以CMOS-MEMS技術開發之整合型DNA檢測系統

Abstract

An integrated DNA detection system using CMOS-MEMS technology was developed in this thesis. The integrated DNA detection system includes two parts: 1. CMOS biochip: The CMOS biochip, which is fabricated by TSMC 0.35 um 2P4M standard CMOS process combined with post-micromachining processes, is composed of DNA biosensors (microelectrodes), a current amplifier circuit, and a temperature system for single base pair mismatch detection. 2. Integrated microfluidic device: A glass substrate where the CMOS biochip was bonded and a PDMS microfluidic chip. A novel technique using a self-assembly method combined with cascode current mirrors to amplify electrical signals is presented. The electric current passing through the gold nanoparticle multilayer, which is formed by complementary target DNA, exceeds that through the gold nanoparticle monolayer by three orders of magnitude. The lowest detectable concentration of target DNA on this biochip is 0.1 nM. After being amplified by the current mirrors, the electrical signal of the multilayer gold nanoparticle structure over a nanogap is successfully amplified to the level of mA and can then be measured by a commercial Volt-ohm-Milliammeter. With temperature sensors and heaters, single mutation of target DNA could be distinguished by about 2oC difference in melting temperature. Finally, after the combination of CMOS biochip and PDMS microfluidic chip, the whole DNA detection system can be portable and the ability of automation can be also increased.