Fluorescence-based detection of protein aggregation and fiber optic-based benchtop instrument
Michael S. Strano, Freddy T. Nguyen, Daichi Kozawa, Xun Gong, Daniel Salem, Soo-Yeon Cho. 2021-02-18
BACKGROUND The biopharmaceutical industry faces several challenges during drug discovery, manufacturing, and scaling processes to produce high quality, reproducible, and effective drugs. New techniques are needed to provide the pharmaceutical industry with the real-time analytical tools needed to accomplish these goals. During the drug manufacturing process, there is an increased need from both a safety and regulatory point of view to ensure the high quality and purity of samples throughout the process and to rapidly discern monomers from aggregates such as dimers, trimers, and polymers of the drug. Protein aggregation in manufacturing poses an enormous challenge as it can decrease the efficacy of the formulations, decrease the product yield, and potentially introduce immunogenicity. SUMMARY Hydrogel-encapsulated, label-free fluorescent nanosensors can be used for the characterization of protein aggregation. For example, the nanosensors can detect the presence of high molecular weight protein species at a concentration as low as one percent. In addition, an apparatus for signal detection, for example, a fiber optic-based benchtop instrument that interfaces with the hydrogels described herein. The instrument allows for a small form factor that is portable and can easily be integrated into different areas of research, for example, a biopharmaceutical synthesis processes.