Cross-polarization Method Research Articles

Miniaturized fundus camera based on cross-polarization and in vivo verification

Abstract As an important part of clinical examination, fundus examination can reveal early symptoms of both eye and chronic physical diseases, thus helping doctors and automated screening to diagnose and treat in time. However, widely used portable fundus cameras are often disturbed by stray light, which seriously affects the quality of fundus imaging, extremely detrimental to the clinic. In this work, we have successfully built a miniaturized fundus camera based on the cross-polarization method, which simplifies the system design while guaranteeing high-quality imaging compared with other methods. The simulation results of the optical path and the imaging effect in vivo show that cross-polarization has a powerful effect on eliminating stray light. Our approach provides a new solution for the field of fundus photography and an application-level advance for the popularization of medical resources.

Artifact suppression using cross-circular polarization for millimeter-wave imaging

Millimeter-wave imaging is widely applied to radar detection, personnel security inspection, environmental perception, and so on. Multipath artifact is a common phenomenon in active millimeter-wave (AMMW) imaging and is difficult to be removed. The suppression methods in image reconstruction and post-processing stage are usually complex or time-consuming. This report proposes a cross-polarization method to suppress multipath artifacts between equivalent two-cylinder structures before image reconstruction. The physical mechanisms of co-polarization and cross-polarization imaging are revealed. The suppression effectiveness is demonstrated by conducting W-band AMMW imaging simulation and measurement experiments of a typical multipath scenario at the central frequency of 100 GHz (97 ∼103 GHz). The proposed method can directly reconstruct the image with artifact suppression and reduce the pressure of post-processing.

Quantifying Micromolar Crystallinity in Pharmaceutical Materials Utilizing 19F Solid-State NMR.

Quantifying low-level components in solid-state analysis presents a significant challenge for most thermal, diffractometric, vibrational, and spectroscopic techniques. In pharmaceutical analysis, identifying and quantifying the physical form of the drug substance in solid dosages is a critical task to ensure the quality of drug products. For example, recrystallization of active pharmaceutical ingredients in amorphous solid dispersions can compromise the stability and bioavailability of drug products. Herein, we have developed and demonstrated fluorine-19 solid-state nuclear magnetic resonance (19F ssNMR) methods and pushed the boundary to quantify minor crystalline contents in amorphous pharmaceuticals. Calibration curves suggest that 19F direct polarization and 1H-19F cross-polarization ssNMR can readily quantify 0.1% w/w crystalline compound I, a commercial fluorinated drug molecule developed by Merck & Co., Inc., Rahway, NJ, U.S.A., in its amorphous formulation. 1H-19F multiple cross-polarization (MultiCP) has been implemented, for the first time, and compared with conventional cross-polarization methods. Most importantly, a relaxation-filtered 19F ssNMR method was utilized to unambiguously identify and quantify as low as 0.04% w/w crystalline components, that is, 6 μmol in a 100 mg tablet at 25% drug loading, by suppressing the signal from the amorphous counterpart. Such a low level of detection offers high confidence and sensitivity to quantify trace amounts of phase change in pharmaceutical amorphous materials in the solid state, which can facilitate formulation development as well as quality control.

Nutraceuticals in Bulk and Dosage Forms: Analysis by 35Cl and 14N Solid-State NMR and DFT Calculations.

This study uses 35Cl and 14N solid-state NMR (SSNMR) spectroscopy and dispersion-corrected plane-wave density functional theory (DFT) calculations for the structural characterization of chloride salts of nutraceuticals in their bulk and dosage forms. For eight nutraceuticals, we measure the 35Cl EFG tensor parameters of the chloride ions and use plane-wave DFT calculations to elucidate relationships between NMR parameters and molecular-level structure, which provide rapid NMR crystallographic assessments of structural features. We employ both 35Cl direct excitation and 1H→35Cl cross-polarization methods to characterize a dosage form containing α-d-glucosamine HCl, observe possible impurity and/or adulterant phases, and quantify the weight percent of the active ingredient. To complement this, we also investigate 14N SSNMR spectroscopy and DFT calculations to characterize nitrogen atoms in the nutraceuticals. This includes a discussion of targeted acquisition experimental protocols (i.e., acquiring a select region of the overall pattern that features key discontinuities) that allow ultrawideline spectra to be acquired rapidly, even for unreceptive samples (i.e., those with long values of T1(14N), short values of T2eff(14N), or very broad patterns). It is hoped that these experimental and computational protocols will be useful for the characterization of various solid forms of nutraceuticals (i.e., salts, polymorphs, hydrates, solvates, cocrystals, amorphous solid dispersions, etc.), help detect impurity and counterfeit solid phases in dosage forms, and serve as a foundation for future NMR crystallographic studies of nutraceutical solid forms, including studies using ab initio crystal structure prediction algorithms.

Maximizing efficiency of dipolar recoupling in solid-state NMR using optimal control sequences.

Dipolar recoupling is a central concept in the nuclear magnetic resonance spectroscopy of powdered solids and is used to establish correlations between different nuclei by magnetization transfer. The efficiency of conventional cross-polarization methods is low because of the inherent radio frequency (rf) field inhomogeneity present in the magic angle spinning (MAS) experiments and the large chemical shift anisotropies at high magnetic fields. Very high transfer efficiencies can be obtained using optimal control–derived experiments. These sequences had to be optimized individually for a particular MAS frequency. We show that by adjusting the length and the rf field amplitude of the shaped pulse synchronously with sample rotation, optimal control sequences can be successfully applied over a range of MAS frequencies without the need of reoptimization. This feature greatly enhances their applicability on spectrometers operating at differing external fields where the MAS frequency needs to be adjusted to avoid detrimental resonance effects.

Broadband adiabatic inversion cross-polarization to integer-spin nuclei with application to deuterium NMR.

Solid-state NMR (SSNMR) spectroscopy of integer-spin quadrupolar nuclei is important for the molecular-level characterization of a variety of materials and biological solids; of the integer spins, 2 H (S = 1) is by far the most widely studied, due to its usefulness in probing dynamical motions. SSNMR spectra of integer-spin nuclei often feature very broad powder patterns that arise largely from the effects of the first-order quadrupolar interaction; as such, the acquisition of high-quality spectra continues to remain a challenge. The broadband adiabatic inversion cross-polarization (BRAIN-CP) pulse sequence, which is capable of cross-polarization (CP) enhancement over large bandwidths, has found success for the acquisition of SSNMR spectra of integer-spin nuclei, including 14 N (S = 1), especially when coupled with Carr-Purcell/Meiboom-Gill pulse sequences featuring frequency-swept WURST pulses (WURST-CPMG) for T2 -based signal enhancement. However, to date, there has not been a systematic investigation of the spin dynamics underlying BRAIN-CP, nor any concrete theoretical models to aid in its parameterization for applications to integer-spin nuclei. In addition, the BRAIN-CP/WURST-CPMG scheme has not been demonstrated for generalized application to wideline or ultra-wideline (UW) 2 H SSNMR. Herein, we provide a theoretical description of the BRAIN-CP pulse sequence for spin-1/2 → spin-1 CP under static conditions, featuring a set of analytical equations describing Hartmann-Hahn matching conditions and numerical simulations that elucidate a CP mechanism involving polarization transfer, coherence exchange, and adiabatic inversion. Several experimental examples are presented for comparison with theoretical models and previously developed integer-spin CP methods, demonstrating rapid acquisition of 2 H NMR spectra from efficient broadband CP.

Field-free molecular orientation by delay- and polarization-optimized two fs pulses

Unless the molecular axis is fixed in the laboratory frame, intrinsic structural information of molecules can be averaged out over the various rotational states. The macroscopic directional properties of polar molecules have been controlled by two fs pulses with an optimized delay. In the method, the first one-color laser pulse provokes molecular alignment. Subsequently, the molecular sample is irradiated with the second two-color laser pulse, when the initial even—J states are aligned, and the odd—J states are anti-aligned in the thermal ensemble. The second pulse selectively orients only the aligned even—J states in the same direction, which results in significant enhancement of the net degree of orientation. This paper reports the results of simulations showing that the two-pulse technique can be even more powerful when the second pulse is cross-polarized. This study shows that the alignment and orientation can be very well synchronized temporally because the crossed field does not disturb the preformed alignment modulation significantly, suggesting that the molecules are very well confined in the laboratory frame. This cross-polarization method will serve as a promising technique for studying ultrafast molecular spectroscopy in a molecule-fixed frame.

The Study of Water Sorption with Hydrolysis Lignin by Solid-State NMR Spectroscopy

Hydrolysis lignin is formed as a by-product of cellulose production and has limited industrial application. The ability of hydrolysis lignin to absorb and retain some water is important aspect for the study of its properties and modification methods. The processes of water sorption by hydrolysis lignin were studied with solid-state NMR spectroscopy. The samples were humidified in desiccators containing different saturated salts solutions with different relative air humidity above them. The sorption capacity of the samples was determined by water sorbed from the air, and it was found that lignin absorbs the amount of water equal to 40% of sample weight at maximum relative humidity of the air. The cross-polarization (CP) and magic angle spinning (MAS) methods were used to register solid-state NMR spectra. Using the 1H-NMR spectra, it was found that the hydrolysis lignin is hydrated in the whole volume, and the water penetrates into the deep layers of polymer, however, the distribution of water at the likely sorption sites is uneven. It was obtained with use of 13C-NMR spectroscopy that hydrolysis lignin hydrates in both hydrophilic and hydrophobic regions of the macromolecule, and the bulk of sorbed water (~64%) concentrates around the hydroxyl and methoxyl groups of lignin and polysaccharide residues.

Study on the cross-polarization method for extracting internal information of objects

In noninvasive near-infrared (NIR) noncontact measurement, a cross-polarization method is employed to eliminate undesired surface reflection and extract useful internal information. Experiments on various samples (both in vitro and in vivo) at different source-detector separations (SDSs) were conducted to investigate the effectiveness of this method. In conclusion, the cross-polarization method is proved to be effective in eliminating surface reflection as well as conducive to the measurement of objects’ internal information and this method is more suitable for scattering objects with smooth surfaces and complex interiors. Furthermore, a larger SDS can lead to a better measurement effect. This study can be a reference for tissue constituent sensing.

14N overtone NMR under MAS: Signal enhancement using cross-polarization methods.

Polarization transfer methods are widely adopted for the purpose of correlating different nuclear species as well as to achieve signal enhancement. Polarization transfer from 1H to the 14N overtone transition (Δm = 2) can be achieved using cross polarization methods under magic-angle spinning conditions, where spin locks of the order of several milliseconds can be obtained on common bio-solids (α-glycine and N-acetylvaline). Signal enhancement factors up to 4.4 per scan, can be achieved under favorable conditions, despite MHz-sized quadrupolar interaction. Moreover, we present a detailed theoretical treatment and accurate numerical simulations which are in excellent agreement the unusual experimental matching conditions observed for cross-polarization to 14N overtone.

Modes coded modulation of vector light beams using spatial phase cross-polarized modulation

Vector light beams (VLBs), manifesting as the non-uniform spatial distribution of polarization states, have shown broad applications in increasing communication capacity. Here, we propose and experimentally demonstrate a spatial phase cross-polarized method for achieving a mode coded modulation of VLBs. By employing the polarization sensitivity of the spatial light modulators (SLMs), the left and the right-handed circularly polarized parts of light beams are modulated with opposite spatial spiral phase to produce VLBs by the coherent combination. Manipulating the spatial phase distribution of the left and the right-handed circularly polarized light beams, the VLBs with 16 modes ([m; l]=[2, 3, 4, 5, 3, 4, 5, 6, 4, 5, 6, 7, 5, 6, 7, 8; 0, −1, −2, −3, 1, 0, −1, −2, 2, 1, 0, −1, 3, 2, 1, 0]) are obtained and used to code digital signals. In the experiment, a 60 × 60 pixels flower gray image with 14 400 quaternary numbers are then coded to the 16 modes and decoded successfully after 1 m transmission in free space. And the flower gray image is also recovered accordingly.

Measurement of component content by a quantitative solid-state NMR method: Targeting systems with coexistence of 13C-19F and 13C-1H polymers

As an essential fluoropolymer, polytetrafluoroethylene (PTFE) is commonly mixed with 13C-1H engineering polymers to obtain favorable physical properties, such as high mechanical strength, excellent wear resistance and high chemical stability. It has been noted that, the relative content of PTFE determines the physical and electrochemical properties of PTFE contained material. However, a proper way to quantify the component content of such PTFE mixture/blend or other 13C-1H/13C-19F systems is still desired. In this work, a quantitative cross polarization (CP) method named dQCPz/dQCPzRC is proposed, which aims to quantify the component content of 13C-1H/13C-19F mixture or immiscible blend. Upon the tests for alanine/PTFE mixture, polystyrene/PTFE mixture and poly(vinyl alcohol)/PTFE blend, the performances of three methods are compared, including cross polarization (CP), direct polarization (DP) and dQCPz/dQCPzRC. It is demonstrated that, CP is not quantitative, whereas dQCPz/dQCPzRC provides an accuracy equivalent to the DP method. Moreover, dQCPz/dQCPzRC consumes notably shorter experimental time than that of DP. Those favorable performances imply that dQCPz/dQCPzRC method has potential to become a routine tool for measuring the component content of 13C-1H/13C-19F systems for industrial and scientific research.

Bulk Nuclear Hyperpolarization of Inorganic Solids by Relay from the Surface.

NMR is a method of choice to determine structural and electronic features in inorganic materials, and has been widely used in the past, but its application is severely limited by its low relative sensitivity. We show how the bulk of proton-free inorganic solids can be hyperpolarized with a general strategy using impregnation dynamic nuclear polarization through homonuclear spin diffusion between low-γ nuclei. This is achieved either through direct hyperpolarization or with a pulse cooling cross-polarization method, transferring hyperpolarization from protons to heteronuclei at particle surfaces. We demonstrate a factor of 50 gain in overall sensitivity for the 119Sn spectrum of powdered SnO2, corresponding to an acceleration of a factor >2500 in acquisition times. The method is also shown for 31P spectra of GaP, 113Cd spectra of CdTe, and 29Si spectra of α-quartz.

Use of reverse cross-polarization for editing solid–state proton NMR spectra

We present here the use of the cross-polarization - reverse cross-polarization (CP-RCP) method for editing proton spectra by identifying protons attached exclusively to a nucleus such as carbon or nitrogen. Experiments have been done at moderate spinning speeds utilizing the Combined Rotation and Multi-Pulse Scheme (CRAMPS) technique which provided resolution of the spectral lines that is sufficient for several small molecular systems. This approach, in addition to being an editing tool, helps to increase resolution further and also leads to identifying protons such as the OH and the SH protons. Here we present results of the application of the CP-RCP scheme to systems at natural abundance of the nuclei 13C and 15N. The utility of the method has been illustrated for the case several amino acids, a tri-peptide and a synthesized cocrystal.

Measurement of Nanowire Optical Modes Using Cross-Polarization Microscopy

A method to detect optical modes from vertical InGaAs nanowires (NWs) using cross-polarization microscopy is presented. Light scattered from the optical modes in the NWs is detected by filtering out the polarized direct reflection with a crossed polarizer. A spectral peak and a valley were seen to red-shift with increasing NW diameter in the measured spectra. The peak was assigned to scattering from the TE01 optical mode and the valley was an indication of the HE11 mode, based on finite-element and scattering matrix method simulations. The cross-polarization method can be used to experimentally determine the spectral positions of the TE01 and HE11 optical modes. The modes are significantly more visible in comparison to conventional reflectance measurements. The method can be beneficial in the characterization of NW solar cells, light-emitting diodes and lasers where precise mode control is required.

Solid-State 77Se NMR of Organoselenium Compounds through Cross Polarization Magic Angle Spinning (CPMAS) Method

Characterization of selenium states by 77Se NMR is quite important to provide vital information for mechanism studies in organoselenium-catalyzed reactions. With the development of heterogeneous polymer-supported organoselenium catalysts, the solid state 77Se NMR comes to the spotlight. It is necessary to figure out an advanced protocol that provides good quality spectra within limited time because solid state 77Se NMR measurements are always time consuming due to the long relaxation time and the relatively low sensitivity. Studies on small molecules and several novel polymer-supported organoselenium materials in this article showed that cross polarization (CP) method with the assistance of magic angle spinning (MAS) was more efficient to get high quality spectra than the methods by using single pulse (SP) or high power 1H decoupling (HPHD) combined with MAS. These results lead to a good understanding of the effect of the molecular structure, the heteronuclear coupling, the long-range ordering of the solid (crystal or amorphous), and the symmetry of 77Se on quality of their spectra.

Rotational resonance for a heteronuclear spin pair under magic-angle spinning in solid-state NMR.

Rotational resonance (R2) is one of the widely applied techniques in solid-state NMR for recoupling a homonuclear dipolar interaction under magic-angle spinning (MAS). R2 occurs as the result of interference between the difference of the chemical shifts and MAS. In this work, we extend R2 to a heteronuclear dipolar interaction in the interaction frame of RF irradiation. Based on the average Hamiltonian theory, we show that the recoupling of the heteronuclear dipolar (I-S) interaction occurs at the recoupling conditions written as ΩI'±ΩS'=kωr (k=0,±1,±2), where ΩX' is the RF offset for spin-X (X = I or S) scaled by RF irradiation. The new recoupling sequence for a heteronuclear spin pair is referred to as offset-driven cross polarization along the z axis (OD-CPZ). With the robustness for RF inhomogeneity and ten recoupling conditions to choose, OD-CPZ can be a useful frequency-selective cross polarization method. Experiments and numerical simulations are shown with the results of the theoretical analysis.

Characterization of biomass char formation investigated by advanced solid state NMR

Char is produced during pyrolysis of biomass and it could be valorised as soil amendment, activated carbon or to produce syngas or heat by further oxidation. The mechanisms of biochars formation have to be better understood in order to tailor their properties. For this purpose, the pyrolysis of biomass was conducted in a fixed bed reactor allowing a good control of pyrolysis conditions. Miscanthus and the macromolecules extracted from this same biomass (holocellulose, cellulose, ethanol organosolv lignin) were pyrolysed to various final temperatures (200–500 °C). The chemical moieties formed in the chars were studied by solid state 13C NMR. A Cross Polarization method at the Magic Angle Spinning with Adiabatic Passage though Hartmann-Hahn conditions (CP/MAS APHH) has been found to give similar spectra than the Direct Polarization quantitative method in much shorter acquisition times. A quantitative study on the formation of aromatic structures in the network of the macromolecules in miscanthus and in the fractionated macromolecules was conducted. It is shown that below 300 °C xylan is the main source of aromatic formation while above this temperature the aromatization of cellulose occurs. The interactions between lignin and carbohydrates inside the network of biomass for aromatic structures formation are discussed.

Quantitative solid-state 13C NMR with signal enhancement by multiple cross polarization

A simple new method is presented that yields quantitative solid-state magic-angle spinning (MAS) 13C NMR spectra of organic materials with good signal-to-noise ratios. It achieves long (>10ms) cross polarization (CP) from 1H without significant magnetization losses due to relaxation and with a moderate duty cycle of the radio-frequency irradiation, by multiple 1-ms CP periods alternating with 1H spin–lattice relaxation periods that repolarize the protons. The new method incorporates previous techniques that yield less distorted CP/MAS spectra, such as a linear variation (“ramp”) of the radio-frequency field strength, and it overcomes their main limitation, which is T1ρ relaxation of the spin-locked 1H magnetization. The ramp of the radio-frequency field strength and the asymptotic limit of cross polarization makes the spectral intensity quite insensitive to the exact field strengths used. The new multiCP pulse sequence is a “drop-in” replacement for previous CP methods and produces no additional data-processing burden. Compared to the only reliable quantitative 13C NMR method for unlabeled solids previously available, namely direct-polarization NMR, the measuring time is reduced by more than a factor of 50, enabling higher-throughput quantitative NMR studies. The new multiCP technique is validated with 14-kHz MAS on amino-acid derivatives, plant matter, a highly aromatic humic acid, and carbon materials made by low-temperature pyrolysis.

A Solid-State NMR Study of Amorphous Ezetimibe Dispersions in Mesoporous Silica

The purpose of this work is to examine the ability of methods based on multinuclear and multidimensional solid-state NMR (SSNMR) to perform detailed characterization of amorphous dispersions of ezetimibe adsorbed on mesoporous silica. Ezetimibe was loaded into two types of mesoporous silica with average pore sizes of 2.5 and 21 nm. The mesoporous materials were characterized by powder X-ray diffraction (PXRD), vibrational spectroscopy, differential scanning calorimetry, and (1)H, (13)C, (19)F, and (29)Si SSNMR analysis including relaxation time measurements. Interactions between the drug and silica were investigated using 1D and 2D SSNMR methods based on dipolar correlation using cross-polarization (CP) and spin diffusion. PXRD was used to show the absence of crystalline ezetimibe in the mesoporous materials, and (19)F SSNMR was used to assess drug physical state and study mobility. (19)F-(29)Si CP methods were used to directly detect adsorbed ezetimibe. (1)H-(13)C, (1)H-(19)F, and (1)H-(29)Si, and heteronuclear correlation and (1)H homonuclear correlation experiments were used to investigate interactions between the drug and silica through (1)H environments. SSNMR methods were able to detect interactions between the drug and the silica substrate. Differences between the drug loaded onto silica with two different pore sizes were observed, including differences in hydrogen bonding environment and molecular mobility. These methods should be useful for characterization of similar systems.