Collaborative Research: Nanopore-gated on-chip trapping for single bioparticle sensing and analysis

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1402848 / 1402880Schmidt / HawkinsNON-TECHNICAL SUMMARY: Detection and analysis of single biological nano particles are critical tools for understanding biological processes on the molecular level. Single particle analysis is employed across a wide range of disciplines such as molecular biology, analytical chemistry, biomedicine, biophysics, physiology, genomics, and proteomics. Despite their success to date, single molecule studies suffer from certain limitations: they typically use a single detection mechanism; they detect particles transiently in flow or tethered to a surface which can interfere with the molecular properties; and, they rely on complex apparatuses or techniques that require a lot of expertise. This project will address these challenges by developing a new device for sensing and analyzing of individual molecules. It will enable holding a single particle in place for prolonged observation without compromising biological function and then investigate the particle for an extended period of time. The integration of these capabilities on a single chip will simplify experimental procedures and enable researchers to analyze many single molecules in rapid succession. In addition to graduate student training in nanoelectronics, micro/nanofabrication, and single molecule analysis, undergraduate students from underrepresented groups will be involved through the IMMERSE program at BYU, and the UC LEADS and CAMP programs at UCSC. Additional outreach to K-12 schools will be implemented at BYU with a program called "Chip Camp" which is conducted through the MICRON Foundation with the assistance of IMMERSE students. In Santa Cruz, a new and unique partnership between UCSC, a local K-8 school, and a children?s museum will be developed to strengthen the connections between the University and the community, and to provide exposure to nanobiology and nanobiosensing at an age-appropriate level. TECHNICAL SUMMARY: This collaborative effort between the Applied Optics group of Holger Schmidt (UC Santa Cruz), the molecular biology group of Harry Noller (UC Santa Cruz), and the Microfabrication group of Aaron Hawkins (Brigham Young University) will explore a new approach to sensing and analyzing single biological nanoparticles by combining nanopore-based electrical detection and fluorescence analysis in a single-particle trap. Detection and analysis of single biological nanoparticles is a critical tool for understanding biological processes on the molecular level and employed across a wide range of disciplines such as molecular biology, analytical chemistry, biomedicine, biophysics, physiology, genomics, and proteomics. The transformative impact of this project will be to create the first integrated device that can trap and analyze single biomolecules using both electrical and optical readouts. This will enable researchers to investigate hundreds to thousands of individual molecules such as viruses or ribosomes in rapid succession, creating robust statistical data sets.This award is being made jointly by two Programs- (1) Nano-Biosensing, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate), and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).