Challenges in fabricating graphene nanodevices for electronic DNA sequencing
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2D Nanomaterials for Healthcare and Lab-on-a-Chip Devices Prospective Article
Challenges in fabricating graphene nanodevices for electronic DNA sequencing Jasper P. Fried, Jacob L. Swett, Xinya Bian, and Jan A. Mol, Department of Materials, University of Oxford, Oxford OX1 3PH, UK Address all correspondence to Jan A. Mol at [email protected] (Received 20 April 2018; accepted 19 August 2018)
Abstract Graphene-based electronic DNA sequencing techniques have received significant attention over the past decade and are hoped to provide a new generation of portable, low-cost devices capable of rapid and accurate DNA sequencing. However, these devices are yet to demonstrate DNA sequencing. This is partly due to complex fabrication requirements resulting in low device yields and limited throughput. In this paper, we review the challenging fabrication of graphene-based electronic DNA sequencing devices. We will place a particular focus on common fabrication challenges and look toward the development of high-throughput, high-yield fabrication of these devices.
Introduction Often referred to as the blueprint to life, deoxyribonucleic acid, or DNA, contains the set of instructions required for the development and functioning of all living organisms. Given the importance of this molecule, it is hardly surprising that there has been significant interest in the development of low-cost methods capable of rapidly reading the sequence of nucleobases in a DNA molecule.[1–4] The development of such a DNA sequencing technique promises to revolutionize modern healthcare with applications ranging from rapid disease diagnosis and treatment to biosecurity and fundamental biological research.[5,6] Many methods to sequence DNA have been proposed, however, a technique known as sequencing by synthesis has come to dominate the current market.[7] This approach typically works by adding and subsequently detecting fluorescently labelled nucleotides to a short fragment of the DNA. This process is repeated for many copies of the strand and the sequence is reconstructed by connecting overlapping regions. While this technique has been significantly optimized over the past decade, the relatively complex sample preparation, short read lengths, and expensive reagents required, place a fundamental limit on the minimum speed and cost that can be achieved using this sequencing method.[8,9] Moreover, as sequencing by synthesis relies on reconstructing the DNA sequence from short read fragments it is not suited for de novo sequencing or sequencing DNA containing large regions of repetition. An alternate sequencing technique that has recently gained significant traction is nanopore-based DNA sequencing.[9–11] These devices consist of a nanometer-sized hole in an impermeable membrane that separates two chambers of an electrolytic solution [Fig. 1(a)]. When a voltage is applied
across the membrane, ions flow through the nanopore resulting in a measurable current. Due to its negative charge, DNA can be electrophoretically driven through a nanopore by the ap
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