We will develop an ink-jet based microdispensing system for in situ synthesis of oligonucleotides in a microarray format for gene expression studies (expression chip). Multi-channel ink-jet devices will be utilized to increase throughput by an order of magnitude over single dispenser per base methods. The ink-jet based approach will: 1) allow flexibility in oligonucleotide design, 2) ensure high-throughput manufacture capabilities 3) provide a low cost alternative to current commercially available oligonucleotide-based microarrays, and 4) generate microarrays in a format that can be used with commercially available fluorescence detection scanners/instruments. The microarrays will facilitate the discovery of drug targets, which may interact with the genes and/or gene products expressed during the disease state. The toxicological and pharmacological responses to these drug leads can also be monitored. The use of such microchips will allow medical professionals to prescribe the most effective drugs, having the least side effects, based on a gene expression profile of an individual. Low cost microarrays will help to place this enabling technology into the hands of all researchers, thereby promoting our understanding of the changes in gene expression during cellular responses to developmental cues, physiological or pathological conditions, or external stimuli.
The in situ oligonucleotide synthesizer will provide low cost custom and """"""""off-the-shelf"""""""" microarrays for various research applications. Data from such arrays can be used to build a bioinformatics database of gene expression profiles of cells and tissues under various conditions to provide for objective measurements of normal and disease states and disease associated pathways. Gene expression microarrays will also provide essential information for the characterization of normal versus diseased states, leading to the development of new treatment.
