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Biotechnology Progress

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https://www.readbyqxmd.com/read/28054475/design-and-control-of-integrated-chromatography-column-sequences
#1
Niklas Andersson, Anton Löfgren, Marianne Olofsson, Anton Sellberg, Peter Tiainen, Bernt Nilsson
To increase the productivity in biopharmaceutical production a natural step is to introduce integrated continuous biomanufacturing which leads to fewer buffer and storage tanks, smaller sizes of integrated unit operations and full automation of the operation. The main contribution of this work is to illustrate a methodology for design and control of a downstream process based on integrated column sequences. For small scale production, e.g. pre-clinical studies, integrated column sequences can be implemented on a single chromatography system...
January 5, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28054473/-screening-different-host-cell-lines-for-the-dynamic-production-of-measles-virus
#2
Tanja A Grein, Felix Schwebel, Marco Kress, Daniel Loewe, Hauke Dieken, Denise Salzig, Tobias Weidner, Peter Czermak
Measles virus (MV) has a natural affinity for cancer cells and oncolytic MV preparations have therefore been investigated in several clinical trials as a potential treatment for cancer. The main bottleneck in the administration of oncolytic MV to cancer patients is the production process, because very large doses of virus particles are required for each treatment. Here we investigated the productivity of different host cells and found that a high infection efficiency did not necessarily result in high virus yields because virus release is also dependent on the host cell...
January 5, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28054464/economic-improvement-of-continuous-pharmaceutical-production-via-the-optimal-control-of-a-multi-feed-bioreactor
#3
Jonathan P Raftery, Melanie R DeSessa, M Nazmul Karim
Projections on the profitability of the pharmaceutical industry predict a large amount of growth in the coming years. Stagnation over the last 20 years in product development has led to the search for new processing methods leading to improvements in profitability by the reduction of operating costs or the improvement of process productivity. This work proposes a novel multi-feed bioreactor system composed of independently controlled feeds for substrate(s) and media used as a supplement and allows for the free manipulation of the bioreactor supply rate and substrate concentrations to maximize bioreactor productivity and substrate utilization while reducing operating costs...
January 5, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28054462/optimization-of-biopharmaceutical-downstream-processes-supported-by-mechanistic-models-and-artificial-neural-networks
#4
Silvia M Pirrung, Luuk A M van der Wielen, Ruud F W C Van Beckhoven, Emile J A X van de Sandt, Michel H M Eppink, Marcel Ottens
Downstream process development is a major area of importance within the field of bioengineering. During the design of such a downstream process, important decisions have to be made regarding the type of unit operations as well as their sequence and their operating conditions. Current computational approaches addressing these issues either show a high level of simplification or struggle with computational speed. Therefore, this article presents a new approach that combines detailed mechanistic models and speed-enhancing artificial neural networks...
January 5, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28019710/mammalian-cell-culture-monitoring-using-in-situ-spectroscopy-is-your-method-really-optimised
#5
Silvère André, Sylvain Lagresle, Zahia Hannas, Éric Calvosa, Ludovic Duponchel
In recent years, as a result of the process analytical technology (PAT) initiative of the US Food and Drug Administration (FDA), many different works have been carried out on direct and in situ monitoring of critical parameters for mammalian cell cultures by Raman spectroscopy and multivariate regression techniques. However, despite interesting results, it cannot be said that the proposed monitoring strategies, which will reduce errors of the regression models and thus confidence limits of the predictions, are really optimized...
December 26, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/28019701/current-state-and-perspectives-in-modeling-and-control-of-human-pluripotent-stem-cell-expansion-processes-in-stirred-tank-bioreactors
#6
REVIEW
Vytautas Galvanauskas, Vykantas Grincas, Rimvydas Simutis, Yuki Kagawa, Masahiro Kino-Oka
Implementation of model-based practices for process development, control, automation, standardization, and validation are important factors for therapeutic and industrial applications of human pluripotent stem cells. As robust cultivation strategies for pluripotent stem cell expansion and differentiation have yet to be determined, process development could be enhanced by application of mathematical models and advanced control systems to optimize growth conditions. Therefore, it is important to understand both the potential of possible applications and the apparent limitations of existing mathematical models to improve pluripotent stem cell cultivation technologies...
December 26, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/28019689/general-solutions-to-decompose-heterogeneous-compositions-using-antibody-afucosylation-as-a-model-system
#7
John D Chung, Peter L Zhan
Methods involving the use of mathematical models of competitive ligand-receptor binding to characterize mixtures of ligands in terms of compositions and properties of the component ligands have been developed. The associated mathematical equations explicitly relate component ligand physical-chemical properties and mole fractions to measurable properties of the mixture including steady state binding activity, 1/Kd,apparent or equivalently 1/EC50, and kinetic rate constants kon,apparent and koff,apparent allowing; 1) component ligand physical property determination and 2) mixture property predictions...
December 26, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/28019688/cell-culture-media-supplementation-of-infrequently-used-sugars-for-the-targeted-shifting-of-protein-glycosylation-profiles
#8
Patrick Hossler, Christopher Racicot, Christopher Chumsae, Sean McDermott, Keith Cochran
Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized...
December 26, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997765/intracellular-cho-cell-metabolite-profiling-reveals-steady-state-dependent-metabolic-fingerprints-in-perfusion-culture
#9
Daniel J Karst, Robert Steinhoff, Marie R G Kopp, Elisa Serra, Miroslav Soos, Renato Zenobi, Massimo Morbidelli
Perfusion cell culture processes allow the steady-state culture of mammalian cells at high viable cell density, which is beneficial for overall product yields and homogeneity of product quality in the manufacturing of therapeutic proteins. In this study, the extent of metabolic steady state and the change of the metabolite profile between different steady states of an industrial Chinese hamster ovary (CHO) cell line producing a monoclonal antibody (mAb) was investigated in stirred tank perfusion bioreactors...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997085/effect-of-guanidine-and-arginine-on-protein-ligand-interactions-in-multimodal-cation-exchange-chromatography
#10
Siddharth Parimal, Shekhar Garde, Steven M Cramer
The addition of fluid phase modifiers provides significant opportunities for increasing the selectivity of multimodal chromatography. In order to optimize this selectivity, it is important to understand the fundamental interactions between proteins and these modifiers. To this end, Molecular Dynamics (MD) simulations were first performed to study the interactions of guanidine and arginine with three proteins. The simulation results showed that both guanidine and arginine interacted primarily with the negatively charged regions on the proteins and that these regions could be readily predicted using electrostatic potential maps...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997084/electrodialytic-separation-of-levulinic-acid-catalytically-synthesized-from-woody-biomass-for-the-use-of-microbial-conversion
#11
Hiroshi Habe, Susumu Kondo, Yuya Sato, Tomoyuki Hori, Manabu Kanno, Nobutada Kimura, Kohtaro Kirimura, Hideaki Koike
Levulinic acid (LA) is produced by the catalytic conversion of a variety of woody biomass. To investigate the potential use of desalting electrodialysis (ED) for LA purification, electrodialytic separation of levulinate from both reagent and cedar-derived LA solution (40-160 g L(-1) ) was demonstrated. When using reagent LA solution with pH5.0 to 6.0, the recovery rates of levulinate ranged from 68 to 99%, and the energy consumption for recovery of 1 kg of levulinate ranged from 0.18 to 0.27 kWh kg(-1) . With cedar-derived LA solution (pH6...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997079/optimization-of-enzymatic-hydrolysis-and-fermentation-conditions-for-improved-bioethanol-production-from-potato-peel-residues
#12
Imen Ben Taher, Patrick Fickers, Sofien Chniti, Mnasser Hassouna
The aim of this work was the optimization of the enzyme hydrolysis of potato peel residues (PPR) for bioethanol production. The process included a pretreatment step followed by an enzyme hydrolysis using crude enzyme system composed of cellulase, amylase and hemicellulase, produced by a mixed culture of Aspergillus niger and Trichoderma reesei. Hydrothermal, alkali and acid pretreatments were considered with regards to the enhancement of enzyme hydrolysis of potato peel residues. The obtained results showed that hydrothermal pretreatment lead to a higher enzyme hydrolysis yield compared to both acid and alkali pretreatments...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997076/biological-pretreatment-of-corn-stover-with-phlebia-brevispora-nrrl-13108-for-enhanced-enzymatic-hydrolysis-and-efficient-ethanol-production
#13
Badal C Saha, Gregory J Kennedy, Nasib Qureshi, Michael A Cotta
Biological pretreatment of lignocellulosic biomass by white-rot fungus can represent a low-cost and eco-friendly alternative to harsh physical, chemical or physico-chemical pretreatment methods to facilitate enzymatic hydrolysis. In this work, solid state cultivation of corn stover with Phlebia brevispora NRRL-13018 was optimized with respect to duration, moisture content and inoculum size. Changes in composition of pretreated corn stover and its susceptibility to enzymatic hydrolysis were analyzed. About 84% moisture and 42 days incubation at 28°C were found to be optimal for pretreatment with respect to enzymatic saccharification...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997074/production-of-8-11-dihydroxy-and-8-hydroxy-unsaturated-fatty-acids-from-unsaturated-fatty-acids-by-recombinant-escherichia-coli-expressing-8-11-linoleate-diol-synthase-from-penicillium-chrysogenum
#14
Min-Ji Kim, Min-Ju Seo, Kyung-Chul Shin, Deok-Kun Oh
Hydroxy unsaturated fatty acids can be used as antimicrobial surfactants. 8,11-Linoleate diol synthase (8,11-LDS) catalyzes the conversion of unsaturated fatty acid to 8-hydroperoxy unsaturated fatty acid, and it is subsequently isomerized to 8,11-dihydroxy unsaturated fatty acid by the enzyme. The optimal reaction conditions of recombinant Escherichia coli cells expressing Penicillium chrysogenum 8,11-LDS for the production of 8,11-dihydroxy-9,12(Z,Z)-octadecadienoic acid (8,11-DiHODE), 8,11-dihydroxy-9,12,15(Z,Z,Z)-octadecatrienoic acid (8,11-DiHOTrE), 8-hydroxy-9(Z)-hexadecenoic acid (8-HHME), and 8-hydroxy-9(Z)-octadecenoic acid (8-HOME) were pH 7...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27997072/structural-and-performance-characteristics-of-representative-anion-exchange-resins-used-for-weak-partitioning-chromatography
#15
Shaojie Zhang, Tim Iskra, William Daniels, Jeffrey Salm, Christopher Gallo, Ranga Godavarti, Giorgio Carta
Weak partitioning chromatography (WPC) has been proposed for the purification of monoclonal antibodies using an anion exchange (AEX) resin to simultaneously remove both acidic and basic protein impurities. Despite potential advantages, the relationship between resin structure and WPC performance has not been evaluated systematically. In this work, we determine the structure of representative AEX resins (Fractogel® EMD TMAE HiCap, Q Sepharose FF, and POROS 50 HQ) using transmission electron microscopy and inverse size exclusion chromatography and characterize protein interactions while operating these resins under WPC conditions using two mAb monomers, a mAb dimer, mAb multimers, and BSA as model products and impurities...
December 20, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27977916/spore-displayed-enzyme-cascade-with-tunable-stoichiometry
#16
Long Chen, Ashok Mulchandani, Xin Ge
Taking the advantages of inert and stable nature of endospores, we developed a biocatalysis platform for multiple enzyme immobilization on Bacillus subtilis spore surface. Among B. subtilis outer coat proteins, CotG mediated a high expression level of Clostridium thermocellum cohesin (CtCoh) with a functional display capability of ∼10(4) molecules per spore of xylose reductase C. termocellum dockerin fusion protein (XR-CtDoc). By co-immobilization of phosphite dehydrogenase (PTDH) on spore surface via Ruminococcus flavefaciens cohesin-dockerin modules, regeneration of NADPH was achieved...
December 15, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27977915/transient-and-stable-cho-expression-purification-and-characterization-of-novel-hetero-dimeric-bispecific-igg-antibodies
#17
Yashas Rajendra, Robert B Peery, Maria D Hougland, Xiufeng Wu, Jonathan R Fitchett, Michael Bacica, Stephen J Demarest, Gavin C Barnard
IgG bispecific antibodies (BsAbs) represent one of the preferred formats for bispecific antibody therapeutics due to their native-like IgG properties and their monovalent binding to each target. Most reported studies utilized transient expression in HEK293 cells to produce BsAbs. However, the expression of biotherapeutic molecules using stable CHO cell lines is commonly used for biopharmaceutical manufacturing. Unfortunately, limited information is available in the scientific literature on the expression of BsAbs in CHO cell lines...
December 15, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27977914/analysis-of-tubespins-as-a-suitable-scale-down-model-of-bioreactors-for-high-cell-density-cho-cell-culture
#18
Natalia Gomez, Malhar Ambhaikar, Li Zhang, Chung-Jr Huang, Hedieh Barkhordarian, Jonathan Lull, Chris Gutierrez
High cell density (HCD) culture increases recombinant protein productivity via higher biomass. Compared to traditional fed-batch cultures, HCD is achieved by increased nutrient availability and removal of undesired metabolic components via regular medium replenishment. HCD process development is usually performed in instrumented lab-scale bioreactors (BR) that require time and labor for set-up and operation. To potentially minimize resources and cost during HCD experiments, we evaluated a two-week 50mL Tubespin (TS) simulated HCD process where daily medium exchanges mimic the medium replacement rate in BR...
December 15, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27977912/characterization-of-tap-ambr-250-disposable-bioreactors-as-a-reliable-scale-down-model-for-biologics-process-development
#19
Ping Xu, Colleen Clark, Todd Ryder, Colleen Sparks, Jiping Zhou, Michelle Wang, Reb Russell, Charo Scott
Demands for development of biological therapies is rapidly increasing, as is the drive to reduce time to patient. In order to speed up development, the disposable Automated Microscale Bioreactor (Ambr 250) system is increasingly gaining interest due to its advantages, including highly automated control, high throughput capacity, and short turnaround time. Traditional early stage upstream process development conducted in 2 - 5 L bench-top bioreactors requires high foot-print, and running cost. The establishment of the Ambr 250 as a scale-down model leads to many benefits in process development...
December 15, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27977910/bioreactor-productivity-and-media-cost-comparison-for-different-intensified-cell-culture-processes
#20
Sen Xu, John Gavin, Rubin Jiang, Hao Chen
Process intensification in biomanufacturing has attracted a great deal of interest in recent years. Manufacturing platform improvements leading to higher cell density and bioreactor productivity have been pursued. Here we evaluated a variety of intensified mammalian cell culture processes for producing monoclonal antibodies. Cell culture operational modes including fed-batch (normal seeding density or high seeding density with N-1 perfusion), perfusion, and concentrated fed-batch (CFB) were assessed using the same media set with the same Chinese Hamster Ovary (CHO) cell line...
December 15, 2016: Biotechnology Progress
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