Rapid Prototyping Method and Design Library for Universal POC Application

描述（由申请人提供）：大多数微流体护理点（POC）分析装置已经使用硅（Si）、玻璃和聚合物作为微流体基底的基底来制造。塑料基材，如聚碳酸酯（PC）、聚对苯二甲酸乙二醇酯（PET）、聚（二甲基硅氧烷）（PDMS）、聚酰亚胺、聚甲基丙烯酸甲酯（PMMA），使用常规模塑工艺以低成本为生物化学或医疗应用提供了广泛的生物相容性参数。市售聚合物/塑料的各种生物相容性表面特性为POC应用提供了优于传统硅或玻璃基制造方法的关键竞争优势。目前，市售POC设备（如血糖仪或i-STAT血液化学测定）无法在护理点提供微生物诊断，从而无法对生物恐怖主义和新兴传染病带来的潜在威胁做出快速反应。学术界和工业研究都对POC器件开发产生了浓厚的兴趣，但高昂的初始资本投资和较长的开发周期显着减少了实际开发工作量。一个快速，廉价，POC测试能够适应现有的分析协议具有高度的准确性将是一个重大的进步。此外，与其从零开始建立POC系统，一个随时可用的POC平台将加快发展努力，以阻止广泛传播的疾病的迅速出现。该SBIR第一阶段应用的总体目标是开发和验证通用床旁（POC）系统的原型制造过程，该系统能够适应生命科学研究和临床诊断的现有检测方案。我们建议建立一个标准分子分析检测的设计库，并为每个研究人员提供POC原型服务，以解决NIH和CDC的高优先级倡议。我们将从可以在I期进行10次多重检测（遗传检测和/或免疫检测）的检测盒设计开始，并扩展到更常见的检测方案，以使检测盒能够在II期进行POC系统的优化、大规模生产和临床研究。利用通过POC盒原型制造的优化盒设计，可以在经由所提出的快速制造方法对原型盒进行分析验证之后通过注射成型来进行盒的大规模制造。在这项为期6个月的第一阶段研究中，我们将建立一个用于POC检测盒原型设计的设计库，并在6小时内制造10个检测特定集成检测盒（ASIC），从设计订单到发货准备就绪。对于第1阶段的10次检测，原型检测盒的良好销售成本（COGS）将低于20美元。POC控制系统的COGS将低于5000美元。 公共卫生相关性：在本提案中，我们将利用我们正在进行的合作协议（NIDCR U 01 DE 017790和U 01 AI 082457）开发用于多重癌症标志物筛查和快速病原体识别的床旁（POC）诊断盒。根据为我们正在进行的合作协议开发和生产这些检测盒所获得的经验和知识，本拟定I期研究将建立一个设计库，以适应最常见的分子分析测定，包括基因检测、免疫测定和电解质检测。在第一阶段成功完成后，我们将把标准测试盒设计模块投入市场，并为任何有兴趣探索POC应用的研究机构提供快速POC测试盒原型制造服务。通过原型制造服务，POC系统开发通常需要的高初始资本投资和长开发周期将不再是POC方法的科学开发和商业化努力的障碍。使用能够同时进行蛋白质和RNA检测的多路病原体鉴定盒作为模型，我们将展示一种通用的POC分子分析系统，该系统可以由最终用户使用现有的协议和试剂在一周内快速适应用于免提POC现场测试。该系统将在非传统环境下的分子分析研究和开发领域产生巨大的有利影响。研究人员可以拥有自己定制的POC系统版本，而无需开发风险和资本投资，以加速床旁检测的进步。

DESCRIPTION (provided by applicant): Most microfluidic point-of-care (POC) analysis devices have been fabricated using silicon (Si), glass and polymer as substrates for the microfluidic substrate. Plastic substrates, such as polycarbonate (PC), polyethylene terephthalate (PET), poly(dimethylsiloxane) (PDMS), polyimide, polymethamethylacrylate (PMMA), offer a wide range of biocompatible property parameters for biochemical or medical applications at low cost using conventional molding process. The wide variety of biocompatible surface properties of commercially available polymer/plastics provides a critical competitive advantage over conventional silicon or glass-based manufacturing method for the POC application. Currently, commercially available POC devices such as glucose meters or i-STAT blood chemistry assays do not provide microbiological diagnosis at the point of care, preventing rapid response to potential threats presented by bioterrorism and emerging infectious diseases. There is a significant amount of interest in POC device development among both academic and industrial research but the high initial capital investment and long development cycle significantly reduce the actual development effort. A rapid, inexpensive, POC test capable of adapting existing assay protocols with a high degree of accuracy would be a major advance. In addition, rather than building a POC system from scratch, a ready-to-use POC platform would accelerate development efforts to impede the rapid emergence of wide spread diseases. The overall goal of this SBIR Phase I application is to develop and validate the prototyping fabrication process of a universal point-of-care (POC) system that is capable of adapting existing assay protocols for life science research and clinical diagnostics. We propose to establish a design library of standard molecular analysis assays and make the POC prototyping service available for every researcher to address the high priority initiatives of NIH and CDC. We will start with a cartridge design that could perform 10 multiplexed assays (genetic assays and/or immunoassays) in Phase I and expand to more common assay protocols to enable cartridges for optimization, large scale production and clinical study of the POC system in Phase II. With an optimized cartridge design through the POC cartridge prototyping fabrication, large scale manufacturing of the cartridges can be done by injection molding after the analytical validation on the prototyping cartridges via the proposed rapid fabrication method. In this proposed 6-month Phase I study, we will establish a design library for POC cartridge prototyping and fabricate 10 assay-specific integrated cartridges (ASICs) from design order to shipment ready in 6 hours. The cost of good sold (COGS) of the prototype cartridge will be less than $20 for 10 assays in Phase 1. The COGS of the POC control system will be less than $5k. PUBLIC HEALTH RELEVANCE: In this proposal, we will leverage our ongoing Cooperative Agreements (NIDCR U01 DE017790 and U01 AI082457) for the development of point-of-care (POC) diagnostic cartridges for multiplexed cancer marker screening and rapid pathogen identification. Based upon the experience and knowledge gained by developing and producing these cartridges for our ongoing Cooperative Agreements, this proposed Phase I study will establish a design library to accommodate the most common molecular analysis assays including genetic testing, immunoassay and electrolyte detection. After the successful completion of Phase I, we will make the standard cartridge design modules commercially available and provide the rapid POC cartridge prototype fabrication service to any research institutions interested in exploring POC applications. With the prototype fabrication service, the high initial capital investment and long development cycle, which are often required for POC system development, will no longer be a road block to the scientific development and commercialization efforts for POC methiods. Using a multiplexed pathogen identification cartridge capable of both protein and RNA detection as a model, we will demonstrate a universal POC molecular analysis system that can be rapidly adapted by end users using existing protocols and reagents for hands-free POC field tests in one week. The system will have an enormous favorable impact in the field of molecular analysis research and development in nontraditional settings. Researchers can have their own customized version of a POC system without the development risk and capital investment to accelerate the advancement in Point-of- Care testing.