SBIR Phase II: Ion Mobility Spectrometer for Macromolecular Analysis

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be the development of an analytical instrument to detect protein changes across all stages of protein production. The production of highly-engineered therapeutic proteins has outpaced the development of analytical assays to guarantee effectiveness, purity, and shelf life of the drug. A key control parameter during manufacturing is protein conformation; currently, this is difficult to monitor with commercially available technology. The goal of this project is to provide manufacturers with a new generation of analytical technology that allows them to identify variations between batches. This technology also provides information about product stability so manufacturers can guarantee a longer shelf life for their products, regardless of storage conditions. It is anticipated that this instrument will increase efficacy at all stages, from discovery through scaled-up production and formulation to pre-release certification. This SBIR Phase II project aims to improve biotherapeutic drug production through the commercialization of analytical technology that provides a new metric for the rapid QC/QA assessment of the conformation of proteins. The gold standard for determining protein conformation is x-ray crystallography - a time-consuming technique that requires high quality crystals and a high-energy physics facility to produce coherent x-rays. The proposed highly sensitive bench-top ion mobility spectrometer detects small variations in the cross-sectional area of a protein and detects small conformational changes. This provides a capability to determine protein stability during discovery when only microgram quantities of recombinantly expressed proteins are available. This process also indicates if a protein refolded after it was subjected to a pH change during purification, and thus it may be used to identify challenges to long-term shelf life. This instrument will be used to demonstrate that for the first time, ion mobility will produce highly-reproducible and biologically relevant measurements of the quality of biomanufactured proteins. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.