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Illustrated is a microfludic cooling crystallization device that can effectively screen polymorphs, growth rates, and morphology of crystalline materials.

Liquid-liquid phase separation (LLPS), also known as oiling-out, is the appearance of the second liquid phase preceding the crystallization. LLPS is an undesirable phenomenon that can occur during the crystallization of active pharmaceutical ingredients (APIs), proteins, and polymers. It is typically avoided during crystallization due to its detrimental impacts on crystalline products due to lowered crystallization rate, the inclusion of impurities, and alteration in particle morphology and size distribution.

Precompetitive collaborations on new enabling technologies for research and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes projects, often with third-party collaborators, to develop new tools and technologies of mutual interest. Here, we report the results of one of the first ETC projects: the development of a user-friendly population balance model (PBM)-based crystallization simulator software. This project required the development of PBM software with integrated experimental data handling, kinetic parameter regression, interactive process simulation, visualization, and optimization capabilities incorporated in a computationally efficient and robust software platform. Inputs from a team of experienced scientists at 10 ETC member companies helped define a set of software features that guided a team of crystallization modelers to develop software incorporating these features. Communication, continuous testing, and feedback between the ETC and the academic team facilitated the software development. The product of this project, a software tool called CrySiV, an acronym for Crystallization Simulation and Visualization, is reported herein. Currently, CrySiV can be used for cooling, antisolvent, and combined cooling and antisolvent crystallization processes, with primary and secondary nucleation, growth, dissolution, agglomeration, and breakage of crystals. This paper describes the features and the numerical methods of the software and presents two case studies demonstrating its use for parameter estimation. In the first case study, a simulated data set is used to demonstrate the capabilities of the software to find kinetic parameters and its goodness of fit to a known solution. In the second case study, the kinetics of an antisolvent crystallization of indomethacin from a ternary solvent system are estimated, providing a practical example of the tool.

Catalytic hydrodeoxygenation is an essential step for bio-oil upgrading. However, hydrodeoxygenation usually requires a high hydrogen pressure and high temperature due to the good stability of the C–O bonds. Here we report an effective multiphase hydrodeoxygenation of lignin-based bio-oil at temperatures

Poly(amide) (PA) based nanofiltration membranes fabricated via interfacial polymerization (IP) are widely studied for water desalination. The formation of hybrid (nanocomposite) membranes comprisin...

Integrating sensors in miniaturized devices allow for fast and sensitive detection and precise control of experimental conditions. One of the potential applications of a sensor-integrated microfluidic system is to measure the solute concentration during crystallization. In this study, a continuous-flow microfluidic mixer is paired with an electrochemical sensor to enable in situ measurement of the supersaturation. This sensor is investigated as the predictive measurement of the supersaturation during the antisolvent crystallization of l-histidine in the water-ethanol mixture. Among the various metals tested in a batch system for their sensitivity toward l-histidine, Pt showed the highest sensitivity. A Pt-printed electrode was inserted in the continuous-flow microfluidic mixer, and the cyclic voltammograms of the system were obtained for different concentrations of l-histidine and different water-to-ethanol ratios. The sensor was calibrated for different ratios of antisolvent and concentrations of l-histidine with respect to the change of the measured anodic slope. Additionally, a machine-learning algorithm using neural networks was developed to predict the supersaturation of l-histidine from the measured anodic slope. The electrochemical sensors have shown sensitivity toward l-histidine, l-glutamic acid, and

Metal-organic frameworks (MOFs) are porous crystalline structures that are composed of coordinated metal ligands and organic linkers. Due to their high porosity, ultra-high surface-to-volume ratio, and chemical and structural flexibility, MOFs have numerous applications. MOFs are primarily synthesized in batch reactors under harsh conditions and long synthesis times. The continuous depletion of metal ligands and linkers in batch processes affects the kinetics of the oligomerization reaction and, hence, their nucleation and growth rates. Therefore, the existing screening systems that rely on batch processes, such as microtiter plates and droplet-based microfluidics, do not provide reliable nucleation and growth rate data. Significant challenges still exist for developing a relatively inexpensive, safe, and readily scalable screening device and ensuring consistency of results before scaling up. Here, we have designed patterned-surface microfluidic devices for continuous-flow synthesis of MOFs that allow effective and rapid screening of synthesis conditions. The patterned surface reduces the induction time of MOF synthesis for rapid screening while providing support to capture MOF crystals for growth measurements. The efficacy of the continuous-flow patterned microfluidic device to screen polymorphs, morphology, and growth rates is demonstrated for the HKUST-1 MOF. The effects of solvent composition and pH modulators on the morphology, polymorphs, and size distribution of HKUST-1 are evaluated using the patterned microfluidic device. Additionally, a time-resolved FT-IR analysis coupled with the patterned microfluidic device provides quantitative insights into the non-monotonic growth of MOF crystals with respect to the progression of the bulk oligomerization reaction. The patterned microfluidic device can be used to screen crystals with a longer induction time, such as proteins, covalent-organic frameworks, and MOFs.

Zeolitic nanotubes Nanotubes generally have solid walls, but a low-dimensional version of zeolites now introduces porosity into such structures. Korde et al . used a structure-directing agent with a hydrophobic biphenyl group center connecting two long alkyl chains bearing hydrophilic bulky quaternary ammonium head groups to direct hydrothermal synthesis with silicon-rich precursors (see the Perspective by Fan and Dong). The nanotubes have a mesoporous central channel of approximately 3 nanometers and zeolitic walls with micropores less than 0.6 nanometers. Electron microscopy and modeling showed that the outer surface is a projection of a large-pore zeolite and the inner surface is a projection of a medium-pore zeolite. —PDS

A synthesis method to obtain new zeolite imidazolate framework (ZIF) materials that are otherwise difficult to synthesize by known techniques such as direct crystallization or solvent-assisted linker exchange, is demonstrated. Treatment of an easily synthesized “template” ZIF (such as ZIF-8) with an acid gas (humid SO2) allows controlled demolition of metal-linker coordination bonds, while preserving overall crystal topology. The partially demolished crystals are then reconstructed into highly crystalline mixed-linker ZIFs with unique characteristics by insertion of different linkers that displace the damaged linkers. One illustration shows the synthesis of a series of mixed-linker ZIFs containing benzimidazole linkers that show entirely different gate-opening and diffusion characteristics from ZIFs of the same composition prepared by direct crystallization. Also shown is the synthesis of new mixed-linker SOD-topology ZIFs containing bulky halobenzimidazole and alkylbenzimidazole linkers, which are very d...

High-quality 2D MFI nanosheet coatings were prepared on α-alumina hollow fiber supports by vacuum filtration and then transformed into molecular sieving membranes by two sequential hydrothermal treatments. This processing method eliminates the need for specially engineered silica-based support materials that have so far been necessary to allow the formation of functional membranes from 2D MFI nanosheets. The sequential steps enhance adhesion of the membrane on the fiber support, fill in nanoscale gaps between the 2D nanosheets, and preserve the desirable (0k0) out-of-plane orientation without the need of any support engineering or modification. The membrane exhibits high performance for separation of n-butane from i-butane, and for other technologically important hydrocarbon separations. The present findings have strong implications on strategies for obtaining thin, highly selective zeolite membranes from 2D zeolites in a technologically scalable manner.