ISFET applications

Huang, I. Y., Huang, R. S., and Lo, L. H. 2003. Improvement of integrated Ag/AgCl thin-film electrodes by KCl-gel coating for ISFET applications. Sens. Actuators B 94 53-64. 

Applicability in biological ion assay is an important factor for biocompatible potentio-metric ion sensors. Attempts were made to determine Na" " concentrations in human blood sera by using silicone-rubber membrane Na+-ISFETs based on (5) [Fig. 17(a)] [29]. The found values for Na concentration in undiluted, 10-fold diluted, and 100-fold diluted serum samples are in good agreement with the Na" " calibration plots. Even in the undiluted serum samples, only a slight potential shift was observed from the calibration. This indicates that the calixarene-based silicone-rubber-membrane Na+-ISFETs are reliable on serum Na assay. For comparison with the silicone-rubber membrane, Na -ISFETs with corresponding plasticized-PVC membrane containing (2) or (5) were also tested for the Na assay. The found values of Na" " concentration... 

J.F. Schenck, Technical difficulties remaining to the application of ISFET devices, in Theory, Design and Biomedical Applications of Solid State Chemical Sensors (P.W. Cheung, ed.), pp. 165—173. CRC Press, Boca Raton (1978). 

The measurement of changes of the surface potential Vo at the interface between an insulator and a solution is made possible by incorporating a thin film of that insulator in an electrolyte/insulator/silicon (EIS) structure. The surface potential of the silicon can be determined either by measuring the capacitance of the structure, or by fabricating a field effect transistor to measure the lateral current flow. In the latter case, the device is called an ion-sensitive field effect transistor (ISFET). Figure 1 shows a schematic representation of an ISFET structure. The first authors to suggest the application of ISFETs or EIS capacitors as a measurement tool to determine the surface potential of insulators were Schenck (15) and Cichos and Geidel (16). 

For correct function of the ISFET, a sufficiently large gate voltage, Vq, must be applied between the leads to the reference electrode and to the substrate, so that a sufficiently large potential difference is formed between the surface and the interior of the substrate for formation of the n-type conductive channel at the insulator/substrate interface. This channel conductively connects drain 1 and source 2, which are connected with the substrate by a p-n transition. On application of voltage Vj between the drain and the source, drain current /p begins to pass. Under certain conditions the drain current is a linear function of the difference between Vq and the Volta potential difference between the substrate and the membrane. 

The above conceptual and operational pH definitions for solutions in non-aqueous and mixed solvents are very similar to those for aqueous solutions [16]. At present, pH values are available for the RVS and some primary standards in the mixtures between water and eight organic solvents (see 5 in Section 6.2) [17]. If a reliable pH standard is available for the solvent under study, the pH can be determined with a pH meter and a glass electrode, just as in aqueous solutions. However, in order to apply the IUPAC method to the solutions in neat organic solvents or water-poor mixed solvents, there are still some problems to be solved. One of them is that it is difficult to get the RVS in such solvents, because (i) the solubility of KHPh is not enough and (ii) the buffer action of KHPh is too low in solutions of an aprotic nature [18].8) Another problem is that the response of the glass electrode is often very slow in non-aqueous solvents,9 although this has been considerably improved by the use of pH-ISFETs [19]. Practical pH measurements in non-aqueous solutions and their applications are discussed in Chapter 6. 

Recently, Ta2Os- and Si3N4-type pH-ISFETs have been used in non-aqueous systems, by preparing them to be solvent-resistant [17]. In various polar non-aqueous solvents, they responded with Nernstian or near-Nernstian slopes and much faster than the glass electrode. The titration curves in Fig. 6.5 demonstrate the fast (almost instantaneous) response of the Si3N4-ISFET and the slow response of the glass electrode. Some applications of pH-ISFETs are discussed in Section 6.3.1. 

LAPS was introduced by Sato et al. [155]. The detection of heavy metal ions by thin films of chalcogenide-glass membranes using the pulsed laser deposition method (PLD) was reported by Mourzina et al. [156]. The PLD technique was also introduced to evaporate A1203 as a pH-sensitive material for LAPS devices [157]. The first practical application of the above-described LAPS card was demonstrated by Kloock et al. for a comparative study of Cd-sensitive chalcogenide glasses for ISFETs, LAPS and pISEs (ion-selective electrodes) [158]. 

With more than 150 publications on LAPS devices, a wide range of possible applications for LAPS has been demonstrated in the past. However, since LAPS devices belong to the family of field-effect-based sensors, results and studies on, e.g., ISFETs and EIS sensors can be easily adapted to LAPS. This includes especially the transfer of alternative sensor materials, which were initially developed for ISFET and EIS devices and will further extend the range of possible applications for LAPS. 

A third application for pTAS is in the biomedical field. Gumbrecht et al. [46, 47] developed a monolithically integrated, ISFET-based sensor system for (bedside) monitoring of blood pH, p02 and pC02 in patients. Here the successful introduction on the market mainly depends on the price of the system, for which reason a CMOS-compatible design of the silicon part is needed. Evidently, such a development is only possible in the case of a high volume market. 

Such an ISFET was originally used for detecting pH changes but by casting with ion selective membranes a lot of different ion-selective sensors can be obtained in principle [38,39]. Even a multi-parameter electrolyte sensitive chip for clinical applications was invented [39]. 

For certain applications, solutions could be found which satisfy the special needs but up to now no general approach has been found that suits a wide range of applications with a single design. Therefore only a few ISFET- pH-sensors entered the market in the last years [49]. 

Due to the fact that nearly all ENFET approaches lead to insufficient or unsatisfactory sensor performance, no ISFET based biosensor has been fully commercialized for wider applications to date. 

Unfortunately, this novel technique is unsuitable for any UV absorbing sensor or mediator but could find a significant application in the realm of ISFET fabrication (3). 

In order to maintain the advantage of the microfabrication approach which is intended for a reproducible production of multiple devices, parallel development of membrane deposition technology is of importance. Using modified on-wafer membrane deposition techniques and commercially available compounds an improvement of the membrane thickness control as well as the membrane adhesion can be achieved. This has been presented here for three electrochemical sensors - an enzymatic glucose electrode, an amperometric free chlorine sensor and a potentiometric Ca + sensitive device based on a membrane modified ISFET. Unfortunately, the on-wafer membrane deposition technique could not yet be applied in the preparation of the glucose sensors for in vivo applications, since this particular application requires relatively thick enzymatic membranes, whilst the lift-off technique is usable only for the patterning of relatively thin membranes. 

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