Standard Manufacturing Process Research Articles

Safety assessment of the world’s first novel cocktail of two monoclonal antibodies in WHO category-III animal-bite patients

ABSTRACT Background: Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods: A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results: In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion: The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Physicochemical Characterization of the Oral Biotherapeutic Drug IMUNOR®.

IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular weights smaller than 12 kDa and a specific portion of nucleotides. The medical uses of IMUNOR include therapeutic applications within its registered range of indications, primarily for the treatment of immunodeficiencies, allergies, and certain acute or relapsing bacterial infections in adults and children. Despite the long-term clinical application of DLE, with strong evidence of positive therapeutic effects and no serious side effects, a detailed physicochemical specification of this mixture was lacking. We developed several methods for more in-depth physicochemical characterization of IMUNOR, including a spectrophotometric method for quantification of the total protein concentration and total DNA concentration in a mixture, several chromatographic methods for identification of individual components present in significant concentrations in IMUNOR, such as HPLC methods and the Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis method, and characterization of amino acid composition of this mixture. For the investigation of the variability among different batches of IMUNOR, five to nine representative batches from a standard manufacturing process on an industrial scale were utilized. Using the analytical methods, we verified and confirmed the batch-to-batch reproducibility of the biological product IMUNOR.

Allogenic and autologous nondiluted serum eye drops-validation strategy compliant with good manufacturing practice.

Serum eye drops alleviate ocular symptoms of diseases such as sicca syndrome, or chronic graft-versus-host disease. This study was designed for good manufacturing practice validation of our standard manufacturing, storage and transport processes for both autologous and allogenic SEDs. Specifications of quality parameters are lacking and were aimed to be defined. Using sterile collected, coagulated whole blood, serum was separated by centrifugation and filled into single-use eye drop applicator vials. Quality control tests included visual inspection, sterility, leukocyte concentration, pH, vitamin A, TGF-ß and VEGF-A. Samples were collected after manufacture and after 24 h and 6 months of frozen storage (-20°C). Sterility testing was performed after opening the SED applicators at specified intervals. For transport validation, SEDs were packed in insulated transport bags and stored at 20-24°C and 30-32°C for 8 h. Vitamin A, TGF-ß and VEGF-A assays showed no difference in concentration between fresh and 24 h frozen serum. All specifications for pH (aim 7.4) and cellular contamination were met and microbiological contamination tests were negative. Shelf-life was defined as 6 months at -20°C. Once opened, the product must be used within 24 h to avoid bacterial outgrowth. Transporting frozen SEDs from the manufacturer via a local pharmacy to the patient within a maximum of 4 h was demonstrated. The GMP compliance of our production, storage and transport processes for autologous and allogenic SEDs was successfully validated. 100% serum eye drops in single-use applicators can be safely used for up to 24 h after opening.

Fecal microbiota live - jslm (Rebyota™/RBL) for management of recurrent Clostridioides difficile infection.

There is an unmet need for effective treatments of Clostridioides difficile infection, an emerging health crisis in the United States. The management of C. difficile infection should include treatment of active infection and a strategy to prevent recurrence. Current gold standard therapy includes oral antibiotics which predispose patients to gut dysbiosis and increase the risk of recurrent infection. Addressing dysbiosis via fecal microbiota transplantation is an active and promising area of research, but studies have lacked standardization which makes outcome and safety data difficult to interpret. Rebyota™, formerly known as RBX2660, is a live biotherapeutic product designed using a standardized protocol and manufacturing process that has been shown to be effective for preventing recurrent C. difficile infection.

Unveiling New IoT Antenna Developments: Planar Multibeam Metasurface Half-Maxwell Fish-Eye Lens with Wavelength Etching

This study introduces a groundbreaking antenna system, the directive Metasurface Half-Maxwell Fish-Eye (MHMF) lens antenna, tailored specifically for Internet-of-Things (IoT) networks. Designed to operate at 60 GHz, this antenna ingeniously integrates a dipole antenna within a parallel-plate waveguide to illuminate a Half-Maxwell Fish-Eye (HMFE) lens. The HMFE lens serves as a focal point, enabling a crucial high gain for IoT operations. The integration of metasurface structures facilitates the attainment of the gradient refractive index essential for the lens surface. By employing commercial Ansys HFSS software, extensive numerical simulations were conducted to meticulously refine the design, focusing particularly on optimizing the dimensions of unit cells, notably the modified H-shaped cells within the parallel waveguides housing the beam launchers. A functional prototype of the antenna was constructed using a standard PCB manufacturing process. Rigorous testing in an anechoic chamber confirmed the functionality of these manufactured devices, with the experimental results closely aligning with the simulated findings. Far-field measurements have further confirmed the effectiveness of the antenna, establishing it as a high-gain antenna solution suitable for IoT applications. Specifically, it operates effectively within the 60 GHz range of the electromagnetic spectrum, which is crucial for ensuring reliable communication in IoT devices. The directive HMFE lens antenna represents a significant advancement in enhancing IoT connectivity and capabilities. Leveraging innovative design concepts and metasurface technology, it heralds a new era of adaptable and efficient IoT systems.

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.

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 & 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.

Post-Marketing Surveillance of the World's First Novel Cocktail of Rabies Monoclonal Antibodies: TwinRab™ in Real \-World Setting.

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies.

Safety, quality, and microbial community analysis of salt-fermented shrimp (Saeu-jeot) in South Korea

This study thoroughly explores the quality and safety aspects of saeu-jeot, a popular salt-fermented shrimp in South Korea, with a specific focus on products fermented in underground tunnels. In this study, an extensive analysis of key quality factors (pH, salinity, total nitrogen [TN], and amino nitrogen [AN]), along with detailed investigation into chemical hazards (volatile basic nitrogen [VBN] and biogenic amines [BAs]), and microbiological hazards (total aerobic bacteria [TAB], fecal indicator bacteria, halophilic bacteria, and foodborne pathogens) were performed. The results indicate that the shrimp grade did not dramatically affect the quality and safety of the saeu-jeot. However, given the prevalent small-scale production of saeu-jeot, the study strongly underscores the pressing need for the establishment of a standardized manufacturing process. The absence of grade-dependent variations in quality highlights the critical importance of implementing standardized procedures to ensure the consistent quality and safety of saeu-jeot, particularly in the context of its frequent small-scale production. These findings provide crucial insights for the industry to enhance practices and meet quality and safety standards effectively.

Integrated Sensors for Soft Medical Robotics.

Minimally invasive procedures assisted by soft robots for surgery, diagnostics, and drug delivery have unprecedented benefits over traditional solutions from both patient and surgeon perspectives. However, the translation of such technology into commercialization remains challenging. The lack of perception abilities is one of the obstructive factors paramount for a safe, accurate and efficient robot-assisted intervention. Integrating different types of miniature sensors onto robotic end-effectors is a promising trend to compensate for the perceptual deficiencies in soft robots. For example, haptic feedback with force sensors helps surgeons to control the interaction force at the tool-tissue interface, impedance sensing of tissue electrical properties can be used for tumor detection. The last decade has witnessed significant progress in the development of multimodal sensors built on the advancement in engineering, material science and scalable micromachining technologies. This review article provides a snapshot on common types of integrated sensors for soft medical robots. It covers various sensing mechanisms, examples for practical and clinical applications, standard manufacturing processes, as well as insights on emerging engineering routes for the fabrication of novel and high-performing sensing devices.

Framework for Designing Quality-Centered Assistance Systems for the Smart Factory

Employee assistance systems are essential for companies to manage the growing complexity of information and processes. However, current systems mainly provide process-oriented support through documentation options, leaving a gap in real-time quality assessment. Real-time or in-process quality assessment becomes increasingly attractive for large and complex components where automated inspection is not feasible. To fill this gap, this paper proposes a new modeling framework for quality-centric assistance systems that are tailored to the Smart Factory environment. The framework integrates digital design principles, standard manufacturing processes, and quality parameters, facilitating seamless integration and standardized data exchange. An expert evaluation of the framework yielded positive ratings across various dimensions, underscoring its potential impact. Feedback from experts indicated the need for further refinement, including enhancing credibility through implementation and field tests, providing more detailed procedure models, and addressing challenges in sensor integration. Overall, this framework represents a significant advancement towards process-oriented assistance in various application areas, with implications for optimizing production and quality processes.

Standard manufacturing process of Aadityapaka Guduchi Taila with unique Pakavidhi (Aadityapaka): a Sneha Kalpana

Abstract BACKGROUND: Since the Vedic era, Ayurveda has promoted natural components to develop a healthy lifestyle and eradicate the disease’s underlying cause by restoring homeostasis. Recently, the acceptability of herbal formulations has grown profusely and garnered global attention. Ayurveda system is enriched with single herbs and polyherbal formulations prepared with different processes. Standardization of a polyherbal formulation process is more essential. Aadityapaka Guduchi Taila (AGT) is a formulation of Chakradutta for Hair fall and is prepared with a peculiar manufacturing process using sunlight. METHODS: AGT was prepared after proper identification and authentication of ingredients as per the standards mentioned in the API. Pharmacognostic and pharmaceutical analyses were carried out to adequately assess the finished product from the viewpoints of efficacy, and quality. RESULTS: The oil prepared from Aadityapaka vidhi was dark orange in color, Ugragandha (strong) in odor pertaining to Jatamansi, and had a greasy consistency. The loss of oil was observed more in the process due to the powder texture of the ingredients. CONCLUSION: There are very few scientific references reported for the Adityapaka process (oil prepared in sunlight). The current study illustrated the standardization of AGT process. The study may be employed as a reference for future research.

High-performance thin-film transistors based on aligned carbon nanotubes for mini- and micro-LED displays

Inorganic mini-LEDs (mLEDs) and micro-LEDs (μLEDs) have ultrahigh luminance and long lifetimes, and are challenging liquid crystal displays (LCDs) and organic light-emitting diode (OLED) displays for next-generation displays. Backplane thin-film transistors (TFTs) for mLED/μLED displays with high mobility and large driving current are under development as currently widely used backplane active materials such as crystalline silicon (CMOS Si), amorphous silicon (a-Si), low-temperature polycrystalline silicon (LTPS), and metal oxides are facing difficulties to meet the requirements. Semiconducting carbon nanotubes (s-CNTs) have long been considered as promising materials for TFTs because of their unique electronic properties. However, TFTs based on s-CNT random networks show inadequate performance due to large amounts of inter-tube junctions. Here, we report high performance TFTs based on wafer-scale, high-density aligned s-CNT array (A-CNT) for mLED/μLED driving backplanes. These A-CNT TFTs with micrometer scale channel length were fabricated using standard semiconductor manufacturing process, and exhibited mobility as high as 160 cm2/Vs and driving current as large as 417 μA/μm at operation voltage of ∼3 V, exceeding commercially available TFTs with similar device sizes. In addition, these A-CNT TFTs have demonstrated good driving capability for commercial mLEDs in a one-transistor-one-diode (1T1D) pixel circuit configuration, and been capable of driving commercially available mLED/μLED displays. Moreover, a prototype display with 2 × 2 mLED array have been demonstrated with full control of each pixel, manifesting the great potential for A-CNT TFT technology for backplane of mLED/μLED displays.

Development and Clinical Validation of an Ultra-Fast CAR-T Manufacturing Platform Enabling Production of CAR-T Cells in Less Than 1 Day

Recently, the use of CAR-T cells has made a major impact on the therapy for a subset of hematologic malignancies including non-Hodgkin lymphoma (NHL) and multiple myeloma. In relapsed/refractory NHL where historically most patients did not respond to chemotherapy, CAR-T cell therapy can lead to initial remission rates >50%. Despite promising outcomes, there are major unmet needs to develop rapid, cost-effective, and scalable CAR-T manufacturing platforms that lead to efficacious and affordable autologous CAR-T cell products. Major barriers to widespread access to CAR-T cell therapy include weeks to months long delays from time of prescription to infusion that leads to disease progression in a significant subset of patients, very elevated costs that preclude access for a majority of patients world-wide, and high relapse rates (~estimated 30-60% within one year) in patients who initially achieve remission. To help address these barriers, we developed an ultra-fast CAR-T manufacturing platform (UF-CAR) that allows production of highly cost-effective CAR-T product in less than 24 hours. The manufacturing workflow was specifically designed to be simple, low cost and rapid to enable its formulation in healthcare facilities without sophisticated equipment or personnel expertise. In addition, we hypothesized that this manufacturing workflow would generate a product that demonstrates dramatically improved efficacy and CAR-T expansion in vivo. Using a BCMA CAR we manufactured CAR-T cell product using both our ultra-fast manufacturing workflow and a traditional 9-day CAR-T cell manufacture workflow. Both workflows led to nearly identical levels of CAR surface expression on the T cells (67% and 66% CAR expression on the UF-BCMA product and 9-day product respectively). To compare the activity of the products, we injected immunodeficient mice intravenously with luciferase labelled MM1.s cells followed by a single intravenous injection of CAR-T cells on day 0. As seen in figure 1A, both products demonstrated efficacy, but the UF-BCMA product induced durable disease control while disease progression started to occur with the 9-day product on day 29 after CAR-T injection. Consistent with the improved efficacy, circulating levels of the UF-BCMA CAR-T cells in the mouse blood were found to be up to 100x higher than the levels of the 9-day BCMA CAR-T product (Figure 1B). Similar increased potency and marked increases in circulating CAR-T cells were observed in a mouse model of human lymphoma when comparing a CD19 CAR manufactured using the UF-CAR workflow as compared to a standard CAR-T manufacturing process. To assess the safety and clinical potential of CAR-T products manufactured with the UF-CAR platform, a phase 1 trial was recently initiated using a CD19 CAR-T product (UF-Kure19). This trial that is open to patients with relapsed/refractory NHL completed treatment of its first patient who had relapsed mantle cell lymphoma. UF-Kure19 product was manufactured successfully in less than 1 day and demonstrated CAR expression of 41%. The product passed all release criteria for infusion and was administered to the patient after lymphodepletion with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 daily for 3 days. UF-Kure19 cells expanded robustly in the patient and peaked around day 10 (23% of circulating CD3) with a strong skewing of CD4/CD8 cells (93% CD8+ T cells on day 10). The patient was found to be in complete metabolic remission by day 28 and ongoing remission was confirmed on day 60. We have developed an ultra-fast CAR-T cell manufacturing platform that enables low-cost production in less than one day. In vitro and animal data suggest this fast-manufacturing platform leads to potent CAR-T cells. Early human testing indicates CAR-T cells generated using this novel system have clinical activity against hematologic malignancies.

Fully enclosed microbeads structured TENG arrays for omnidirectional wind energy harvesting with a portable galloping oscillator

To facilitate the transition of triboelectric nanogenerators (TENG) from early stages to large-scale real-world applications, urgent mass production is imperative, necessitating standardized manufacturing processes. In this study, a novel “pause-and-insert” and “print-in-place” 3D printing approach has been devised, employing widely available fused deposition modeling (FDM) printers along with conductive (as electrodes) and nonconductive (for casing and support) filaments to make encapsulate microbeads triboelectric nanogenerator (MB-TENG). This innovation results in a fully enclosed freestanding-mode TENG pack, seamlessly integrated with a lightweight wind-induced oscillator featuring tuning systems, thus enabling efficient, safe, and noiseless omnidirectional wind energy harvesting. Through adept design and manufacturing techniques, systematic inner-structure optimization has been achieved, yielding superior output and industrialization levels compared to similar efforts. MB-TENG’s surface charge density is as high as 19.9 µC/m2. The average power density is 13.8 W/m3. Moreover, the elimination of postprocessing significantly streamlines standard manufacturing, enhancing the prospects for device commercialization. Beyond its wind energy application, the versatile energy packs can serve as both ocean wave and human motion harvesters within network configurations, capable of powering a massive real-time monitoring sensor array.

Simulation process flow for the implementation of industry-standard FD-SOI quantum dot devices

The spin of an electron confined to a semiconductor quantum dot is one of the main technology platforms currently evaluated in the pursuit of qubit implementation. In this study, we developed and optimized a full simulation process flow used to model an Ultra-Thin Body and Buried oxide (UTBB) Fully Depleted Silicon-On-Insulator (FD-SOI) quantum dot device fabricated using STMicroelectronics' standard manufacturing process. Here, we report optical, geometrical, electrical, and quantum numerical results that allowed us to assess the device performance before its eventual fabrication.

Light-weighting of battery casing for lithium-ion device energy density improvement

Battery casings are essential components in all types of lithium and lithium-ion batteries (LIBs) and typically consist of nickel-coated steel hard casings for 18650 and 21700 cell formats. These steel casings comprise over one quarter of total battery cell mass and do not actively contribute to battery capacity. It is therefore possible to achieve considerable battery performance improvements, in terms of device energy density, by reducing the mass of the battery casing. Following successful completion of an industry-academic technology programme of light-weighting battery casings, this paper reports our research activities to understand the practical performance of aluminium hard casings which are 63 % lighter than a state-of-the-art steel casing. A popular exemplary battery chemistry, Lithium Titanate anode / Lithium Iron Phosphate cathode, which is well-known for high power and good safety, was employed. Research investigations include (a) the optimisation of standard commercial LIB manufacturing process for aluminium casings, (b) the production of 18650 LIBs using aluminium casings, (c) electrochemical analysis and safety testing of the cells, comparing with those assembled with steel. The aluminium casings could readily be incorporated into standard commercial LIB manufacturing process with minimal process changes and provided a > 25 % boost to energy density. Crucially, stress testing of the cells revealed no added safety challenges associated with the material change. Lightweight Al hard casings have presented a possible solution to help address weight sensitive applications of lithium-ion batteries that require high power (or high energy). The approaches herein are battery materials agnostic and can be applied to different cell geometries to help fast-track battery performance improvements.

Optimizing tumor-associated antigen-stimulated autologous dendritic cell and cytokine-induced killer cell coculture to enhance cytotoxicity for cancer immunotherapy in manufacturing

BackgroundDendritic Cell Cytokine-induced killer cell (DC-CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells.ResultsWe evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells’ immunological specificity to tumors in the presence of tumor-associated antigens.ConclusionIn vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells’ cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.

Formula optimization and thermodynamic evolution of high-performance large-sized porcelain thin ceramic tiles mainly enhanced by contrivable multi-phases

Owing to the high expenses and numerous potential avenues for formula research in ceramic production, obtaining cost-effective and high-quality ceramic formulas for high-performance ceramics poses significant challenges. To address this issue, a flux formula optimization procedure is proposed to develop the predictive ceramic formula P18, which allows precise control of the Al/Si ratio and is compatible with standard manufacturing processes. This cost-effective method enables the visual examination of ceramics’ physical, mechanical and thermodynamic properties. It is found that sintering temperature plays a crucial role in phase and microstructure evolution by classical phenomenological kinetic theory. Moreover, the sintered sample P18 exhibits remarkable mechanical performance, with a strength of 96.82 ± 2.0 MPa and fracture toughness of 1.89 ± 0.02 MPa·m1/2. These outstanding properties can be attributed to the reinforcing effects of multiple phases, such as high-strength corundum and in situ mullite whiskers. The mechanical mechanisms of the resulting ceramic tiles include particle reinforcement, microcrack deflection, intergranular and transgranular fracture, and in situ mullite whisker bridge pull-out, which collectively contribute to increase energy consumption per unit length, thus reducing the risk of brittle fractures.

Cryogenic Temperature Deposition of High-Performance CoFeB/MgO/CoFeB Magnetic Tunnel Junctions on ϕ300 mm Wafers

We developed a cryogenic temperature deposition process for high-performance CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) on ϕ300 mm thermally oxidized silicon wafers. The effect of the deposition temperature of the CoFeB layers on the nanostructure, magnetic, and magneto-transport properties of the MTJs was investigated in detail. When CoFeB was deposited at 100 K, the MTJs exhibited a perpendicular magnetic anisotropy (PMA) of 214 μJ/m2 and a voltage-controlled magnetic anisotropy (VCMA) coefficient of −45 fJ/V m, corresponding to 1.4- and 1.7-fold enhancements in PMA and VCMA, respectively, compared to the case of room-temperature deposition of CoFeB. The improvement in the MTJ properties was not simply due to the morphology of the MTJ films. The interface-sensitive magneto-transport properties indicated that interfacial qualities such as intermixing and oxidation states at the MgO/CoFeB interfaces were improved by the cryogenic temperature deposition. A cryogenic temperature sputtering deposition is expected to be a standard manufacturing process for next-generation magnetoresistive random-access memory.