Characterization of Proteins and Their Aggregates at High Concentration

DESCRIPTION (provided by applicant): Scattering Solutions, LLC proposes to develop a method to characterize proteins and protein aggregation in highly concentrated suspensions by the combination of three new techniques: (1) cross correlation of light scattered within a single speckle to suppress the detrimental effect of multiple scattering; (2) optical homodyne amplification to suppress flare and errors arising from properties of the sample or its containment vessel; and (3) a new signal processing scheme to access a larger simultaneous dynamic range than formerly possible, with internally generated estimates of accuracy. Phase I research tasks build on previous research and development to confirm the feasibility of Scattering Solutions' light scattering technology for the characterization of highly concentrated proteins, and prepare for more advanced research and development which seeks to extend the range of measurements to include smaller sizes, dilute concentrations, small sample volumes, and shape characterization. This research specifically addresses stability issues which present efficacy and safety concerns to high concentration final dosage formulations of therapeutic agents. In addition, an investigation is proposed to examine the effect of protein concentration on fibril formation, a common structural feature in several degenerative conditions such as Parkinson and Alzheimer's diseases. This research addresses the aims of NIH in its objective to lay the foundation for advances in disease diagnosis, treatment, and prevention since it addresses an issue which is vital to patient care (drug administration), pharmaceutical development, and fundamental biochemistry and medical research. Phase II will yield the design and fabrication of an inexpensive yet versatile instrument with highly desirable capabilities not currently available. It will also include extensive studies with commercial therapeutic proteins provided by multiple collaborators, and studies concerning disease-correlated protein aggregation phenomena.