| Active electrochemical complementary metal-oxide-semiconductor (CMOS) biochips could eliminate the need for physically-bulky and expensive optical instruments required in traditional fluorescence-based deoxyribonucleic acid (DNA) assays, enabling the design of low-cost, portable devices for clinical and point-of-care genetic diagnostic applications. Unlike fluorescence detection, which can function well using a passive substrate such as a glass slide, multiplexed electrochemical genomic assays require an electronically-active substrate to analyze each array site. CMOS technology is well-suited to this application because it can incorporate electrochemical transducers, enables integration of electronic instrumentation to reduce platform size, and can be manufactured at relatively low cost.;The design of a second CMOS biochip that supports interfacial impedance measurements for label-free genomic assays is also presented. This chip contains a 10x6 working-electrode array multiplexed to five acquisition channels. Each channel consists of a programmable transimpedance amplifier, buffer, switched-capacitor variable-gain amplifier, and cyclic ADC. This platform does not require the use of redox-labelled DNA targets and, therefore, reduces the time and cost associated with DNA sample preparation.;This thesis presents the design, implementation, post-processing details, and validation of an active 0.25-mum CMOS biochip for electrochemical-based genomic assays using DNA target molecules conjugated with the electroactive molecule ferrocene. Integrated potentiostat electronics drive redox reactions, sense DNA hybridization occurring at a 4x4 array of on-chip gold working electrodes using dedicated current-input dual-slope analog-to-digital converters (ADCs), and transmit digital data off chip for analysis. A novel post-processing technique is used to microfabricate a surface-electrode array that is corrosion resistant and biologically compatible. Experimental results from quantitative, multiplexed, and specific DNA detection down to solution target concentrations of 4 nM demonstrate the utility of this platform. In addition, multiplexed, real-time sensing of DNA hybridization is demonstrated with the active CMOS biochip, a task that is difficult, if not impossible, using traditional fluorescence-based DNA microarrays. |
