Large-scale Manufacturing Processes Research Articles

Abstract 3210: Raptamer-drug conjugates as molecularly targeted cancer therapeutics

Abstract The use of aptamers as a therapeutic targeting moiety holds the promise of building on the success of antibody-drug conjugates (ADCs). While ADCs are an attractive modality, they face limitations, including limited penetration into solid tumors and a complicated production process for large-scale manufacturing. Aptamers have several potential advantages over antibodies as a targeting moiety including: (i) a smaller size that enables better tumor penetration; (ii) chemical synthesis which allows rapid scale-up and ease of incorporating modifications; (iii) a superior safety profile from lack of immunogenicity and (iv) room temperature stability. Therefore, the use of aptamers in conjunction with drugs (similar to ADCs) holds promise for development of targeted therapeutics. We have identified a novel therapeutic target for certain cancers (COF-01) using proteomics data and immunohistochemistry from patient-derived tumors. Both the COF-01 protein and related mRNA expression was shown to be significantly increased in non-small cell lung cancer, head and neck cancer and pancreatic cancer. Here, we present a new therapeutic approach that targets COF-01-positive cancer cells using next generation aptamer conjugates. We performed a cell- and protein-based selection using our proprietary bead-based combinatorial libraries to generate next-generation base-modified ssDNA aptamers (Raptamers) against COF-01. Binding affinities of the COF-01 Raptamer candidates were determined by concentration curves using biolayer interferometry. The dissociation constants for the COF-01 Raptamers ranged from 80 nM - 200 nM. COF-01-specific Raptamer-drug conjugates (Rap-DCs) were developed by conjugating the Raptamers to monomethyl auristatin E via a cleavable linker. In vitro efficacy data showed the COF-01 Rap-DC can selectively induce cytotoxicity in different types of COF-01-positive human cancer cells (A431, CAL 27, BxPC-3). There was a significant decrease in cell viability of COF-01-positive cells when compared to COF-01-negative control cells (IC50 values ranged from 5.19 nM - 14.11 nM). In vivo efficacy testing in a COF-01-postive cell-derived xenograft mouse model showed a significant decrease in tumor volume in animals treated with the COF-01 Rap-DC when compared to saline- and erlotinib-treated controls. This provides proof-of concept for the use of high-affinity Raptamers against novel molecular targets, such as COF-01. This platform can be used to develop Rap-DCs against emergent neo-antigens on cancer cells that have escaped chemotherapy. Citation Format: Stephanie P. Vega, Nancy E. Ward, Uksha Saini, Leniher Castan-Chibas, Garima Kaushik, Daniel Ciznadija, Dev Chatterjee, Michael J. Heffernan, Atul Varadhachary, Michael Ritchie. Raptamer-drug conjugates as molecularly targeted cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3210.

Pediatric Formulations Developed by Extrusion-Based 3D Printing: From Past Discoveries to Future Prospects.

Three-dimensional printing (3DP) technology in pharmaceutical areas is leading to a significant change in controlled drug delivery and pharmaceutical product development. Pharmaceutical industries and academics are becoming increasingly interested in this innovative technology due to its inherent inexpensiveness and rapid prototyping. The 3DP process could be established in the pharmaceutical industry to replace conventional large-scale manufacturing processes, particularly useful for personalizing pediatric drugs. For instance, shape, size, dosage, drug release and multi-drug combinations can be tailored according to the patient's needs. Pediatric drug development has a significant global impact due to the growing needs for accessible age-appropriate pediatric medicines and for acceptable drug products to ensure adherence to the prescribed treatment. Three-dimensional printing offers several significant advantages for clinical pharmaceutical drug development, such as the ability to personalize medicines, speed up drug manufacturing timelines and provide on-demand drugs in hospitals and pharmacies. The aim of this article is to highlight the benefits of extrusion-based 3D printing technology. The future potential of 3DP in pharmaceuticals has been widely shown in the last few years. This article summarizes the discoveries about pediatric pharmaceutical formulations which have been developed with extrusion-based technologies.

From Fluids to Pharmaceuticals: How Computational Fluid Dynamics (CFD) Transforms Drug Design

Computational Fluid Dynamics (CFD) is a powerful tool that helps scientists and engineers understand how fluids behave and move, whether in the air, liquids, or biopharmaceutical manufacturing processes. This technology, which uses computer simulations to replicate real-world scenarios, plays a critical role in various industries, including medicine and drug development. By creating virtual experiments on computers, CFD allows researchers to gain insights into the interaction of biological components for drug production at different scales, from small laboratory experiments to large-scale manufacturing processes and fast-track process optimisation. The strategy and implementation of CFD for a bioreactor system has been explained in this article.

A generalized method aiming at predicting the polymer melt flow field in the metering zone of large-scale single-screw extruders

Single-screw extruders (SSE) are commonly used in a wide variety of applications, ranging from polymer-extrusion to pellet additive manufacturing (PAM). Existing mathematical models focus on Newtonian and power-law rheologies to model melt flow in the last screw vanes. However, molten polymers usually follow more complex rheological patterns, and a generalized extrusion model is still lacking. Therefore, a semi-analytical model aiming at describing the flow of molten polymers in SSE is presented, to encompass a wide range of non-Newtonian fluids, including generalized non-Newtonian fluids (GNF). The aim is to evaluate the molten polymer flow field under the minimum set of dimensionless parameters. The effect of dimensionless extrusion temperature, flow rate, channel width, and height on the flow field has been investigated. A full factorial plane has been chosen, and it was found that the impact of dimensionless flow rate is the most prominent. The results were initially compared to numerical computations, revealing a strong agreement between the simulations and the proposed GNF method. However, significant deviations emerged when employing the traditional power-law model. This is particularly true at high values of flow rate and extrusion temperature: the mean error on overall flow speed is reduced from 12.91% (traditional power-law method) to 1.04% (proposed GNF method), while keeping a reasonable computational time (time reduction: 96.70%, if compared to fully numerical solutions). Then, the predicted pressure drop in the metering section was benchmarked against established literature data for industrial-scale extruders, to show the model’s accuracy and reliability. The relative errors of the traditional model range between 34.33 and 62%. The proposed method reduces this gap (errors ranging between 5.34% and 10.97%). The low computational time and high accuracy of the GNF method will pave the way for its integration in more complex mathematical models of large-scale additive manufacturing processes.

A Novel Quality-Related Distributed Fault Diagnosis Framework for Large-Scale Sequential Manufacturing Processes

A Novel Quality-Related Distributed Fault Diagnosis Framework for Large-Scale Sequential Manufacturing Processes

Modeling and Fundamental Dynamics of Vacuum, Gas, and Antisolvent Quenching for Scalable Perovskite Processes.

Hybrid perovskite photovoltaics (PVs) promise cost-effective fabrication with large-scale solution-based manufacturing processes as well as high power conversion efficiencies. Almost all of today's high-performance solution-processed perovskite absorber films rely on so-called quenching techniques that rapidly increase supersaturation to induce a prompt crystallization. However, to date, there are no metrics for comparing results obtained with different quenching methods. In response, the first quantitative modeling framework for gas quenching, anti-solvent quenching, and vacuum quenching is developed herein. Based on dynamic thickness measurements in a vacuum chamber, previous works on drying dynamics, and commonly known material properties, a detailed analysis of mass transfer dynamics is performed for each quenching technique. The derived models are delivered along with an open-source software framework that is modular and extensible. Thereby, a deep understanding of the impact of each process parameter on mass transfer dynamics is provided. Moreover, the supersaturation rate at critical concentration is proposed as a decisive benchmark of quenching effectiveness, yielding ≈ 10-3 - 10-1s-1 for vacuum quenching, ≈ 10-5 - 10-3s-1 for static gas quenching, ≈ 10-2 - 100s-1 for dynamic gas quenching and ≈ 102s-1 for antisolvent quenching. This benchmark fosters transferability and scalability of hybrid perovskite fabrication, transforming the "art of device making" to well-defined process engineering.

Using Local Concentration to Model the Progress of Acoustophoretic Assembly of Microspheres in Planar Standing Waves

Abstract Acoustophoretic assembly uses a standing acoustic field to move dispersed small particles into a geometric pattern. The technique relies on the acoustic radiation force (ARF), which arises from the interaction between the acoustic field and the particles, and drives the particles toward the pressure nodes or antinodes of the standing wave. Acoustophoretic assembly shows potential for a wide range of applications, including organizing filler materials in composites, creating metamaterials, and fabricating functional biological tissue. However, the method has not yet been incorporated into large-scale manufacturing processes. One barrier is the incomplete understanding of the assembly process. While an ideal final pattern geometry can be calculated from the acoustic field and material properties, there are currently no widespread metrics for measuring the progress of the pattern formation. As a result, it is difficult to know how long the acoustic field should be applied during manufacturing. Our approach uses the local particle concentration to model the acoustophoretic assembly process in bulk acoustic waves. We show that the time-dependent local particle concentration can be derived from the force balance on the particles and a control volume analysis. The analysis is applied to microspheres in a planar standing wave, and an analytical expression is obtained, which yields a time parameter for pattern assembly and suggests a cutoff time. We then use the local concentration to define measurements for the quality of the assembled microsphere pattern. Experiments were carried out using polystyrene microspheres in a glycerol–water mixture to validate the theoretical results.

UV–VIS-NIR optical properties of micrometric-thick polyimide membranes for lightweight devices in space

The optical properties of micrometric-thick polyimide membranes were analyzed between 200 nm and 2500 nm to assess their potential use as substrates for the fabrication of wide optical devices for space applications. These membranes were prepared from fully aromatic polyimides containing trifluoromethyl functional groups which have already been used in space and have shown excellent resistance to the space environment. Various membranes have been synthesized using two different solvents and thermal treatments. Spectrophotometric and ellipsometric measurements were performed to estimate the spectral refractive index (n) and extinction coefficient (k) of various membranes synthesized using a standard solvent, such as N,N-dimethylacetamide (DMAc) and an alternative bio-based solvent, that is dimethyl isosorbide (DMI). The investigation has been extended to consider the morphological properties of the surface and the consequences they have on the diffusion of incident light. This work demonstrates that it is possible to use a green and non-hazardous solvent for the synthesis of thin polyimide membranes, even in the perspective of a large-scale manufacturing process that is greener and more sustainable. Using similar synthesis methods, the surface topography of the polyimide obtained with DMI is found to be smoother. Results suggest that membranes obtained by this bio-based solvent can also be used for optical devices where the scattered component of reflected and transmitted radiation needs to be minimized.

Understanding the environmental impacts of large-scale cellulose nanocrystals production: Case studies in regions dependent on renewable and fossil fuel energy sources

Favorable functional properties of cellulose nanocrystals (CNCs) in several end-use applications as well as its ‘green’ credential as a bio-based material, stimulate significant interest in scaling up the manufacture of CNCs. As in any other process, there exist several design options for the overall process and decisions on adoption of a specific plant configuration should be based on the economic as well as the environmental data, preferably from the life cycle assessment (LCA) perspective. In this study we establish a benchmark LCA of a conceptual large-scale CNC manufacturing process based on sulfuric acid hydrolysis. We then employ the benchmark process model to explore several plant configurations under different acid recycling scenarios and targeting two different CNC materials, revealing key findings: (1) without acid recycling environmental impacts are dominated by input materials; (2) introducing acid recycling shifts environmental impacts from input materials to energy consumption: thus, complete acid recycling requires ∼ 14 times more energy; (3) based on the LCA study we recommend optimizing plant configuration through partial acid recycling for a balance between materials and energy consumption. Regions with abundant low-carbon energy, like Quebec and Sweden, favour high acid recycling, while fossil-dominated regions benefit from limited acid recycling. This study provides benchmark values of LCA impacts of CNC manufacture, which could be used for the assessment of carbon footprint and other environmental metrics of final products manufactured from CNCs.

Scale preparation of core–shell bacterial healing agent for concrete and evaluation of shell protection and core mineralization ability

Repairing cracks is a pivotal research direction in the field of concrete. Utilizing bacteria to generate calcium carbonate and fill cracks has demonstrated feasibility. However, the highly alkaline concrete environment hampers the long-term effectiveness of bacteria. Using a carrier to protect the bacteria is considered the most promising solution. Regrettably, there is a notable absence of substantial reports on large-scale manufacturing processes for bacterial healing agents, greatly impeding their widespread application. This study presents a comprehensive large-scale preparation process for core–shell bacterial healing agents to address this knowledge gap. The investigation examines the influence of different binder wetting agent types, calcium source composite processes, and curing systems on the properties of the healing agent. The study examined the influence of different binder wetting agent types, calcium source composite processes, and curing systems on the properties of the healing agent. Additionally, the protective effect of the shell on the core material under extreme environmental conditions was evaluated. The results demonstrate that the healing agent prepared using this process exhibits a core–shell structure, wherein the shell effectively safeguards the bacteria even after experiencing freeze–thaw cycles and high temperatures. The bacteria within the healing agent can mineralize and produce calcite to repair even after 500 d. These research findings provide practical insights for the long-term self-healing performance of concrete, laying a solid foundation for the widespread adoption and promotion of bacterial healing agents.

RIE-Induced VIA Defect Inspection Using In-line Voltage Contrast Technique – 0.18 µm Technology

Optical inspection is used in large-scale manufacturing processes to identify the pattern defect. However, the capture rate of killer defects is low due to the resolution limit of optical inspection. The Voltage Contrast (VC) technique of Scanning Electron Microscope (SEM) was developed to detect killer defects. The VC electron beam inspection is a widely used method in the IC manufacturing industry for the monitoring and characterisation of electrical defects at an early stage. The major drawback of E-Beam inspection is low throughput. To enhance the chip yield, some defects should be detected and reduced in the early stage of fabrication. Herein, we present the Back End of Line (BEOL) fabrication with 0.18 µm process technology and the application of VC methodology to inspect electrical defects. The defects mostly occur due to marginal process window, which affects the etching and lithography process. These effects lead to metal shorts and partial etch of interconnect producing open VIA12. Using inline VC-SEM the invisible defects can be detected at an early stage and chip yield can be further improved.

Thermal investigation of nanofluid-filled hexagonal fillet cavity under the influence of heated and concentered cylinder

The incorporation of nanoparticles is very advantageous to address the challenges of heat transmission in numerous industrial frameworks. Double-diffusive Natural Convection (DDNC) is a key component of large-scale industrial manufacturing processes, including chemical processing, heat exchangers, and cooling systems. Understanding and optimizing DDNC can enhance process efficiency, reduce energy consumption, and improve product quality. The prime motive of current disquisition is to explicate enhancement in thermal attributes of ordinary water by adding MWCNT's saturated in hexagonal enclosure. A circular heated and concentrated cylinder is placed at the center to generate optimize thermal and concentration gradients. Additionally, magnetic field of uniform strength is applied horizontally to the domain. Problem formulation containing thermophysical relation of inducted nanoparticles are well established and solved numerically by finite element method. Outcomes of involved sundry parameters like, Rayleigh, Hartmann, Lewis numbers are displayed through snapshots. Through observation, it has been noted that the velocity field demonstrates a rising trend in the hydrodynamic case (Ha=0) in contrast to the hydromagnetic case (Ha≠0), as indicated by the stream function's magnitude. More specifically, the maximum value of 〖| |ψ|max reaches 9.8 in the absence of a magnetic field, while it decreases to 3.8 when a magnetic field is present.

Mechatronic Design of Two-Jaw Pleating End-Effector for Large-Scale Carbon Fibre Reinforced Polymer Manufacturing

Large-scale composite manufacturing processes, particularly vacuum injection moulding, are often hampered by expensive labour costs and low-levels of automation. The current process of manufacturing carbon fibre reinforced polymers (CFRP) for airplane fuselage workpieces requires experienced workers to spend hours manually placing, pleating and migrating multiple layers of fabrics in order to produce the desired composite part. A promising solution is to utilize robot platforms as assistants to alleviate the physical demands of the tasks. In this paper, we present the design and evaluate the performance of our novel Vacuum Infusion Moulding End-Effector (VIMEE) prototype in the pleating procedure of a simulated CFRP manufacturing vacuum bagging process, where our gripper system performs pleat loading, height detection and migration tasks. Experimental results show successful manipulation of nylon pleats by our mechatronic systems design. These results are promising, demonstrating our VIMEE design's potential value in vacuum injection moulding.

Trial in Progress: AB-101, an Allogeneic, Non-Engineered, Cord Blood-Derived Natural Killer (NK) Cell Therapy, As Monotherapy or in Combination with Rituximab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma

Background: Natural Killer (NK) cells are known to eliminate tumors directly or via antibody-dependent cellular cytotoxicity (ADCC) which is dependent on the maturation, activation and FcγRIIIA (CD16) phenotype of NK cells. Many cancer patients have low NK cell number and dysfunctional innate immunity, which has been correlated with outcomes to monoclonal antibody (mAb) therapy. AB-101 is an allogeneic, non-genetically modified cord blood-derived NK cell therapy, developed to potentially enhance patients' innate anti-tumor activity in combination with approved oncology products with known ADCC mechanism of action. AB-101 has been optimized for combination with mAbs through the novel AlloNK™ proprietary large scale manufacturing process utilizing donor cord blood units. The cord blood unit is selected for key attributes, including an immunoglobulin-like receptor B (KIR-B) haplotype and the natural high-affinity variant of CD16 (158V/V polymorphism). The AlloNK™ process results in an activated and mature NK cell product with increased cell surface expression of CD16, NKG2D, NKp30/44/46, and DNAM-1, without any requirement for genetic engineering. Additionally, the process generates sufficient NK cells to treat hundreds to thousands of patients from a single cord blood unit and produces a consistently active NK cell product, with little donor-to-donor variability. The combination of AB-101 and rituximab has demonstrated strong cytotoxic activity in preclinical studies; the combination led to improved survival over rituximab or NK cells alone in xenograft mouse models. As a cryopreserved, "off-the-shelf", and infusion-ready product, AB-101 is being evaluated for the treatment of hematologic malignancies in combination with standard of care antibody therapies. Study Design, Treatment and Methods: AB-101-01 is a first in human, Phase 1/2, multi-center, open-label study to evaluate the safety and anti-tumor activity of AB-101 as monotherapy and in combination with rituximab in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) of B-cell origin or CLL. This study has 3 parts: Phase 1, 1b, and 2. Phase 1 will evaluate 2 dose levels as monotherapy or in combination with rituximab using the 3+3 dose escalation method. Phase 1b will enroll up to 45 patients in combination with rituximab to determine the recommended phase 2 dose (RP2D). Phase 2 will enroll an additional 15 patients at the RP2D. AB-101 will be given at 1 or 4 billion cells per dose. All enrolled patients will receive at least 1 treatment cycle of 4 doses of AB-101, administered once weekly. Prior to receiving the first dose of AB-101, patients will receive 3 consecutive days of lymphodepleting chemotherapy consisting of fludarabine (30 mg/m2/day) and cyclophosphamide (250 or 500 mg/m2/day). After each AB-101 infusion, patients will receive interleukin-2 (IL-2) at 1×106 IU/m2/dose or 6×106 IU/dose to potentiate NK cell activation and persistence. If given, 375 mg/m2 of rituximab is dosed on the second day of lymphodepletion and with the second and fourth dose of AB-101. Patients who have a complete or partial response or maintain stable disease with the first cycle of the combination may receive 3 additional cycles such that cycle 2 is given with lymphodepletion and cycles 3 and 4 do not include lymphodepletion. Eligible patients must have a diagnosis of B-cell NHL or CLL and must have received at least 2 prior lines of therapy, including an anti-CD20 antibody therapy. Treatment with prior CD19 CAR T-cell therapy is permitted. Patients must be at least 18 years of age, have ECOG PS of 0 or 1, and have measurable disease per Lugano 2014 at the time of enrollment. The primary objectives of each phase are as follows: in Phase 1, the evaluation of the safety of 1 and 4 billion cells/dose of AB-101 as monotherapy or in combination with rituximab through the incidence of AEs and DLTs; in Phase 1b, determination of the RP2D based on safety and antitumor response to AB-101 with rituximab; and in Phase 2, further characterization of the efficacy profile. The study is currently enrolling at 10 U.S. centers. (ClinicalTrials.gov Identifier: NCT04673617)

MAbs N-glycosylation: Implications for biotechnology and analytics

Monoclonal antibodies (mAbs) are amazingly successful in treating diseases such as various types of cancers, immune disorders, and infections. Currently, mAbs are considered the most versatile therapeutic available. Seminal scientific progress over the last decade on elucidating the functional role of antibody N-glycosylation revealed the significance of this post-translational modification on the stability, half-life, and biological activity of antibodies. Therefore, antibody N-glycosylation became a key aspect of biopharmaceutical mAb production in large-scale manufacturing processes. This Mini-Review summarizes the recent scientific attempts of producing mAbs in glycoengineered animal-, plant-, and yeast cell lines. Furthermore, we also describe novel approaches for analyzing mAb N-glycosylation.

Clinical grade lentiviral vector purification and quality control requirements.

Lentiviral vectors have been proven to be a powerful tool in gene therapies that includes the ability to perform long-term gene editing in both dividing and non-dividing cells. In order to meet the rising demand for clinical-grade lentiviral vectors for future clinical trials and requirements by regulatory agencies, new methods and technologies were developed, including the rapid optimization of production and purification processes. However, gaps still exist in achieving ideal yields and recovery rates in large-scale manufacturing process steps. The downstream purification process is a critical step required to obtain a sufficient quantity and high-quality lentiviral vectors products, which is challenged by the low stability of the lentiviral vector particles and large production volumes associated with the manufacturing process. This review summarizes the most recent and promising technologies and enhancements used in the large-scale purification process step of lentiviral vector manufacturing and aims to provide a significant contribution towards the achievement of providing sufficient quantity and quality of lentiviral vectors in scalable processes.

Applications, performance, challenges and current progress of 3D concrete printing technologies as the future of sustainable construction – A state of the art review

The construction industry is moving closer to 3D printing in concrete for the manufacture of architectural or building components. Construction Industry is expected to drastically modify current processing methods and perhaps lead to disruptive technologies for instance 3D concrete printing (3DCP), resulting in significant variations in the construction industry. Around the world, the construction industry and research initiatives are concentrating on automated construction technologies. There have been several technologies for 3DCP of concrete elements developed, and their use in building projects is increasing. 3DP's growth isn't confined to Earth; it's also gaining traction as a means of constructing space habitats. 3DCP allows for freeform building without the need for costly formwork, which has several advantages over the traditional method of pouring concrete into a formwork. In recent years, several 3DCP technologies have been created. Techniques and procedures that have been tested include on-site and off-site manufacturing of building components employing industrial robots, gantry systems, and tethered autonomous vehicles. This article presents the current state-of-the-art in the subject of 3D printing of buildings and construction components. The purpose of this research is to describe the technical, socioeconomic, and environmental components of 3DCP of concrete structures in order to provide a comprehensive overview of the 3DCP technology, applications, challenges, and future research and market opportunities in the construction sector. This research focuses mostly on current breakthroughs in 3D concrete printing, as well as other research and development projects in this subject, notably its use in alien habitats. There are several advantages to using this strategy, including cost and time savings, decreased pollutants, and a reduction in accidents and fatalities on construction sites. Despite the various benefits and prospects, the results raise certain concerns, owing to the technology's existing limitations. According to this comprehensive review, researchers should examine the challenges such as on-site fabrication, large scale manufacturing process and limitations of 3D concrete printing further in order to increase mechanical performance, durability, and sustainability, as well as create appropriate standard criteria for printing structures.

Copper inks for printed electronics: a review.

Conductive inks have attracted tremendous attention owing to their adaptability and the convenient large-scale fabrication. As a new type of conductive ink, copper-based ink is considered to be one of the best candidate materials for the conductive layer in flexible printed electronics owing to its high conductivity and low price, and suitability for large-scale manufacturing processes. Recently, tremendous progress has been made in the preparation of cooper-based inks for electronic applications, but the antioxidation ability of copper-based nanomaterials within inks or films, that is, long-term reliability upon exposure to water and oxygen, still needs more exploration. In this review, we present a comprehensive overview of copper inks for printed electronics from ink preparation, printing methods and sintering, to antioxidation strategies and electronic applications. The review begins with an overview of the development of copper inks, followed by a demonstration of various preparation methods for copper inks. Then, the diverse printing techniques and post-annealing strategies used to fabricate conductive copper patterns are discussed. In addition, antioxidation strategies utilized to stabilize the mechanical and electrical properties of copper nanomaterials are summarized. Then the diverse applications of copper inks for electronic devices, such as transparent conductive electrodes, sensors, optoelectronic devices, and thin-film transistors, are discussed. Finally, the future development of copper-based inks and the challenges of their application in printed electronics are discussed.

Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19.

Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.

Aerosol printing and flash sintering of conformal conductors on 3D nonplanar surfaces

Printing techniques have been extensively studied as a promising route towards large-scale, low-cost and high-throughput manufacturing process for electronic devices. With the recently emerging applications in wearable electronics and customizable conformal electronics, it calls for the necessity to develop printed electronics that function on complex, 3D nonplanar architectures. In this study, aerosol printing and flash sintering of conformal conductors on nonplanar surfaces are demonstrated. Various printed patterns are fabricated by aerosol printing of conductive ink by copper nanoparticles (Cu NPs) on both planar and nonplanar surfaces. Pulsed flash light introduces rapid sintering of the printed Cu patterns in the ambient environment. For the nonplanar patterns, a back reflector is utilized to improve the uniformity of sintering. As a result, highly conductive customizable nonplanar Cu patterns with conductivity at 10%–12% of that of bulk Cu are obtained. Effects of different sintering conditions, including sintering voltage and mounting distance on the conductivity of sintered patterns are studied. For nonplanar patterns, conductivity values at different localized spots on the nonplanar rod are also investigated to evaluate the uniformity of nonplanar sintering. The processes of aerosol printing and flash sintering have provided a facile manufacturing route for conformal conductors on arbitrary nonplanar objects.