SBIR Phase I: Pathogen Interception: A new method for finding and identifying genetic sequences

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响将是能够快速，廉价地确定各种病原体的存在和基因序列。最重要的是，这项技术可以在没有预先假设哪些生物是预期的情况下实施。测序将通过直接电鉴定基因组序列的结构单元（碱基）来完成。这项技术的潜在社会影响是提供一种快速（在一分钟内）筛查个人感染的方法。在入境口岸和适当的社区环境中进行筛查将最大限度地减少疾病传播，并允许在美国边境快速识别和治疗任何感染者。此外，除了直接应用外，该技术还可以提高对任何生物体中正常基因序列的科学理解。如果其预期的速度，高精度和低成本得以实现，该技术可能会在人类体外诊断和人类基因组测序中找到应用。第一阶段项目的研究将为一种自动化的商业仪器提供概念验证。该项目旨在确定遗传构建块（核苷酸碱基）的身份和顺序，这些碱基包括样品溶液中存在的任何基因组序列。该测序将通过检查序列中的每个碱基在其通过电泳穿过两个非常紧密间隔的隧穿电极时改变隧穿电流的能力来进行。隧穿是一种众所周知的量子力学效应，它对存在于其电极之间的物体（这里是给定的特定核苷酸碱基）的电配置非常敏感。迄今为止，这项技术的实验一直不成功，因为基因序列不能在隧道电极上移动得足够慢，从而无法区分它们的碱基。这里的研究将克服这个问题，通过修改的几何形状和溶液条件的电泳和可能的改进方法的隧道电流检测。通过应用该技术获得的数据有望增强目前对核苷酸碱基化学的理解。该解决方案可能允许检测潜在的生物和医学重要性的核苷酸碱基修饰。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase I project will be the ability to quickly and inexpensively determine the presence and genetic sequence of a wide variety of pathogenic organisms. Most importantly, this technology could be implemented without prior assumptions as to which organisms are expected. Sequencing will be accomplished by direct electrical identification of the building blocks, the bases, of the genomic sequence. The potential societal impact of this technology is to provide a method to screen individuals quickly (under a minute) for the presence of infections. Screening at ports of entry and in appropriate community settings will minimize disease transmission and allow for the quick identification and treatment of any infected individuals at US borders. In addition, beyond this immediate application, the technology may also enhance scientific understanding of normal genetic sequences in any organism. If its anticipated speed, high accuracy, and low cost are realized, this technology may find applications in human in vitro diagnostics and human genome sequencing. The studies in this Phase I project will lead to a proof-of-concept demonstration for an automated, commercial instrument.The project seeks to determine the identity and order of the genetic building blocks, the nucleotide bases, comprising any genomic sequences present in a sample solution. This sequencing will be done by examining the ability of each base in the sequence to modify a tunneling current as it is passed by electrophoresis across two very closely spaced tunneling electrodes. Tunneling is a well-known quantum mechanical effect, and it is quite sensitive to the electrical configuration of the object (here a given specific nucleotide base) present between its electrodes. Experiments with this technology to date have been unsuccessful because genetic sequences have not been able to be moved slowly enough across the tunneling electrodes for their bases to be distinguished. The studies here will overcome this problem by modifications of the geometry and solution conditions of the electrophoresis and possibly with improved methods of tunneling current detection. The data obtained through the application of this technology is expected to enhance the current understanding of nucleotide base chemistry. The solution may permit the detection of nucleotide base modifications of potential biological and medical importance.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.