| 1. |
- Gomis-Fons, Joaquín, et al.
(författare)
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Model-based design and control of a small-scale integrated continuous end-to-end mAb platform
- 2020
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Ingår i: Biotechnology progress (Print). - : John Wiley and Sons Inc.. - 8756-7938 .- 1520-6033.
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Tidskriftsartikel (refereegranskat)abstract
- A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained.
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| 2. |
- Gomis-Fons, Joaquin, et al.
(författare)
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Optimization study on periodic counter-current chromatography integrated in a monoclonal antibody downstream process
- 2020
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Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1621
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Tidskriftsartikel (refereegranskat)abstract
- An optimization study of an integrated periodic counter-current chromatography (PCC) process in a monoclonal antibody (mAb) downstream process at lab scale, is presented in this paper. The optimization was based on a mechanistic model of the breakthrough curve in the protein-A capture step. Productivity and resin utilization were the objective functions, while yield during the loading of the capture column was set as a constraint. Different integration approaches were considered, and the effect of the feed concentration, yield and the protein-A resin was studied. The breakthrough curve and the length of the product recovery, which depended on the integration approach, determined the process scheduling. Several optimal Pareto solutions were obtained. At 0.5 mg mL−1 and 99% yield, a maximum productivity of 0.38 mg mL−1 min−1 with a resin utilization of 60% was obtained. On the other hand, the maximum resin utilization was 95% with a productivity of 0.10 mg mL−1 min−1. Due to the constraint of the process scheduling, a lower productivity could be achieved in the integration approaches with higher recovery time, which was more remarkable at higher concentrations. Therefore, it was shown that a holistic approach, where all the purification steps are considered in the process optimization, is needed to design a PCC in a downstream process.
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| 3. |
- Moreno-gonzález, Mónica, et al.
(författare)
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Continuous adsorption in food industry: The recovery of sinapic acid from rapeseed meal extract
- 2020
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Ingår i: Separation and Purification Technology. - : Elsevier BV. - 1383-5866. ; 254
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Tidskriftsartikel (refereegranskat)abstract
- Efficient recovery and utilization of valuable components from industrial food side streams is a main driver towards a circular economy. Among different available purification techniques, adsorption can effectively recover these components. However, the conventional batch mode of operation can limit its applicability in food processes due to limited efficiency. This work compares conventional batch packed bed adsorption with semi-continuous adsorption (so-called CaptureSMB) for the recovery of sinapic acid at industrial scale, using a food grade resin AmberliteTM FPX66. A mathematical mechanistic model able to describe semi-continuous operation is successfully validated and used to identify optimum operating parameters to maximize productivity and resin capacity utilization in batch and semi-continuous operating modes. The results indicate that CaptureSMB outperforms batch operation, increasing productivity from 5.18 g/L/h to 10.3 g/L/h for a given yield (>97%). A resin capacity utilization (RU) of around 70% is observed in both operating modes when productivity is maximized. A 92% RU can be accomplished for a given yield using the CaptureSMB process at a productivity of 7.0 g/L/h, higher than for conventional batch operation. The use of semi-continuous adsorption operation in food industry contributes to more efficient processes at reduced purification costs.
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| 4. |
- Sanchis Sebastia, Miguel, et al.
(författare)
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Techno-Economic Evaluation of Biorefineries Based on Low-Value Feedstocks Using the BioSTEAM Software: A Case Study for Animal Bedding
- 2020
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Ingår i: Processes. - : MDPI AG. - 2227-9717. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Biofuels are still too costly to compete in the energy market and it has been suggested that low-value feedstocks could provide an opportunity for the production of low-cost biofuels; however, the lower quality of these feedstocks requires the introduction of a conditioning step in the biorefinery process. The aim of this study was to evaluate whether feedstock savings cover the cost of conditioning in the case of animal bedding. The BioSTEAM software was used to simulate a wheat straw biorefinery and an animal bedding biorefinery, whose economic performance was compared. The wheat straw biorefinery could deliver ethanol at a minimum selling price of USD 0.61 per liter, which is similar to prices in the literature. The cost of producing ethanol in the animal bedding biorefinery without water recycling was almost 40% higher, increasing the minimum selling price to USD 1.1 per liter of ethanol. After introducing water recycling in the conditioning step, the animal bedding biorefinery could deliver ethanol at a minimum selling price of USD 0.38 per liter, which is 40% lower than in the case of the wheat straw biorefinery. This demonstrates that low-value feedstocks can be used to reduce the biofuel price, as feedstock savings easily cover the additional conditioning cost.
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