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

这个小型企业创新研究(SBIR)第一阶段项目的更广泛影响将是能够快速和廉价地确定各种病原体的存在和遗传序列。最重要的是，这项技术可以在不预先假设预期哪些生物体的情况下实施。测序将通过对基因组序列的构建块、碱基进行直接电气鉴定来完成。这项技术的潜在社会影响是提供一种方法，快速(不到一分钟)筛查个人是否存在感染。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，除了这种直接的应用，这项技术还可以加强对任何生物体中正常基因序列的科学理解。如果实现其预期的速度、高精度和低成本，这项技术可能会在人类体外诊断和人类基因组测序中得到应用。该第一阶段项目中的研究将导致一种自动化的商业仪器的概念验证演示。该项目寻求确定遗传构建块的身份和顺序，即核苷酸碱基，包括样本溶液中存在的任何基因组序列。这种测序将通过检测序列中每个碱基的能力来完成，因为当隧道电流通过两个间隔非常紧密的隧道电极通过电泳传递时，该序列中的每个碱基都可以修改隧道电流。隧道效应是一种众所周知的量子力学效应，它对存在于电极之间的物体(这里是给定的特定核苷酸碱基)的电学构型非常敏感。到目前为止，这项技术的实验一直没有成功，因为基因序列在隧道电极上的移动速度还不够慢，无法区分它们的碱基。这里的研究将通过改变电泳的几何结构和溶液条件，并可能通过改进隧道电流检测方法来克服这一问题。通过应用这项技术获得的数据有望加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。该裁决反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.