CUSTOM HIGH-DENSITY, HIGH-SELECTIVITY DNA ARRAYS

提出了一种将高密度合成DNA阵列与高选择性斑点DNA阵列相结合的方法。它是基于一项专有技术，允许快速和负担得起的定制阵列序列。合成DNA阵列和斑点DNA阵列都有各自的优点和问题。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、经济地定制。点阵通常具有较长的探针，因此具有较高的选择性。在研究实验室中定制它们更容易，也更便宜。然而，探针与底物的多点附着降低了探针分子结合的可用性，并可能在定量分析中引入序列特异性偏差。此外，制造用于定位的探针既昂贵又耗时。该方案旨在将合成阵列的高密度与斑点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执行器在每个合成步骤中精确地将试剂液滴定位在同一区域上。因此，由位置误差引起的噪声本质上是低的，允许每个合成步骤引入的副产物含量极低。这将允许合成更长的探针，弥合目前两种可用阵列技术之间的差距。建议的商业应用：基因组学研究和基因测试工具已经是一个价值数百万美元的市场，并且正在迅速增长。所提出的技术的独特优势可能使Nanolytics公司成为这些应用的一次性和仪器的主要供应商。Nanolytics为用户提供了快速、经济地在内部合成高密度DNA阵列的能力，这将导致市场扩张。

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.