Sequencing DNA by transverse electrical measurements in Nanochannels

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DESCRIPTION (provided by applicant): We propose to develop a sequencing method for DNA that is based on transverse electrical measurements through the molecule. Our platform will be built around manipulating stretched and linearized DNA in nanofluidic channels, and detection using nanoelectrodes. The nanochannel platform will enable ultralong read frames of >100 kbp, which will greatly help assembly of whole genomes. Nanochannel handling will also enable multiple reads of the same molecule, and good control over the translocation speed. We expect that the technique will ultimately fulfill the cost and performance demands of the $1000- genome. In this exploratory R21 phase we aim to experimentally establish that the basic principles underlying the propose method are viable. This will form the basis of the development of a device that meets the defined figures of merit. For this exploratory grant (R21) we aim to demonstrate that we can fabricate functional nanoelectrodes/nanochannel device using proven semiconductor and nanoelectronics fabrication techniques (ebeam lithography, electromigration, nanoplating), that an electrical signal due to the DNA exists, and that the obtained signal is sequence specific. We will investigate the mechanism by which the signal arises, and will in particular examine tunneling, electrochemistry, or polarization of counterions as possible candidates. In order to understand the nature of the signal and its usefulness to sequencing, we will prepare electrode configurations with gaps between sub-5 nm (1nm) and 50 nm. Devices will be evaluated using both single and double stranded DNA. We will assess the resolution and quality of the obtained data by sequencing or GC-content mapping of synthetic block oligomers and genomic DNA samples.