Development Of Manufacturing Processes Research Articles

New Approach for Extrusion Additive Manufacturing of Soft and Elastic Articles from Liquid-PVC-Based Consumable Materials.

The article deals with the experimental development of a novel additive manufacturing (AM) process using a liquid consumable based on polyvinyl chloride plastisol. A conventional additive manufacturing system designed for deposition of melt filaments was converted to deposition of liquid material. Additive manufacturing with liquid plastisol enables the production of parts with low Shore A hardness and high ductility, surpassing the performance of the conventional filament process. The novel AM process enables the production of articles with a Shore A hardness of 5 to 60, and the mechanical properties of the additively manufactured articles are similar to those produced in the mold. This was achieved by varying the parameters of the AM process as well as the composition of the plastisol composition, including those filled with an inorganic filler. The application of different material distribution patterns also has a significant effect on the mechanical properties of the samples. A potential application of the investigated AM method was proposed and practically evaluated.

Manufacturing Process Development and Rig Validation of Slurry Environmental Barrier Coatings for SiC Ceramic and SiC Composite Sub-Components

The process scale-up of fully oxide-based environmental barrier coatings (EBCs) on sintered SiC and chemical vapor infiltration (CVI) SiC/SiC ceramic matrix composite (CMC) sub-components was investigated using various slurry manufacturing processes (dip, spray, spin–dip). The performance of EBC-coated sub-components (SiC heating element, SiC/SiC ceramic matrix mini-composite, SiC airfoil, SiC/SiC CMC airfoil) was evaluated in steam oxidation and combustion rigs. Steam oxidation was conducted at 1427 °C in 90 vol.% H2O (g) + 10 vol.% O2 (g) with a 1 h hold at 1427 °C per cycle (1 h hot and 20 min cooling). For high-pressure combustion rig testing, the EBC surface temperature ranged between 1354 °C and 1538 °C with the temperature gradient through CMC + EBC ranging between 100 °C and 150 °C. Dip and spin–dip are non-line-of-sight processes, whereas spray is a line-of-sight process. The three processes, collectively, demonstrated the capability to manufacture slurry EBCs on sub-components with various shapes and sizes. There was no discernable disparity in the EBC steam oxidation performance between the coupons and sub-components in this study and coupons in a previous study. The dependence of steam oxidation rates on the substrate chemistry reported previously was confirmed. The steam oxidation rate of EBC-coated sintered SiC, compared with EBC-coated CVI CMC, was ~2 times and ~1.5 times higher after 100 h and 500 h, respectively, due to the boron sintering aid in sintered SiC. An EBC-coated CMC airfoil after 150 15-h-long cycles in a high-pressure combustion rig test showed only limited EBC spallation along the leading edge and more substantial spallation along the trailing edge, demonstrating the feasibility of an oxide-based bond coat to meet the extreme temperature requirements of next-generation EBCs.

Study on mass concentration and morphology of SMAW fume particles with a new covered electrode using nano-CaTiO3 as an arc stabilizer

Advances in manufacturing emphasize on the development of sustainable and green manufacturing processes. Welding is a popular manufacturing process practiced worldwide. The paper presented here describes a new covered electrode for a shielded metal arc welding (SMAW) process wherein nano-sized calcium titanate (CaTiO3) powder was used as an arc stabilizer, replacing the conventional micro sized CaTiO3 in the flux. The effect of this flux modification on the mass concentration and morphology of welding fume particulates was systematically investigated. The mass concentration of coarse, fine and sub-micron sized fume particulates was measured by segregating the fumes in a four-stage personal cascade impactor. The particle mass distribution was estimated from the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the fume particulates. The morphology of fumes at each impactor stage was analysed using scanning electron microscopy and its count median diameter (CMD) was determined. The results indicated as much as 48 % reduction in total fumes and 54 % reduction in the breathing zone concentration of fumes when the entire CaTiO3 in the electrode flux was substituted with nano-CaTiO3. Morphological analysis indicated that a large fraction of the fumes from the conventional electrode were polydispersed particles, while the new electrodes predominantly contained monodispersed particles which have a relatively faster rate of removal from the lungs. Overall, the present work indicated that introducing nano sized CaTiO3 as an arc stabilizer to the flux covering of SMAW electrode could not only reduce the hazardous fume emissions but also reduce its biological activity and toxicity, thus making the process more sustainable and environment friendly.

An arc profile-based approach to evaluate gas pollutants in welding.

Welding is widely used to make assembly of structural components and it will trigger serious environmental pollution, especially waste gas, i.e., carbon dioxide (CO2), ozone (O3), nitrogen oxide (NOx), and particulate matter (PM). It is hard to accurately measure gas pollutants because of their fluidity and diffusivity. However, the pollutants could be evaluated by exploring its generation procedure, i.e., how these pollutants are produced and how to quantify these pollutants. In this paper, an arc profile-based approach to evaluate the emissions of gas pollutants in welding was proposed. The emission of gas pollutants in welding can be calculated according to the chemical reaction and corresponding reaction condition, i.e., the intensity of discharge that determines the coverage volume of the welding arc. To obtain the coverage volume, the welding arc was observed using a high-speed camera and the arc edge was extracted and reconstructed by a binarization processing based method. A welding experiment was performed for recording the arc shape and measuring the emission of gas pollutants. Results show that the measured concentrations of NOx and O3 are 70% and 79% of the calculated emissions of gas pollutants, respectively. It demonstrates the proposed method is credible and feasible, which can help quantitatively analyze the emission of gas pollutants. Meanwhile, the influence of welding time, welding current, and arc length on the emission of gas pollutants was investigated for lowering emission of gas pollution in welding, in order to support the development of sustainable manufacturing processes.

Two-Dimensional Titanium Carbides (Ti3C2) Mxene-Based Patterned-Electrodes for High Capacity Micro-Supercapacitors

With the fast growth of wearable & miniaturized electronic devices, internet of things (IoT), and 5G telecommunications, the need for ultrathin, lightweight, and flexible energy storage devices has expanded significantly. Micro-supercapacitors (MSCs) with electrically isolated interdigitated electrodes, have attracted great interest as major power sources for micro-electronic devices, offering high power efficiency, superior rate capability, and excellent cycle durability. MXenes, two-dimensional (2D) metal carbides and nitrides, have been considered as a promising candidate for state-of-the-art energy storage applications, due to their intriguing combinational properties such as excellent electrical conductivity, large surface area, tunable surface chemistry, and pseudo-capacity. 1 In this work, we report titanium carbides (Ti3C2) MXene-based MSCs with sub-micron gap between electrodes exhibiting high areal capacitance and superior rate capability, realized by microfabrication method based on focused ion beam (FIB) and photolithography.2 We also demonstrate a facile and reliable process for scalable manufacturing of on-chip and flexible MSCs for wearable/portable and miniaturized microelectronics. The MXene MSCs fabricated utilizing the cutting-edge nanofabrication technology in an 8-inch wafer have shown an outstanding volumetric capacitance and stable cyclic performances, suggesting the developed manufacturing process can accelerate commercialization of MXene-based energy storage devices as power sources for next-generation wearable and miniaturized microelectronics.3 [References] 1 Energy Environ. Sci. 9 2847 (2016) 2 Nano Energy 81 (2021), 105616 3 Chem. Eng. J., 450, 138456 (2022)

Tales, tips & teachable moments from applications support veterans

Charlotte Barker, Editor, BioInsights speaks to three Field Application Scientist Managers at Corning Life Sciences: Chris Suarez, Catherine Siler & Austin Mogen Dr Chris Suarez is the Manager of the Field Application Scientist team at Corning Life Sciences. He received his PhD in Medicinal Chemistry and Molecular Pharmacology from Purdue University working on viral production, cell line engineering, and cancer biology. Dr Suarez has held positions in academia focusing on translational research to overcome mechanisms of therapeutic resistance in breast and prostate cancer using 3D tumor organoid models. Dr Suarez works extensively with process development groups, optimizing production capabilities and cellular scale-up conditions from viral production to cellular therapeutics. In addition, he focuses on collaborations utilizing 3D technology like the Corning spheroid and Elplasia® microplates, Transwell® inserts and extracellular matrices to provide more predictive models for therapeutic response.Dr Catherine Siler is an accomplished Field Application Scientist for Corning Life Sciences, with a PhD in Biology from Johns Hopkins University. Dr Siler enables scientists and researchers in the life science industry to overcome challenges with cell culture and scale-up for clinical manufacturing of advanced therapies. She also utilizes her research and teaching experience to drive the adoption of an industry-leading global product portfolio of innovative single-use consumables for research, process development and bioprocessing applications.Dr Austin Mogen is a Field Application Scientist Manager for Western United States and Latin America at Corning Life Sciences. He received his doctorate from the University of Florida and gained industry experience as a Senior Scientist of upstream process development and manufacturing supervisor for viral vector manufacturing. In this position he focused on bioprocess development, closed system solutions for cell culture scale-up, and viral vector production. Since joining Corning Dr Mogen works extensively with academic researchers and process development groups, optimizing cell culture assays and cellular scale-up conditions for viral production, cellular therapeutics, and biologics.

Ultrasonic nondestructive characterization and its role in the development and implementation of additive manufacturing processes

Advancements in manufacturing processes, such as metal 3D printing, are deeply reliant on our understanding of the resulting internal features and microstructures that dictate material behavior. Microstructure characterization is often relegated to techniques that require extensive sample sectioning and surface preparation, which are inherently limited to a small portion of the bulk material. In this presentation, I will show how elastic wave propagation methods (namely, ultrasonic testing) can be combined with physics-based models to extract microstructural parameters in fit-for-service parts. Example results are given for binder jet printed metals (namely, stainless steel 316 and SS316 infiltrated with bronze) where microstructure is characterized over large volumes nondestructively. These methods are correlated to both destructive metrics of microscale features and mechanical properties, which are linked to processing conditions and sample geometry. Finally, I will provide a broader outlook for the impact these techniques may have on the development and implementation of quality assurance protocols for additively manufactured parts.

Preface

Advances in Mechanical Engineering in both fundamentals and applied research are going to facilitate the new digital era of automated machines & manufacturing processes to expedite local socio-economic development. These advances are going to be integrated in the near future for development of new manufacturing processes and new digital automated world. They will be important part of the automotive technology, advance machining processes, renewable energy sources, IOT based mechanical controls, aviation technology & electric vehicles etc. However, advance design and analysis methods, bio medical implant’s by additive manufacturing, advance materials, MEMS, advances in propulsions and power concepts, advance aerodynamics and CFD, FEA optimization, vibration and acoustics, virtual instrumentation with IOT, robotics are key challenges, and they need to be solved through advances in Mechanical engineering through focused and integrated efforts with the use of smart technologies. These advance technologies performs an important role in the ‘Digital Technology Transformation’ to integrate environmental friendly Mechanical systems (e.g. Industry Automation, Advance Energy conversion, Robotics, New Modeling and simulation methods etc.) for the sustainable development. The necessity for ‘Advance Mechanical systems’ is broadly understood and shared, as the world starts to embrace a transition towards new methods and technology for sustainable development in Industry 4.0. As the Editors of the Proceeding of ICAME-2022 in IOP Conference series Material Science & Engineering Journal (ISSN: 1757-899X), we wish to express sincere gratitude to the authors for diligent research dissemination as well as to the reviewers for providing constructive and critical comments in improving the quality of the selected articles. The objective of this volume is to present advancements in advance technologies for environment friendly automation systems and their management, policies for making an energy transition towards sustainable societies. The ICAME-2022 is a major multidisciplinary sustainable engineering conference organized with the objective of bringing together academia, industry practitioners and engineering graduates to analyze scientific studies focusing on advance mechanical system design and analysis with IOT controls and smart material concepts to integrate the relationship among them. The ICAME-2022 is envisioned to analyze the increasing penetration of environment friendly technologies with energy efficiency and management as central topics with effective participation from the academicians, industry practitioners, governmental policy makers, as well as of community service providers. The ICAME-2022 has been jointly organized by G H Raisoni College of Engineering (GHRCE) Nagpur & G H Raisoni Institute of Engineering Technology (GHRIET)Nagpur, India on 27-28 May 2022. As editor(s) of this ICAME-2022, we want to tribute deep sense of appreciations to the international Publishing agency IOP Science for acceptance of our presented papers in IOP Conference Series, Material Science & Engineering Journal. We wish to express our sincere appreciation to the authors, plenary speakers, presenters, participants, supporters, reviewers, technical committee members as well as the entire team of G. H. Raisoni College of Engineering(GHRCE), Nagpur & G H Raisoni Institute of Engineering & Technology(GHRIET), Nagpur(INDIA). We are very grateful to Shri Sunil Raisoni, Chairperson of the Raisoni Group of Institutions; Dr. Sachin Untawale, Director, GHRCE, Nagpur; Dr. Vivek Kapur, Director, GHRIET, Nagpur, Dr. P.V. Walke, Dr. S.B. Jaju, Dr. R.S. Shelke, Dr. Vinod Bhaiswar, Dr. Abhay Khalatkar, Dr. Dheeraj Deshmukh, Dr. A. S.Raut, Mr. Amol Pitale, Dr.A.K. Mahalle, Dr. Manish Gupta, Dr. V. W. Khond, Mr. T.C. Parshiwankar, Dr. A. S. Shahare and the ICAME-2022 organizing committee members for contributing effectively in making the ICAME-2022 and publication of the volume in IOP Proceedings successful. We strongly believe that the ICAME-2022 has provided an effective platform to integrate academia, industry practitioners and engineering graduates to share their research and innovations for the sustainable development of the society.

Bioindustrial manufacturing readiness levels (BioMRLs) as a shared framework for measuring and communicating the maturity of bioproduct manufacturing processes.

Readiness level (RL) frameworks such as technology readiness levels and manufacturing readiness levels describe the status of a technology/manufacturing process on its journey from initial conception to commercial deployment. More importantly, they provide a roadmap to guide technology development and scale-up from a ‘‘totality of system’’ approach. Commercialization risks associated with too narrowly focused R&D efforts are mitigated. RLs are defined abstractly so that they can apply to diverse industries and technology sectors. However, differences between technology sectors make necessary the definition of sector specific RL frameworks. Here, we describe bioindustrial manufacturing readiness levels (BioMRLs), a classification system specific to bioindustrial manufacturing. BioMRLs will give program managers, investors, scientists, and engineers a shared vocabulary for prioritizing goals and assessing risks in the development and commercialization of a bioindustrial manufacturing process.

Physical properties and biological impact of 90Y microspheres prepared by sol-gel method for liver radioembolization

Microspheres for liver radioembolization for human use have high requirements in terms of their toxicity and biocompatibility on the one hand, but also typical properties such as physical and chemical durability or specific activity on the other hand. Developed manufacturing process based on the sol-gel method allowed to obtain spherical, yttrium trioxide grains of fully polycrystalline structure with diameters between 20 μm and 100 μm. The work is focused on a further investigation concerning the Y2O3 microspheres including physical, radiometric, dosimetric, and biological experiments. Neutron activation analysis confirmed a high concentration of radioactive 90Y in the sample. The developed procedure for determining the specific activity of a single microsphere showed that at the time of administration, the activity can be specified at the level of 2600–3200 Bq per microsphere. FLUKA Monte Carlo code was used to prepare model for the calculation of dose distributions at the microscopic level, indicating that locally occurring heterogeneities can lead to cold spots during radioembolization. The data obtained from the simulation enabled analysis of the absorbed dose delivered by gel 90Y2O3 microspheres as a function of radioactivity concentration, initial specific activity, or microsphere concentration in the sample. The reduction in colorectal cancer cell proliferation in vitro confirms the significant influence of beta ray radiation from yttrium-90 trioxide microspheres. Histopathological examination of the distribution of microspheres in the porcine model confirmed the proper location of yttrium trioxide microspheres inside blood vessels in a porcine model. Gel Y2O3 microspheres manufactured using the sol-gel method showed relevant properties, indicating the possible use of microspheres for further biological and preclinical studies.

The Influence of Employee Engagement to Support Corporate Sustainability at PT Wiza

The development of industrial manufacturing processes around the world has resulted in various environmental damage. Companies that carry out business activities in addition to generating profits must also assist in solving related social problems. The community is increasingly aware of the social and environmental impacts that require companies to try to overcome the phenomenon of environmental damage. In general, this study analyzes the influence of employee engagement to support corporate sustainability. This study aims to analyze the influence of talent management and leadership on corporate sustainability through employee engagement. The research sample was 141 people from a total population of 520 employees of PT Wiza. This study uses a quantitative analysis approach, data collection is done using a questionnaire. The data analysis method uses Partial Least Square (PLS) with software version 3.2.9. directly talent management has a significant positive effect on employee engagement, employee engagement has a significant positive effect on corporate sustainability, and talent management and leadership have no effect on corporate sustainability. indirectly employee engagement mediates talent management and leadership on corporate sustainability.

Bioreactor as the root cause of the "manganese effect" during Aspergillus niger citric acid fermentations.

High-yield citric acid production by the filamentous Ascomycete fungus Aspergillus niger requires a combination of extreme nutritional conditions, of which maintaining a low manganese (II) ion concentration (<5 μg L−1) is a key feature. Technical-scale production of citric acid predominantly uses stainless-steel tank fermenters, but glass bioreactors used for strain improvement and manufacturing process development also contain stainless steel components, in which manganese is an essential alloying element. We show here that during citric acid fermentations manganese (II) ions were leaching from the bioreactor into the growth media, resulting in altered fungal physiology and morphology, and significant reduction of citric acid yields. The leaching of manganese (II) ions was dependent on the fermentation time, the acidity of the culture broth and the sterilization protocol applied. Manganese (II) ion leaching was partially mitigated by electrochemical polishing of stainless steel components of the bioreactor. High concentrations of manganese (II) ions during early cultivation led to a reduction in citric acid yield. However, the effect of manganese (II) ions on the reduction of citric acid yield diminished towards the second half of the fermentation. Since maintaining low concentrations of manganese (II) ions is costly, the results of this study can potentially be used to modify protocols to reduce the cost of citric acid production.

Manufacturing considerations underpinning viral and non-viral platform selection

With an ever-increasing range of viral and non-viral technologies available to advanced biotherapeutics developers, manufacturing considerations must play a key role in the decision-making process behind platform selection. These considerations include the current level of innovation in the bioprocessing toolkit and its corresponding capability to address the specific challenges facing individual technology areas.In this article a panel of experts spanning the lentiviral vector (LVV), exosome, and oncolytic virus fields discuss the impact of manufacturing considerations on their respective platform selection and ongoing product/process development strategies, comparing the state of the art in enabling technology in each application area, and discussing related challenges, needs, and opportunities.Allison Hagerman, P.Eng., PMP, MBTVice President, Product Development, Oncolytics BiotechA Professional Engineer focused on biotechnology, Ms. Hagerman joined Oncolytics in 2010 and has been integral to the progress of its product development program ever since. Prior to being appointed as Vice President of Product Development, Ms. Hagerman was the Director, Manufacturing and Engineering from 2013-2017 and Project Manager from 2010-2013, during which time she led the process performance qualification for pelareorep drug substance. Ms. Hagerman is a Professional Engineer (P.Eng., APEGA) and Project Management Professional (PMP, PMI). She holds a Master of Biomedical Technology (MBT) degree from the University of Calgary, and B.Sc. degrees in both Chemical Engineering and Biological Sciences. She is an accomplished equestrian and spends her spare time on horseback.Aaron NoyesVice President of Development, Codiak BiosciencesAaron is a Vice President of Integrated Drug Substance Development at Codiak BioSciences where he leads a team focused on developing scalable production processes for exosomes and robust technology to load varied payloads into exosomes. At the start of his industrial career, Aaron worked at Millipore before joining Wyeth Biopharma/Pfizer Biotech for 12 years where he developed purification processes and focused on scale-up of biologics, including mAbs, recombinant proteins, ADCs, vaccines, cell therapies, and viral vectors. Aaron received a B.S in Biochemistry from the University of Massachusetts at Amherst, a M.E in Biotechnology Engineering from Tufts University and an Engineering Doctorate in Biochemical Engineering at University College London.Laurens SierkstraSenior Director, Business Leader, Purification Thermo Fisher ScientificLaurens received his PhD in biotechnology in 1994 from the University of Utrecht after studying biology at the University of Leiden. He then joined Unilever as Project Manager and Unit Leader. In 2005, after the spinout of BAC BV from Unilever, he became CEO of BAC BV and set up the business in using single- domain antibodies for affinity purification, called CaptureSelect, which was sold in 2013 to Life Technologies. Since the acquisition by Thermo Fisher Scientific, he has been the business leader for the affinity purification business within the Bioproduction Division.Dr. Vladimir SlepushkinGlobal Head of Manufacturing, MedTherapy BiotechnologyDr. Vladimir Slepushkin is Global Head of Manufacturing at MedTherapy Biotechnology. He is leading all functions associated with manufacturing of CAR-T cells and viral vectors. Previously he was Executive Director of Vector Technology at Autolus Therapeutics, leading process development for manufacturing of lentivirus vectors in suspension cell culture, guiding assay development to support process de&#172;velopment for lentiviral vectors, managing CMO for GMP vector production and T-cell processing. Before that, Dr. Slepushkin was directing research vector core, and providing lentiviral, retroviral and AAV vectors for Kite Pharma. Vladimir proved successful in developing novel high-quality products by managing diverse technical groups and cross-functional teams, developing first-in-class clinical product from scratch, including facilities, equipment, manufacturing process, quality systems, regulatory CMC submissions and clinical trials design. He has proven expertise in technically understanding and leading the development and improvement of cell culture and purification processes, and operations and analytical methods, adhering to customer, regulatory, safety and environmental requirements and guidelines. Vladi&#172;mir is experienced in identifying and resolving regulatory and manufacturing technical problems, as well as intellectual property assessment and licensing. He has authored 61 scientific papers in peer-reviewed journals and he’s an author on 14 patents and patent applications.

A New Model for the Economic Rise of China

Based on economic mechanics and Chinese time series data from 1978 to 2018, this paper has measured and analyzed production forces, transaction capacity and consumption power to determine how they impact the growth of national wealth in China. We found that all three significantly influence the national fiscal revenue. The drivers of economic growth include developing manufacturing processes; improving production forces; increasing finance and investment to improve infrastructure, logistics and telecommunication; improving human capital and social institutions to enhance transaction capacity; and boosting the consumption power through a range of efforts to elevate the production force, although consumption power lost its statistical significance in this paper. These factors all impact the fiscal revenue growth and lead to economic rise in China.

Microbial Contamination and Public Health: An Overview

Food contamination with microbial agents can take place at any stage of the food chain, from farm to fork. For this reason, good hygienic and manufacturing practices must be followed along the entire food chain to prevent microbiological food contamination due to microbes which can cause high incidence of morbidity and mortality among consumers. Recent research have been focused on the implementation of innovative technologies for enhancing the quality and safety of food without compromising its organoleptic and nutritional characteristics. Studies should be addressed to the development of simple, less expensive, and fast tests for monitoring and controlling microbial food contamination, as well as to the development of new food manufacturing processes.

Abstract 2746: Preclinical activity and manufacturing feasibility of genetically modified PDCD-1 knockout (KO) tumor-infiltrating lymphocyte (TIL) cell therapy

Abstract Background: Adoptive cell therapy with autologous TIL has demonstrated an objective response rate (ORR) of 36% in the post-immune checkpoint inhibitor (ICI) setting in patients (pts) with advanced/unresectable melanoma (Sarnaik JCO 2021), while in ICI-naïve pts who received early-line combination of TIL and pembrolizumab, the ORR was 60%, with a 30% CR rate (O’Malley SITC 2021). Although effective, anti-PD-1 therapy is limited by poor penetration into the tumor, internalization, and endocytic clearance, in contrast with TIL, which overcome this inherent limitation. PDCD-1 gene inactivation (PD-1 KO) may enhance TIL cell therapy efficacy in the post-ICI setting and abrogate the need for systemic anti-PD-1 therapy in ICI-naïve pts. In preclinical studies, PD-1 KO TIL maintain robust effector function and phenotypic markers indicative of functional TIL (Ritthipichai ESMO 2020). We describe preclinical activity, clinical-scale manufacturing process development, and characterization of IOV-4001, an autologous PD-1 KO TIL cell product. Methods: hIL-2 NOG mice engrafted with melanoma tumor cells received adoptive transfer of autologous PD-1 KO TIL (developed with TALEN® gene editing technology in collaboration with Cellectis), mock TIL (electroporation without TALEN), mock TIL + anti-PD-1 antibody, or no adoptive transfer (n=14 each). Tumor size was measured 2×/wk for 39 days. A 22-day clinical-scale manufacturing process was established, including pre-rapid expansion protocol (pre-REP), activation, electroporation, resting, and REP, for the generation of PD-1 KO TIL. Final PD-1 KO TIL product was characterized for total viable cells (TVC), purity (% viability), identity (% CD45+CD3+), and function (PD-1 KO efficiency). Results: Day 39 mean ± SEM tumor size (mm2) for mice treated with PD-1 KO TIL (6 ± 2.8) showed superior tumor control relative to mock TIL (26 ± 8.5, P&amp;lt;0.05), mock TIL + anti-PD-1 (33 ± 8.8, P&amp;lt;0.01), and no adoptive TIL transfer (112 ± 8.4, P&amp;lt;0.0001). Product attributes from 6 clinical-scale manufacturing runs for PD-1 KO TIL were acceptable, with a median (range) TVC, purity, and identity of 8.3 × 109 (0.9×109-35.7×109), 94% (91%-99%), and 99% (98%-99%), respectively. Median (range) PD-1 KO efficiency was 48% (31%-84%). PD-1 KO TIL function and phenotype (differentiation, memory, activation, and exhaustion) were comparable to mock TIL. Conclusions: Anti-tumor activity of PD-1 KO TIL was superior to mock TIL suggesting that endogenous PD-1 inhibition may confer a functional advantage to the TIL over an antibody combination. PD-1 KO TIL clinical manufacturing was feasible and the TIL product quality attributes and phenotype were acceptable; importantly, lack of complete PD-1 KO may spare other PD-1-dependent in vivo cellular functions. Together, these data support clinical investigation of IOV-4001, an autologous PD-1 KO TIL cell therapy. Citation Format: Arvind Natarajan, Anand Veerapathran, Adrian Wells, Kenneth Onimus, Marcus Machin, Seth Wardell, Jamie L. Blauvelt, Madan Jagasia, Rafael Cubas. Preclinical activity and manufacturing feasibility of genetically modified PDCD-1 knockout (KO) tumor-infiltrating lymphocyte (TIL) cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2746.

A New Method of the Positioning and Analysis of the Roughness Deviation in Five-Axis Milling of External Cylindrical Gear

Abstract Five-axis milling is a modern, flexible and constantly developing manufacturing process, which can be used for the machining of external cylindrical gears by means of cylindrical end mills and special disc mills on universal multi-axis machining centres. The article presents a new method of positioning the tip and the axis of the end mill and the disc cutter in order to ensure a constant value of deviation of the theoretical roughness Rth along the entire length of the tooth profile. The first part presents a mathematical model of the five-axis milling process of the cylindrical gear and an algorithm for calculating the Rth deviation values. The next section describes the positioning of the end mill and the disc cutter. Then, a new method for the empirical determination of the distribution of the involute root angle Δui and the data description by means of the interpolation function are presented and described. In the conducted numerical tests, the influence of the geometrical parameters of the cylindrical gear on the deviation Rth is determined, assuming a constant Rth value in the five-axis milling process.

Optimal design of shape changing mechanical metamaterials at finite strains

Programmable metamaterials establish a new subset of metamaterials offering controllable and variable physical properties. As metamaterials, they are artificial materials and exhibit exotic and counter-intuitive material behavior, but are more specifically tailored for engineering purposes. Whereas for metamaterials a mostly homogeneous layout of unit cells is considered, programmable materials are constructed by an individual distribution in order to satisfy custom intentions regarding a specific shape change under given loading conditions. In order to tackle this customization of material response, a computational optimization framework similar to topology or material optimization is proposed. Our work is based on a multiscale and data approach, allowing a broad range of application with different classes of unit cells and target functions under finite strains. In this contribution, we present the complete process chain from a parametrized unit cell to the final model of the programmable material, ready to be manufactured. We show numerical results with different unit cells and compare them to fully resolved simulations. Further, with the development of new generative manufacturing processes, the production of such programmable materials consisting of spatially varying cells has also become possible on an industrial scale. One example of lab-scale production is shown in the paper and compared to simulation results.

Development of paste extrusion-based metal additive manufacturing process

PurposeThis study aims to explore a technique of metal additive manufacturing (MAM) for producing parts in aluminium. The proposed technique mimics the process of metal injection moulding but with the tools meant for fused freeform fabrication machines.Design/methodology/approachThe work focusses on the preparation of novel feedstock by mixing the aluminium powder with binders made from different compositions of high-density polyethylene, paraffin wax, petroleum jelly and stearic acid. Further, a novel experimental setup with a paste extruder was designed to print the test samples. A sintering cycle was developed in-house along with a thermal debinding procedure. An experimental campaign was also carried with the proposed technique to establish a proof-of-concept. Produced samples were tested for part density, hardness, compressive strength and tensile strength.FindingsThe results indicate geometrical accuracy was an issue owing to the presence of petroleum jelly in the binder-powder mixture. Therefore, machining as a post-processing operation seems to be unavoidable. The study also elucidates that the printed specimen may require further heat treatment to replace wrought alloys. However, the sintered parts show hardness and compressive strength similar to that of wrought aluminium alloy.Originality/valueThe novelty of the work is to develop the cost effective and scalable powder extrusion-based MAM process for printing the aluminium parts.

Analysis on the development of semiconductor manufacturing process

The computing speed of chips depends on the number of transistors. In other words, if you have more transistors, the computing speed of chips will be faster. Supposing the area of a chip is limited, we need to develop ways to fit in more transistors. To put more transistors in chips, minimizing the existing microelectronic device is a good way. To achieve that goal, we need to develop effective semiconductor manufacturing process to develop the performance of chips. In this paper, the research topic is to introduce the development of processes and also show their relevant applications of process. This paper intends to let more people realize the importance of semiconductor manufacturing processes and how it applies to our daily lives. This paper will investigate the following question: until October 2021, which is the most advanced manufacturing process? What are some other areas that we can expand through manufacturing process? The conclusion is that until October 2021, the most advanced process is N5P. Semiconductor manufacturing processes apply to areas like Adaptive Substatistical PCA, complicated material modeling tools and methods.