Electronic Sequencing in Graphene Nanopores

Harvard University, Cambridge MA

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Abstract

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.