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

这个i-Corps项目的更广泛的影响/商业潜力是通过向医疗保健提供商提供快速、低成本和易于使用的DNA测序仪用于临床，从而彻底改变医疗保健行业。DNA存储着所有生物的遗传信息，一种快速、低成本的DNA测序技术的成功开发和商业化不仅对于推进生物标志物发现和肿瘤学研究的基础医学研究具有重要意义，而且对于依赖于根据患者独特的基因组组成治疗个体的个性化医学的未来发展也具有重要意义。商业测序方法，如SMRT和NGS，要么需要很高的测序费用，要么需要大量的资本投资。基于纳米流体的DNA测序仪是一种直接测序技术，比现有的商业方法更具成本效益。I-Corps项目为DNA测序开辟了一条新的道路。基于纳米流体的DNA测序仪的核心技术是嵌入纳米电极的纳米通道芯片，能够通过测量单个核苷酸独特的电子隧道特性来确定单链DNA的序列。纳米流体系统的制造包括MEMS处理、原子力显微镜和聚焦离子束的顺序应用。该纳米流体系统属于一组基于芯片的新型DNA测序技术，该技术利用一次性芯片直接测量DNA序列。与大多数依赖生化处理的商业方法不同，基于芯片的方法不需要耗时的样品前处理步骤，如聚合酶链式反应，也不需要昂贵的并行处理设施。纳米流体系统测量单个DNA链在拖过一组纳米电极时的电子隧道电流。由于DNA链中核苷酸的分子结构不同，它们的隧道电流也不同。纳米流体系统通过分析DNA链上隧道电流的变化来确定DNA序列。

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.