CAREER: Ultrafast molecular separation and integrated near-field light-metal-fluorophore interactions for biomarker detection at point-of-care

Cancer, obesity, and opioid abuse pose a combined threat to the health of the people in the United States, affecting a significant portion and costing more than $250 billion per year in medical expenses. The unavailability of sensing technologies addressing the fundamental molecular changes related to disease initiation, progression, and therapeutic interventions is a critical roadblock for successfully combating these diseases.

MicroRNA (miRNAs) are short non-coding RNA fragments (~17–25 nucleotides) that are involved in post-transcriptional regulation of gene expression either by degrading or repressing translation of multiple target mRNAs. Since miRNAs are involved in early gene regulations that initiate biochemical cascades for many diseases, they could provide reliable and clinically relevant information earlier than other downstream biomarkers (e.g., antigens).

Also, miRNA biomarkers are stably expressed in circulating blood and, therefore, miRNA detection could be used to develop sensitive, minimally invasive, and low-cost diagnostics tests. Unfortunately, miRNAs have not yet been translated or utilized in the clinical diagnosis of any disease. This is in part due to the lack of sensitive and low-cost miRNA detection approaches that are applicable at clinics, hospitals, and medical centers.

The outcome of this research plan will be a complete, ready-to-go miRNA detection platform that includes data collection, quality control, and built-in statistical methods for data analysis. In addition, proposed broader impact activities aim to introduce research into the undergraduate electrical engineering curriculum of North Dakota State University.

Also, outreach efforts will aim to attract underrepresented groups (middle school girls and Native American community college students) to the field of engineering by introducing biosensor concepts and providing an opportunity to produce a technical solution to a societal or community problem. The PI will also work with high school STEM teachers in Native American schools to help them develop learning plans for their students.

These activities will broaden the participation of underrepresented groups in STEM education and the workforce.

The research goals of this project are to study three fundamental concepts in the areas of small nucleic acid-field (electric and temperature) interactions and near-field light-to-metal-to-fluorophore energy transfer: (1) study of fundamental nucleic acid and field (electric and temperature) interactions to selectively separate fluorophore-labeled short (~17–25 nucleotide) miRNA-DNA duplex molecules from other single-stranded nucleic acid molecules of similar lengths and concentrate them near electrodes, (2) study of AC electric fields to maximize each near-field light-metal-fluorophore interaction that contributes to enhancing the fluorescence intensity of fluorophores, and 3) integration of multiple interactions to enhance the fluorescence intensity well beyond current capabilities. This new knowledge will be used to develop a template for a universal biosensor that detects any individual or combination of biomarker-types in any buffer.

Specifically, the proposed 5-year project will develop miRNA-based point-of-care technology to address the critical need for the analysis of clinical samples.This project is jointly funded by the Electrical, Communications and Cyber Systems Division (ECCS), and the Established Program to Stimulate Competitive Research (EPSCoR).

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.