EPSCoR Research Fellows: NSF: Development of Electrochemical Aptamer-based Sensors for Multi-analyte Detection of Cardiovascular Disease Biomarkers

This Research Infrastructure Improvement (RII) EPSCoR Research Fellows project would provide a fellowship to an Assistant Professor and training for a graduate student at the University of South Carolina Columbia. Cardiovascular diseases (CVDs) represent a major global health challenge, making early diagnosis critical for effective treatment. Traditional methods like enzyme-linked immunosorbent assays (ELISA) detect CVD biomarkers accurately but are limited by high costs, long processing times, complex procedures, and potential errors.

To address these challenges, this project aims to develop and fundamentally characterize electrochemical aptamer-based (E-AB) sensors to rapidly and accurately identify multiple CVD-related markers at low concentrations. E-AB sensors utilize lab-synthesized DNA or RNA pieces known as aptamers, which act as keys that bind specifically to target molecules.

The interactions between these aptamers and target analytes produce detectable changes in electrochemical signals. However, existing E-AB sensors face stability issues due to their reliance on large gold electrode surfaces, making reuse challenging. The proposed E-AB sensors will overcome these limitations by integrating carbon-based electrode arrays with nano-sized designs and advanced aptamer technology to enhance the sensor’s stability and performance.

Students involved in this project will gain hands-on experience in designing and characterizing biosensors, enhancing their technical and measurement skills. Additionally, the Simoska Laboratory will involve undergraduate and K-12 students from diverse backgrounds and minority-serving institutions in South Carolina via research and outreach programs, inspiring them to pursue STEM careers.

Given that CVDs are the leading cause of death globally, developing robust analytical sensing methods for early detection is critical. The overarching goal of this proposal is to design and fundamentally characterize chemically specific electrochemical sensors for the rapid detection, direct measurement, and continuous monitoring of physiologically relevant CVD metabolites.

This work will be conducted under the mentorship of collaborators at the University of Cincinnati, a leading expert in electrochemical instrumentation and E-AB sensors. The proposed multiplexed sensors will evaluate and implement multi-analyte detection strategies using nucleic acid recognition elements at electrochemical carbon ultramicroelectrode arrays (CUAs), offering high reliability, reproducibility, and improved specificity for biomarkers.

Compared to large, planar gold electrode surfaces typically used with E-AB sensors, CUAs are a versatile electrode platform for functionalization with aptamers. Additionally, the Systematic Evolution of Ligands by Enrichment (SELEX) technique will be used to tailor-design aptamers with high specificity and functionalize them with novel redox probes for CVD biomarker detection, enhancing sensor reliability.

Continuous square-wave voltammetry (cSWV) will be employed to study sensor surface behavior and aptamer folding kinetics. The array-based E-AB sensors will enable rapid, sensitive, and multi-analyte detection of CVD biomarkers. The broader impacts include advanced E-AB sensing technologies for South Carolina, training students through research and courses at USC, and engaging economically disadvantaged schools in STEM outreach, fostering a diverse future in the field.

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.