Development of an integrated CMOS DNA detection biochip

This paper presents a CMOS DNA detection biochip using an electrical detection method with self-assembly multilayer gold nanoparticles (AuNPs). Each measuring spot of this biochip consists of three major parts; a pair of electrodes with a nanogap, a current amplifier circuit, and a heater with an embedded temperature sensor. The biochip is first fabricated by a TSMC (Taiwan Semiconductor Manufacturing Company Ltd.) 0.35 μm 2P4M standard CMOS process. Then, post-CMOS micromachining etch processes are used to expose the surface of the nanogap to test samples for the establishment of multilayer AuNPs through hybridization between single strand DNAs in the samples. The gap distance between a pair of electrodes is 350 nm. Before taking DNA detection measurements, self-assembly monolayer AuNPs is established on the nanogap surface between two microelectrodes. Multilayer AuNPs can be observed if hybridization between single strand DNAs occurs. An approximately 1000-fold increase in electric current between the multilayer AuNPs over the monolayer AuNPs serves an indication of the presence of target DNA in test samples. After integrating the electrodes with an embedded current amplifier, the electric current of multilayer AuNPs is amplified to the order of mA that can be easily measured by a commercial Volt-Ohm-Milliammeter. The heating system with a heating element and a temperature sensor can be used to distinguish single base-pair mismatch hybridization from complementary hybridization for the establishment of multilayer AuNPs. The lowest detectable concentration of target DNA on this biochip is 0.1 nM.