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An ion-sensitive field-effect transistor (ISFET) is a
field-effect transistor The field-effect transistor (FET) is a type of transistor that uses an electric field to control the flow of current in a semiconductor. FETs (JFETs or MOSFETs) are devices with three terminals: ''source'', ''gate'', and ''drain''. FETs co ...
used for measuring ion concentrations in solution; when the ion concentration (such as H+, see pH scale) changes, the current through the
transistor upright=1.4, gate (G), body (B), source (S) and drain (D) terminals. The gate is separated from the body by an insulating layer (pink). A transistor is a semiconductor device used to Electronic amplifier, amplify or electronic switch, switch ...
will change accordingly. Here, the solution is used as the gate electrode. A voltage between substrate and
oxide An oxide () is a chemical compound that contains at least one oxygen atom and one other element in its chemical formula. "Oxide" itself is the dianion of oxygen, an O2– (molecular) ion. with oxygen in the oxidation state of −2. Most of the E ...
surfaces arises due to an ion sheath. It is a special type of
MOSFET The metal–oxide–semiconductor field-effect transistor (MOSFET, MOS-FET, or MOS FET) 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 d ...
(metal-oxide-semiconductor field-effect transistor), and shares the same basic structure, but with the
metal gate A metal gate, in the context of a lateral metal–oxide–semiconductor (MOS) stack, is the gate electrode separated by an oxide from the transistor's channel – the gate material is made from a metal. In most MOS transistors since about the mid ...
replaced by an ion-sensitive
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...
,
electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon ...
solution and
reference electrode A reference electrode is an electrode which has a stable and well-known electrode potential. The high stability of the electrode potential is usually reached by employing a redox system with constant (buffered or saturated) concentrations of ea ...
. Invented in 1970, the ISFET was the first biosensor FET (BioFET). The surface
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...
of Si–OH groups of the gate materials varies in aqueous solutions due to pH value. Typical gate materials are SiO2, Si3N4, Al2O3 and Ta2O5. The mechanism responsible for the oxide surface charge can be described by the ''site binding model'', which describes the equilibrium between the Si–OH surface sites and the H+ ions in the solution. The hydroxyl groups coating an oxide surface such as that of SiO2 can donate or accept a proton and thus behave in an amphoteric way as illustrated by the following acid-base reactions occurring at the oxide-electrolyte interface: :—Si–OH + H2O     ↔   —Si–O     + H3O+ :—Si–OH + H3O+   ↔   —Si–OH2+ + H2O An ISFET's source and drain are constructed as for a
MOSFET The metal–oxide–semiconductor field-effect transistor (MOSFET, MOS-FET, or MOS FET) 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 d ...
. The gate electrode is separated from the channel by a barrier which is sensitive to
hydrogen ion A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particle ...
s and a gap to allow the substance under test to come in contact with the sensitive barrier. An ISFET's
threshold voltage The threshold voltage, commonly abbreviated as Vth or VGS(th), of a field-effect transistor (FET) is the minimum gate-to-source voltage (VGS) that is needed to create a conducting path between the source and drain terminals. It is an important s ...
depends on the pH of the substance in contact with its ion-sensitive barrier.


Practical limitations due to the reference electrode

An ISFET electrode sensitive to H+ concentration can be used as a conventional
glass electrode A glass electrode is a type of ion-selective electrode made of a doped glass membrane that is sensitive to a specific ion. The most common application of ion-selective glass electrodes is for the measurement of pH. The pH electrode is an exampl ...
to measure the pH of a solution. However, it also requires a
reference electrode A reference electrode is an electrode which has a stable and well-known electrode potential. The high stability of the electrode potential is usually reached by employing a redox system with constant (buffered or saturated) concentrations of ea ...
to operate. If the reference electrode used in contact with the solution is of the AgCl or Hg2Cl2 classical type, it will suffer the same limitations as conventional pH electrodes (junction potential, KCl leak, and
glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
leak in case of gel electrode). A conventional reference electrode can also be bulky and fragile. A too large volume constrained by a classical reference electrode also precludes the miniaturization of the ISFET electrode, a mandatory feature for some biological or ''in vivo'' clinical analyses (disposable mini-catheter pH probe). The breakdown of a conventional reference electrode could also make problem in on-line measurements in the pharmaceutical or food industry if highly valuable products are contaminated by electrode debris or toxic chemical compounds at a late production stage and must be discarded for the sake of safety. For this reason, since more than 20 years many research efforts have been dedicated to on-chip embedded tiny reference field effect transistors (REFET). Their functioning principle, or operating mode, can vary, depending on the electrode producers and are often proprietary and protected by patents. Semi-conductor modified surfaces required for REFET are also not always in thermodynamical equilibrium with the test solution and can be sensitive to aggressive or interfering dissolved species or not well characterized aging phenomena. This is not a real problem if the electrode can be frequently re-calibrated at regular time interval and is easily maintained during its service life. However, this may be an issue if the electrode has to remain immersed on-line for prolonged period of time, or is inaccessible for particular constrains related to the nature of the measurements itself (geochemical measurements under elevated water pressure in harsh environments or under anoxic or reducing conditions easily disturbed by atmospheric oxygen ingress or pressure changes). A crucial factor for ISFET electrodes, as for conventional glass electrodes, remains thus the reference electrode. When troubleshooting electrode malfunctions, often, most of the problems have to be searched for from the side of the reference electrode.


Low-frequency noise of ISFET

For ISFET-based sensors, low-frequency noise is most detrimental to the overall SNR as it can interfere with biomedical signals which span in the same frequency domain. The noise has mainly three sources. The noise sources outside the ISFET itself are referred to as the external noise, such as environmental interference and instrument noise from terminal read-out circuits. The intrinsic noise refers to that appearing in the solid part of an ISFET, which is mainly caused by the trapping and de-trapping of carriers at the Oxide/Si interface. And the extrinsic noise is generally rooted in the liquid/oxide interface causing by the ion exchange at the liquid/oxide interface. Many methods are invented to suppress the noise of ISFET. For example, to suppress the external noise, we can integrate a bipolar junction transistor with ISFET to realize immediate the internal amplification of drain current. And to suppress the intrinsic noise we can replace the noisy oxide/Si interface by a Schottky junction gate.


History

The basis for the ISFET is the
MOSFET The metal–oxide–semiconductor field-effect transistor (MOSFET, MOS-FET, or MOS FET) 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 d ...
. Dutch engineer Piet Bergveld, at the
University of Twente The University of Twente (Dutch: ''Universiteit Twente''; , abbr. ) is a public technical university located in Enschede, Netherlands. The university has been placed in the top 170 universities in the world by multiple central ranking tables. I ...
studied the MOSFET and realized it could be adapted into a
sensor A sensor is a device that produces an output signal for the purpose of sensing a physical phenomenon. In the broadest definition, a sensor is a device, module, machine, or subsystem that detects events or changes in its environment and sends ...
for
electrochemical Electrochemistry is the branch of physical chemistry concerned with the relationship between electrical potential difference, as a measurable and quantitative phenomenon, and identifiable chemical change, with the potential difference as an outc ...
and
biological Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary in ...
applications. This led to Bergveld's invention of the ISFET in 1970. He described the ISFET as "a special type of MOSFET with a gate at a certain distance". It was the earliest Biosensor FET (BioFET). ISFET sensors could be implemented in
integrated circuit An integrated circuit or monolithic integrated circuit (also referred to as an IC, a chip, or a microchip) is a set of electronic circuits on one small flat piece (or "chip") of semiconductor material, usually silicon. Large numbers of tiny ...
s based on
CMOS Complementary metal–oxide–semiconductor (CMOS, pronounced "sea-moss", ) is a type of metal–oxide–semiconductor field-effect transistor (MOSFET) fabrication process that uses complementary and symmetrical pairs of p-type and n-type MOSF ...
(complementary MOS) technology. ISFET devices are widely used in
biomedical Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine)
applications, such as the detection of DNA hybridization,
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
detection from
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
,
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
detection,
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
measurement and pH sensing. The ISFET is also the basis for later BioFETs, such as the DNA field-effect transistor (DNAFET), used in genetic technology.


See also

*
Chemical field-effect transistor 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 wi ...
* Ion-selective electrodes *
MISFET The metal–oxide–semiconductor field-effect transistor (MOSFET, MOS-FET, or MOS FET) 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 ...
: metal–insulator–semiconductor field-effect transistor *
MOSFET The metal–oxide–semiconductor field-effect transistor (MOSFET, MOS-FET, or MOS FET) 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 d ...
: metal–oxide–semiconductor field-effect transistor * pH *
pH meter A pH meter is a scientific instrument that measures the hydrogen-ion activity in water-based solutions, indicating its acidity or alkalinity expressed as pH. The pH meter measures the difference in electrical potential between a pH elect ...
* Potentiometry * Quinhydrone electrode *
Saturated calomel electrode The saturated calomel electrode (SCE) is a reference electrode based on the reaction between elemental mercury and mercury(I) chloride. It has been widely replaced by the silver chloride electrode, however the calomel electrode has a reputation o ...
*
Silver chloride electrode A silver chloride electrode is a type of reference electrode, commonly used in electrochemical measurements. For environmental reasons it has widely replaced the saturated calomel electrode. For example, it is usually the internal reference el ...
*
Standard hydrogen electrode The standard hydrogen electrode (abbreviated SHE), is a redox electrode which forms the basis of the thermodynamic scale of oxidation-reduction potentials. Its absolute electrode potential is estimated to be at 25 °C, but to form a basis ...


References


Bibliography

* *
ISFET pH Sensors


Further reading

* * * * * * * * * * * * * * * * * * * * * * * * {{Electronic components Acid–base chemistry Biosensors Electrochemistry Electrodes Field-effect transistors Measuring instruments MOSFETs Sensors Transistor types