Resonant interactions of energetic electrons with electromagnetic whistler‐mode waves (
Protein precipitates that arise during bioprocessing can cause manufacturing challenges, but they can also aid in clearance of host‐cell protein (HCP) and DNA impurities. Such precipitates differ from many protein precipitates that have been studied previously in their heterogeneous composition, particularly in the presence of high concentrations of the product protein. Here, we characterize the precipitates that form after neutralization of protein A purified and viral‐inactivated material of an Fc‐fusion protein produced in Chinese hamster ovary cells. The physical growth of precipitate particles was observed by optical microscopy, transmission electron microscopy, dynamic light scattering, and small‐angle and ultra‐small‐angle X‐ray scattering to characterize the precipitate microstructure and growth mechanism. The precipitate microstructure is well‐described as a mass fractal with fractal dimension approximately 2. The growth is governed by a diffusion‐limited aggregation mechanism as indicated by a power‐law dependence on time of the size of the principal precipitate particles. Optical microscopy shows that these primary particles can further aggregate into larger particles in a manner that appears to be promoted by mixing. Absorbance experiments at varying pH and salt concentrations reveal that the growth is largely driven by attractive electrostatic interactions, as growth is hindered by an increase in ionic strength. The solution conditions that resulted in the most significant particle growth are also correlated with the greatest removal of soluble impurities (DNA and HCPs). Proteomic analysis of the precipitates allows identification of
- NSF-PAR ID:
- 10065690
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Biotechnology and Bioengineering
- Volume:
- 115
- Issue:
- 10
- ISSN:
- 0006-3592
- Page Range / eLocation ID:
- p. 2489-2503
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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