Design and fabrication of microwell array chips for a solution-based, photogenerated acid-catalyzed parallel oligonuclotide DNA synthesis

Abstract

Development of synthesis methods using high yield acid-labile rather than photolabile group protected monomers is desirable to produce microarrays of superior quality, general adaptability and reduced cost of genetic research. However, using solution photochemistry for acid-labile deprotection requires the reaction sites being isolated from each other to prevent diffusion of reagents during a photolytic reaction. We present fabrication methods of two types of microwell array chips with different isolation strategies for carrying out parallel oligonucleotide DNA (oDNA) synthesis in the liquid phase: electroplated microwell array chips with an isolation wall and a mechanical sealing, and etched patterned microwell array chips with surface tension isolation. Both surface and bulk micromachining technologies were used for fabrication of those chips. We also discuss various problems regarding fabrication and use. The validated fidelity from the single mismatch detection of oligonucleotide DNA microwell array chips is also given to prove successful isolation of the liquid during a photolytic reaction.