Nanoparticles are ubiquitous yet notoriously difficult to detect and measure-practical technologies for their characterization are effectively restricted to particles larger than about 500 nanometers in diameter. This limitation is acutely felt in the drug development industry: Because aggregate drug particles in parenteral formulations elicit a severe immune response in some recipients, their detection is a major safety concern for manufacturers and patients. Millions of these critical tests are performed each year across the pharmaceutical industry, and the lack of effective particle sizing technology significantly increases the time and cost of these tests: a 1000-fold reduction in both time and reagents required for each test would be realized if molecular aggregates could be reliably detected at diameters of 50 nanometers rather than 500 nanometers. Spectradyne will address this unmet need by commercializing an innovative particle sizing technology that completely changes the way submicron aggregates are detected and measured in the pharmaceutical industry. The Spectradyne instrument will be capable of 1) robust detection of individual particles as small as 20 nanometers in diameter, more than ten times smaller than existing commercially available methods, with 2) size discrimination better than 5%, enabling resolution of polydisperse samples and 3) detection rates higher than 100,000 particles per second, (1000-fold faster than other commercially available methods). The platform will comprise single-use consumable nanofluidic cartridges and a compact, benchtop instrument capable of controlling flow in the cartridge and performing electrical readout of particles as they flow through the sensor. To accomplish these goals three specific aims will be met.
In Aim 1, reliable and repeatable manufacture of the consumable nanofluidic cartridges will be demonstrated-successful completion of this aim will define a viable path to mass manufacture of these components, a critical requirement for the success of the technology.
In Aim 2, an instrument prototype will be developed that is capable of automated control of fluid flow in the cartridge and electrical readout. Success in Aims 1 and 2 will produce a reliable control system with which to systematically evaluate the performance of the technology. Lastly, in Aim 3 the key performance metrics of the system will be characterized: limit of detection, linear dynamic range, and measurement accuracy and precision. The fully characterized instrument prototype will then be validated for use in drug development applications by analyzing authentic formulations provided by our collaborators in the pharmaceutical industry. This technology will significantly reduce the time, money and materials required for the development of new drug formulations, in particular the detection of particle aggregation, and reduce the overall time and cost of drug development.
All parenteral drug formulations must be continually tested for the formation of aggregate drug particles, which are known to illicit severe immune responses in some recipients and which can require weeks or months to grow to a size large enough to be detected using currently available methods (about 500 nanometers in diameter). This project will develop an innovative new technology that integrates state-of-the-art nanofluidic technology with rapid electronic sensing in a practical, compact instrument to reduce the minimum detectable particle size to below 50 nanometers. The ability to detect particles in this size range will enable 1000-fold reductions in both the time required to detect aggregation and the quantity of sample required for analysis, thus greatly reducing the time and cost in this step of drug development.