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），独特地将高灵敏度和速度相结合，以克服现有技术的局限性。该项目将为遗传物质检测提供紧凑、快速、准确和用户友好的设备。当遗传物质在外部电场中振动时，这些装置通过测量遗传物质的电反应来工作。这种创新具有彻底改变生物工程的潜力，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，它有望加强大流行病管理和全球卫生保健。这个项目的一个关键方面是它的教育推广。该计划旨在吸引从幼儿园到大学的各个层次的学生，特别强调将女性和在科学、技术、工程和数学（STEM）领域代表性不足的群体纳入其中。该项目设想了学术机构、工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进该领域和确保拟议研究的广泛应用和影响至关重要。低丰度核酸寡聚物的无扩增电子检测对于推进各种疾病的即时诊断具有重要的前景。然而，已知的全电方法难以同时实现高灵敏度和快速检测。本研究的目的是开发一种纳米机电转导方法，并将其与微流控通道纵轴横向电泳相结合，将核酸检测的灵敏度和时间效率提高两个数量级。为了实现总体目标，将实现以下具体目标：1)确定与石墨烯晶体管相连并在交变电场中振荡的核酸纳米结构的纳米机电转导原理；2)通过将纳米机电转导与横向电泳相结合，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，因为它脱离了电核酸传感器的现状，即直接将探针-靶标核酸杂交的发生转化为电响应，通过实现一种新的纳米机电转导途径，依靠未配对和配对DNA链之间内在的柔韧性差异，一种内在的力学性质。该项目的预期成果包括全面理解纳米机电转导原理，以最大限度地提高核酸检测的多样性，选择性和灵敏度（特定目标1），并基于微设置实现超高灵敏度和时间效率的核酸检测（特定目标2）。这些结果预计将对生物工程的进步和快速、准确的即时核酸检测产生重大的积极影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.