Challenges and trends in bioseparations

Asenjo, Juan A.; Andrews, Bárbara A.

doi:10.1002/jctb.1851

Cited by 26 publications

(12 citation statements)

References 19 publications

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“…This is the result of the optimization of recombinant protein production. The final concentration of the product and yield are virtually hundreds of times higher than they were 15 years ago [59]. Furthermore, the urgent need to develop bioseparation processes to obtain low molecular weight non-protein products will demand new bioengineering strategies.…”

Section: Future Trends and Challengesmentioning

confidence: 99%

Extraction and Purification of Bioproducts and Nanoparticles using Aqueous Two‐Phase Systems Strategies

et al. 2008

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Aqueous Two-Phase Systems (ATPS) is a primary recovery technique that has shown great potential for the efficient extraction and purification of high value biological compounds. The main advantages of this technique include scaling up feasibility, process integration capability and biocompatibility. In this review, the efficient use of ATPS for the extraction of proteins, genetic material, low molecular weight compounds, bioparticles, nanoparticles and cells is highlighted. The important role of ATPS in process integration, i.e., extractive conversion, extractive fermentation, cell disruption integrated with product recovery, and extractive purification, is discussed. A novel approach to protein molecular characterization combining ATPS and 2-dimension electrophoresis (2-DE) is introduced as a first step in the process development. Novel approaches for downstream processing using ATPS and dielectrophoresis are presented. Finally, trends concerning the application of ATPS strategies to address the future challenges of bioseparation are discussed.

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Section: Future Trends and Challengesmentioning

confidence: 99%

Extraction and Purification of Bioproducts and Nanoparticles using Aqueous Two‐Phase Systems Strategies

et al. 2008

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“…Proteins with special properties, such as therapeutic and catalytic properties, are one of the most attractive products in the biotechnology industry today. The production of recombinant proteins, in the large majority of cases, has been optimized and has become very efficient; product protein yields and concentration are virtually hundreds of times higher than they were 15 years ago (Asenjo and Andrews, 2008).…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of elution curves for a protein mixture in ion exchange chromatography applied to high protein concentration

Orellana

Shene

Asenjo

2009

Biotech & Bioengineering

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Protein elution curves in ion exchange chromatography (IEC) were simulated with a rate model. Three pure proteins and their mixture were used (a-lactalbumin, BSA, and conalbumin) under different operational conditions. The anionic matrix Q-Sepharose FF was used packed in a 1 mL column. A high protein concentration (37.5 mg/mL of total protein injected into the column) was used in order to extend the utility of the model. Mass transfer parameters were calculated using empiric correlations, where the axial dispersion was negligible (Pe > 300) and the mass transfer was controlled by the intraparticle diffusion (Bi > 10). The model assumes a modulator-eluite relationship were the equilibrium constant of the Langmuir isotherm was a function of salt concentration. Adsorption kinetic parameters were estimated from experimental data. The parameters for pure proteins were determined, and elution curves for changes in flow rate, ionic strength gradient, concentration, and sample size were predicted by the model. Then the kinetic parameters of the mixture were determined under the same operational conditions and some of the parameters had to be modified to take into account effects such as protein-protein interactions, competition, and displacement. Experimental elution curves obtained for changes in operational conditions such as flow rate and ionic strength gradient were simulated by the rate model for the protein mixture with a relative error in retention time of visible peaks <5%. IEC operational conditions and the peak fraction collection can be selected using a cost function of the production process which considers yield, purity, concentration, and process time that are obtained from simulations. Operational conditions that gave the minimum cost were selected. Simulations allows to diminish experimental time and cost.

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“…1a. These three stages have been formulated after careful consideration of previous literature and reports on bioseparations and downstream processing by Belter, Cussler and Hu [31], Harrison [32,80], Chisti [81][82][83][84][85], Asenjo [16,22,27,86,87], and Bogle [39,88,89]. Each stage has multiple technologies available for every task, as shown in Table 1.…”

Section: Stage-wise Separation Schemementioning

confidence: 99%

Synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions

Yenkie

Maravelias

2019

BMC Chem Eng

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Recent advances in metabolic engineering have enabled the production of chemicals via bio-conversion using microbes. However, downstream separation accounts for 60-80% of the total production cost in many cases. Previous work on microbial production of extracellular chemicals has been mainly restricted to microbiology, biochemistry, metabolomics, or techno-economic analysis for specific product examples such as succinic acid, xanthan gum, lycopene, etc. In these studies, microbial production and separation technologies were selected apriori without considering any competing alternatives. However, technology selection in downstream separation and purification processes can have a major impact on the overall costs, product recovery, and purity. To this end, we apply a superstructure optimization based framework that enables the identification of critical technologies and their associated parameters in the synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions. We divide extracellular chemicals into three categories based on their physical properties, such as water solubility, physical state, relative density, volatility, etc. We analyze three major extracellular product categories (insoluble light, insoluble heavy and soluble) in detail and provide suggestions for additional product categories through extension of our analysis framework. The proposed analysis and results provide significant insights for technology selection and enable streamlined decision making when faced with any microbial product that is released extracellularly. The parameter variability analysis for the product as well as the associated technologies and comparison with novel alternatives is a key feature which forms the basis for designing better bioseparation strategies that have potential for commercial scalability and can compete with traditional chemical production methods.

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Challenges and trends in bioseparations

Cited by 26 publications

References 19 publications

Extraction and Purification of Bioproducts and Nanoparticles using Aqueous Two‐Phase Systems Strategies

Extraction and Purification of Bioproducts and Nanoparticles using Aqueous Two‐Phase Systems Strategies

Mathematical modeling of elution curves for a protein mixture in ion exchange chromatography applied to high protein concentration

Synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions

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