Effect of K+ Force Fields on Ionic Conductivity and Charge Dynamics of KOH in Ethylene Glycol.

Predicting ionic conductivity is crucial for developing efficient electrolytes for energy storage and conversion and other electrochemical applications. An accurate estimate of ionic conductivity requires understanding complex ion-ion and ion-solvent interactions governing the charge transport at the molecular level. Molecular simulations can provide key insights into the spatial and temporal behavior of electrolyte constituents. However, such insights depend on the ability of force fields to describe the underlying phenomena. In this work, molecular dynamics simulations were leveraged to delineate the impact of force field parameters on ionic conductivity predictions of potassium hydroxide (KOH) in ethylene glycol (EG). Four different force fields were used to represent the K+ ion. Diffusion-based Nernst-Einstein and correlation-based Einstein approaches were implemented to estimate the ionic conductivity, and the predicted values were compared with experimental measurements. The physical aspects, including ion-aggregation, charge distribution, cluster correlation, and cluster dynamics, were also examined. A force field was identified that provides reasonably accurate Einstein conductivity values and a physically coherent representation of the electrolyte at the molecular level.

Pathway toward Scalable Energy-Efficient Li-Mediated Ammonia Synthesis.

Lithium-mediated ammonia synthesis (LiMAS) is an emerging electrochemical method for NH3 production, featuring a meticulous three-step process involving Li+ electrodeposition, Li nitridation, and Li3N protolysis. The essence lies in the electrodeposition of Li+, a critical phase demanding current oscillations to fortify the solid-electrolyte interface (SEI) and ensure voltage stability. This distinctive operational cadence orchestrates Li nitridation and Li3N protolysis, profoundly influencing the NH3 selectivity. Increasing N2 pressure enhances the NH3 faradaic efficiency (FE) up to 20 bar, beyond which proton availability controls selectivity between Li nitridation and Li3N protolysis. The proton donor, typically alcohols, is a key factor, with 1-butanol observed to yield the highest NH3 FE. Counterion in the Li salt is also observed to be significant, with larger anions (e.g., exemplified by BF4-) improving SEI stability, directly impacting LiMAS efficacy. Notably, we report a peak NH3 FE of ∼70% and an NH3 current density of ∼-100 mA/cm2 via a delicate balance of process conditions, encompassing N2 pressure, proton donor, Li salt, and their respective concentrations. In contrast to the recent literature, we find that the theoretical maximum energy efficiency of LiMAS hinges significantly on the proton source, with LiMAS utilizing H2O calculated to have a maximum achievable energy efficiency of 27.8%. Despite inherent challenges, a technoeconomic analysis suggests high-pressure LiMAS to be more feasible than both ambient LiMAS and a modified green Haber-Bosch process. Our analysis finds that, at a 100 mA/cm2 NH3 current density and a 6 V cell voltage, LiMAS delivers green NH3 at an all-inclusive cost of $456 per ton, significantly lower than conventional cost barriers. Our economic analysis underscores high-pressure LiMAS as a potentially transformative technology that may revolutionize large-scale NH3 production, paving the way for a sustainable future.

Engineering advancements in microfluidic systems for enhanced mixing at low Reynolds numbers.

Mixing within micro- and millichannels is a pivotal element across various applications, ranging from chemical synthesis to biomedical diagnostics and environmental monitoring. The inherent low Reynolds number flow in these channels often results in a parabolic velocity profile, leading to a broad residence time distribution. Achieving efficient mixing at such small scales presents unique challenges and opportunities. This review encompasses various techniques and strategies to evaluate and enhance mixing efficiency in these confined environments. It explores the significance of mixing in micro- and millichannels, highlighting its relevance for enhanced reaction kinetics, homogeneity in mixed fluids, and analytical accuracy. We discuss various mixing methodologies that have been employed to get a narrower residence time distribution. The role of channel geometry, flow conditions, and mixing mechanisms in influencing the mixing performance are also discussed. Various emerging technologies and advancements in microfluidic devices and tools specifically designed to enhance mixing efficiency are highlighted. We emphasize the potential applications of micro- and millichannels in fields of nanoparticle synthesis, which can be utilized for biological applications. Additionally, the prospects of machine learning and artificial intelligence are offered toward incorporating better mixing to achieve precise control over nanoparticle synthesis, ultimately enhancing the potential for applications in these miniature fluidic systems.

Snap-on Adaptor for Microtiter Plates to Enable Continuous-Flow Microfluidic Screening and Harvesting of Crystalline Materials.

Microtiter plate assay is a conventional and standard tool for high-throughput (HT) screening that allows the synthesis, harvesting, and analysis of crystals. The microtiter plate screening assays require a small amount of solute in each experiment, which is adequate for a solid-state crystal analysis such as X-ray diffraction (XRD) or Raman spectroscopy. Despite the advantages of these high-throughput assays, their batch operational nature results in a continuous decrease in supersaturation due to crystal nucleation and growth. Continuous-flow microfluidic mixer devices have evolved as an alternate technique for efficiently screening crystals under controlled supersaturation. However, such a microfluidic device requires a minimum of two inlets per micromixer to create cyclonic flow, thereby creating physical limitations for implementing such a device for HT screening. Additionally, the monolithic design of these microfluidic devices makes it challenging to harvest crystals for post-screening analysis. Here, we develop a snap-on adapter that can be reversibly attached to a microtiter plate and convert it into a continuous-flow microfluidic mixer device. The integration of the snap-on adapter with a flow distributor and concentration gradient generator provides greater control over screening conditions while minimizing the number of independent inlets and pumps required. The three-dimensional (3D)-printed snap-on adaptor is plugged into a 24-well plate assay to demonstrate salt screening of naproxen crystals. Different naproxen salts are crystallized using four different salt formers (SFs)-sodium hydroxide, potassium hydroxide, pyridine, and arginine-and four different solvents-ethanol, methanol, isopropyl alcohol, and deionized water. The wells are further inspected under an optical microscope to identify their morphological forms and yields. The crystals are then harvested for solid-state characterization using XRD and Fourier transform infrared spectroscopy, followed by measurement of their dissolution rates. The flexibility of the snap-on adapter to fit on a wide range of microtiter plates and the ease in harvesting and analyzing crystals postscreening are two significant advantages that make this device versatile for various applications.

Determination of spinal tracer dispersion after intrathecal injection in a deformable CNS model.

Background: Traditionally, there is a widely held belief that drug dispersion after intrathecal (IT) delivery is confined locally near the injection site. We posit that high-volume infusions can overcome this perceived limitation of IT administration. Methods: To test our hypothesis, subject-specific deformable phantom models of the human central nervous system were manufactured so that tracer infusion could be realistically replicated in vitro over the entire physiological range of pulsating cerebrospinal fluid (CSF) amplitudes and frequencies. The distribution of IT injected tracers was studied systematically with high-speed optical methods to determine its dependence on injection parameters (infusion volume, flow rate, and catheter configurations) and natural CSF oscillations in a deformable model of the central nervous system (CNS). Results: Optical imaging analysis of high-volume infusion experiments showed that tracers spread quickly throughout the spinal subarachnoid space, reaching the cervical region in less than 10 min. The experimentally observed biodispersion is much slower than suggested by the Taylor-Aris dispersion theory. Our experiments indicate that micro-mixing patterns induced by oscillatory CSF flow around microanatomical features such as nerve roots significantly accelerate solute transport. Strong micro-mixing effects due to anatomical features in the spinal subarachnoid space were found to be active in intrathecal drug administration but were not considered in prior dispersion theories. Their omission explains why prior models developed in the engineering community are poor predictors for IT delivery. Conclusion: Our experiments support the feasibility of targeting large sections of the neuroaxis or brain utilizing high-volume IT injection protocols. The experimental tracer dispersion profiles acquired with an anatomically accurate, deformable, and closed in vitro human CNS analog informed a new predictive model of tracer dispersion as a function of physiological CSF pulsations and adjustable infusion parameters. The ability to predict spatiotemporal dispersion patterns is an essential prerequisite for exploring new indications of IT drug delivery that targets specific regions in the CNS or the brain.

Microkinetic insights into the role of catalyst and water activity on the nucleation, growth, and dissolution during COF-5 synthesis.

The chemical pathway for synthesizing covalent organic frameworks (COFs) involves a complex medley of reaction sequences over a rippling energy landscape that cannot be adequately described using existing theories. Even with the development of state-of-the-art experimental and computational tools, identifying primary mechanisms of nucleation and growth of COFs remains elusive. Other than empirically, little is known about how the catalyst composition and water activity affect the kinetics of the reaction pathway. Here, for the first time, we employ time-resolved in situ Fourier transform infrared spectroscopy (FT-IR) coupled with a six-parameter microkinetic model consisting of ∼10 million reactions and over 20 000 species. The integrated approach elucidates previously unrecognized roles of catalyst pKa on COF yield and water on growth rate and size distribution. COF crystalline yield increases with decreasing pKa of the catalysts, whereas the effect of water is to reduce the growth rate of COF and broaden the size distribution. The microkinetic model reproduces the experimental data and quantitatively predicts the role of synthesis conditions such as temperature, catalyst, and precursor concentration on the nucleation and growth rates. Furthermore, the model also validates the second-order reaction mechanism of COF-5 and predicts the activation barriers for classical and non-classical growth of COF-5 crystals. The microkinetic model developed here is generalizable to different COFs and other multicomponent systems.

Achievements, Challenges, and Perspectives on Nitrogen Electrochemistry for Carbon-Neutral Energy Technologies.

Unrestrained anthropogenic activities have severely disrupted the global natural nitrogen cycle, causing numerous energy and environmental issues. Electrocatalytic nitrogen transformation is a feasible and promising strategy for achieving a sustainable nitrogen economy. Synergistically combining multiple nitrogen reactions can realize efficient renewable energy storage and conversion, restore the global nitrogen balance, and remediate environmental crises. Here, we provide a unique aspect to discuss the intriguing nitrogen electrochemistry by linking three essential nitrogen-containing compounds (i.e., N2 , NH3 , and NO3 - ) and integrating four essential electrochemical reactions, i.e., the nitrogen reduction reaction (N2 RR), nitrogen oxidation reaction (N2 OR), nitrate reduction reaction (NO3 RR), and ammonia oxidation reaction (NH3 OR). This minireview also summarizes the acquired knowledge of rational catalyst design and underlying reaction mechanisms for these interlinked nitrogen reactions. We further underscore the associated clean energy technologies and a sustainable nitrogen-based economy.

In-line measurement of liquid-liquid phase separation boundaries using a turbidity-sensor-integrated continuous-flow microfluidic device.

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. In situ monitoring of phase separation enables investigating LLPS and identifying the phase separation boundaries. Various process analytical technologies (PATs) have been implemented to determine the LLPS boundaries prior to crystallization to prevent oiling out of compounds. The LLPS measurements using PATs can be time-consuming, expensive, and challenging. Here, we have implemented a fully integrated continuous-flow microfluidic device with a turbidity sensor to quickly and accurately evaluate the LLPS boundaries for a ß-alanine, water, and IPA mixture. The turbidity-sensor-integrated continuous-flow microfluidic device is also placed under an optical microscope to visually track and record the appearance and disappearance of oil droplets. Streams of an aqueous solution of ß-alanine, pure solvent (water), and pure antisolvent (IPA or ethanol) are pumped into the continuous-flow microfluidic device at various flow rates to obtain the compositions at which the solution becomes turbid. The onset of turbidity is measured using a custom-designed, in-line turbidity sensor. The LLPS boundaries can be estimated using the turbidity-sensor-integrated microfluidic device in less than 30 min, which will significantly improve and enhance the workflow of the pharmaceutical drug (or crystalline material) development process.

Autocatalysis and Oriented Attachment Direct the Synthesis of a Metal-Organic Framework.

Synthesis of porous, covalent crystals such as zeolites and metal-organic frameworks (MOFs) cannot be described adequately using existing crystallization theories. Even with the development of state-of-the-art experimental and computational tools, the identification of primary mechanisms of nucleation and growth of MOFs remains elusive. Here, using time-resolved in-situ X-ray scattering coupled with a six-parameter microkinetic model consisting of ∼1 billion reactions and up to ∼100 000 metal nodes, we identify autocatalysis and oriented attachment as previously unrecognized mechanisms of nucleation and growth of the MOF UiO-66. The secondary building unit (SBU) formation follows an autocatalytic initiation reaction driven by a self-templating mechanism. The induction time of MOF nucleation is determined by the relative rate of SBU attachment (chain extension) and the initiation reaction, whereas the MOF growth is primarily driven by the oriented attachment of reactive MOF crystals. The average size and polydispersity of MOFs are controlled by surface stabilization. Finally, the microkinetic model developed here is generalizable to different MOFs and other multicomponent systems.

Machine Learning-Driven, Sensor-Integrated Microfluidic Device for Monitoring and Control of Supersaturation for Automated Screening of Crystalline Materials.

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 o-aminobenzoic acid, which consist of functional groups present in almost 80% of small-molecule drugs on the market. The machine learning-guided electrochemical sensors can be applied to other small molecules with similar functional groups for automated screening of crystallization conditions in microfluidic devices.

Selective desolvation in two-step nucleation mechanism steers crystal structure formation.

The two-step nucleation (TSN) theory and crystal structure prediction (CSP) techniques are two disjointed yet popular methods to predict nucleation rate and crystal structure, respectively. The TSN theory is a well-established mechanism to describe the nucleation of a wide range of crystalline materials in different solvents. However, it has never been expanded to predict the crystal structure or polymorphism. On the contrary, the existing CSP techniques only empirically account for the solvent effects. As a result, the TSN theory and CSP techniques continue to evolve as separate methods to predict two essential attributes of nucleation - rate and structure. Here we bridge this gap and show for the first time how a crystal structure is formed within the framework of TSN theory. A sequential desolvation mechanism is proposed in TSN, where the first step involves partial desolvation to form dense clusters followed by selective desolvation of functional groups directing the formation of crystal structure. We investigate the effect of the specific interaction on the degree of solvation around different functional groups of glutamic acid molecules using molecular simulations. The simulated energy landscape and activation barriers at increasing supersaturations suggest sequential and selective desolvation. We validate computationally and experimentally that the crystal structure formation and polymorph selection are due to a previously unrecognized consequence of supersaturation-driven asymmetric desolvation of molecules.

Patterned microfluidic devices for rapid screening of metal-organic frameworks yield insights into polymorphism and non-monotonic growth.

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.

Advanced continuous-flow microfluidic device for parallel screening of crystal polymorphs, morphology, and kinetics at controlled supersaturation.

A flow-controlled microfluidic device for parallel and combinatorial screening of crystalline materials can profoundly impact the discovery and development of active pharmaceutical ingredients and other crystalline materials. While the existing continuous-flow microfluidic devices allow crystals to nucleate under controlled conditions in the channels, their growth consumes solute from the solution leading to variation in the downstream composition. The materials screened under such varying conditions are less reproducible in large-scale synthesis. There exists no continuous-flow microfluidic device that traps and grows crystals under controlled conditions for parallel screening. Here we show a blueprint of such a microfluidic device that has parallel-connected micromixers to trap and grow crystals under multiple conditions simultaneously. The efficacy of a multi-well microfluidic device is demonstrated to screen polymorphs, morphology, and growth rates of l-histidine via antisolvent crystallization at eight different solution conditions, including variation in molar concentration, vol% of ethanol, and supersaturation. The overall screening time for l-histidine using the multi-well microfluidic device is ∼30 min, which is at least eight times shorter than the sequential screening process. The screening results are also compared with the conventional 96-well microtiter device, which significantly overestimates the fraction of stable form as compared to metastable form and shows high uncertainty in measuring growth rates. The multi-well microfluidic device paves the way for next-generation microfluidic devices that are amenable to automation for high-throughput screening of crystalline materials.

2D High-Entropy Transition Metal Dichalcogenides for Carbon Dioxide Electrocatalysis.

High-entropy alloys combine multiple principal elements at a near equal fraction to form vast compositional spaces to achieve outstanding functionalities that are absent in alloys with one or two principal elements. Here, the prediction, synthesis, and multiscale characterization of 2D high-entropy transition metal dichalcogenide (TMDC) alloys with four/five transition metals is reported. Of these, the electrochemical performance of a five-component alloy with the highest configurational entropy, (MoWVNbTa)S2 , is investigated for CO2 conversion to CO, revealing an excellent current density of 0.51 A cm-2 and a turnover frequency of 58.3 s-1 at ≈ -0.8 V versus reversible hydrogen electrode. First-principles calculations show that the superior CO2 electroreduction is due to a multi-site catalysis wherein the atomic-scale disorder optimizes the rate-limiting step of CO desorption by facilitating isolated transition metal edge sites with weak CO binding. 2D high-entropy TMDC alloys provide a materials platform to design superior catalysts for many electrochemical systems.

Fundamental insight into electrochemical oxidation of methane towards methanol on transition metal oxides.

Electrochemical oxidation of CH4 is known to be inefficient in aqueous electrolytes. The lower activity of methane oxidation reaction (MOR) is primarily attributed to the dominant oxygen evolution reaction (OER) and the higher barrier for CH4 activation on transition metal oxides (TMOs). However, a satisfactory explanation for the origins of such lower activity of MOR on TMOs, along with the enabling strategies to partially oxidize CH4 to CH3OH, have not been developed yet. We report here the activation of CH4 is governed by a previously unrecognized consequence of electrostatic (or Madelung) potential of metal atom in TMOs. The measured binding energies of CH4 on 12 different TMOs scale linearly with the Madelung potentials of the metal in the TMOs. The MOR active TMOs are the ones with higher CH4 binding energy and lower Madelung potential. Out of 12 TMOs studied here, only TiO2, IrO2, PbO2, and PtO2 are active for MOR, where the stable active site is the O on top of the metal in TMOs. The reaction pathway for MOR proceeds primarily through *CH x intermediates at lower potentials and through *CH3OH intermediates at higher potentials. The key MOR intermediate *CH3OH is identified on TiO2 under operando conditions at higher potential using transient open-circuit potential measurement. To minimize the overoxidation of *CH3OH, a bimetallic Cu2O3 on TiO2 catalysts is developed, in which Cu reduces the barrier for the reaction of *CH3 and *OH and facilitates the desorption of *CH3OH. The highest faradaic efficiency of 6% is obtained using Cu-Ti bimetallic TMO.

Constitutive relationship and governing physical properties for magnetophoresis.

Magnetophoresis is an important physical process with application to drug delivery, biomedical imaging, separation, and mixing. Other than empirically, little is known about how the magnetic field and magnetic properties of a solution affect the flux of magnetic particles. A comprehensive explanation of these effects on the transport of magnetic particles has not been developed yet. Here we formulate a consistent, constitutive equation for the magnetophoretic flux of magnetic nanoparticles suspended in a medium exposed to a stationary magnetic field. The constitutive relationship accounts for contributions from magnetic diffusion, magnetic convection, residual magnetization, and electromagnetic drift. We discovered that the key physical properties governing the magnetophoresis are magnetic diffusion coefficient, magnetic velocity, and activity coefficient, which depend on relative magnetic energy and the molar magnetic susceptibility of particles. The constitutive equation also reveals previously unknown ballistic and diffusive limits for magnetophoresis wherein the paramagnetic particles either aggregate near the magnet or diffusive away from the magnet, respectively. In the diffusive limit, the particle concentration is linearly proportional to the relative magnetic energy of the suspension of paramagnetic particles. The region of the localization of paramagnetic particles near the magnet decreases with increasing the strength of the magnet. The dynamic accumulation of nanoparticles, measured as the thickness of the nanoparticle aggregate, near the magnet compares well with the theoretical prediction. The effect of convective mixing on the rate of magnetophoresis is also discussed for the magnetic targeting applications.

Organophilicity of Graphene Oxide for Enhanced Wettability of ZnO Nanorods.

Interfacing two-dimensional graphene oxide (GO) platelets with one-dimensional zinc oxide nanorods (ZnO) would create mixed-dimensional heterostructures suitable for modern optoelectronic devices. However, there remains a lack in understanding of interfacial chemistry and wettability in GO-coated ZnO nanorods heterostructures. Here, we propose a hydroxyl-based dissociation-exchange mechanism to understand interfacial interactions responsible for GO adsorption onto ZnO nanorods hydrophobic substrates. The proposed mechanism initiated from mixing GO suspensions with various organics would allow us to overcome the poor wettability (θ ∼ 140.5°) of the superhydrophobic ZnO nanorods to the drop-casted GO. The addition of different classes of organics into the relatively high pH GO suspension with a volumetric ratio of 1:3 (organic-to-GO) is believed to introduce free radicals (-OH and -COOH), which consequently result in enhancing adhesion (chemisorption) between ZnO nanorods and GO platelets. The wettability study shows as high as 75% reduction in the contact angle (θ = 35.5°) when the GO suspension is mixed with alcohols (e.g., ethanol) prior to interfacing with ZnO nanorods. The interfacial chemistry developed here brings forth a scalable tool for designing graphene-coated ZnO heterojunctions for photovoltaics, photocatalysis, biosensors, and UV detectors.

Solvent fluctuations in the solvation shell determine the activation barrier for crystal growth rates.

Solution crystallization is a common technique to grow advanced, functional crystalline materials. Supersaturation, temperature, and solvent composition are known to influence the growth rates and thereby properties of crystalline materials; however, a satisfactory explanation of how these factors affect the activation barrier for growth rates has not been developed. We report here that these effects can be attributed to a previously unrecognized consequence of solvent fluctuations in the solvation shell of solute molecules attaching to the crystal surface. With increasing supersaturation, the average hydration number of the glutamic acid molecule decreases and can reach an asymptotic limit corresponding to the number of adsorption sites on the molecule. The hydration number of the glutamic acid molecule also fluctuates due to the rapid exchange of solvent in the solvation shell and local variation in the supersaturation. These rapid fluctuations allow quasi-equilibrium between fully solvated and partially desolvated states of molecules, which can be used to construct a double-well potential and thereby to identify the transition state and the required activation barrier. The partially desolvated molecules are not stable and can attach spontaneously to the crystal surface. The activation barrier versus hydration number follows the Evans-Polanyi relation. The predicted absolute growth rates of the α-glutamic acid crystal at lower supersaturations are in reasonable agreement with the experimental observations.

Continuous-flow, well-mixed, microfluidic crystallization device for screening of polymorphs, morphology, and crystallization kinetics at controlled supersaturation.

Screening of crystal polymorphs and morphology and measurement of crystallization kinetics in a controlled supersaturated environment is crucial for the development of crystallization processes for pharmaceuticals, agrochemicals, semiconductors, catalysts, and other specialty chemicals. Most of the current tools including microtiter plates and droplet-based microfluidic devices suffer from depleting supersaturation in small compartments due to nucleation and growth of crystals. Such variation in supersaturation not only affects the outcome but also leads to impediments during the scale-up of the crystallizer. Here we develop an innovative technique using H-shaped and cyclone mixer designs to study crystallization at constant supersaturation maintained by a continuous flow of solution. While the H-shaped design can be used to screen crystals with slower kinetics, the cyclone mixer is better suited for crystals with faster kinetics. The polymorphs and morphology of o-aminobenzoic acid (o-ABA) at different supersaturations are analyzed using the cyclone mixer design and compared with the microtiter plate. While the polymorphs and morphology of o-ABA are affected by depleting supersaturation in a microtiter plate, the cyclone mixer design consistently screened stable and metastable polymorphs. These novel devices will also play an important role in supporting the FDA's initiative to spur innovation in continuous manufacturing for the advancements in drug development.

Cellular Obstruction Clearance in Proximal Ventricular Catheters Using Low-Voltage Joule Heating.

OBJECTIVE: Proximal obstruction due to cellular material is a major cause of shunt failure in hydrocephalus management. The standard approach to treat such cases involves surgical intervention which unfortunately is accompanied by inherent surgical risks and a likelihood of future malfunction. We report a prototype design of a proximal ventricular catheter capable of noninvasively clearing cellular obstruction. Methods: In-vitro cell-culture methods show that low-intensity ac signals successfully destroy a cellular layer in a localized manner by means of Joule heating induced hyperthermia. A detailed electrochemical model for determining the temperature distribution and ionic current density for an implanted ventricular catheter supports our experimental observations. RESULTS: In-vitro experiments with cells cultured in a plate as well as cells seeded in mock ventricular catheters demonstrated that localized heating between 43 °C and 48 °C caused cell death. This temperature range is consistent with hyperthermia. The electrochemical model verified that Joule heating due to ionic motion is the primary contributor to heat generation. CONCLUSION: Hyperthermia induced by Joule heating can clear cellular material in a localized manner. This approach is feasible to design a noninvasive self-clearing ventricular catheter system. SIGNIFICANCE: A shunt system capable of clearing cellular obstruction could significantly reduce the need for future surgical interventions, lower the cost of disease management, and improve the quality of life for patients suffering from hydrocephalus.