SBIR-STTR Award

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.

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.