Development Of Manufacturing Processes Research Articles

Enhancing heat transfer in microchannels: A systematic evaluation of crescent-like fin and wall geometries with secondary flow

Recent developments in additive manufacturing processes, coupled with the demands of modern microelectronics, have spurred research in heat sinks at the micro-scale. The present study introduces microchannel designs resembling crescent-like walls and fins inside a coolant-based heat sink to enhance its thermal performance. Three different microchannel designs, namely the crescent-like fin design (CF design), the crescent-like wall design (CW design), and the crescent-like wall design with secondary flow (CWSF design) have been proposed and evaluated for their ability to transfer heat while maintaining a low pressure drop penalty. Furthermore, these geometries were tested with different inlet–outlet configurations. The paper investigates flow profile, pressure drop, and temperature profiles for a wide range of flow rates and explores certain hydrodynamic phenomena, such as the Coanda effect and vortex formation generated by the network of convex and concave surfaces that induce flow disruption, thus increasing the potential for enhanced thermal performance. Velocity and temperature maldistribution analyses have also been included to compare the stress distribution around the microchannel walls, highlighting the relative potential for structural failure. The findings suggest that incorporating secondary flow passages inside the crescent-like walls would result in a 28–51% reduction in pressure drop, indicating the potential to meet the thermal management needs of modern microchips. The main objective of the paper is to study how varying the attributes of crescent-like geometries affects the flow profile and thermal performance of a heat sink. The study aligns with the requirements of modern microchips, such as the 13th Gen Intel® Core™ processor, and serves as a guideline for the manufacturing of microchannel heat sinks with crescent-like morphologies.

Optimizing environmental sustainability in pharmaceutical 3D printing through machine learning

3D Printing (3DP) of pharmaceuticals could drastically transform the manufacturing of medicines and facilitate the widespread availability of personalised healthcare. However, with increasing awareness of the environmental damage of manufacturing, 3DP must be eco-friendly, especially when it comes to carbon emissions. This study investigated the environmental effects of pharmaceutical 3DP. Using Design of Experiments (DoE) and Machine Learning (ML), we looked at energy use in pharmaceutical Fused Deposition Modeling (FDM). From 136 experimental runs across four common dosage forms, we identified several key parameters that contributed to energy consumption, and consequently CO2 emission. These parameters, identified by both DoE and ML, were the number of objects printed, build plate temperature, nozzle temperature, and layer height. Our analysis revealed that minimizing trial-and-error by being more efficient in R&D and reducing the build plate temperature can significantly decrease CO2 emissions. Furthermore, we demonstrated that only the ML pipeline could accurately predict CO2 emissions, suggesting ML could be a powerful tool in the development of more sustainable manufacturing processes. The models were validated experimentally on new dosage forms of varying geometric complexities and were found to maintain high accuracy across all three dosage forms. The study underscores the potential of merging sustainability and digitalization in the pharmaceutical sector, aligning with the principles of Industry 5.0. It highlights the comparable learning traits between DoE and ML, indicating a promising pathway for wider adoption of ML in pharmaceutical manufacturing. Through focused efforts to reduce wasteful practices and optimize printing parameters, we can pave the way for a more environmentally sustainable future in pharmaceutical 3DP.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods that could obviate or reduce its use are desirable. Developed herein is an alternative, oxidative biocatalytic approach that enables purification of alkyl monoglucosides (essential bio-based surfactant components). Implementing an immobilised engineered alcohol oxidase, a long-chain alcohol by-product derived from alkyl monoglucoside synthesis (normally removed by distillation) is selectively oxidised to an aldehyde, conjugated to an amine resin and then removed by simple filtration. This affords recovery of the purified alkyl monoglucoside. The approach lays a blueprint for further development of sustainable alkylglycoside purification using biocatalysis and, importantly, for refining other important chemical feedstocks that currently rely on distillation.

A novel approach to the manufacture of dissolving microneedles arrays using aerosol jet printing

Despite much research over the last few decades, microneedle arrays for the transdermal delivery of drugs have failed to live up to their initial promise. This may be changing however as companies close in on the commercial delivery of vaccines via this technology. These breakthroughs will undoubtably increase the interest in the use of microneedles arrays for the delivery of biopharmaceuticals but will also drive research into the development of scalable manufacturing processes for their fabrication. While 3D printing is an exciting development in this field, conventional Additive Manufacturing (AM) techniques are unsuitable for biopharmaceuticals due to the harsh processing conditions which can cause degradation of the active ingredient.In this paper we report the first use of Aerosol Jet Printing (AJP) as an AM technique for the fabrication of dissolving microneedle arrays. A formulation of poly(vinyl pyrrolidone), trehalose and glycerol dissolved in water was prepared and characterised. The formulation was aerosolised using ultrasonication and deposited onto a silicon substrate. Critical process parameters such as Computer Aided Design (CAD) design, flow rate, temperature, print speed and focussing ratio were studied to determine their impact on the microneedle quality attributes. 4 × 4 microneedle arrays were printed, with needle heights > 500 µm achieved with print times of 30 mins or less. The resulting needles had sufficient strength and sharpness to penetrate porcine skin samples. Importantly, the microneedles can be fabricated under benign conditions which should be suitable for the processing and subsequent delivery of biopharmaceuticals across the skin.

A collaboration-based multi-objective algorithm for distributed hybrid flowshop scheduling with resource constraints

With the development of the realistic manufacturing process, the distributed scheduling, machine velocity, and resource constraints have attracted much attention. This paper addresses the distributed hybrid flowshop scheduling problem (DHFSP) with machine velocity and resource constraints to minimize the makespan and total energy consumption simultaneously. A mathematical model of the problem is formulated. To solve the proposed problem, a collaboration-based multi-objective algorithm (CBMA) is developed. First, a machine velocity adjustment rule considering resource constraints is proposed by analyzing the characteristics of the problem. In the proposed algorithm, each solution is represented by a well-designed three-dimensional vector. Then, an objective-balanced machine selection strategy is employed to balance the quality and diversity of the initial population. Next, a Pareto knowledge-based collaborative search mechanism enhances the global search ability in each iteration. To improve the convergence of the algorithm, a distributed machine velocity adjustment rule is embedded into the local search. Finally, a set of instances based on realistic industrial processes are tested. The effective performance of the proposed algorithm is verified through computational comparisons.

Overcoming Complex Analytical Challenges Posed by Targeted Multispecific Antibody Cancer Therapeutics

Complex multispecific antibodies overcome the limitations of standard monoclonal antibodies (mAbs), and have complex three-dimensional structures, greater heterogeneity, and often novel disulfide linkages and unusual post-translational modifications. As a result, the comprehensive characterization essential to the development of cost-effective manufacturing processes and safe and efficacious cancer treatments is much more challenging using traditional analytical instruments and techniques. Fortunately, there are new solutions available that provide fast results, often with greater sensitivity and resolution, even for these novel, complex molecules. The application of various new methods and instruments for the analysis of multispecifics is discussed as a means of highlighting their ability to facilitate the development of these important new modalities.

Development and Research Application of Optical Waveguide Microstructure Component Manufacturing Process for Triangle Roller Imprinting

This research integrates the stable pressuring of the flat surface of roll-to-plate (R2P) imprinting, the fast production features of roll-to-roll (R2R) imprinting, and compound layer ring-type microstructure mold cavity manufacturing technology. Using the compound multilayer method with air molecule assistance, the stability of the roller imprinting process is enhanced. In addition, with precision modulation of the triangle roll-to-plate (TR2P) system, a stable microstructure roller imprinting manufacturing process is achieved. The experimental results indicate that the developed triangle roll-to-plate system can stabilize the imprinting process of the continuous microstructure array components. Also, by modulating the angles of the roller axis and the ring, the exterior features of the microstructure can also be adjusted. Gas-molecule-assisted continuous pressuring effectively elevated the roll imprinting angle and continuous pressuring time and reached a high replication rate of 99.14%. The optical waveguide microstructure component produced by this process and the average waveguide propagation losses of approximately 1.2~1.4 dB/cm show that it has optical stability and transparency after optical testing. The research proves that the manufacturing process can effectively provide an innovative process for the equipment and application of the microstructure component.

Flow stress and dynamic recrystallization behavior and modeling of GH4738 superalloy during hot compression

GH4738 superalloy is a key material for gas turbine engines, yet its relatively poor thermoplasticity and narrow temperature range for hot working deteriorate grain structure uniformity and thereafter service performance. Employing hot compression experiments and finite element analysis (FEA), the present study examined the thermoplasticity of the GH4738 alloy and proposed a fast approach to establishing its dynamic recrystallization (DRX) model. The hot working conditions were considered in the 1000–1160 °C temperature range under strain rates of 2–26 s−1 up to a true compressive strain of 0.69. Friction- and temperature-corrected stress-strain curves were obtained, based on which the efficiency of power dissipation and constitutive equations were constructed. It reveals that DRX is the dominant softening mechanism in the GH4738 alloy, where the sensitivity of flow softening positively correlates with lower temperatures and higher strain rates. The appropriate hot working condition for the alloy is temperatures around 1040–1080 °C and a strain rate larger than 8 s−1. The final grain sizes (d) and fractions of DRX (Xdyn) were minimized using the stochastic gradient descent algorithm based on 120 sets of data within the framework of the Avrami equation. It is shown that the formulated model and its integration into the FEA not only yield satisfactory agreement with the experiment but effectively avoid the complexity involved in the traditional method. The study provides key inputs for predicting the flow behavior and grain structure of the GH4738 superalloy, which shall be critical for process development and optimization of industrial manufacturing processes.

Dry Extrusion Process for Manufacturing of High-Energy Cathodes for Lithium-Ion Batteries

For a sustainable production of lithium ion batteries, more environmentally friendly, energy saving and faster strategies are required. For cathode production NCM/NCA layered oxides are commonly used as active materials. Nevertheless, application of the very toxic and teratogenic solvent N-methylpyrrolidone (NMP) is still common for the industrial production of these cathodes. Besides the high toxicity, the NMP recovery after coating is very energy-, time- and cost-intensive.As an alternative, to conventional NMP-based cathode production, we developed a dry extrusion process coupled with slot-die coating, to manufacture high-energy cathodes. The extrusion process offers continuous production, alongside a very good scalability to industrial demands and a significant reduction of mixing time. Since the process is NMP-free and the drying step is saved, it overcomes typical shortcomings of the wet coating as crack formation or binder migration occurring during solvent evaporation. In addition, producing high-energy electrodes leads to lower material costs and space savings, since less layers of Al/Cu foil and separator are required on cell level, compared to a battery of the same capacity and lower electrode mass loading.Herein, we present the development of a dry cathode manufacturing process, a suitable recipe for dry processing, consisting of NCM622, PVdF, carbon black and a superplasticizer, as well as the optimization of the formulation in terms of processability and active material content. We also discuss the influence of process parameters such as temperature or rotation speed on the viscosity of the cathode paste. As a proof of concept, we processed powder mixtures, corresponding to our optimized formulation with about 90 % of NCM, in a pilot scale twin-screw extruder. By melt extrusion through a slot die, we create a thin film from the cathode composite that we directly apply on an Al current collector. We show a schematic representation of the process in the attracted graphic. By repositioning of the electrode coil, we also produce double-sided coatings. After calendaring, we characterize the dry processed electrodes electrochemically in half-cells. The electrochemical performance data is comparable to state of the art cathodes and results are promising that even higher active material contents can be reached. Therefore, the solvent free extrusion of cathodes is highly relevant for industrial applications.AcknowledgementThe presented work was financially supported by BMBF within the project Tropex under the reference number 03XP0235C. Figure 1

Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety.

To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of "stemness." After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC deficiency. Four of these patients received CALEC transplants, establishing preliminary feasibility. Clinical case histories are reported, with no primary safety events. On the basis of these results, a second recruitment phase of the trial was opened to provide longer term safety and efficacy data on more patients.

Vacuum Brazing of 18MAR300 Nickel Maraging Steel Joints Based on Additively Manufactured and Conventional Material Grades

Laser powder bed fusion (LPBF) processes offer the best possible design options for the production of highly complex components with unique functionalities. Although the development of additive manufacturing processes is progressing impressively and build rates have already been significantly increased, the economic production of high‐volume components is still particularly truncated. Comparatively expensive powders, machine‐hour rates, and a limited construction space demonstrate a high demand for joining LPBF components to conventionally manufactured parts. Vacuum brazing is an excellent technology for manufacturing and simultaneous heat treatment of such hybrid components. The aim of this study is to investigate the brazeability and the joint properties of ultrahigh‐strength nickel maraging steel 18MAR300 (1.2709, X3NiCoMoTi18‐9‐5) using BVAg‐30 (Ag68Cu27Pd5) as brazing filler metal. For this purpose, the effect of nickel‐plated surfaces on the wettability and the microstructure of the joint is studied for conv./conv.‐, LPBF/conv.‐, and LPBF/LPBF joints. Furthermore, the quasi‐static and quasi‐dynamic joint strength is evaluated. The results prove that nickel‐plated surfaces are vital to achieve a sufficient process control. The coating assures a deoxidized and sealed surface which favors the formation of NiCu(Fe,Pd,Ag) phases within the braze metal thus enhancing the joint strength. In addition, LPBF/LPBF joint features have significantly higher tensile strength than conv./conv. joints (825–627 MPa).

Mass-produced gram-negative bacterial outer membrane vesicles activate cancer antigen-specific stem-like CD8+ T cells which enables an effective combination immunotherapy with anti-PD-1.

Despite the capability of extracellular vesicles (EVs) derived from Gram-negative and Gram-positive bacteria to induce potent anti-tumour responses, large-scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size-exclusion chromatography, we isolated 357mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/μg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass-produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen-expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen-specific CD8+ T cells with high expression of TCF-1 and PD-1. Furthermore, E. coli OMVs showed synergistic anti-tumour activity with anti-PD-1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen-specific stem-like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti-tumour activities of mass-produced E. coli OMVs as a novel candidate for developing next-generation cancer immunotherapeutic agents.

Scalable Synthesis of Porous Silicon by Acid Etching of Atomized Al-Si Alloy Powder for Lithium-Ion Batteries.

Si anodes have attracted considerable attention for their potential application in next-generation lithium-ion batteries because of their high specific capacity (Li15Si4, 3579 mAh g-1) and elemental abundance. However, Si anodes have not yet been practically applied in lithium-ion batteries because the volume change associated with lithiation and delithiation degrades their capacity during cycling. Instead of considering the active material, we focused on the structural design and developed a scalable process for producing Si anodes with excellent cycle characteristics while precisely controlling the morphology. Al-Si alloy powders were prepared by gas atomization, and porous Si with a skeletal structure was prepared by leaching Al using HCl. Porous Si (p-Si12, p-Si19) prepared from Al88Si12 and Al81Si19 comprised resinous eutectic Si, and porous Si (p-Si25) prepared from Al75Si25 comprised lumpy primary Si and resinous eutectic Si. The porosity of the Si anodes varied from 63% to 76%, depending on the Si composition. The p-Si19 anode displayed the finest pore distribution (20-200 nm), excellent rate characteristics, a reversible discharge capacity of 1607 mAh g-1 after 200 cycles at a rate of 0.1 C with a Coulombic efficiency of over 97%, and high stability. The performances of the p-Si25 and p-Si19 electrodes began to decrease after 250 and 850 cycles, respectively, with a constant-charge capacity of 1000 mAh g-1 and at a rate of 0.2 C. In contrast, the p-Si12 anode maintained its discharge capacity at 1000 mAh g-1 for up to 1000 cycles without degradation. Therefore, the developed manufacturing process is expected to produce porous Si as an active material in lithium-ion batteries for high capacity and long life at an industrial scale.

Development of the Commercial Manufacturing Process for Nirmatrelvir in 17 Months

Development of the Commercial Manufacturing Process for Nirmatrelvir in 17 Months

Process development for the hybrid additive manufacturing of metallic structures on polymer substrates

3D hybrid additive manufacturing describes the combined application of different additive manufacturing processes in order to manufacture a component with almost unlimited design freedom and free choice of materials. One challenge in the hybrid additive manufacturing lies in the different conditions of individual additive manufacturing processes. For example, in the combined application of the laser powder bed fusion (PBF-LB) of metals with the fused filament fabrication (FFF) of polymers, damage can occur in the plastic due to the higher processing temperatures of PBF-LB. Therefore, in this work a process strategy for the buildup of metallic structures in the PBF-LB process on polymer base structures was developed. By reducing the laser energy density in combination with increasing the height of the first layer, a processing window could be identified. The built hybrid components were investigated with micro-computed tomography and the effects of different processing parameters on the interface between the polymer and metal part are discussed. Finally, a strategy to increase the strength of the interface is presented.

The influence of shoulder-workpiece clearance on channel formation during friction stir channeling at low and high heat inputs

Friction stir channeling (FSC) is a newly developed manufacturing process that can replace the traditional fabrication processes of cooling channels for heat exchangers. Regardless of its application, the size and shape of a cooling channel are fundamental to its efficiency. In FSC, clearance between the shoulder of the tool and the workpiece top surface is a prime factor that significantly influences channel size and shape. This study examined the effect of clearance on channel characteristics using two different clearance values, 0.8 mm and 1.2 mm, respectively. The process parameters are chosen in such a way that the effect of clearance can be understood under low and high heat input conditions on several characteristics. These include channel geometry, dimensions, roof thickness, the roughness of the internal surface of the channel walls, and their topography. A rectangular channel geometry with a larger height and width was found to form at 1.2 mm clearance with high heat input parameters. Lower clearance at low heat input resulted in a successful channel, but a higher clearance value produced a defective channel for the same parameters. In conclusion, the results demonstrate how clearance and the amount of heat input are co-dependent to produce a channel with enhanced characteristics that may directly influence the performance of a cooling channel in various heat exchanger applications.

Survey of Reliability Research on 3D Packaged Memory

As the core carrier of information storage, a semiconductor memory device is a basic product with a large volume that is widespread in the integrated circuit industry. With the rapid development of semiconductor manufacturing processes and materials, the internal structure of memory has gradually shifted from a 2D planar packaging structure to a 3D packaging structure to meet industry demands for high-frequency, high-speed, and large-capacity devices with low power consumption. However, advanced 3D packaging technology can pose some reliability risks, making devices prone to failure, especially when used in harsh environmental conditions, including temperature changes, high temperature and humidity levels, and mechanical stress. In this paper, the authors introduce the typical structure characteristics of 3D packaged memory; analyze the reasons for device failure caused by stress; summarize current research methods that utilize temperature, mechanical and hygrothermal theories, and failure models; and present future challenges and directions regarding the reliability research of 3D packaged memory.

Practical and Environmentally Friendly Manufacturing Process for Ensitrelvir, a SARS-CoV-2 Antiviral Candidate

Key words ensitrelvir - COVID-19 - manufacturing process development

Environmental Impact and Sustainable Solutions for Pharmaceutical Waste Management: An Empirical Investigation

The expansion of the pharmaceutical industry has raised concerns about the environmental repercussions stemming from pharmaceutical waste. Inadequate management of waste and disposal have caused hazardous chemicals to be released into the environment, putting the wildlife and people in danger. This summary delves into the environmental consequences of pharmaceutical waste and highlights sustainable solutions for efficient waste management. Pharmaceutical waste encompasses expired or unused medications, packaging materials, and by-products from manufacturing processes. It contains biologically active compounds that can persist in the environment for extended periods. These materials have been found in lakes, soil, and animals, and can cause an imbalance in the ecology and can damage different marine species. To make matters worse, incorrect disposal of pharmaceutical drugs can pollute drinking water, thus posing a serious risk to people's health. Addressing these pressing issues necessitates the implementation of sustainable solutions for pharmaceutical waste management. This abstract explores various approaches, including source reduction, proper disposal practices, and the adoption of advanced treatment technologies. Source reduction involves minimizing the generation of pharmaceutical waste by implementing measures such as improved inventory management and the development of eco-friendly manufacturing processes. Less waste generated can help the environment. The right way to discard medicines is to drop them off at designated areas or take advantage of return programs. These initiatives aim to prevent inappropriate disposal of pharmaceuticals in household waste or by flushing them down the toilet. By establishing dedicated channels for disposal, the risks of environmental contamination can be significantly reduced. Additionally, the exploration of advanced treatment technologies, such as incineration, chemical treatment, and biodegradation, is crucial for effective pharmaceutical waste management. These technologies aim to eliminate or neutralize hazardous compounds present in pharmaceutical waste, thereby minimizing the environmental impact.

RESEARCH OF PROPERTIES OF CERAMIC COMPOSITE FIBER PRINTED USING FUSED DEPOSITION MODELING TECHNOLOGY

This research article presents a comprehensive study on ceramic materials using Fused filament fabrication of ceramic (FFFC) for the production of test samples. The study investigates the effects of different production strategies on three types of ceramic materials: experimental ceramic composite fiber (e.c.c.f.)(composite material produced by STU FCHPT), Zirconium Silicate, and White Zirconia. The primary objective is to compare the production times of the different strategies and investigate their effects on the properties of the samples. This research is important because production time is a crucial factor in the manufacturing industry, and minimizing production time without compromising quality is essential. The study aims to explore the impact of various production strategies on the production time and properties of the test samples, such as hardness, porosity, and flexural strength. The experimental procedure involves printing test samples using a MakerBot METHOD X 3D Printer with FDM technology and varying the layer thickness, raster angle, infill density, and other production strategies. The study aims to identify the optimal production strategy for each ceramic material, which can significantly reduce production time while maintaining the desired quality of the parts. Overall, the research provides valuable insights into the optimal production strategies for different types of ceramic materials and contributes to the development of novel, cost-effective, and efficient manufacturing processes for ceramic composites.