Bio-FET

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A field-effect transistor-based biosensor, also known as a biosensor field-effect transistor (Bio-FET [1] or BioFET), field-effect biosensor (FEB), [2] or biosensor MOSFET, [3] is a field-effect transistor (based on the MOSFET structure) [3] that is gated by changes in the surface potential induced by the binding of molecules. When charged molecules, such as biomolecules, bind to the FET gate, which is usually a dielectric material, they can change the charge distribution of the underlying semiconductor material resulting in a change in conductance of the FET channel. [4] [5] A Bio-FET consists of two main compartments: one is the biological recognition element and the other is the field-effect transistor. [1] [6] The BioFET structure is largely based on the ion-sensitive field-effect transistor (ISFET), a type of metal–oxide–semiconductor field-effect transistor (MOSFET) where the metal gate is replaced by an ion-sensitive membrane, electrolyte solution, and reference electrode. [7]

Contents

In a typical BioFET, an electrically and chemically insulating layer (e.g. Silica) separates the analyte solution from the semiconducting device. A polymer layer, most commonly APTES, is used to chemically link the surface to a receptor which is specific to the analyte (e.g. biotin or an antibody). Upon binding of the analyte, changes in the electrostatic potential at the surface of the electrolyte-insulator layer occur, which in turn results in an electrostatic gating effect of the semiconductor device, and a measurable change in current between the source and drain electrodes. BioFET.jpg
In a typical BioFET, an electrically and chemically insulating layer (e.g. Silica) separates the analyte solution from the semiconducting device. A polymer layer, most commonly APTES, is used to chemically link the surface to a receptor which is specific to the analyte (e.g. biotin or an antibody). Upon binding of the analyte, changes in the electrostatic potential at the surface of the electrolyte-insulator layer occur, which in turn results in an electrostatic gating effect of the semiconductor device, and a measurable change in current between the source and drain electrodes.

Mechanism of operation

Bio-FETs couple a transistor device with a bio-sensitive layer that can specifically detect bio-molecules such as nucleic acids and proteins. A Bio-FET system consists of a semiconducting field-effect transistor that acts as a transducer separated by an insulator layer (e.g. SiO2) from the biological recognition element (e.g. receptors or probe molecules) which are selective to the target molecule called analyte. [8] Once the analyte binds to the recognition element, the charge distribution at the surface changes with a corresponding change in the electrostatic surface potential of the semiconductor. This change in the surface potential of the semiconductor acts like a gate voltage would in a traditional MOSFET, i.e. changing the amount of current that can flow between the source and drain electrodes. [9] This change in current (or conductance) can be measured, thus the binding of the analyte can be detected. The precise relationship between the current and analyte concentration depends upon the region of transistor operation. [10]

Fabrication of Bio-FET

The fabrication of Bio-FET system consists of several steps as follows:

  1. Finding a substrate suitable for serving as a FET site, and forming a FET on the substrate,
  2. Exposing an active site of the FET from the substrate,
  3. Providing a sensing film layer on active site of FET,
  4. Providing a receptor on the sensing film layer in order to be used for ion detection,
  5. Removing a semiconductor layer, and thinning a dielectric layer,
  6. Etching the remaining portion of the dielectric layer to expose an active site of the FET,
  7. Removing the photoresist, and depositing a sensing film layer followed by formation of a photoresist pattern on the sensing film,
  8. Etching the unprotected portion of the sensing film layer, and removing the photoresist [11]

Advantages

The principle of operation of Bio-FET devices based on detecting changes in electrostatic potential due to binding of analyte. This the same mechanism of operation as glass electrode sensors which also detect changes in surface potential but were developed as early as the 1920s. Due to the small magnitude of the changes in surface potential upon binding of biomolecules or changing pH, glass electrodes require a high impedance amplifier which increases the size and cost of the device. In contrast, the advantage of Bio-FET devices is that they operate as an intrinsic amplifier, converting small changes in surface potential to large changes in current (through the transistor component) without the need for additional circuitry. This means BioFETs have the capability to be much smaller and more affordable than glass electrode-based biosensors. If the transistor is operated in the subthreshold region, then an exponential increase in current is expected for a unit change in surface potential.

Bio-FETs can be used for detection in fields such as medical diagnostics, [12] [11] biological research, environmental protection and food analysis. Conventional measurements like optical, spectrometric, electrochemical, and SPR measurements can also be used to analyze biological molecules. Nevertheless, these conventional methods are relatively time-consuming and expensive, involving multi-stage processes and also not compatible to real-time monitoring, [13] in contrast to Bio-FETs. Bio-FETs are low weight, low cost of mass production, small size and compatible with commercial planar processes for large-scale circuitry. They can be easily integrated into digital microfluidic devices for Lab-on-a-chip. For example, a microfluidic device can control sample droplet transport whilst enabling detection of bio-molecules, signal processing, and the data transmission, using an all-in-one chip. [14] Bio-FET also does not require any labeling step, [13] and simply utilise a specific molecular (e.g. antibody, ssDNA [15] ) on the sensor surface to provide selectivity. Some Bio-FETs display fascinating electronic and optical properties. An example FET would is a glucose-sensitive based on the modification of the gate surface of ISFET with SiO2 nanoparticles and the enzyme glucose oxidase (GOD); this device showed obviously enhanced sensitivity and extended lifetime compared with that without SiO2 nanoparticles. [16]

Bio-FETs are classified based on the bio recognition element used for detection: En-FET which is an enzyme-modified FET, Immuno-FET which is an immunologically modified FET, DNA-FET which is a DNA-modified FET, CPFET which is cell-potential FET, beetle/chip FET and artificial BioFET-based. Classification of BioFET.jpg
Bio-FETs are classified based on the bio recognition element used for detection: En-FET which is an enzyme-modified FET, Immuno-FET which is an immunologically modified FET, DNA-FET which is a DNA-modified FET, CPFET which is cell-potential FET, beetle/chip FET and artificial BioFET-based.

Optimization

The choice of reference electrode (liquid gate) or back-gate voltage determines the carrier concentration within the field effect transistor, and therefore its region of operation, therefore the response of the device can be optimised by tuning the gate voltage. If the transistor is operated in the subthreshold region then an exponential increase in current is expected for a unit change in surface potential. The response is often reported as the change in current on analyte binding divided by the initial current (), and this value is always maximal in the subthreshold region of operation due to this exponential amplification. [10] [17] [18] [19] For most devices, optimum signal-to-noise, defined as change in current divided by the baseline noise, () is also obtained when operating in the subthreshold region, [10] [20] however as the noise sources vary between devices, this is device dependent. [21]

One optimization of Bio-FET may be to put a hydrophobic passivation surface on the source and the drain to reduce non-specific biomolecular binding to regions which are not the sensing-surface. [22] [23] Many other optimisation strategies have been reviewed in the literature. [10] [24] [25]

History

1957, Diagram of one of the SiO2 transistor devices made by Frosch and Derick 1957(Figure 9)-Gate oxide transistor by Frosch and Derrick.png
1957, Diagram of one of the SiO2 transistor devices made by Frosch and Derick

The MOSFET was invented at Bell Labs between 1955 and 1960, after Frosch and Derick discovered surface passivation by silicon dioxide and used their finding to create the first planar transistors, the first in which drain and source were adjacent at the same surface. [27] [28] [29] [30] [31] [32]

In 1962, Leland C. Clark and Champ Lyons invented the first biosensor. [33] [34] Biosensor MOSFETs (BioFETs) were later developed, and they have since been widely used to measure physical, chemical, biological and environmental parameters. [3]

The first BioFET was the ion-sensitive field-effect transistor (ISFET), invented by Piet Bergveld for electrochemical and biological applications in 1970. [35] [36] Other early BioFETs include the adsorption FET (ADFET) patented by P.F. Cox in 1974, and a hydrogen-sensitive MOSFET demonstrated by I. Lundstrom, M.S. Shivaraman, C.S. Svenson and L. Lundkvist in 1975. [3] The ISFET is a special type of MOSFET with a gate at a certain distance, [3] and where the metal gate is replaced by an ion-sensitive membrane, electrolyte solution and reference electrode. [37] The ISFET is widely used in biomedical applications, such as the detection of DNA hybridization, biomarker detection from blood, antibody detection, glucose measurement, pH sensing, and genetic technology. [37]

By the mid-1980s, other BioFETs had been developed, including the gas sensor FET (GASFET), pressure sensor FET (PRESSFET), chemical field-effect transistor (ChemFET), reference ISFET (REFET), enzyme-modified FET (ENFET) and immunologically modified FET (IMFET). [3] By the early 2000s, BioFETs such as the DNA field-effect transistor (DNAFET), gene-modified FET (GenFET), and cell-potential BioFET (CPFET) had been developed. [37] Current research in this area has produced new formations of the BioFET such as the Organic Electrolyte Gated FET (OEGFET). [38]

See also

Related Research Articles

<span class="mw-page-title-main">Transistor</span> Solid-state electrically operated switch also used as an amplifier

A transistor is a semiconductor device used to amplify or switch electrical signals and power. It is one of the basic building blocks of modern electronics. It is composed of semiconductor material, usually with at least three terminals for connection to an electronic circuit. A voltage or current applied to one pair of the transistor's terminals controls the current through another pair of terminals. Because the controlled (output) power can be higher than the controlling (input) power, a transistor can amplify a signal. Some transistors are packaged individually, but many more in miniature form are found embedded in integrated circuits. Because transistors are the key active components in practically all modern electronics, many people consider them one of the 20th century's greatest inventions.

<span class="mw-page-title-main">MOSFET</span> Type of field-effect transistor

In electronics, the metal–oxide–semiconductor field-effect transistor is a type of field-effect transistor (FET), most commonly fabricated by the controlled oxidation of silicon. It has an insulated gate, the voltage of which determines the conductivity of the device. This ability to change conductivity with the amount of applied voltage can be used for amplifying or switching electronic signals. The term metal–insulator–semiconductor field-effect transistor (MISFET) is almost synonymous with MOSFET. Another near-synonym is insulated-gate field-effect transistor (IGFET).

<span class="mw-page-title-main">Sensor</span> Converter that measures a physical quantity and converts it into a signal

A sensor is a device that produces an output signal for the purpose of detecting a physical phenomenon.

A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The sensitive biological element, e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc., is a biologically derived material or biomimetic component that interacts with, binds with, or recognizes the analyte under study. The biologically sensitive elements can also be created by biological engineering. The transducer or the detector element, which transforms one signal into another one, works in a physicochemical way: optical, piezoelectric, electrochemical, electrochemiluminescence etc., resulting from the interaction of the analyte with the biological element, to easily measure and quantify. The biosensor reader device connects with the associated electronics or signal processors that are primarily responsible for the display of the results in a user-friendly way. This sometimes accounts for the most expensive part of the sensor device, however it is possible to generate a user friendly display that includes transducer and sensitive element. The readers are usually custom-designed and manufactured to suit the different working principles of biosensors.

<span class="mw-page-title-main">High-electron-mobility transistor</span> Type of field-effect transistor

A high-electron-mobility transistor, also known as heterostructure FET (HFET) or modulation-doped FET (MODFET), is a field-effect transistor incorporating a junction between two materials with different band gaps as the channel instead of a doped region. A commonly used material combination is GaAs with AlGaAs, though there is wide variation, dependent on the application of the device. Devices incorporating more indium generally show better high-frequency performance, while in recent years, gallium nitride HEMTs have attracted attention due to their high-power performance.

<span class="mw-page-title-main">Organic field-effect transistor</span> Type of field-effect transistor

An organic field-effect transistor (OFET) is a field-effect transistor using an organic semiconductor in its channel. OFETs can be prepared either by vacuum evaporation of small molecules, by solution-casting of polymers or small molecules, or by mechanical transfer of a peeled single-crystalline organic layer onto a substrate. These devices have been developed to realize low-cost, large-area electronic products and biodegradable electronics. OFETs have been fabricated with various device geometries. The most commonly used device geometry is bottom gate with top drain and source electrodes, because this geometry is similar to the thin-film silicon transistor (TFT) using thermally grown SiO2 as gate dielectric. Organic polymers, such as poly(methyl-methacrylate) (PMMA), can also be used as dielectric. One of the benefits of OFETs, especially compared with inorganic TFTs, is their unprecedented physical flexibility, which leads to biocompatible applications, for instance in the future health care industry of personalized biomedicines and bioelectronics.

<span class="mw-page-title-main">ISFET</span> Type of field-effect transistor

An ion-sensitive field-effect transistor (ISFET) is a field-effect transistor used for measuring ion concentrations in solution; when the ion concentration (such as H+, see pH scale) changes, the current through the transistor will change accordingly. Here, the solution is used as the gate electrode. A voltage between substrate and oxide surfaces arises due to an ion sheath. It is a special type of MOSFET (metal–oxide–semiconductor field-effect transistor), and shares the same basic structure, but with the metal gate replaced by an ion-sensitive membrane, electrolyte solution and reference electrode. Invented in 1970, the ISFET was the first biosensor FET (BioFET).

A ChemFET is a chemically-sensitive field-effect transistor, that is a field-effect transistor used as a sensor for measuring chemical concentrations in solution. When the target analyte concentration changes, the current through the transistor will change accordingly. Here, the analyte solution separates the source and gate electrodes. A concentration gradient between the solution and the gate electrode arises due to a semi-permeable membrane on the FET surface containing receptor moieties that preferentially bind the target analyte. This concentration gradient of charged analyte ions creates a chemical potential between the source and gate, which is in turn measured by the FET.

<span class="mw-page-title-main">History of biotechnology</span>

Biotechnology is the application of scientific and engineering principles to the processing of materials by biological agents to provide goods and services. From its inception, biotechnology has maintained a close relationship with society. Although now most often associated with the development of drugs, historically biotechnology has been principally associated with food, addressing such issues as malnutrition and famine. The history of biotechnology begins with zymotechnology, which commenced with a focus on brewing techniques for beer. By World War I, however, zymotechnology would expand to tackle larger industrial issues, and the potential of industrial fermentation gave rise to biotechnology. However, both the single-cell protein and gasohol projects failed to progress due to varying issues including public resistance, a changing economic scene, and shifts in political power.

<span class="mw-page-title-main">Multigate device</span> MOS field-effect transistor with more than one gate

A multigate device, multi-gate MOSFET or multi-gate field-effect transistor (MuGFET) refers to a metal–oxide–semiconductor field-effect transistor (MOSFET) that has more than one gate on a single transistor. The multiple gates may be controlled by a single gate electrode, wherein the multiple gate surfaces act electrically as a single gate, or by independent gate electrodes. A multigate device employing independent gate electrodes is sometimes called a multiple-independent-gate field-effect transistor (MIGFET). The most widely used multi-gate devices are the FinFET and the GAAFET, which are non-planar transistors, or 3D transistors.

<span class="mw-page-title-main">Biointerface</span>

A biointerface is the region of contact between a biomolecule, cell, biological tissue or living organism or organic material considered living with another biomaterial or inorganic/organic material. The motivation for biointerface science stems from the urgent need to increase the understanding of interactions between biomolecules and surfaces. The behavior of complex macromolecular systems at materials interfaces are important in the fields of biology, biotechnology, diagnostics, and medicine. Biointerface science is a multidisciplinary field in which biochemists who synthesize novel classes of biomolecules cooperate with scientists who have developed the tools to position biomolecules with molecular precision, scientists who have developed new spectroscopic techniques to interrogate these molecules at the solid-liquid interface, and people who integrate these into functional devices. Well-designed biointerfaces would facilitate desirable interactions by providing optimized surfaces where biological matter can interact with other inorganic or organic materials, such as by promoting cell and tissue adhesion onto a surface.

<span class="mw-page-title-main">Bio-MEMS</span>

Bio-MEMS is an abbreviation for biomedical microelectromechanical systems. Bio-MEMS have considerable overlap, and is sometimes considered synonymous, with lab-on-a-chip (LOC) and micro total analysis systems (μTAS). Bio-MEMS is typically more focused on mechanical parts and microfabrication technologies made suitable for biological applications. On the other hand, lab-on-a-chip is concerned with miniaturization and integration of laboratory processes and experiments into single chips. In this definition, lab-on-a-chip devices do not strictly have biological applications, although most do or are amenable to be adapted for biological purposes. Similarly, micro total analysis systems may not have biological applications in mind, and are usually dedicated to chemical analysis. A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions. The interdisciplinary nature of bio-MEMS combines material sciences, clinical sciences, medicine, surgery, electrical engineering, mechanical engineering, optical engineering, chemical engineering, and biomedical engineering. Some of its major applications include genomics, proteomics, molecular diagnostics, point-of-care diagnostics, tissue engineering, single cell analysis and implantable microdevices.

A biotransducer is the recognition-transduction component of a biosensor system. It consists of two intimately coupled parts; a bio-recognition layer and a physicochemical transducer, which acting together converts a biochemical signal to an electronic or optical signal. The bio-recognition layer typically contains an enzyme or another binding protein such as antibody. However, oligonucleotide sequences, sub-cellular fragments such as organelles and receptor carrying fragments, single whole cells, small numbers of cells on synthetic scaffolds, or thin slices of animal or plant tissues, may also comprise the bio-recognition layer. It gives the biosensor selectivity and specificity. The physicochemical transducer is typically in intimate and controlled contact with the recognition layer. As a result of the presence and biochemical action of the analyte, a physico-chemical change is produced within the biorecognition layer that is measured by the physicochemical transducer producing a signal that is proportionate to the concentration of the analyte. The physicochemical transducer may be electrochemical, optical, electronic, gravimetric, pyroelectric or piezoelectric. Based on the type of biotransducer, biosensors can be classified as shown to the right.

<span class="mw-page-title-main">Field-effect transistor</span> Type of transistor

The field-effect transistor (FET) is a type of transistor that uses an electric field to control the current through a semiconductor. It comes in two types: junction FET (JFET) and metal-oxide-semiconductor FET (MOSFET). FETs have three terminals: source, gate, and drain. FETs control the current by the application of a voltage to the gate, which in turn alters the conductivity between the drain and source.

<span class="mw-page-title-main">Chemiresistor</span> Material with changing electrical resistance according to its surroundings

A chemiresistor is a material that changes its electrical resistance in response to changes in the nearby chemical environment. Chemiresistors are a class of chemical sensors that rely on the direct chemical interaction between the sensing material and the analyte. The sensing material and the analyte can interact by covalent bonding, hydrogen bonding, or molecular recognition. Several different materials have chemiresistor properties: semiconducting metal oxides, some conductive polymers, and nanomaterials like graphene, carbon nanotubes and nanoparticles. Typically these materials are used as partially selective sensors in devices like electronic tongues or electronic noses.

Piet Bergveld is a Dutch electrical engineer. He was professor of biosensors at the University of Twente between 1983 and 2003. He is the inventor of the ion-sensitive field-effect transistor (ISFET) sensor. Bergveld's work has focused on electrical engineering and biomedical technology.

<span class="mw-page-title-main">Deblina Sarkar</span> Indian scientist and inventor

Deblina Sarkar is an electrical engineer, and inventor. She is an assistant professor at the Massachusetts Institute of Technology (MIT) and the AT&T Career Development Chair Professor of the MIT Media Lab. Sarkar has been internationally recognized for her invention of an ultra thin quantum mechanical transistor that can be scaled to nano-sizes and used in nanoelectronic biosensors. As the principal investigator of the Nano Cybernetic Biotrek Lab at MIT, Sarkar leads a multidisciplinary team of researchers towards bridging the gap between nanotechnology and synthetic biology to build new nano-devices and life-machine interfacing technologies with which to probe and enhance biological function.

A chemical sensor array is a sensor architecture with multiple sensor components that create a pattern for analyte detection from the additive responses of individual sensor components. There exist several types of chemical sensor arrays including electronic, optical, acoustic wave, and potentiometric devices. These chemical sensor arrays can employ multiple sensor types that are cross-reactive or tuned to sense specific analytes.

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