OLIGONUCLEOTIDE MICROARRAYS FOR GENE EXPRESSION

申请人？我们将开发一种基于喷墨的微点胶技术 用于原位合成微阵列形式寡核苷酸的系统， 基因表达研究（表达芯片）。多通道喷墨装置将 用于将吞吐量提高一个数量级， 分配器根据基础方法。基于喷墨的方法将：1）允许 寡核苷酸设计灵活性，2）确保高通量生产 能力3）提供对当前商业上的低成本替代方案 可获得的基于多核苷酸的微阵列，以及4）在 可与市售荧光检测一起使用的格式 扫描仪/仪器。 微阵列将有助于发现药物靶点， 与疾病期间表达的基因和/或基因产物相互作用 状态对这些药物的毒理学和药理学反应可以 也被监控。这种微芯片的使用将使医疗专业人员 处方最有效的药物，副作用最小，基于 个体的基因表达谱。低成本的微阵列将有助于 把这项技术交给所有研究人员， 促进我们对细胞周期中基因表达变化的理解， 对发育线索、生理或病理条件的反应，或 外部刺激。 拟定商业应用： 原位寡核苷酸合成仪将提供低成本的定制和“现成的” 用于各种研究应用的微阵列。 来自这些阵列的数据可用于构建 一个生物信息学数据库的基因表达谱的细胞和组织下， 提供客观测量正常和疾病状态以及疾病的条件 相关路径。 基因表达微阵列也将提供必要的信息 用于表征正常与疾病状态，从而导致 新疗法

APPLICANT?S DESCRIPTION: 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. PROPOSED COMMERCIAL APPLICATION: 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.