Decoupling Protein Concentration and Aggregate Content Using Diffusion and Water NMR.

Protein-based biopharmaceutical drugs, such as monoclonal antibodies, account for the majority of the best-selling drugs globally in recent years. For bioprocesses, key performance indicators are the concentration and aggregate level for the product being produced. In water NMR (NMR), the use of the water transverse relaxation rate [(HO)] has been previously used to determine protein concentration and aggregate level; however, it cannot be used to separate between them without using an additional technique.

Operando Nuclear Magnetic Resonance (NMR) Studies of a Trickle-bed Reactor Using D-T2 Correlations.

Catalytic conversions in fine-chemical and pharmaceutical production are increasingly performed in trickle-bed rectors. Optimisation of these processes is usually based on end of pipe measurement made at specific residence times. This process is both time-consuming and the data sometimes challenging to interpret.

Molecular Dynamics of Ionic Liquids from Fast-Field Cycling NMR and Molecular Dynamics Simulations.

Understanding the connection between the molecular structure of ionic liquids and their properties is of paramount importance for practical applications. However, this connection can only be established if a broad range of physicochemical properties on different length and time scales is already available. Even then, the interpretation of the results often remains ambiguous due to the natural limits of experimental approaches.

Characterization of Mixtures of Linear and Branched Hydrocarbons Confined within Porous Media Using 2D DQF-COSY NMR Spectroscopy.

The analysis of 1D anti-diagonal spectra from the projections of 2D double-quantum filtered correlation spectroscopy NMR spectra is presented for the determination of the compositions of liquid mixtures of linear and branched alkanes confined within porous media. These projected spectra do not include the effects of line broadening and therefore retain high-resolution information even in the presence of inhomogeneous magnetic fields as are commonly found in porous media. A partial least-square regression analysis is used to characterize the mixture compositions.

A simple liquid state H NMR measurement to directly determine the surface hydroxyl density of porous silica.

Silica is widely used in industrial applications and its performance is partially decided by its surface hydroxyl density . Here we report a quick, simple liquid H NMR method to determine using a benchtop H NMR spectrometer. The results show excellent agreement with the literature with an range from 4.

Diagnostic Ureteroscopy in CT Urography-Diagnosed Upper Tract Urothelial Carcinoma: Delay in Definitive Treatment and Increased Intravesical Recurrence.

Purpose To investigate the effect of diagnostic ureteroscopy (URS) on the delay to surgical treatment of upper tract urothelial carcinoma (UTUC) detected by imaging and the risk of intravesical recurrence. Materials and methods We undertook a retrospective case-note analysis of all patients who underwent radical nephroureterectomy (NUU) from November 2012 to July 2019. We identified those who underwent diagnostic ureteroscopy prior to NUU as Group 1 and those who did not undergo diagnostic URS as Group 2.

Characterizing pore-scale structure-flow correlations in sedimentary rocks using magnetic resonance imaging.

Quantitative, three-dimensional (3D) spatially resolved magnetic resonance flow imaging (flow MRI) methods are presented to characterize structure-flow correlations in a 4-mm-diameter plug of Ketton limestone rock using undersampled k- and q-space data acquisition methods combined with compressed sensing (CS) data reconstruction techniques. The acquired MRI data are coregistered with an X-ray microcomputed tomography (μCT) image of the same rock sample, allowing direct correlation of the structural features of the rock with local fluid transport characteristics. First, 3D velocity maps acquired at 35 μm isotropic spatial resolution showed that the flow was highly heterogeneous, with ∼10% of the pores carrying more than 50% of the flow.

Experimental Determination of H and CO Diffusion Coefficients in a Wax Mixture Confined in a Porous Titania Catalyst Support.

The ability to measure and predict molecular diffusion coefficients in multicomponent mixtures is not only of fundamental scientific interest but also of significant relevance in understanding how catalytic processes proceed. In the present work, the direct measurement of the molecular diffusion of H and CO gas-phase species diffusing in -alkane mixtures using pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) methods is reported. The work is of direct relevance to Fischer-Tropsch (FT) catalysis, with the measurements being made of the gas-wax system with the wax in both the bulk liquid state and when confined within a titania catalyst support, at temperatures and pressures typical of low-temperature FT synthesis.

The effect of hydrogen bonding on diffusion and permeability in UV-cured Polyacrylate-based networks for controlled release.

Polyacrylates are important polymers widely used in pharmaceutical industry such as drug coatings due to their low cost, processability and ease of functionalisation. Chemical functionalities (e.g.

NMR and Thermal Studies for the Characterization of Mass Transport and Phase Separation in Paracetamol/Copovidone Hot-Melt Extrusion Formulations.

The formulation of drug/polymer amorphous solid dispersions (ASDs) is one of the most successful strategies for improving the oral bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Hot-melt extrusion (HME) is one method for preparing ASDs that is growing in importance in the pharmaceutical industry, but there are still substantial gaps in our understanding regarding the dynamics of drug dissolution and dispersion in viscous polymers and the physical stability of the final formulations. Furthermore, computational models have been built to predict optimal processing conditions, but they are limited by the lack of experimental data for key mass transport parameters, such as the diffusion coefficient.

Determination of Carbon Number Distributions of Mixtures of Linear Hydrocarbons Confined within Porous Media Using Pulsed Field Gradient NMR.

Pulsed field gradient (PFG) NMR measurements, combined with a novel optimization method, are used to determine the composition of hydrocarbon mixtures of linear alkanes (C7-C16) in both the bulk liquid state and when imbibed within a porous medium of mean pore diameter 28.6 nm. The method predicts the average carbon number of a given mixture to an accuracy of ±1 carbon number and the mole fraction of a mixture component to within an average root-mean-square error of ±0.

Identification of sampling patterns for high-resolution compressed sensing MRI of porous materials: 'learning' from X-ray microcomputed tomography data.

There exists a strong motivation to increase the spatial resolution of magnetic resonance imaging (MRI) acquisitions so that MRI can be used as a microscopy technique in the study of porous materials. This work introduces a method for identifying novel data sampling patterns to achieve undersampling schemes for compressed sensing MRI (CS-MRI) acquisitions, enabling 3D spatial resolutions of 17.6 µm to be achieved.

Observation of high-temperature macromolecular confinement in lyophilised protein formulations using terahertz spectroscopy.

Characterising the structural dynamics of proteins and the effects of excipients are critical for optimising the design of formulations. In this work we investigated four lyophilised formulations containing bovine serum albumin (BSA) and three formulations containing a monoclonal antibody (mAb, here mAb1), and explored the role of the excipients polysorbate 80, sucrose, trehalose, and arginine on stabilising proteins. By performing temperature variable terahertz time-domain spectroscopy (THz-TDS) experiments it is possible to study the vibrational dynamics of these formulations.

Enabling High Spectral Resolution of Liquid Mixtures in Porous Media by Antidiagonal Projections of Two-Dimensional H NMR COSY Spectra.

The noninvasive, in situ chemical identification of liquid mixtures confined in porous materials is experimentally challenging. NMR is chemically resolved and applicable to optically opaque systems but suffers from a significant loss in spectral resolution in the presence of the magnetic field inhomogeneities typical of porous media. In this work, we introduce a method of analysis of conventional two-dimensional (2D) H NMR correlation spectroscopy (COSY) spectra based on the extraction of 1D antidiagonal projections, which are free from line-broadening effects and can therefore be used for chemical species identification.

Microstructure evolution during nano-emulsification by NMR and microscopy.

Hypothesis: Microstructure evolution in emulsions as a function of composition is of great interest but fundamentals have not yet been fully elucidated. Here, pulsed-field gradient (PFG) NMR diffusion measurements have been combined with confocal laser scanning microscopy (CLSM) to assess evolution of dynamics and microstructure during nano-emulsification.

Experiments: Diffusion coefficients of emulsions made of water, mineral oil and surfactants (Span 20 and Tween 80) were measured as a function of water composition and compared with the morphological features of the emulsions obtained by CLSM.

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution.

Purpose: Dynamic in-situ proton (H) magnetic resonance imaging (MRI) and H T-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumin (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time.

Methods: Rapid two-dimensional H MRI and diffusion weighted MRI were used to study the temporal changes in solids dissolution and characterise water mass transport characteristics. One-shot T relaxation time measurements were also acquired in an attempt to quantify the reconstitution time.

Spatially-resolved H NMR relaxation-exchange measurements in heterogeneous media.

In the last decades, the H NMR T-T relaxation-exchange (REXSY) technique has become an essential tool for the molecular investigation of simple and complex fluids in heterogeneous porous solids and soft matter, where the mixing-time-evolution of cross-correlated T-T peaks enables a quantitative study of diffusive exchange kinetics in multi-component systems. Here, we present a spatially-resolved implementation of the T-T correlation technique, named z-T-T, based on one-dimensional spatial mapping along z using a rapid frequency-encode imaging scheme. Compared to other phase-encoding methods, the adopted MRI technique has two distinct advantages: (i) is has the same experimental duration of a standard (bulk) T-T measurement, and (ii) it provides a high spatial resolution.

Optimising sampling patterns for bi-exponentially decaying signals.

A recently reported method, based on the Cramér-Rao Lower Bound theory, for optimising sampling patterns for a wide range of nuclear magnetic resonance (NMR) experiments is applied to the problem of optimising sampling patterns for bi-exponentially decaying signals. Sampling patterns are optimised by minimizing the percentage error in estimating the most difficult to estimate parameter of the bi-exponential model, termed the objective function. The predictions of the method are demonstrated in application to pulsed field gradient NMR data recorded for the two-component diffusion of a binary mixture of methane/ethane in a zeolite.

Under-sampling and compressed sensing of 3D spatially-resolved displacement propagators in porous media using APGSTE-RARE MRI.

A method for under-sampling and compressed sensing of 3D spatially-resolved propagators is presented and demonstrated for flow in a packed bed and a heterogeneous carbonate rock. By sampling only 12.5% of q,k-space, the experimental acquisition time was reduced by almost an order of magnitude.

In situ reaction monitoring in heterogeneous catalysts by a benchtop NMR spectrometer.

Understanding the reactivity and mass transport properties of porous heterogenous catalysts is important for the development of new materials. Whereas MRI has previously been used to correlate chemical kinetics and hydrodynamics under operando conditions, this paper demonstrates that a modern benchtop NMR spectrometer is a suitable alternative to obtain diverse reaction information in porous heterogeneous catalyst materials on a smaller scale. Besides information about the chemical conversion within the pores, it can also be used to study changes of surface interaction by T/T NMR relaxometry techniques and changes in mass transport by PFG NMR from a single chemical reaction.

An integrated total neutron scattering - NMR approach for the study of heterogeneous catalysis.

Nuclear magnetic resonance (NMR) and total neutron scattering techniques are established methods for the characterisation of liquid phases in confined pore spaces during chemical reactions. Herein, we describe the first combined total neutron scattering - NMR setup as a probe for the catalytic heterogeneous reduction of benzene-d6 with D2 in 3 wt% Pt/MCM-41.

Acquisition of spatially-resolved displacement propagators using compressed sensing APGSTE-RARE MRI.

A method is presented for accelerating the acquisition of spatially-resolved displacement propagators via under-sampling of an Alternating Pulsed Gradient Stimulated Echo - Rapid Acquisition with Relaxation Enhancement (APGSTE-RARE) data acquisition with compressed sensing image reconstruction. The method was demonstrated with respect to the acquisition of 2D spatially-resolved displacement propagators of water flowing through a packed bed of hollow cylinders. The q,k-space was under-sampled according to variable-density pseudo-random sampling patterns.

Diffusion, Ion Pairing and Aggregation in 1-Ethyl-3-Methylimidazolium-Based Ionic Liquids Studied by H and F PFG NMR: Effect of Temperature, Anion and Glucose Dissolution.

In this work, using H and F PFG NMR, we probe the effect of temperature, ion size/type and glucose dissolution on the rate of transport in 1-ethyl-3-methylimidazolium ([EMIM] )-based ionic liquids by measuring self-diffusion coefficients. Using such data, we are able to establish the degree of ion pairing and quantify the extent of ionic aggregation during diffusion. For the neat 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]) a strong degree of ion pairing is observed.

In Situ Chemically-Selective Monitoring of Multiphase Displacement Processes in a Carbonate Rock Using 3D Magnetic Resonance Imaging.

Accurate monitoring of multiphase displacement processes is essential for the development, validation and benchmarking of numerical models used for reservoir simulation and for asset characterization. Here we demonstrate the first application of a chemically-selective 3D magnetic resonance imaging (MRI) technique which provides high-temporal resolution, quantitative, spatially resolved information of oil and water saturations during a dynamic imbibition core flood experiment in an Estaillades carbonate rock. Firstly, the relative saturations of dodecane ( and water ( , as determined from the MRI measurements, have been benchmarked against those obtained from nuclear magnetic resonance (NMR) spectroscopy and volumetric analysis of the core flood effluent.

Modelling and upscaling of transport in carbonates during dissolution: Validation and calibration with NMR experiments.

We present an experimental and numerical study of transport in carbonates during dissolution and its upscaling from the pore (∼μm) to core (∼cm) scale. For the experimental part, we use nuclear magnetic resonance (NMR) to probe molecular displacements (propagators) of an aqueous hydrochloric acid (HCl) solution through a Ketton limestone core. A series of propagator profiles are obtained at a large number of spatial points along the core at multiple time-steps during dissolution.