Rational and systematic protein purification process development: the next generation

Nfor, Beckley K.; Verhaert, Peter; Wielen, Luuk A.M. van der; Hubbuch, Jürgen; Ottens, Marcel

doi:10.1016/j.tibtech.2009.09.002

Cited by 96 publications

(57 citation statements)

References 45 publications

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“…The excellent selectivity properties and relatively mild conditions in liquid chromatography have made it indispensable in the downstream process development of therapeutic proteins for which very high purity of the active product is paramount and the time-to-market short [1,2]. While the vast majority of chromatographic media used for protein purification today are designed to operate in single interaction mode such as size exclusion, electrostatic interaction, hydrophobic interaction and bioaffinity interaction [3], multimodal or mixed mode chromatographic media, on the other hand, are intentionally functionalized with ligands capable of two or more orthogonal modes of interactions to effect the separation.…”

Section: Introductionmentioning

confidence: 99%

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

Nfor

Noverraz

Chilamkurthi

et al. 2010

Journal of Chromatography A

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156

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Section: Introductionmentioning

confidence: 99%

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

Nfor

Noverraz

Chilamkurthi

et al. 2010

Journal of Chromatography A

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156

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“…Indeed, in our opinion it seems most likely that process development will benefit most from the application of miniaturized systems. There is a growing group of bioprocess practitioners that share this view, working not only on development problems related to applied biocatalysis [18][19][20], but also fermentation [21] and protein recovery for biopharmaceutical applications [22]. Some of the key motivators are reduced development costs and accelerated process development, compared to conventional technologies in the ml scale.…”

Section: Process Development Using Microfluidic Miniaturized Systemsmentioning

confidence: 99%

Biocatalytic process development using microfluidic miniaturized systems

Krühne

Heintz

Ringborg

et al. 2014

Green Processing and Synthesis

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Abstract:The increasing interest in biocatalytic processes means there is a clear need for a new systematic development paradigm which encompasses both protein engineering and process engineering. This paper argues that through the use of a new microfluidic platform, data can be collected more rapidly and integrated with process modeling, can provide the basis for validating a reduced number of potential processes. The miniaturized platform should use a smaller reagent inventory and make better use of precious biocatalysts. The EC funded BIOINTENSE project will use ω-transaminase based synthesis of chiral amines as a test-bed for assessing the viability of such a high throughput biocatalytic process development, and in this paper, such a vision for the future is presented.

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“…Major decisions affecting the lifecycle of the process are made during development of the first process flowsheet. Experiencebased process synthesis can often result in overall suboptimal processes with inefficient utilization of energy and auxiliary materials (Nfor et al, 2009). Therefore, systematic process development based on identification of justified optima is essential for efficient utilization of time and resources.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, systematic process development based on identification of justified optima is essential for efficient utilization of time and resources. Nfor et al (2009) identified four types of process synthesis strategies applicable to chemical industries: heuristics or knowledge-based strategies (Cziner et al, 2005), optimization-based strategies (Steimel et al, 2013;Grossmann and Daichendt, 1996), high-throughput experimentation strategies (Bhambure et al, 2011;Schuldt and Schembecker, 2013) and a combination of the aforementioned strategies (Ahamed et al, 2006). Each approach has strengths and weaknesses as discussed elsewhere (Nfor et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Nfor et al (2009) identified four types of process synthesis strategies applicable to chemical industries: heuristics or knowledge-based strategies (Cziner et al, 2005), optimization-based strategies (Steimel et al, 2013;Grossmann and Daichendt, 1996), high-throughput experimentation strategies (Bhambure et al, 2011;Schuldt and Schembecker, 2013) and a combination of the aforementioned strategies (Ahamed et al, 2006). Each approach has strengths and weaknesses as discussed elsewhere (Nfor et al, 2009). Mathematical optimization based method can offer significant advantages to hydrometallurgical process development: clarification of interactions between unit operations, utilization of validated models for process optimization, user-independence after formulation of the search space, and the ability to identify the optimal process meeting the set criteria (Nfor et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of hydrometallurgical processes for valorization of secondary raw materials using ant colony optimization and key performance indicators

2015

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An algorithm-based method for synthesis of hydrometallurgical processes using limited amounts of experimental data is presented. The method enables simultaneous selection and sequencing of unit operations and optimization of operating parameters. An ant colony optimization (ACO) based algorithm is used to identify the most economic process alternative in an iterative manner. Key performance indicators are used for comparison of candidate processes: a purification performance index measures purity improvement and a separation cost indicator is used as an objective function in process optimization. Computational times were reduced significantly with the suggested method compared to an algorithm which evaluates all the possible process options. The practical applicability of the method to hydrometallurgy is demonstrated by investigating zinc recovery from argon oxygen decarburization dust with two alternative leaching methods and recovery of lanthanides from nickel metal hydride (NiMH) batteries. In the first zinc recovery process, 150 min normal batch leaching with 0.5 M H 2 SO 4 is used, and in the other one 270 min batch leaching with H 2 SO 4 is done by controlling the pH (N 3.0). In both cases the leachate is extracted with D2EHPA at pH 4.27, and stripped with circulating solution from zinc electrolysis. For lanthanides recovery the algorithm suggested a process in which the raw material is leached with 1.3 M HCl, the leachate is extracted with D2EHPA at pH 2.2, organic phase is stripped with 2.0 M HCl and 99% pure Ln-oxalates are precipitated with oxalic acid at pH 0.6. Compared to previously suggested process for the same raw material, the algorithm suggests operating the leaching step such that higher selectivity is achieved by sacrificing some yield. AbbreviationsACO ant colony optimization AOD argon oxygen decarburization CPU central processing unit EDR energy dissipation rate IRR internal rate of return KPI key performance indicator PPI purification performance index SCI separation cost indicator Notation A flow rate, m 3 /s c i concentration of contaminants, kg/m 3 E concentration of extractant, m 3 /m 3 K cost, item of expenses, €/kg k L specific cost of a leaching step, €/kg k pur,l specific cost of a purification step, €/kg L probability M number of components in a chemical system N number of ants in a colony n number of process steps P number of discrete values of operating parameters SL solvent loss in solvent extraction T concentration of a target metal in the system, kg/m 3 t b batch time in leaching, s U number of unit operations V L volume of leaching vessel, m 3 x purity Y yieldGreek symbols α the degree of importance of the pheromones ξ parameter used to control the scale of the global updating of the pheromone τ l,u,p amount of pheromone in a cell ρ pheromone decay factor Hydrometallurgy 153 (2015) 121-133

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Rational and systematic protein purification process development: the next generation

Cited by 96 publications

References 45 publications

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

Biocatalytic process development using microfluidic miniaturized systems

Synthesis of hydrometallurgical processes for valorization of secondary raw materials using ant colony optimization and key performance indicators

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