Single-step Process Research Articles

Tangential flow filtration for continuous processing of crystallized proteins

Protein crystallization has the potential to provide nearly pure protein products in a single processing step. Most previous studies of protein crystallization have used centrifugation for dewatering and washing the crystallized solids, but this approach would be difficult to adopt in continuous bioprocessing operations. This study provides the first demonstration that crystallized proteins can be successfully filtered using hollow fiber tangential flow filtration (TFF) modules. Experiments were performed with human serum albumin (HSA) crystallized by the addition of trivalent CeCl3, both with and without polyethylene glycol (PEG). Greater than 85 % protein yield was achieved using 4.5 mM CeCl3 in the presence of 3 wt% PEG with the crystallization occurring in less than 20 s, which is ideal for continuous processing. The addition of PEG had minimal effect on the crystallization yield, but it did lead to the formation of larger and denser crystals and a corresponding increase in the critical flux, which is the maximum value of the flux that causes minimal increase in the transmembrane pressure (i.e., minimal fouling). Filtration experiments performed at optimal conditions were successfully run for 24 h with the transmembrane pressure remaining below 5 kPa, demonstrating the feasibility of using continuous crystallization with tangential flow filtration for the purification of high value protein products.

Sketching feasibility of additively manufactured different size gradient conventional hollow capsular shells (HCSs) by selective laser sintering (SLS): From design to applications

Additive manufacturing (AM) is widely used to fabricate 3D printed objects from Computer-aided Design (CAD) prepared using the SolidWorks CAD modelling software. Different printing techniques are used to fabricate desired 3D objects; among all these techniques, it is widely accepted that SLS is one of the most effective methods of 3D printing for fabricating drug-loaded solid oral dosage forms (SODFs) in bulk quantities using the single-step process. Different SODFs, such as pills, miniprintlets, dual miniprintlets, and tablets, were fabricated with different sizes and shapes. In this study, for the first time, we introduce SLS-mediated hollow capsular shells (HCSs) with the help of the SLS 3D printing technique. This work aimed to explore the sinterability and feasibility of sketching HCSs using the SLS-mediated sintering technique with different marketed sizes of capsules ranging from 000 to 5. Here, we have utilized Kolliphor P 188 (KP 188) and Kollidon SR (KSR) in a 1:1 ratio as a matrix-forming agent and 1% charcoal as a laser absorption-enhancing material. In accordance with the CAD models, we have fabricated the gradient conventional different sizes of HCSs ranging from 000 to 5 using the constant printing parameters and composition. Fabricated all biobased HCSs were subjected to the assessment of mechanistic and physicochemical parameters using varied analytical tools. In the current study, tartrazine dye is used to assess the release pattern from HCSs, which resulted in the modified release pattern. The adapted approach will be the futuristic approach to replace animal-based gelatin capsules with pharmaceutical-grade polymer-based HCSs with a modified release with optimum mechanical strength.

A Drop-and-Drain Method for Convenient and Efficient Fabrication of MOF/Fiber Composites.

The fabrication of flexible composites by integrating metal-organic frameworks (MOFs) with flexible substrates is a critical strategy for developing advanced materials with excellent feasibility and processability. These flexible MOF-based composites play a particularly important role in the separation and purification processes. However, several drawbacks remain challenge to overcome such as long processing time, high-cost, complicated processes, or harsh reaction conditions. In this paper, a convenient and efficient method is reported for fabricating MOF/fiber composites using a simple drop-and-drain (D&D) process. By exploiting the electrostatic interactions between the positively charged MOF particles and negatively charged fiber-based flexible substrates, a uniform coating of MOF on flexible fibers are achieved. This is accomplished by allowing the MOF ink to drop and drain through a substrate using a custom-made Teflon cell. Additionally, the D&D method enables the production of multiple layers of composites in a single-step process. UiO-66 and ZIF-8 submicroparticles and various substrates such as cotton-pad, cotton-fabric, nylon-fabric, PET-fabric, and filter-paper are employed to create flexible MOF/fiber composites. These composites demonstrate outstanding capacities for capturing negatively charged organic dyes, including methyl orange and indigo carmine. Furthermore, the MOF/fiber composites can be reused for dye capture after a simple washing process.

In Situ Probing the Crystallization Kinetics in Gas‐Quenching‐Assisted Coating of Perovskite Films

AbstractThe pursuit of commercializing perovskite photovoltaics is driving the development of various scalable perovskite crystallization techniques. Among them, gas quenching is a promising crystallization approach for high‐throughput deposition of perovskite films. However, the perovskite films prepared by gas‐quenching assisted blade coating are susceptible to the formation of pinholes and frequently show inferior crystallinity if the interplay between film coating, film drying, and crystallization kinetics is not fully optimized. That arguably requires a thorough understanding of how single processing steps influence the crystallization kinetics of printed perovskite films. Here, in situ optical spectroscopies are integrated into a doctor‐blading setup that allows to real‐time monitor film formation during the gas‐quenching process. It is found that the essential role of gas quenching treatment is in achieving a smooth and compact perovskite film by controlling the nucleation rate. Moreover, with the assistance of phase‐field simulations, the role of excessive methylammonium iodide is revealed to increase grain size by accelerating the crystal growth rate. These results show a tailored control of crystal growth rate is critical to achieving optimal film quality, leading to fully printed solar cells with a champion power conversion efficiency of 19.50% and mini solar modules with 15.28% efficiency are achieved.

Femtosecond-laser direct-write photoconductive patterns on tellurite glass

We report the formation of arbitrary photoconductive patterns made of tellurium (Te) nanocrystals by exposing a tellurite (TeO2-based) glass to femtosecond laser pulses. During this process, Te/TeO2-glass nanocomposite interfaces with photoconductive properties form on the tellurite glass substrate. We show that these laser-written patterns exhibit a photoresponse, from the near ultraviolet (263 nm) to the visible spectrum, stable over a few months. Specifically, high responsivity (16.55 A/W) and detectivity (5.25 × 1011 Jones) of a single laser-written line pattern are measured for an illumination dose of 0.07 mW/cm2 at 400 nm. This work illustrates a pathway for locally turning a tellurite glass into a functional photoconductor of arbitrary shape, without adding materials and using a single laser process step. Published by the American Physical Society 2024

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts.

N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense, this new method creates two C-N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste.

Orthotropic organization of a cellulose nanocrystal suspension realized via the combined action of frontal ultrafiltration and ultrasound as revealed by in situ SAXS

HypothesisRodlike cellulose nanocrystals (CNCs) exhibit significant potential as building blocks for creating uniform, sustainable materials. However, a critical hurdle lies in the need to enhance existing or devise novel processing that provides improved control over the alignment and arrangement of CNCs across a wide spatial range. Specifically, the challenge is to achieve orthotropic organization in a single-step processing, which entails creating non-uniform CNC orientations to generate spatial variations in anisotropy. ExperimentsA novel processing method combining frontal ultrafiltration (FU) and ultrasound (US) has been developed. A dedicated channel-cell was designed to simultaneously generate (1) a vertical acoustic force thanks to a vibrating blade at the top and (2) a transmembrane pressure force at the bottom. Time-resolved in situ small-angle X-ray scattering permitted to probe the dynamical structural organization/orientation of CNCs during the processing. FindingsFor the first time, a typical three-layer orthotropic structure that resembles the articular cartilage organization was achieved in one step during the FU/US process: a first layer composed of CNCs having their director aligned parallel to the horizontal membrane surface, a second intermediate isotropic layer, and a third layer of CNCs with their director vertically oriented along the direction of US wave propagation direction.

Electrochemical investigations on cathodic reduction processes at graphite electrode in LiCl-KCl eutectic melt

Sequence of redox processes in LiCl-KCl eutectic at graphite electrode was studied in temperature range 698-798 K using cyclic voltammetry and electrochemical impedance spectroscopy. There were two reduction steps observed when potential was scanned from −0.25 to −1.50 V (vs.▪); a single-step two-electron transfer process due to reduction of carbon to ▪ followed by reduction of ▪. Electrolysis at −1.20 V at 773 K led to formation of ▪ on graphite surface. Complex impedance data were modelled using equivalent circuits and it was established that ▪ film formed around graphite electrode restricting both diffusion of ▪ in melt and metallic ▪ into graphite framework. These results are relevant in terms of their consequences in molten salt electrorefining of metal fuels.

Additively manufactured vacuum grippers for the flexible handling and assembly of hairpin coils in electric motor production

Hairpin technology has recently become the predominant winding technology for the manufacturing of stators used in electric traction motors. In contrast to conventional winding techniques, the manufacturing process chain is based on rectangular wire which is bent into a three-dimensional U-shape – so-called hairpin coils. These hairpin coils have to be individually gripped and assembled to form the stator winding. There can be hundreds of hairpin coils in a single stator, which can also differ in shape. Therefore, gripping and moving the individual hairpin coils is a challenging task in terms of flexibility and cycle time. This paper presents an approach to meet the outlined requirements using additively manufactured vacuum grippers. A concept is investigated in which the vacuum is generated in a conventional vacuum ejector and fed to the vacuum gripper via hose lines. In contrast, the concept of a functionally integrated vacuum gripper manufactured by a new laser-sintering process with automated continuous fibre reinforcement is presented. Based on the laser-sintering process, a lightweight vacuum gripper with an integrated vacuum ejector can be manufactured in a single process step without additional costs for purchased parts. After a review of the state of the art in both hairpin-specific and additively manufactured lightweight grippers, experimental test series are carried out concerning the vacuum quality and the grip strength of the different vacuum gripper designs. Pull-off tests show that high holding forces of several Newtons are possible proving the basic usability of vacuum grippers for hairpins, even though the achievable vacuum quality of the functionally integrated vacuum gripper is lower than that of the conventional ejector. Comparison of the novel approaches with a conventional mechanical hairpin gripper regarding weight, production costs and production time show promising improvements.

Improved wear resistance of AISI-4340 steel by Ti–Nb–C–N and MoS2 composite coating by cathodic cage plasma deposition

A cathodic cage plasma deposition (CCPD) system was used to deposit titanium-niobium-carbon-nitrogen (Ti–Nb–C–N) and molybdenum-disulfide (MoS2) composite coating with a modification in the lid of the cathodic cage by inserting composite material rings in the holes. For this purpose, the combination of mixed material rings made up of (80 % TiO2+10 % graphite and 10 % Nb2O5) and 100 % MoS2 were uniformly inserted into the cage lid holes. The nano-hardness of untreated steel (2.7 GPa) was upgraded to 9.3, 11, and 12.4 GPa by composite coating at 300, 350, and 400 °C, respectively. The coating comprised TiN, Ti2N, NbN, NbC, and MoS2 phases, irrespective of the processing temperature. The thickness of the composite coating was 10.5, 13.8, and 18.6 μm. The wear volume (245 × 10−6 mm3) was reduced significantly in each condition, specifically at 400 °C temperature (∼0.1 × 10−6 mm3). The friction coefficient was smoother and lower by coating deposition, whereas the machining temperature during the wear test was reduced. The novelty of this work is that besides improving hardness, wear resistance is also improved due to the self-lubrication performance of the composite coating. In addition, the coating deposition by this system is a single-step process; less treatment time is required, and treatment is relatively low-cost.

Ruthenium-catalysed direct C-H amidation of 4-aryl-pyrrolo[2,3-d]pyrimidines with acyl/phosphoryl azides.

A ruthenium-catalysed arene ortho C-H amidation of 4-aryl-pyrrolo[2,3-d]pyrimidine derivatives with acyl azides or phosphoryl azides as the nitrogen sources toward C-N bond formation was developed. This protocol could offer a novel and direct approach to access a series of amidated and phosphoramidated pyrrolo[2,3-d]pyrimidine derivatives in moderate to good yields, thereby evading the general Curtius rearrangement. The protocol features significant functional group tolerance and a single-step process, with the release of only innocuous molecular nitrogen as the byproduct.

Separation of platelets by size in a microfluidic device based on controlled incremental filtration.

The significant biological and functional differences between small and large platelets suggested by recent studies could have profound implications for transfusion medicine. However, investigating the relationship between platelet size and function is challenging because separating platelets by size without affecting their properties is difficult. A standard approach is centrifugation, but it inevitably leads to premature activation and aggregation of separated platelets. This paper describes the development and validation of a microfluidic device based on controlled incremental filtration (CIF) for separating platelets by size without the cell damage and usability limitations associated with centrifugation. Platelet samples derived from whole blood were used to evaluate the dependence of the CIF device separation performance on design parameters and flow rate, and to compare the properties of PLT fractions generated by the CIF device with those produced using a centrifugation protocol in a split-sample study. This was accomplished by quantifying the platelet size distribution, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet activation before and after processing for all input and output samples. The 'large platelet' fractions produced by the CIF device and the centrifugation protocol were essentially equivalent (no significant difference in MPV and P-LCR). Platelets in the 'small platelet' fraction produced by the CIF device were significantly smaller than those produced by centrifugation (lower MPV and P-LCR). This was because the CIF 'small platelet' fraction was contaminated by much fewer large platelets (∼2-times lower recovery of >12 fL platelets) and retained the smallest platelets that were discarded by the centrifugation protocol. There was no significant difference in platelet activation between the two methods. However, centrifugation required a substantial amount of additional anticoagulant to prevent platelet aggregation during pelleting. Unlike centrifugation, the CIF device offered continuous, flow-through, single-step processing that did not cause platelet aggregation. Such a capability has the potential to accelerate the basic studies of the relationship between platelet size and function, and ultimately improve transfusion practice, particularly in the pediatric setting, where the need for low-volume, high-quality platelet transfusions is most urgent.

Utilization of charged microdroplets for the controlled rapid synthesis of hollow sodium chloride single crystals.

Charged microdroplets are favored in microfluidic control, biomedicine, chemistry and materials processing due to their unique physicochemical environment, including interface double layers, high electric fields, surface concentration enrichment, and more. Herein, we investigated the crystallization of charged sodium chloride microdroplets and achieved the formation of hollow single crystals in a single-step process lasting only a few seconds, without the use of templates. Additionally, we discussed the plausible crystal growth mechanism, which appears to be an unconventional outward-inward growth process.

Phenylboronate-salicylate ester cross-linked self-healing hydrogel composed of modified hyaluronan at physiological pH.

Several hydrogels with boronate/diol ester cross-linking have been reported. However, multiple synthetic steps or expensive reagents are required to modify some diol moieties into polymers. Therefore, diol-modified polymers, which are easily and inexpensively prepared via a single-step process, are required for the formation of boronate esters. This study reports a novel hydrogel composed of phenylboronic acid-modified hyaluronic acid and salicylic acid-modified hyaluronic acid. This hydrogel is injectable, can self-heal at physiological pH, and can be easily and inexpensively prepared. The polymer system behaved as a sol at pH 12.0 and a weak gel at pH 9.4 and 11.2, whereas it behaved as a gel over a wide pH range of 4.0-8.2. The viscoelasticity of the system decreased in response to sugar at pH 7.3. Thus, salicylic acid can be considered a promising diol moiety for hydrogel formation via boronate ester cross-linking.

Bolometric IR photoresponse based on a 3D micro-nano integrated CNT architecture.

A new 3D micro-nano integrated M-shaped carbon nanotube (CNT) architecture was designed and fabricated. It is based on vertically aligned carbon nanotube arrays composed of low-density, mainly double-walled CNTs with simple lateral external contacts to the surroundings. Standard optical lithography techniques were used to locally tailor the width of the vertical block structure. The complete sensor system, based on a broadband blackbody absorber region and a high-resistance thermistor region, can be fabricated in a single chemical vapor deposition process step. The thermistor resistance is mainly determined by the high junction resistances of the adjacent aligned CNTs. This configuration also provides low lateral thermal conductivity and a high temperature coefficient of resistance (TCR). These properties are advantageous for new bolometric sensors with high voltage responsivity and broadband absorption from the infrared (IR) to the terahertz spectrum. Preliminary performance evaluations have shown current and voltage responsivities of 2 mA/W and 30 V/W, respectively, in response to IR (980 nm) absorption for a 20 × 20 μm2 device. The device exhibits an exceptionally fast response time of ≈0.15 ms, coupled with a TCR of -0.91 %/K. These attributes underscore its high operating speed and responsivity, respectively. In particular, the device maintains excellent thermal stability and reliable operation at elevated temperatures in excess of 200 °C, extending its potential utility in challenging environmental conditions. This design allows for further device miniaturization using optical lithography techniques. Its unique properties for mass production through large-scale integration techniques make it important for real-time broadband imaging systems.

Low-loss grating coupler with a subwavelength structure on a thin-film lithium niobate substrate.

We demonstrated a low-loss O-band grating coupler on an x-cut thin-film lithium niobate substrate by implementing subwavelength and apodized structures. The subwavelength gratings were used to mitigate the refractive index discontinuity between the input taper and grating region, which was the first application of such a structure for grating coupler optimization on a thin-film lithium niobate substrate. The coupling efficiency was measured to be -1.99 dB/coupler at a wavelength of 1312.8 nm, which was the lowest loss among the reported lithium niobate grating couplers that do not use metal mirrors. The proposed design does not require metal mirrors or any additional material layers and can be easily fabricated with a single-step lithography and etching processes.

Realizing one-step two-electron transfer of naphthalene diimides via a regional charge buffering strategy for aqueous organic redox flow batteries.

Naphthalene diimide derivatives show great potential for application in neutral aqueous organic redox flow batteries (AORFBs) due to their highly conjugated molecular structure and stable two-electron storage capacity. However, the two-electron redox process of naphthalene diimides typically occurs via two separate steps with the transfer of one electron per step ("two-step two-electron" transfer process), which leads to an inevitable loss of voltage and energy. Herein, we report a novel regional charge buffering strategy that utilizes the core-substituted electron-donating group to adjust the redox properties of naphthalene diimides, realizing two electron transfer via a single-step redox process ("one-step two-electron" transfer process). The symmetrical battery testing of NDI-DEtOH revealed exceptional intrinsic stability lasting for 11 days with a daily decay rate of only 0.11%. Meanwhile, AORFBs with NDI-DMe/FcNCl and NDI-DEtOH/FcNCl exhibited a remarkable 40% improvement in peak power density at 50% state of charge (SOC) in comparison to NDI/FcNCl-based AORFBs. In addition, the battery's energy efficiency has increased by 24%, resulting in much more stable output power and significantly improved energy efficiency. These results are of great significance to practical applications of AORFBs.

Self-assembled monolayer of poly(o-phenylenediamine)/silver core-shell hybrid-based enzyme-free impedimetric glucose sensor for blood samples.

A core-shell hybrid of poly(o-phenylenediamine)/silver was prepared by a simple single-step process and self-assembled on a glassy carbon electrode to design an enzyme-free electrochemical glucose sensor. The working electrode was fabricated by self-assembling a dimethyl sulfoxide (DMSO) solution of the prepared hybrid on a glassy carbon electrode. The electrochemical properties of the fabricated electrode were analyzed by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in an aqueous potassium chloride electrolyte containing the [Fe(CN)6]3-/4- redox couple. The electrochemical sensing responses towards varying concentrations of glucose were studied by CV and EIS in the same redox electrolyte medium. The poly(o-phenylenediamine)/silver core-shell hybrid-based sensor was found to show a reliable response in the EIS experiment over the CV experiment. By analyzing the EIS sensing responses, the experimental limit of detection was determined to be 10 μL of ∼80 mg per dL glucose solution in 25 mL of 1 (M) KCl electrolyte containing the 10-3 M [Fe(CN)6]3-/4- redox couple with a sensitivity of 298 Ω mg-1 dL cm-2. Excellent selectivity towards glucose was confirmed over various bioactive interfering biomolecules like ascorbic acid, dopamine, uric acid, lactose, fructose and sucrose. The glucose content in the human blood sample was verified by the designed sensor with almost 100% recovery.

Single-step synthesis of ternary metal chalcogenides (sf-CuInS2 and sf-CuInSe2) stripped off the organic cover and their use as a catalyst for symmetric Glaser-Hay coupling reactions.

Generally, inorganic nano/microparticles produced by chemical routes are covered by organic surfactants or polymers to control their agglomeration during their synthesis. However, these surfactants and polymers negatively affect their catalytic activity because these molecules mask the surface. This work presents the synthesis of surfactant-free CuInS2 and CuInSe2 (sf-CuInS2 and sf-CuInSe2) nano/microparticles through simple reactions without surfactant or polymer coatings using LiBH4 under a thermodynamically favourable condition. These reactions are rare observations of a single-step process to produce ternary metal chalcogenides without any template assistance. We have also demonstrated efficient catalysis by sf-CuInS2 nanoparticles in the coupling reaction of substituted phenylacetylenes. We tested it as catalysts in dimerizing 1,3-diyne derivatives while using 8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base. These Glassar-Hay coupling reactions are conducted at room temperature in acetonitrile (4-7 h, depending on the substrate) using 10 mg of sf-CuInS2. The maximum yield obtained in these reactions is 97%, while the catalyst is reusable for five cycles with little difference in its ability to catalyse. The effectiveness of the catalyst is credited to the availability of a free catalytic surface.

Sequential nucleophilic aromatic substitutions on cyanuric chloride: synthesis of BODIPY derivatives and mechanistic insights.

Herein we report a study on the sequential substitution of different nucleophiles on cyanuric chloride to obtain potential candidates for metal sensors (5a-c). The set of nucleophiles on the 1,3,5-triazine ring includes a phenolic BODIPY, an aminoalkyl pyridine and aminoalkyl phosphoramidates, each one designed to play a specific role in the final fluoroionophore. Three new triazine triads were synthesized in similar yields: 5a (45%), 5b (43%) and 5c (52%) after a methodical sequential combination of the nucleophiles via thermodependent nucleophilic aromatic substitution of the three chlorine atoms of cyanuric chloride. To ratify the synthetic results we simulated the reaction mechanisms for the different nucleophiles, aiming to address the distinctive orthogonality and temperature control inherent in this process, identifying and providing a sound rationale for any preferential sequence of nucleophiles inserted into the triazine core. According to our experimental and computational analysis (thermo- and kinetic preferences), we have identified the following preferential order for the sequential substitution: p-hydroxybenzaldehyde > 2-(pyridin-2-yl)ethanamine > aminoalkyl phosphoramidate, indicating that all steps follow a single-step process (concerted) in two stages, where nucleophilic addition precedes leaving group dissociation. The Meisenheimer σ-complex was identified as a transition state structure, with insufficient stability to exist as an intermediate. We observed a consistent and progressive increase in barrier height: 2-8 kcal mol-1 for the first step, 9-15 kcal mol-1 for the second step, and >15 kcal mol-1 for the third substitution. These findings align with the experimental observation of thermodependency in the sequential substitution.