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Kenis, Paul J. A.

Publications and source records attributed to Kenis, Paul J. A..

17 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Solution Coating of Pharmaceutical Nanothin Films and Multilayer Nanocomposites with Controlled Morphology and Polymorphism

Nanosizing is rapidly emerging as an alternative approach to enhance solubility and thus the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Although numerous techniques have been developed to perform nanosizing of API crystals, precise control and modulation of their size in an energy and material efficient manner remains challenging. As such, in this study, we present meniscus-guided solution coating as a new technique to produce pharmaceutical thin films of nanoscale thickness with controlled morphology. We demonstrate control of aspirin film thickness over more than 2 orders of magnitude, from 30 nm to 1.5 μm. By varying simple process parameters such as the coating speed and the solution concentration, the aspirin film morphology can also be modulated by accessing different coating regimes, namely the evaporation regime and the Landau–Levich regime. Using ellipticine—a poorly water-soluble anticancer drug—as another model compound, we discovered a new polymorph kinetically trapped during solution coating. Furthermore, the polymorphic outcome can be controlled by varying coating conditions. We further performed layer-by-layer coating of multilayer nanocomposites, with alternating thin films of ellipticine and a biocompatible polymer, which demonstrate the potential of additive manufacturing of multidrug-personalized dosage forms using this approach.

36 MATERIALS SCIENCE↗
DOE OSTI2018

X-ray transparent microfluidic platforms for membrane protein crystallization with microseeds

Crystallization of membrane proteins is a critical step for uncovering atomic resolution 3-D structures and elucidating structure–function relationships. Microseeding, the process of transferring sub-microscopic crystal nuclei from initial screens into new crystallization experiments, is an effective, yet underutilized approach to grow crystals suitable for X-ray crystallography. In this work, we report simplified methods for crystallization of membrane proteins that utilize microseeding in X-ray transparent microfluidic chips. First, a microfluidic method for introduction of microseed dilutions into metastable crystallization experiments is demonstrated for photoactive yellow protein and cytochrome bo3 oxidase. As microseed concentration decreased, the number of crystals decreased while the average size increased. Second, we demonstrate a microfluidic chip for microseed screening, where many crystallization conditions were formulated on-chip prior to mixing with microseeds. Crystallization composition, crystal size, and diffraction data were collected and mapped on phase diagrams, which revealed that crystals of similar diffraction quality and size typically grow in distinct regions of the phase diagram.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

X-ray transparent microfluidic chips for high-throughput screening and optimization of in meso membrane protein crystallization

Elucidating and clarifying the function of membrane proteins ultimately requires atomic resolution structures as determined most commonly by X-ray crystallography. Many high impact membrane protein structures have resulted from advanced techniques such as in meso crystallization that present technical difficulties for the set-up and scale-out of high-throughput crystallization experiments. In prior work, we designed a novel, low-throughput X-ray transparent microfluidic device that automated the mixing of protein and lipid by diffusion for in meso crystallization trials. Here, in this work, we report X-ray transparent microfluidic devices for high-throughput crystallization screening and optimization that overcome the limitations of scale and demonstrate their application to the crystallization of several membrane proteins. Two complementary chips are presented: (1) a high-throughput screening chip to test 192 crystallization conditions in parallel using as little as 8 nl of membrane protein per well and (2) a crystallization optimization chip to rapidly optimize preliminary crystallization hits through fine-gradient re-screening. We screened three membrane proteins for new in meso crystallization conditions, identifying several preliminary hits that we tested for X-ray diffraction quality. Further, we identified and optimized the crystallization condition for a photosynthetic reaction center mutant and solved its structure to a resolution of 3.5 Å.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo- N -(pyridin-2-yl)-2 H -1λ 6 ,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2 H -1λ 6 ,2-benzothiazine-3-amido)pyridin-1-ium–2,5-dihydroxybenzoic acid, 2C 15 H 13 N 3 O 4 S·C 7 H 6 O 4 ] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809(2):0.191(2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Microfluidic pressure amplifier circuits and electrostatic gates for pneumatic microsystems

An electrostatic actuator is provide that can include a fluidic line, a first electrode, and a second electrode such that a gate chamber portion of the fluidic line is sandwiched between the first electrode and the second electrode. The electrostatic actuator can also include a pressure-balancing channel in fluid communication with the gate chamber portion where the first electrode is sandwiched between the pressure-balancing channel and the gate chamber portion. A pneumatic valve system is provided which includes an electrostatic gate and a fluidic channel fluidly separate from a fluidic control line. A pneumatic valve portion of the fluidic control line can be positioned relative to a portion of the fluidic channel such that expansion of the pneumatic valve portion restricts fluid flow through the fluidic channel. Methods of using an electrostatic actuator and a pneumatic valve system are also provided.

42 ENGINEERING↗
DOE OSTI2016

Enhanced emission of quantum dots embedded within the high-index dielectric regions of photonic crystal slabs

We demonstrate a method for combining sputtered TiO{sub 2} deposition with liquid phase dip-coating of a quantum dot (QD) layer that enables precise depth placement of QD emitters within a high-index dielectric film, using a photonic crystal (PC) slab resonator to demonstrate enhanced emission from the QDs when they are located at a specific depth within the film. The depth of the QDs within the PC is found to modulate the resonant wavelength of the PC as well as the emission enhancement efficiency, as the semiconducting material embedded within the dielectric changes its spatial overlap with the resonant mode.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Microreactor and method for preparing a radiolabeled complex or a biomolecule conjugate

A microreactor for preparing a radiolabeled complex or a biomolecule conjugate comprises a microchannel for fluid flow, where the microchannel comprises a mixing portion comprising one or more passive mixing elements, and a reservoir for incubating a mixed fluid. The reservoir is in fluid communication with the microchannel and is disposed downstream of the mixing portion. A method of preparing a radiolabeled complex includes flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, where the downstream mixing portion includes one or more passive mixing elements, and flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion. The ligand solution and the radiometal solution are passively mixed while in the downstream mixing portion to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator. The chelation reaction is completed to form a radiolabeled complex.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2014

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. The X-ray transparency of the chip enables diffraction data collection from multiple crystals residing in microfluidic wells, eliminating the normally required manual harvesting and mounting of individual crystals. We validated our approach by on-chip crystallization of photosynthetic reaction center, a membrane protein from Rhodobacter sphaeroides, followed by solving its structure to a resolution of 2.5 Å using X-ray diffraction data collected on-chip under ambient conditions. A moderate conformational change in hydrophilic chains of the protein was observed when comparing the on-chip, room temperature structure with known structures for which data were acquired under cryogenic conditions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2012

Contaminant Removal from Oxygen Production Systems for In Situ Resource Utilization

The In Situ Resource Utilization (ISRU) project has been developing technologies to produce oxygen from lunar regolith to provide consumables to a lunar outpost. The processes developed reduce metal oxides in the regolith to produce water, which is then electrolyzed to produce oxygen. Hydrochloic and hydrofluoric acids are byproducts of the reduction processes, as halide minerals are also reduced at oxide reduction conditions. Because of the stringent water quality requirements for electrolysis, there is a need for a contaminant removal process. The Contaminant Removal from Oxygen Production Systems (CROPS) team has been developing a separation process to remove these contaminants in the gas and liquid phase that eliminates the need for consumables. CROPS has been using Nafion, a highly water selective polymeric proton exchange membrane, to recover pure water from the contaminated solution. Membrane thickness, product stream flow rate, and acid solution temperature and concentration were varied with the goal of maximizing water permeation and acid rejection. The results show that water permeation increases with increasing solution temperature and product stream flow rate, while acid rejection increases with decreasing solution temperature and concentration. Thinner membranes allowed for higher water flux and acid rejection than thicker ones. These results were used in the development of the hardware built for the most recent Mars ISRU demonstration project.

Anthony, Stephen M.↗
NASA NTRS2012

Optimization of a Nafion Membrane-Based System for Removal of Chloride and Fluoride from Lunar Regolith-Derived Water

A long-term human presence in space will require self-sustaining systems capable of producing oxygen and potable water from extraterrestrial sources. Oxygen can be extracted from lunar regolith, and water contaminated with hydrochloric and hydrofluoric acids is produced as an intermediate in this process. We investigated the ability of Nafion proton exchange membranes to remove hydrochloric and hydrofluoric acids from water. The effect of membrane thickness, product stream flow rate, and acid solution temperature and concentration on water flux, acid rejection, and water and acid activity were studied. The conditions that maximized water transport and acid rejection while minimizing resource usage were determined by calculating a figure of merit. Water permeation is highest at high solution temperature and product stream flow rate across thin membranes, while chloride and fluoride permeation are lowest at low acid solution temperature and concentration across thin membranes. The figure of merit varies depending on the starting acid concentration; at low concentration, the figure of merit is highest across a thin membrane, while at high concentration, the figure of merit is highest at low solution temperature. In all cases, the figure of merit increases with increasing product stream flow rate.

Anthony, Stephen M.↗