ISFET with CMOS IC Combined with DNA Aptamer to Detect NT-proBNP

We present application of an ISFET with integrated CMOS readout circuits for the detection of N terminal prohormone of brain natriuretic peptide using specific DNA aptamer. The ISFET was based on a MOSFET with a gate extended to the surface of the chip through aluminum metallization, with a sensitive area covered by a tantalum oxide film deposited using ALD method. A reading circuit based on an operational amplifier in repeater mode has been developed. All circuits are integrated into a $7 \times 7 \mathrm{~mm}$ test chip. DC measurements of the manufactured circuits have been carried out and $\mathrm{I}-\mathrm{V}$ and pH dependence characteristics are shown. Sensitive surface of individual ISFETs was pointwise modified with DNA aptamer using click reaction. Aptamer was then hybridized to a short complementary DNA strand. Addition of N-terminal prohormone of brain natriuretic peptide to the ISFET gate caused aptamer structure reorganization and release of the complementary DNA which was detected by the sensor. The ISFET response was selective to the target protein. Thus, the developed ISFET with integrated CMOS readout circuits can serve for the development of aptasensors.