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). The surface hydrolysis 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 gate electrode is separated from the channel by a barrier which is sensitive to hydrogen ions and a gap to allow the substance under test to come in contact with the sensitive barrier. An ISFET's threshold voltage depends on the pH of the substance in contact with its ion-sensitive barrier. An ISFET electrode sensitive to H+ concentration can be used as a conventional glass electrode to measure the pH of a solution. However, it also requires a reference electrode 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 leak in case of gel electrode).

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