CMOS Biosensors for the Detection of DNA Hybridization in High Ionic-Strength Solutions

Label-free detection of biomolecules using ion-sensitive field-effect transistors (ISFETs) in physiological solutions is limited by the Debye charge-screening effect of the electrical double layer. Most ISFET measurements are therefore performed in diluted ionic-strength solutions to detect the interface potential change on specific binding of biomolecules. The novel CMOS ISFETs proposed in this study have a capacitor structure in the oscillator readout to provide modulation of the surface electric field to reduce the charge screening and nonideal signal drift. Signal modulation was applied at frequencies higher than the ion-strength-dependent cut-off frequency, with the highest applied frequency being approximately 100 MHz among the four proposed designs. The measured results revealed a pH sensitivity from 52.3 to 54.4 mV/pH in terms of the floating-gate potential change. Direct DNA hybridization in a high ionic-strength solution was successfully measured with a near picomolar-level resolution.