I-Corps: Nanofluidic System for Rapid DNA Sequencing and Biomolecule Analysis

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The broader impact/commercial potential of this I-Corps project is to revolutionize the healthcare industry by providing a fast, low-cost, and easy-to-use DNA sequencer to healthcare providers for clinical use. DNA stores the genetic information of all living organisms and the successful development and commercialization of a fast and low cost DNA sequencing technique will be important not only to the advancement of fundamental medical research in biomarker discovery and oncology studies, but also to the future development of personalized medicine which relies on treating individual patients based on their unique genomic composition. The commercial sequencing methods such as SMRT and NGS require either a high sequencing charge or a large capital investment. The nanofluidic based DNA sequencer is a ?direct' sequencing technique that can be significantly more cost effective than the existing commercial methods.This I-Corps project opens up a new path for DNA sequencing. The core technology of the nanofluidic based DNA sequencer is a nanochannel chip with embedded nanoelectrodes capable of determining the sequence a single-stranded DNA by measuring the unique electron tunneling properties of individual nucleotides. Manufacturing of the nanofluidic system involves a sequential application of MEMS processing, atomic force microscopy, and focused ion beam. The nanofluidic system belongs to a group of novel chip-based DNA sequencing techniques which utilize disposable chips to directly measure the DNA sequence. Unlike the commercial methods which rely mostly on biochemical processing, the chip-based methods do not require time-consuming sample pre-processing steps such as PCR nor expensive facilities for parallel processing. The nanofluidic system measures the electron tunneling current of a single DNA strand as it is dragged across a set of nanoelectrodes. Since the molecular structures of the nucleotides in the DNA strand are different, their tunneling currents are also different. The nanofluidic system determines the DNA sequence by analyzing the variation of the tunneling current along the DNA strand.