Department of Chemical Engineering, University of Virginia, Charlottesville, VA, USA.
Vaccine Process Research and Development, Merck & Co., Inc., West Point, PA, USA.
J Chromatogr A. 2021 Aug 16;1651:462314. doi: 10.1016/j.chroma.2021.462314. Epub 2021 Jun 6.
Structural and functional characteristics of the two core-shell resins Capto™ Core 400 and 700, which are useful for the flow-through purification of bioparticles such as viruses, viral vectors, and vaccines, are compared using bovine serum albumin (BSA) and thyroglobulin (Tg) as models for small and large protein contaminants. Both resins are agarose-based and contain an adsorbing core surrounded by an inert shell. Although shell thicknesses are comparable (3.6 and 4.2 µm for Capto Core 400 and 700, respectively), the two resins differ substantially in pore size (pore radii of 19 and 50 nm, respectively). Because of the smaller pores and higher surface area, the BSA binding capacity of Capto Core 400 is approximately double that of Capto Core 700. However, for the much larger Tg, the attainable capacity is substantially larger for Capto Core 700. Mass transfer in both resins is affected by diffusional resistances through the shell and within the adsorbing core. For BSA, core and shell effective pore diffusivities are about 0.25 × 10 and 0.6 × 10 cm/s, respectively, for Capto Core 400, and about 1.6 × 10 and 2.6 × 10 cm/s, respectively, for Capto Core 700. These values decrease dramatically for Tg to 0.022 × 10 and 0.088 × 10 cm/s and to 0.13 × 10 and 0.59 × 10 cm/s for Capto Core 400 and 700, respectively. Adsorbed Tg further hinders diffusion of BSA in both resins. Column measurements show that, despite the higher static capacity of Capto Core 400 for BSA, the dynamic binding capacity is greater for Capto Core 700 as a result of its faster kinetics. However, some of this advantage is lost if the feed is a mixture of BSA and Tg since, in this case, Tg binding leads to greater diffusional hindrance for BSA.
对比了两种核壳树脂 Capto™ Core 400 和 700 的结构和功能特性，这两种树脂可用于通过流穿方式纯化病毒、病毒载体和疫苗等生物颗粒，使用牛血清白蛋白 (BSA) 和甲状腺球蛋白 (Tg) 作为小分子和大分子蛋白污染物的模型。两种树脂均为琼脂糖基，含有一个吸附核，周围是惰性壳。尽管壳厚度相当（Capto Core 400 和 700 的壳厚度分别为 3.6 和 4.2 µm），但两种树脂的孔径差异很大（分别为 19 和 50 nm）。由于孔径较小且表面积较大，Capto Core 400 的 BSA 结合能力约为 Capto Core 700 的两倍。但是，对于 Tg 这种更大的分子，Capto Core 700 可达到的载量要大得多。两种树脂的传质都受到壳层和吸附核内扩散阻力的影响。对于 BSA，Capto Core 400 的核和壳有效孔扩散系数分别约为 0.25×10 和 0.6×10 cm/s，Capto Core 700 的分别约为 1.6×10 和 2.6×10 cm/s。对于 Tg，这些值会急剧下降至 0.022×10 和 0.088×10 cm/s 和 0.13×10 和 0.59×10 cm/s，Capto Core 400 和 700 分别如此。吸附的 Tg 进一步阻碍了两种树脂中 BSA 的扩散。柱测量表明，尽管 Capto Core 400 对 BSA 的静态容量较高，但由于动力学更快，Capto Core 700 的动态结合容量更大。但是，如果进料是 BSA 和 Tg 的混合物，那么这种优势会部分丧失，因为在这种情况下，Tg 的结合会导致 BSA 的扩散受到更大的阻碍。
