Mechanical Properties of Raw Filaments and Printed Specimens: Effects of Fiber Reinforcements and Process Parameters.

Fused Deposition Modeling (FDM) is a well-established manufacturing method for producing both prototype and functional components. This study investigates the mechanical properties of FDM components by material and process-related influencing variables. Tensile tests were conducted on seven different materials in their raw filament form, two of which were fiber-reinforced, to analyze their material-related influence. To cover a wide range from standard to advanced materials relevant for load-carrying components as well as their respective variations, polylactic acid (PLA), 30% wood-fiber-reinforced PLA, acrylonitrile butadiene styrene (ABS), polycarbonate (PC), a blend of ABS and PC, Nylon, and 30% glass-fiber-reinforced Nylon were selected. The process-related influencing variables were studied using the following process parameters: layer thickness, nozzle diameter, build orientation, nozzle temperature, infill density and pattern, and raster angle. The first test series revealed that the addition of wood fibers significantly worsened the mechanical behavior of PLA due to the lack of fiber bonding to the matrix and significant pore formation. The polymer blend of ABS and PC only showed improvements in stiffness. Significant strength and stiffness improvements were found by embedding glass fibers in Nylon, despite partially poor fiber-matrix bonding. The materials with the best properties were selected for the process parameter analysis. When examining the impact of layer thickness on part strength, a clear correlation was evident. Smaller layer thicknesses resulted in higher strength, while stiffness did not appear to be affected. Conversely, larger nozzle diameters and lower nozzle temperatures only positively impacted stiffness, with little effect on strength. The part orientation did alter the fracture behavior of the test specimens. Although an on-edge orientation resulted in higher stiffness, it failed at lower stresses. Higher infill densities and infill patterns aligned with the load direction led to the best mechanical results. The raster angle had a significant impact on the behavior of the printed bodies. An alternating raster angle resulted in lower strengths and stiffness compared to a unidirectional raster angle. However, it also caused significant stretching due to the rotation of the beads.

Ultra-early prediction of the process parameters of coal chemical production.

Most accidents in a chemical process are caused by abnormal or deviations of the process parameters, and the existing research is focused on short-term prediction. When the early warning time is advanced, many false and missing alarms will occur in the system, which will cause certain problems for on-site personnel; how to ensure the accuracy of early warning as much as possible while the early warning time is a technical problem requiring an urgent solution. In the present work, a bidirectional long short-term memory network (BiLSTM) model was established according to the temporal variation characteristics of process parameters, and the Whale optimization algorithm (WOA) was used to optimize the model's hyperparameters automatically. The predicted value was further constructed as a Modified Inverted Normal Loss Function (MINLF), and the probability of abnormal fluctuations of process parameters was calculated using the residual time theory. Finally, the WOA-BiLSTM-MINLF process parameter prediction model with inherent risk and trend risk was established, and the fluctuation process of the process parameters was transformed into dynamic risk values. The results show that the prediction model alarms 16 min ahead of distributed control systems (DCS), which can reserve enough time for operators to take safety protection measures in advance and prevent accidents.

Optimization of Membrane Condenser Process with PTFE Hollow Fiber Membrane.

A membrane condenser (MC) is a novel membrane separation technology that utilizes the hydrophobic nature of porous membranes to capture water vapor from humid gas. Factors such as temperature, pressure, flow rate, and gas composition entering the membrane condenser play a crucial role in water recovery efficiency. This study utilized hydrophobic polytetrafluoroethylene (PTFE) hollow fiber membranes to create multiple identical membrane modules. This research investigated the impact of temperature, flow rate, pressure on the intake side, gas flow on the cooling side, membrane area, and other variables on the performance of the membrane condenser process. This study compared water extraction efficiency under different conditions, focusing on feed flow temperature and sweeping flow. Results showed that at a temperature of 60 °C, the water recovery rate was 24.7%, while a sweep gas flow rate of 4 L/min resulted in a recovery rate of 22.7%. The efficiency of the membrane condenser decreased with higher feed flow rates but increased with larger membrane areas. A proportional relationship between inlet flow and membrane area was observed, suggesting an optimal range of 0.51-0.67 cm/s for both parameters. These findings offer valuable insights for the practical implementation of hydrophobic membrane-based membrane condenser technology.

Analysis of the effect of vibrational stress relief process parameters on 2024Aluminium alloy.

In principle, after all manufacturing processes are performed, a set of residual stresses occur in the product that have their particular distribution given the manufacturing process performed. The residual stresses must be removed to achieve the desired dimensional accuracy and quality. Among stress-relieving processes performed for a piece following the manufacturing process, we can refer to thermal and vibratory stress relief (VSR). Both methods perform the same function as they enter a part or all of a piece into the plastic phase, causing a fracture of residual stresses to be released with local plastic deformations. The process is as follows: The stress induced by thermal or vibratory loads is added to the residual stresses and exceeds the yield stress. This research, which is focused on VSR, aims to evaluate the effect of the main parameters of the VSR method, including load amplitude or amount, load application frequency, and cycle numbers. The general trend of the problem is that the VSR process is performed for a piece with residual stress, and the effect of the abovementioned parameters on reducing its residual stresses is evaluated.

QbD Assisted Development of a Compartment and Sequential Drug Delivery System for Periodontotherapy.

Periodontitis, the burgeoning disease, is at an alarming stage. Although this has triggered dedicated research in this area, as the disease itself demands a multi-component therapy, there is an unmet need for a compartment and sequential drug delivery system to ameliorate disease symptoms completely. The hypothesized work consists of multitherapeutic agents such as an antibiotic, a COX-II inhibitor, an MMP inhibitor, and a bone regenerating agent in an insitu gel. However, for the development of the system, as mentioned above, a thorough investigation at each stage is necessary; therefore, the quality-by-design approach was adopted. Furthermore, the current work is a pursuit of studying the quality by design aspects for the fabrication of a compartment system, i.e., in-situ gel for periodontal delivery. The proposed system in-situ gel consists of antibiotic and nano-encapsulating microcapsules. Furthermore, the microcapsules contain a COX-II inhibitor and nanoparticles of MMP inhibitor and bone regenerating agent for complete amelioration of periodontitis. To develop the system as per the QbD approach, the first initial trials and runs were conducted, which helped to decide the quality target product profile (QTPP). However, based on QTPP, critical quality attributes (CQA), critical process parameters (CPP), and critical material attributes (CMAs) were decided for each stage product, i.e., in-situ gel, microcapsules, and nanoparticles. To assess the influence of CPPs and CMAs on CQAs, Pareto charts were constructed, and various risks, along with possible failure modes were studied. In conclusion, the above work will serve as a well-designed scientific mouthpiece for developing a compartment system for periodontotherapy.

Response Surface Methodology Optimization of Resistance Welding Process for Unidirectional Carbon Fiber/PPS Composites.

The use of thermoplastic composites (TPCs) as one of the lightweight solutions will inevitably encounter problems in connection. Resistance welding has the characteristics of high strength, simplicity, and high reliability, and is considered a very potential hot-melt connection technology. The resistance welding technology of unidirectional carbon fiber-reinforced polyphenylene sulfide composites (UCF/PPS) was systematically studied. The experimental results show that the 100-mesh brass mesh has the best resin wetting effect and heating efficiency, and the PPS/oxidized 100-mesh brass mesh composite resistance element (Ox-RE/PPS) has the highest welding strength. The welding failure mode changes from interface failure and RE failure to interlayer structure damage and fiber fracture. The single-factor experimental results show that the maximum welding strength is reached at 310 °C, 1.15 MPa, and 120 kW/m2. According to the conclusion of the single-factor experiment, the Box-Behnken method was further used to design a three-factor, three-level experiment, and a quadratic regression model was established according to the test results. The results of variance analysis, fitting curve analysis, and perturbation plot analysis proved that the model had high fitting and prediction abilities. From the 3D surface diagram analysis, the influence of power density is the largest, and the interaction between welding temperature and power density is the most significant. Combined with the analysis of Design Expert 13 software, the optimal range of process parameters was obtained as follows: welding temperature 313-314 °C, welding pressure 1.04-1.2 MPa, and power density 124-128 kW/m2. The average strength of resistance welding joints prepared in the optimal range of process parameters was 13.58 MPa.

Quality by Design Perspective for Designing Foam-based Formulation: Current State of Art.

Foam-based delivery systems contain one or more active ingredients and dispersed solid or liquid components that transform into gaseous form when the valve is actuated. Foams are an attractive and effective delivery approach for medical, cosmetic, and pharmaceutical uses. The foams-based delivery systems are gaining attention due to ease of application as they allow direct application onto the affected area of skin without using any applicator or finger, hence increasing the compliance and satisfaction of the patients. In order to develop foam-based delivery systems with desired qualities, it is vital to understand which type of material and process parameters impact the quality features of foams and which methodologies may be utilized to investigate foams. For this purpose, Quality-by-Design (QbD) approach is used. It aids in achieving quality-based development during the development process by employing the QbD concept. The critical material attributes (CMAs) and critical process parameters (CPPs) were discovered through the first risk assessment to ensure the requisite critical quality attributes (CQAs). During the initial risk assessment, the high-risk CQAs were identified, which affect the foam characteristics. In this review, the authors discussed the various CMAs, CPPs, CQAs, and risk factors associated in order to develop an ideal foam-based formulation with desired characteristics.

Investigation and Prediction of Nano-Silver Line Quality upon Various Process Parameters in Inkjet Printing Process Based on an Experimental Method.

As an emerging additive manufacturing technology, inkjet printing has been increasingly applied in microelectronics field. However, due to the impacting and rebounding behaviors of conductive ink droplets impinging onto flat substrates, it is challenging to fabricate conductive lines with desired quality, such as suitable line width and line thickness, and matching resistance when it is used for interconnecting multifarious electronic components if there is not a proper configuration of operating parameters. To address this research gap, this article aims to investigate the effect of process parameters on the quality of conductive lines, including the platform temperature, printing speed, number of layers, and delay time (droplet interarrival time), are selected to conduct a full factorial experiment. First, the approximate parameter ranges for ensuring the continuity of conductive lines are determined. Second, this study analyzes the interactive effect among process parameters on line quality. Third, an artificial neural network (ANN) is constructed to predict the quality of printed lines. Results show that the line width does not increase with an increased number of layers, while the line thickness shows an increasing trend. The low resistance and high aspect ratio of printed line are achieved by printing 5 layers with the platform temperature of 70°C, the delay time of 12.2 ms, and the printing speed of 1139.39 mm/min. Moreover, the ANN model can be used to predict line width and line thickness with excellent performance, except for the resistance due to the irregular line edge. This study provides a useful guide for the selection of appropriate printing parameters to realize a diverse range of quality properties for 3D printed conductive lines in integrated circuits.

3D Printing onto Textiles: A Systematic Analysis of the Adhesion Studies.

The article reviews the literature focused on investigating the adhesion strength between the 3D-printed polymers and the textile substrates, and its dependence on different factors related to materials, printing parameters, and fabrics type and structure. 3D printing (3DP) onto textiles is a domain in expansion as it allows developing products with new functionalities by gathering the advantages of design freedom, tailor-fit, comfort, variety, and mass customization provided by both the textiles and the additive manufacturing technology. In this context, it becomes important to document and understand how the adherence of different 3D-printed molten polymer to diverse textiles substrates can be improved for obtaining products more resistant to specific conditions, such as washing, wear, or ironing. Following a systematic search of electronic databases, 28 articles were selected for the full-text read and data extraction. The summarized information was grouped per 3DP material and analyzed factors, and then discussed in terms of variables influencing the adherence, including pretreatments and post-treatments applied to fabrics or 3D-printed onto fabrics specimens and objects. A case study of a customized polylactic acid-cotton-elastane wrist-hand orthosis is also presented to exemplify the modality in which the information synthetized in this review can be used in the development process of a new product.

Manufacturing process of liposomal Formation: A coarse-grained molecular dynamics simulation.

A method of producing liposomes has been previously developed using a continuous manufacturing technology that involves a co-axial turbulent jet in co-flow. In this study, coarse-grained molecular dynamics (CG-MD) simulations were used to gain a deeper understanding of how the self-assembly process of liposomes is affected by the material attributes (such as the concentration of ethanol) and the process parameters (such as temperature), while also providing detailed information on a nano-scale molecular level. Specifically, the CG-MD simulations yield a comprehensive internal view of the structure and formation mechanisms of liposomes containing DPPC, DPPG, and cholesterol molecules. The importance of this work is that structural details on the molecular level are proposed, and such detail is not possible to obtain through experimental studies alone. The assessment of structural properties, including the area per lipid, diffusion coefficient, and order parameters, indicated that a thicker bilayer was observed at higher ethanol concentrations, while a thinner bilayer was present at higher temperatures. These conditions led to more water penetrating the interior of the bilayer and an unstable structure, as indicated by a larger contact area between lipids and water, and a higher coefficient of lipid lateral diffusion. However, stable liposomes were found through these evaluations at lower ethanol concentrations and/or lower process temperatures. Furthermore, the CG-MD model was further compared and validated with experimental and computational data including liposomal bilayer thickness and area per lipid measurements.

Process Parameter Optimization for CO2 Laser Polishing of Fused Silica Using the Taguchi Method.

Fused silica was polished to a high quality by a CO2 laser beam with a rapid scanning rate. The rapid scanning rate produced a line laser heat source, resulting in a "polishing line" during the polishing process. The Taguchi method was used to evaluate the comprehensive influence of polishing process parameters on the polishing qualities. Four factors, namely the length of laser reciprocating scanning (A), laser beam scanning speed (B), feed speed (C), and defocusing amount (D), were investigated in this study. The optimal process parameter combination (A1B1C1D1) was obtained. The surface roughness of fused silica was reduced from Ra = 0.157 µm to 0.005 µm. Through analysis of variance (ANOVA), it was found that laser beam scanning speed (B) had a significant influence on the polishing quality. The interaction of the two factors plays a decisive role in the determination of the best process parameters, and the influence of other multi-factor interaction can be ignored; the interaction between A × B is the largest, with a contribution of 42.69%.

Sorption capacity of Eichhornia crassipes (Mart.) Solms for zinc removal from electroplating industry wastewater.

Various industrial operations in the dye, fertilizer, pesticide, battery, mining, and chemical industries have been associated with releasing heavy metals in wastewater, such as lead, zinc, copper, arsenic, cadmium, chromium, nickel, and mercury. These metals are dangerous to aquatic life as well as to humans, who may consume them directly or indirectly. Therefore, before being released into open water and land resources, it is necessary to minimize the concentration of toxic ions below the discharge limit. This study used Eichhornia crassipes (Mart.) Solms to remove zinc from wastewater from the electroplating industry in a constructed wetland. Experimental investigations were conducted for removing zinc ions from electroplating industry wastewater using various process parameters such as nutrient dosages, dilution ratios, potential of hydrogen ions, biomasses, and contact times. The outcome of this study revealed that the maximum zinc removal percentage in electroplating industrial wastewater was found for the optimum nutrient dosages of 60 g, dilution ratios of 10, potential hydrogen ion levels of 8, and biomass amounts of 100 g. The maximum zinc removal by Eichhornia crassipes (Mart.) Solms was found to be 88.3 ± 0.6 and 93.4 ± 0.4% at the optimum parameter values for the electroplating industry wastewater and the aqueous solution, respectively, against the optimum contact time of 22 days. This study suggests using this phytoremediation technology to remove all pollutants from industrial wastewater in general, not just wastewater from the electroplating industry.

Continuous direct compression of a commercially batch-manufactured tablet formulation with two different processing lines.

The transfer from batch-based to continuous tablet manufacturing increases the quality and efficiency of processes. Nonetheless, as in the development of a batch process, the continuous process design requires optimization studies to ensure a robust process. In this study, processing of a commercially batch-manufactured tablet product was tested with two continuous direct compression lines while keeping the original formulation composition and tablet quality requirements. Tableting runs were conducted with different values of process parameters. Changes in parameter settings were found to cause differences in tablet properties. Most of these quality properties could be controlled and maintained within the set limits effortlessly already at this stage of studies. However, the API content and content uniformity seemed to require more investigation. The observed content uniformity challenges were traced to individual tablets with a high amount of API. This was suspected to be caused by API micro-agglomerates since tablet weight variability did not explain the issue. This could be solved by adding a mill between two blenders in the process line. Overall, this case study produced promising results with both tested manufacturing lines since many tablet properties complied with the test result limits without optimization of process parameter settings.

Microbiological safety of dry-cured fish from the raw material to the end of processing.

The commercialization of processed fish products is rising in restaurants and small to medium enterprises. However, there is a lack of data related to the microbiological safety of such products. In this study total aerobic colony count and Enterobacteriaceae, as proxy of process hygiene criteria, and detection of Listeria monocytogenes and concentration of histamine, as food safety criteria, were investigated in Salmo salar (salmon), Xiphias gladius (swordfish) and Thunnus albacares (yellowfin tuna), before, during, and at the end of a dry-curing process, performed in a dedicated cabinet, at controlled temperature, relative humidity and ventilation, up to 240 h. The microbiological parameters were investigated in the tested fish products by culture methods and shotgun metagenomic, while the presence of histamine, and other biogenic amines, was quantified by High Performance Liquid Chromatography. In the raw material, and up to the end of the dry curing process, the concentration of Enterobacteriaceae was always lower than 10 CFU/g, while total aerobic colony counts ranged between 3.9 and 5.4 Log CFU/g in salmon; 5.5 and 5.9 Log CFU/g in swordfish; 4.4 and 4.8 Log CFU/g in tuna. The pH values were significantly different between fish species, in the raw materials and during processing except for T4, occurring 70 h after the start of the process for salmon and after 114 h for swordfish and tuna. Water activity was different at specific sampling points and at the end of processing. Overall, 79 % of the sequences identified in the tested fish samples were assigned to y bacteria. The most abundant phyla were Pseudomonadota, Bacillota and Mycoplasmatota. The microbial populations identified by shotgun metagenomic in the tested fish species clustered well separated one from the other. Moreover, the microbial richness was significantly higher in salmon and tuna in comparison to swordfish. Listeria monocytogenes was not detected in the raw material by using the reference cultural method and very few reads (relative abundance <0.007) were detected in swordfish and tuna by shotgun metagenomic. Histamine producing bacteria, belonging to the genera Vibrio, Morganella, Photobacterium and Klebsiella, were identified primarily in swordfish. However, histamine and other biogenic amines were not detected in any sample. To the best of our knowledge this is the first paper reporting time point determinations of microbiological quality and safety parameters in salmon, swordfish and tuna, before, during and at the end of a dry-curing process. The data collected in this paper can help to predict the risk profile of ready to eat dry-cured fish products during storage before consumption.

Surface Roughness of Interior Fine Flow Channels in Selective Laser Melted Ti-6Al-4V Alloy Components.

A challenge remains in achieving adequate surface roughness of SLM fabricated interior channels, which is crucial for fuel delivery in the space industry. This study investigated the surface roughness of interior fine flow channels (1 mm diameter) embedded in SLM fabricated TC4 alloy space components. A machine learning approach identified layer thickness as a significant factor affecting interior channel surface roughness, with an importance score of 1.184, followed by scan speed and laser power with scores of 0.758 and 0.512, respectively. The roughness resulted from thin layer thickness of 20 µm, predominantly formed through powder adherence, while from thicker layer of 50 µm, the roughness was mainly due to the stair step effect. Slow scan speeds increased melt pools solidification time at roof overhangs, causing molten metal to sag under gravity. Higher laser power increased melt pools temperature and led to dross formation at roof overhangs. Smaller hatch spaces increased roughness due to overlapping of melt tracks, while larger hatch spaces reduced surface roughness but led to decreased part density. The surface roughness was recorded at 34 µm for roof areas and 26.15 µm for floor areas. These findings contribute to potential adoption of TC4 alloy components in the space industry.

Process Investigation on Robust Electrospinning of Non-Aligned and Aligned Polyvinylidene Fluoride Nanofiber Mats for Flexible Piezoelectric Sensors.

Polyvinylidene fluoride (PVDF) nanofiber mats have played a significant role in wearable electronic devices that have been in great demand in recent decades. Although manifold PVDFbased freely stacked or well-aligned nanofiber mats created via the electrospinning process have been demonstrated to achieve multisensory capabilities with high sensitivity and long detection range, rarely have any of them proved their ability with a stable process and accurate processing parameters. In this work, we successfully developed freely stacked and well-aligned PVDF nanofiber mats with diameters ranging from micrometers to nanometers, providing stable performance for wearable electronic devices. Through in-depth investigations into material preparation, electrospinning, and fiber collection processes, we revealed the relationship between the nanofiber morphology, ß-phase fraction, and piezoelectric output with various process parameters. Characterized by analytical methods, we have established a mature, reliable nanofiber mat fabrication system capable of mass-producing PVDF nanofibers with the required diameter and consistent properties. At 18 kV voltage and 60% RH humidity, the uniformity of the fiber diameter and ß-phase content was maintained in a favorable range. When the drum speed increased to 2000 r/s, the fiber orientation and ß-phase content increased. We assembled aligned PVDF nanofiber mats with conductive fabric in a flexible piezoelectric sensor that successfully monitored different body movements and produced an output voltage of 0.1 V. This study provides the necessary process parameters for the large-scale production of high-quality PVDF nanofiber mats and provides clear guidance for beginners in the field of nanofiber mat manufacturing.

Pilot-scale membrane-covered composting of food waste: Initial moisture, mature compost addition, aeration time and rate.

The impact of different operational parameters on the composting efficiency and compost quality during pilot-scale membrane-covered composting (MCC) of food waste (FW) was evaluated. Four factors were assessed in an orthogonal experiment at three different levels: initial mixture moisture (IMM, 55 %, 60 %, and 65 %), aeration time (AT, 6, 9, and 12 h/d), aeration rate (AR, 0.2, 0.4, and 0.6 m3/h) and mature compost addition ratio (MC, 2 %, 4 %, and 6 %). Results indicated that 55 % IMM, 6 h/d AT, 0.4 m3/h AR, and 4 % MC addition ratio simultaneously provided the compost with the maximum cumulative temperature and the minimum moisture. It was shown that the IMM was the driving factor of this optimum composting process. On contrary, the optimal parameters for reducing carbon and nitrogen loss were 65 % IMM, 6 h/d AT, 0.4 m3/h AR, and 2 % MC addition ratio. The AR had the most influence on reducing carbon and nitrogen losses compared to all other factors. The optimal conditions for compost maturity were 55 % IMM, 9 h/d AT, 0.2 m3/h AR, and 6 % MC addition ratio. The primary element influencing the pH and electrical conductivity values was the AR, while the germination index was influenced by IMM. Protein was the main organic matter limiting the composting efficiency. The results of this study will provide guidance for the promotion and application of food waste MCC technology, and contribute to a better understanding of the mechanisms involved in MCC for organic solid waste treatment.

[Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept].

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.

Identification of critical process parameters for expansion of clinical grade human Wharton's jelly-derived mesenchymal stromal cells in stirred-tank bioreactors.

Cell therapies based on multipotent mesenchymal stromal cells (MSCs) are traditionally produced using 2D culture systems and platelet lysate- or serum-containing media (SCM). Although cost-effective for single-dose autologous treatments, this approach is not suitable for larger scale manufacturing (e.g., multiple-dose autologous or allogeneic therapies with banked MSCs); automated, scalable and Good Manufacturing Practices (GMP)-compliant platforms are urgently needed. The feasibility of transitioning was evaluated from an established Wharton's jelly MSCs (WJ-MSCs) 2D production strategy to a new one with stirred-tank bioreactors (STRs). Experimental conditions included four GMP-compliant xeno- and serum-free media (XSFM) screened in 2D conditions and two GMP-grade microcarriers assessed in 0.25 L-STRs using SCM. From the screening, a XSFM was selected and compared against SCM using the best-performing microcarrier. It was observed that SCM outperformed the 2D-selected medium in STRs, reinforcing the importance of 2D-to-3D transition studies before translation into clinical production settings. It was also found that attachment efficiency and microcarrier colonization were essential to attain higher fold expansions, and were therefore defined as critical process parameters. Nevertheless, WJ-MSCs were readily expanded in STRs with both media, preserving critical quality attributes in terms of identity, viability and differentiation potency, and yielding up to 1.47 × 109 cells in a real-scale 2.4-L batch.

Modeling the selective growth advantage of genetically variant human pluripotent stem cells to identify opportunities for manufacturing process control.

BACKGROUND AIMS: The appearance of genetically variant populations in human pluripotent stem cell (hPSC) cultures represents a concern for research and clinical applications. Genetic variations may alter hPSC differentiation potential or cause phenotype variation in differentiated cells. Further, variants may have properties such as proliferative rate, or response to the culture environment, that differ from wild-type cells. As such, understanding the behavior of these variants in culture, and any potential operational impact on manufacturing processes, will be necessary to control quality of putative hPSC-based products that include a proportion of variant threshold in their quality specification. METHODS: Here we show a computational model that mathematically describes the growth dynamics between commonly occurring genetically variant hPSCs and their counterpart wild-type cells in culture. RESULTS: We show that our model is capable of representing the growth behaviors of both wild-type and variant hPSCs in individual and co-culture systems. CONCLUSIONS: This representation allows us to identify three critical process parameters that drive critical quality attributes when genetically variant cells are present within the system: total culture density, proportion of variant cells within the culture system and variant cell overgrowth. Lastly, we used our model to predict how the variability of these parameters affects the prevalence of both populations in culture.