EAGER: Nanopipette-based immunosensor

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Mirkin1251232Intellectual Merit Solid-state nanopores have been widely employed in different sensing applications from Coulter counter to DNA sequencing devices. These versatile sensors can detect analytes of different size ranging from single molecules to bacteria. However, most reported applications of nanopores are qualitative, and their physical size and geometry are often not suitable for in situ measurements in microenvironments. This proposal is aimed at developing a new biosensor platform for the detection of antibodies and protein biomarkers based on the use of nanometer-sized pipettes. Like a nanopore, a pipette can sense the analyte that enters its aperture and partially blocks the ion current flowing through it. However, a nanopipette offers several important advantages including the ease of fabrication, small physical size, and needle-like geometry that makes it suitable as a probe for scanning electrochemical microscopy (SECM). The translocation of metal nanoparticles will be used as a model system to establish the principles of resistive-pulse sensing with nanopipettes. By thoroughly characterizing the pipette size and geometry, we will demonstrate the quantitative relationship between the frequency of the recorded single particle events and the diffusion flux of particles to the orifice. This will enable quantitative determination of analyte species in solution. Following proof-of-concept experiments with bare metal particles, we will work on the detection and quantitation of antibodies (e.g., antipeanut antibody) attached to nanoparticles and cancer biomarkers (e.g., prostate specific antigen, PSA). Overall, the proposed work will result in the development of a new biosensing platform for quantitative analysis at the level of single biomolecules or single nanoparticles. This potentially transformative concept can cause the paradigm shift in bioelectroanalytical chemistry.Broader Impacts The proposed approach to biosensing can enable accurate diagnostics of allergies, cancer and other diseases based on the detection of low concentrations of antibodies and protein biomarkers. It can find other applications in biomedical testing including DNA sequencing.The requested support is mostly for graduate and postdoctoral stipends. The graduate students and postdoctoral fellows involved in this project will get multidisciplinary research experience in sensors, electrochemistry, bioanalytical chemistry and nanoscience. The results of this research will be broadly disseminated through publications and professional presentations. The requested funds will enable us to contribute to ongoing CUNY efforts to recruit underrepresented minority STEM students and participate in its diversity initiatives. This project will provide research opportunities to undergraduates and high school students.