Mathematical Modeling of Protein Chromatograms

Abstract

Artículo de publicación ISIThe most used mathematical models with a phenomenological basis for simulating chromatographic curves of proteins in size exclusion chromatography, ion exchange chromatography, affinity chromatography, and hydrophobic interaction chromatography are reviewed. The plate model (PM) and the general rate model (GRM) are briefly described, followed by various applications of these models to the different chromatographic strategies. Based on these examples it is concluded that the GRM is the most complete and informative model, despite it needs several parameters that have to be estimated from theoretical correlations nonspecific for proteins. Additionally, values for the effective pore diffusion coefficient are not generally available. Appropriate calibration leads in most cases to predictions that compare favorably with experimental data. The possibility to predict chromatographic curves under different operational conditions similar to those used at industrial scale by applying mathematical models is still a challenge because it could contribute to the reduction of costs involved in suitable purification processes. In addition, new proteins are continually designed and for each case different conditions are needed.Fondecyt 1100437 1080143 11080016 Institute for Cell Dynamics and Biotechnology (ICDB): A Center for System Biology P05-001-

Simulation of mono‐PEGylated lysozyme separation in heparin affinity chromatography using a general rate model

“…The general rate model (GRM) is a mathematical model used for studying chromatographic phenomena using rate expressions which represent the mass transfer of the components (protein and modulator or salt) in the system. The GRM considers in the mathematical formulation the adsorbent properties, process conditions and different mass transfer processes . The model is integrated by three sets of differential equations (Equation to in Supplementary material), two of them describing the mass balance of the components in the bulk‐fluid phase and in the particle phase inside the bed, and the third representing the adsorption mechanism of the proteins to the adsorbent.…”

“…There is an instantaneous equilibrium between macropore surfaces and the stagnant fluid inside the particles; diffusional and mass transfer parameters are constant and independent from the mixing effects of the components involved; the column was pre‐equilibrated. Before the sample load the system does not contain protein; symmetric distribution of the compounds inside the adsorbent; and the column outlet protein dispersion flux is null …”

“…The theoretical relationships in a process such as chromatography are described in a mathematical model, a set of expressions; then these equations are solved under specific conditions . Among the most used models to represent and simulate the behavior of adsorptive chromatography with proteins is the general rate model (GRM) . However, in affinity chromatography, examples of the application of the GRM are few.…”

Comparación de diferentes algoritmos metaheurísticos en la estimación de parámetros del modelo relacional general de cromatografía líquida en columna

“…Los modelos de cromatografía son útiles para comprender los sistemas existentes, para así optimizarlos y escalarlos. El modelo relacional general (MRG) es uno de los modelos que mejor refleja los mecanismos de transporte y adsorción del proceso [15].…”

Desarrollo y producción recombinante de un péptido bloqueador de TNF para el tratamiento de trastornos autoinmunes inflamatorios.

“…Por otro lado, el GRM es el modelo más completo y exhibe una mayor versatilidad ya que permite describir y simular procesos cromatográficos en condiciones variables de carga de la molécula de interés (cantidad de molécula por unidad de la fase estacionaria). Esta versatilidad se debe a que este modelo está basado en fenómenos de transferencia de momento y masa que ocurren en el interior de la partícula (fase estacionaria) y en la fase móvil [47,50,163,164].…”