Protein adsorption in anion exchange resins – effects of polymer grafting, support structure porosity, and protein size

Abstract

BACKGROUND: Anion exchange resins are used extensively for the purification of acidic proteins. Grafting charged polymers to a rigid porous structure has been shown to improve performance under varying conditions. Understanding the underlying mechanisms is important for the optimum design and selection of material properties and operating conditions. RESULTS: Positively charged grafted polymers incorporated into a rigid, porous polymeric backbone structure are found to significantly enhance adsorption capacity and kinetics of the proteins bovine serum albumin (BSA, M r ∼ 65 kDa) and thyroglobulin (Tg, M r ∼ 660 kDa) but under different conditions. For the smaller BSA, binding increases with grafted polymer length and content and decreases with salt concentration. For the much larger Tg, binding increases with the addition of some salt for the polymer-grafted resins but can be lower than that observed for ungrafted resins without added salt. This behavior is caused by diffusional hindrance due to the bound protein. Increasing the length of the grafted polymer or the pore size of the backbone improves the Tg adsorption kinetics. CONCLUSION: Protein adsorption is controlled by different mechanisms dependent on polymer grafting, backbone structure, and size of the adsorbed protein. Optimum selection of resin properties and conditions is needed to maximize adsorption capacity and mass transfer kinetics.

Synthesis of polyaminophosphonic acid-functionalized poly(glycidyl methacrylate) for the efficient sorption of La(III) and Y(III)

“…R esistance t o i ntraparticle d iffusion is usually an important limiting step in the control of uptake kinetics (in addition to resistance to film d iffusion, pr edominant du ring th e first minutes of contact, bulk diffusion, and the proper reaction rate). Using small particle sizes obviously limits the effect o f r esistance t o intraparticle diffusion; this effect can be even minored when the sorbent is highly porous (high specific surface area, pore size, pore volume, etc) [64][65][66]. The textural properties (analyzed by BET method) showed that the specific surface area was relatively small (i.e., 16 m 2 g −1 ).…”

High‐capacity multimodal anion‐exchange membranes for polishing of therapeutic proteins

“…In line with the stoichiometric displacement model, the anions compete with proteins for binding sites on the positively charged ligand, and the more negatively charged anions are harder to displace, which ultimately results in a lower DBC 10. 23 …”

Protein adsorption and separation with monomodal and multimodal anion exchange chromatography resins. Part I. Multicomponent adsorption properties and frontal chromatography

“…Nuvia HP-Q and Nuvia aPrime 4A (henceforth referred to as Nuvia aPrime) were obtained from Bio-Rad Laboratories (Hercules, CA, USA), while Capto Adhere ImpRes (henceforth referred to as Capto Adhere) was obtained from Cytiva (Marlborough, MA, USA). Relevant physical properties of these resins have been reported previously 18,19 and are summarized in Table 1. Nuvia HP-Q is the same as the prototype identified as BRX-Q4 in Zhu et al, 19 while Nuvia aPrime 4A is the same as the prototype identified as Nuvia aPrime 1 in Roberts et al 18 Both Nuvia resins are based on a hydrophilic synthetic polymeric matrix with a bimodal pore distribution consisting of large pores (>100 nm radius) and small pores (<20 nm radius).…”