SBIR Phase I: A low-cost instrument for rapid sub-micron particle size and concentration measurement

这个小企业创新研究的第一阶段项目解决了快速、高精度纳米颗粒上浆的挑战，这是一个广泛的行业的关键问题，通过开发一种革命性的纳米颗粒上浆仪器。这个项目有可能使人们更深入地了解纳米材料及其在广泛行业中的应用，从制药开始。目前，纳米颗粒分析仪器在生命科学领域的市场规模约为56亿美元。由于蛋白质聚集直接影响药物性能并可能导致不良的免疫原性，每年进行数百万次测试。同样，疫苗开发人员必须密切测量病毒载量，以达到所需的免疫反应水平。能够快速有效地解析0.4微米以下纳米颗粒的颗粒分析仪将在这些应用中提供更快的周转时间和更有效的操作。这将导致直接的成本节约和更好的治疗效果。然而，纳米颗粒分析的重要性远远超出了治疗领域，因为人们越来越关注食品和化妆品等消费品中纳米颗粒的存在。了解纳米颗粒对健康的影响的一个主要挑战仅仅是检测它们的存在和大小分布。基于库尔特原理的纳米流体扩展，该仪器利用了已知的基本技术，并将其与纳米制造、流体学和电子学方面的最新技术相结合。本发明的初始目标应用是在药物开发过程中分析蛋白质聚集。目前的技术在粒径小于0.4微米的颗粒的大小和计数上都缺乏精度，而且通常不能准确地分析多分散溶液。第一阶段工作的重点将集中在以下目标上：1)改进流体电路控制，实现无需手动用户干预的可重复测量，2)紧密集成电子，流体和用户界面，以支持使用一次性设备的快速测量；3)改进信号分析算法，量化误报率；4)表征仪器输出与纳米流体器件制造的变化，其中包括塑料成型和纳米制造技术。第一阶段的项目成果将是一个能够对客户样品进行半自动重复测量的原型。

This Small Business Innovation Research Phase I project addresses the challenge of fast, high-precision nanoparticle sizing - a critical issue for a wide range of industries - by the development of a revolutionary nanoparticle sizing instrument. This project has the potential to enable a deeper understanding of nanomaterials and their application in a wide range of industries, starting with pharmaceuticals. Currently, the market for nanoparticle analysis instrumentation in the life sciences is about $5.6 billion. Millions of tests are run each year because protein aggregation directly affects drug performance and can lead to undesirable immunogenicity. Similarly, vaccine developers must closely measure viral loads to achieve a desired level of immune response. A particle analyzer able to quickly and efficiently resolve nanoparticles below 0.4 microns would provide quicker turn-around and more efficient operations in these applications. This would lead to direct cost savings and better therapeutic outcomes. The importance of nanoparticle analysis goes well beyond therapeutics though, as there is increasing concern about the presence of nanoparticles in consumer products such as food and cosmetics. A major challenge in understanding the health impacts of nanoparticles is simply in detecting their presence and size distribution. Based on a nanofluidic extension of the Coulter principle, the instrument leverages a known fundamental technology and combines it with state-of-the-art techniques in nanofabrication, fluidics, and electronics. The initial target application for this invention is in the analysis of protein aggregation during the drug development process. Current techniques lack precision both in sizing and counting particles of diameter less than about 0.4 microns, and generally cannot accurately analyze polydisperse solutions. The focus of the Phase I work will be on the following objectives: 1) improved fluidic circuit control enabling repeatable measurements without manual user intervention, 2) tightly integrated electronics, fluidics, and user interface in support of rapid measurements using disposable devices; 3) improvement in signal analysis algorithms, with quantification of the rate of false positives; and 4) characterization of instrument output versus variation in nanofluidic device fabrication, which consists of both plastic molding and nanofabrication techniques. The Phase I project outcome will be a prototype capable of semi-automated reproducible measurements of customer samples.