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

1402848/1402880施密特/霍金斯非技术摘要：单个生物纳米颗粒的检测和分析是在分子水平上理解生物过程的关键工具。单粒子分析应用于广泛的学科，如分子生物学、分析化学、生物医学、生物物理学、生理学、基因组学和蛋白质组学。尽管迄今为止取得了成功，但单分子研究仍存在一定的局限性：它们通常使用单一的检测机制；它们检测流动中的瞬时颗粒或被拴在表面的颗粒，这可能会干扰分子的性质；它们依赖于需要大量专业知识的复杂仪器或技术。该项目将通过开发一种新的感测和分析单个分子的设备来应对这些挑战。它将能够在不损害生物功能的情况下，将单个颗粒保持在适当的位置进行长时间的观察，然后对该颗粒进行更长时间的研究。将这些能力集成在一块芯片上将简化实验程序，使研究人员能够快速连续地分析许多单分子。除了纳米电子学、微/纳米制造和单分子分析方面的研究生培训外，来自代表性不足群体的本科生将通过杨百翰大学的沉浸式课程以及加州大学洛杉矶分校的加州大学Leads和CAMP课程参与其中。杨百翰大学将通过一个名为“芯片营？”的项目，向K-12学校提供更多的服务。这是通过美光基金会在沉浸式学生的帮助下进行的。在圣克鲁斯，加州大学圣克鲁斯分校、当地的一所K-8学校和S儿童博物馆将建立一个新的独特的合作伙伴关系，以加强大学和社区之间的联系，并在适合年龄的水平上提供纳米生物学和纳米生物传感的机会。技术摘要：这项由加州大学霍尔格·施密特(加州大学圣克鲁斯分校)的应用光学小组、哈里·诺勒(加州大学圣克鲁斯分校)的分子生物学小组和亚伦·霍金斯(布里格姆·杨大学)的微制造小组将探索一种新的方法，通过在单粒子陷阱中结合基于纳米孔的电检测和荧光分析来传感和分析单个生物纳米颗粒。单个生物纳米颗粒的检测和分析是在分子水平上了解生物过程的重要工具，广泛应用于分子生物学、分析化学、生物医学、生物物理学、生理学、基因组学和蛋白质组学等学科。该项目的变革性影响将是创造第一个集成设备，可以使用电子和光学读数来捕获和分析单个生物分子。这将使研究人员能够快速连续地研究成百上千个单独的分子，如病毒或核糖体，创建强大的统计数据集。

1402848 / 1402880 Schmidt / HawkinsNON-TECHNICAL SUMMARY: Detection and analysis of single biological nanoparticles is a critical tool 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.