Miniaturization, of ISEs

An alternative approach to miniaturization of ISEs has been through ion-selective field effect transistors (ISFETs). Essentially, these integrate the ISE with the field effect transistor (FET) of the input stage of a pH/millivoltmeter, which takes the high-impedance signal of an ISE and outputs a low-impedance signal which is less sensitive to noise pick-up. 

Symmetrical placement of the ion-selective membrane is typical for the conventional ISE. It helped us to define the operating principles of these sensors and most important, to highlight the importance of the interfaces. Although such electrodes are fundamentally sound and proven to be useful in practice, the future belongs to the miniaturized ion sensors. The reason for this is basic there is neither surface area nor size restriction implied in the Nernst or in the Nikolskij-Eisenman equations. Moreover, multivariate analysis (Chapter 10) enhances the information content in chemical sensing. It is predicated by the miniaturization of individual sensors. The miniaturization has led to the development of potentiometric sensors with solid internal contact. They include Coated Wire Electrodes (CWE), hybrid ion sensors, and ion-sensitive field-effect transistors. The internal contact can be a conductor, semiconductor, or even an insulator. The price to be paid for the convenience of these sensors is in the more restrictive design parameters. These must be followed in order to obtain sensors with performance comparable to the conventional symmetrical ion-selective electrodes. 

There were several advances in this product first of all, the miniaturized instrument, just a pen with a small screen, where the current, recalculated in mg/dL of glucose was directly displayed. Then the concept of disposable screen printed elearodes, which allowed discarding the sensor after the use, and more important allowed the elimination of the calibration step. This was an incredible step in the sensor community. All sensors known, from pH glass electrodes to all kind of ISE, etc should pass the calibration step", where the sensor must be calibrated every day and sometimes before every measurement. The disposable screen printed electrodes do not need the calibration which simplifies enormously the use of it. The sensors became simple and user-friendly objects and diabetic people started to use it for individual monitoring and a large market was created. In 1996 Exatech was sold to Abbott for 867 million of US dollars. 

Despite the problems mentioned ISEs are inherently simple, easy-to-use devices, suitable for automated analysis and miniaturization, their operation does not require the addition of chemical reagents or the use of explosive gases. These advantages have been quite decisive in the rapid expansion of ISEs used in clinical analysis in the last two decades. 

Miniature Shapes. Miniaturization of liquid-membrane ISEs uses the same techniques as are used with solid-membrane electrodes. Coated-wire electrodes are manufactured by dip-coating a metallic wire with a polymer layer of e.g. PVC. The oldest example (Fig. 7.9, left) is a piece of platinum wire soldered to the internal lead of a coaxial cable. The end of the wire was formed into the shape of a ball by melting it in a hot flame. The polymer coating was applied by repeated dipping into the polymer solution (Freiser 1980). 

The resistance of potentiometric sensors does not seem to be a cracial point a priori. Membranes with a very low conductivity (lower than 10S cm- ) are sometimes used in ISE devices. Nevertheless, a too-high resistance leads to a capacitive behavior of the sensor. The parasitic charges which appear in the circuit or electrical noise (intrinsic or extrinsic) may lead to erroneous results. To avoid this disadvantage, thin sensitive membranes may be used (pH or pNa glass membranes), but they are very fragile. Generally, a conductivity of about 10- to 10- S cm- is required. Miniaturization of devices allows a lower resistance of the SIC to be obtained, but the interface impedance is not fundamentally modified because it depends on the electrochemical kinetics, which is a function of the interfacial area. 

Concerning future prospects, new fast ionic conductors coitld be used as membranes for ISE devices or in gauges of the second kind. The miniaturization of devices is a promising way for mass production, using microtechnologies. Solid materials are very well adapted for such devices. The major difficulty is the achievement of a reproducible composition of the SIC. Another advantage of such microdevices is a lowering of their impedance, but, as was mentioned previously, only the resistance of the SIC is decreased. The intrinsic response time is not modified any more. 

The main task and challenge of the sensor development was the miniaturization of the ISEs. When the active area of the internal reference element reservoir (pHEMA) was decreased, the sensors lost their ability to operate for more than a few days, if at all. Keeping the reservoir O.D. of 3 mm, the membrane diameter was then decreased from 6 to 7 mm to 4 mm (Fig. 6.9). When performing studies... 

The first dielectric material that was used on open gates of field effect transistors (ion-sensitive field effect transistor, ISFET) was silicon dioxide by Bergveld in 1970. The problem in the ISFET structure is the poor insulation between the device and the solutions. The ISFET structure was improved by using ion-sensitive electrodes (ISE). With field effect transistors the gate area can be extended by using a conductive wire covered with the sensitive membrane. This new approach helps in enhancing the stability, sensitivity, and flexibility in shaping i.e., miniaturization of pH-sensitive devices. 

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