CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids

该项目的目的是开发一种新的方法来检测遗传物质，如脱氧核糖核酸(DNA)和核糖核酸(RNA)，独特地结合了高灵敏度和快速，以克服现有技术的局限性。该项目将带来紧凑、快速、准确和用户友好的遗传物质检测设备。这些设备通过测量遗传物质在外部电场中振动时的电反应来运行。这种创新有可能给生物工程带来革命性的变化，能够更有效地测试遗传物质，特别是在没有先进实验室设施的地区。因此，它承诺加强大流行管理和全球医疗保健。该项目的一个关键方面是其教育宣传。该计划旨在让从幼儿园到大学的所有级别的学生参与进来，特别强调纳入女性和通常在科学、技术、工程和数学(STEM)领域代表性较低的群体。该项目设想了学术机构、行业和其他关键组织之间的合作。这种伙伴关系对于进一步推动该领域的发展和确保拟议研究的广泛应用和影响至关重要。低丰度核酸寡聚体的免放大电子检测对于推进各种疾病的医疗点诊断具有重要的前景。然而，已知的全电子方法难以同时实现高灵敏度和快速检测。这项研究的目的是开发一种纳米机电转换方法，并将其与沿微流控通道纵轴运行的电泳相结合，将核酸检测的灵敏度和时间效率提高两个数量级。为了实现这一总体目标，将实现以下具体目标：1)确定绑在石墨烯晶体管上并在交变电场中振荡的核酸纳米结构的纳米机电转换原理；2)将纳米机电转换与横向电泳相结合，实现快速、高灵敏度的核酸检测。该研究项目具有很高的创新性，因为它不同于电子核酸传感器的现状，通过实施一种新的纳米机电转导途径，直接将探针-目标核酸杂交的发生转化为电响应，这依赖于未配对和配对DNA链之间柔韧性的内在机械性能差异。该项目的预期成果包括全面了解纳米机电转导原理，以最大限度地提高核酸检测的多重性、选择性和灵敏度(具体目标1)，并在微观设置的基础上实现超高灵敏度和时效性核酸检测(具体目标2)。这些结果预计将对生物工程的进步和快速、准确的护理点核酸测试产生重大的积极影响。这一奖项反映了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 aim of this project is to develop a novel method for detecting genetic materials such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), uniquely combining high sensitivity with speed to overcome the limitations of existing techniques. The project will lead to compact, quick, accurate, and user-friendly devices for genetic material detection. These devices operate by measuring the electrical responses of genetic materials when they vibrate in an external electric field. Such innovation holds the potential to revolutionize bioengineering, enabling more efficient testing of genetic materials, especially in regions without advanced laboratory facilities. Consequently, it promises to enhance pandemic management and global healthcare. A key aspect of this project is its educational outreach. The plan aims to engage students across all levels, from kindergarten through college, placing special emphasis on the inclusion of women and groups typically underrepresented in science, technology, engineering, and mathematics (STEM) fields. The project envisions collaboration among academic institutions, industry, and other key organizations. Such partnerships are essential for further advancing the field and ensuring the widespread application and impact of the proposed research.Amplification-free electronic detection of low-abundance nucleic-acid oligomers holds significant promise for advancing point-of-care diagnostics of various diseases. However, known all-electrical methods struggle to simultaneously achieve high sensitivity and rapid detection. The objective of this proposed research is to develop a nanomechanoelectrical transduction approach and integrate it with electrophoresis running transversal to the longitudinal axis of a microfluidic channel, to enhance both the sensitivity and time efficiency of nucleic acid detection by two orders of magnitude. To attain the overall objective, the following specific aims will be met: 1) Determine the nanomechanoelectrical transduction principle of nucleic-acid nanostructures tethered to a graphene transistor and oscillating in an alternating electric field, 2) Achieve rapid, high-sensitivity nucleic-acid detection by integrating the nanomechanoelectrical transduction with transversal electrophoresis. The research project is highly innovative because it departs from the status quo of electrical nucleic-acid sensors, which directly convert the occurrence of probe-target nucleic-acid hybridization into electrical response, by implementing a new nanomechanoelectrical transduction pathway relying on the intrinsic difference in pliability, an intrinsic mechanical property, between unpaired and paired DNA strands. The expected outcomes of this project include a comprehensive understanding of the nanomechanoelectrical transduction principle for maximizing the multiplexity, selectivity, and sensitivity in nucleic-acid detection (specific aim 1) and accomplishing ultra-high sensitivity and time-efficient nucleic-acid detection based on a micro setup (specific aim 2). These outcomes are expected to generate significant positive impact on bioengineering advancement and rapid, accurate point-of-care nucleic-acid testing.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.