A study on ion-sensing using field effect transistor (FET) was begun by Bergveld in the 1970s [1][2][3]. The ion-sensitive (IS) FET is now widely used as a miniaturized pH sensor, commercialized by some companies. First, the principle and structure of the ISFET are introduced in this section. A basic design of ISFET is shown in Fig. 10.1a. ISFET has silicon substrate with field-effect structures such as electrolyte/IS layer/(insulator)/semiconductor structures; the space charge region in the semiconductor is modulated depending on the gate voltage (V g ), same as a typical metal-oxide-semiconductor (MOS) FET. A typical bias V g versus drain-source current (I ds ) characteristic of the device that has silicon nitride/silicon dioxide/silicon is shown in Fig. 10.1b. This characteristic is quite similar to the MOSFET. A prominent difference between ISFET and MOSFET is that the gate voltage for the operation of the device is applied by an electrochemical reference electrode through the electrolyte in contact with the gate insulator. The threshold voltage (V th ) could shift according to the value of the pH of the solution. In the MOSFET, the V th would shift