Xiaochuan Zhou¹, Robert Setterquist¹, Xiaolian Gao², Peilin Yu², Eric LeProust², Laëtitia Sonigo², Jean Philippe Pellois², Hua Zhang², Erdogan Gulari³, and Ning Gulari^3 
1 Xeotron Corporation, Houston, TX 77030 
² University of Houston, Department of Chemistry, Houston, TX 77204-5641 
³ University of Michigan, Department of Chemical Engineering and Center for Display Technology and Manufacturing, Ann Arbor, MI 48109 
xczhou@email.msn.com 

Practical advancement in biochip technologies for routine use in drug discovery and genomic applications will require a flexible and affordable chip-fabrication technology. To address this need, a multidiscipline project has been initiated. A programmable, light-directed DNA/RNA array synthesizer that uses solution-based photochemical synthesis is being developed for efficient production of high-density DNA/RNA chips. This presentation reports on the latest results of instrument development and photochemistry effort. 

The project consists of three main integrated tasks: (1) design and construction of a programmable photolithographic system, (2) development of a novel solution photochemistry for nucleic acid synthesis, and (3) design and fabrication of synthesis microreactors. At the heart of the photolithographic system is a commercially available digital spatial optical modulator, which accurately produces light patterns that are used for initiating parallel high-density nucleic acid synthesis. The digital spatial optical modulator effectively replaces the necessity for using photomasks technologies. The solution photochemistry under investigation is a modification of well-established conventional synthesis protocols. Microreactors are being developed using standard microfabrication processes in order to implement the DNA/RNA synthesis photochemistry. Each reactor contains an array of microfabricated reaction wells (synthesis sites). Each microwell serves to individually isolate each reaction during the light-directed parallel sequence syntheses. 

The outcome of the undertaken project will lead to a prototype DNA/RNA array synthesizer. The prototype instrument will be further developed into a commercial model. The envisioned instrument will allow researchers to make high-density and high fidelity DNA/RNA-chips of their own designs at an affordable cost. In addition, there is obvious potential to expand the light-directed chemical approach in this project for synthesis of other combinatorial arrays (peptide, carbohydrate, and small molecule).