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

该小型企业创新研究（SBIR）第二阶段项目支持开发纳米颗粒表征仪器，该仪器将满足快速准确测量30纳米至1微米纳米颗粒尺寸和分布的关键未满足需求。最初，该技术将针对两个应用：生物制药中的蛋白质聚集和医学中的纳米颗粒（例如，肿瘤靶向药物递送）。然而，纳米颗粒分析的重要性远远超出了治疗学。目前，整个生命科学领域的纳米颗粒分析仪器市场规模为56亿美元，人们越来越关注食品和化妆品等消费品以及饮用水、污水和环境中的纳米颗粒。了解纳米颗粒对健康影响的一个主要挑战是准确和容易地检测它们的存在和尺寸分布。此外，改进的纳米粒子仪器将使生物技术和环境与健康科学的新发现。这一挑战可以通过开发一种实用的方法来计数和测量多分散混合物中的亚微米颗粒来应对。NSF I/IB阶段资金支持开发了一种原型仪器，该仪器可以检测单个纳米颗粒并以非常高的计数率准确测量其大小。该仪器已经成功地证明了对直径小至60 nm的单个颗粒的稳健检测，速度接近每秒10，000个颗粒，并且已经开始为制药行业的颗粒制造商提供有用的信息，并持续测量实际客户样品。第二阶段的支持将通过解决几个突出的技术挑战，大大提高该仪器的实用性;最重要的是，通过扩展可检测颗粒的范围，以跨越30 nm至1000 nm的整个范围，并通过进一步最大化可测量颗粒浓度的范围。 此外，第二阶段的工作将在控制软件创新的推动下，推动功能和易用性的重大改进。最后，该仪器将使用制药领域以外的各种相关颗粒类型进行进一步验证。

This Small Business Innovation Research (SBIR) Phase II project supports development of a nanoparticle characterization instrument that will fill the critical unmet need to rapidly and accurately measure the size and distribution of nanoparticles from 30 nanometers to 1 micron. Initially the technology will target two applications: protein aggregation in biopharmaceuticals, and nanoparticles in medicine (e.g., tumor-targeted drug delivery). The importance of nanoparticle analysis, however, goes well beyond therapeutics. Currently the market for nanoparticle analysis instrumentation across the life sciences is $5.6 billion, and there are increasing concerns about nanoparticles in consumer products such as food and cosmetics, as well as in drinking water, effluents, and the environment. A major challenge in understanding the health impacts of nanoparticles is simply in accurately and easily detecting their presence and size distribution. Additionally, improved nanoparticle instrumentation will enable new discoveries in biotechnology and environmental and health sciences.This challenge can be met by developing a practical method for counting and sizing submicron particles in polydisperse mixtures. NSF Phase I/IB funds supported development of a prototype instrument that detects individual nanoparticles and accurately measures their size, at very high count rates. This instrument has successfully demonstrated robust detection of individual particles as small as 60 nm in diameter at rates approaching 10,000 particles per second, and has already begun to deliver useful information to particle manufacturers in the pharmaceutical industry, with on-going measurements of actual customer samples. The Phase II support will considerably enhance the utility of this instrument by addressing several outstanding technical challenges; most significantly, by extending the range of detectable particles to span the full range from 30 nm to 1000 nm, and by further maximizing the range of measurable particle concentrations. In addition, the Phase II work will drive significant improvements in functionality and ease of use, driven by innovations in its control software. Finally, the instrument will be further validated using a wide variety of particle types relevant beyond the pharmaceutical space.