Protein therapeutics are a rapidly growing portion of the pharmaceuticals market and have many significant advantages over traditional small molecule drugs. As this market expands, however, critical regulatory and quality control issues remain, most notably the problem of protein aggregation. Individual target proteins often aggregate into larger masses which trigger an immune response in the body, which can reduce the efficacy of the drug for its intended purpose, or cause serious anaphylactic side-effects. Although detecting and minimizing aggregate formation is critical to ensure an effective product, aggregation dynamics are often highly complicated and there is little hope of reliable prediction and prevention from first principles. This problem is compounded for aggregates in the subvisible range of 100 nm to 10 micrometers where traditional techniques for detecting aggregates have significant limitations.
Here, we present an integrated optofluidic platform for detecting nanoscale protein aggregates and characterizing interactions between these aggregates and a reference surface. By delivering light to a solution of proteins with an optical waveguide, scattered light from individual protein aggregates can be detected and analyzed to determine the force profile between each particle and the waveguide surface. Unlike existing methods which only determine size or charge, our label-free screening technique can directly measure the surface interaction forces between single aggregates and the glass substrate. This direct measurement capability may allow for better empirical predictions of the stability of protein aggregates during drug manufacturing and storage.
Perry Schein, Dakota O'Dell, and David Erickson, "An integrated platform for assessing biologics
(Conference Presentation)," Proc. SPIE 9711, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, 97110B (Presented at SPIE BiOS: February 15, 2016; Published: 27 April 2016); https://doi.org/10.1117/12.2210748.4848767199001.
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