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

1402848 /1402880 Schmidt/ HawkinsNON-TECHNICAL SUMMARY：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某些局限性：它们通常使用单一检测机制;它们检测流动中的瞬时颗粒或束缚在表面上的颗粒，这些颗粒可能会干扰分子特性;并且它们依赖于需要大量专业知识的复杂设备或技术。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。它将能够将单个颗粒保持在适当的位置进行长时间观察，而不会损害生物功能，然后长时间研究颗粒。将这些功能集成在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个分子。除了纳米电子学，微/纳米纤维和单分子分析的研究生培训外，来自代表性不足群体的本科生将通过杨百翰大学的IMMERSE计划以及UCSC的UC LEADS和CAMP计划参与其中。杨百翰大学将通过一个名为“芯片营”的项目，在IMMERSE学生的协助下，通过MICRON基金会开展对K-12学校的额外宣传。在圣克鲁斯，一个新的和独特的合作伙伴关系之间的UCSC，当地的K-8学校，和一个孩子？大学将建立一个博物馆，以加强大学与社区之间的联系，并提供适合年龄的纳米生物学和纳米生物传感。技术概要：Holger施密特（加州大学圣克鲁斯分校）的应用光学小组，Harry Noller（加州大学圣克鲁斯分校）的分子生物学小组和Aaron Hawkins（杨百翰大学）的微制造小组之间的合作努力将探索一种新的方法，通过将基于纳米孔的电检测和荧光分析结合在单粒子阱中来检测和分析单个生物纳米粒子。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，并且在诸如分子生物学、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的广泛学科中使用。该项目的变革性影响将是创建第一个集成设备，可以使用电学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至数千个单个分子，如病毒或核糖体，创建强大的统计数据集。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的纳米生物传感（工程理事会），和（2）生物基础设施司（生物科学理事会）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).