Scale-up Evaluation Research Articles

Scale-up and process integration of sugar production by acidolysis of municipal solid waste/corn stover blends in ionic liquids

BackgroundLignocellulosic biorefineries have tonnage and throughput requirements that must be met year round and there is no single feedstock available in any given region that is capable of meeting the price and availability demands of the biorefineries scheduled for deployment. Significant attention has been historically given to agriculturally derived feedstocks; however, a diverse range of wastes, including municipal solid wastes (MSW), also have the potential to serve as feedstocks for the production of advanced biofuels and have not been extensively studied. In addition, ionic liquid (IL) pretreatment with certain ILs is receiving great interest as a potential process that enables fractionation of a wide range of feedstocks. Acid catalysts have been used previously to hydrolyze polysaccharides into fermentable sugars following IL pretreatment, which could potentially provide a means of liberating fermentable sugars from lignocellulose without the use of costly enzymes. However, successful optimization and scale-up of the one-pot acid-assisted IL deconstruction for further commercialization involve challenges such as reactor compatibility, mixing at high solid loading, sugar recovery, and IL recycling, which have not been effectively resolved during the development stages at bench scale.ResultsHere, we present the successful scale-up demonstration of the acid-assisted IL deconstruction on feedstock blends of municipal solid wastes and agricultural residues (corn stover) by 30-fold, relative to the bench scale (6 vs 0.2 L), at 10% solid loading. By integrating IL pretreatment and acid hydrolysis with subsequent centrifugation and extraction, the sugar and lignin products can be further recovered efficiently. This scale-up development at Advanced Biofuels/Bioproducts Process Demonstration Unit (ABPDU) will leverage the opportunity and synergistic efforts toward developing a cost-effective IL-based deconstruction technology by drastically eliminating enzyme, reducing water usage, and simplifying the downstream sugar/lignin recovery and IL recycling.ConclusionResults indicate that MSW blends are viable and valuable resource to consider when assessing biomass availability and affordability for lignocellulosic biorefineries. This scale-up evaluation demonstrates that the acid-assisted IL deconstruction technology can be effectively scaled up to larger operations and the current study established the baseline of scaling parameters for this process.

Mainstreaming an Effective Intervention: Evidence from Randomized Evaluations of 'Teaching at the Right Level' in India

Previous randomized studies have shown that addressing children’s current learning gaps, rather than following an over-ambitious uniform curriculum, can lead to significant learning gains. In this study, we evaluate a series of efforts to scale up the NGO Pratham’s approach to teaching children according to their actual learning level, in four Indian States. While this approach was previously shown to be extremely effective when implemented with community volunteers outside of school, the objective of these new scale-up evaluations was to develop a model that could be implemented within the government school system. In the first two instances (Bihar and Uttarakhand), the methodology was not adopted by government schoolteachers, despite well-received training sessions and Pratham support. Motivated by the quantitative and qualitative analysis of these early attempts, we adapted the approach and designed large-scale experiments in the states of Haryana and Uttar Pradesh to test two new scale-up models. In Haryana, teachers received support from government resource persons trained by Pratham, and implemented the approach during a dedicated hour. In Uttar Pradesh, Pratham volunteers implemented high-intensity, short-burst “learning camps” for 40 days, in school and during school hours, with additional 10-day summer camps. Both models proved effective, with gains in language of 0.15 standard deviation in Haryana, and 0.70 standard deviations in Uttar Pradesh, on all students enrolled in these schools at baseline. These two models provide blueprints that can be replicated inside other government systems.

Scale-up evaluation of the anaerobic digestion of food-processing industrial wastes

This work proposes a semi-pilot scale procedure for the evaluation of biogas production potential and the employment of its results for the scale-up of the process. AD tests were performed at 35 °C in 6 L reactors, feeding 3–6% w/w TS in a fed-batch mode. Several substrates, generated by food-processing industries, were considered in the study. Assuming solubilization as the limiting step, a theoretical model was proposed and the values of the disintegration kinetic constant (kdis) were calculated from the experimental data. The obtained model was employed as a control tool during tests afterward performed on pilot scale in a 300 L digester fed in a semi-continuous mode. Biogas yields between 0.5 and 0.9 Nm3/kgVS, and methane contents of 55–63% v/v were obtained on both scales. The model derived from the results of the proposed procedure appeared adequate for a consistent evaluation of the scale-up of the AD process.

Evaluation of scale-up from analytical to preparative supercritical fluid chromatography

An approach for reliable transfer from analytical to preparative scale supercritical fluid chromatography was evaluated. Here, we accounted for the conditions inside the columns as well as to the fact that most analytical instruments are volume-controlled while most preparative scale units are mass-controlled. The latter is a particular problem when performing pilot scale experiments and optimizations prior to scaling up to production scale. This was solved by measuring the mass flow, the pressure and the temperature on the analytical unit using external sensors. Thereafter, it was revealed with a design of experiments approach that the methanol fraction and the pressure are the two most important parameters to control for preserved retention throughout the scale-up; for preserved selectivity the temperature was most important in this particular system. Using this approach, the resulting chromatograms from the preparative unit agreed well with those from the analytical unit while keeping the same column length and particles size. A brief investigation on how the solute elution volume varies with the volumetric flow rate revealed a complex dependency on pressure, density and apparent methanol content. Since the methanol content is a parameter of great importance to control during the scale up, we must be careful when changing operational and column design conditions which generates deviations in pressure, density and methanol content between different columns.

Scale-Up of Ionic Liquid-Based Fractionation of Single and Mixed Feedstocks

Lignocellulosic biorefineries have tonnage and throughput requirements that must be met year round, and there is no single feedstock available in any given region that is capable of meeting the price and availability demands of the biorefineries. Ionic liquid (IL) pretreatment with certain ILs is receiving significant attentions as a potential process that enables fractionation of a wide range of feedstocks and produces high yields of fermentable sugars suitable for biofuel production. Building on the large-scale demonstration of a single herbaceous feedstock (switchgrass), this work extends scale-up of IL pretreatment to woody (eucalyptus) and mixed feedstock (mixtures of two) by 30-fold, relative to the bench scale (6 vs 0.2 L) at 10 % solid loading. The mixed feedstock recovered similar yields of glucan (99.7 %), xylan (62.8 %), and lignin (59.9 %) as switchgrass and eucalyptus at 6-L scale operation, and results of all three feedstocks are better than those obtained from small-scale studies. By integrating the process of IL pretreatment with efficient and scalable homogenization, washing, and product recovery system, IL contents in the recovered materials were decreased to 0.2 %, mitigating the risk to downstream enzymatic saccharification and microbial fermentation. Results indicate that mixed feedstock are viable and valuable resource to consider when assessing biomass availability and affordability for lignocellulosic biorefineries. This scale-up evaluation demonstrates that IL pretreatment technology is feedstock agnostic and can be effectively scaled to larger operations.

Biosorbents Derived from Fruit Wastes for Removal of Anionic Dyes in Wastewater

In this paper, the use of biosorbents prepared from fruit wastes for removal of anionic dyes in wastewater was investigated. A versatile, scalable and configurable envelop protocol was developed for biosorbents screening and process scale-up evaluations. The results obtained show that enveloped systems did not alter equilibrium and kinetics profiles from those of the standard free sorbent-sorbate systems under the experimental conditions studied. Inherent non-ideal sorbent-sorbate interactions were likely contributor to the observed discriminating features of the linear isotherm fits of the enveloped systems. The results also showed that sorbent weight:sorbate volume ratio (S/L ratio) could be used to characterise the sorbent-sorbate system.

Considerations in the efficacy and effectiveness of virtual reality interventions for stroke rehabilitation: moving the field forward.

In the past 2 decades, researchers have demonstrated the potential for virtual reality (VR) technologies to provide engaging and motivating environments for stroke rehabilitation interventions. Much of the research has been focused on the exploratory phase, and jumps to intervention efficacy trials and scale-up evaluation have been made with limited understanding of the active ingredients in a VR intervention for stroke. The rapid pace of technology development is an additional challenge for this emerging field, providing a moving target for researchers developing and evaluating potential VR technologies. Recent advances in customized games and cutting-edge technology used for VR are beginning to allow for researchers to understand and control aspects of the intervention related to motivation, engagement, and motor control and learning. This article argues for researchers to take a progressive, step-wise approach through the stages of intervention development using evidence-based principles, take advantage of the data that can be obtained, and utilize measurement tools to design effective VR interventions for stroke rehabilitation that can be assessed through carefully designed efficacy and effectiveness trials. This article is motivated by the recent calls in the field of rehabilitation clinical trials research for carefully structured clinical trials that have progressed through the phases of research.

Systematic monitoring of male circumcision scale-up in Nyanza, Kenya: exploratory factor analysis of service quality instrument and performance ranking.

BackgroundConsiderable conceptual and operational complexities related to service quality measurements and variability in delivery contexts of scaled-up medical male circumcision, pose real challenges to monitoring implementation of quality and safety. Clarifying latent factors of the quality instruments can enhance contextual applicability and the likelihood that observed service outcomes are appropriately assessed.ObjectiveTo explore factors underlying SYMMACS service quality assessment tool (adopted from the WHO VMMC quality toolkit) and; determine service quality performance using composite quality index derived from the latent factors.Study designUsing a comparative process evaluation of Voluntary Medical Male Circumcision Scale-Up in Kenya site level data was collected among health facilities providing VMMC over two years. Systematic Monitoring of the Medical Male Circumcision Scale-Up quality instrument was used to assess availability of guidelines, supplies and equipment, infection control, and continuity of care services. Exploratory factor analysis was performed to clarify quality structure.ResultsFifty four items and 246 responses were analyzed. Based on Eigenvalue >1.00 cut-off, factors 1, 2 & 3 were retained each respectively having eigenvalues of 5.78; 4.29; 2.99. These cumulatively accounted for 29.1% of the total variance (12.9%; 9.5%; 6.7%) with final communality estimates being 13.06. Using a cut-off factor loading value of ≥0.4, fifteen items loading on factor 1, five on factor 2 and one on factor 3 were retained. Factor 1closely relates to preparedness to deliver safe male circumcisions while factor two depicts skilled task performance and compliance with protocols. Of the 28 facilities, 32% attained between 90th and 95th percentile (excellent); 45% between 50th and 75th percentiles (average) and 14.3% below 25th percentile (poor).Conclusionthe service quality assessment instrument may be simplified to have nearly 20 items that relate more closely to service outcomes. Ranking of facilities and circumcision procedure using a composite index based on these items indicates that majority performed above average.

Community Living and Participation: Embracing the Complexity and Forging Forward

Community Living and Participation: Embracing the Complexity and Forging Forward

The effects of moisture content, particle size and binding agent content on oil palm shell pellet quality parameters

Waste-to-energy represents a challenge for the oil palm industry worldwide. Bio-pellet production is an alternative way of adding value to oil palm biomass. This would mean that a product having major energy density becomes more mechanically stable and achieves better performance during combustion. This paper deals with oil palm shell pelleting; using binding agents having up to 25% mass keeping average particle size less than 1mm and moisture content up to 18.7% (d.b.) were evaluated. An experimental factorial design used binding agent mass percentage, milled shell particle size and moisture content as factors. Pellet density response surfaces and durability index were obtained. Pellet performance during thermal-chemical transformation was also evaluated by using thermogravimetry equipment. The results led to technical evaluation of scale-up at industrial production level.

Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

BackgroundHighly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system.Principal FindingThe current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3×106 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1±0.3×108 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera.ConclusionsThe advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production.

Two‐dimensional difference fluorescence gel electrophoresis to verify the scale‐up of a non‐affinity‐based downstream process for isolation of a therapeutic recombinant antibody

For therapeutic antibody production Protein A chromatography is often replaced by non-affinity-based purification sequences, which are considered as more economical. 2-D DIGE was applied for evaluation of scale-up of non-affinity based process of a humanized monoclonal antibody, anti-Rh(D) IgG(1), in comparison with other conventional analytical methods, like SDS-PAGE, Western blot, or SEC. Due to a high sensitivity of this technique (125 pg protein/spot) and high dynamic range of five orders of magnitude, low molecular weight impurities were detected in purified samples. Cation exchange chromatography was efficient capture step for IgG(1) purification in laboratory and pilot scale. The differences between samples after first purification step in laboratory and pilot scale were compensated with second purification step where almost the same protein pattern was observed. 2-D DIGE is a helpful tool for monitoring of purification effects and for scale-up verification of downstream processes.

Catalytic effectiveness, a measure of enzyme proficiency for industrial applications

Recent attention has been paid to the inadequacy of using the ratio Vmax/KM as a measure of enzyme performance, particularly in the context of industrial biocatalysis. This can lead to misleading expectations of enzyme performance and can be troublesome when used to select among different variants for scale-up evaluation under process conditions. To address these issues, we derive the average velocity based on the time-integrated behavior of the enzyme over the course of the reaction. The resulting expression, deemed catalytic effectiveness, captures important features of the system that have heretofore been ignored (such as highly variable substrate and/or product concentrations and inhibition) and offers a rigorous way to compare enzymes for their capacity to carry out industrial transformations.

Modelling of mass transfer in gas–liquid stirred tanks agitated by Rushton turbine and CD-6 impeller: A scale-up study

A combined computational fluid dynamics (CFD) and population balance model (PBM) approach has been applied to the simulation of gas–liquid stirred tanks agitated by (i) a Rushton turbine or (ii) a CD-6 impeller, operating at aeration numbers from 0.017 to 0.038. The multiphase simulations were realised via an Eulerian–Eulerian two-fluid model and the drag coefficient of spherical and distorted bubbles was modelled using the Ishii–Zuber equations. The effect of the void fraction on the drag coefficient was modelled using the correlation by Behzadi et al. [Behzadi, A., Issa, R.I. and Rusche, H., 2004, Modelling of dispersed bubble and droplet flow at high phase fractions, Chem Eng Sci, 59: 759–770]. The local bubble size distribution was obtained by solving the PBM using the quadrature method of moments (QMOM). The local k L a was estimated using both the Higbie penetration theory and the surface renewal model. The predicted gas–liquid hydrodynamics, local bubble sizes and dissolved oxygen concentration were in good agreement with experimental measurements reported in the literature. A slight improvement in the prediction of the aerated power number was obtained using the non-uniform bubble size distribution resulting from the coupled CFD–PBM simulation. Evaluation of the prospective scale-up approaches indicates a higher probability of maintaining a similar level of mass transfer in a larger tank by keeping the P g / V and VVM constant. Considering its predictive capability, the method outlined in this work can provide a useful scale-up evaluation of gas–liquid stirred tanks.

Scale-up and Cost Evaluation of a Foamed Emulsion Bioreactor

In the present paper, the potential of the foamed emulsion bioreactor (FEBR), a novel biological reactor for air pollution control was evaluated. Experimental data obtained on a laboratory-scale prototype were used to scale-up the process for a hypothetical case consisting of a contaminated air flow rate of 10,000 m3 h−1, a toluene inlet concentration of 1 g m−3 and minimum required treatment efficiency of 92%. Reactor design and operating issues for the full-scale FEBR were identified. They included the requirement for stable foam generation with appropriate air distributors, and recycling of the auxiliary organic phase, surfactants and cells from the discharge of the reactor. The capital and operating costs for the concept full-scale FEBR were evaluated and compared to those of competing technologies, namely biofiltration, biotrickling filtration and catalytic and thermal oxidation. All three biological techniques had significantly lower capital and operating costs. Among the biological techniques, the FEBR had the lowest estimated capital cost since its greater effectiveness allowed a smaller reactor to meet the treatment objectives. The operating costs for the FEBR were higher than those of biofilters and biotrickling filters because of the requirements for nutrients and auxiliary chemicals. Overall, the results highlight that biotreatment is much more cost effective than thermal and catalytic oxidation. They further suggest that the FEBR may an interesting alternative to biofilters and biotrickling filters where the available space for air pollution control equipment is limited

Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi

To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals.

Scale-up of fermentation and purification of recombinant allophycocyanin over-expressed in Escherichia coli

Phycobiliprotein is a photosynthetic antenna pigment found in cyanobacteria, rhodophytes, cryptophytes and certain dinoflagellates, which has been found to have anti-oxidative and anti-tumour activities. In this paper, a recombinant allophycocyanin (rAPC) had been expressed in Escherichia coli for anti-tumour effect. E. coli cells were cultured using glucose fed-batch method to achieve high cell densities. The biomass of rAPC was up to 3.52 g/L broth. The rAPC was purified from soluble E. coli cell lysate employing hydrophobic interaction chromatographic (HIC) method developed at the bench scale using 20 mL column. The process was performed at the pilot scale using 500 mL column for evaluation of scale-up. An amylose affinity column was used to improve the purity of final product in pilot scale purification. The purification process resulted in greater than 98% pure product and yielded up to 2.0 g/kg wet cells at the bench scale and 1.2 g/kg wet cells at the pilot scale. Peptide mapping was used to prove the identity of rAPC purified from bench scale and pilot scale process. Purified rAPC at the pilot scale was found to have remarkable inhibition on S-180 carcinoma in mice.

The Scale-up and Economic Evaluation of Non-Thermal Plasma Technology for a Coal Fired Power Plant Exhaust Gas Emission Control

Abstract Economies of pollution control devices are critical to the decision-making in power plant emission control upgrades. The computer code (SUENTP) to predict scale up and economic evaluation of several eligible non-thermal plasma processes for power plant gaseous pollution controls was developed for electron beam, pulsed corona, and corona radical shower processes. This code was written by the spread sheet type MS Excel with visual basic for application and comprises data input procedure, scale-up (design) procedure, economic calculation procedure, and output procedures. Data obtained from pilot plant tests was used as an input data together with general data so that they might be led to the conceptual design data of commercial plants by scaleup procedure. The economic evaluation procedure consisted of the total capital investment and the total annual cost. The total capital investment was presented as the indirect annual cost in items of capital recovery. The levelized cost and the levelized bus bar cost were shown in the output table. Typical calculation was presented to evaluate the cost of three non-thermal systems based on existing pilot plant experiments. The results show that the economy of the non-thermal plasma systems are similar or less costs by compared with a conventional wet-scrubber/selective catalytic reduction combined system.

Efficient Recovery of Lanthanides by Continuous Ion Exchange

Continuous annular sorption is a recent innovation that uses a slowly rotating annular sorbent bed to continuously separate components as a function of angular position. The current application of this technology, continuous ion exchange (CIEx), utilizes eluent in a much more efficient manner than the previous chromatographic applications. The efficient recovery of semidilute levels (10−20 mM) of lanthanide mixtures by CIEx is demonstrated experimentally, and a mathematical model of the process is used to predict equipment performance. Results from batch shake tests and fixed-bed runs support the CIEx modeling effort and are useful separative benchmarks. The implications of the results for scaleup and economic evaluation are examined.

Genetically engineered antibodies.

The technology needed to genetically engineer antibodies is evolving rapidly and the potential utility of these novel reagents is being explored with vigor. The process includes cloning of the antibody genes, their in vitro manipulation and mutagenesis, expression in a suitable host/vector system, and, for commercial production, scale-up, purification, and product evaluation. At each step, significant advances have been achieved recently. For example: at first, antibody genes were cloned from genomic libraries by using adjacent DNA probes; techniques for rapid sequencing by primer extension of total mRNA allowed more specific screening with synthesized oligomers; finally, antibody genes can now be created de novo by chemical synthesis. Moreover, such synthesis allows total control over the antibody sequence so that molecules of any configuration can be produced. New reagents created in this way include murine antibodies whose constant regions and variable-region frameworks have been replaced with human sequence to enhance immunocompatibility with patients, to switch immunoglobulin class, or both.