Merit: This project focuses on developing a plasmonic-based electrochemical impedance microscope (P-EIM). Impedance has been widely used to detect and study biological processes, but it lacks spatial resolution and thus imaging capability. The PIs have shown that impedance can be converted into a plasmonic signal. This paradigm shift approach allows them to measure local impedance optically, and leads to a novel microscope that can images electrical or electrochemical responses of a biological sample. Since most biological molecules carry charges or partial charges (proteins, DNA and many small molecules) or change surface impedance upon binding to the surface, P-EIM can detect and image them via electrical responses, which is in contrast to mass, fluorescence or refractive index-based detection principle. It can study binding affinity and kinetics of small molecules and proteins in microarray format, follow the binding events of single viruses, and image various cellular and subcellular processes, including ion channel and GPCR activities, with sub-micron spatial resolution and sub-millisecond temporal resolution. P-EIM is label free, which overcomes limitations associated with label-based detection and imaging technologies. The PIs have recently established the basic principle of P-EIM, and successfully applied it to study several molecular, viral and cellular-level processes and activities, including ultra-small volume and ultra-fast protein binding kinetics, single virus-antibody interactions, and imaging single cell apoptosis and electroporation. To maximize the impact of this new capability on biological research, this project will integrate P-EIM with total internal reflection fluorescence and surface plasmon resonance microscopy into a multi-functional microscope, and work with researchers in different fields, including proteomics, immunology, neurology and cell biology, to develop new applications. Specific objectives include: 1) Real time high-throughput measurement of molecular interactions and kinetics, particularly small molecule- protein interactions; 2) Monitoring kinetics of virus binding and invasion; 3) Single and sub-cellular kinetics with milliseconds time resolution. Broader impacts: Optical microscopy has enabled many breakthroughs in biological research, and evolved into a truly indispensable tool in nearly every life science research lab. Continued advances in biology will benefit from new imaging capabilities that provide unique and complementary information to the current microscopy technologies. The present project will introduce an impedance-imaging mode to optical microscopy, allowing for optical imaging of electrical and electrochemical responses of biological samples, a capability that current optical microscopy lacks. A key task of the project is to integrate this advance into the conventional optical microscope to provide simultaneous bright field, fluorescence, surface plasmon resonance and electrochemical impedance imaging capability. In order to transform the new imaging capability into a powerful tool for biological research, the PIs will collaborate with over ten research groups to develop different biological applications, create tutorial materials via Youtube, Wikipedia, and a dedicated website, and work with the university technology transfer office to facilitate commercialization. The project will provide unique opportunities for interdisciplinary training and nurturing the next generation of scientists and engineers. In addition to training graduate and postdoctoral students, the PIs propose new educational initiatives in undergraduate research taking advantage of several existing programs and infrastructures at ASU. Examples include the NSF REU program, Biodesign high school student internship, and Fulton Undergraduate Research Initiative (FURI) at ASU, which provide additional resources for recruiting and supporting undergraduate students, including groups underrepresented in science and engineering, at the early stages of their studies in the college. The project will also provide students with unique international and interdisciplinary collaboration experience.
|Effective start/end date||8/1/12 → 7/31/16|
- NSF: Directorate for Biological Sciences (BIO): $651,205.00
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