Excellence in Research: a PEC-AbP Dual Signal Amplification Method and its Mechanistic Study of Signal Transduction for DNA Sensing

DNA sensing techniques have been widely applied in daily life such as medical diagnosis, biowarfare defense, forensic science, and environmental monitoring, and were significantly promoted during the past pandemic, e.g., reverse transcription polymerase chain reaction (RT-PCR) test for COVID-19. Rapid DNA detection with high sensitivity, specificity, and accuracy is in high demand, however limited by signal readout. This project is aimed at developing an innovative dual signal amplification method by integrating two different signal amplification methods, i.e., materials science- and optical-based. The research goals are to strengthen signal readouts and build field-friendly DNA sensors that are amenable to point-of-need applications with ultrasensitivity. The discovery of fundamental science and transformative technology will potentially enable a reliable multiplexed high-throughput DNA analysis platform that may greatly benefit health care in society and facilitate research and applications in biomedical and life science. The scientific learning of this interdisciplinary research performed at the HBCU (NC A&T) and MSI (UNC Greensboro) will advance sensing mechanism understanding, instruct and train students especially underrepresented students, in research and education, and engage K-12 STEM educators and students in science. Genetic information with or without variation coded within nucleic acids, indicating an illness or health outcome, is termed a nucleic acid biomarker, thus plays a crucial role in precision medicine. Sensitive and selective detection of nucleic acid biomarkers with rapid signal amplification is the key for early screening and diagnosis of human diseases. This project is aimed at developing an innovative dual signal amplification method and understanding the signal transduction mechanism for enhanced DNA sensing. The work is built on the seamless integration between amplification-by-polymerization (AbP) in DNA sensing for optical clarity change on surface based on effective mass growth upon DNA recognition and in-planar metallic film nanoarrays for plasmon-exciton coupling (PEC) optical enhancement. The research will be conducted in three stages to (1) fully explore the potential of the AbP-PEC dual signal amplification platform, (2) investigate the fundamental mechanism of the amplified signal transduction pertaining to the AbP-produced film thickness and plasmonic nanoslit structure, and (3) optimize the AbP-PEC platform for a portable DNA sensor in point-of-care diagnostics. The outcome may be transformative towards a multiplexed, rapid, highly sensitive, visible (by naked eyes) analysis of DNA in biofluids. 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.