Development Of Manufacturing Processes Research Articles

Coupling Taguchi experimental designs with deep adaptive learning enhanced AI process models for experimental cost savings in manufacturing process development

The Aluminum alloy AA7075 workpiece material is observed under dry finishing turning operation. This work is an investigation reporting promising potential of deep adaptive learning enhanced artificial intelligence process models for L18 (6133) Taguchi orthogonal array experiments and major cost saving potential in machining process optimization. Six different tool inserts are used as categorical parameter along with three continuous operational parameters i.e., depth of cut, feed rate and cutting speed to study the effect of these parameters on workpiece surface roughness and tool life. The data obtained from special L18 (6133) orthogonal array experimental design in dry finishing turning process is used to train AI models. Multi-layer perceptron based artificial neural networks (MLP-ANNs), support vector machines (SVMs) and decision trees are compared for better understanding ability of low resolution experimental design. The AI models can be used with low resolution experimental design to obtain causal relationships between input and output variables. The best performing operational input ranges are identified for output parameters. AI-response surfaces indicate different tool life behavior for alloy based coated tool inserts and non-alloy based coated tool inserts. The AI-Taguchi hybrid modelling and optimization technique helped in achieving 26% of experimental savings (obtaining causal relation with 26% less number of experiments) compared to conventional Taguchi design combined with two screened factors three levels full factorial experimentation.

Mass Balance Analysis for Therapeutic Peptides: Case Studies, Applications, and Perspectives

The concept of mass balance is discussed as it pertains to the pharmaceutical development of therapeutic peptides. Case studies are presented demonstrating how to perform a mass balance assessment on solid drug substance and solution drug product, and the role of mass balance in the context of the overall product control strategy is discussed. Utilizing mass balance as a specification test where the result is calculated from other critical quality attribute tests, each with their own specification, offers little value as a formalized quality acceptance criterion and may create more deviations, non-value added investigations, and potential batch failures. While useful in characterizing the performance of analytical methods and as part of a rigorous understanding of the manufacturing process and control strategy development, mass balance should not be required as a specification control and should instead be demonstrated during method development and through well-designed forced degradation experiments. Analytical method variability is discussed in relation to the analytical target profile, and the overall impact of sources of variability on the mass balance calculation is described in support of this position.

Design and Assessment of an Austenitic Stainless Alloy for Laser Powder Bed Additive Manufacturing

Recent developments in metallic additive manufacturing (AM) processes for the production of high-performance industrial pieces have been hampered by the limited availability of reliably processable or printable alloys. To date, most of the alloys used in AM are commercial grades that have been previously optimized for different manufacturing techniques. This study aims to design new alloys specifically tailored for AM processes, to minimize defects in the final products and to optimize their properties. A computational approach is proposed to design novel and optimized austenitic alloy compositions. This method integrates a suite of predictive tools, including machine learning, calculation of phase diagrams (CALPHAD) and physical models, all piloted by a multi-objective genetic algorithm. Within this framework, several material-dependent criteria are examined and their impact on properties and on the occurrence of defects is identified. To validate our approach, experimental tests are performed on a selected alloy composition: powder is produced by gas atomization and samples are fabricated by laser powder bed fusion. The microstructure and mechanical properties of the alloys are evaluated and its printability is compared with a commercial 316L stainless steel taken as a reference. The optimized alloy performs similarly to 316L in terms of coefficient of thermal expansion, hardness and elongation, but has a 17% lower yield strength and ultimate tensile strength (UTS), indicating that further optimization is required.

Mechanisms, Applications, and Challenges of Utilizing Nanomaterials in Cryopreservation

Cryopreservation of biological samples, including cells, tissues, and organs, has become an essential component in various biomedical research and applications, such as cellular therapy, tissue engineering, organ transplantation, and conservation of endangered species. However, it faces critical challenges throughout the cryopreservation process, such as loading/unloading of cryoprotective agent (CPA), ice inhibition during cooling, and ultrafast and uniform heating during rewarming. Applying nanomaterials in cryopreservation has emerged as a promising solution to address these challenges in each step due to their unique properties. For instance, in order to deliver nonpermeating CPA into cells, some nanomaterials, such as polymeric nanocapsule, can carry nonpermeating CPA to penetrate into the cells, regulating the intracellular ice crystal. During cooling, some nanomaterials, such as graphene oxide, can bind to basal or prism planes of ice crystals, suppressing the ice growth. During rewarming, some nanomaterials, such as magnetic nanoparticles, can improve the heating performance, preventing devitrification and recrystallization during rewarming. However, challenges in nanomaterials‐assisted cryopreservation remain, including the need for comprehensive studies on nanomaterials toxicity and the development of scalable manufacturing processes for industrial applications. This review examines the role of nanomaterials in cryopreservation, focusing on their mechanisms, applications, and associated challenges.

Heterogeneous E‐Textiles: Materials, Manufacturing and Sustainability

AbstractElectronic textiles (e‐textiles) combine electronic functions (e.g., sensing, actuating, data processing) with textiles. E‐textiles are a platform technology with the potential for ubiquitous deployment in any application scenario where textiles can be found. E‐textiles have attracted significant research interests from materials and manufacturing process development to applications such as sports/fitness, healthcare, and workwear. While significant advances have been made in the research domain regarding the integration of electronic functionality, the technology is relatively immature and significant challenges remain in the manufacturing of commercialized e‐textile systems. This paper reviews the state of the art in e‐textile manufacturing including materials (e.g., yarns, inks), fabrication (e.g., weaving, knitting, printing), electronic integration and interconnections. This paper also reviews the key principles of textile sustainability and electronic waste (e‐wastemanagement, which provide useful guidance on e‐textile design and manufacturing to minimize their impact on the environment. Examples are given to demonstrate the early work toward sustainable e‐textiles. The remaining research challenges regarding scalable and sustainable manufacturing of e‐textiles are presented.

20 Seconds to fabricate high-performance NiFe-based anode for seawater electrolysis via bidirectional pulse current method

Direct electrolysis of seawater to produce green hydrogen has attracted great attention. While the development of efficient and rapid manufacturing processes for high-performance electrodes, particularly for the oxygen evolution reaction (OER), remains trail. Here, we introduce an innovative approach to fabricate high-performance NiFe-based OER electrodes using an ultrafast and eco-friendly bidirectional pulse current (BPC) method, which remarkably shortens the production time to only 20 s. Our BPC method alternates oxidation and reduction currents within a single period, promoting the in-situ formation of porous NiFe(oxy)hydroxide nanosheets through dissolution/deposition processes. Moreover, this methodology creatively utilizes the “Cl− induced effect”, typically a hindrance in other electrochemical systems involving seawater or brine, to enhance the synthesis of electrodes from NaCl-based electrolyte devoid of additional Ni/Fe cations. The prepared NiFe-based electrode (NFF O-R 20 s) demonstrates remarkable OER catalytic activity, with optimal overpotentials (ηj) of 272, 308 and 367 mV at current densities (j) of 10, 100 and 1000 mA cm−2, respectively. Impressively, it maintains a low cell voltage of 1.59 V after enduring 1000 h of operation under the industrially current density of 300 mA cm−2, with a direct current energy consumption of 3.8 kWh Nm−3 H2 for overall alkaline seawater electrolysis. Our BPC preparation approach provides a promising path to construction high-catalytic activity, good-stability electrode, and low-energy consumption direct seawater electrolyzer.

Pharmaceutical Product Development: Quality by Design (QbD)

A popular modern strategy in pharmaceutical development is called "quality by design," or QBD, which started with established goals including the product's safety and efficacy. Safety and product efficacy are the primary goals of QBD in pharmaceutical development. With QBD, the design itself is emphasized for excellence. QBD was introduced by the Food and Drug Administration in order to comprehend the production process. An overview of the pharmaceutical quality system, quality risk management, and international council for harmonization (ICH) rules for product development is provided in this article in order to preserve product quality. The scientific foundation of QBD, regulatory industry perspectives, and QBD technologies were briefly discussed. There was a focus on excipients, manufacturing process development, container closure systems, and pharmacological substances. The Q9 guidelines for quality risk management, Q10 guidelines for pharmaceutical quality systems, and Q8 guidelines for pharmaceutical development form its basis. In the research and production of pharmaceuticals, it also provides an application of Quality by Design.

Wavelength-influenced electrical performance of laser-written flexible copper-based structures

The one-step direct laser writing process has been an efficient strategy for constructing flexible metal structures. However, the effect of laser wavelength on the structuring process remains unclear, thus restricting the universal manufacturing process development. In this work, the feasibility of one-step writing of flexible Cu structures with different wavelength continuous diode lasers has been verified. Here, photothermal reactions dominate in the decomposition of the reducing agent to form copper structures. Differences in the wavelength primarily affect the photothermal reaction amplitude for structuring, resulting in a variation in the formation of Cu structures. Under our processing conditions, the photothermal reaction induced by 532 nm laser is higher than 808 nm laser, a higher reduced-joining degree of the Cu structure can be achieved by 532 nm laser. This results in a superior conductivity, adhesion, and bendability of Cu structures fabricated by 532 nm laser than that of 808 nm laser. Furthermore, strain sensors that can detect different bending angles and bending frequencies have been fabricated by 532 nm laser-written structures to demonstrate their practical applications.

Understanding the Effects of Forced and Bubble-Induced Convection in Transport-Limited Organic Electrosynthesis

Organic electrosynthesis offers a sustainable path to decarbonize the chemical industry by integrating renewable energy in chemical manufacturing. However, achieving the selectivity and energy efficiency required for industrial applications is challenging due to the inherent mass transport limitations of most electro-organic reactions. Electrochemical reactions rely on transport of reactants to the electrode surface and become mass transport-limited when the reactant diffusion rate is lower than the reaction rate at the electrode. In organic electrosynthesis with several possible products, mass transport limitations can result in decreased selectivity towards the desired product as the various reaction pathways compete. Convection can mitigate mass transport limitations, but fundamental engineering guidelines for selecting and scaling up convection methods in electrochemical systems do not exist. As a result, the impact of convection on industrial-scale complex organic electrochemical processes remain poorly understood. Here we show that the Sherwood number (Sh)—the ratio of convective mass transport to diffusive mass transport—is a crucial metric to characterize mass transport, determine reactor performance, and enable effective scale-up. We investigate the interplay between mass transport and electrochemical reaction rates under convective flows in the context of the electrosynthesis of adiponitrile, one of the largest organic electrochemical processes in the industry. We use experiments and data-driven predictive models to demonstrate that forced liquid convection and bubble-induced convection produce nearly equivalent mass transport conditions when the corresponding Sherwood numbers are equal. This conclusion shows that the Sherwood number characterizes the mass transport condition independent of the underlying convection mechanism. Additionally, we show that the reactor performance scales with the Sherwood number for a given current density and reactant concentration. This scaling enables accurate prediction of performance irrespective of the convection method, and demonstrates that adiponitrile Faradaic efficiencies of >80% can be achieved for current densities of up to 200 mA/cm2 when Sh > 100. Our results provide guidelines for the design and selection of convection methods, from lab to industrial scale, and contribute to the development of more sustainable chemical manufacturing processes.

Strategy to Simultaneously Manipulate Direct Zn Nucleation and Hydrogen Evolution via Surface Modifier Hydrolysis for High-Performance Zn-Ion Batteries.

The demand for safer batteries is growing rapidly due to fire incidents in electronic devices that use Li-ion batteries. Zn-ion batteries are among the most promising candidates to replace Li-ion batteries because they use a water-based electrolyte and are not explosive. However, Zn-ion batteries suffer from persistent corrosion and dendritic crystal formation during the charge-discharge process, which decrease their reversibility and hinder their commercial usage. Extensive research has been conducted to address these issues, but there are significant limitations due to high process and time costs. In this study, the modulation of the Zn-electrolyte interface to overcome these challenges is attempted using acetamide-derived thioacetamide (TAA), a surface modifier used in electroplating. TAA undergoes hydrolysis in an aqueous solution and produces weakly acidic byproducts and sulfide ions. These species are adsorbed onto the Zn metal surface, which induces uniform Zn2+ deposition, facilitates the formation of a stable interfacial layer, and inhibits side reactions due to the reduced water activity. Consequently, the symmetric cell with TAA achieves a low polarization of 50 mV and stable cycling for 700 h at 1 mA cm-2. Additionally, a Zn|V6O13 full cell exhibits electrochemical reversibility, maintaining a capacity retention of 64% over 300 cycles. Therefore, this study offers useful insights into the development of a simple manufacturing process to ensure the competitiveness of Zn-ion batteries for practical applications using functional electrolyte additives.

Highly Efficient Laser Bidirectional Graphene Printing: Integration of Synthesis, Transfer and Patterning.

Graphene has tremendous potential in future electronics due to its superior force, electrical, and thermal properties. However, the development of graphene devices is limited by its complex, high-cost, and low-efficiency preparation process. This study proposes a novel laser bidirectional graphene printing (LBGP) process for the large-scale preparation of patterned graphene films. In LBGP, a sandwich sample composed of a thermoplastic elastomer (TPE) substrate, carbon precursor powder, and a glass cover is irradiated by a nanosecond pulsed laser. The laser photothermal effect converts the carbon precursor into graphene, with partial graphene sheets deposited directly on the TPE substrate and the remaining transferred to the glass cover via a laser-induced plasma plume. This method simultaneously prepares two face-to-face graphene films in a single laser irradiation, integrating synthesis, transfer, and patterning. The resulting graphene patterns demonstrate good performance in flexible pressure sensing and Joule heating, showcasing high sensitivity (7.7kPa-1), fast response (37ms), and good cycling stability (2000 cycles) for sensors, and high heating rate (1°Cs-1) and long-term stability (3000s) for heaters. It is believed that the simple, low-cost, and efficient LBGP process can promote the development of graphene electronics and laser manufacturing processes.

Hybrid modeling of T-shaped partial least squares regression and transfer learning for formulation and manufacturing process development of new drug products

T-shaped partial least squares regression (T-PLSR) is a valuable machine learning technique for the formulation and manufacturing process development of new drug products. An accurate T-PLSR model requires experimental data with multiple formulations and process conditions. However, it is usually challenging to collect comprehensive experimental data using large-scale manufacturing equipment because of the cost, time, and large consumption of raw materials. This study proposes a hybrid modeling of T-PLSR and transfer learning (TL) to enhance the prediction performance of a T-PLSR model for large-scale manufacturing data by exploiting a large amount of small-scale manufacturing data for model building. The proposed method of T-PLSR+TL was applied to a practical case study focusing on scaling up the tableting process from an experienced compaction simulator to a less-experienced rotary tablet press. The T-PLSR+TL models achieved significantly better prediction performance for tablet quality attributes of new drug products than T-PLSR models without using large-scale manufacturing data with new drug products. The results demonstrated that T-PLSR+TL is more capable of addressing new drug products than T-PLSR by using small-scale manufacturing data to cover a scarcity of large-scale manufacturing data. Furthermore, T-PLSR+TL holds the potential to streamline formulation and manufacturing process development activities for new drug products using an extensive database.

Effects of homogenization and deep cryogenic treatments on microstructure and mechanical property of D2 tool steel fabricated by laser direct energy deposition

The integration of laser direct energy deposition (L-DED) for manufacturing high-hardness D2 tool steel components presents a promising avenue for addressing the increasing complexity of product geometries demanded by modern industry. However, the inherent variability in microstructure and mechanical properties induced by L-DED across the build height necessitates the employment of post-processing techniques to achieve material homogeneity. This study explores the synergistic application of homogenization and deep cryogenic treatment (DCT) as a novel post-processing strategy aimed at mitigating microstructural inhomogeneities and enhancing the mechanical properties of L-DED-fabricated D2 tool steel. Initial analysis of the as-built samples revealed a microstructure characterized by a fine network of eutectic carbides enveloping an FCC matrix, which imposed constraints on martensite transformation during DCT. Homogenization was found to effectively alleviate these constraints, promoting compositional and microstructural uniformity and enabling a more consistent transformation to martensite across the samples upon subsequent DCT. The strategic combination of homogenization and DCT resulted in achieving uniformly distributed high hardness levels exceeding 750 HV throughout the entire sample, regardless of their initial positions within the build. This study demonstrates the potential of combining homogenization with DCT as an effective approach to enhance the structural integrity and mechanical performance of L-DED-fabricated D2 tool steel, offering valuable insights for the development of advanced manufacturing processes for alloyed materials.

One-click fabrication of triboelectric nanogenerators through multiple fused filaments fabrication

The efficiency and cost of manufacturing large-scale triboelectric nanogenerators (TENG) plays an important role in determining the application of TENG in various fields. However, the commonly employed direct ink writing (DIW) technique encounters challenges in the manufacturing process, such as difficulties in achieving automatic material switching, intricate procedures, and high costs. In this paper, we have developed a conductive polymer filament comprising thermoplastic polyurethane/polylactic acid/carbon nanotubes/graphene (TPCG) and proposed a one-click preparation approach for building TENG utilizing Fused Filament Fabrication (FFF) technology. This approach can automatically switch multiple printing materials and thus efficiently prepare TENG without any human intervention. The influence of printing parameters on the output performance of TENG was investigated. As a demonstration, we utilized the one-click method to construct a self-powered cathodic protection system, effectively safeguarding Q235 carbon steel from corrosion. This work presents an advanced TENG fabrication solution based on the developed TPCG conductive polymer filament, enhancing production efficiency and promoting the development of standardized and scalable manufacturing processes.

Impurity study of tecovirimat

This article delineates the systematic identification, synthesis, and impurity control methods used during the manufacturing process development of tecovirimat, an antiviral drug that treats monkeypox. Critical impurities were synthesized, and their chemical structure was confirmed through NMR analysis, GC, and HPLC mass spectrometry. The results established a thorough approach to identify, address, and control impurities to produce high-quality tecovirimat drug substance in accordance with International Conference on Harmonization (ICH)-compliant standards. This study is the first of its kind to evaluate both process and genotoxic impurities in tecovirimat, demonstrating effective control measures during commercial sample investigations and scaling up to a 60-kg batch size. The findings highlight the importance of critical impurity characterization and control in pharmaceutical development and production to ensure the safety and efficacy of the final product.

Development of a gas metal arc based prototype for direct energy deposition with micrometric wire

In recent years, efforts have been focused on the development of metal additive manufacturing (AM) processes to address the growing trend of miniaturization in industries such as aerospace and electronics. Thus, new technologies have been developed based on a downscaled approach using direct energy deposition (DED) processes, now referred to as μ-DED. In this context, the development of a downscaled DED prototype based on gas metal arc (GMA) working with micrometric wires (μ-GMA) has the potential to unify the positive characteristics of GMA-based DED, increasing the complexity of the design and resolution of the produced parts. Therefore, this work focuses on developing a μ-GMA prototype and assessing its technical feasibility. This paper describes the development of the μ-GMA prototype, characterizes the metallic transfer mode, and statistically analyzes the effect of deposition parameters on bead width and height. Additionally, microstructural analysis, Vickers microhardness, and reduced Young's modulus tests were performed. The μ-GMA prototype demonstrated the capability to deposit beads with an approximate width of 1 mm, nearly 5 times thinner than standard GMA-based DED deposition, with a build rate of 30 cm3/h, which is lower than GMA-based DED but higher than other μ-DED processes. Furthermore, the mechanical properties of the μ-GMA depositions are comparable to regular GMA-based DED parts.

Development of a Continuous Process for the Large-Scale Asymmetric Manufacture of (R)-3-Methoxy-2-(4-methylpiperazin-1-yl)propanoic Acid

Development of a Continuous Process for the Large-Scale Asymmetric Manufacture of (<i>R</i>)-3-Methoxy-2-(4-methylpiperazin-1-yl)propanoic Acid

Development of standard manufacturing process of Tryushanadya Lauha – An organo-metalic preparation

Tryushanadya Lauha (TL) is one of the herbo-mineral formulations in many Ayurvedic texts. Tryushanadya Lauha consists Loha Bhasma and Tryushana, which includes Pippali (Piper longum Linn), Maricha (Piper nigrum Linn), and Shunti (Zingiber officinale Roscoe), Cavya (Piper chaba Hunter), Citraka (Plumbago zeylanica Linn), Bakuchi (Psoralea Corylifolia Linn), and Lavana (salt), which includes Saindhava (Sodium chloride), Aubhida (sodium carbonate), Vida (Ammonium chloride), and Sauvarchala (Sodium sulphate). This study is an effort to develop the standard operating process for manufacturing of Loha Bhasma and Tryushanadya Lauha. As per the reference of Rasatarangini, Loha Bhasma (incinerated ash of iron) was prepared in three batches. The processing of Loha Bhasma (ash of iron) was performed by adopting, Shodhana (purification), a special heating process and Marana (incineration). For the process of Levigation decoction of Triphala was used. Puta (heating process) was given in Electric Muffle Furnace at a temperature of 500 0C. The percentage of loss was 49.9% after purification. During Loha Bhasma (incinerated ash of iron) preparation 14.7%loss and 85.3% gain were observed. This Loha Bhasma was used for the preparation of TL. During TL preparation, 0.6% loss was observed &amp; 99.3% was obtained. This study will give the direction for the standard manufacturing process of Loha Bhasma (incinerated ash of iron) and Tryushanadya Lauha.

Identification and quantification of chain-pairing variants or mispaired species of asymmetric monovalent bispecific IgG1 monoclonal antibody format using reverse-phase polyphenyl chromatography coupled electrospray ionization mass spectrometry

Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants. Here, we report a highly sensitive reverse-phase polyphenyl ultra-high-performance liquid chromatography (RP-UHPLC) method to accurately measure mispaired species of Duet mAb format, an asymmetric IgG1 bispecific mAb, for both process development and quality control analytical tests. Coupled with electrospray ionization mass spectrometry (ESI-MS), it enabled direct online characterization of mispaired species. This single direct assay detected diverse mispaired IgG-like species and LMWS. The method resolved eight disulfide bonds dissociated LMWS and three mispaired LMWS. It also resolved three different types of IgG-like mispaired species, including two homodimers and one heterodimer. The characterization and quantification simultaneously enabled the cell line selection that produces a lesser heterogeneity and lower levels of mispaired species with the desired correctly paired product. The biological activity assessment of samples with increased levels of these species quantified by the method exhibited a linear decline in potency with increasing levels of mispaired species in the desired product. We also demonstrated the utility of the technique for testing in-process intermediate materials to determine and assess downstream purification process capability in removing diverse mispaired IgG-like species and LMWS to a certain level during the downstream purification process. Our investigation demonstrates that adopting this method was vital in developing asymmetric bispecific mAb from the initial stage of cell line development to manufacturing process development. Therefore, this tool could be used in the control strategy to monitor and control mispaired species during manufacturing, thus improving the quality control of the final product.

Manufacturing Process Development of Tegoprazan as a Potassium-Competitive Acid Blocker (P-CAB)

Manufacturing Process Development of Tegoprazan as a Potassium-Competitive Acid Blocker (P-CAB)