Ordered Arrays for Advanced Sequencing Systems

描述（由申请人提供）：尽管人类基因组的测序在几年前就基本完成了，但对DNA序列数据的生产仍然有巨大的需求。可测序的生物体和个体的数量仍然受到当今桑格测序方法的长时间、高复杂性和过高成本的显著限制。目前正在努力创造新的化学物质，以在不使用电泳的情况下读出DNA链的碱基;然而，为这些测序系统提供的样品制备过程尚未完全制定和优化。许多先进的测序方法需要数百万组扩增的DNA片段，每组由数百万个相同的片段组成。这些集合被附着到固体支持物上，然后处理固体支持物以读出序列;然而，在玻璃支持物上产生DNA模板阵列目前需要一组复杂的步骤。在第一阶段，我们将研究生产有序格式与随机格式的样品阵列的好处，并将生产原型高密度有序阵列。成功完成第一阶段的里程碑，以及随后的第二和第三阶段项目的完成，将导致开发一个超高通量原型系统，该系统可以生产具有成本效益的高密度芯片，用于与先进的DNA测序仪器结合使用。最终，下一代样品制备和测序技术可以比现有系统更便宜和更快地产生几个数量级的DNA序列，可以帮助实现个性化医疗的承诺。最终，为复杂生物体的基因组产生非常便宜的详细DNA序列信息的能力将加速整个生物学的发现，并为药物基因组学提供基础，药物基因组学是一种新的治疗模式，其中药物是基于个体基因型而不仅仅是观察到的症状。一个可以廉价地对特定肿瘤内的DNA进行测序的系统将有助于癌症研究人员了解与各种类型癌症相关的突变，并有助于找到更有效的治疗方法。由于一个人的基因组序列永远不会改变，因此在未来，每个人都有可能在出生时对其基因组进行测序，电子记录并使用其一生的流量来定制他们的医疗保健。

DESCRIPTION (provided by applicant): Although the sequence of the human genome was substantially completed a few years ago, there is still a huge need for the production of DNA sequence data. The number of organisms and individuals which may be sequenced is still significantly constrained by the lengthy time, high complexity and exorbitant costs of today's Sanger sequencing methods. Significant effort is currently going into the creation of new chemistries to read out the bases of DNA strands without the use of electrophoresis; however, the sample preparation processes to feed these sequencing systems has yet to be fully worked out and optimized. Many of the advanced sequencing methods require many millions of sets of amplified DNA fragments, with each set being comprised of millions of identical fragments. These sets are attached to a solid support which is then processed to read out the sequence; however, the generation of the array of DNA templates on a glass support currently requires a complex set of steps. In Phase I, we will examine the benefits of producing arrays of samples in an ordered format versus a random one and will produce prototype high-density ordered arrays. Successful accomplishment of the Phase I milestones and completion of subsequent Phase II and Phase III projects will result in the development of an ultra-high throughput prototype system which can produce cost-effective high-density chips for use in conjunction with advanced DNA sequencing instruments. Ultimately, this next generation of sample preparation and sequencing technologies, which can produce DNA sequence several orders of magnitude cheaper and faster than existing systems, can help to make the promise of personalized medicine a reality. Ultimately, the ability to produce very inexpensive detailed DNA sequence information for complex organisms' genomes will both lead to accelerated discoveries throughout biology and provide the basis for pharmacogenomics, a new paradigm in therapeutics wherein medicines are prescribed based on individual genotypes rather than just observed symptoms. A system which could inexpensively sequence the DNA within a specific tumor will help cancer researchers understand the mutations associated with various types of cancers and help lead to more effective treatments. Since one's genomic sequence never changes, it is likely in the future that everyone will have their genomes sequenced at birth, recorded electronically and used throughput their lifetime to customize their healthcare.