Potentiometric sensors ISFET

Although a few amperometric pH sensors are reported [32], most pH electrodes are potentiometric sensors. Among various potentiometric pH sensors, conventional glass pH electrodes are widely used and the pH value measured using a glass electrode is often considered as a gold standard in the development and calibration of other novel pH sensors in vivo and in vitro [33], Other pH electrodes, such as metal/metal oxide and ISFETs have received more and more attention in recent years due to their robustness, fast response, all-solid format and capability for miniaturization. Potentiometric microelectrodes for pH measurements will be the focus of this chapter. 

Besides, potentiometric sensors with ion-selective ionophores in modified poly(vinyl chloride) (PVC) have been used to detect analytes from human serum [128], Cellular respiration and acidification due to the activity of the cells has been measured with CMOS ISFETS [129], Some potentiometric methods employ gas-sensing electrodes for NH3 (for deaminase reactions) and C02 (for decarboxylase reactions). Ion-selective electrodes have also been used to quantitate penicillin, since the penicillinase reaction may be mediated with I or GST. 

The first representative of a potentiometric sensor was the pH-glass electrode invented in 1906 [35]. Decades of development resulted in the invention of many more ion-selective electrodes including more recently those based on neutral carrier membranes [36] and of the microelectronic fabricated ion selective field effect transistor (ISFET) [37]. 

The ion sensitive field-effect transistor (ISFET) is a special member of the family of potentiometric chemical sensors [6,7. Like the other members of this family, it transduces information from the chemical into the electrical domain. Unlike the common potentiometric sensors, however, the principle of operation of the ISFET cannot be listed on the usual table of operation principles of potentiometric sensors. These principles, e.g., the determination of the redox potential at an inert electrode, or of the electrode potential of an electrode immersed in a solution of its own ions (electrode of the first kind), all have in common that a galvanic contact exists between the electrode and the solution, allowing a faradaic current to flow, even when this is only a very small measuring current. 

Redox [26], ion-selective [27-30] and ISFET [31-32] potentiometric sensors have been widely used in FIA applications. In contrast, voltammetric [33,34] and potentiometric [35,36] stripping, couiometry [37,38] and conductimetry [39-41] have received less attention from FIA researchers. 

The general tendency to miniaturize chemical sensors and to make them more convenient has led to the developement of potentiometric sensors with solid internal contact. These sensors include coated wire electrodes (CWE), hybrid sensors and ion sensitive field-effect transistors (ISFET). The contact can be a conductor, semiconductor or even an insulator. The price which has to be paid for the convenience of these sensors is in the more restrictive design rules which have to be followed in order to obtain a sensor with the performance comparable to the conventional symmetrical ion-selective electrode. 

Solution potentiometric sensors, such as ion-selective electrodes and ISFETs, rely on measurement of potential difference between two electrodes, the indicator (working) and the auxiliary (reference). This signal has its... 

Electrolyte-insulator-semiconductors are the basis for silicon field-effect chemical sensors and include ISFETs/ChemFETs, light-addressable potentiometric sensors (LAPSs) and capacitive sensors. The first ISFET was invented in 1970. ... 

Ion solvation has been studied extensively by potentiometry [28, 31]. Among the potentiometric indicator electrodes used as sensors for ion solvation are metal and metal amalgam electrodes for the relevant metal ions, pH glass electrodes and pH-ISFETs for H+ (see Fig. 6.8), univalent cation-sensitive glass electrodes for alkali metal ions, a CuS solid-membrane electrode for Cu2+, an LaF3-based fluoride electrode for l , and some other ISEs. So far, method (2) has been employed most often. The advantage of potentiometry is that the number and the variety of target ions increase by the use of ISEs. 

On-wafer membrane deposition and patterning is an important aspect of the fabrication of planar, silicon based (bio)chemical sensors. Three examples are presented in this paper amperometric glucose and free chlorine sensors and a potentiometric ISRET based calcium sensitive device. For the membrane modified ISFET, photolithographic definition of both inner hydrogel-type membrane (polyHEMA) and outer siloxane-based ion sensitive membrane, of total thickness of 80 pm, has been performed. An identical approach has been used for the polyHEMA deposition on the free chlorine sensor. On the other hand, the enzymatic membrane deposition for a glucose electrode has been performed by either a lift-off technique or by an on-chip casting. 

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. 

A new development in the field of potentiometric enzyme sensors came in the 1980s from the work of Caras and Janata (72). They describe a penicillin-responsive device which consists of a pH-sensitive, ion-selective field effect transistor (ISFET) and an enzyme-immobilized ISFET (ENFET). Determining urea with ISFETs covered with immobilized urease is also possible (73). Current research is focused on the construction and characterization of ENFETs (27,73). Although ISFETs have several interesting features, the need to compensate for variations in the pH and buffering capacity of the sample is a serious hurdle for the rapid development of ENFETs. For detailed information on the principles and applications of ENFETs, the reader is referred to several recent reviews (27, 74) and Chapter 8. 

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