Micro pH Sensors and Biosensors Based on Electrochemical Field Effect Transistors

  • Junji Sasano
  • Daisuke Niwa
  • Tetsuya Osaka
Part of the Nanostructure Science and Technology book series (NST)


A study on ion-sensing using field effect transistor (FET) was begun by Bergveld in the 1970s [1–3]. The ion-sensitive (IS) FET is now widely used as a miniaturized pH sensor, commercialized by some companies. First, the principle and structure of the ISFET are introduced in this section. A basic design of ISFET is shown in Fig. 10.1 a. ISFET has silicon substrate with field-effect structures such as electrolyte/IS layer/(insulator)/semiconductor structures; the space charge region in the semiconductor is modulated depending on the gate voltage (V g), same as a typical metal-oxide-semiconductor (MOS) FET. A typical bias V g versus drain-source current (I ds) characteristic of the device that has silicon nitride/silicon dioxide/silicon is shown in Fig. 10.1 b. This characteristic is quite similar to the MOSFET. A prominent difference between ISFET and MOSFET is that the gate voltage for the operation of the device is applied by an electrochemical reference electrode through the electrolyte in contact with the gate insulator. The threshold voltage (V th) could shift according to the value of the pH of the solution. In the MOSFET, the V th would shift depending on the change in the space charge region in the MOS capacitor structure by the application of V g. On the other hand, the V th in ISFET would shift according to the change in the surface potential in the electrolyte/IS layer interface. Therefore, the IS layers and their interfaces in ISFET play an important role in the performance of pH responsibility. It is well-known that the silicon nitride surface shows a good pH response in solution. The silicon nitride layer is often formed by plasma-enhanced chemical vapor deposition (PECVD), which is generally formed at the thickness of 100–500 nm. The V g vs. I ds, characteristics of the silicon nitride-based ISFET indicate a good pH responsibility of 58 mV/decade that shows Nernstian response (Fig. 10.1 c). The shift of the V th depends on the changes of surface potential at electrolyte/silicon nitride interface. On the silicon nitride surface immersed in aqueous solution, both amphoteric Si–OH sites and basic Si–NH2 sites (Fig. 10.1 d) are produced by hydrolysis. These sites directly interact with the solution to either bind or release hydrogen ions, leading to bear a certain surface charge on the nitride surface that was opposed to an ionic charge in the solution. This formed a double-layer capacitance across which the potential drop occurs. Therefore, the threshold voltage shifted accompanied by the pH change in solution.


Gate Voltage Space Charge Region Field Effect Transistor Organic Monolayer Nernstian Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Matsuo T, Esashi M (1981) Methods of ISFET fabrication. Sens Actuators 1:77–96CrossRefGoogle Scholar
  2. 2.
    Bergveld P (1972) Development, operation, and application of the ion-sensitive field-effect transistor as a tool for electrophysiology. IEEE Trans Biomed Eng BME-19:342–351CrossRefGoogle Scholar
  3. 3.
    Matsuo T, Wise KD (1974) An integrated field-effect electrode for biopotential recording. IEEE Trans Biomed Eng BME-21:485–487CrossRefGoogle Scholar
  4. 4.
    Bousse L, Mostarshed S, Van der Schoot B, de Rooij NF (1994) Comparison of the hysteresis of Ta2O5 and Si3N4 pH-sensing insulators. Sens Actuators B 17:157–164CrossRefGoogle Scholar
  5. 5.
    Niwa D, Yamada Y, Homma T, Osaka T (2004) Formation of molecular templates for fabricating on-chip biosensing devices. J Phys Chem B 108:3240–3245CrossRefGoogle Scholar
  6. 6.
    Niwa D, Homma T, Osaka T (2004) Fabrication of organic monolayer modified ion-sensitive field effect transistors with high chemical durability. Jpn J Appl Phys 43:L105–L107CrossRefGoogle Scholar
  7. 7.
    Niwa D, Omichi K, Motohashi N, Homma T, Osaka T (2006) Organosilane self-assembled monolayer-modified field effect transistors for on-chip ion and biomolecule sensing. Sens Actuator B 108:721–726CrossRefGoogle Scholar
  8. 8.
    Kuroiwa S, Wang J, Satake D, Nomura S, Osaka T (2009) Effect of surface morphology of reference field effect transistor modified by octadecyltrimethoxysilane on ionic responses. J Electrochem Soc 156:J67–J72Google Scholar
  9. 9.
    Wang J, Ito K, Nakanishi T, Kuroiwa S, Osaka T (2009) Tb3+-enhanced potentiometric detection of single nucleotide polymorphism by field effect transistors. Chem Lett 38:376–377Google Scholar
  10. 10.
    Ulman A (1991) An introduction to ultra thin organic films from langmuir-blodgett to self-asembly. Academic, San Diego, CAGoogle Scholar
  11. 11.
    Wasserman SR, Tao Y-T, Whitesides GM (1989) Structure and reactivity of alkylsiloxane monolayers formed by reaction of alkyltrichlorosilanes on silicon substrates. Langmuir 5:1074–1087CrossRefGoogle Scholar
  12. 12.
    Schwartz DK (2001) Mechanisms and kinetics of self-assembled monolayer formation. Annu Rev Phys Chem 52:107–137CrossRefGoogle Scholar
  13. 13.
    Doudevski I, Hayes WA, Schwartz DK (1998) Submonolayer island nucleation and growth kinetics during self-assembled monolayer formation. Phys Rev Lett 81:4927–4930CrossRefGoogle Scholar
  14. 14.
    Leitner T, Friedbacher G, Vallant T, Brunner H, Mayer U, Hoffmann H (2000) Investigations of the growth of self-assembled octadecylsiloxane monolayers with atomic force microscopy. Mikrochim Acta 133:331–336CrossRefGoogle Scholar
  15. 15.
    Iimura K, Nakajima Y, Kato T (2000) A study on structures and formation mechanisms of self-assembled monolayers of n-alkyltrichlorosilanes using infrared spectroscopy and atomic force microscopy. Thin Solid Films 379:230–239CrossRefGoogle Scholar
  16. 16.
    Wang Y, Lieberman M (2003) Growth of ultrasmooth octadecyltrichlorosilane self-assembled monolayers on SiO2. Langmuir 19:1159–1167CrossRefGoogle Scholar
  17. 17.
    Sugimura H, Ushiyama K, Hozumi A, Takai O (2000) Micropatterning of alkyl- and fluoroalkylsilane self-assembled monolayers using vacuum ultraviolet light. Langmuir 16:885–888CrossRefGoogle Scholar
  18. 18.
    Hozumi A, Ushiyama K, Sugimura H, Takai O (1999) Fluoroalkylsilane monolayers formed by chemical vapor surface modification on hydroxylated oxide surfaces. Langmuir 15:7600–7604CrossRefGoogle Scholar
  19. 19.
    Sugimura H, Nakagiri N (1997) Organosilane monolayer resists for scanning probe lithography. J Photopolym Sci Technol 10:661–666CrossRefGoogle Scholar
  20. 20.
    Sugimura H, Nakagiri N (1996) Scanning probe anodization: nanolithography using thin films of anodically oxidizable materials as resists. J Vac Sci Technol A 14:1223–1223CrossRefGoogle Scholar
  21. 21.
    Hozumi A, Sugimura H, Yokogawa Y, Kameyama T, Takai O (2001) ζ-potentials of planar silicon plates covered with alkyl- and fluoroalkylsilane self-assembled monolayers. Colloid Surf A 182:257–261CrossRefGoogle Scholar
  22. 22.
    Hayashi K, Saito N, Sugimura H, Takai O, Nakagiri N (2002) Regulation of the surface potential of silicon substrates in micrometer scale with organosilane self-assembled monolayers. Langmuir 18:7469–7472CrossRefGoogle Scholar
  23. 23.
    Sugimura H, Hanji T, Hayashi K, Takai O (2002) Surface potential nanopatterning combining alkyl and fluoroalkylsilane self-assembled monolayers fabricated via scanning probe lithography. Adv Mater 14:524–526CrossRefGoogle Scholar
  24. 24.
    Siqueira PDF, Wenz G, Schunk P, Schimmel T (1999) An improved method for the assembly of amino-terminated monolayers on SiO2 and the vapor deposition of gold layers. Langmuir 15:4520–4523CrossRefGoogle Scholar
  25. 25.
    DePalma V, Tillman N (1989) Friction and wear of self-assembled trichlorosilane monolayer films on silicon. Langmuir 5:868–872CrossRefGoogle Scholar
  26. 26.
    Barrelet CJ, Robinson DB, Cheng J, Hunt TP, Quate CF, Chidsey CED (2001) Surface characterization and electrochemical properties of alkyl, fluorinated alkyl, and alkoxy monolayers on silicon. Langmuir 17:3460–3465CrossRefGoogle Scholar
  27. 27.
    Cicero RL, Linford MR, Chidsey CED (2000) Photoreactivity of unsaturated compounds with hydrogen-terminated silicon(111). Langmuir 16:5688–5695CrossRefGoogle Scholar
  28. 28.
    Niu MN, Ding XF, Tong QY (1996) Effect of two types of surface sites on the characteristics of Si3N4-gate pH-ISFETs. Sens Actuators B 37:13–17CrossRefGoogle Scholar
  29. 29.
    Birge RR (ed) (1994) Molecular electronics and bioelectronics. Am Chem Soc, Washington, DCGoogle Scholar
  30. 30.
    Bard AJ (1994) Integrated chemical systems. Wiley, New YorkGoogle Scholar
  31. 31.
    Spochiger-Kuller UE (1998) Chemical sensors and biosensors for medical and biological applications. Wiley, WashingtonCrossRefGoogle Scholar
  32. 32.
    Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470CrossRefGoogle Scholar
  33. 33.
    MacBeath G, Schreiber SL (2000) Printing proteins as microarrays for high-throughput function determination. Science 289:1760–1763Google Scholar
  34. 34.
    Wilson DS, Nock S (2003) Recent developments in protein microarray technology. Angew Chem Int Ed 42:494–500CrossRefGoogle Scholar
  35. 35.
    Frutos AG, Smith LM, Corn RM (1998) Enzymatic ligation reactions of DNA “words” on surfaces for DNA computing. J Am Chem Soc 120:10277–10282CrossRefGoogle Scholar
  36. 36.
    Lamture JB, Beattie KL, Burke BE, Eggers MD, Ehrlich DJ, Fowler R, Hollis MA, Kosicki BB, Reich RK, Smith SR, Varma RS, Hogen ME (1994) Direct detection of nucleic acid hybridization on the surface of a charge coupled device. Nucleic Acids Res 22:2121–2125CrossRefGoogle Scholar
  37. 37.
    Souteyrand E, Cloarec JP, Martin JR, Wilson C, Lawrence I, Mikkelsen S, Lawrence MF (1997) Direct detection of the hybridization of synthetic homo-oligomer DNA sequences by field effect. J Phys Chem B 101:2980–2985CrossRefGoogle Scholar
  38. 38.
    Niwa D, Omichi K, Motohashi N, Homma T, Osaka T (2004) Formation of micro and nanoscale patterns of monolayer templates for position selective immobilization of oligonucleotide using ultraviolet and electron beam lithography. Chem Lett 33:176–177CrossRefGoogle Scholar
  39. 39.
    Osaka T, Matsunaga T, Nakanishi T, Arakaki A, Niwa D, Iida H (2006) Synthesis of magnetic nanoparticles and their application to bioassays. Anal Bioanal Chem 384:593–600Google Scholar
  40. 40.
    Osaka T, Komaba S, Seyama M, Tanabe K (1996) High-sensitivity urea-sensor based on the composite film of electroinactive polypyrrole with polyion complex. Sens Actuators B 36:463–469CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Consolidated Research Institute for Advanced Science and Medical CareWaseda UniversityShinjuku-kuJapan
  2. 2.Department of Production Systems EngineeringToyohashi University of TechnologyToyohashiJapan
  3. 3.Nano Bionics R&D Center, ROHM Co., Ltd.KyotoJapan
  4. 4.School of Science and EngineeringWaseda UniversityShinjuku-kuJapan

Personalised recommendations