Label-free CMOS DNA sensor with on-chip noise reduction scheme for real-time dna quantification

Abstract

In this research, we have been proposed and demonstrated a label-free field-effect sensing array integrated with CMOS readout circuitry to detect the surface potential determined by the negative charge in deoxyribonucleic acid (DNA) molecules for real-time detection and quantification of the products generated by polymerase chain reaction (PCR) process. Moreover, we have explored a non-surface binding detection technique which is the measurements of DNA molecules without immobilizing them on the sensing surface for the real-time sequential monitoring of their concentrations because DNA detection method using immobilization and hybridization is not suitable for real-time measurement. For implementing field-effect sensing array with CMOS readout circuitry, we have proposed a BioFET with the top-layer metal (90×90 $\mu m^2$ native $Al_2O_3$/Al) electrode which is connected to the floating gate of the sensing transistor. This allows the device to be fully compatible with standard CMOS process. The sensing electrodes are easily formed by sharing the same passivation layer opening mask with the bonding pads pattern, so that no additional processes are required to fabricate the sensing devices. For direct measurement of the surface potential change due to DNA molecules, we have proposed an operational amplifier circuit scheme by replacing proposed BioFET in one of the input transistors in a differential input stage. The field-effect transistor connected to the sensing electrode is integrated into the differential input stage of the folded-cascode amplifier to configure a voltage follower. From this circuit configuration, we can acquire the output voltage equal to the surface potential of the sensing electrode. Furthermore, the proposed sensor includes an on-chip noise reduction circuitry for suppressing offset fixed pattern noise and 1/f noise of the devices. A prototype sensor has been fabricated using 1-㎛ double-poly double-metal standard CMOS process. In this...