Electronic Sequencing in Graphene Nanopores

我们的研究表明，单层石墨烯是制备高分辨率纳米孔探测器的理想膜，用于检测单个DNA分子及其碱基的存在。我们的目标是开发实现可扩展纳米孔测序设备所需的工具和程序，该设备将显著减少未来的从头测序 通过直接识别单链基因组DNA分子上的核苷酸碱基，这些DNA分子通过一系列精确尺寸的石墨烯纳米孔顺序驱动，从而降低了成本。最终的系统旨在提供相对高质量的序列，使用不到100万个细胞的DNA覆盖6.5倍的基因组，而不需要扩增或标记。具体的 目的是：a)实施石墨烯边缘溅射工艺，以促进纳米孔阵列的高精度制造；b)使用离子电流阻挡或当单链DNA聚合物通过石墨烯纳米孔时平面内电导变化来优化对DNA的四个核苷酸的区分；以及c)支持跨越石墨烯孔的脂双层以 提高蛋白质孔阵列平行记录的可行性。这些目标的成功完成将为纳米孔测序设备提供关键的构建块，该设备可以以不到1,000美元的成本准确地对整个人类基因组进行测序。廉价而准确地对完整基因组进行测序的能力有可能显著改善人类生活和社会的许多方面，包括对疾病的理解、诊断、治疗和预防。

Our research has shown that a single layer of graphene is an ideal membrane in which to fabricate high resolution nanopore detectors to sense the presence of single DNA molecules and their nucleobases. Our objective is to develop the tools and procedures needed to realize a scalable nanopore sequencing device which will significantly reduce future de novo sequencing cost by directly identifying the nucleobases on single stranded genomic DNA molecules that are driven sequentially through an array of precisely dimensioned graphene nanopores. The final system is intended to provide a relatively high quality sequence from >6.5-fold coverage of a genome using DNA from fewer than 1 million cells, with no amplification or labeling. The specific aims are to: a) implement a graphene edge-sputtering process to facilitate high precision fabrication of nanopore arrays; b) optimize discrimination between the four nucleotides of DNA using ionic current blockades or in-plane conductivity change when ssDNA polymers are driven through graphene nanopores; and c) support lipid bilayers across graphene apertures to enhance the feasibility of parallel recordings from arrays of protein pores. Successful completion of these aims will provide the key building blocks of a nanopore sequencing device that can accurately sequence an entire human genome at a cost of less than $1,000. The ability to inexpensively and accurately sequence complete genomes has the potential of remarkably improving many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease.