Collaborative Research: An Enzyme-free Amplification Technique for Ultrasensitive ELISA of Disease Biomarkers

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Technologies for diagnosis of diseases are essential to the improvement of our standard of living. Increasing detection sensitivity of a diagnostic technology can enable earlier diagnosis of diseases especially cancers and infectious diseases, thus improving treatment outcomes. The goal of this project is to establish a highly sensitive diagnostic platform through the development of a nanoparticle-based signal amplification technique. The broader impacts of the proposed research program include multidisciplinary training for graduate and undergraduate students particularly from underrepresented groups, as well as outreach activities such as mentoring local high-school students and student exchange between two institutes in summer.Enzyme-linked immunosorbent assay (ELISA) technology has been extensively used in research labs and clinical diagnostics for decades. However, its limit of detection has not been substantially improved in recent years. The proposed work seeks to develop a novel enzyme-free signal amplification technique that can substantially enhance the detection sensitivity of ELISA. This technique relies on the release of millions of tiny nanoparticles preloaded in gold vesicles. Each released nanoparticle can catalyze colorimetric reaction more effectively than a commonly-used enzyme in an ELISA. By substituting enzymes in a conventional ELISA with such nanoparticles-encapsulated gold vesicles, an enzyme-free ELISA with substantially enhanced sensitivity is established. To optimize the signal amplification system and thus enhance the detection sensitivity of associated enzyme-free ELISA, physicochemical properties of both nanoparticles and gold vesicles will be carefully controlled. To achieve the goal of this project, following research aims will be pursued: 1) Building the nanoparticles based signal amplification system; 2) Establishing the enzyme-free ELISA; and 3) Applying the enzyme-free ELISA to detecting human blood samples spiked with biomarker standards. The signal amplification technique is expected to impact the general field of in-vitro diagnostics and find a broad range of applications in biomedicine. This project will benefit the engagement of graduate and undergraduate students, especially women and minorities, into research. The research will also be integrated into outreach activities for K-12 students.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.