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.
