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一种革命性的纳米颗粒测量仪器，解决了快速、高精度纳米颗粒测量的挑战-这是一个广泛行业的关键问题。该项目有可能加深对纳米材料及其在从制药开始的广泛行业中的应用的了解。目前，生命科学中纳米颗粒分析仪器的市场价值约为56亿美元。每年要进行数百万次测试，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，疫苗研发人员必须密切测量病毒载量，以实现所需的免疫反应水平。一种能够快速有效地分解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。这将带来直接的成本节约和更好的治疗结果。然而，纳米颗粒分析的重要性远远超出了治疗学，因为人们越来越担心食品和化妆品等消费品中存在纳米颗粒。理解纳米颗粒对健康的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延伸，该仪器利用了一项已知的基本技术，并将其与纳米制造、流体学和电子学方面的最先进技术相结合。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。目前的技术在直径小于约0.4微米的颗粒的大小和计数方面都缺乏精度，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放在以下目标上：1)改进射流电路控制，无需用户手动干预即可重复测量；2)紧密集成电子、流体和用户界面，支持使用一次性设备进行快速测量；3)改进信号分析算法，量化假阳性率；4)表征纳米射流器件制造中仪器输出与变化的关系，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本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.