PH-sensitive ISFET

Recently, Van der Schoot and Bergveld74 developed an ISFET-based microlitre titrator by combination with a microcoulometric pH actuator. As a result of integrated circuit technology they could integrate ten pH-sensitive ISFETs... 

Figure 1. Schematic representation of the basic pH-sensitive ISFET structure, assuming that the insulator is SiOj.

The hydrolysed surface of Ihe Si3N4 insulator functions as a pH-sensitive membrane [90, 105, 116, 179]. A penicillin-sensitive ISFET is based on this membrane that is covered by an immobilized layer of penicillinase, converting penicillin into the penicillanic acid anion with liberation of hydrogen ions [24]. Another version of pH-sensitive ISFETs has membrane gates made of TajOs [3] or of a suitable glass [39]. The latter ISFET with a gate made of alumino- or borosilicate glass is sensitive to sodium ions. Other ISFETs are sensitive to halide ions [22, 153, 178], [105, 115, 130] and Ca [90, 105]. 

Although our results show that a complete elimination of the sensitivity of such REFETs can be achieved, in a number of situations the combination of a pH sensitive ISFET and an ACE REFET can be used to measure pH values with an integrated FET device (Figure 4). An example of a differential measurement with a TajOj ISFET/REFET combination is given in Figure 5. 

The titration of an acid or base can be carried out by choosing a cathodic or anodic current, respectively. The ions produced cause a local change in the pH. which can easily be measured by the pH-sensitive ISFET. located in the direct vicinity of the actuator electrode [15]. This change in pH will lead to simultaneous diffusion and chemical reaction of protons and hydroxyl ions in the membrane. These diffusion processes will be delayed as a result of protein dissociation reactions of immobilized protein molecules 110[. The description of the diffusion and the effect of the concentration of immobilized protein on the... 

Furthermore, the gate area of pH-sensitive ISFET s (ion-sensitive field-effect transistor) has been covered with pH changing enzymes, such as urease and )8-lactamase [12]. Furthermore, ATPase, glucose oxidase, and trypsin were used for ATP, glucose, and peptide ENFET s (enzyme-field-effect transistor). 

To show an actual example of the calibration procedure of a pH-sensitive ISFET, the response of a two-point calibration on two injected calibration samples obtained with a system like the one described here is included in Figure 14. 

The pH-sensitive ISFET can also be used to determine hypoxanthine, an indicator of the freshness of fish [192]. Xanthine oxidase (XO) is immobilized on a polyvinylbutyral membrane over the insulating layer of Si02, and catalyses simultaneously two successive reactions ... 

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