Label-free sub-picomolar protein detection with extended-gate field-effect transistors (original) (raw)
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Direct Protein Detection with a Nano-Interdigitated Gate MOSFET
A new protein sensor is demonstrated by replacing the gate of a metal oxide semiconductor field effect transistor (MOSFET) with a nano-interdigitated array (nIDA). The sensor is able to detect the binding reaction of a typical antibody Ixodes ricinus immunosuppressor (anti-Iris) protein at a concentration lower than 1 ng/ml. The sensor exhibits a high selectivity and reproducible specific detection. We provide a simple model that describes the behavior of the sensor and explains the origin of its high sensitivity. The simulated and experimental results indicate that the drain current of nIDA-gate MOSFET sensor is significantly increased with the successive binding of the thiol layer, Iris and anti-Iris protein layers. It is found that the sensor detection limit can be improved by well optimizing the geometrical parameters of nIDA-gate MOSFET. This nanobiosensor, with real-time and label-free capabilities, can easily be used for the detection of other proteins, DNA, virus and cancer markers. Moreover, an on-chip associated electronics nearby the sensor can be integrated since its fabrication is compatible with complementary metal oxide semiconductor (CMOS) technology.
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Sensors
During recent years, field-effect transistor biosensors (Bio-FET) for biomedical applications have experienced a robust development with evolutions in FET characteristics as well as modification of bio-receptor structures. This review initially provides contemplation on this progress by briefly summarizing remarkable studies on two aforementioned aspects. The former includes fabricating unprecedented nanostructures and employing novel materials for FET transducers whereas the latter primarily synthesizes compact molecules as bio-probes (antibody fragments and aptamers). Afterwards, a future perspective on research of FET-biosensors is also predicted depending on current situations as well as its great demand in clinical trials of disease diagnosis. From these points of view, FET-biosensors with infinite advantages are expected to continuously advance as one of the most promising tools for biomedical applications.
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Science (New York, N.Y.), 2018
Detection of analytes with field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the "Debye length" limitation). We detected small molecules under physiological high ionic-strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphinghosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.
Predicting Future Prospects of Aptamers in Field-Effect Transistor Biosensors
Molecules, 2020
Aptamers, in sensing technology, are famous for their role as receptors in versatile applications due to their high specificity and selectivity to a wide range of targets including proteins, small molecules, oligonucleotides, metal ions, viruses, and cells. The outburst of field-effect transistors provides a label-free detection and ultra-sensitive technique with significantly improved results in terms of detection of substances. However, their combination in this field is challenged by several factors. Recent advances in the discovery of aptamers and studies of Field-Effect Transistor (FET) aptasensors overcome these limitations and potentially expand the dominance of aptamers in the biosensor market.
Nanoscale, 2012
The combination of optimized and passivated Field Effect Transistors (FETs) based on carbon nanotubes (CNTs) together with the appropriate choice and immobilization strategy of aptamer receptors and buffer concentration have allowed the highly sensitive and real time biorecognition of proteins in a liquid-gated configuration. Specifically we have followed the biorecognition process of thrombin by its specific aptamer. The aptamer modified device is sensitive enough to capture a change in the electronic detection mechanism, one operating at low protein concentrations and the other in a higher target concentration range. The high sensitivity of the device is also sustained by the very low detection limits achieved (20 pM) and their high selectivity when other target proteins are used. Moreover, the experimental results have allowed us to quantify the equilibrium constant of the proteinaptamer binding and confirm its high affinity by using the Langmuir equation.
EGOFET Peptide Aptasensor for Label-Free Detection of Inflammatory Cytokines in Complex Fluids
Advanced Biosystems
Organic electronic transistors are rapidly emerging as ultra-high sensitive label-free biosensors suited for point of care or in-field deployed applications. Most organic biosensors reported to date are based on immunorecognition between the relevant biomarkers and the immobilized antibodies, whose use is hindered by large dimensions, poor control of sequence and relative instability. Here, we report an Electrolyte Gated Organic Field Effect Transistor (EGOFET) biosensor where the recognition units are surface immobilized peptide aptamers (Affimerä proteins) instead of antibodies. We demonstrate our peptide aptasensor for the detection of the pro-inflammatory cytokine Tumor Necrosis Factor alpha (TNFa) with a 1pM limit of detection. Ultra-low sensitivity is met even in complex solutions such as cell culture media containing 10 % serum, demonstrating the remarkable ligand specificity of our device. The device performances, together with the simple one-step immobilization strategy of the recognition moieties and the low operational voltages, all prompt EGOFET peptide aptasensors as candidates for early diagnostics and monitoring at the point-of-care.
2010
Semiconductor field effect transistors (FETs) are widely used as biosensors, although a potentially powerful application of FET sensing technology (planar immunoFETs sensing proteins at physiological salt concentrations) has long been argued to be intrinsically infeasible. The infeasibility assessment has come under increasing scrutiny of late, and has been found to be lacking on conceptual and empirical grounds. This paper summarizes some, but, by no means all, of the strategies that have been pursued to render the use of immunoFETs, and analogous FET sensors that detect the electrical fields of proteins bound to affinity elements on FET sensing channels (protein-sensing bioFETs), practical in high-salt biological buffers. This paper provides original characterization of oxidized AlGaN surfaces and interfacial polymer/protein films of protein-sensing AlGaN/GaN HFETs. It shows those films to influence significantly FET sensitivity/signal accumulation. The data indicate that re-assessment of the classical assertion of immunoFET infeasibility is long overdue. Beyond substantiating the feasibility of immunoFET operation under solution conditions as found in vivo, data presented here also suggest that transition away from costly AlGaN/GaN HFETs to inexpensive silicon-based immunoMOSFETs may be possible. If so, immunoFETs, dismissed as infeasible 20 years ago, may yet become powerful clinical tools.
Fabrication of BioFET linear array for detection of protein interactions
Microelectronic Engineering, 2010
An extended-gate MOSFETs (metal-oxide-semiconductor field-effect transistors) based biosensing linear array has been fabricated for label-free protein interaction detection. The device was realized using a combination of very low leakage current MOSFET transistors and an external gate where the chemical reaction would take place. Peptide aptamers that recognize cyclin-dependent kinase (CDK), a protein cancer marker, were used as a biological test system. The test results showed a high sensitive in the detection of CDK.