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

这个小型企业创新研究第一阶段项目通过开发革命性的纳米颗粒尺寸测量仪器，解决了快速，高精度纳米颗粒尺寸测量的挑战-这是广泛行业的关键问题。 该项目有可能使人们更深入地了解纳米材料及其在从制药业开始的广泛行业中的应用。目前，生命科学中纳米颗粒分析仪器的市场约为56亿美元。每年进行数百万次测试，因为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。同样，疫苗开发人员必须密切测量病毒载量，以达到所需的免疫应答水平。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和更有效的操作。这将导致直接节省成本和更好的治疗效果。然而，纳米颗粒分析的重要性远远超出了治疗学，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影响的一个主要挑战是检测它们的存在和尺寸分布。 基于库尔特原理的纳米流体扩展，该仪器利用了已知的基础技术，并将其与纳米纤维、流体和电子学领域的最新技术相结合。 本发明的最初目标应用是在药物开发过程中分析蛋白质聚集。 目前的技术在对直径小于约0.4微米的颗粒进行尺寸测量和计数方面都缺乏精确度，并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是以下目标：1）改进的流体回路控制，使可重复的测量，而无需手动用户干预，2）紧密集成的电子，流体和用户界面，支持使用一次性设备的快速测量; 3）改进信号分析算法，量化假阳性率;以及4）表征仪器输出与纳米流体装置制造中的变化，其由塑料模塑和纳米纤维技术组成。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可重复测量的原型。

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.