Development of Digital Pneumatic Microfluidic Systems For NGS Sample Preparation

用于 NGS 样品制备的数字气动微流体系统的开发

• 批准号: 8980881
• 负责人: Seth Stern
• 金额: $ 65.98万
• 依托单位: GENAPSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-21 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980881
• 关键词: Address; Air; Architecture; Biological; Biomedical Research; Characteristics; Chemicals; Clinic; Clinical; DNA; DNA Sequence; DNA Sequence Analysis; Development; Devices; Elastomers; Film; Furuncles; Future; Genomics; Glass; Health; Healthcare; High temperature of physical object; Housing; Human; Individual; Laboratories; Libraries; Link; Liquid substance; Magnetism; Medical Research; Methods; Microfluidic Microchips; Microfluidics; Molecular Biology; Output; Performance; Phase; Play; Preparation; Process; Production; Protocols documentation; Pump; Reagent; Research; Resources; Risk; Sampling; Small Business Innovation Research Grant; Structure; System; Technology; Temperature; Time; Training; Transition Temperature; Vacuum; Work; base; clinical practice; commercialization; cost; cost effective; design; digital; elastomeric; empowered; flexibility; improved; innovation; instrument; instrumentation; magnetic beads; miniaturize; next generation sequencing; pressure; prototype; public health relevance; solute; surfactant; targeted sequencing; trend; wasting

 DESCRIPTION (provided by applicant): In recent years rapid improvements in DNA sequencing technology have positively and dramatically impacted biomedical research in the US and around the world. This progress is on-going, as the capabilities of DNA sequencing instruments continue to increase, while their cost continues to decline. Moreover, DNA sequencing technology is now on the verge of directly impacting health care as it becomes an integral part of clinical practice. Sequencing of DNA, however, first requires its isolation from is normal biological context, as well as its adaptation to a form compatible with sequencing technology. These activities are referred to as sample and library preparation, respectively. Recently it has become clear that the costs and logistical burdens associated with sample and library preparation are now, and will increasingly in the future, negatively impact dissemination of DNA sequencing technology. This is because, unlike DNA sequencing itself, which is automated within increasingly efficient DNA sequencing instruments, the costs and user burdens associated with sample and library preparation have not declined significantly. The overall aim of this Phase II SBIR application is to eliminate this critical bottleneck for both research and clinical DNA sequencing applications. GenapSys has developed innovative Digital Pneumatic Microfluidic (DPM) technology to address directly the cost and user-burden deficiencies of existing sample and library preparation methods. DPM chips and instruments promise to transform expensive and logistically burdensome sample and library preparation tasks to a convenient plug-and-play format that will reduce costs in existing applications and remove barriers to deployment of new ones. Unlike previous microfluidic technologies, DPM chips will be fabricated from low-cost materials, and with low-cost mass-production methods. They will be manufactured pre-loaded with virtually all the chemicals and reagents necessary for their function, and will reduce costs further by requiring only small quantities of each of these. n addition DPM instruments will be relatively inexpensive and compact, requiring only a small space in the laboratory or clinic. The specific aims of this Phase II SBIR proposal are designed to de-risk commercialization of DPM technology by optimizing our existing methods and designs, and by providing additional proof-of-concept for certain important features. This work involves optimization of our designs and manufacturing methods for microfluidic pumps and valves, improved high-temperature performance, and demonstration of methods to package and store chemicals and reagents on-chip. The proposed work culminates in demonstration of reliable and high quality library preparation by DPM chips and prototype instruments.

 描述（由申请人提供）：近年来，DNA测序技术的快速改进对美国和世界各地的生物医学研究产生了积极而显著的影响。随着DNA测序仪器的能力不断提高，同时其成本不断下降，这一进展正在进行中。此外，DNA测序技术现在正处于直接影响医疗保健的边缘，因为它成为临床实践的一个组成部分。然而，DNA测序首先需要将其从正常的生物环境中分离出来，以及使其适应与测序技术相容的形式。这些活动分别称为样品和文库制备。最近，已经清楚的是，与样品和文库制备相关的成本和后勤负担现在并且将来将越来越多地对DNA测序技术的传播产生负面影响。这是因为，与在日益高效的DNA测序仪器内自动化的DNA测序本身不同，与样品和文库制备相关的成本和用户负担并未显著下降。该阶段II SBIR应用的总体目标是消除研究和临床DNA测序应用的这一关键瓶颈。GenapSys开发了创新的数字气动微流控（Digital Pneumatic Microfluidic，简称PMEMS）技术，以直接解决现有样品和文库制备方法的成本和用户负担缺陷。可编程芯片和仪器有望将昂贵且后勤负担沉重的样品和文库制备任务转变为方便的即插即用格式，从而降低现有应用的成本，并消除部署新应用的障碍。与以前的微流控技术不同，微流控芯片将由低成本材料和低成本大规模生产方法制造。它们将在制造时预装其功能所需的几乎所有化学品和试剂，并将通过仅需要少量的每种化学品和试剂来进一步降低成本。此外，超声仪器将相对便宜和紧凑，在实验室或诊所中仅需要很小的空间。第二阶段SBIR提案的具体目标是通过优化我们现有的方法和设计，以及为某些重要功能提供额外的概念验证，来降低物联网技术商业化的风险。这项工作涉及优化我们的微流体泵和阀的设计和制造方法，改进高温性能，以及演示在芯片上包装和存储化学品和试剂的方法。建议的工作最终在示范的可靠和高品质的图书馆制备的芯片和原型仪器。