CUSTOM HIGH-DENSITY, HIGH-SELECTIVITY DNA ARRAYS

定制高密度、高选择性 DNA 阵列

• 批准号: 6144432
• 负责人: ALEXANDER D SHENDEROV
• 金额: $ 29.97万
• 依托单位: NANOLYTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6144432
• 关键词: DNA; microarray technology; nucleic acid chemical synthesis; oligonucleotides; technology /technique development

An approach combining the high density of synthetic DNA arrays with high selectivity of spotted ones is proposed. It is based on a proprietary technology allowing rapid and affordable customization of the array sequences. Both synthetic and spotted DNA arrays have distinct advantages and problems. Synthetic arrays have higher density, allowing higher throughput. However, at present they can not be rapidly and cost- effectively customized. Spotted arrays usually have longer probes and therefore higher selectivity. They are much easier and cheaper to customize in a research laboratory. However, multi-point attachment of the probe to the substrate reduces the probe molecules' availability for binding, and possibly introduces a sequence-specific bias in quantitative assays. Besides, generating the probes for spotting is expensive and time-consuming. This proposal is aimed at combining the high density of synthetic arrays with the high selectivity and customization capability of the spotted ones. Electrowetting actuators for reagent delivery precisely position reagent droplets over the same area at each synthesis step. Therefore, the noise due to positional errors is inherently low, allowing an extremely low content of byproducts introduced per synthesis step. This will allow longer probes to be synthesized, bridging the gap between the two currently available array technologies. PROPOSED COMMERCIAL APPLICATIONS: Tools for genomics research and genetic testing are already a multimillion- dollar market, and rapidly growing. The unique advantages of the proposed technology may allow Nanolytics Company to become a major supplier of disposables and instruments for these applications. The ability to rapidly and affordably synthesize high-density DNA arrays in-house, offered to users by Nanolytics, will lead to market expansion.

提出了一种结合高密度合成DNA阵列和高选择性点样DNA阵列的方法。它是基于一种专有技术，允许快速和负担得起的定制阵列序列。合成的和点样的DNA阵列都有明显的优点和问题。 合成阵列具有更高的密度，允许更高的吞吐量。 然而，目前它们还不能快速和成本有效地定制。斑点阵列通常具有较长的探针，因此具有较高的选择性。在研究实验室里定制它们要容易得多，也便宜得多。然而，探针与底物的多点连接降低了探针分子结合的可用性，并可能在定量测定中引入序列特异性偏差。此外，生成用于点样的探针是昂贵且耗时的。该建议旨在将高密度的合成阵列与点样阵列的高选择性和定制能力相结合。用于试剂输送的电润湿致动器在每个合成步骤中将试剂液滴精确定位在相同区域上。因此，由于位置误差引起的噪声固有地低，从而允许每个合成步骤引入极低含量的副产物。这将允许合成更长的探针，弥合两种当前可用的阵列技术之间的差距。拟议的商业应用：基因组学研究和基因检测工具已经是一个数百万美元的市场，并迅速增长。该技术的独特优势可能使Nanolytics公司成为这些应用的一次性用品和仪器的主要供应商。Nanolytics向用户提供的快速且经济实惠的内部合成高密度DNA阵列的能力将导致市场扩张。