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P. Bergveld first described the principle of an ion-selective field effect transistor (ISFET) based on the known MOSFET structure in a short paper "Development of an Ion-Sensitive Solid-State Device for Neurophysiological Measurements" (Bergveld P., 1970). Instead of applying a gate voltage like in usual MOSFET applications he immersed the transistor in an aqueous solution. Thus a double layer between the solution and the oxide of the transistor was formed that could induce a conductive channel between source and drain without applying a gate voltage. First experiments showed a dependance of the drain-source-current on the ion activity near this double layer.


In 1977 A.G. Revesz of the COMSAT Laboratories in Clarksburg, USA published a paper “On the mechanism of the ion-sensitive field effect transistor” (Revesz A.G., 1977) and presented therewith the fundamental build-up of an early ISFET and its function. He discovered that it was possible to control the channel width of the field effect transistor via charge injection on the SiO2 Layer.


M. Bos discovered a method for measuring pH with ISFETs (“The ion-sensitive field effect transistor in rapid acid-base titrations”, Bos M., 1979). Therefore he replaced the gate metal with silicon nitride or a polymeric pH-selective membrane. Using an ISFET instead of a standard glass electrode, it was possible to execute the measurements up to five times faster and accuracies of +/- 1%.


In the following years, many variations and modifications of the ISFET concept were developed. On the one hand, the ISFET became an important substructure for biosensors, such as the ENFET (enzyme field effect transistor). With a thin polymer layer containing immobilized enzymes as gate electrode (Miyahara Y., 1985) allows to measure pH variations caused by the chemic reaction with the analyte (“The development and application of FET-based biosensors”, Bergveld P., 1987).
Another milestone in the history of ISFETs was the invention of the so called reference field effect transistor (REFET). Its distinctive feature is the MISFET structure (metal insulator field effect transistor). Instead of an ion sensitive layer, the REFET gate consists of an insulator layer covered by a metal contact. For this reason, the channel width of the REFET is not dependent on the ion concentration of the electrolyte but determined by the applied gate potential. Its main operation purpose is the realization of a solid-state ISFET system. Thus the major drawback of pH-ISFETs - the need of a conventional Ag/AgCl reference electrode within a barrel filled with 3M KCl- can be eroded out, when using a ISFET/REFET system working in differential mode with an additional quasi-reference electrode (Errachid A., 1999) which can easily be integrated on the chip. As the REFETs output voltage is absolutely independent from the electrolyte, it can be used to compensate irregularities of reference electrodes. Furthermore it is possible to measure the REFET output without any substance, so errors in the REFET measurement point to errors in the substrate manufacturing process.
Also future applications of ISFETs, especially in the field of dynamic measurements were analysed ("Future Applications of ISFETs", Bergveld P., 1991). It was pointed out that ISFETs thanks to their quick response time and small size show their potential especially in dynamic applications, for example when used in flow-through cells.


In 1995, Kim and Sohn of KNU, South Korea, were the first to realize a method of measuring dissolved oxygen in aqueous solutions by implementing a noble metal electrode (NME) which surrounds the standard ISFET structure on a silicon chip (Sohn BK and Kim CS, 1996). As soon as a voltage of -700mV is applied to the NME, the dissolved oxygen becomes reduced to OH- ions which can be detected by the ISFET. This ISFET was fabricated by a conventional CMOS process: the gate electrode consists of 50nm SiO2 and 50nm SiN4, the NME of a 150nm thick platinum layer.


Lehmann et al. published a paper on “Simultaneous measurement of cellular respiration and acidification with a single CMOS ISFET” (Lehmann M. et al., 2001) where a system which facilitates the measurement of the pH value and the dissolved oxygen concentration at the same site is described. Like the O2-FET introduced by Kim and Sohn in 1996, this version was manufactured in CMOS technology using the same specifications for the ISFET of Kim and Sohn. Though Lehmann et al. succeeded to realize the NME using palladium instead of platinum. By this means it was possible to pass on the titanium glue layer, which was necessary to sputter platinum on the chip substrate.


In 2006 Wiest et al. presented a paper on finite elements method simulation of the novel nMOS O2-FET (Wiest J. et al., 2006). Under consideration of diffusion as mass transport, the simulation showed basically the same values as the test results with PBS.


Scientists from the Heinz Nixdorf - Lehrstuhl für Medizinische Elektronik of Technische Universität München introduced the idea of a so called CV-FET (cyclovoltammetry field effect transistor) based on the O2FET concept. The CV-FET allows the detection of concentrations of all substances that deliver hydroxide or hydrogen ions by reducing, as long as the reducing voltage is smaller than then the dissociation voltage of water (1200mV). As the NME voltage is slowly increased from -1200mV to 1200mV, the drain-source-current IDS is recorded and compared to experiments with other concentrations. The change of this current is proportional to the concentration of the reduced substance. An experiment with KMnO4 (Eminaga Y., 2009) in different concentrations showed variations of the drain-source-current in the range of 225µA/mM.


The knowledge in the field of ISFETs/O2-FETs/CV-FETs was integrated in the cellasys IMOLA-IVD system. The intelligent mobile lab offers the possibility to measure the vitality of living cells with a BioChip that uses, among others, ISFET and O2-FET sensors for the determination of the pH value and dissolved oxygen concentration of cell based assays.


The principle of the CV-FET was presented at the "IMCS 2012 - The 14th International Meeting on Chemical Sensors" including some new experiments with hydroquinone / quinone (Eminaga Y., 2012).