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

摘要：单个生物纳米粒子的检测和分析是在分子水平上理解生物过程的关键工具。单粒子分析被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。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；它们可以检测瞬时流动或附着在表面的粒子，这些粒子会干扰分子特性；而且，他们依靠复杂的设备或技术，需要很多专业知识。该项目将通过开发一种用于传感和分析单个分子的新设备来解决这些挑战。它可以在不影响生物功能的情况下对单个粒子进行长时间观察，然后对该粒子进行长时间的研究。将这些功能集成到单个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项目、加州大学圣地亚哥分校的UC LEADS和CAMP项目参与其中。杨百翰大学将通过美光基金会（MICRON Foundation）在immersion学生的帮助下，实施一个名为“芯片营”（Chip Camp）的项目，向K-12学校提供额外的服务。在圣克鲁斯，加州大学圣克鲁兹分校、当地一所K-8学校和一名儿童之间建立了一种新的、独特的合作伙伴关系。的博物馆将会发展，以加强大学与社会的联系，并提供适合年龄的纳米生物学和纳米生物传感的机会。技术总结：Holger Schmidt的应用光学小组（加州大学圣克鲁斯分校）、Harry Noller的分子生物学小组（加州大学圣克鲁斯分校）和Aaron Hawkins的微加工小组（杨百翰大学）将在单粒子陷阱中结合纳米孔电检测和荧光分析，探索一种传感和分析单个生物纳米粒子的新方法。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，并被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。这个项目的变革性影响将是创造出第一个集成设备，可以利用电子和光学读数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数百到数千个单个分子，如病毒或核糖体，从而创建可靠的统计数据集。该奖项由两个项目联合颁发——(1)化学、生物工程、环境和运输系统部门（工程局）的纳米生物传感，以及(2)生物基础设施部门（生物科学局）的生物研究仪器开发。

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).