PFI:AIR-RA: Commercializing of a Molecular Analysis Platform for Plant Genomics in an Industry/University Ecosystem

PFI：AIR-RA：工业/大学生态系统中植物基因组学分子分析平台的商业化

• 批准号: 1538813
• 负责人: Abraham Lee
• 金额: $ 80万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1538813&HistoricalAwards=false
• 关键词: PFI; AIR; RA; Commercializing; Molecular

This PFI: AIR Research Alliance project focuses on the translation and transfer of an integrated microfluidic based screening and testing analysis platform that has the potential to dramatically improve the efficiency and effectiveness of breeding plants. In the current agriculture biotech industry, genetic analyses of complex communities of plant cells are typically carried out in a homogenized, whole community fashion where the output is global information on the average state of the population of cells. This can mask the true extent of cellular heterogeneity that is present by averaging properties and potentially missing intriguing outliers. Molecular analysis at the single cell level would lead to better capability to develop enhanced strains of plant cells that thrive under various conditions. Thus there is a need for a tool that can provide single cell-molecular analysis in large populations, capable of high throughput while preserving heterogeneity information, and tailored to the agriculture genetics industry. The goal of this project is to develop such a tool by applying microfluidic lab-on-a-chip technologies for molecular and single cell analyses derived from the NSF I/UCRC "Center for Advanced Design and Manufacturing of Integrated Microfluidics" (CADMIM) where expertise and discoveries in the design, microfabrication, and manufacturing of microfluidic devices for cellular and molecular processing and detection are utilized. Not only will the proposed technology enable the single cell analysis, it also has the potential to lower the cost per molecular test by an order of magnitude over current methodologies. Current technology used in the agriculture biotech industry relies on discrete, bulky robotic systems that are time and labor intensive and require larger amounts of power, sample, and reagents resulting in much higher cost per test to analyze large numbers of samples.The innovation ecosystem that will be enhanced includes CADMIM, UC Irvine, Johns Hopkins University, and DuPont Pioneer. The UC Irvine site of CADMIM brings microfluidic cellular manipulation, lysing, and micro-scale fluidic handling expertise. Johns Hopkins University brings microfluidic molecular processing and detection expertise. DuPont Pioneer, a leading developer and supplier of plant genetics to farmers worldwide, brings the plant genomic expertise and agriculture biotech business knowledge. Students and post-doctoral fellows from both universities will gain entrepreneurial and technology translation experience through their frequent interactions with DuPont Pioneer's technical team in understanding the current limitations in plant genotyping biotechnology, how a multi-continent international company works to solve large-scale problems, what is required for disruptive technology to displace current working technology paradigms, and how interdisciplinary teams communicate to develop cutting edge solutions.This project addresses several technology gaps as it translates from research discovery toward commercial application. Plant cell genotype screening requires millions of cell-level verification tests and subsequent further massive molecular analyses of specific cell types. The current plant cell processing and molecular analysis platforms consist of multiple cumbersome and expensive cell processing machines that are time consuming and rely on skilled lab workers operating them in sequence. This greatly limits the throughput of cells being analyzed and makes it cost prohibitive for applications that require field-based plant seed sampling and testing. With the integrated microfluidic technologies developed in this project, the multiple steps will be integrated on a compact and potentially portable platform, using smaller liquid volumes to obtain faster results.

该 PFI：AIR 研究联盟项目专注于基于微流体的集成筛选和测试分析平台的翻译和转让，该平台有可能显着提高植物育种的效率和效果。在当前的农业生物技术行业中，复杂植物细胞群落的遗传分析通常以同质化、整体群落的方式进行，其输出是关于细胞群平均状态的全局信息。 这可能掩盖了细胞异质性的真实程度，这种异质性是通过平均属性和可能丢失的有趣的异常值而存在的。 单细胞水平的分子分析将有助于开发出在各种条件下茁壮成长的增强型植物细胞株。 因此，需要一种能够在大量群体中提供单细胞分子分析、能够在保留异质性信息的同时实现高通量、并且适合农业遗传学行业的工具。该项目的目标是通过应用来自 NSF I/UCRC“集成微流体先进设计和制造中心”(CADMIM) 的微流体芯片实验室技术来开发这样的工具，该技术用于分子和单细胞分析，该中心拥有用于细胞和分子处理和检测的微流体装置的设计、微加工和制造方面的专业知识和发现。 被利用。所提出的技术不仅能够实现单细胞分析，而且还有可能将每个分子测试的成本比现有方法降低一个数量级。 目前农业生物技术行业使用的技术依赖于离散、笨重的机器人系统，这些系统是时间和劳动力密集型的，需要大量的电力、样品和试剂，导致每次分析大量样品的测试成本更高。将得到增强的创新生态系统包括 CADMIM、加州大学欧文分校、约翰霍普金斯大学和杜邦先锋大学。 CADMIM 加州大学欧文分校分校提供微流体细胞操作、裂解和微尺度流体处理专业知识。约翰·霍普金斯大学带来了微流体分子处理和检测专业知识。杜邦先锋是一家领先的植物遗传学开发商和供应商，为全球农民提供植物基因组专业知识和农业生物技术业务知识。两所大学的学生和博士后将通过与杜邦先锋技术团队的频繁互动获得创业和技术翻译经验，了解当前植物基因分型生物技术的局限性、跨洲国际公司如何解决大规模问题、颠覆性技术需要什么来取代当前的工作技术范式，以及跨学科团队如何沟通以开发尖端技术 该项目解决了从研究发现到商业应用的几个技术差距。植物细胞基因型筛选需要数百万次细胞水平验证测试以及随后对特定细胞类型的进一步大规模分子分析。 目前的植物细胞处理和分子分析平台由多台笨重且昂贵的细胞处理机器组成，这些机器耗时且依赖熟练的实验室工作人员依次操作。 这极大地限制了被分析细胞的通量，并且使得需要现场植物种子采样和测试的应用的成本过高。 通过该项目开发的集成微流体技术，多个步骤将集成在一个紧凑且可能便携式的平台上，使用更小的液体体积来获得更快的结果。