Multi-state steric mass action model and case study on complex high loading behavior of mAb on ion exchange tentacle resin

Diedrich, Juliane; Heymann, William; Leweke, Samuel; Hunt, S.; Todd, R.; Kunert, Christian; Johnson, Will; Lieres, Eric von

doi:10.1016/j.chroma.2017.09.039

Cited by 24 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, there may be specific adsorbent structural factors that give rise to this time‐dependent recovery. Application of ligand functionalized polymers grafted to the membrane surface, present in the Q‐membranes used here, has been suggested to display complex multistate binding in protein systems as the polymer tentacle gradually wraps around the protein (Diedrich et al, 2017; Nestola et al, 2014). Similar phenomena may be present in LV AIEX systems where tentacled polymer ligands are able to increase multipoint attachment with time due to their flexible and dynamic structure.…”

Section: Discussionmentioning

confidence: 99%

“…The SMA model also assumes no structural changes in the bound state occur. More complex AIEX isotherms accounting for different binding states have however been suggested for protein systems (Diedrich et al, 2017). Thus, the perception that viral particles of all types are a homogenous target existing in a relatively stable and unchanging bound form is likely an oversimplification of the adsorption process, particularly when considering the large size, molecular complexity, and enveloped nature of LVs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Time‐dependent sorption behavior of lentiviral vectors during anion‐exchange chromatography

Pamenter,

Davies,

Knevelman

et al. 2023

Biotech & Bioengineering

View full text Add to dashboard Cite

Use of lentiviral vectors (LVs) in clinical Cell and Gene Therapy applications is growing. However, functional product loss during capture chromatography, typically anion-exchange (AIEX), remains a significant unresolved challenge for the design of economic processes. Despite AIEX's extensive use, variable performance and generally low recovery is reported. This poor understanding of product loss mechanisms highlights a significant gap in our knowledge of LV adsorption and other types of vector delivery systems. This work demonstrates HIV-1-LV recovery over quaternary-amine membrane adsorbents is a function of time in the adsorbed state.Kinetic data for product loss in the column bound state was generated. Fitting a second order-like rate model, we observed a rapid drop in functional recovery due to increased irreversible binding for vectors encoding two separate transgenes (t Y1/2 = 12.7 and 18.7 min). Upon gradient elution, a two-peak elution profile implicating the presence of two distinct binding subpopulations is observed.Characterizing the loss kinetics of these two subpopulations showed a higher rate of vector loss in the weaker binding peak. This work highlights time spent in the adsorbed state as a critical factor impacting LV product loss and the need for consideration in LV AIEX process development workflows.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Time‐dependent sorption behavior of lentiviral vectors during anion‐exchange chromatography

Pamenter,

Davies,

Knevelman

et al. 2023

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…This discrepancy might be attributed to the occurrence of multilayer adsorption at high loading density, and variants with protein-protein interaction might tend to elute earlier as a "preshoulder" (Seelinger et al, 2023). While the current model can only describe the case of single-layer adsorption (Equation 2), other models like multistate adsorption model (Diedrich et al, 2017), multicomponent model (Seelinger et al, 2022), asymmetric activity coefficient (Huuk et al, 2017), hybrid model (Narayanan et al, 2021), and colloidal particle adsorption model (Briskot et al, 2021;Rischawy et al, 2022) The analysis results indicated that when extending the well-fitted model parameters to higher loading density, a re-evaluation is necessary. The reassessment should not only encompass the model accuracy but, more importantly, the impact of the model's accuracy on the products attributes.…”

Section: Dt Test Under Extreme Conditionsmentioning

confidence: 92%

Realization of digital twin for dynamic control toward sample variation of ion exchange chromatography in antibody separation

Shi,

Chen,

Zhong

et al. 2024

Biotech & Bioengineering

View full text Add to dashboard Cite

Digital twin (DT) is a virtual and digital representation of physical objects or processes. In this paper, this concept is applied to dynamic control of the collection window in the ion exchange chromatography (IEC) toward sample variations. A possible structure of a feedforward model‐based control DT system was proposed. Initially, a precise IEC mechanistic model was established through experiments, model fitting, and validation. The average root mean square error (RMSE) of fitting and validation was 8.1% and 7.4%, respectively. Then a model‐based gradient optimization was performed, resulting in a 70.0% yield with a remarkable 11.2% increase. Subsequently, the DT was established by systematically integrating the model, chromatography system, online high‐performance liquid chromatography, and a server computer. The DT was validated under varying load conditions. The results demonstrated that the DT could offer an accurate control with acidic variants proportion and yield difference of less than 2% compared to the offline analysis. The embedding mechanistic model also showed a positive predictive performance with an average RMSE of 11.7% during the DT test under >10% sample variation. Practical scenario tests indicated that tightening the control target could further enhance the DT robustness, achieving over 98% success rate with an average yield of 72.7%. The results demonstrated that the constructed DT could accurately mimic real‐world situations and perform an automated and flexible pooling in IEC. Additionally, a detailed methodology for applying DT was summarized.

show abstract

“…Clark et al (2007) used an acoustically actuated resonant membrane sensor to monitor the changes of surface energy and found that the changes persist long after mass loading of the protein has reached the steady state. Therefore, more sophisticated adsorption models, such as the multi-state sma (Diedrich et al, 2017) based on the spreading model (Ghosh et al, 2013(Ghosh et al, , 2014, have been proposed to describe dynamic protein-ligand interactions. Although these kinetics describe more accurately the adsorption behaviors by taking orientation changes into consideration, the strong nonlinearity of kinetics exerts tremendous difficulties in deriving analytical formulae to calculate flowrates, as it is in the triangle theory.…”

Section: Figure 1: Schematic Of Four-zone Smb Chromatographymentioning

confidence: 99%

Model-based process design of a ternary protein separation using multi-step gradient ion-exchange SMB chromatography

Lieres

Sun

et al. 2020

Computers & Chemical Engineering

Self Cite

View full text Add to dashboard Cite

Model-based process design of ion-exchange simulated moving bed (iex-smb) chromatography for center-cut separation of proteins is studied. Use of nonlinear binding models that describe more accurate adsorption behaviours of macro-molecules could make it impossible to utilize triangle theory to obtain operating parameters. Moreover, triangle theory provides no rules to design salt profiles in iex-smb. In the modelling study here, proteins (i.e., ribonuclease, cytochrome and lysozyme) on the chromatographic columns packed with strong cation-exchanger SP Sepharose FF is used as an example system. The general rate model with steric mass-action kinetics was used; two closed-loop iex-smb network schemes were investigated (i.e., cascade and eight-zone schemes). Performance of the iex-smb schemes was examined with respect to multi-objective indicators (i.e., purity and yield) and productivity, and compared to a single column batch system with the same amount of resin utilized. A multi-objective sampling algorithm, Markov Chain Monte Carlo (mcmc), was used to generate samples for constructing the Pareto optimal fronts. mcmc serves on the sampling purpose, which is interested in sampling the Pareto optimal points as well as those near Pareto optimal. Pareto fronts of the three schemes provide the full information of trade-off between the conflicting indicators of purity and yield. The results indicate the cascade iex-smb scheme and the integrated eight-zone iex-smb scheme have the similar performance that both outperforms the single column batch system.

show abstract

Multi-state steric mass action model and case study on complex high loading behavior of mAb on ion exchange tentacle resin

Cited by 24 publications

References 31 publications

Time‐dependent sorption behavior of lentiviral vectors during anion‐exchange chromatography

Time‐dependent sorption behavior of lentiviral vectors during anion‐exchange chromatography

Realization of digital twin for dynamic control toward sample variation of ion exchange chromatography in antibody separation

Model-based process design of a ternary protein separation using multi-step gradient ion-exchange SMB chromatography

Contact Info

Product

Resources

About