16 resultados para Expansion Process
em Aston University Research Archive
Resumo:
Human mesenchymal stem cell (hMSC) therapies are currently progressing through clinical development, driving the need for consistent, and cost effective manufacturing processes to meet the lot-sizes required for commercial production. The use of animal-derived serum is common in hMSC culture but has many drawbacks such as limited supply, lot-to-lot variability, increased regulatory burden, possibility of pathogen transmission, and reduced scope for process optimization. These constraints may impact the development of a consistent large-scale process and therefore must be addressed. The aim of this work was therefore to run a pilot study in the systematic development of serum-free hMSC manufacturing process. Human bone-marrow derived hMSCs were expanded on fibronectin-coated, non-porous plastic microcarriers in 100mL stirred spinner flasks at a density of 3×105cells.mL-1 in serum-free medium. The hMSCs were successfully harvested by our recently-developed technique using animal-free enzymatic cell detachment accompanied by agitation followed by filtration to separate the hMSCs from microcarriers, with a post-harvest viability of 99.63±0.03%. The hMSCs were found to be in accordance with the ISCT characterization criteria and maintained hMSC outgrowth and colony-forming potential. The hMSCs were held in suspension post-harvest to simulate a typical pooling time for a scaled expansion process and cryopreserved in a serum-free vehicle solution using a controlled-rate freezing process. Post-thaw viability was 75.8±1.4% with a similar 3h attachment efficiency also observed, indicating successful hMSC recovery, and attachment. This approach therefore demonstrates that once an hMSC line and appropriate medium have been selected for production, multiple unit operations can be integrated to generate an animal component-free hMSC production process from expansion through to cryopreservation.
Resumo:
External combustion heat cycle engines convert thermal energy into useful work. Thermal energy resources include solar, geothermal, bioenergy, and waste heat. To harness these and maximize work output, there has been a renaissance of interest in the investigation of vapour power cycles for quasi-isothermal (near constant temperature) instead of adiabatic expansion. Quasi-isothermal expansion has the advantage of bringing the cycle efficiency closer to the ideal Carnot efficiency, but it requires heat to be transferred to the working fluid as it expands. This paper reviews various low-temperature vapour power cycle heat engines with quasi-isothermal expansion, including the methods employed to realize the heat transfer. The heat engines take the form of the Rankine cycle with continuous heat addition during the expansion process, or the Stirling cycle with a condensable vapour as working fluid. Compared to more standard Stirling engines using gas, the specific work output is higher. Cryogenic heat engines based on the Rankine cycle have also been enhanced with quasi-isothermal expansion. Liquid flooded expansion and expander surface heating are the two main heat transfer methods employed. Liquid flooded expansion has been applied mainly in rotary expanders, including scroll turbines; whereas surface heating has been applied mainly in reciprocating expanders. © 2014 Elsevier Ltd.
Resumo:
Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the full value of this emerging field can be realized. The characterization of input material for cell-based therapy bioprocesses from multiple donors is necessary to identify and understand the potential implications of input variation on process development. In this work, we have characterized bone marrow derived human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of the measurable input variation on the development of autologous and allogeneic cell-based therapy manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has been demonstrated that this variation results in a range in the process time between these donor hMSC lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of 29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent of donor variability throughout the expansion process. Measuring informative product attributes during process development will facilitate progress towards consistent manufacturing processes, a critical step in the translation cell-based therapies.
Resumo:
Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-economic-environmental factors. Adequate consideration of all the factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, technical and socio-economic-environmental factors were then identified. Third, a database was developed for each site with respect to each factor. Fourth, a hierarchical model in analytic hierarchy process (AHP) framework was then developed. Fifth, the relative ranking of the alternate sites was then derived through pair wise comparison in all the levels and through subsequent synthesizing of the results across the hierarchy through computer software (Expert Choice). The study reveals that an integrated framework using the AHP can help select a site for the quarry expansion project in Barbados.
Resumo:
Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-environmental factors. Adequate consideration of all factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, socio-environmental conditions were described and potential impacts identified. Third, a comparative matrix was constructed to evaluate relative site characteristics with respect to physical, ecological, socio-cultural and economic factors. The study shows that environmental factors were essential to the final site recommendation.
Resumo:
The study examines factors influencing language planning decisions in contemporary France. It focuses upon the period 1992-1994, which witnessed the introduction of two major language policy measures, the first an amendment to the French Constitution, in 1992, proclaiming the language of the Republic as French, the second, in 1994, legislation to extend the ambit of the loi Bas-Lauriol, governing the use of the French language in France. The thesis posits a significant role for the pro-reform movement led by the French language association Avenir de la Langue Francaise (ALF) in the introduction and formulation of the policy measures concerned. The movement is depicted as continuing the traditional pattern of intellectual involvement in language planning, whilst also marking the beginning of a highly proactive, and increasingly political approach. Detailed examination of the movement's activities reveals that contextual factors and strategic strength combined to facilitate access to the levers of power, and enabled those involved to exert an impact on policy initiation, formulation, and ultimately implementation. However, ALF's decision to pursue the legislative route led to the expansion of the network of actors involved in language policymaking, and the development of counter-pressure from sectoral groups. It is suggested that this more interventionist approach destabilised the traditionally consensual language policy community, and called into question the quasi-monopoly of the intelligentsia in respect of language policymaking. It raised broader questions relating to freedom of expression and the permissible limits of language regulation in a democracy such as France. It also exposed ongoing ambiguities and inconsistencies in the interpretation of the tenets of language planning.
Resumo:
Investment in capacity expansion remains one of the most critical decisions for a manufacturing organisation with global production facilities. Multiple factors need to be considered making the decision process very complex. The purpose of this paper is to establish the state-of-the-art in multi-factor models for capacity expansion of manufacturing plants within a corporation. The research programme consisting of an extensive literature review and a structured assessment of the strengths and weaknesses of the current research is presented. The study found that there is a wealth of mathematical multi-factor models for evaluating capacity expansion decisions however no single contribution captures all the different facets of the problem.
Resumo:
Bed expansion occurs during the operation of gas-fluidized beds and is influenced by particle properties, gas properties and distributor characteristics. It has a significant bearing on heat and mass transfer phenomena within the bed. A method of predicting bed expansion behavior from other fluidizing parameters would be a useful tool in the design process, dispensing with the need for small-scale trials. This study builds on previous work on fluidized beds with vertical inserts to produce a correlation that links a modified particle terminal velocity, minimum fluidizing velocity and distributor characteristics with bed voidage in the relationship with P as the pitch between holes in the perforated distributor plate. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Resumo:
Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-environmental factors. Adequate consideration of all factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, socio-environmental conditions were described and potential impacts identified. Third, a comparative matrix was constructed to evaluate relative site characteristics with respect to physical, ecological, socio-cultural and economic factors. The study shows that environmental factors were essential to the final site recommendation.
Resumo:
This article demonstrates the use of embedded fibre Bragg gratings as vector bending sensor to monitor two-dimensional shape deformation of a shape memory polymer plate. The shape memory polymer plate was made by using thermal-responsive epoxy-based shape memory polymer materials, and the two fibre Bragg grating sensors were orthogonally embedded, one on the top and the other on the bottom layer of the plate, in order to measure the strain distribution in both longitudinal and transverse directions separately and also with temperature reference. When the shape memory polymer plate was bent at different angles, the Bragg wavelengths of the embedded fibre Bragg gratings showed a red-shift of 50 pm/°caused by the bent-induced tensile strain on the plate surface. The finite element method was used to analyse the stress distribution for the whole shape recovery process. The strain transfer rate between the shape memory polymer and optical fibre was also calculated from the finite element method and determined by experimental results, which was around 0.25. During the experiment, the embedded fibre Bragg gratings showed very high temperature sensitivity due to the high thermal expansion coefficient of the shape memory polymer, which was around 108.24 pm/°C below the glass transition temperature (Tg) and 47.29 pm/°C above Tg. Therefore, the orthogonal arrangement of the two fibre Bragg grating sensors could provide a temperature compensation function, as one of the fibre Bragg gratings only measures the temperature while the other is subjected to the directional deformation. © The Author(s) 2013.
Resumo:
Groundwater salinity is a widespread problem that contributes to the freshwater deficit of humanity. Consequently, where conventional energy supply is also lacking, organic Rankine cycle (ORC) engines are being considered as a feasible option to harness readily available low-grade heat (<180°C) to drive the desalination of the saline water via reverse osmosis (RO). However, this application is still not very well developed, and has significantly high specific energy consumption (SEC). Hence, this study explores the isothermal expansion of the ORC working fluid to achieve improved efficiency for driving a batch-RO desalination process, "DesaLink". Here, the working fluid is directly vaporized in the expansion cylinder which is heated externally by heat transfer fluid, thus obviating the need for a separate external boiler and high-pressure piping. Experimental investigations with R245fa have shown cycle efficiency of 8.8%. And it is predicted that the engine could drive DesaLink to produce 256 L of freshwater per 8 h per day, from 4000 ppm saline water, with a thermal and mechanical SEC of 2.5 and 0.36 kWh/m3, respectively, representing a significant improvement on previously reported or predicted SEC values. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.
Resumo:
Though the principle of the solar Rankine cycle is well known, with several examples reported in the literature, there is yet a scarcity of engines that could be efficiently applied in small-scale (<100 KW) applications. Hence, this paper presents a variant of the engine that uses an isothermal expansion to achieve a theoretical efficiency close to the Carnot limit. Generation of steam inside the power cylinder obviates the need for an external boiler. The device is suitable for slow-moving applications and is of particular interest for driving a batch-desalination process. Preliminary experiments have shown cycle efficiency of 16%, and a high work ratio of 0.997. ©The Author 2013. Published by Oxford University Press. All rights reserved.
Resumo:
Background aims: The cost-effective production of human mesenchymal stromal cells (hMSCs) for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony-forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter-batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence through a correlation (R2 = 0.8705) across all conditions. PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost-effectiveness and reduce the risk in these manufacturing processes.
Resumo:
Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.
Resumo:
Agriculture accounts for ~70% of freshwater usage worldwide. Seawater desalination alone cannot meet the growing needs for irrigation and food production, particularly in hot, desert environments. Greenhouse cultivation of high-value crops uses just a fraction of freshwater per unit of food produced when compared with open field cultivation. However, desert greenhouse producers face three main challenges: freshwater supply, plant nutrient supply, and cooling of the greenhouse. The common practice of evaporative cooling for greenhouses consumes large amounts of fresh water. In Saudi Arabia, the most common greenhouse cooling schemes are fresh water-based evaporative cooling, often using fossil groundwater or energy-intensive desalinated water, and traditional refrigeration-based direct expansion cooling, largely powered by the burning of fossil fuels. The coastal deserts have ambient conditions that are seasonally too humid to support adequate evaporative cooling, necessitating additional energy consumption in the dehumidification process of refrigeration-based cooling. This project evaluates the use of a combined-system liquid desiccant dehumidifier and membrane distillation unit that can meet the dual needs of cooling and freshwater supply for a greenhouse in a hot and humid environment.