10b Integrated Microfluidic and Electrasense Microarray Biochips for DNA Analysis

Robin H. Liu and Sho Fuji. CombiMatrix Corp., 6500 Harbour Heights Parkway, Mukilteo, WA 98275

Microarray-based bioassays have become a key enabling technology in molecular biology. We have developed semiconductor microarrays, each with over 12,000 features and has the potential to detect hundreds of different viruses and bacteria simultaneously. These microarrays are manufactured using in situ synthesis of over 12,000 unique DNA oligonucleotides based on a modification of phosphoamidite chemistry under electrochemical control. In addition to conventional fluorescence-based microarrays, we have developed a unique electrochemical detection (ECD) based ElectraSense microarray platform, which eliminates the need for an expensive and sensitive laser-based optical system and fluorescent reagents.

In addition, we have investigated different approaches for integrating microfluidics and automating sample processing and fluidic handling with microarray. DNA microarray assays involve multi-stage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Using microfluidic technology to integrate and automate all these steps in a single device is highly desirable in many practical applications. We developed a self-contained and fully integrated device that consists of a microfluidic plastic cartridge and 12K CustomArray chip. Microfluidic components such as electrochemical pumps, bubbling micromixers, and normally close check valves, are integrated in the cartridge. Gene expression study of the human leukemia cell line (K562) and genotyping tests to identify influenza A subtypes have been successfully performed in the devices.