CUSTOM HIGH-DENSITY, HIGH-SELECTIVITY DNA ARRAYS

提出了一种结合高密度合成DNA阵列和高选择性斑点DNA阵列的方法。它基于一种专有技术，允许快速且负担得起的阵列序列定制。合成DNA阵列和斑点DNA阵列都有明显的优势和问题。合成阵列具有更高的密度，从而允许更高的吞吐量。然而，目前还不能快速、经济地对它们进行定制。斑点阵列通常具有更长的探针，因此具有更高的选择性。在研究实验室定制它们要容易得多，成本也低得多。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，并可能在定量分析中引入序列特异性偏差。此外，制造用于定位的探头既昂贵又耗时。该方案旨在结合合成阵列的高密度和斑点阵列的高选择性和定制化能力。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同一区域。因此，由于位置误差导致的噪声本质上很低，使得每个合成步骤引入的副产品含量极低。这将允许合成更长的探针，弥合目前可用的两种阵列技术之间的差距。拟议的商业应用：用于基因组研究和基因测试的工具已经是一个价值数百万美元的市场，而且还在迅速增长。拟议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向用户提供的在内部快速且可负担得起地合成高密度DNA阵列的能力将导致市场扩大。

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.