An ion-sensitive field-effect transistor is a field-effect transistor used for measuring ion concentrations in solution; when the ion concentration 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, 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. 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: 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.
Practical limitations due to the reference electrode
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 Hg2Cl2classical type, it will suffer the same limitations as conventional pH electrodes. 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. 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. 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. 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.
History
The basis for the ISFET is the MOSFET, which was originally invented by Egyptian engineer Mohamed M. Atalla and Korean engineer Dawon Kahng in 1959. In 1962, Leland C. Clark and Champ Lyons invented the biosensor. Dutch engineer Piet Bergveld, at the University of Twente, later studied the MOSFET and realized it could be adapted into a sensor for electrochemical and biological 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. ISFET sensors could be implemented in integrated circuits based on CMOS technology. ISFET devices are widely used in biomedical applications, such as the detection of DNA hybridization, biomarker detection from blood, antibody detection, glucose measurement and pH sensing. The ISFET is also the basis for later BioFETs, such as the DNA field-effect transistor, used in genetic technology.
