewed and challenges along with their strengths are discussed.Comment: COVID-19, Biosensor, Graphene Field-effect transistor, Virus detectio

Signal amplification in electrochemical detection of buckwheat allergenic protein using field effect transistor biosensor by introduction of anionic surfactant

AbstractFood allergens, especially buckwheat proteins, sometimes induce anaphylactic shock in patients after ingestion. Development of a simple and rapid screening method based on a field effect transistor (FET) biosensor for food allergens in food facilities or products is in demand. In this study, we achieved the FET detection of a buckwheat allergenic protein (BWp16), which is not charged enough to be electrically detected by FET biosensors, by introducing additional negative charges from anionic surfactants to the target proteins. A change in the FET characteristics reflecting surface potential caused by the adsorption of target charged proteins was observed when the target sample was coupled with the anionic surfactant (sodium dodecyl sulfate; SDS), while no significant response was detected without any surfactant treatment. It was suggested that the surfactant conjugated with the protein could be useful for the charge amplification of the target proteins. The surface plasmon resonance analysis revealed that the SDS-coupled proteins were successfully captured by the receptors immobilized on the sensing surface. Additionally, we obtained the FET responses at various concentrations of BWp16 ranging from 1ng/mL to 10μg/mL. These results suggest that a signal amplification method for FET biosensing is useful for allergen detection in the food industry

High-sensitive Low Power Tunneling Field Effect Transistor Biosensor for Multiplexed Sensing Application

학위논문 (박사)-- 서울대학교 대학원 : 전기·정보공학부, 2017. 2. 박병국.As fabrication technology has continued to develop, various nano-size biomedical sensors have been widely researched since the size of biological entities, such as DNA, proteins, and viruses are similar to their size. Especially, chemical and biomedical sensors using fluorescent labeling and parallel optical detection techniques have received much attention for high sensitivity. However, they have a number of drawbacks such as expensive and time-consuming processes for sample preparation and data analysis. To overcome these limitations, silicon nanowire (SiNW) Ion Sensitive Field Effect Transistors (ISFET) have been proposed as one of the most promising chemical/biomedical sensors since it has good characteristics such as label-free, real-time detection, and excellent sensitivity caused by high surface-to-volume ratio. In terms of the fabrication process, SiNW ISFETs also have compatibility with CMOS technology. Various fabrication methods of SiNW ISFETs have been reported. Recently, our group demonstrated a novel SiNW MOSFET sensor which can be integrated with a CMOS device by using top-down fabrication process. However, the proposed top-down process cannot avoid the damage of the sensing material by the plasma damage because the sensing area is formed by the dry-etch process, which leads to the degradation of the sensitivity and the current drift. Furthermore, it is impossible to fine-tune the various threshold voltages (Vth) of the circuit devices by the implant process, which results in circuit malfunction and reduction in amplification factor. In this thesis, the novel top-down approached fabrication method using top SiO2-SiN-bottom SiO2 (ONO) dielectric stacks is proposed and implemented to obtain sensors with defect-free sensing oxide and Vth-tunable devices in CMOS read-out circuits. By wet-etching the top SiO2 and the SiN, the sensor with defect-free sensing oxide is obtained. Also, the Vth-tunable circuit devices with the ONO stacks are simultaneously achieved by protecting the ONO stacks from the wet-etching. Through the measurements of pH response and current drift in the sensor and program operations in the circuit device, it is confirmed that the pH/biomolecule response and the current drift of the sensor are improved and the Vth of the circuit device can be fine-controlled. Although the defect-free sensing material improves the drift and the sensitivity, the MOSFET sensor has a theoretical limitation on the maximum sensitivity because MOSFETs cannot implement sub-60mV/dec SS at room temperature. To achieve the higher sensitivity, a TFET sensor is proposed and fabricated since it can achieve sub-kT/qS at room temperature by using band-to-band tunneling as carrier injection mechanism. From TCAD simulations, it is revealed that the TFET sensor has two ID saturations by the saturation of the source-to-channel tunneling width and the drain-side carrier injection. Moreover, it is experimentally confirmed that the TFET sensor is the superior sensitivity up to the first ID saturation region and there is no difference in sensitivity from the second ID saturation region as compared to the MOSFET sensor. Finally, the possibility of multiplexed sensing is verified with the fabricated MOSFET and TFET sensors. To form two different sensing materials reacted with GBP-Ala/Anti-AI and SBP-H1N1/Anit-H1N1 for the multiplexed-sensing, gold is partially covered on the SiO2 by a lift-off process. Then, the changes of saturation and GIDL current are monitored in the MOSFET sensor after the reactions of GBP-Ala/Anti-AI (SBP-H1N1/Anit-H1N1) to the gold (SiO2). Two different biomolecules are independently detected by the changes in the saturation and the GIDL currents. To solve the problems of the MOSFET sensor by the dependence of the gold formation position on the sensitivity and the large current difference between the saturation and the GIDL currents, the changes of tunneling and ambipolar currents are measured in the TFET sensor. As a result, it is revealed that two different biomolecules can be detected without interference regardless of the position of the gold layer by the changes of the tunneling and ambipolar currents with almost equivalent current level.Chapter 1 Introduction 1 1.1 SINW ISFET CO-INTEGRATED WITH CMOS READ-OUT CIRCUITS 1 1.2 ISSUES IN TOP-DOWN APPROACHED SINW-CMOS HYBRID SYSTEM 3 1.3 SENSITIVITY IMPROVEMENT 4 1.4 SCOPE OF THESIS 7 Chapter 2 Process Flow and Biomolecules/pH Measurement Setting 10 2.1 PROCESS FLOW OF TOP-DOWN APPROACHED MOSFET/TFET SENSORS-CMOS HYBRID SYSTEM 10 2.2 FABRICATION TEST OF CRITICAL UNIT PROCESS 15 2.3 INVESTIGATION OF FABRICATED DEVICES 21 2.4 SURFACE TREATEMENT AND MEASURENMENT SETTING 24 Chapter 3 Co-integration of Sensors with Defect-free Sensing Material and Vth-tunable Devices 27 3.1 CONCEPT OF ISFET 27 3.2 PROBLEMS IN SENSING AREA ETCHING PROCESS 31 3.3 FABRICATION PROCESS USING ONO DIELECTRIC STACKS 32 3.3 ELECTRICAL CHARACTERISTICS OF DEVICES USING ONO STACKS 40 Chapter 4 TFET Sensor 45 4.1 SENSITIVITY SIMULATION 45 4.2 MEASUREMENTS OF FABRICATED TFET SENSOR 50 Chapter 5 Multiplexed Sensing 56 4.1 CONCEPT OF MULTIPLEXED SENSING 56 4.2 MULTIPLEXED SENSING IN MOSFET SENSOR 58 4.3 FABRICATION PROCESS AND BIOMOLECULES REACTION 59 4.4 MULTIPLEXED SENSING MEASUREMENTS IN MOSFET SENSOR 62 4.5 MULTIPLEXED SENSING IN TFET SENSOR 65 Chapter 6 71 Conclusions 71 Bibliography 74 Korean Abstract 82Docto