Exploration of Materials for Three-Dimensional NMR Microcoil Production via CNC Micromilling and Laser Etching.

The excellent versatility of 5-axis computer numerical control (CNC) micromilling has led to its application for prototyping NMR microcoils tailored to mass-limited samples (reducing development time and cost). However, vibrations during 5-axis milling can hinder the creation of complex 3D volume microcoils (i.e., solenoids and saddle coils). To address these limitations, a high-resolution NSCNC ELARA 4-axis milling machine was developed with the extra precision required for making complex 3D volume microcoils. Upon investigating the performance of resonators made with various copper-coated dielectrics, resonators with poly(methyl methacrylate) (PMMA) provided the best SNR/line shape. Thus, complex 1.7 mm microcoil designs were machined from Cu-coated PMMA. A milled 6.4 mm solenoid also provided 6.6× the total carbon signal for a 13C-labeled broccoli seed compared to a commercial inverse 5 mm NMR probe (demonstrating potential for larger coil designs). However, the manufacture of coils <1.7 mm with copper-coated PMMA rods was challenging as ∼0.5 mm of remaining PMMA was needed to retain their structural integrity. To manufacture smaller microcoils, both a solenoid and saddle coil (both with 1 mm O.D., 0.1 mm thick walls) were etched from Cu-coated glass capillaries using a UV picosecond laser that was mounted onto an NSCNC 5-axis MiRA7L. Both resonators showed excellent signal and identified a wide range of metabolites in a 13C-labeled algae extract, while the solenoid was further tested on two copepod egg sacs (∼4 µg of total sample). In summary, the flexibility to prototype complex microcoils in-house allows laboratories to tailor microcoils to specific mass-limited samples while avoiding the costs of cleanrooms.

Rapid reaction optimization by robust and economical quantitative benchtop 19F NMR spectroscopy.

The instrumental analysis of reaction mixtures is usually the rate-determining step in the optimization of chemical processes. Traditionally, reactions are analyzed by gas chromatography, HPLC or quantitative NMR spectroscopy on high-field spectrometers. However, chromatographic methods require elaborate work-up and calibration protocols, and high-field NMR spectrometers are expensive to purchase and operate. This protocol describes an inexpensive and highly effective analysis method based on low-field benchtop NMR spectroscopy. Its key feature is the use of fluorine-labeled model substrates that, because of the wide chemical shift range and high sensitivity of 19F, enable separate, quantitative detection of product and by-product signals even on low-field, permanent magnet spectrometers. An external lock/shim device obviates the need for deuterated solvents, permitting the direct, noninvasive measurement of crude reaction mixtures with minimal workup. The low field-strength facilitates a homogeneous excitation over a wide chemical shift range, minimizing systematic integration errors. The addition of the optimal amount of the nonshifting relaxation agent tris(acetylacetonato) iron(III) minimizes relaxation delays at full resolution, reducing the analysis time to 32 s per sample. The correct choice of processing parameters is also crucial. A step-by-step guideline is provided, the influence of all parameters, including adjustments needed when using high-field spectrometers, is discussed and potential pitfalls are highlighted. The wide applicability of the analytical protocol for reaction optimization is illustrated by three examples: a Buchwald-Hartwig amination, a Suzuki coupling and a C-H arylation reaction.

Reproducibility of absolute quantification of adenosine triphosphate and inorganic phosphate in the liver with localized 31P-magnetic resonance spectroscopy at 3-T using different coils.

Concentrations of the key metabolites of hepatic energy metabolism, adenosine triphosphate (ATP) and inorganic phosphate (Pi), can be altered in metabolic disorders such as diabetes mellitus. 31Phosphorus (31P)-magnetic resonance spectroscopy (MRS) is used to noninvasively measure hepatic metabolites, but measuring their absolute molar concentrations remains challenging. This study employed a 31P-MRS method based on the phantom replacement technique for quantifying hepatic 31P-metabolites on a 3-T clinical scanner. Two surface coils with different size and geometry were used to check for consistency in terms of repeatability and reproducibility and absolute concentrations of metabolites. Day-to-day (n = 8) and intra-day (n = 6) reproducibility was tested in healthy volunteers. In the day-to-day study, mean absolute concentrations of γ-ATP and Pi were 2.32 ± 0.24 and 1.73 ± 0.26 mM (coefficient of variation [CV]: 7.3% and 8.8%) for the single loop, and 2.32 ± 0.42 and 1.73 ± 0.27 mM (CVs 6.7% and 10.6%) for the quadrature coil, respectively. The intra-day study reproducibility using the quadrature coil yielded CVs of 4.7% and 6.8% for γ-ATP and Pi without repositioning, and 6.3% and 7.1% with full repositioning of the volunteer. The results of the day-to-day data did not differ between coils and visits. Both coils robustly yielded similar results for absolute concentrations of hepatic 31P-metabolites. The current method, applied with two different surface coils, can be readily utilized in long-term and interventional studies. In comparison with the single loop coil, the quadrature coil also allows measurements at a greater distance between the coil and liver, which is relevant for studying people with obesity.

Salivary Metabolites in Patients with Mucopolysaccharidosis

ABSTRACT Objective: To identify the salivary metabolites profile of Mucopolysaccharidosis (MPS) types I, II, IV, and VI patients. Material and Methods: The participants were asked to refrain from eating and drinking for one hour before sampling, performed between 7:30 and 9:00 a.m. Samples were centrifuged at 10.000 × g for 60 min at 4°C, and the supernatants (500µl) were stored at −80°C until NMR analysis. The salivary proton nuclear magnetic resonance (1H-NMR) spectra were acquired in a 500 MHz spectrometer, and TOCSY experiments were used to confirm and assign metabolites. Data were analyzed descriptively. Results: Differences in salivary metabolites were found among MPS types and the control, such as lactate, propionate, alanine, and N-acetyl sugar. Understanding these metabolite changes may contribute to precision medicine and early detection of mucopolysaccharidosis and its monitoring. Conclusion: The composition of low molecular weight salivary metabolites of mucopolysaccharidosis subjects may present specific features compared to healthy controls.

Evaluación del tracto de salida del ventrículo derecho mediante resonancia magnética con flujo 4D en pacientes sometidos a recambio valvular pulmonar transcatéter / 4D flow magnetic resonance imaging to assess right ventricular outflow tract in patients undergoing transcatheter pulmonary valve replacement

Introducción y objetivos: La resonancia magnética (RM) con flujo 4D suele utilizarse para evaluar el ventrículo derecho y las arterias pulmonares antes del implante percutáneo de la válvula pulmonar (IPVP). Como el IPVP está limitado por el tamaño del tracto de salida del ventrículo derecho (TSVD), se necesita medirlo con precisión para planificar la intervención. El objetivo del presente estudio es comparar diferentes modalidades de RM con la medición invasiva del TSVD con balón.MétodosEstudio unicéntrico prospectivo de pacientes sometidos a IPVP por insuficiencia pulmonar aislada evaluada mediante RM con flujo 4D, precesión libre en estado estacionario/gradiente eco 3D (3D SSFP/GRE) y angiografía por RM con contraste. La medición con balón se consideró la referencia.ResultadosSe incluyó a 23 adultos (media de edad, 38,4±12,5 años). En 18 pacientes el IPVP fue exitoso. El diámetro medio del TSVD más pequeño fue de 25,4±4,3 mm medido con balón y 25,6±3,8 mm y 21,8±3,6 mm por RM con flujo 4D en sístole y diástole respectivamente. Comparados con los medidos con balón, los diámetros de TSVD se correlacionaron mejor cuando se estimaron mediante RM con flujo 4D sistólico (r=0,89; p<0,001) que mediante RM con flujo 4D diastólico (r=0,71; p<0,001), angiografía por R; 3D con contraste (r=0,73; p<0,001) o 3D SSFP/GRE (r=0,50; p=0,04), y no se correlacionaron de manera significativa cuando se realizaron en 2D en diástole o sístole. La diferencia media entre la RM con flujo 4D sistólico y la medición con balón fue de 0,2 mm (IC95%, –3,5 a 3,9 mm), en tanto que con las otras técnicas fue mayor.ConclusionesAdemás de la cuantificación de la insuficiencia de la válvula pulmonar, la RM con flujo 4D permite una estimación fiable de los diámetros del TSVD, sobre todo en sístole, lo que es fundamental antes de planificar el IPVP. (AU)

Introduction and objectives: Magnetic resonance imaging (MRI) including 4D flow is used before percutaneous pulmonary valve implantation (PPVI). As PPVI is limited by the size of the right ventricular outflow tract (RVOT), accurate sizing is needed to plan the intervention. The aim of this study was to compare different MRI modalities and invasive angiogram to balloon sizing of RVOT.MethodsSingle-centre prospective study of patients who underwent PPVI for isolated pulmonary regurgitation assessed by 4D flow MRI, 3D steady-state free precession/gradient echo (3D SSFP/GRE) and contrast magnetic resonance angiogram. Balloon sizing was considered as the reference.ResultsA total of 23 adults were included (mean age, 38.4±12.5 years). Eighteen patients underwent successful primary PPVI. The average of the narrowest RVOT diameter was 25.4±4.3mm by balloon sizing. Compared to balloon sizing, RVOT diameters were better correlated when estimated by systolic 4D flow MRI (r=0.89, P<0.001) than by diastolic 4D flow MRI (r=0.71, P<0.001), 3D contrast magnetic resonance angiography (r=0.73; P<.001) and 3D SSFP/GRE (r=0.50; P=.04) and not significantly correlated when estimated by 2D in diastole and systole. The mean difference between systolic 4D flow MRI and balloon sizing was 0.2mm (95%CI, –3.5 to 3.9 mm), whereas it was wider with other techniques.ConclusionsBeyond the quantification of pulmonary valve regurgitation, 4D flow allows accurate estimation of RVOT diameters, especially in systole, which is fundamental before planning PPVI. (AU)

A hybrid strategy combining solution NMR spectroscopy and isothermal titration calorimetry to characterize protein-nanodisc interaction.

NMR is a powerful tool for characterizing intermolecular interactions at atomic resolution. However, the nature of the complex interactions of membrane-binding proteins makes it difficult to elucidate the interaction mechanisms. Here, we demonstrated that structural and thermodynamic analyses using solution NMR spectroscopy and isothermal titration calorimetry (ITC) can clearly detect a specific interaction between the pleckstrin homology (PH) domain of ceramide transport protein (CERT) and phosphatidylinositol 4-monophosphate (PI4P) embedded in the lipid nanodisc, and distinguish the specific interaction from nonspecific interactions with the bulk surface of the lipid nanodisc. This NMR-ITC hybrid strategy provides detailed characterization of protein-lipid membrane interactions.

Utilidad de la jeringa 10 ml precargada de solución salina (ClNa 0. 9%) para la inyección de medios de contraste en tomografía computarizada o resonancia magnética en pacientes con cáncer de mama, cuello uterino y estómago / Utilidad de la jeringa 10 ml precargada de solución salina (ClNa 0. 9%) para la inyección de medios de contraste en tomografía computarizada o resonancia magnética en pacientes con cáncer de mama, cuello uterino y estómago

ANTECEDENTES: En cumplimiento del inciso e, sobre nuestras funciones como UFETS, que dice: "Desarrollar evaluaciones de tecnologías sanitarias, incluyendo medicamentos, dispositivos y equipos médicos, procedimientos médicos o quirúrgicos y sistemas de organización, en forma sistémica y objetiva aplicadas a la salud, basándose en la mejor evidencia científica disponible", realizamos esta revisión rápida sobre la utilidad de la jeringa 10 ml precargada de solución salina (ClNa 0.9%) para la inyección de medios de contraste en tomografía computarizada o resonancia magnética. ESTRATEGIA DE BÚSQUEDA DE INFORMACIÓN: Pregunta Clínica: En pacientes con cáncer de mama, cuello uterino y estómago que requieren inyección de medios de contraste ¿Cuál es la utilidad de la jeringa 10ml precarga de solución salina (NaCl 0.9%) en la realización de una tomografía computarizada o resonancia magnética con contraste? Recolecciòn de los Manuscritos a Revisar: Tipos de estudios: La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA) Estudios Observacionales (cohortes, caso y control, descriptivos) No hubo limitaciones acerca de la fecha de publicación o el idioma para ningún estudio. Fuentes de información: De acceso libre o Bases de datos: Pubmed y Cochrane Fecha de búsqueda: Desde el inicio de los tiempos hasta la actualidad. Términos de Búsqueda Considerando la pregunta PICO se construyó una estrategia de búsqueda. Sin restricciones en el idioma y año. DISCUSIÓN: Durante la sesión de panel se discutió los artículos encontrados, así como las búsquedas realizadas en las principales agencias de evaluación de tecnologías sanitarias y las guías que reportan información al respecto de jeringas precargadas 10 ml NaCl 0.9%. Con respecto a los estudios encontrados se ha evidenciado que el uso de jeringas precargadas NaCl 0.9% en los 03 estudios ha sido favorable en reducción de infecciones del torrente sanguíneo relacionadas a catéter, disminución en el riesgo de reemplazo del catéter venoso periférico, disminución del riesgo para pacientes y mejoras en la seguridad de los trabajadores de salud y también podría llevar a una reducción en costos asociados. El primer estudio si bien fue realizado en pacientes oncológicos, se realizó en ambientes de quimioterapia y el segundo estudio fue un estudio cuasi experimental que abarco pacientes que acudieron o estaban en diferentes áreas hospitalarias y en el caso del tercer estudio no se logró tener acceso al manuscrito en versión extensa debido a que fue publicado hace menos de un mes y el acceso era limitado. Por ello, se ha planteado que la evidencia obtenida con respecto al uso de jeringas precargadas es indirecta por lo cual es difícil establecer una conclusión con respecto a su uso en un área específica como previo a la realización de tomografía con contraste o una resonancia magnética. CONCLUSIONES: En el Instituto Nacional de Enfermedades Neoplásicas se realizan anualmente aproximadamente 45000 exámenes radiológicos de tipo TC ó RM que requieren el uso de contraste en pacientes con cáncer de mama, estómago o cuello uterino en donde se utilizaría jeringas 10 mL precargadas con solución salina 0.9%. Se realizó una búsqueda sistemática y una búsqueda dirigida de la evidencia para evaluar la utilidad de la jeringa precargada 10 mL con solución salina 0.9% y no se encontró evidencia directa de su uso en la población específica; sin embargo, se han reportado algunos artículos científicos que encuentran evidencia favorable de su uso comparado con la jeringa cargada manualmente. Se encontraron 03 artículos que comparando la tecnología sanitaria "Jeringa 10 mL precargada con NaCl 0.9%" con la jeringa de carga manual, las jeringas precargadas presentan: un menor porcentaje de remoción de jeringa por complicaciones, reducción de la tasa de infección del torrente sanguíneo relacionada con el catéter y reducción de la tasa de fallo de colocación del catéter venoso. Adicionalmente, según informes de contraloría y en base análisis internos de la institución se ha priorizado un presupuesto para la atención del cáncer de mama, cáncer de cuello uterino y cáncer de estómago para el estadiaje y tratamiento que en base al riesgo identificado "contaminación por uso de jeringas cargadas manualmente" se establezca la medida de control "utilizar jeringa precargada previo al examen". Con respecto a la adquisición, está disponible en Latinoamérica y es de fácil adquisición a solicitud. Finalmente, en base a la evidencia encontrada y los documentos revisados a nivel institucional el panel establece la necesidad de que el área de costos realice un análisis de impacto presupuestario que nos permita conocer si la inclusión de la tecnología sanitaria "Jeringa 10 mL precargada con NaCl 0.9%" implicaría una reducción de costos en el área específica en la cual se va a implementar.

Proton MRS on sub-microliter volume in rat brain using implantable NMR microcoils.

The use of miniaturized NMR receiver coils is an effective approach for improving detection sensitivity in studies using MRS and MRI. By optimizing the filling factor (the fraction of the coil occupied by the sample), and by increasing the RF magnetic field produced per unit current, the sensitivity gain offered by NMR microcoils is particularly interesting when small volumes or regions of interest are investigated. For in vivo studies, millimetric or sub-millimetric microcoils can be deployed in tissues to access regions of interest located at a certain depth. In this study, the implementation and application of a tissue-implantable NMR microcoil with a detection volume of 850 nL is described. The RF magnetic field generated by the microcoil was evaluated using a finite element method simulation and experimentally determined by high spatial resolution MRI acquisitions. The performance of the microcoil in terms of spectral resolution and limit of detection was measured at 7 T in vitro and in vivo in rodent brains. These performances were compared with those of a conventional external detection coil. Proton MR spectra were acquired in the cortex of rat brain. The concentrations of main metabolites were quantified and compared with reference values from the literature. In vitro and in vivo results obtained with the implantable microcoil showed a gain in sensitivity greater than 50 compared with detection using an external coil. In vivo proton spectra of diagnostic value were obtained from brain regions of a few hundred nanoliters. The similarities between spectra obtained with the implanted microcoil and those obtained with the external NMR coil highlight the minimally invasive nature of the coil implantation procedure. These implantable microcoils represent new tools for probing tissue metabolism in very small healthy or diseased regions using MRS.

An In-vivo 1H-MRS short-echo time technique at 7T: Quantification of metabolites in chronic multiple sclerosis and neuromyelitis optica brain lesions and normal appearing brain tissue.

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain lesions in 11 MS and 4 AQP4Ab-NMOSD patients using an optimised MRS methodology at ultra-high field strength (7T) incorporating correction for T2 water relaxation differences between lesioned and normal tissue. MS metabolite results were in keeping with the existing literature: total N-acetylaspartate (NAA) was lower in lesions compared to normal appearing brain white matter (NAWM) with reciprocal findings for myo-Inositol. An unexpected subtlety revealed by our technique was that total NAA differences were likely driven by NAA-glutamate (NAAG), a ubiquitous CNS molecule with functions quite distinct from NAA though commonly quantified together with NAA in MRS studies as total NAA. Surprisingly, AQP4Ab-NMOSD showed no significant differences for total NAA, NAA, NAAG or myo-Inositol between lesion and NAWM sites, nor were there any differences between MS and AQP4Ab-NMOSD for a priori hypotheses. Post-hoc testing revealed a significant correlation between NAWM Ins:NAA and disability (as measured by EDSS) for disease groups combined, driven by the AP4Ab-NMOSD group. Utilising an optimised MRS methodology, our study highlights some under-explored subtleties in MRS profiles, such as the absence of myo-Inositol concentration differences in AQP4Ab-NMOSD brain lesions versus NAWM and the potential influence of NAAG differences between lesions and normal appearing white matter in MS.

Valor adicional de la tecnología híbrida de PET/RM frente a la RM y la PET en la enfermedad cardiovascular / Additional value of hybrid PET/MR imaging versus MR or PET performed separately to assess cardiovascular disease

Introducción y objetivos Los sistemas híbridos de tomografía por emisión de positrones (PET) y resonancia magnética (RM) son una tecnología prometedora para el diagnóstico por imagen, pero su aplicación cardiovascular en nuestro entorno clínico es desconocida. Nuestro objetivo es evaluar el valor de los equipos integrados de PET/RM frente a la RM y la PET por separado. Métodos Se incluyó prospectivamente a 49 pacientes, 30 para valoración de viabilidad miocárdica (grupo coronario) y 19 para estudio de enfermedad inflamatoria, infecciosa y tumoral (grupo no coronario), a los que se realizó una PET/RM cardiaca con 18F-fluorodesoxiglucosa, incluyendo secuencias de corrección de atenuación y, simultáneamente a la PET, secuencias de cine, caracterización tisular o realce tardío de RM, según indicación clínica. Resultados El 87,8% de los estudios de PET/RM fueron inicialmente interpretables. La PET/RM mejoró el diagnóstico en el 42,1% de los pacientes del grupo coronario respecto a la PET o la RM por separado, y en el 88,9% del grupo no coronario. De los casos no concluyentes según la RM o la PET, la PET/RM reclasificó a estudio diagnóstico al 87,5% de los pacientes del grupo coronario y el 70% de los del no coronario. Conclusiones En nuestra serie, la tecnología multimodal de PET/RM añade valor diagnóstico en algunos pacientes con enfermedad cardiovascular, sobre todo en enfermedad no coronaria y con hallazgos no concluyentes por RM o PET, y complementa cada técnica por separado. Los principales beneficios incluyen la adquisición simultánea, la integración de imágenes anatómicas, funcionales y metabólicas y la interacción entre distintos profesionales expertos en imagen. (AU)

Introduction and objectives Hybrid positron emission tomography (PET) and magnetic resonance (MR) imaging is an emerging technology in the diagnosis of cardiovascular disease; however, there have been no reports of its use in the national clinical setting. Our objective was to evaluate the additional value of integrated PET/MR systems compared with MR and PET performed separately in this setting. Methods We prospectively included 49 patients, 30 to assess myocardial viability (coronary group) and 19 to assess inflammatory, infectious, and tumoral diseases (noncoronary heart disease group). All patients underwent cardiac 18F-fluorodeoxyglucose PET/MR. PET/MR studies included attenuation correction sequences, followed by simultaneous cardiac PET and cardiac MR acquisition, with protocols adapted to the clinical indication (cine, tissue characterization and/or late enhancement imaging). Results Most (87.8%) PET/MR studies were initially interpretable. Use of PET/MR improved diagnosis vs PET or MR performed separately in 42.1% of coronary cases and 88.9% of noncoronary cases. PET/MR enabled reclassification of 87.5% of coronary cases initially classified as showing inconclusive results on MR or PET and 70% of noncoronary cases. Conclusions In our series, multimodality PET/MR technology provided additional diagnostic value in some patients with cardiovascular disease compared with MR and PET performed separately, especially in cases of noncoronary heart disease and in those with inconclusive results on MR or PET. In our experience, the main benefits of PET/MR include the possibility of simultaneous acquisition, the in vivo integration of anatomical/functional/metabolic aspects, and the interaction of different experts in imaging modalities. (AU)

MRM Microcoil Performance Calibration and Usage Demonstrated on Medicago truncatula Roots at 22 T.

This protocol describes a signal-to-noise ratio (SNR) calibration and sample preparation method for solenoidal microcoils combined with biological samples, designed for high-resolution magnetic resonance imaging (MRI), also referred to as MR microscopy (MRM). It may be used at pre-clinical MRI spectrometers, demonstrated on Medicago truncatula root samples. Microcoils increase sensitivity by matching the size of the RF resonator to the size of the sample of interest, thereby enabling higher image resolutions in a given data acquisition time. Due to the relatively simple design, solenoidal microcoils are straightforward and cheap to construct and can be easily adapted to the sample requirements. Systematically, we explain how to calibrate new or home-built microcoils, using a reference solution. The calibration steps include: pulse power determination using a nutation curve; estimation of RF-field homogeneity; and calculating a volume-normalized signal-to-noise ratio (SNR) using standard pulse sequences. Important steps in sample preparation for small biological samples are discussed, as well as possible mitigating factors such as magnetic susceptibility differences. The applications of an optimized solenoid coil are demonstrated by high-resolution (13 x 13 x 13 µm3, 2.2 pL) 3D imaging of a root sample.

Microfluidic Overhauser DNP chip for signal-enhanced compact NMR.

Nuclear magnetic resonance at low field strength is an insensitive spectroscopic technique, precluding portable applications with small sample volumes, such as needed for biomarker detection in body fluids. Here we report a compact double resonant chip stack system that implements in situ dynamic nuclear polarisation of a 130 nL sample volume, achieving signal enhancements of up to - 60 w.r.t. the thermal equilibrium level at a microwave power level of 0.5 W. This work overcomes instrumental barriers to the use of NMR detection for point-of-care applications.

High-field and benchtop NMR spectroscopy for the characterization of new psychoactive substances.

New psychoactive substances (NPS) have become a serious threat to public health in Europe due to their ability to be sold in the street or on the darknet. Regulating NPS is an urgent priority but comes with a number of analytical challenges since they are structurally similar to legal products. A number of analytical techniques can be used for identifying NPS, among which NMR spectroscopy is a gold standard. High field NMR is typically used for structural elucidation in combination with others techniques like GC-MS, Infrared spectroscopy, together with databases. In addition to their strong ability to elucidate molecular structures, high field NMR techniques are the gold standard for quantification without any physical isolation procedure and with a single internal standard. However, high field NMR remains expensive and emerging "benchtop" NMR apparatus which are cheaper and transportable can be considered as valuable alternatives to high field NMR. Indeed, benchtop NMR, which emerged about ten years ago, makes it possible to carry out structural elucidation and quantification of NPS despite the gap in resolution and sensitivity as compared to high field NMR. This review describes recent advances in the field of NMR applied to the characterization of NPS. High-field NMR methods are first described in view of their complementarity with other analytical methods, focusing on both structural and quantitative aspects. The second part of the review highlights how emerging benchtop NMR approaches could act as a game changer in the field of forensics.

Mobile low field magnetic resonance hardware development.

Typically, NMR systems are bulky and expensive laboratory based equipment. For half a century after its scientific discovery taking NMR outside of a laboratory environment is still not a common practice due to the complexity of the underlining physical phenomena and its low sensitivity, to the myriad of technical challenges when integrating a complete system. The scarcity of compact and mobile NMR systems has prevented its proliferation into many other areas and applications. This paper describes the progress in the development of compact electronic spectrometers that we coupled with handheld sensors in order to provide complete mobile solutions. The key to this progress has been the modern advances in computing, electronics and permanent magnet technologies. Mobile NMR is now feasible as a valuable, non-invasive tool for industrial and medical applications. By leveraging the strengths of NMR, which is to probe at the molecular level and gain information about molecular structure, organisation, abundance and orientation, NMR is intrinsically suitable for non-destructive testing of a wide range of materials and their manufacturing processes. The development of complete NMR systems benefits from working across various disciplines and organisations. By embracing a collaborative approach we believe it will accelerate NMR technology to become more ubiquitous in the near future.

Nuclear magnetic resonance immunoassay of tetanus antibodies based on the displacement of magnetic nanoparticles.

A nuclear magnetic resonance (NMR) immunoassay based on the application of carbon-coated iron nanoparticles conjugated with recognition molecules was designed. The principle of the assay is that ELISA plates are coated with a capture element, and then an analyte is added and detected by conjugating the magnetic nanoparticles with recognition molecules. Afterwards, the elution solution (0.1-M sodium hydroxide) is added to displace the magnetic nanoparticles from the well surfaces into the solution. The detached magnetic nanoparticles reduce transverse relaxation time (T2) values of protons from the surrounding solution. A portable NMR relaxometer is used to measure the T2. Magnetic nanoparticles conjugated with streptavidin, monoclonal antibodies, and protein G were applied for the detection of biotinylated albumin, prostate-specific antigen, and IgG specific to tetanus toxoid (TT). The limit of detection of anti-TT IgG was 0.08-0.12 mIU/mL. The reproducibility of the assay was within the acceptable range (CV < 7.4%). The key novelty of the immunoassay is that the displacement of the nanoparticles from the solid support by the elution solution allows the advantages of the solid phase assay to be combined with the sensitive detection of the T2 changes in a volume of liquid.

Quantitative NMR (qNMR) for pharmaceutical analysis: The pioneering work of George Hanna at the US FDA.

In the last two decades, quantitative NMR (qNMR) has become increasingly important for the analysis of pharmaceuticals, chemicals, and natural products including dietary supplements. For the purpose of quality control and chemical standardization of a large variety of pharmaceutical, chemical, and medicinal products, qNMR has proven to be a valuable orthogonal quantification method and a compelling alternative to chromatographic techniques. This work reviews a fundamental component of the early development of qNMR, reflected in the pioneering work of the late George M. Hanna during the years between 1984 and 2006 at the US Food and Drug Administration (FDA). Because Hanna performed the majority of his groundbreaking work on a 90-MHz instrument, his legacy output connects with recent progress in low-field benchtop NMR instrumentation. Hanna gradually established the utility of qNMR for the routine quality control analyses practiced in pharmaceutical and related operations well ahead of his peers. His work has the potential to inspire new developments in qNMR applied to small molecules of biomedical importance.

Resolving the omega-3 methyl resonance with long echo time magnetic resonance spectroscopy in mouse adipose tissue at 9.4 T.

Tissue omega-3 (ω-3) content is biologically important to disease; however, its quantification with magnetic resonance spectroscopy in vivo is challenging due to its low concentration. In addition, the ω-3 methyl resonance (≈ 0.98 ppm) overlaps that of the non-ω-3 (≈ 0.90 ppm), even at 9.4 T. We demonstrate that a Point-RESolved Spectroscopy (PRESS) sequence with an echo time (TE) of 109 ms resolves the ω-3 and non-ω-3 methyl peaks at 9.4 T. Sequence efficacy was verified on five oils with differing ω-3 fat content; the ω-3 content obtained correlated with that measured using 16.5 T NMR (R2 = 0.97). The PRESS sequence was also applied to measure ω-3 content in visceral adipose tissue of three different groups (all n = 3) of mice, each of which were fed a different 20% w/w fat diet. The fat portion of the diet consisted of low (1.4%), medium (9.0%) or high (16.4%) ω-3 fat. The sequence was also applied to a control mouse fed a standard chow diet (5.6% w/w fat, which was 5.9% ω-3). Gas chromatography (GC) analysis of excised tissue was performed for each mouse. The ω-3 fat content obtained with the PRESS sequence correlated with the GC measures (R2 = 0.96). Apparent T2 times of methyl protons were assessed by obtaining spectra from the oils and another group of four mice (fed the high ω-3 diet) with TE values of 109 and 399 ms. Peak areas were fit to a mono-exponentially decaying function and the apparent T2 values of the ω-3 and non-ω-3 methyl protons were 906 ± 148 and 398 ± 78 ms, respectively, in the oils. In mice, the values were 410 ± 68 and 283 ± 57 ms for ω-3 and non-ω-3 fats, respectively.

Characteristics of Starch Extracted from the Stem of Pineapple Plant (Ananas comosus) - an Agro Waste from Pineapple Farms

Abstract The present study focused on the use of pineapple plant stem, which is an agro-waste, for the production of starch (11.08 % ± 0.77). Characters were studied using X-ray diffraction, nuclear magnetic resonance spectroscopy (NMR), fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and rheological methods. The granular size of stem starch was comparatively smaller than corn starch granules. The X-ray diffraction data revealed that stem starch has an A-type crystal structure. The molecular structure was similar to those obtained for native starches, which is confirmed by NMR and FTIR. The gelatinization temperature was observed to be higher than corn starch and rheological studies revealed; stem starch is more viscous than corn starch. The purity analysis showed that the harmful heavy metals were in negligible quantity and the tested pesticides were absent. This could make this a good source of starch for food industries. Results revealed that this agro-waste has a high potential for the production of good quality starch.

5-Axis CNC Micromilling for Rapid, Cheap, and Background-Free NMR Microcoils.

The superior mass sensitivity of microcoil technology in nuclear magnetic resonance (NMR) spectroscopy provides potential for the analysis of extremely small-mass-limited samples such as eggs, cells, and tiny organisms. For optimal performance and efficiency, the size of the microcoil should be tailored to the size of the mass-limited sample of interest, which can be costly as mass-limited samples come in many shapes and sizes. Therefore, rapid and economic microcoil production methods are needed. One method with great potential is 5-axis computer numerical control (CNC) micromilling, commonly used in the jewelry industry. Most CNC milling machines are designed to process larger objects and commonly have a precision of >25 µm (making the machining of common spiral microcoils, for example, impossible). Here, a 5-axis MiRA6 CNC milling machine, specifically designed for the jewelry industry, with a 0.3 µm precision was used to produce working planar microcoils, microstrips, and novel microsensor designs, with some tested on the NMR in less than 24 h after the start of the design process. Sample wells could be built into the microsensor and could be machined at the same time as the sensors themselves, in some cases leaving a sheet of Teflon as thin as 10 µm between the sample and the sensor. This provides the freedom to produce a wide array of designs and demonstrates 5-axis CNC micromilling as a versatile tool for the rapid prototyping of NMR microsensors. This approach allowed the experimental optimization of a prototype microstrip for the analysis of two intact adult Daphnia magna organisms. In addition, a 3D volume slotted-tube resonator was produced that allowed for 2D 1H-13C NMR of D. magna neonates and exhibited 1H sensitivity (nLODω600 = 1.49 nmol s1/2) close to that of double strip lines, which themselves offer the best compromise between concentration and mass sensitivity published to date.