Particle formation during peristaltic pumping of therapeutic proteins: Hofmeister anions effect

This study reveals specific ion effects on particle formation during peristaltic pumping of a monoclonal Antibody (Antibody A). For this purpose, three anions in the direct Hofmeister series were selected, ranging from the kosmotropic SO₄^2- to the more neutral Cl^- and the chaotropic SCN^-. Protein particle formation during peristaltic pumping is described primarily as a surface-driven mechanism. Therefore, the effect of the anions was hypothesised to affect the particle formation with the smallest amount of protein adsorbing and the least particles formed in the presence of SCN^-, followed by the highest in SO₄^2-. The alternative hypothesis was that most protein particles would be formed in SCN^- due to the lower intrinsic stability of Antibody A. On the other hand, if none of the factors dominates the particle formation, it would not necessarily follow the Hofmeister series linearly. This was shown to be the case as significantly more particles were formed in the presence of NaCl, which could be explained by the interplay of the protein's intrinsic, colloidal, and interfacial stability. Antibody A had the highest protein adsorption in NaCl and the lowest colloidal stability compared to Na₂SO₄ or NaSCN, which led to the highest amount of subvisual particles formed during pumping.