High-yield Process Research Articles

High-Yielding Process for the Synthesis of Hydroxychloroquine under Concentrated Conditions: Nucleophilic Amination of Chloropyridines Promoted by Dimethyl Sulfoxide or Catalyzed by 3,5-Bis(trifluoromethyl)phenol

High-Yielding Process for the Synthesis of Hydroxychloroquine under Concentrated Conditions: Nucleophilic Amination of Chloropyridines Promoted by Dimethyl Sulfoxide or Catalyzed by 3,5-Bis(trifluoromethyl)phenol

High -yield Fabrication of Thin Glass Interposers

Thin glass substrates with through vias (TGV) have excellent properties for a new generation of interposers. Glass has a large bulk resistance and low loss at high frequency (RF, mmWave). Physically, it is moisture insensitive, highly dimensionally stable, and has a thermal expansion coefficient that can be tailored to match silicon. The surface of as-received glass has roughness below 1 nm, like silicon wafers, and thus supports fine line/space patterning and advanced processes like damascene. A key focus of our current work involves metallizing thin glass interposers with TGVs, including both copper electroplating of TGVs and patterning of redistribution layers. We demonstrate void-free fill for vias ranging from in aspect ratio from 2:1 to 8:1, in a bottoms-up process like that used for through silicon vias. The vias are hermetic by helium leak detection, even after annealing in some cases to 450C. Since thin (≤ 200 micron) free-standing glass substrates are difficult to handle in current fabs, we discuss an advanced temporary bond approach using silicon or glass handles which enables high-yield processing. The bond is robust to temperatures exceeding 400 °C, and creates handle/glass stacks with total thickness variation (TTV) similar to that of a silicon wafer. The end result is a bonded pair that can be processed like a silicon wafer, with a simple mechanical debond to yield the processed thin glass. We discuss the bond and debond processes, showing the ability to control the bond strength. Data on the bonded glass stack resistance to various processing steps will also be shown.

Crystallization of sucrose by using microwave vacuum evaporation

Sucrose crystallization was performed by using a custom designed microwave vacuum evaporation system. Process was designed to mimic a semi-batch crystallization starting from beet syrup concentration to crystal slurry formation. The effect of microwave power and feeding time on the process yield and product attributes (particle size, solution color and turbidity) were investigated. Microwave treatment was shown to affect the sucrose crystal morphology and the quality parameters significantly. Process yield was significantly affected by both crystallization power and feeding time (p < 0.05). Longer feeding time (15 min) and medium microwave power (30%) resulted in the highest process yield (∼55%). The results revealed that microwave processing can be a promising alternative over commercial crystallization.

Gum arabic and soy protein concentrate as binding agents on quality and nutritional properties of mushroom-based sausage analogues

Replacement of meat in meat-reduced analogue products is difficult because of the functional properties of meat. The effect of binding agents (gum Arabic and soy protein concentrate) on the quality characteristics and nutritional properties of mushroom-based sausage analogues was investigated at different concentrations (0–3%), using 20% button mushrooms and 60% lean meat. Mushroom-substituted sausages containing either gum Arabic or soy concentrate had significantly higher (p < 0.05) proximate composition (protein, fat, ash and fibre content) than the controls without gum Arabic or soy concentrate. On physical properties, mushroom-substituted sausages with gum Arabic or soy concentrate had lower (p < 0.05) diameter and length shrinkage and cook loss compared with the control samples. Process yield, water holding capacity (WHC), and oil holding capacity (OHC) increased with the increase of either gum Arabic or soy concentrate. However, 2% gum Arabic/ soy concentrate samples had the lowest cooking loss, highest process yield, WHC, and OHC. Treatments containing gum Arabic and soy concentrate recorded lower (p < 0.05) total coliform counts than the control sausages, demonstrating antimicrobial properties of the binders. For all the parameters, gum Arabic or soy concentrate increased the sensory scores, although treatments with 2% and 2.5% gum Arabic or 2% soy concentrate had significantly higher (p < 0.05) hedonic scores than the controls and the treatments with 3% soy concentrate. The study demonstrated that gum Arabic and soy concentrate can be used as binders to modulate the functional properties of mushroom-based sausage analogues. This could lead to the development of healthier meat-reduced sausages.

Novel lansoprazole/glycyrrhizin spray dried complex: Physiochemical properties, photostability, and anti-ulcer activity on rats

Lansopraole (LNS) is one of the most frequently used anti-ulcer drug, but its poor aqueous solubility, low bioavailability, and instability limits its clinical application. In this study, glycyrrhizin (GLY), a natural complexing agent obtained from licorice was used to deliver lansoprazole (LNS) for the treatment of ulcer. LNS/GLY complexes with and without magnesium oxide (MgO) as an alkalizer were prepared using spray drying method in order to improve the release and stability of LNS, and examine its anti-ulcer effects on rats. Among three developed complexes (F1-F3), F3 complex (LNS/GLY (1:1.5 w/w, with MgO) was optimized with highest process yield (85.7 ± 2.3%) and drug content (91 ± 4.3%). The optimized spray-dried complex (F3) was further evaluated for DSC, FTIR, PXRD, SEM, photostability and in-vitro release studies. An enhanced drug release and improved photo-protection was confirmed by NMR studies. Further in-vivo anti-ulcer studies showed a significant alleviated macroscopic and microscopic stomach damage and reduction in hemorrhagic lesions and ulcer index.

Enhanced mechanical property through high-yield fabrication process with double laser scanning method in two-photon lithography

Two-photon lithography (TPL) is a representative fabrication process for micro 3D structures with a sub-micron fabrication resolution. As the TPL process is developed and commercialized, the TPL process requires higher process yield to be a considered reliable manufacturing technique for mass production. However, delamination is one of the main factors that reduce the yield of the TPL process. In this study, a double-step laser scanning method is proposed as a reliable high-yield TPS process to reduce the delamination effect. The method entails a simple process that polymerizes the initial interfacial layer between the structures and substrate twice. The additional laser scanning step induces a strong crosslinking in the polymer, and thereby preventing swelling and delamination. Furthermore, the effectiveness of the method is evaluated with large-scale microlens arrays. Although the process time is slightly increased, the process yield is significantly improved through the use of the double-step laser scanning method. Hence, the double-step laser scanning process can be employed as a reliable additive manufacturing process for various 3D microscale devices, and more importantly, it can be used to increase the manufacturing yield through the reduction of defects caused by surface delamination.

Detachable Optical Chiplet Connector for Co-Packaged Photonics

A key barrier to mainstream adoption of co-package photonics is a high-yielding and scalable assembly process. The current industry state-of-the-art for edge coupling is to attach fibers directly onto V-grooves etched into the silicon. With no ability for rework, any errors in this process will lead to loss of the entire package along with the expensive silicon committed to it. This problem is exacerbated by the yield compounding effect as the number of photonic chips on a package increases. In this paper, we discuss a novel approach to overcome this limitation. Our solution relies on a glass optical bridge with integrated waveguides and connector mechanical alignment features that can be attached to the photonics silicon at die level to produce a photonics module. The bridge attach can take place using existing V-grooves or alternate registration features in the silicon for alignment. Each photonic module is then tested to ensure it is known-good prior to committing it to the package, and overall yield is no longer compounded by the number of photonic modules on the package. Other benefits of this approach are the elimination of fiber pigtails which simplifies material handling in the manufacturing flow, and results in a fully detachable solution where the low-reliability fibers are no longer permanently attached to the expensive silicon. Low loss coupling was demonstrated using an optical bridge, with average losses from fiber into PIC of 1.41 dB. Average detachable connector losses of 0.33 dB were demonstrated along with integration into a photonic-electronic co-packaged assembly.

Optimization of radial extrusion and pellet coating processes using PAT approaches

FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant advancement that has emerged is the implementation of process analytical technology (PAT), which has opened doors for understanding and controlling complex technological processes. Two such processes, radial extrusion and pellet coating, offer a solid foundation for the application of PAT tools due to their numerous critical process parameters. The aim of the first part of the study was to optimize the neutral pellet production to produce the pellets with properties desired for successful film coating using design of experiments (DoE). In the second part the optimized pellets underwent film coating and the coating quantity was predicted in real or near real-time using in-line and at-line NIR probes and the performance of both probes was compared.The desired properties of the pellets, narrow particle size distribution, high sphericity and high process yield, were successfully achieved. Models for film coating quantity prediction using in-line and at-line NIR probe were successfully calibrated and tested by coating two additional batches. Despite the limited sample size for model calibration, at-line NIR exhibited excellent prediction performance and enabled accurate determination of process end-point. The coating quantity determined by UV/VIS spectroscopy in both test batches deviated by less than 2.0 % from the target value. However, the in-line NIR probe, primarily due to its inferior spectral resolution, displayed a slightly lower quality of the calibrated model and notable overprediction for the tested batches.

Advancements in salbutamol sulphate formulation: Spray-drying technique for the production of porous particles with enhanced properties for inhalation drug delivery

A fast, simple and cost-effective technique has been used to produce spray-drying porous particles of salbutamol sulfate (SS) for inhalation drug delivery. The particles were produced using water as solvent and ammonium bicarbonate as pore-forming agent. A full factorial experimental design (24) with a central point was used to evaluate the influence of process parameters (drying air inlet temperature, atomization air volume flowrate, feed volume flowrate and the pore-forming agent concentration) on process yield, moisture content, densities and particle size. In addition, particle morphology, in-vitro aerosolization properties, stability and cytotoxicity of selected samples were studied. Within the experimental design parameters window, it was shown that the highest inlet temperature and pore-forming agent concentration were the factors that more affected the process yield and tap density values. Particles with the lowest tap densities values exhibited porous morphology. In addition, the pore-forming agent concentration proved to be the most significant variable affecting particle size. The highest pore-forming agent concentration, the largest particle size. The porous particles exhibit remarkable aerosolization performance, surpassing the performance of previously reported SS porous particles and a commercial formulation. These powders showed a high process yield and the absence of ammonium bicarbonate in the final product, as confirmed by FT-IR. Furthermore, the powders presented good stability even over long periods of time and did not exhibit cytotoxicity on the murine alveolar macrophage cell line RAW 264.7.

Recombinant Human CD19 in CHO-K1 Cells: Glycosylation Patterns as a Quality Attribute of High Yield Processes.

CD19 is an essential protein in personalized CD19-targeting chimeric antigen receptor (CAR)-T cell-based cancer immunotherapies and CAR-T cell functionality evaluation. However, the recombinant expression of this "difficult to-express" (DTE) protein is challenging, and therefore, commercial access to the protein is limited. We have previously described the successful stable expression of our soluble CD19-AD2 fusion protein of the CD19 extracellular part fused with human serum albumin domain 2 (AD2) in CHO-K1 cells. The function, stability, and secretion rate of DTE proteins can be improved by culture conditions, such as reduced temperature and a shorter residence time. Moreover, glycosylation, as one of the most important post-translational modifications, represents a critical quality attribute potentially affecting CAR-T cell effector function and thus impacting therapy's success. In this study, we increased the production rate of CD19-AD2 by 3.5-fold through applying hypothermic culture conditions. We efficiently improved the purification of our his-tagged CD19-AD2 fusion protein via a Ni-NTA-based affinity column using a stepwise increase in the imidazole concentration. The binding affinity to commercially available anti-CD19 antibodies was evaluated via Bio-Layer Interferometry (BLI). Furthermore, we revealed glycosylation patterns via Electrospray Ionization Mass Spectrometry (ESI-MS), and five highly sialylated and multi-antennary N-glycosylation sites were identified. In summary, we optimized the CD19-AD2 production and purification process and were the first to characterize five highly complex N-glycosylation sites.

Oxymatrine Loaded Cross-Linked PVA Nanofibrous Scaffold: Design and Characterization and Anticancer Properties.

This study focuses on the fabrication, characterization and anticancer properties of biocompatible and biodegradable composite nanofibers consisting of poly(vinyl alcohol) (PVA), oxymatrine (OM), and citric acid (CA) using a facile and high-yield centrifugal spinning process known as Forcespinning. The effects of varying concentrations of OM and CA on fiber diameter and molecular cross-linking are investigated. The morphological and thermo-physical properties, as well as water absorption of the developed nanofiber-based mats are characterized using microscopical analysis, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. In vitro anticancer studies are conducted with HCT116 colorectal cancer cells. Results show a high yield of long fibers embedded with beads. Fiber average diameters range between 462 and 528nm depending on OM concentration. The thermal analysis results show that the fibers are stable at room temperature. The anticancer study reveals that PVA nanofiber membrane with high concentrations of OM can suppress the proliferation of HCT116 colorectal cancer cells. The study provides a comprehensive investigation of OM embedded into nanosized PVA fibers and the prospective application of these membranes as a drug delivery system.

Multipurpose active scanning probe cantilevers for near-field spectroscopy, scanning tunnel imaging, and atomic-resolution lithography

In this work, we report progress on developing a multipurpose scanning probe cantilever applying gallium nitride nanowires as the probe tip. Gallium nitride nanowires possess high potential as probes due to their straight profile, tunable electrical and optical properties, high Young’s Modulus, durability, and high-yield fabrication process. Their wide bandgap enables them to be pumped to emit ultraviolet pulses which can be used for optical imaging and spectroscopy. They can be doped during growth to be electrically conductive, and their sharp tips obtained during epitaxial growth enable confinement of a high electric field at tip–sample interface. Their sharp tips are obtained during fabrication by their epitaxial growth which eliminates the need for postprocess sharpening that is typically required for standard STM tips. We present results of using gallium nitride nanowires for scanning tunnel microscopy applications of atomic-resolution imaging and lithography, and atomic force microscopy applications of imaging and lithography in vacuum and atmospheric environments.

Impact of Spheroidization of Natural Graphite on Fast-Charging Capability of Anodes for LIB

Despite numerous research on new active materials for anodes, graphite remains the most commonly used material in Li-ion batteries. The spherical shape of the graphite particles has proven to be beneficial for application in electric vehicles, especially for fast charging. So far, the spheroidization of natural flake graphite is conducted by a rigid and inefficient cascade process. In this work, a scalable classifier system was used for spheroidization, and it was demonstrated that a spheroidization time of 15 min is sufficient to improve material properties and enhance electrochemical performance while maintaining high process yields of 55%. Insights into the influence of the morphology on the intrinsic and structural properties of the graphite particles and manufactured electrodes are provided. Spheroidization creates a more efficient pore network in the coating layer while reducing the internal resistance and increasing the surface area of the particles by a factor of 1.8. We demonstrate that the spherical shape improves the discharge rate capability by 1.8, and the specific charge capacity could be enhanced by more than 237% at a C-rate of 3. An additional carbon coating could significantly decrease the specific surface area and increase the specific capacity at high C-rates.

ASSESSMENT OF MORPHOLOGICAL TRAITS IN TOMATO HYBRIDS FOR IMPROVED CULTIVATION PRACTICES

Tomato is widely used as a vegetable and plays an important role in the diet for its health benefits. The present research was carried out at the vegetable section of Barani Agricultural Research Institute (BARI), Chakwal, Pakistan, during the summer season of 2022. The experimental material used for the present study comprised 8 genotypes of tomato. Plant material was collected from the vegetable section of the plant breeding and genetics department in BARI Chakwal. Indeterminate genotype used for morphological characterization was LITH-904, LITH-908, LITH-942, LITH-949, LITH-970, SANDEL-F1, SAHEL-F1, and ANNA-F1. These genotypes were analyzed based on different morphological parameters. The observations recorded were subjected to different statistical analyses, and significant variations were observed among all the genotypes. The advantages of hybrid tomato cultivars are uniformity in shape and size, increased vigor, early maturity, high-yield, and resistance to specific pests and pathogens. The growth characteristics varied significantly among different tomato hybrids. The present research was conducted to evaluate different indeterminate tomato hybrids through various qualitative and quantitative traits to boost the future breeding programs of tomatoes to develop new high-yielding varieties. High yield and good processing qualities are the pre-requisites for the general acceptance of the hybrid by the farmers and the end consumer.

Fixed Bed Batch Slow Pyrolysis Process for Polystyrene Waste Recycling

This study evaluates the potential of recycling polystyrene (PS) plastic wastes via a fixed bed (batch) slow pyrolysis reactor. The novelty lies in examining the reactor design, conversion parameters, and reaction kinetics to improve the process yield, activation energy, and chemical composition. PS samples were pyrolyzed at 475–575 °C for 30 min under 10–15 psi. Process yield and product attributes were evaluated using different methods to understand PS thermal degradation characteristics better. The results show that PS decomposition started within 2 min from all temperatures, and the total decomposition point of 97% at 475 °C at approximately 5 min. Additionally, analytical results indicate that the average necessary activation energy is 191 kJ/mol. Pyrolysis oil from PS was characterized by gas chromatography–mass spectrometry. The results show that styrene was produced 57–60% from all leading oil compounds (i.e., 2,4-diphenyl-1-butene, 2,4,6-triphenyl-1-hexene, and toluene), and 475 °C has the major average of conversion effectiveness of 91.3%. The results show that the reactor temperature remains the main conversion parameter to achieve the high process yield for oil production from PS. It is concluded that pyrolysis provides a sustainable pathway for PS waste recycling and conversion to value-added products, such as resins and polymers. The proposed method and analytical results are compared with earlier studies to identify directions for future studies.

Substantial thinning of melt-spun ribbons by an optimised and high-yield ball-milling process

Melt-spun Fe-based ribbons are widely used as the core of transformers and inductors due to their high flux density and low coercivity. However due to their high thickness (∼19 µm) these ribbons are prone to large eddy current losses at MHz frequencies. Despite low yield, ball milling has been widely used to break such ribbons down to thinner flakes to suppress the eddy current losses at high frequency. In this work, we demonstrated an optimized ball milling process with increased yield for flakes in the desired size range (2–4 µm). We have demonstrated that reducing pre milling annealing temperature from 450 to 350 °C increases the yield in desired size range from 2% to 5% and further increasing batch size from 10 to 20 g increases the yield to 21%. The coercivity of the milled flakes increases from 139 to 1352 A/m due to the ball milling process. A post-mill annealing at 350 °C in Ar atmosphere decreases the coercivity to 341 A/m. X-ray diffraction analysis showed no sign of crystallization during ball milling. The result presented here demonstrates an efficient approach to fabricate ultra-thin flakes out of soft magnetic ribbons for high-frequency applications.

Thermodynamic Control of Intramolecular Singlet Fission and Exciton Transport in Linear Tetracene Oligomers.

We newly synthesized a series of homo- and hetero-tetracene (Tc) oligomers to propose a molecular design strategy for the efficient exciton transport in linear oligomers by promoting correlated triplet pair (TT) dissociation and controlling sequential exciton trapping process of individual doubled triplet excitons (T+T) by intramolecular singlet fission. First, entropic gain effects on the number of Tc units are examined by comparing Tc-homo-oligomers [(Tc)n : n=2, 4, 6]. Then, a comparison of (Tc)n and Tc-hetero-oligomer [TcF3 -(Tc)4 -TcF3 ] reveals the vibronic coupling effect for entropic gain. Observed entropic effects on the T+T formation indicated that the exciton migration is rationalized by number of possible TT states increased both by increasing the number of Tc units and by the vibronic levels at the terminal TcF3 units. Finally, we successfully observed high-yield exciton trapping process (trapped triplet yield: ΦTrT =176 %).

Solid-state synthesis of Pt/C cathode catalysts for direct methanol fuel cells

In this study, we have used a facile and high-yield solid-state synthesis process to synthesize a highly dispersed and efficient Pt/C cathode catalyst for direct methanol fuel cell applications.

Depletion force optimization for high-purity gold nanotriangles prepared using different growth methods.

A homogeneous structural distribution in metal nanoparticle is commonly required for their application, and despite high-yield growth techniques, unavoidable structural heterogeneity remains a concern in metal nanoparticle synthesis. Gold nanotriangles (AuNTs) were synthesized using seed-mediated and seedless growth methods. Recent advancements in high-yield synthesis processes have enabled easy handling of AuNTs, which exhibit unique localized surface plasmon resonance characteristics due to their anisotropic triangular form. The flocculation and subsequent precipitation technique was used to purify AuNTs of different sizes synthesized using seed-mediated and seedless growth methods. The optimal conditions for obtaining high-purity AuNTs were explored by introducing a high concentration of cetyltrimethylammonium chloride. Additionally, the depletion force necessary for achieving high-purity AuNTs was calculated to reveal variations in the required depletion forces for AuNTs synthesized using different growth techniques. The alternations in the size distribution of AuNTs during the flocculation step were tracked using dynamic light scattering, and the surface charge of AuNTs synthesized through different growth methods was evaluated by ζ-potential. The high purity of the AuNTs produced using the seedless growth method required a larger depletion force than the seed-mediated grown AuNTs. The difference in the required depletion forces results from the difference in the electrostatic forces caused by the different growth methods.

Colloidal Quantum Dots: Synthesis, Composition, Structure, and Emerging Optoelectronic Applications

AbstractIn recent decades, quantum dots (QDs) with tunable bandgap, large absorption coefficient, high quantum yield, multiexciton effect, and easy solution processing have unparalleled advantages in photoelectric conversion. Optoelectronic devices based on QDs of different composition have made great progress. However, there is still a lack of reviews on comparing the optoelectronic application level of semiconductor quantum dots (SQDs), perovskite quantum dots (PQDs), and carbon quantum dots (CDs), and also rarely providing a comprehensive summary of photocatalysis. First, this review almost completely summarizes advantages and disadvantages of common synthesis methods for QDs, especially pointing out the importance of optimization strategies for preparing high‐quality QDs such as ligand engineering, ion exchange, and purification separation. Then, compositions of SQD, PQD, CD, and corresponding optoelectronic properties are introduced, respectively. Next, the strengths and weaknesses of the four QDs structures are compared in detail. Finally, the flourishing development in various optoelectronic applications is separately demonstrated, and development degree of SQDs, PQDs, and CDs is compared to discover the most suitable application scenarios for each. On these bases, bottlenecks and opportunities are also put forwarded, hoping to stimulate more breakthroughs in this field.