CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids

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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.