Direct label-free protein detection in high ionic strength solution and human plasma using dual-gate nanoribbon-based ion-sensitive field-effect transistor biosensor (original) (raw)
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Analytical Chemistry, 2016
The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilising an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerisation. The polymerisation resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/ml with a linear detection range from 0.1 pg/ml to 1 ng/ml PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.
Scientific reports, 2017
In this study, a new type of field-effect transistor (FET)-based biosensor is demonstrated to be able to overcome the problem of severe charge-screening effect caused by high ionic strength in solution and detect proteins in physiological environment. Antibody or aptamer-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) are used to directly detect proteins, including HIV-1 RT, CEA, NT-proBNP and CRP, in 1X PBS (with 1%BSA) or human sera. The samples do not need any dilution or washing process to reduce the ionic strength. The sensor shows high sensitivity and the detection takes only 5 minutes. The designs of the sensor, the methodology of the measurement, and the working mechanism of the sensor are discussed and investigated. A theoretical model is proposed based on the finding of the experiments. This sensor is promising for point-of-care, home healthcare, and mobile diagnostic device.
Bulletin of the Korean Chemical Society
In this study, we have developed a new detection method using Si field effect transistor (FET)-type biosensors, which enables the direct monitoring of antigen-antibody binding within very high-ionic-strength solutions such as 1×PBS and human serum. In the new method, as no additional dilution or desalting processes are required, the FET-type biosensors can be more suitable for ultrasensitive and real-time analysis of raw sample solutions. The new detection scheme is based on the observation that the strength of antigen-antibody-specific binding is significantly influenced by the ionic strength of the reaction solutions. For a prostate specific antigen (PSA), in some conditions, the binding reaction between PSA and anti-PSA in a low-ionic strength reaction solution such as 10 µM phosphate buffer is weak (reversible), while that in high-ionic strength reaction solutions such as 1×PBS or human serum is strong.
The region ion sensitive field effect transistor, a novel bioelectronic nanosensor
Biosensors and Bioelectronics, 2007
A novel type of bioelectronic region ion sensitive field effect transistor (RISFET) nanosensor was constructed and demonstrated on two different sensor chips that could measure glucose with good linearity in the range of 0-0.6 mM and 0-0.3 mM with a limit of detection of 0.1 and 0.04 mM, respectively. The sensor is based on the principle of focusing charged reaction products with an electrical field in a region between the sensing electrodes. For glucose measurements, negatively charged gluconate ions were gathered between the sensing electrodes. The signal current response was measured using a low-noise pico ammeter (pA). Two different sizes of the RISFET sensor chips were constructed using conventional electron beam lithography. The measurements are done in partial volumes mainly restricted by the working distance between the sensing electrodes (790 and 2500 nm, respectively) and the influence of electrical fields that are concentrating the ions. The sensitivity was 28 pA/mM (2500 nm) and 830 pA/mM (790 nm), respectively. That is an increase in field strength by five times between the sensing electrodes increased the sensitivity by 30 times. The volumes expressed in this way are in low or sub femtoliter range. Preliminary studies revealed that with suitable modification and control of parameters such as the electric control signals and the chip electrode dimensions this sensor could also be used as a nanobiosensor by applying single enzyme molecule trapping. Hypotheses are given for impedance factors of the RISFET conducting channel.
Review—Field-Effect Transistor Biosensing: Devices and Clinical Applications
ECS Journal of Solid State Science and Technology, 2018
Biosensor research has been addressed as an interested field recently. Within different kinds of developed biosensing technologies, field-effect transistor (FET) based biosensors stand out due to their attractive features, such as ultra-sensitivity detection, massproduction capability, and low-cost manufacturing. To promote understandings of the FET based biosensing technology, in this review, its sensing mechanism is introduced, as well as major FET-based biosensing devices: ion sensitive field-effect transistor (ISFET), silicon nanowire, organic FET, graphene FET, and compound-semiconductor FET. In addition to FET-based biosensing devices, clinical applications, such as cardiovascular diseases (CVDs), cancers, diabetes, HIV, and DNA sequence, are also reviewed. In the end, several critical challenges of FET-based biosensing technology are discussed to envision next steps in healthcare technologies.
Dual-gate polysilicon nanoribbon biosensors enable high sensitivity detection of proteins
We demonstrate the advantages of dual-gate polysilicon nanoribbon biosensors with a comprehensive evaluation of different measurement schemes for pH and protein sensing. In particular, we compare the detection of voltage and current changes when top- and bottom-gate bias is applied. Measurements of pH show that a large voltage shift of 491 mV pH −1 is obtained in the subthreshold region when the top-gate is kept at a fixed potential and the bottom-gate is varied (voltage sweep). This is an improvement of 16 times over the 30 mV pH −1 measured using a top-gate sweep with the bottom-gate at a fixed potential. A similar large voltage shift of 175 mV is obtained when the protein avidin is sensed using a bottom-gate sweep. This is an improvement of 20 times compared with the 8.8 mV achieved from a top-gate sweep. Current measurements using bottom-gate sweeps do not deliver the same signal amplification as when using bottom-gate sweeps to measure voltage shifts. Thus, for detecting a small signal change on protein binding, it is advantageous to employ a double-gate transistor and to measure a voltage shift using a bottom-gate sweep. For top-gate sweeps, the use of a dual-gate transistor enables the current sensitivity to be enhanced by applying a negative bias to the bottom-gate to reduce the carrier concentration in the nanoribbon. For pH measurements, the current sensitivity increases from 65% to 149% and for avidin sensing it increases from 1.4% to 2.5%.
Enhanced biosensing resolution with foundry fabricated individually addressable dual-gated ISFETs
2014
The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In contrast to conventional SOI ISFETs, each transistor has an individually addressable back-gate and a gate oxide that is directly exposed to the solution. The elimination of the commonly used floating gate architecture reduces the chance of electrostatic discharge and increases the potential achievable transistor density. We show that when operated in a "dualgate" mode, the transistor response can exhibit sensitivities to pH changes beyond the Nernst limit. This enhancement in sensitivity was shown to increase the sensor's signal-to-noise ratio, allowing the device to resolve smaller pH changes. An improved resolution can be used to enhance small signals and increase the sensor accuracy when monitoring small pH dynamics in biological reactions. As a proof of concept, we demonstrate that the amplified sensitivity and improved resolution result in a shorter detection time and a larger output signal of a loop-mediated isothermal DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing benefits of the new structure for biosensing applications.
Biosensors and Bioelectronics, 2016
We have demonstrated label-free and real-time detection of prostate specific antigen (PSA) in human serum using silicon nanowire field effect transistors (NW FETs) with Schottky contacts (Si-Ti). The NW FETs were fabricated from SOI material using high-resolution e-beam lithography, thin film vacuum deposition and reactive-ion etching processes eliminating complicated processes of doping and thermal annealing. This allowed substantial simplifying the transistors manufacturing. A new method for covalent immobilization of half-fragments of antibodies on silicon modified by 3-glycidopropyltrimethoxysilane with thiol groups and 5 nm gold nanoparticles (GNPs) was established. NW FETs functionalized by GNPs revealed extremely high pH sensitivity of 70 mV/pH and enhanced electrical performance in the detection of antigen due to enhanced surface/volume ratio, favorable orientation of antibody active sites and approaching the source of the electric field close to the transistor surface. Si NWFETs were applied for quantitative detection of PSA in a buffer and human serum diluted 1/100. Response time was about 5-10 s, and analysis time per sample was 1 min. The limit of PSA detection was of 23 fg/mL, concentration range of 23 fg/mL-500 ng/mL (7 orders of magnitude). The PSA concentrations determined by the NW FETs in serum were compared with well-established ELISA method. The results matched well with the correlation coefficient of 0.97.
A comprehensive Analysis of Nanoscale Transistor Based Biosensor: A Review
2021
Imperative introduction of biosensor in the field of medicine, defence, food safety, security and environmental contamination detection acquired paramount attraction. Thus the foundation of the fame of biosensors in detecting wide scope of biomolecules in innumerable fields has driven researchers in advancement of biosensor and enhancing more updates in devices. Among all semiconductor-FET based biosensors grab attraction due to their miniaturization, mass production, ultra-sensitive in nature, improved lifetime, rapid response and reduce thermal budgets. In this review, field effect based biosensors sensitive to ions their principle model along with pros and cons of different structures. Various performance characteristics for semiconductor based biosensor are explored along with detection of label free analytes such as tuberculosis, glucose, antigen 85-B with ISFET. Following with comprehensive detail on MOSFET junction less Silicon based Dual Gate Biosensor with their design para...
Small, 2010
Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field-effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening. A general solution to this limitation with the development of a hybrid nanoelectronic enzyme-linked immunosorbent assay (ne-ELISA) that combines the power of enzymatic conversion of a bound substrate with electronic detection is demonstrated. This novel configuration produces a local enzyme-mediated pH change proportional to the bound ligand concentration. It is shown that nanowire FETs configured as pH sensors can be used for the quantitative detection of interleukin-2 in physiologically buffered solution at concentrations as low as 1.6 pg mL À1. By successfully bypassing the Debye screening inherent in physiological fluids, the ne-ELISA promises wide applicability for ligand detection in a range of relevant solutions.