NMR and conductivity study of the protonic conductor HPb2Nb3O10 center dot nH(2)O

Electrical conductivity and H-1 Nuclear Magnetic Resonance (NMR) techniques were used to investigate the ion-exchanged layered lead-niobate perovskite HPb2Nb3O10. nH(2)O, over the temperature range 90-350 K. Compounds were synthesized by the sol-gel method and calcinated at 650 degreesC. Analysis of the NMR data gives activation energies for the proton motion in the range 0.14-0.40 eV, which are dependent on the water content. The frequency and temperature dependencies of the proton spin-lattice relaxation times show that the character of the motion of the: water molecules is essentially two-dimensional, reflecting the layered structure of the material. The H-1 line-narrowing transition and the single spin-lattice relaxation rate maximum, observed in the hydrated compounds, are consistent with a Grotthuss-like mechanism for the proton diffusion. (C) 2000 Elsevier B.V. B.V. All rights reserved.

H-1 low- and high-field NMR study of the effects of plasma treatment on the oil and water fractions in crude heavy oil

The chemical and physical properties of a Brazilian heavy oil submitted to plasma treatment were investigated by H-1 low-and high-field nuclear magnetic resonance (NMR) combined to the characterization of rheological properties, thermogravimetry and measurement of basic sediments and water (BSW) content. The crude oil was treated in a dielectric barrier discharge plasma reactor, using natural gas, CO2 or H-2 as working gas. The results indicated a large drop in the water content of the plasma-treated samples as compared to the crude oil, giving rise to a reduction in the viscosity. No significant chemical change was produced in the oil portion itself, as observed by H-1 NMR. The water contents determined by H-1 low-field NMR analyses agreed well with those obtained by BSW, indicating the low-field NMR methods as a useful tool for following the effects of plasma treatments on heavy oils, allowing the separation of the effects caused on the water and oil fractions. (C) 2011 Elsevier Ltd. All rights reserved.

Length scales of dynamic heterogeneities of low and high molecular weight glass formers from multidimensional NMR

Das Ziel der vorliegenden Arbeit ist die Untersuchung der räumlichen und zeitlichen Aspekte der heterogenen Dynamik in Modellglasbildnern. Dabei wird vor allem die langsame alpha-Relaxationsdynamik oberhalb des Glasüberganges Tg untersucht. Die nukleare Magnetresonanz zeigt ihre einmalige Vielseitigkeit bei der Untersuchung molekularer Dynamik, wenn die angewandten Techniken und Experimente durch Simulationen unterstützt werden. Die räumliche Aspekt dynamischer Heterogenitäten wird untersucht durch ein reduziertes vierdimensionales Spindiffusionsexperiment (4D3CP), ein Experiment, das Reorientierungsraten örtlich korreliert. Eine Simulation dieses Experimentes an einem System harter Kugeln liefert wertvolle Informationen über die Auswertemethode des 4D3CP Experiments. Glycerol und o-terphenyl werden durch das 4D3CP Experiment untersucht. Die erhaltenen Resultate werden mit bereits publizierten Daten des polymeren Glasbildners PVAc verglichen. Während PVAc und o-terphenyl eine Längenskale von 3.7 nm bzw. 2.9 nm aufweisen, ist die Längenskale von Glycerol signifikant kleiner bei 1.1 nm. Ein neues Experiment, welches sensitiv auf Translationsbewegung reagiert, wird vorgestellt. Durch Verwendung eines pi-Impulszuges kann eine separate Evolution unter dem Hamiltonian der dipolaren Kopplung und der chemischen Verschiebungsanisotropie erreicht werden.

NMR spectroscopy and imaging of hyperpolarized gases

Since the discovery of the nuclear magnetic resonance (NMR) phenomenon, countless NMR techniques have been developed that are today indispensable tools in physics, chemistry, biology, and medicine. As one of the main obstacles in NMR is its notorious lack of sensitivity, different hyperpolarization (HP) methods have been established to increase signals up to several orders of magnitude. In this work, different aspects of magnetic resonance, using HP noble gases, are studied, hereby combining different disciplines of research. The first part examines new fundamental effects in NMR of HP gases, in theory and experiment. The spin echo phenomenon, which provides the basis of numerous modern experiments, is studied in detail in the gas phase. The changes of the echo signal in terms of amplitude, shape, and position, due to the fast translational motion, are described by an extension of the existing theory and computer simulations. With this knowledge as a prerequisite, the detection of intermolecular double-quantum coherences was accomplished for the first time in the gas phase. The second part of this thesis focuses on the development of a practical method to enhance the dissolution process of HP 129Xe, without loss of polarization or shortening of T1. Two different setups for application in NMR spectroscopy and magnetic resonance imaging (MRI) are presented. The continuous operation allows biological and multidimensional spectroscopy in solutions. Also, first in vitro MRI images with dissolved HP 129Xe as contrast agent were obtained at a clinical scanner.

Influence of spatial constraints in non-crystalline regions on the polymer dynamics in semi-crystalline polyethylene: a solid state NMR study

A broad variety of solid state NMR techniques were used to investigate the chain dynamics in several polyethylene (PE) samples, including ultrahigh molecular weight PEs (UHMW-PEs) and low molecular weight PEs (LMW-PEs). Via changing the processing history, i.e. melt/solution crystallization and drawing processes, these samples gain different morphologies, leading to different molecular dynamics. Due to the long chain nature, the molecular dynamics of polyethylene can be distinguished in local fluctuation and long range motion. With the help of NMR these different kinds of molecular dynamics can be monitored separately. In this work the local chain dynamics in non-crystalline regions of polyethylene samples was investigated via measuring 1H-13C heteronuclear dipolar coupling and 13C chemical shift anisotropy (CSA). By analyzing the motionally averaged 1H-13C heteronuclear dipolar coupling and 13C CSA, the information about the local anisotropy and geometry of motion was obtained. Taking advantage of the big difference of the 13C T1 relaxation time in crystalline and non-crystalline regions of PEs, the 1D 13C MAS exchange experiment was used to investigate the cooperative chain motion between these regions. The different chain organizations in non-crystalline regions were used to explain the relationship between the local fluctuation and the long range motion of the samples. In a simple manner the cooperative chain motion between crystalline and non-crystalline regions of PE results in the experimentally observed diffusive behavior of PE chain. The morphological influences on the diffusion motion have been discussed. The morphological factors include lamellar thickness, chain organization in non-crystalline regions and chain entanglements. Thermodynamics of the diffusion motion in melt and solution crystallized UHMW-PEs is discussed, revealing entropy-controlled features of the chain diffusion in PE. This thermodynamic consideration explains the counterintuitive relationship between the local fluctuation and the long range motion of the samples. Using the chain diffusion coefficient, the rates of jump motion in crystals of the melt crystallized PE have been calculated. A concept of "effective" jump motion has been proposed to explain the difference between the values derived from the chain diffusion coefficients and those in literatures. The observations of this thesis give a clear demonstration of the strong relationship between the sample morphology and chain dynamics. The sample morphologies governed by the processing history lead to different spatial constraints for the molecular chains, leading to different features of the local and long range chain dynamics. The knowledge of the morphological influence on the microscopic chain motion has many implications in our understanding of the alpha-relaxation process in PE and the related phenomena such as crystal thickening, drawability of PE, the easy creep of PE fiber, etc.

Diffusion of laser polarized gases in MRI

The use of Magnetic Resonance Imaging (MRI) as a diagnostic tool is increasingly employing functional contrast agents to study or contrast entire mechanisms. Contrast agents in MRI can be classified in two categories. One type of contrast agents alters the NMR signal of the protons in its surrounding, e.g. lowers the T1 relaxation time. The other type enhances the Nuclear Magnetic Resonance (NMR) signal of specific nuclei. For hyperpolarized gases the NMR signal is improved up to several orders of magnitude. However, gases have a high diffusivity which strongly influences the NMR signal strength, hence the resolution and appearance of the images. The most interesting question in spatially resolved experiments is of course the achievable resolution and contrast by controlling the diffusivity of the gas. The influence of such diffusive processes scales with the diffusion coefficient, the strength of the magnetic field gradients and the timings used in the experiment. Diffusion may not only limit the MRI resolution, but also distort the line shape of MR images for samples, which contain boundaries or diffusion barriers within the sampled space. In addition, due to the large polarization in gaseous 3He and 129Xe, spin diffusion (different from particle diffusion) could play a role in MRI experiments. It is demonstrated that for low temperatures some corrections to the NMR measured diffusion coefficient have to be done, which depend on quantum exchange effects for indistinguishable particles. Physically, if these effects can not change the spin current, they can do it indirectly by modifying the velocity distribution of the different spin states separately, so that the subsequent collisions between atoms and therefore the diffusion coefficient can eventually be affected. A detailed study of the hyperpolarized gas diffusion coefficient is presented, demonstrating the absence of spin diffusion (different from particle diffusion) influence in MRI at clinical conditions. A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. The experimental measured diffusion agrees with theoretical simulations. Therefore, the molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this allows for images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion.

NMR studies on supramolecular aggregates in solution and the solid state

The aim of this work presented here is the characterization of structure and dynamics of different types of supramolecular systems by advanced NMR spectroscopy. One of the characteristic features of NMR spectroscopy is based on its high selectivity. Thus, it is desirable to exploit this technique for studying structure and dynamics of large supramolecular systems without isotopic enrichment. The observed resonance frequencies are not only isotope specific but also influenced by local fields, in particular by the distribution of electron density around the investigated nucleus. Barbituric acid are well known for forming strongly hydrogen-bonded complexes with variety of adenine derivatives. The prototropic tautomerism of this material facilitates an adjustment to complementary bases containing a DDA(A = hydrogen bond acceptor site, D = hydrogen bond donor site) or ADA sequences, thereby yielding strongly hydrogen-bonded complexes. In this contribution solid-state structures of the enolizable chromophor "1-n-butyl-5-(4-nitrophenyl)-barbituric acid" that features adjustable hydrogen-bonding properties and the molecular assemblies with three different strength of bases (Proton sponge, adenine mimetic 2,6-diaminopyridine (DAP) and 2,6-diacetamidopyridine (DAC)) are studied. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for measuring the diffusion coefficient, thereby reflecting the effective size and shape of a molecular species. In this work the investigation of supramolecular aggregates in solution state by means of DOSY NMR techniques are performed. The underlying principles of DOSY NMR experiment are discussed briefly and more importantly two applications demonstrating the potential of this method are focused on. Calix[n]arenes have gained a rather prominent position, both as host materials and as platforms to design specific receptors. In this respect, several different capsular contents of tetra urea calix[4]arenes (benzene, benzene-d6, 1-fluorobenzene, 1-fluorobenzene-d5, 1,4-difluorobenzene, and cobaltocenium) are studied by solid state NMR spectroscopy. In the solid state, the study of the interaction between tetra urea calix[4]arenes and guest is simplified by the fact that the guests molecule remains complexed and positioned within the cavity, thus allowing a more direct investigation of the host-guest interactions.

Hundertneunundzwanzig Xe NMR for investigations of complex and dynamic systems

In this work, the remarkable versatility and usefulness of applications of Xe-129 NMR experiments is further extended. The application of Xe-129 NMR spectroscopy to very different system is studied, including dynamic and static, solid and liquid, porous and non-porous systems. Using the large non-equilibrium polarization created by hyperpolarization of Xe-129, time-resolved NMR measurements can be used for the online-monitoring of dynamic systems. In the first part of this work, several improvements for medical applications of hyperpolarized Xe-129 are achieved and their feasibility shown experimentally. A large gain in speed and reproducibility of the accumulation process of Xe-129 as ice and an enhancement of the usable polarization in any experiment requiring prior accumulation are achieved. An enhancement of the longitudinal relaxation time of Xe-129 is realized by admixture of a buffer gas during the storage of hyperpolarized Xe-129. Pursuing the efforts of simplifying the accumulation process and enhancing the storage time of hyperpolarized Xe-129 will allow for a wider use of the hyperpolarized gas in (medical) MRI experiments. Concerning the use of hyperpolarized Xe-129 in MRI, the influence of the diffusion coefficient of the gas on parameters of the image contrast is experimentally demonstrated here by admixture of a buffer gas and thus changing the diffusion coefficient. In the second part of this work, a polymer system with unique features is probed by Xe-129 NMR spectroscopy, proving the method to be a valuable tool for the characterization of the anisotropic properties of semicrystalline, syndiotactic polystyrene films. The polymer films contain hollow cavities or channels with sizes in the sub-nanometer range, allowing for adsorption of Xe-129 and subsequent NMR measurements. Despite the use of a ’real-world’ system, the transfer of the anisotropic properties from the material to adsorbed Xe-129 atoms is shown, which was previously only known for fully crystalline materials. The anisotropic behavior towards atomar guests inside the polymer films is proven here for the first time for one of the phases. For the polymer phase containing nanochannels, the dominance of interactions between Xe-129 atoms in the channels compared to interactions between Xe atoms and the channel walls are proven by measurements of a powder sample of the polymer material and experiments including the rotation of the films in the external magnetic field as well as temperature-dependent measurements. The characterization of ’real-world’ systems showing very high degrees of anisotropy by Xe-129 are deemed to be very valuable in future applications. In the last part of this work, a new method for the online monitoring of chemical reactions has been proposed and its feasibility and validity are experimentally proven. The chemical shift dependence of dissolved Xe-129 on the composition of a reaction mixture is used for the online monitoring of free-radical miniemulsion polymerization reactions. Xe-129 NMR spectroscopy provides an excellent method for the online monitoring of polymerization reactions, due to the simplicity of the Xe-129 NMR spectra and the simple relationship between the Xe-129 chemical shift and the reaction conversion. The results of the time-resolved Xe-129 NMR measurements are compared to those from calorimetric measurements, showing a good qualitative agreement. The applicability of the new method to reactions other than polymerization reactions is investigated by the online monitoring of an enzymatic reaction in a miniemulsion. The successful combination of the large sensitivity of Xe-129, the NMR signal enhancements due to hyperpolarization, and the solubility of Xe-129 gives access to the large new field of investigations of chemical reaction kinetics in dynamic and complex systems like miniemulsions.

The use of mobile single-sided NMR for the diagnosis of osteoporosis: a preliminary study

Una nuova ed originale tecnica è stata messa a punto, finalizzata alla realizzazione di una procedura per la diagnosi dell’osteoporosi, mediante l’utilizzo di scanner low field single-sided NMR. Tre differenti scanner (NMR MOLE, MOUSE PM 10 e MOUSE PM5) sono stati usati per determinare il Bone Volume-to-Total Volume ratio (BV/TV), parametro che fornisce indicazioni sulla microstruttura dell’osso. I risultati sono stati confrontati con le analisi micro-CT. Gli esperimenti sono stati condotti nel Lab. NMR del dipartimento DIFA di UNIBO e nel Lab. NMR della Victoria University di Wellington (NZ), durante un periodo di visita di cinque mesi, supportato da una borsa di studio della “Facoltà di Scienze” di UNIBO. Le analisi micro-CT sono state condotte presso il Lab. di Tecnologie Mediche dell’Istituto Ortopedico Rizzoli, Bologna. La ricerca è stata parzialmente finanziata dalla “Fondazione del Monte di Bologna e Ravenna”. La caratterizzazione dell’osso trabecolare di campioni animali e dei tessuti che lo circondano (come cartilagine e muscolo) è stata condotta tramite mappe di correlazione T1-T2 e D-T2 , dove T1 e T2 sono, rispettivamente, il tempo di rilassamento longitudinale e trasversale del nucleo 1H, e D è il coefficiente di autodiffusione molecolare. E’ stata sviluppata una sequenza di impulsi (Diffusion-Weighted T1-T2) per ottenere mappe T1-T2 pesate in diffusione. I risultati hanno consentito di mettere a punto una procedura che elimina il segnale NMR proveniente da cartilagine e muscolo, rendendo più realistico lo scenario di applicazione in-vivo. I tre diversi dispositivi NMR hanno dato risultati consistenti tra loro e con le immagini micro-CT. L’intera catena di esperimenti condotti ha mostrato che dispositivi NMR single-sided possono essere usati per valutare il BV/TV di ossa trabecolari, con il vantaggio di essere portatili, a basso costo e non invasivi, permettendo campagne di screening della popolazione a rischio osteoporosi.

Characterization of HgCl2 Tridentate Amine Complexes by X-ray Crystallography, NMR and ESI-MS

Two new HgCl2 complexes of tridentate nitrogen ligands were characterized by X-ray crystallography, proton NMR spectroscopy and ESI-MS. The five-coordinate complex [Hg(BMPA)Cl-2] (1) (BMPA = bis(2-pyridylmethyl)amine) crystallized from acetonitrile/m-xylene by slow evaporation in the monoclinic space group P2(1)/n with a = 8.3896(8) , b = 12.8020(13) , c = 13.3526(13) , alpha = 90A degrees, beta A = 90.480(2)A degrees, gamma A = 90A degrees and z = 4. The square pyramidal structure (tau = 0.009) has approximate C (s) symmetry. Despite comparable Hg-N bond lengths in 1, inversion of the central nitrogen was rapid on the chemical shift time scale in dilute solution except at very low temperatures. The related complex [Hg(BEPA)Cl-2] (2) (BEPA = bis(2-{pyrid-2-yl}ethyl)amine) crystallized from acetonitrile/ethyl acetate/hexanes by slow diffusion in the orthorhombic space group Pnma with a = 13.424(3) , b = 14.854(3) , c = 8.118(2) , alpha = 90A degrees, beta A = 90A degrees, gamma A = 90A degrees and z = 4. The mixed geometry structure (tau = 0.56) also has crystallographic mirror symmetry as well as C (s) point group symmetry. In dilute acetonitrile solution, 1 was stable while 2 slowly converted to a more thermodynamically stable complex.

Hydrodynamic Characterization of Bile Salt Host-Guest Complexes by Pulsed Field Gradient NMR Spectroscopy

The work described herein is aimed at understanding primary and secondary aggregation of bile salt micelles and how micelles can perform chiral recognition of binapthyl analytes. Previous work with cholate and deoxycholate using micellar electrokinetic chromatography (MEKC) and nuclear magnetic resonance (NMR) has provided insightinto cholate and deoxycholate micelle formation, especially with respect to the critical micelle concentration (CMC). Chiral separations of the model analyte, 1,1â??-binaphthyl-2,2â??-diyl hydrogen phosphate (BNDHP), via cholate (C) and deoxycholate (DC) mediated MEKC separataions previously have shown the DC CMC to be 7-10 mM andthe cholate CMC at 14 mM at ph 12. A second model analyte,1,1â??-binaphthol (BN), was also previously investigated to probe micellar structure, but the MEKC data for this analyte implied a higher CMC, which may be interpreted as secondary aggregation. Thiswork extends the investigation of bile salts to include pulsed field gradient spin echo (PFGSE) NMR experiments being used to gain information about the size and degree of polydispersity of cholate and deoxycholate micelles. Concentrations of cholate below 10mM show a large variation in effective radius likely due to the existence of transient preliminary aggregates. The onset of the primary micelle shows a dramatic increase in effective radius of the micelle in cholate and deoxycholate. In the region of expectedsecondary aggregation a gradual increase of effective radius was observed with cholate; deoxycholate showed a persistent aggregate size in the secondary micelle region that is modulated by the presence of an analyte molecule. Effective radii of cholate anddeoxycholate (individually) were compared with and without R- and S-BNDHP in order to observe the effective radius difference of micelles with and without analyte present. The presence of S-BNDHP consistently resulted in a larger effective aggregate radius incholate and deoxycholate, confirming previous data of the S-BNDHP interacting more with the micelle than R-BNDHP. In total, various NMR techniques, like diffusion NMR can be used to gain a greater understanding of the bile salt micellization process and chiral resolution.

A MICROFLUIDIC METHOD TO MEASURE DIFFUSION IN HYDROGELS

A novel microfluidic method is proposed for studying diffusion of small molecules in a hydrogel. Microfluidic devices were prepared with semi-permeable microchannels defined by crosslinked poly(ethylene glycol) (PEG). Uptake of dye molecules from aqueous solutions flowing through the microchannels was observedoptically and diffusion of the dye into the hydrogel was quantified. To complement the diffusion measurements from the microfluidic studies, nuclear magnetic resonance(NMR) characterization of the diffusion of dye in the PEG hydrogels was performed. The diffusion of small molecules in a hydrogel is relevant to applications such asdrug delivery and modeling transport for tissue-engineering applications. The diffusion of small molecules in a hydrogel is dependent on the extent of crosslinking within the gel, gel structure, and interactions between the diffusive species and the hydrogel network. These effects were studied in a model environment (semi-infinite slab) at the hydrogelfluid boundary in a microfluidic device. The microfluidic devices containing PEG microchannels were fabricated using photolithography. The unsteady diffusion of small molecules (dyes) within the microfluidic device was monitored and recorded using a digital microscope. The information was analyzed with techniques drawn from digital microscopy and image analysis to obtain concentration profiles with time. Using a diffusion model to fit this concentration vs. position data, a diffusion coefficient was obtained. This diffusion coefficient was compared to those from complementary NMR analysis. A pulsed field gradient (PFG) method was used to investigate and quantify small molecule diffusion in gradient (PFG) method was used to investigate and quantify small molecule diffusion in hydrogels. There is good agreement between the diffusion coefficients obtained from the microfluidic methods and those found from the NMR studies. The microfluidic approachused in this research enables the study of diffusion at length scales that approach those of vasculature, facilitating models for studying drug elution from hydrogels in blood-contacting applications.

Quantifying The Diffusion And Erosion Of Degradable Hydrogels Using A Microfluidic Technique

Hydrogels are composed of cross-linked networks of hydrophilic polymers that are biocompatible due to their high water content. Mass transfer through hydrogels has been suggested as an effective method of drug delivery, specifically in degradable polymers to minimize lasting effects within the body. Diffusion of small molecules in poly (ethylene glycol) diacrylate (PEG-DA) and dextran methacrylate (dex-MA) hydrogels was characterized in a microfluidic device and by complementary techniques. Microfluidic devices were prepared by crosslinking a formulation of hydrogel and photo-initiator, with and without visible dye, using photolithography to define a central microchannel. Channel sizes within the devices were approximately 600 ¿m to simulate vessels within the body. The microfluidic technique allows for both image and effluent analyses. To visualize the diffusive behavior within the dextran hydrogel, methylene blue and sulforhodamine 101 dyes were used in both elution and uptake experiments. Three analysis techniques for measuring diffusion coefficients were used to quantify the diffusion of solute in the hydrogel, including optical microscopy, characterization of device effluent, and NMR analyses. The optical microscopy technique analyzes images of the dye diffusion captured by a stereomicroscope to generate dye concentration v. position profiles. The data was fit to a diffusion model to determine diffusion coefficients and the dye release profile. In a typical elution experiment, aqueous solution is pumped through the microchannel and dye diffuses out of the hydrogel and into the aqueous phase. During elution, images are taken at regular time intervals and the effluent was collected. Analysis of the device effluent was performed using ultraviolet-visible (UV/Vis) spectroscopy to determine the effluent dye concentration and thus a short-time diffusion coefficient. Nuclear magnetic resonance (NMR) was used to determine a free diffusion coefficient of molecules in hydrogel without the effect of a concentration gradient. Diffusion coefficients for methylene blue and sulforhodamine 101 dyes in dex-MA hydrogel calculated using the three analysis methods all agree well. It was determined that utilizing a combination of the three techniques offers greater insight into molecular diffusion in hydrogels than employing each technique individually. The use of the same microfluidic devices used to measure diffusion is explored in the use of studying the degradation of dex-MA hydrogels. By combining what is known about the degradation rate in regards to the effect of pH and crosslinking and the ability to use a dye solution in contrast to establish the hydrogel boundaries could be a novel approach to studying hydrogel degradation.

A Microfluidic Method to Measure Small Molecule Diffusion in Hydrogels

Drug release from a fluid-contacting biomaterial is simulated using a microfluidic device with a channel defined by solute-loaded hydrogel; as water is pumped through the channel, solute transfers from the hydrogel into the water. Optical analysis of in-situ hydrogels, characterization of the microfluidic device effluent, and NMR methods were used to find diffusion coefficients of several dyes (model drugs) in poly( ethylene glycol) diacrylate (PEG-DA) hydrogels. Diffusion coefficients for methylene blue and sulforhodamine 101 in PEG-DA calculated using the three methods are in good agreement; both dyes are mobile in the hydrogel and elute from the hydrogel at the aqueous channel interface. However, the dye acid blue 22 deviates from typical diffusion behavior and does not release as expected from the hydrogel. Importantly, only the microfluidic method is capable of detecting this behavior. Characterizing solute diffusion with a combination of NMR, optical and effluent methods offer greater insight into molecular diffusion in hydrogels than employing each technique individually. The NMR method made precise measurements for solute diffusion in all cases. The microfluidic optical method was effective for visualizing diffusion of the optically active solutes. The optical and effluent methods show potential to be used to screen solutes to determine if they elute from a hydrogel in contact with flowing fluid. Our data suggest that when designing a drug delivery device, analyzing the diffusion from the molecular level to the device level is important to establish a complete picture of drug elution, and microfluidic methods to study such diffusion can play a key role. (C) 2013 Elsevier B.V. All rights reserved.

Improved impurity fingerprinting of heparin by high resolution (1)H NMR spectroscopy

For improving the identification of potential heparin impurities such as oversulfated chondroitin sulfate (OSCS) the standard 2D (1)H-(1)H NMR NOESY was applied. Taking advantage of spin diffusion and adjusting the experimental parameters accordingly additional contaminant-specific signals of the corresponding sugar ring protons can easily be detected. These are usually hidden by the more intense heparin signals. Compared to the current 1D (1)H procedure proposed for screening commercial unfractionated heparin samples and focusing on the contaminants acetyl signals more informative and unique fingerprints may be obtained. Correspondingly measured (1)H fingerprints of a few potential impurities are given and their identification in two contaminated commercial heparin samples is demonstrated. The proposed 2D NOESY method is not intended to replace the current 1D method for detecting and quantifying heparin impurities but may be regarded as a valuable supplement for an improved and more reliable identification of these contaminants.