Showing papers on "Bioprocess published in 2016"
University of California, San Diego1, Agency for Science, Technology and Research2, University of Natural Resources and Life Sciences, Vienna3, University of Queensland4, Johns Hopkins University5, Technical University of Denmark6, University of Chile7, University of Iceland8, King Abdullah University of Science and Technology9, National University of Singapore10
TL;DR: The models accurately predict growth phenotypes and known auxotrophies in CHO cells and show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway.
Abstract: Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.
203 citations
TL;DR: A sustainable bioprocess for the production of 1,4-butanediol from carbohydrate feedstocks was developed and an overall process that successfully performed at commercial scale for direct production of bio-BDO from dextrose is highlighted.
186 citations
TL;DR: The technological feasibility of bio-based chemical production is discussed in terms of the feedstocks and different bioprocessing approaches, including the consolidation of enzyme production, enzymatic hydrolysis of biomass, and fermentation.
185 citations
TL;DR: The results exhibited that the combined bioprocess for hydrogen production from food waste was feasible and is an important study for attracting investment and industrialization interest for hydrogenProduction from food Waste in the industrial scale.
149 citations
TL;DR: The technology involved in the bioprocess is discussed and the available strategies and main advances in microbial fermentation and purification process to obtain biopharmaceuticals are described.
132 citations
TL;DR: The concept of "morphology engineering" is proposed here, where many more genes are to be exploited for various cell morphologies and the limits of bacterial lengths and diameters may depend on how the genes are manipulated, to enhance bioprocess competitiveness.
90 citations
TL;DR: The use of dynamic metabolic control strategies to engineer productive and robust stationary phase biocatalysts in combination with advanced two-stage fermentation has the potential to both increase process level metrics, including specific productivity, volumetric rates, titers and yields.
Abstract: Bioprocessing technology offers a potentially promising and more sustainable alternative to many traditional chemical process technologies; however to date this potential has largely not been realized. For large-scale bioprocessing to have larger penetration into larger volume chemical markets, new technologies need to both exploit the key advantages of biocatalysts over chemical catalysts, while addressing the key limitations of bioprocessing as compared to more traditional chemical process technology. The use of dynamic metabolic control strategies to engineer productive and robust stationary phase biocatalysts in combination with advanced two-stage fermentation has the potential to both increase process level metrics, including specific productivity, volumetric rates, titers and yields, while leveraging the unique ability of whole cell biocatalysts to perform multiple complex chemical conversions in a single unit operation.
89 citations
TL;DR: Different bioprocess applications of mixed cultures, currently in practice along with types of positive microbial interactions involved, have been reviewed and Complexity of Mixed cultures from the perspective of multiple types of intra-culture relationships has been explained in detail.
Abstract: The utilization of mixed consortia or mixed culture has become a current research trend of applied microbiology, bioprocess engineering and biotechnology. The constituent microorganisms of such mixed cultures can jointly perform complex processes efficiently, yielding the desired product at an augmented rate, in comparison to monocultures. It is understandable that the interactions between the microbial partners in these mixed cultures are expected to have a significant impact on the combined performance of the microorganisms and the bioprocess as a whole. Prevalence of positive interactions (commensalism or mutualism) among microbial members of a mixed culture or consortia can significantly enhance the product outcome of the bioprocess, ensuring their industrial application and long-term stability. On the contrary, negative interaction (parasitism, predation or ammensalism) leads to elimination of microbial members from the consortia causing the destruction of community structure as well as disruption of cumulative performance. Therefore, a priori knowledge on the type of interaction between the microorganisms is also essential for the optimization of the performance of the designed consortia. This could only be achieved through the study of inter-microbial interaction prevailing in a mixed culture. In the present article, different bioprocess applications of mixed cultures, currently in practice along with types of positive microbial interactions involved, have been reviewed. Complexity of mixed cultures from the perspective of multiple types of intra-culture relationships has been explained in detail. Overall, the necessity for more in-depth research studies on "microbial interaction" in mixed culture bioprocesses has been stressed in the article.
63 citations
TL;DR: This mini-review will examine the current best practices and understanding of nanoparticle (NP) formation kinetics and mechanisms to establish a path forward for this technology.
63 citations
TL;DR: The article has opined, which organisms and what bioproducts should be the focus, while exploiting glycerol as feed, and a novel eco-biotechnological strategy employs metabolically diverse bacteria, which ensures higher reproducibility and economics.
Abstract: The biodiesel industry has the potential to meet the fuel requirements in the future. A few inherent lacunae of this bioprocess are the effluent, which is 10 % of the actual product, and the fact that it is 85 % glycerol along with a few impurities. Biological treatments of wastes have been known as a dependable and economical direction of overseeing them and bring some value added products as well. A novel eco-biotechnological strategy employs metabolically diverse bacteria, which ensures higher reproducibility and economics. In this article, we have opined, which organisms and what bioproducts should be the focus, while exploiting glycerol as feed.
60 citations
TL;DR: In this article, a novel bioprocess combining solid state fermentation and dark fermentation for H2 production from food waste (FW) was investigated, which was designed with capacity of 10 ton/day and lifetime of 10 years.
TL;DR: This study demonstrates that thermophilic anaerobes are capable of producing ethanol at high yield and at titers greater than 60 g/L from purified substrates, but additional work is needed to produce the same ethanol titers from pre-treated hardwood.
Abstract: The thermophilic, anaerobic bacterium Thermoanaerobacterium saccharolyticum digests hemicellulose and utilizes the major sugars present in biomass. It was previously engineered to produce ethanol at yields equivalent to yeast. While saccharolytic anaerobes have been long studied as potential biomass-fermenting organisms, development efforts for commercial ethanol production have not been reported. Here, we describe the highest ethanol titers achieved from T. saccharolyticum during a 4-year project to develop it for industrial production of ethanol from pre-treated hardwood at 51–55 °C. We describe organism and bioprocess development efforts undertaken to improve ethanol production. The final strain M2886 was generated by removing genes for exopolysaccharide synthesis, the regulator perR, and re-introduction of phosphotransacetylase and acetate kinase into the methyglyoxal synthase gene. It was also subject to multiple rounds of adaptation and selection, resulting in mutations later identified by resequencing. The highest ethanol titer achieved was 70 g/L in batch culture with a mixture of cellobiose and maltodextrin. In a “mock hydrolysate” Simultaneous Saccharification and Fermentation (SSF) with Sigmacell-20, glucose, xylose, and acetic acid, an ethanol titer of 61 g/L was achieved, at 92 % of theoretical yield. Fungal cellulases were rapidly inactivated under these conditions and had to be supplemented with cellulosomes from C. thermocellum. Ethanol titers of 31 g/L were reached in a 100 L SSF of pre-treated hardwood and 26 g/L in a fermentation of a hardwood hemicellulose extract. This study demonstrates that thermophilic anaerobes are capable of producing ethanol at high yield and at titers greater than 60 g/L from purified substrates, but additional work is needed to produce the same ethanol titers from pre-treated hardwood.
TL;DR: The results demonstrated a promising combined bioprocess for hydrogen production from food waste with the best hydrogen yield of 52.4 mL H2/g food waste was achieved at food waste mass ratio of 5% (w/v).
TL;DR: Results demonstrated that archaeal and bacterial community structure was affected by changes in the acid/alkalinity ratio in the bioprocess, which could be useful for future implementations of two-stage anaerobic digestion processes at both bench- and full-scale.
Abstract: Two-stage technologies have been developed for anaerobic digestion of waste-activated sludge. In this study, the archaeal and bacterial community structure dynamics and bioprocess performance of a bench-scale two-stage anaerobic digester treating urban sewage sludge have been studied by the means of high-throughput sequencing techniques and physicochemical parameters such as pH, dried sludge, volatile dried sludge, acid concentration, alkalinity, and biogas generation. The coupled analyses of archaeal and bacterial communities and physicochemical parameters showed a direct relationship between archaeal and bacterial populations and bioprocess performance during start-up and working operation of a two-stage anaerobic digester. Moreover, results demonstrated that archaeal and bacterial community structure was affected by changes in the acid/alkalinity ratio in the bioprocess. Thus, a predominance of the acetoclastic methanogen Methanosaeta was observed in the methanogenic bioreactor at high-value acid/alkaline ratio, while a predominance of Methanomassilicoccaeceae archaea and Methanoculleus genus was observed in the methanogenic bioreactor at low-value acid/alkaline ratio. Biodiversity tag-iTag sequencing studies showed that methanogenic archaea can be also detected in the acidogenic bioreactor, although its biological activity was decreased after 4 months of operation as supported by physicochemical analyses. Also, studies of the VFA producers and VFA consumers microbial populations showed as these microbiota were directly affected by the physicochemical parameters generated in the bioreactors. We suggest that the results obtained in our study could be useful for future implementations of two-stage anaerobic digestion processes at both bench- and full-scale.
TL;DR: A modularly engineered Corynebacterium glutamicum strain suitable for CBP using hemicellulosic biomass (xylan) as a feedstock is reported, and the direct production of lysine from xylan was successfully demonstrated with the engineered pathway.
Abstract: Hemicellulose, which is the second most abundant polysaccharide in nature after cellulose, has the potential to become a major feedstock for microbial fermentation to produce various biofuels and chemicals. To utilize hemicellulose economically, it is necessary to develop a consolidated bioprocess (CBP), in which all processes from biomass degradation to the production of target products occur in a single bioreactor. Here, we report a modularly engineered Corynebacterium glutamicum strain suitable for CBP using hemicellulosic biomass (xylan) as a feedstock. The hemicellulose-utilizing pathway was divided into three distinct modules, and each module was separately optimized. In the module for xylose utilization, the expression level of the xylose isomerase (xylA) and xylulokinase (xylB) genes was optimized with synthetic promoters of different strengths. Then, the module for xylose transport was engineered with combinatorial sets of synthetic promoters and heterologous transporters to achieve the fastest c...
TL;DR: Modelling relevant to lignocellulosic bioprocess including cell modelling based on kinetics, stoichiometry and integrative approaches and fermentation kinetic modelling for process performance assessment are discussed.
Abstract: Lignocellulosic feedstocks, which are currently under-exploited, can be used for the production of biofuels, such as ethanol, and for biorefinery applications to produce a variety of value-added products. Although bioconversion of lignocellulose by microbial or yeast fermentation have been reported, efficient and economical lignocellulosic fermentation process is still a challenge due to multiple process parameters involved for bioprocess design, optimization and scale-up. Bioprocess modelling strategies have been proven effective for achieving
high-production process* efficiency in yield, productivity or titer of desired product. Several types of bioprocess modelling for lignocellulosic application have been developed and successfully validated as a promising alternative for rapid design, optimization and scaling up of biomass-based process. This review aims to summarize the important development of bioprocess modelling for lignocellulosic bioprocess applications towards the success of biorefineries and bio-based economy. In particular, we discuss modelling relevant to lignocellulosic bioprocess including cell modelling based on kinetics, stoichiometry and integrative approaches and fermentation kinetic modelling for process performance assessment. An overview of these modelling approaches and their application for systematic design of efficient and economical lignocellulose-based bioprocesses are given.
TL;DR: It is shown that the statistical analysis of diverse legacy bioprocess data can provide insight into biop rocessing capabilities of CHO cell lines used in industry.
TL;DR: This study aims at optimizing the bioprocess variables viz. carbon/nitrogen sources, medium pH and fermentation time, by using a Design of Experiments approach for achieving enhanced production of ionic liquid tolerant cellulase from a bacterial isolate Bacillus subtilis SV1.
Abstract: Pretreatment is the requisite step for the bioconversion of lignocellulosics. Since most of the pretreatment strategies are cost/energy intensive and environmentally hazardous, there is a need for the development of an environment-friendly pretreatment process. An ionic liquid (IL) based pretreatment approach has recently emerged as the most appropriate one as it can be accomplished under ambient process conditions. However, IL-pretreated biomass needs extensive washing prior to enzymatic saccharification as the enzymes may be inhibited by the residual IL. This necessitated the exploration of IL-stable saccharification enzymes (cellulases). Current study aims at optimizing the bioprocess variables viz. carbon/nitrogen sources, medium pH and fermentation time, by using a Design of Experiments approach for achieving enhanced production of ionic liquid tolerant cellulase from a bacterial isolate Bacillus subtilis SV1. The cellulase production was increased by 1.41-fold as compared to that under unoptimized conditions. IL-stable cellulase was employed for saccharification of IL (1-ethyl-3-methylimidazolium methanesulfonate) pretreated pine needle biomass in a newly designed bioprocess named as “one pot consolidated bioprocess” (OPCB), and a saccharification efficiency of 65.9% was obtained. Consolidated bioprocesses, i.e., OPCB, offer numerous techno-economic advantages over conventional multistep processes, and may potentially pave the way for successful biorefining of biomass to biofuel, and other commercial products.
TL;DR: A new strategy in using the biotrophic smut fungus Ustilago maydis for the degradation of plant cell wall components by activating its intrinsic enzyme potential during axenic growth is presented.
Abstract: The microbial conversion of plant biomass to valuable products in a consolidated bioprocess could greatly increase the ecologic and economic impact of a biorefinery. Current strategies for hydrolyzing plant material mostly rely on the external application of carbohydrate-active enzymes (CAZymes). Alternatively, production organisms can be engineered to secrete CAZymes to reduce the reliance on externally added enzymes. Plant-pathogenic fungi have a vast repertoire of hydrolytic enzymes to sustain their lifestyle, but expression of the corresponding genes is usually highly regulated and restricted to the pathogenic phase. Here, we present a new strategy in using the biotrophic smut fungus Ustilago maydis for the degradation of plant cell wall components by activating its intrinsic enzyme potential during axenic growth. This fungal model organism is fully equipped with hydrolytic enzymes, and moreover, it naturally produces value-added substances, such as organic acids and biosurfactants. To achieve the deregulated expression of hydrolytic enzymes during the industrially relevant yeast-like growth in axenic culture, the native promoters of the respective genes were replaced by constitutively active synthetic promoters. This led to an enhanced conversion of xylan, cellobiose, and carboxymethyl cellulose to fermentable sugars. Moreover, a combination of strains with activated endoglucanase and β-glucanase increased the release of glucose from carboxymethyl cellulose and regenerated amorphous cellulose, suggesting that mixed cultivations could be a means for degrading more complex substrates in the future. In summary, this proof of principle demonstrates the potential applicability of activating the expression of native CAZymes from phytopathogens in a biocatalytic process.
IMPORTANCE This study describes basic experiments that aim at the degradation of plant cell wall components by the smut fungus Ustilago maydis. As a plant pathogen, this fungus contains a set of lignocellulose-degrading enzymes that may be suited for biomass degradation. However, its hydrolytic enzymes are specifically expressed only during plant infection. Here, we provide the proof of principle that these intrinsic enzymes can be synthetically activated during the industrially relevant yeast-like growth. The fungus is known to naturally synthesize valuable compounds, such as itaconate or glycolipids. Therefore, it could be suited for use in a consolidated bioprocess in which more complex and natural substrates are simultaneously converted to fermentable sugars and to value-added compounds in the future.
TL;DR: This study demonstrated that the one-step bioprocess that integrated endo-inulinase production, FOS fermentation, and non-FOS sugars removal into one reactor was simple and highly efficient to produce high-content FOS from inulin.
TL;DR: In this article, a plasmid system termed rep/cap split packaging was proposed to improve the performance of recombinant adeno-associated virus (rAAV) based therapies, achieving a 12-fold increase in rAAV vector titers compared to the pDG standard system.
Abstract: Viral vectors used for gene and oncolytic therapy belong to the most promising biological products for future therapeutics. Clinical success of recombinant adeno-associated virus (rAAV) based therapies raises considerable demand for viral vectors, which cannot be met by current manufacturing strategies. Addressing existing bottlenecks, we improved a plasmid system termed rep/cap split packaging and designed a minimal plasmid encoding adenoviral helper function. Plasmid modifications led to a 12-fold increase in rAAV vector titers compared to the widely used pDG standard system. Evaluation of different production approaches revealed superiority of processes based on anchorage- and serum-dependent HEK293T cells, exhibiting about 15-fold higher specific and volumetric productivity compared to well-established suspension cells cultivated in serum-free medium. As for most other viral vectors, classical stirred-tank bioreactor production is thus still not capable of providing drug product of sufficient amount. We show that manufacturing strategies employing classical surface-providing culture systems can be successfully transferred to the new fully-controlled, single-use bioreactor system Integrity(TM) iCELLis(TM) . In summary, we demonstrate substantial bioprocess optimizations leading to more efficient and scalable production processes suggesting a promising way for flexible large-scale rAAV manufacturing.
TL;DR: Very similar results were observed when comparing the metabolic phenotype and bioprocess performance of STR–PFR and STR–STR configuration, although opposed back mixing profiles were present.
Abstract: In the last two decades, scale‐down studies based on compartmented reactor setups became the standard procedure to mimic inhomogeneous cultivation conditions. In the academic field and with application to industrial‐scale, two basic scale‐down bioreactor configurations both showing a stirred tank reactor (STR) as main compartment predominate this research field. The connection to a plug flow reactor (PFR) generates oscillatory gradients with a distinct residence time of the culture, while the STR provides a broad residence time distribution leading to more heterogeneous oscillations. The influence of these opposed hydrodynamic profiles for their applicability for scale‐down bioreactor setups as well as their specific influence on the metabolic phenotype of l‐lysine producing Corynebacterium glutamicum DM1800 strain was investigated. Batch cultivations under oscillatory oxygen deprivation and substrate excess were carried out in STR–PFR and STR–STR scale‐down devices. In both setups, the induced inhomogeneity resulted in a reduction of growth rate and increased the l‐lactate and l‐glutamate by‐product formation, while biomass and product yields stayed nearly constant. Apart from differing side‐product levels, very similar results were observed when comparing the metabolic phenotype and bioprocess performance of STR–PFR and STR–STR configuration, although opposed back mixing profiles were present.
TL;DR: It is testified that the three-stage enzymatic hydrolysis could greatly improve the efficiency of the bioprocess from high solid loading SECS to SCO by Mortierella isabellina.
TL;DR: Recent measures to improve monomer-free COS production using chitosanase/non-specific enzymes and purification/fractionation of these molecules using ultrafiltration and column chromatographic techniques are covered.
Abstract: Biological activities of chitosan oligosaccharides (COS) are well documented, and numerous reports of COS production using specific and non-specific enzymes are available. However, strategies for improving the overall yield by making it monomer free need to be developed. Continuous enzymatic production from chitosan derived from marine wastes is desirable and is cost-effective. Isolation of potential microbes showing chitosanase activity from various ecological niches, gene cloning, enzyme immobilization, and fractionation/purification of COS are some areas, where lot of work is in progress. This review covers recent measures to improve monomer-free COS production using chitosanase/non-specific enzymes and purification/fractionation of these molecules using ultrafiltration and column chromatographic techniques. Various bioprocess strategies, gene cloning for enhanced chitosanase enzyme production, and other measures for COS yield improvements have also been covered in this review. COS derivative preparation as well as COS-coated nanoparticles for efficient drug delivery are being focused in recent studies.
TL;DR: An economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling, showing that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both biop rocesses overlap.
Abstract: Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two-phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling does not impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques.
TL;DR: Using protein spikes, the accuracy of the B CA protein quantification could be improved fivefold, taking the BCA protein quantifying to a level of accuracy comparable to other, more expensive methods.
Abstract: Determining total protein content is a routine operation in many laboratories. Despite substantial work on assay optimization interferences, the widely used bicinchoninic acid (BCA) assay remains widely recognized for its robustness. Especially in the field of bioprocess engineering the inaccuracy caused by interfering substances remains hardly predictable and not well understood. Since the introduction of the assay, sample pre-treatment by trichloroacetic acid (TCA) precipitation has been indicated as necessary and sufficient to minimize interferences. However, the sample matrix in cultivation media is not only highly complex but also dynamically changing over process time in terms of qualitative and quantitative composition. A significant misestimation of the total protein concentration of bioprocess samples is often observed when following standard work-up schemes such as TCA precipitation, indicating that this step alone is not an adequate means to avoid measurement bias. Here, we propose a modification of the BCA assay, which is less influenced by sample complexity. The dynamically changing sample matrix composition of bioprocessing samples impairs the conventional approach of compensating for interfering substances via a static offset. Hence, we evaluated the use of a correction factor based on an internal spike measurement for the respective samples. Using protein spikes, the accuracy of the BCA protein quantification could be improved fivefold, taking the BCA protein quantification to a level of accuracy comparable to other, more expensive methods. This will allow reducing expensive iterations in bioprocess development to due inaccurate total protein analytics.
TL;DR: It is demonstrated that this compound when spiked at meaningful concentrations 72 h into culture considerably reduces the maximum cell density achieved, reinforcing the requirement for the complete characterization of all potential leachable compounds from disposable materials to assess their risk not only to the patient but also to the production pipeline itself.
Abstract: The biopharmaceutical industry has invested considerably in the implementation of single-use disposable bioreactors in place of or in addition to their stainless steel-counterparts. This new wave of construction materials for disposable bioprocess containers encompass a plethora of uncharacterized secondary compounds that, when in contact with the culture media, can leach, contaminating the bioprocess. One such cytotoxic leachable already receiving attention is bis(2,4-di-tert-butylphenyl)-phosphate (bDtBPP), a breakdown product of the secondary antioxidant Irgafos 168 in polyethylene-film based bags. This compound has been demonstrated to inhibit cell growth at concentrations ranging from 0.12 to 0.73 mg/L across an array of cell lines. Here we demonstrate that a further two CHO cell lines exhibit sensitivity to bDtBPP exposure at concentrations lower than that previously reported (0.035-0.1 mg/L). Furthermore, these inhibitory concentrations reflect bDtBPP levels found to leach early into the bioprocess, exposing reactor inoculums to serious risk. Quantitative label-free LC-MS/MS revealed that irrespective of cell line or concentration of bDtBPP, 8 proteins were found to be commonly differentially expressed in response to exposure to the compound highlighting biological processes related to cellular stress. Although the glycoprofile of the recombinant antibody remains primarily unchanged, we demonstrate that this compound when spiked at meaningful concentrations 72 h into culture considerably reduces the maximum cell density achieved. Studies like this reinforce the requirement for the complete characterization of all potential leachable compounds from disposable materials to assess their risk not only to the patient but also to the production pipeline itself. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1547-1558, 2016.
TL;DR: A decisional tool that is designed to identify cost-effective process designs for drug screening products derived from human induced pluripotent stem cells (hiPSC) and predicted the level of performance improvements required in iPSC expansion and differentiation so as to achieve an acceptable cost of goods (COG).
01 Jan 2016
TL;DR: The different pretreatment methods that have been investigated to date will be explored to understand the pretreatment goals as well as evaluate the methods for potential industrial viability.
Abstract: This chapter focuses on the utilization of biomass for ethanol production. The characteristics of biomass are introduced as well as the main sources of biomass. Following that, the different pretreatment methods that have been investigated to date will be explored to understand the pretreatment goals as well as evaluate the methods for potential industrial viability. The pretreatment products are then used in the enzymatic hydrolysis process. Finally, consolidated bioprocessing is examined as well as the information and the tools that will be used for strain development in consolidated bioprocessing microorganisms.
TL;DR: The BioLector® Pro system from m2p‐labs GmbH uses microtiter plates (MTPs) with an integrated microfluidic chip to achieve continuous feeding and pH control on an MTP format for the first time.
Abstract: The BioLector® Pro system from m2p‐labs GmbH uses microtiter plates (MTPs) with an integrated microfluidic chip. By using microfluidic technology, the system can successfully carry out small‐scale fed‐batch cultivations. Working volumes of 0.8–1.5 mL are used to conduct cultivations as they were only as yet possible in lab fermenters. The measurements of biomass, fluorescence, pH and dissolved oxygen are performed by non‐invasive optical methods. The control of pH and feeding rates are realized by micro‐valves and micro‐channels. For the first time, these unique microfluidic components achieve continuous feeding and pH control on an MTP format. Altogether, 32 bioreactor wells and 16 reservoir wells are placed on one plate. That means 32 fed‐batch cultivations can be run in parallel, completely automated, with extensive data output.