Model based design and optimization of high capacitive membrane adsorbers

  • Modellbasiertes Design und Optimierung von hochkapazitiven Membranadsorbern

Hagemann, Franziska Maria Dorothee Gertrud; Wessling, Matthias (Thesis advisor); Boi, Cristiana (Thesis advisor)

Aachen : RWTH Aachen University (2021, 2022)
Book, Dissertation / PhD Thesis

In: Aachener Verfahrenstechnik series - AVT.CVT - chemical process engineering 23 (2022)
Page(s)/Article-Nr.: 1 Online-Ressource : Illustrationen, Diagramme

Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2021


In order to isolate cell derived target molecules from the respective fermentation broth, faster and more efficient unit operations are required. Due to mass transfer limitations, resin chromatography typically shows a strong dependence of the binding capacity on the residence time and is therefore limited in separation velocity. Small particles cause thinner convective channels and therefore create a higher pressure drop over the chromatographic bed. Convective chromatography e.g. based on membranes, is a promising approach, representing nearly residence time independent separation processes with respect to the binding capacity, yielding high process productivity. Due to the inherent structural properties of purely convective separation media, the specific surface area and thus the binding capacity often become limiting factors. Membrane adsorbers with a biporous structure can improve the downstream process in bioprocesses, because mass transfer limitations are drastically reduced compared to conventional resin chromatography materials. Convective pores enable fast mass transfer and diffusive pores in the membrane bridges provide surface for binding. The diffusive pathways in membranes are much smaller than conventional bead diameters, allowing higher flow rates in the process. The aim of this thesis is the model based optimization of such membrane adsorbers. The membrane is optimized regarding bed height, convective porosity, permeability, diffusive pore structure and the length of diffusive pathway. The impact of the target molecule size and the flow rate are taken into account.The diffusive pore structure was modeled with a cubic grid model, which provides information of the pore and filament diameters. Pore diffusion coefficients were determined using the general rate model. Due to the large diameter to bed height ratio of membrane adsorbers, the adequate flow distribution is very important. Therefore, residence time distributions (RTD) of the devices were investigated using CFD simulations. The impact of bed height and dead volume in the devices was analyzed. Moreover, the influence of the housing and the membrane on the RTD of the total device were separated using CFD simulations. It was possible to simulate experimentally obtained membrane adsorber breakthrough curves with a modification of the general rate model. This model was used to determine productivities of different potential membrane adsorber configurations. The process productivity is increased by the factor of 90 for an optimized membrane adsorber compared to conventional state of the art resin processes, assuming an ideal flow distribution. The current status membrane material is already 22 times better than the resin process.