Patterns of protein adsorption in ion-exchange particles and columns: Evolution of protein concentration profiles during load, hold, and wash steps pre dicte d for pore and solid diffusion mechanisms

被引:7
作者
Beck, Juergen [1 ]
von Lieres, Eric [2 ]
Zaghi, Negar [3 ]
Leweke, Samuel [2 ,5 ]
Carta, Giorgio [4 ]
Hahn, Rainer [1 ]
机构
[1] BOKU Vienna, Dept Biotechnol, Vienna, Austria
[2] Forschungszentrum Julich, IBG Biotechnol 1, D-52425 Julich, Germany
[3] Univ British Columbia, Dept Chem & Biol Engn, Vancouver, BC, Canada
[4] Univ Virginia, Dept Chem Engn, Charlottesville, VA USA
[5] Bayer AG, Appl Math Engn & Technol, Leverkusen, Germany
关键词
Pore diffusion; Solid diffusion; Confocal laser scanning microscopy; Mechanistic modelling; Ion exchange chromatography; MASS-TRANSFER; CATION-EXCHANGERS; RESINS; CHROMATOGRAPHY; TRANSPORT; SURFACE; PURIFICATION; SIMULATION; MICROSCOPY; DESORPTION;
D O I
10.1016/j.chroma.2021.462412
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Elucidation of protein transport mechanism in ion exchanges is essential to model separation performance. In this work we simulate intraparticle adsorption profiles during batch adsorption assuming typical process conditions for pore, solid and parallel diffusion. Artificial confocal laser scanning microscopy images are created to identify apparent differences between the different transport mechanisms. Typical sharp fronts for pore diffusion are characteristic for Langmuir equilibrium constants of K L >= 1. Only at K L = 0.1 and lower, the profiles are smooth and practically indistinguishable from a solid diffusion mechanism. During hold and wash steps, at which the interstitial buffer is removed or exchanged, continuation of diffusion of protein molecules is significant for solid diffusion due to the adsorbed phase concentration driving force. For pore diffusion, protein mobility is considerable at low and moderate binding strength. Only when pore diffusion if completely dominant, and the binding strength is very high, protein mobility is low enough to restrict diffusion out of the particles. Simulation of column operation reveals substantial protein loss when operating conditions are not adjusted appropriately. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
引用
收藏
页数:10
相关论文
共 57 条
[1]   Protein Adsorption and Transport in Cation Exchangers with a Rigid Backbone Matrix with and without Polymeric Surface Extenders [J].
Almodovar, Ernie X. Perez ;
Tao, Yinying ;
Carta, Giorgio .
BIOTECHNOLOGY PROGRESS, 2011, 27 (05) :1264-1272
[2]   Parameter estimation for the simulation of liquid chromatography [J].
Altenhoner, U ;
Meurer, M ;
Strube, J ;
SchmidtTraub, H .
JOURNAL OF CHROMATOGRAPHY A, 1997, 769 (01) :59-69
[3]   Insights into Protein Sorption and Desorption on Dextran-Modified Ion-Exchange Media [J].
Bowes, Brian D. ;
Traylor, Steven J. ;
Timmick, Steven M. ;
Czymmek, Kirk J. ;
Lenhoff, Abraham M. .
CHEMICAL ENGINEERING & TECHNOLOGY, 2012, 35 (01) :91-101
[4]   Protein adsorption and transport in dextran-modified ion-exchange media. II. Intraparticle uptake and column breakthrough [J].
Bowes, Brian D. ;
Lenhoff, Abraham M. .
JOURNAL OF CHROMATOGRAPHY A, 2011, 1218 (29) :4698-4708
[5]   Protein adsorption and transport in dextran-modified ion-exchange media. I: Adsorption [J].
Bowes, Brian D. ;
Koku, Harun ;
Czymmek, Kirk J. ;
Lenhoff, Abraham M. .
JOURNAL OF CHROMATOGRAPHY A, 2009, 1216 (45) :7774-7784
[6]   CONSTRAINED BROWNIAN-MOVEMENT OF SPHERICAL-PARTICLES IN CYLINDRICAL PORES OF COMPARABLE RADIUS - MODELS OF DIFFUSIVE AND CONVECTIVE TRANSPORT OF SOLUTE MOLECULES IN MEMBRANES AND POROUS-MEDIA [J].
BRENNER, H ;
GAYDOS, LJ .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1977, 58 (02) :312-356
[7]   STERIC MASS-ACTION ION-EXCHANGE - DISPLACEMENT PROFILES AND INDUCED SALT GRADIENTS [J].
BROOKS, CA ;
CRAMER, SM .
AICHE JOURNAL, 1992, 38 (12) :1969-1978
[8]   Protein mass transfer kinetics in ion exchange media: Measurements and interpretations [J].
Carta, G ;
Ubiera, AR ;
Pabst, TM .
CHEMICAL ENGINEERING & TECHNOLOGY, 2005, 28 (11) :1252-1264
[9]  
Carta G., 2020, Protein chromatography: process development and scale-up, V2, DOI [10.1002/9783527824045, DOI 10.1002/9783527824045]
[10]   Analysis of diffusion models for protein adsorption to porous anion-exchange adsorbent [J].
Chen, WD ;
Dong, XY ;
Sun, Y .
JOURNAL OF CHROMATOGRAPHY A, 2002, 962 (1-2) :29-40