Elasticity in Macrophage-Synthesized Biocrystals.

Supramolecular crystalline assembly constitutes a rational approach to bioengineer intracellular structures. Here, biocrystals of clofazimine (CFZ) that form in vivo within macrophages were measured to have marked curvature. Isolated crystals, however, showed reduced curvature suggesting that intracellular forces bend these drug crystals.

Distinct responses of compartmentalized glutathione redox potentials to pharmacologic quinones targeting NQO1.

Deoxynyboquinone (DNQ), a potent novel quinone-based antineoplastic agent, selectively kills solid cancers with overexpressed cytosolic NAD(P)H:quinone oxidoreductase-1 (NQO1) via excessive ROS production. A genetically encoded redox-sensitive probe was used to monitor intraorganellar glutathione redox potentials (E) as a direct indicator of cellular oxidative stress following chemotherapeutic administration. Beta-lapachone (β-lap) and DNQ-induced spatiotemporal redox responses were monitored in human lung A549 and pancreatic MIA-PaCa-2 adenocarcinoma cells incubated with or without dicumarol and ES936, potent NQO1 inhibitors.

Crystal structure of a 2:1 piroxicam-gentisic acid co-crystal featuring neutral and zwitterionic piroxicam mol-ecules.

A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hy-droxy-1,1-dioxo--(pyridin-2-yl)-2-1λ,2-benzo-thia-zine-3-carboxamide-2-(4-oxido-1,1-dioxo-2-1λ,2-benzo-thia-zine-3-amido)-pyridin-1-ium-2,5-di-hydroxy-benzoic acid, 2CHNOS·CHO] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam mol-ecule is in its neutral form and an intra-molecular O-H⋯O hydrogen bond is observed. The other piroxicam mol-ecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intra-molecular N-H⋯O hydrogen bonds occur.

Electroreduction of Carbon Dioxide to Hydrocarbons Using Bimetallic Cu-Pd Catalysts with Different Mixing Patterns.

Electrochemical conversion of CO holds promise for utilization of CO as a carbon feedstock and for storage of intermittent renewable energy. Presently Cu is the only metallic electrocatalyst known to reduce CO to appreciable amounts of hydrocarbons, but often a wide range of products such as CO, HCOO, and H are formed as well. Better catalysts that exhibit high activity and especially high selectivity for specific products are needed.

A metal-free electrocatalyst for carbon dioxide reduction to multi-carbon hydrocarbons and oxygenates.

Electroreduction of carbon dioxide into higher-energy liquid fuels and chemicals is a promising but challenging renewable energy conversion technology. Among the electrocatalysts screened so far for carbon dioxide reduction, which includes metals, alloys, organometallics, layered materials and carbon nanostructures, only copper exhibits selectivity towards formation of hydrocarbons and multi-carbon oxygenates at fairly high efficiencies, whereas most others favour production of carbon monoxide or formate. Here we report that nanometre-size N-doped graphene quantum dots (NGQDs) catalyse the electrochemical reduction of carbon dioxide into multi-carbon hydrocarbons and oxygenates at high Faradaic efficiencies, high current densities and low overpotentials.

A Nitrogen-Doped Carbon Catalyst for Electrochemical CO Conversion to CO with High Selectivity and Current Density.

We report characterization of a non-precious metal-free catalyst for the electrochemical reduction of CO to CO; namely, a pyrolyzed carbon nitride and multiwall carbon nanotube composite. This catalyst exhibits a high selectivity for production of CO over H (approximately 98 % CO and 2 % H ), as well as high activity in an electrochemical flow cell. The CO partial current density at intermediate cathode potentials (V=-1.

A Gross-Margin Model for Defining Technoeconomic Benchmarks in the Electroreduction of CO2.

We introduce a gross-margin model to evaluate the technoeconomic feasibility of producing different C1 -C2 chemicals such as carbon monoxide, formic acid, methanol, methane, ethanol, and ethylene through the electroreduction of CO2 . Key performance benchmarks including the maximum operating cell potential (Vmax ), minimum operating current density (jmin ), Faradaic efficiency (FE), and catalyst durability (tcatdur ) are derived. The Vmax values obtained for the different chemicals indicate that CO and HCOOH are the most economically viable products.

Microfluidic Preparation of a 89Zr-Labeled Trastuzumab Single-Patient Dose.

Unlabelled: (89)Zr-labeled antibodies are being investigated in several clinical trials; however, the time requirement for synthesis of clinical doses can hinder patient throughput because of scheduling difficulties. Additionally, low specific activity due to poor labeling efficiency can require larger amounts of the radiopharmaceutical to be administered, possibly leading to adverse side effects. Here, we describe the design and evaluation of a microfluidic reactor capable of synthesizing a single clinical dose of (89)Zr-labeled antibody.

The effect of electrolyte composition on the electroreduction of CO2 to CO on Ag based gas diffusion electrodes.

The electroreduction of CO2 to C1-C2 chemicals can be a potential strategy for utilizing CO2 as a carbon feedstock. In this work, we investigate the effect of electrolytes on the electroreduction of CO2 to CO on Ag based gas diffusion electrodes. Electrolyte concentration was found to play a major role in the process for the electrolytes (KOH, KCl, and KHCO3) studied here.

High temperature continuous flow synthesis of CdSe/CdS/ZnS, CdS/ZnS, and CdSeS/ZnS nanocrystals.

Continuous flow reactors show great promise for large-scale synthesis of quantum dots. Here, we discuss results for the synthesis of multi-layered Cd-based hybrid nanocrystals - CdSe/CdS/ZnS, CdS/ZnS, and CdSeS/ZnS - in a continuous flow reactor. The simple reactor design and liquid-phase chemistry obviate the need for preheating or in-line mixing, and the chosen reactor dimensions and operating conditions allow for high flow rates (∼10 mL min(-1)).

Towards time-resolved serial crystallography in a microfluidic device.

Serial methods for crystallography have the potential to enable dynamic structural studies of protein targets that have been resistant to single-crystal strategies. The use of serial data-collection strategies can circumvent challenges associated with radiation damage and repeated reaction initiation. This work utilizes a microfluidic crystallization platform for the serial time-resolved Laue diffraction analysis of macroscopic crystals of photoactive yellow protein (PYP).

Thiol-based antioxidants elicit mitochondrial oxidation via respiratory complex III.

Excessive oxidation is widely accepted as a precursor to deleterious cellular function. On the other hand, an awareness of the role of reductive stress as a similar pathological insult is emerging. Here we report early dynamic changes in compartmentalized glutathione (GSH) redox potentials in living cells in response to exogenously supplied thiol-based antioxidants.

Region specific enhancement of quantum dot emission using interleaved two-dimensional photonic crystals.

The power efficiency, spectral characteristics, and output directionality of light emitting diodes (LEDs) used for lighting and video display may be tailored by integrating nanostructures that interact with photon emitters. In this work, we demonstrate an approach in which visible-wavelength-emitting quantum dots (QDs) are integrated within a polymer-based photonic crystal (PC) and excited by an ultraviolet-emitting LED. The PC design incorporates two interleaved regions, each with distinct periods in orthogonal directions.

Chemical Analysis of Drug Biocrystals: A Role for Counterion Transport Pathways in Intracellular Drug Disposition.

In mammals, highly lipophilic small molecule chemical agents can accumulate as inclusions within resident tissue macrophages. In this context, we characterized the biodistribution, chemical composition, and structure of crystal-like drug inclusions (CLDIs) formed by clofazimine (CFZ), a weakly basic lipophilic drug. With prolonged oral dosing, CFZ exhibited a significant partitioning with respect to serum and fat due to massive bioaccumulation and crystallization in the liver and spleen.

A method of cryoprotection for protein crystallography by using a microfluidic chip and its application for in situ X-ray diffraction measurements.

We demonstrate a seamless and contactless method from protein crystallization to X-ray analysis using a microfluidic chip with the aim of obtaining a complete crystallographic data set of a protein crystal under cryogenic conditions. Our microfluidics-based approach did not require direct manipulation of the protein crystal. Therefore, the microfluidic chip approach is suitable for novices of X-ray analysis of protein crystals.

Development of a microfluidic "click chip" incorporating an immobilized Cu(I) catalyst.

We have developed a microfluidic "click chip" incorporating an immobilized Cu(I) catalyst for click reactions. The microfluidic device was fabricated from polydimethylsiloxane (PDMS) bonded to glass and featured ~14,400 posts on the surface to improve catalyst immobilization. This design increased the immobilization efficiency and reduces the reagents' diffusion time to active catalyst site.

serial Laue diffraction on a microfluidic crystallization device.

Renewed interest in room-temperature diffraction has been prompted by the desire to observe structural dynamics of proteins as they function. Serial crystallography, an experimental strategy that aggregates small pieces of data from a large uniform pool of crystals, has been demonstrated at synchrotrons and X-ray free-electron lasers. This work utilizes a microfluidic crystallization platform for serial Laue diffraction from macroscopic crystals and proposes that a collection of small slices of Laue data from many individual crystals is a realistic solution to the difficulties in dynamic studies of irreversible biochemical reactions.

Microfluidic platform for the study of intercellular communication via soluble factor-cell and cell-cell paracrine signaling.

Diffusion of autocrine and paracrine signaling molecules allows cells to communicate in the absence of physical contact. This chemical-based, long-range communication serves crucial roles in tissue function, activation of the immune system, and other physiological functions. Despite its importance, few in vitro methods to study cell-cell signaling through paracrine factors are available today.

X-ray Transparent Microfluidic Chip for Mesophase-Based Crystallization of Membrane Proteins and On-Chip Structure Determination.

Crystallization from lipidic mesophase matrices is a promising route to diffraction-quality crystals and structures of membrane proteins. The microfluidic approach reported here eliminates two bottlenecks of the standard mesophase-based crystallization protocols: (i) manual preparation of viscous mesophases and (ii) manual harvesting of often small and fragile protein crystals. In the approach reported here, protein-loaded mesophases are formulated in an X-ray transparent microfluidic chip using only 60 nL of the protein solution per crystallization trial.

Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction.

Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE.

Triazine-based tool box for developing peptidic PET imaging probes: syntheses, microfluidic radiolabeling, and structure-activity evaluation.

This study was aimed at developing a triazine-based modular platform for targeted PET imaging. We synthesized mono- or bis-cyclo(RGDfK) linked triazine-based conjugates specifically targeting integrin αvβ3 receptors. The core molecules could be easily linked to targeting peptide and radiolabeled bifunctional chelator.

Inhibition of glutathione synthesis distinctly alters mitochondrial and cytosolic redox poise.

The glutathione couple GSH/GSSG is the most abundant cellular redox buffer and is not at equilibrium among intracellular compartments. Perturbation of glutathione poise has been associated with tumorigenesis; however, due to analytical limitations, the underlying mechanisms behind this relationship are poorly understood. In this regard, we have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real-time glutathione redox potentials in the cytosol and mitochondrial matrix of tumorigenic and non-tumorigenic cells.

Silver supported on titania as an active catalyst for electrochemical carbon dioxide reduction.

Although significant research efforts have focused on the exploration of catalysts for the electrochemical reduction of CO2 , considerably fewer reports have described how support materials for these catalysts affect their performance, which includes their ability to reduce the overpotential, and/or to increase the catalyst utilization and selectivity. Here Ag nanoparticles supported on carbon black (Ag/C) and on titanium dioxide (Ag/TiO2 ) were synthesized. In a flow reactor, 40 wt % Ag/TiO2 exhibited a twofold higher current density for CO production than 40 wt % Ag/C.

Oscillatory behavior of neutrophils under opposing chemoattractant gradients supports a winner-take-all mechanism.

Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis. These chemoattractants include formylated peptides and various chemokines.

Effects of detergent β-octylglucoside and phosphate salt solutions on phase behavior of monoolein mesophases.

Using small-angle x-ray scattering (SAXS), we investigated the phase behavior of mesophases of monoolein (MO) mixed with additives commonly used for the crystallization of membrane proteins from lipidic mesophases. In particular, we examined the effect of sodium and potassium phosphate salts and the detergent β-octylglucoside (βOG) over a wide range of compositions relevant for the crystallization of membrane proteins in lipidic mesophases. We studied two types of systems: 1), ternary mixtures of MO with salt solutions above the hydration boundary; and 2), quaternary mixtures of MO with βOG and salt solutions over a wide range of hydration conditions.