Protein Adsorption on Core-shell Particles: Comparison of Capto™ Core 400 and 700 Resins

Mi, Xue; Fuks, Preston; Wang, Sheng-ching; Winters, Michael A.; Carta, Giorgio

doi:10.1016/j.chroma.2021.462314

Cited by 18 publications

(19 citation statements)

References 34 publications

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“…All the model proteins used are acidic, with isoelectric points around 5. 35,36 T A B L E 1 Relevant properties of the resins used in this study 9,10…”

Section: Protein and Nanoparticle Characterizationmentioning

confidence: 99%

“…Because of its smaller pore size and, hence, larger surface area, Capto Core 400 was found to have a much larger binding capacity for BSA than Capto Core 700. 10 Conversely, for the much larger Tg, the attainable binding capacity was found to be larger for Capto Core 700 since mass transfer of Tg in Capto Core 400 is highly hindered. As a result, over practical time scales, only a small amount of Tg can bind to Capto Core 400.…”

mentioning

confidence: 93%

“…Core-shell resins [7][8][9][10] have been developed to prevent binding on the outer surface of the resin beads during the flow-through purification of large biomolecules and bioparticles. These resins comprise a functionalized adsorbent core surrounded by an inert porous shell, which prevents binding of the target product while allowing smaller impurities to diffuse and bind in the core.…”

mentioning

confidence: 99%

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Protein adsorption on core‐shell resins for flow‐through purifications: Effect of protein molecular size, shape, and salt concentration

Wang²,

Winters³

et al. 2022

Biotechnology Progress

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This work addresses the functional properties of the core‐shell resins Capto Core 400 and 700 for a broad range of proteins spanning 66.5 to 660 kDa in molecular mass, including bovine serum albumin (BSA) in monomer and dimer form, fibronectin, thyroglobulin, and BSA conjugates with 10 and 30 kDa poly(ethylene glycol) chains. Negatively charged latex nanoparticles (NPs) with nominal diameters of 20, 40, and 100 nm are also studied as surrogates for bioparticles. Protein binding and its trends with respect to salt concentration depend on the protein size and are different for the two agarose‐based multimodal resins. For the smaller proteins, the amount of protein bound over practical time scales is limited by the resin surface area and is larger for Capto Core 400 compared with Capto Core 700. For the larger proteins, diffusion is severely restricted in Capto Core 400, resulting in lower binding capacities than those observed for Capto Core 700 despite the larger surface area. Adding 500 mM NaCl reduces the local bound protein concentration and diffusional hindrance resulting in higher binding capacities for the large proteins in Capto Core 400 compared with low ionic strength conditions. The NPs are essentially completely excluded from the Capto Core 400 pores. However, 20 and 40 nm NPs bind significantly to Capto Core 700, further hindering protein diffusion. A model is provided to predict the dynamic binding capacities as a function of residence time.

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“…All the model proteins used are acidic, with isoelectric points around 5. 35,36 T A B L E 1 Relevant properties of the resins used in this study 9,10…”

Section: Protein and Nanoparticle Characterizationmentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

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Protein adsorption on core‐shell resins for flow‐through purifications: Effect of protein molecular size, shape, and salt concentration

Wang²,

Winters³

et al. 2022

Biotechnology Progress

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“…Multiple chromatographic modeling options can also be rapidly explored. For example, studies on CaptoCore ligands and shells detail their binding, adsorption, and diffusion properties and enable the development of accurate predictive models characterizing the capture of proteins as a function of their size [66,92,105].…”

Section: Trends In Biotechnologymentioning

confidence: 99%

Quality by Design for enabling RNA platform production processes

Daniel¹,

Kis²,

Kontoravdi³

et al. 2022

Trends in Biotechnology

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“…The CIP of the Capto Core 700 resin is expected to be challenging since the nature of its functionalized inner core can lead to irreversible binding of solutes that may not be easily interrupted. [ 15 ] This challenge is further compounded in that the resin is often applied in flowthrough mode, typically as the first step in a purification process following primary recovery. Hence, a higher content of diverse solutes bind to the resin and require removal prior to resin re‐use.…”

Section: Introductionmentioning

confidence: 99%

Regeneration of Capto Core 700 resin through high throughput and laboratory scale studies and impact on production of a SARS‐CoV‐2 vaccine candidate

Konstantinidis

Reinhart

Castagna

et al. 2022

Biotechnology Journal

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During the development of a SARS‐CoV‐2 vaccine candidate, at the height of the COVID‐19 pandemic, raw materials shortages, including chromatography resins, necessitated the determination of a cleaning in place (CIP) strategy for a multimodal core‐shell resin both rapidly and efficiently. Here, the deployment of high throughput (HT) techniques to screen CIP conditions for cleaning Capto Core 700 resin exposed to clarified cell culture harvest (CCCH) of a SARS‐CoV‐2 vaccine candidate produced in Vero adherent cell culture are described. The best performing conditions, comprised of 30% n‐propanol and ≥0.75 N NaOH, were deployed in cycling experiments, completed with miniature chromatography columns, to demonstrate their effectiveness. The success of the CIP strategy was ultimately verified at the laboratory scale. Here, its impact was assessed across the entire purification process which also included an ultrafiltration/diafiltration step. It is shown that the implementation of the CIP strategy enabled the re‐use of the Capto Core 700 resin for up to 10 cycles without any negative impact on the purified product. Hence, the strategic combination of HT and laboratory‐scale experiments can lead rapidly to robust CIP procedures, even for a challenging to clean resin, and thus help to overcome supply shortages.

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Protein Adsorption on Core-shell Particles: Comparison of Capto™ Core 400 and 700 Resins

Cited by 18 publications

References 34 publications

Protein adsorption on core‐shell resins for flow‐through purifications: Effect of protein molecular size, shape, and salt concentration

Protein adsorption on core‐shell resins for flow‐through purifications: Effect of protein molecular size, shape, and salt concentration

Quality by Design for enabling RNA platform production processes

Regeneration of Capto Core 700 resin through high throughput and laboratory scale studies and impact on production of a SARS‐CoV‐2 vaccine candidate

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