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),[1] and shares the same basic structure, but with the metal gate replaced by an ion-sensitive membrane, electrolyte solution and reference electrode.[2] Invented in 1970, the ISFET was the first biosensor FET (BioFET).

The schematic view of an ISFET. Source and drain are the two electrodes used in a FET system. The electron flow takes place in a channel between the drain and source. The gate potential controls the flow of current between the two electrodes.

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.

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 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). 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.

History

The basis for the ISFET is the MOSFET (metal-oxide-semiconductor field-effect transistor),[1] which was originally invented by Egyptian engineer Mohamed M. Atalla and Korean engineer Dawon Kahng in 1959.[3] In 1962, Leland C. Clark and Champ Lyons invented the biosensor.[4][5]

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.[6][1] This led to Bergveld's invention of the ISFET in 1970.[7][6] He described the ISFET as "a special type of MOSFET with a gate at a certain distance".[1] It was the earliest Biosensor FET (BioFET).[4]

ISFET sensors could be implemented in integrated circuits based on CMOS (complementary MOS) 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.[2] The ISFET is also the basis for later BioFETs, such as the DNA field-effect transistor (DNAFET),[2][7] used in genetic technology.[2]

See also

References

  1. ^ a b c d Bergveld, Piet (October 1985). "The impact of MOSFET-based sensors" (PDF). Sensors and Actuators. 8 (2): 109–127. Bibcode:1985SeAc....8..109B. doi:10.1016/0250-6874(85)87009-8. ISSN 0250-6874.
  2. ^ a b c d Schöning, Michael J.; Poghossian, Arshak (10 September 2002). "Recent advances in biologically sensitive field-effect transistors (BioFETs)" (PDF). Analyst. 127 (9): 1137–1151. Bibcode:2002Ana...127.1137S. doi:10.1039/B204444G. ISSN 1364-5528. PMID 12375833.
  3. ^ "1960: Metal Oxide Semiconductor (MOS) Transistor Demonstrated". The Silicon Engine: A Timeline of Semiconductors in Computers. Computer History Museum. Retrieved August 31, 2019.
  4. ^ a b Park, Jeho; Nguyen, Hoang Hiep; Woubit, Abdela; Kim, Moonil (2014). "Applications of Field-Effect Transistor (FET)–Type Biosensors" (PDF). Applied Science and Convergence Technology. 23 (2): 61–71. doi:10.5757/ASCT.2014.23.2.61. ISSN 2288-6559.
  5. ^ Clark, Leland C.; Lyons, Champ (1962). "Electrode Systems for Continuous Monitoring in Cardiovascular Surgery". Annals of the New York Academy of Sciences. 102 (1): 29–45. Bibcode:1962NYASA.102...29C. doi:10.1111/j.1749-6632.1962.tb13623.x. ISSN 1749-6632. PMID 14021529.
  6. ^ a b Bergveld, P. (January 1970). "Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements". IEEE Transactions on Biomedical Engineering. BME-17 (1): 70–71. doi:10.1109/TBME.1970.4502688.
  7. ^ a b Chris Toumazou; Pantelis Georgiou (December 2011). "40 years of ISFET technology: From neuronal sensing to DNA sequencing". Electronics Letters. 47: S7. doi:10.1049/el.2011.3231. Retrieved 13 May 2016.

Bibliography

  • Bergveld, P. (2003). "Thirty years of ISFETOLOGY, What happened in the past 30 years and what may happen in the next 30 years". Sensors and Actuators B: Chemical. 88: 1–20. doi:10.1016/S0925-4005(02)00301-5.
  • Bergveld, P. (2003). ISFET, theory and practice (PDF). IEEE Sensor Conference, October 2003. Toronto: IEEE. p. 26.
  • ISFET pH Sensors

Further reading

  • Rothberg, Johnathan M (2011). "An integrated semiconductor device enabling non-optical genome sequencing". Nature. 475 (7356): 348–52. doi:10.1038/nature10242. ISSN 1476-4687. PMID 21776081.
  • Bergveld, P. (1985). "The impact of MOSFET-based sensors". Sensors and Actuators. 8 (2): 109–127. Bibcode:1985SeAc....8..109B. doi:10.1016/0250-6874(85)87009-8. ISSN 0250-6874.
  • Bergveld, P. (1986). "The development and application of FET-based biosensors". Biosensors. 2 (1): 15–33. doi:10.1016/0265-928X(86)85010-6. ISSN 0265-928X. PMID 3790175.
  • Bergveld, P. (1991). "A critical evaluation of direct electrical protein detection methods". Biosensors and Bioelectronics. 6 (1): 55–72. doi:10.1016/0956-5663(91)85009-L. ISSN 0956-5663. PMID 2049171.
  • Bergveld, P. (2003). "Thirty years of ISFETOLOGY: What happened in the past 30 years and what may happen in the next 30 years". Sensors and Actuators B: Chemical. 88 (1): 1–20. doi:10.1016/S0925-4005(02)00301-5. ISSN 0925-4005.
  • Bergveld, P. (2003). ISFET, theory and practice (PDF). IEEE Sensor Conference Toronto, October 2003. Toronto: IEEE. pp. 26 pp. Archived from the original (PDF) on 2008-08-20.
  • Bergveld, P; A Van den Berg; PD Van der Wal; M Skowronska-Ptasinska; EJR Sudhölter; DN Reinhoudt (1989). "How electrical and chemical requirements for REFETs may coincide". Sensors and Actuators. 18 (3–4): 309–327. doi:10.1016/0250-6874(89)87038-6. ISSN 0250-6874.
  • Chudy, M; W Wróblewski; Z Brzózka (1999). "Towards REFET". Sensors and Actuators B: Chemical. 57 (1–3): 47–50. doi:10.1016/S0925-4005(99)00134-3. ISSN 0925-4005.
  • Chudy, Michal; Wojciech Wróblewski; Zbigniew Brzózka (1999). "Towards REFET". Sensors and Actuators B: Chemical. 57 (1–3): 47–50. doi:10.1016/S0925-4005(99)00134-3. ISSN 0925-4005.
  • Collins, S.D. (1993). "Practical limits for solid-state reference electrodes". Sensors and Actuators B: Chemical. 10 (3): 169–178. doi:10.1016/0925-4005(93)87002-7. ISSN 0925-4005.
  • Duroux, P; C Emde; P Bauerfeind; C Francis; A Grisel; L Thybaud; D Armstrong; C Depeursinge; A L Blum (1991). "The ion sensitive field effect transistor (ISFET) pH electrode: a new sensor for long term ambulatory pH monitoring". Gut. 32 (3): 240–245. doi:10.1136/gut.32.3.240. ISSN 0017-5749. PMC 1378826. PMID 2013417.
  • Errachid, A.; J. Bausells; N. Jaffrezic-Renault (1999). "A simple REFET for pH detection in differential mode". Sensors and Actuators B: Chemical. 60 (1): 43–48. doi:10.1016/S0925-4005(99)00242-7. ISSN 0925-4005.
  • Ghallab, Y.H.; W. Badawy; K.V.I.S. Kaler. "A novel pH sensor using differential ISFET current mode read-out circuit". Proceedings International Conference on MEMS, NANO and Smart Systems. International Conference on MEMS, NANO and Smart Systems. Banff, Alta., Canada. pp. 255–258. doi:10.1109/ICMENS.2003.1222002.
  • Guth, U; F Gerlach; M Decker; W Oelßner; W Vonau (2009). "Solid-state reference electrodes for potentiometric sensors". Journal of Solid State Electrochemistry. 13 (1): 27–39. doi:10.1007/s10008-008-0574-7. ISSN 1432-8488.
  • Huang, I-Yu. "Chemical sensors research group". Retrieved 2010-11-01. Cite journal requires |journal= (help)
  • Huang, I-Yu; Ruey-Shing Huang; Lieh-Hsi Lo (2002). "A new structured ISFET with integrated Ti/Pd/Ag/AgCl Electrode and micromachined back-side P+ contacts". Journal of the Chinese Institute of Engineers. 25 (3): 327–334. doi:10.1080/02533839.2002.9670707. Archived from the original on 2011-07-03. Retrieved 2010-11-01.
  • Kal, S.; Bhanu, P. V. (2007). Design and modeling of ISFET for pH sensing. TENCON 2007 - 2007 IEEE Region 10 Conference. Taipei. pp. 1–4. doi:10.1109/TENCON.2007.4428805. ISBN 978-1-4244-1272-3.
  • Kisiel, Anna; Agata Michalska; Krzysztof Maksymiuk (September 2007). "Plastic reference electrodes and plastic potentiometric cells with dispersion cast poly(3,4-ethylenedioxythiophene) and poly(vinyl chloride) based membranes". Bioelectrochemistry. 71 (1): 75–80. doi:10.1016/j.bioelechem.2006.09.006. ISSN 1567-5394. PMID 17107827.
  • Lee, YC; BK Sohn (2002). "Development of an FET-type reference electrode for pH detection". Journal of the Korean Physical Society. 40 (4): 601–604. Bibcode:2002JKPS...40..601Y. doi:10.3938/jkps.40.601. ISSN 0374-4884.
  • Lisdat, F.; W. Moritz (August 1993). "A reference element based on a solid-state structure". Sensors and Actuators B: Chemical. 15 (1–3): 228–232. doi:10.1016/0925-4005(93)85057-H. ISSN 0925-4005.
  • Skowronska-Ptasinska, M; PD Van Der Wal; A Van Den Berg; P Bergveld; EJR Sudhölter; DN Reinhoudt (1990). "Reference field effect transistors based on chemically modified ISFETs". Analytica Chimica Acta. 230: 67–73. doi:10.1016/s0003-2670(00)82762-2. ISSN 0003-2670.
  • Suzuki, Hiroaki; Taishi Hirakawa; Satoshi Sasaki; Isao Karube (1998-02-15). "Micromachined liquid-junction Ag/AgCl reference electrode". Sensors and Actuators B: Chemical. 46 (2): 146–154. doi:10.1016/S0925-4005(98)00110-5. ISSN 0925-4005.
  • van den Berg, A.; A. Grisel; H.H. van den Vlekkert; N.F. de Rooij (January 1990). "A micro-volume open liquid-junction reference electrode for pH-ISFETs". Sensors and Actuators B: Chemical. 1 (1–6): 425–432. doi:10.1016/0925-4005(90)80243-S. ISSN 0925-4005.
  • Vonau, W.; W. Oelßner; U. Guth; J. Henze (2010-02-17). "An all-solid-state reference electrode". Sensors and Actuators B: Chemical. 144 (2): 368–373. doi:10.1016/j.snb.2008.12.001. ISSN 0925-4005.