Session: Rising Stars of Mechanical Engineering Celebration & Showcase

Paper Number: 149749

149749 - Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids 

Amplification-free electronic detection of low-abundance nucleic-acid oligomers holds significant promise for advancing point-of-care (PoC) diagnostics of various diseases, including COVID-19, Ebola, HIV, and cancer. 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 electrical sample-delivery techniques to enhance both the sensitivity and time efficiency of nucleic acid detection by two orders of magnitude. Reaching this objective is important because it will deliver nucleic-acid sensors with a 100-fold improvement in both time efficiency and sensitivity, bringing these attributes into a practically applicable range for rapid, accurate PoC nucleic-acid testing.

The central hypothesis of the proposal is that, with target nucleic-acid oligomers delivered, nanostructural nucleic-acid probe strands tethered to a graphene transistor and oscillating in an alternating electric field produce transistor current spectra that are highly characteristic of the probe hybridization status. These characteristics are determined by the difference in pliability between the hybridized and unhybridized nucleic-acid strands and are therefore immune to non-specific electrostatic and electrochemical interferences. To attain the overall objective, I will pursue the following specific aims: 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 the sample-delivery techniques. 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 developing and implementing a new nanomechanoelectrical transduction pathway relying on the intrinsic difference in pliability — a 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). This project will advance the state of knowledge in all-electronic nucleic-acid biosensing, focusing on (1) how the characteristic current spectra of a graphene transistor depend on the hybridization status of oscillatory nanostructural nucleic-acid oligomers tethered to it, (2) how to implement the nanomechanoelectrical transduction principle to boost both sensitivity and time efficiency, and (3) how to synergize the nanomechanoelectrical transduction approach with other bioengineering technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR) and hybridization chain reaction (HCR). 

Presenting Author: Jinglei Ping University of Massachusetts Amherst

Presenting Author Biography: Jinglei Ping is an Associate Professor of Mechanical and Industrial Engineering at UMass Amherst, also affiliated to Biomedical Engineering. He received his B.S. and M.Phil from Sun Yat-sen University in 2003 and 2008, respectively and his Ph.D. from the University of Maryland–College Park in 2013. Before joining UMass in 2018, He first served as an occupational trainee at Monash University, then became a postdoctoral fellow, and later a research associate, at the University of Pennsylvania. Jinglei Ping's research aims to elucidate and harness innovative physicochemical principles at the micro/nano scale, enabling the development of devices and systems for processing, detecting, and stimulating biosystems. He is the recipient of the AFOSR YIP Award in 2019, the NIBIB Trailblazer Award in 2021, the NIGMS MIRA Award in 2023, and the NSF CAREER Award in 2024.

Authors:

Jinglei Ping University of Massachusetts Amherst