Continuous Processing Techniques Research Articles

Biobased, catalyst-free non-isocyanate polythiourethane foams: Highly dynamic nature affords fast reprocessability, extrudability and refoamability

We have developed a series of reprocessable, re-foamable, biobased, catalyst-free non-isocyanate polythiourethane (NIPTU) network foams crosslinked via the auto-oxidation of the pendant thiol groups into disulfides. Capitalizing on the interplay of fast ring-opening of cyclic thiocabonate to create linear backbones and slightly slower thiol auto-oxidation to create disulfide crosslinks, the gelling reaction synchronized well with the vaporization of the physical blowing agent. Different physical blowing agents were used to achieve facile tunability of morphological and physical properties. In addition, incorporating a small amount of trifunctional crosslinker significantly enhanced the compressive mechanical properties of the foam. Moreover, we leveraged the rapid and catalyst-free disulfide dynamic exchange to achieve both reprocessability and extrudability of the NIPTU foams. We demonstrated that the foams are intrinsically self-healable and reprocessable by compression molding. We observed rapid stress relaxation at temperatures above 160 °C, prompting us to explore continuous processing techniques like extrusion and pseudo-injection molding. Spent foams can be extruded into bulk films at 180 °C with excellent property retention. Additionally, with our NIPTU system we demonstrated, for the first time, foam-to-foam recycling of non-isocyanate polyurethanes. By adding a small amount of sodium bicarbonate blowing agent into the spent foams prior to extrusion, CO2 gas was generated during extrusion, leading to a cellular structure. This work highlights the advantages of NIPTU foams: the catalyst-free, rapid synthesis of foams and property tunability, self-healing capability, and amenability towards a family of reprocessing techniques including compression molding, extrusion into bulk films, and foam-to-foam extrusion.

R2R‐Based Continuous Production of Patterned and Multilayered Elastic Substrates with Liquid Metal Wiring for Stretchable Electronics

AbstractThe roll‐to‐roll (R2R) process for fabricating elastic substrates is essential for the social implementation of next‐generation stretchable devices with soft interfaces. In recent years, there is a growing demand for soft heterostructures with multiple monolithically patterned organic materials. However, a continuous processing technique for substrates with heterostructures patterned using highly stretchable wiring has not yet been developed. Conventional manufacturing methods for stretchable electronics lack production capacity. This study introduces an R2R‐based method for the continuous production of multilayered substrates composed of various elastic materials, integrated with liquid metal (LM) wiring, suitable for stretchable electronics. Continuous fabrication of polymer films is achieved with pattern areas as small as 0.78 mm2, using three different polymers varying in hardness. The R2R coating process, paired with liquid metal wiring dispensing printing, allows for the creation of lines as fine as 140 microns. This process supports the batch production of 15 stretchable hybrid devices at a time and enables the creation of large‐area devices up to 400 cm2. The fabrication technique developed herein holds promise for the future manufacturing of not only stretchable electronics but also cutting‐edge soft electronics like smart packaging. This is expected to be a factor leading to the commercialization of stretchable electronics.

Chemical control of the aromatic disulfide exchange kinetics for tailor-made epoxy vitrimers

Aromatic disulfides containing epoxy vitrimers are one of the most versatile materials and the top candidates for employment in industrial applications, as they offer many advantages compared to other existing vitrimers (scalability, simplicity, easy processing and excellent mechanical properties) and their use in industrial applications is straight forward. The capability of tuning the mechanical and dynamic properties of vitrimers is one of the most explored fields in vitrimer materials. Herein we present tailor-made aromatic disulfide containing epoxy vitrimers trough the understanding of the effect of having: i) different hardener structure (Ortho or Para); ii) free pending amine groups or; iii) catalyst in the system. Our study shows that the relaxation time is highly dependent on regioisomerism of the aromatic hardener, stoichiometry and presence of catalyst. In the present study we found that equivalent Ortho and Para vitrimers show huge difference in the activation energy (Ea) ranging from 200 kJ/mol for Para vitrimers up to 350 kJ/mol for Ortho vitrimers. In the absence of free pending amine groups, the exchange kinetics are slowed down limiting their use for continuous processing techniques. In contrast, both free pending amine groups and imidazole catalyst permit to reduce the stress relaxation time ending up in relaxation times below 5 s at 180 °C. These results confirm the high tuning capability of aromatic disulfide containing epoxy vitrimers providing a methodology to tune the dynamic properties to design the right vitrimer for the right application and processing technology.

Continuous Processing of Cellulose Nanofibril Sheets Through Conventional Single-Screw Extrusion

Extrusion-based processes are one of the most widely used continuous polymer processing techniques because of their commercial availability, versatility, and cost-effective scalability. For these r...

Abstract B45: High-throughput label-free isolation and expansion of circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients for personalized treatments

Abstract Background: Circulating tumor cell (CTC) clusters are emerging as clinically significant harbingers of metastases in solid organ cancers. Prior to engaging these CTC clusters in animal models of metastases, it is imperative for technology to identify them with high sensitivity. These clusters often present heterogeneous surface markers, and current methods for isolation of clusters may fall short. Methods: We have applied the inertial microfluidic Labyrinth device for high-throughput, biomarker-independent, size-based isolation of CTCs and CTC clusters from patients with metastatic non-small cell lung cancer (NSCLC). Results: Using the Labyrinth device, CTCs (PanCK+/DAPI+/CD45-) were isolated from metastatic NSCLC patients (n=25). Heterogeneous CTC populations were detected, including CTCs expressing epithelial (EpCAM), mesenchymal (vimentin), or both markers. CTCs were isolated from 100% of patients (417±1023 CTCs/mL), and CTCs that were EpCAM negative were significantly higher in numbers than EpCAM+ CTCs. Cell clusters of ≥2 CTCs were observed in 96% of patients, of which 75% were negative for EpCAM. Patients with higher number of CTC clusters than single CTCs had worse progression-free survival (PFS) (p=0.05). Recovered CTCs from patients with RET, ROS1, and ALK-rearranged tumors revealed identical genetic aberrations as the primary tumor for each gene using FISH analysis. We have successfully expanded the recovered CTCs from 2 patients and screened for therapeutic targeting. We have found that TPX-0005 might be effective in these patients and would direct them to a clinical trial using this compound. Conclusions: The label-free Labyrinth device demonstrated the capability of collecting recovered CTCs from the device using a continuous processing technique while in a suspension state. This advantage opens the opportunities not only for CTC expansion off-chip, but also for ex vivo drug testing to direct patient-specific therapies. Citation Format: Mina Zeinali, Wei Huang, Maggie Lee, Arthi Nadhan, Anvya Mathur, Casey Hedman, Eric Lin, Ramdane Harouaka, Max S. Wicha, Lili Zhao, Nallasivam Palanisamy, Mathias Hafner, Rishindra Reddy, Gregory P. Kalemkerian, Bryan J. Schneider, Khaled A. Hassan, Nithya Ramnath, Sunitha Nagrath. High-throughput label-free isolation and expansion of circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patients for personalized treatments [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B45.

Abstract 1332: High Throughput isolation and expansion of circulating tumor cells (CTCs) from Non-small cell lung cancer (NSCLC) patients for personalized treatments

Abstract Background: Circulating tumor cells (CTCs) have emerged as important blood-based surrogate markers of primary tumors. Current methods for isolation of lung CTCs mostly rely on biomarker dependent antibody-based capture, missing populations that may be stem-like in nature. Results: We have applied the microfluidic Labyrinth device for high throughput, label-free, size-based isolation of CTCs from non-small cell lung cancer patients (NSCLC). The Labyrinth device was optimized and tested for inertial separation of cancer cells using the human lung cancer cell line H1650. The recovery and purity were >82% and >78%, respectively, operating at a flow rate of 2.5 mL/min. Using the biomarker-independent Labyrinth separation device, heterogeneous CTC populations were isolated from metastatic NSCLC patients (n=21). Heterogeneous CTC populations were detected, including CTCs (PanCK+ and CD45-), CTCs expressing EpCAM or Vimentin, and CTCs expressing both markers representing an EMT-like population of CTCs. Using Labyrinth, we were able to isolate CTCs from 100% of patients with an average yield of 180±168 CTCs/mL. Among the captured CTCs, EpCAM- CTCs were significantly more common than EpCAM+ CTCs (115.7 vs. 39.1 CTCs/mL respectively). Cell clusters of 2 or more CTCs were also observed in 95% of patients; 79% of these clusters were negative for EpCAM expression, whereas 35% expressed Vimentin, suggestive of an EMT phenotype. Recovered CTCs from patients with RET, ROS1 and ALK rearranged tumors showed aberrations matching with the primary tumor for each gene using FISH analysis. We have successfully expanded the recovered CTCs from 2 patients and screened for therapeutic targeting. We have found that TPX-0005 might be effective in these patients and would direct them to a clinical trial using this compound. Conclusion: The label-free Labyrinth device demonstrated the capability of collecting recovered CTCs from the device using a continuous processing technique while in a suspension state. This advantage opens the opportunities not only for CTC expansion off-chip, but also for ex-vivo drug testing to direct patient-specific therapies. Citation Format: Mina Zeinali, Maggie Lee, Arthi Nadhan, Anvya Mathur, Wei Huang, Eric Lin, Ramdane Harouaka, Max S. Wicha, Nallasivam Palanisamy, Mathias Hafner, Rishindra Reddy, Gregory P. Kalemkerian, Bryan J. Schneider, Khaled A. Hassan, Nithya Ramnath, Sunitha Nagrath. High Throughput isolation and expansion of circulating tumor cells (CTCs) from Non-small cell lung cancer (NSCLC) patients for personalized treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1332.

Manufacturing of tungsten and tungsten composites for fusion application via different routes

Tungsten is a refractory metal with the highest melting point of all metals, which is considered as a promising candidate material for plasma-facing materials in the future fusion reactor. However, tungsten faces several challenges from intrinsic embrittlement, irradiation embrittlement and recrystallization embrittlement during the operation of the fusion reactor. To satisfy the fusion engineering application, an advanced tungsten material with the fine grain and dense microstructure is required and developed. This paper briefly introduces the application background of the tungsten materials and mainly illustrates a series of common techniques for manufacturing advance tungsten materials, such as powder preparation technologies, bulk densification techniques, continuous processing technologies and the coating and additive manufacturing technologies. Furthermore, the development prospects for manufacturing techniques of tungsten materials are also presented in the end. Considering the tungsten materials employed in the fusion engineering application, combining these scalable techniques of the wet-chemical method, pressureless sintering and continuous deformation processing techniques would be the possible research and development routes to realize the manufacture of the advanced tungsten materials.

Processing of nanocomposites using supercritical fluid assisted extrusion for stress/strain sensing applications

The problem of dispersion of nano-additives in thermoplastic elastomers using continuous processing techniques still prevails in scientific and engineering applications. To address this, supercritical fluid (SCF) assisted extrusion was utilised to develop elastic, isotropic and electrically superior materials, which contain elastomeric microphases of Poly(styrene-ethylene-butylene-styrene [SEBS] with homogeneously dispersed conductive nano-additives of carbon black [CB]. SEBS-SCF/CB 5 wt% extrudates showed 46% and 14% higher storage modulus compared to their counterparts in transverse and longitudinal direction respectively. Similarly, piezo-resistive properties of SEBS-SCF/CB composites were found to have a superior strain gauge factor with linear decrease in conductivity with increasing strain, compared to nonlinear increase/decrease in piezoresistive behaviour of SEBS/CB composites. Piezo-resistivity of SEBS-SCF/CB 5 wt% nanocomposites were found to be highly sensitive in both bending (3.6% change in resistance per degree for 1.7 cm thick sample) and tensile strain conditions (gauge factor ca. 9) for smart applications.

Potential of Continuous Manufacturing for Liposomal Drug Products.

Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g., improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application.

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood’s apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood’s apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

Phase-Transfer Ligand Exchange of Lead Chalcogenide Quantum Dots for Direct Deposition of Thick, Highly Conductive Films.

The use of semiconductor nanocrystal quantum dots (QDs) in optoelectronic devices typically requires postsynthetic chemical surface treatments to enhance electronic coupling between QDs and allow for efficient charge transport in QD films. Despite their importance in solar cells and infrared (IR) light-emitting diodes and photodetectors, advances in these chemical treatments for lead chalcogenide (PbE; E = S, Se, Te) QDs have lagged behind those of, for instance, II-VI semiconductor QDs. Here, we introduce a method for fast and effective ligand exchange for PbE QDs in solution, resulting in QDs completely passivated by a wide range of small anionic ligands. Due to electrostatic stabilization, these QDs are readily dispersible in polar solvents, in which they form highly concentrated solutions that remain stable for months. QDs of all three Pb chalcogenides retain their photoluminescence, allowing for a detailed study of the effect of the surface ionic double layer on electronic passivation of QD surfaces, which we find can be explained using the hard/soft acid-base theory. Importantly, we prepare highly conductive films of PbS, PbSe, and PbTe QDs by directly casting from solution without further chemical treatment, as determined by field-effect transistor measurements. This method allows for precise control over the surface chemistry, and therefore the transport properties of deposited films. It also permits single-step deposition of films of unprecedented thickness via continuous processing techniques, as we demonstrate by preparing a dense, smooth, 5.3-μm-thick PbSe QD film via doctor-blading. As such, it offers important advantages over laborious layer-by-layer methods for solar cells and photodetectors, while opening the door to new possibilities in ionizing-radiation detectors.

ESCAPE: Effective Scalable Clustering Approach for Parallel Execution of Continuous Position-Based Queries in Position Monitoring Applications

Massive data sets of continuous position-based queries (CPQs) in position monitoring applications offer a challenge of time ingestion while forwarding the position-based data within wireless search space area. As a result of recurrent modifications in network topology due to the mobility of users, processing of large CPQ data sets and roaming CPQs is one of the challenges in position monitoring. Therefore, the parallel algorithm is proposed in this paper for clustering and parallel processing of roaming CPQs which will recognize solid clusters in the wireless search space area. We present an algorithm which proposes the use of search space areas for clustering and introduce a parallel framework for parallel processing of CPQ data sets. The wireless search space area from wireless networks are used for scalable and effective calculation of clusters and dimensions in wireless networks. Present continuous query processing techniques cannot competently process roaming CPQs in the wireless search space area. The proposed algorithm is demonstrated to have practically best speedups in processing roaming CPQs. Results indicate that the proposed work determine improved ability of CPQs over existing mechanisms and attain small query latency and high precision in position monitoring applications.

The use of optimization algorithm for assessing effects of Carboxyl Functionalized MWCNTs on the productivity of nidltrusion process

Among the several available techniques to produce the braided composite rods for construction industry, nidltrusion process is becoming the most widespread and cost-effective continuous processing technique. The work mentions the influence of carboxyl functionalized multiwalled carbon nanotubes (MWCNTs) on the maximum speed of manufacturing process. The epoxy polymer is diglycidyl ether of bisphenol F and the curing agent is an aromatic diamine. Appropriate temperature settings were determined using the optimization algorithm for two-dimensional heat transfer and curing model implemented to 8-mm diameter reinforcement with 0, 0.1, 0.2 and 0.3 wt% MWCNT. Final results allow concluding that only the use of 0.2 wt% MWCNT gives the highest nidltrusion speed. Other two batches (0.1 wt% and 0.3 wt% MWCNT) showed worse results compared to neat sample. The developed optimization algorithm can be further applied in the modeling of pultrusion process with using of different type of resin, curing agents and nanofillers.

Microstructure evolution and mechanical properties of Mg–9Li–3Al–2Sr alloy in change channel angular pressing

Change channel angular pressing is a specially designed continuous processing technique to prepare bulk ultrafine grained materials. The extrusion process and structure evolution of Mg–9Li–3Al–2Sr alloy were analysed. The long strip phases of α-Mg and β-Li were sheared into short pieces during extrusion. The continuous distribution Al4Sr phases were extruded into small particles, which are mainly observed in the α/β phase interface and β-Li matrix phase. Structure homogeneity can be achieved, and the mechanical properties were improved with one pass processing. The effect of Al4Sr phase on the microstructure and mechanical properties of Mg–9Li–3Al–2Sr alloy was observed to be different due to the various extrusion modes and parts.

ChemInform Abstract: Flow Chemistry Meets Advanced Functional Materials

AbstractReview: [68 refs.

Flow chemistry meets advanced functional materials.

Flow chemistry and continuous processing techniques are beginning to have a profound impact on the production of functional materials ranging from quantum dots, nanoparticles and metal organic frameworks to polymers and dyes. These techniques provide robust procedures which not only enable accurate control of the product material's properties but they are also ideally suited to conducting experiments on scale. The modular nature of flow and continuous processing equipment rapidly facilitates reaction optimisation and variation in function of the products.

Continuous Top-k Dominating Queries

Top-k dominating queries use an intuitive scoring function which ranks multidimensional points with respect to their dominance power, i.e., the number of points that a point dominates. The k points with the best (e.g., highest) scores are returned to the user. Both top-k and skyline queries have been studied in a streaming environment, where changes to the data set are very frequent. In such an environment, continuous query processing techniques are required toward efficient monitoring of query results, since periodic query re-execution is computationally intensive, and therefore, prohibitive. This work contains the first study of continuous top-k dominating queries over data streams. In comparison to continuous top-k and skyline queries, continuous top-k dominating queries pose additional challenges. Three exact algorithms (BFA, EVA, ADA) are studied, and among them ADA, which is enhanced with additional optimization techniques, shows the best overall performance. In some cases, we are willing to trade accuracy for speed. Toward this direction, two approximate algorithms are proposed (AHBA and AMSA). AHBA offers probabilistic guarantees regarding the accuracy of the result based on the Hoeffding bound, whereas AMSA performs a more aggressive computation resulting in more efficient processing. Evaluation results, based on real-life and synthetic data sets, show the efficiency and scalability of our techniques.

Finite Element Analysis of the Deformation Distribution During Multi-Pass Rotary-Die ECAP

Rotary-die equal channel angular pressing (RD-ECAP) is a specially designed continuous processing technique to prepare bulk ultrafine-grained/nanostructure (UFG/NS) materials. In this article, an Al-7wt.% Si-0.35wt.% Mg alloy was processed by up to four RD-ECAP passes. The deformation behavior was studied by experiments and FEM simulation, including the observation of the scribed deformation patterns, the macrostructures, the simulated flow lines feature, and the equivalent stain distribution after different RD-ECAP passes. The results show that the shear deformation can accumulate effectively all over the entire billet via multi-pass RD-ECAP. The observed zigzag shape metal flow is formed after three ECAP passes, and the structure homogeneity can be achieved by RD-ECAP with more processing passes.

시공간 데이터 스트림 처리를 위한 영역 기반의 연산자 공유 기법

In ubiquitous environments, many continuous query processing techniques make use of operator network and sharing methods on continuous data stream generated from various sensors. Since similar continuous queries with the location information intensively occur in specific regions, we suggest a new operator sharing method based on grid partition for the spatial continuous query processing for location-based applications. Due to the proposed method shares moving objects by the given grid cell without sharing spatial operators individually, our approach can not only share spatial operators including similar conditions, but also increase the query processing performance and the utilization of memory by reducing the frequency of use of spatial operators.

Synthesis of acetal protected building blocks using flow chemistry with flow I.R. analysis: preparation of butane-2,3-diacetal tartrates

The syntheses of butane-2,3-diacetal protected tartrate derivatives are described using continuous flow processing techniques with in-line purification and I.R. analytical protocols.