Federico Casanova

Small Magnets for Portable NMR Spectrometers

High-resolution nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical tools used to probe details of molecular structure and dynamics. The study of large molecules such as proteins requires high sensitivity and high spectral resolution, which are both achieved with strong magnetic fields. These fields are generated by huge superconducting magnets, which are made stronger and bigger each year to tackle larger and larger molecules. The results of this amazing technological effort are bulky and static magnets permanently installed in dedicated NMR laboratories. The size of the superconducting magnets, their sensitivity to harsh environments, and the cost of maintenance and operation keep this technology away from fume hoods and production sites, where simpler devices that provide access to medium-size molecules would be needed. Robust NMR magnets can be made from permanent magnets like those used for NMR spectroscopy in the 1960s and 1970s. But to achieve high resolution for standard sample volumes, the permanent magnets then were as big as superconducting magnets today and weighed several hundred kilograms. Considering that the magnetic field strength remains constant when the volume of the magnet is scaled down to gain portability and that fields of up to 2 T are generated by permanent magnets, small magnets would offer a sensitivity only a factor of three smaller than that achieved in a standard (7 T) superconducting magnet (see the dotteddashed lines in Figure 1). This limitation is an affordable price to be paid for a small and portable system. However, a second factor seriously compromises the signal-to-noise ratio in the miniaturization process: the reduction of sample volume. For each magnet geometry the ratio between the magnet size and the size of the sensitive volume is a constant. When the size of the magnet is reduced, a smaller volume of highfield homogeneity is generated. For example, if the oldfashioned Varian T-60 magnet, with a volume of about 1 m, is reduced to palm-size dimensions, a sensitivity loss of about three orders of magnitude is expected (circle in Figure 1). Although this approach is valid in cases where the amount of sample is limited (capillary NMR), this sensitivity loss is simply unacceptable for most applications. We report herein on the construction of a small permanent magnet with an extraordinarily homogeneous magnetic field B0 suitable for measuring H NMR spectra of solutions in standard 5 mm NMR sample tubes (Figure 2). Weighing only 500 grams, the magnet can be transported along with the spectrometer, and NMR measurements can be performed on demand with this robust device at minimal maintenance cost. To efficiently reduce the sensor volume by three orders of magnitude over that of typical C-magnet designs, individual magnet blocks were compactly arranged in a cylindrical array based on the design by Halbach. This array provides a generous volume for sample positioning (large bore/magnet size ratio), and generates a magnetic field perpendicular to its cylinder axis (Figure 2), which allows the use of sensitive solenoidal radio-frequency (rf) coils to detect the NMR signals. In theory, the magnetic field generated by an infinitely long magnet built from perfect magnet blocks would be highly homogeneous along the length of the sample tube with almost zero stray field. However, in practice, the finite length of the magnet and the statistical imperfections of the sintered magnet blocks deteriorate the predicted homogeneity by several orders of magnitude. The new design presented herein combines three Halbach rings with different geometric proportions optimized to account for the field distortions along the cylinder axis due to the finite magnet length. To tackle the important source of inhomogeneity introduced by the variability of the pieces, each ring is composed of fixed trapezoidal elements with parallel gaps between them that guide the movement of rectangular magnet blocks (Figure 2). These pieces can be moved radially in and out to mechanically shim the magnetic field with highly efficiency and accuracy. By displacing the rectangular blocks in each ring with defined angular modulations and amplitudes, it is possible to independently Figure 1. Signal-to-noise ratio (SNR) for permanent and superconducting magnets as a function of the field strength B0. Squares show the SNR for water in a 5 mm NMR tube. Dashed and dotted lines correspond to solenoidal and birdcage rf coils used with permanent and superconducting magnets, respectively. The circle indicates the SNR value for a reduced sample volume in a capillary with a diameter of 0.3 mm.

Ex Situ NMR in Highly Homogeneous Fields: 1H Spectroscopy

Portable single-sided nuclear magnetic resonance (NMR) magnets used for nondestructive studies of large samples are believed to generate inherently inhomogeneous magnetic fields. We demonstrated experimentally that the field of an open magnet can be shimmed to high homogeneity in a large volume external to the sensor. This technique allowed us to measure localized high-resolution proton spectra outside a portable open magnet with a spectral resolution of 0.25 part per million. The generation of these experimental conditions also simplifies the implementation of such powerful methodologies as multidimensional NMR spectroscopy and imaging.

Two-dimensional imaging with a single-sided NMR probe.

A new low field unilateral NMR sensor equipped with a two-dimensional gradient coil system was built. A new NMR-MOUSE concept using a simple bar magnet instead of the classical U-shaped geometry was used to produce magnetic field profiles comparatively homogeneous in extended lateral planes defining a suitable field of view for 2D spatial localization. Slice selection along the depth direction is obtained by means of the highly constant static magnetic field gradient produced by this magnet geometry. Implementing a two-dimensional phase-encoding imaging method 2D cross sections of objects were obtained with high spatial resolution. By retuning the probe it was possible to change the depth of the selected slice obtaining a 3D imaging method. The details of the construction of the new device are presented together with imaging tests to show the quality of space encoding.

Noninvasive Testing of Art and Cultural Heritage by Mobile NMR

Nuclear magnetic resonance (NMR) has many applications in science, medicine, and technology. Conventional instrumentation is large and expensive, however, because superconducting magnets offer maximum sensitivity. Yet NMR devices can also be small and inexpensive if permanent magnets are used, and samples need not be placed within the magnet but can be examined externally in the stray magnetic field. Mobile stray-field NMR is a method of growing interest for nondestructive testing of a diverse range of materials and processes. A well-known stray-field sensor is the commercially available NMR-MOUSE, which is small and can readily be carried to an object to be studied. In this Account, we describe mobile stray-field NMR, with particular attention to its use in analyzing objects of cultural heritage. The most common data recorded are relaxation measurements of (1)H because the proton is the most sensitive NMR nucleus, and relaxation can be measured despite the inhomogeneous magnetic field that typically accompanies a simple magnet design. Through NMR relaxation, the state of matter can be analyzed locally, and the signal amplitude gives the proton density. A variety of stray-field sensors have been designed. Small devices weighing less than a kilogram have a shallow penetration depth of just a few millimeters and a resolution of a few micrometers. Access to greater depths requires larger sensors that may weigh 30 kg or more. The use of these sensors is illustrated by selected examples, including examinations of (i) the stratigraphy of master paintings, (ii) binder aging, (iii) the deterioration of paper, (iv) wood density in master violins, (v) the moisture content and moisture profiles in walls covered with paintings and mosaics, and (vi) the evolution of stone conservation treatments. The NMR data provide unique information to the conservator on the state of the object--including past conservation measures. The use of mobile NMR remains relatively new, expanding from field testing of materials such as roads, bridge decks, soil, and the contents of drilled wells to these more recent studies of objects of cultural heritage. As a young field, noninvasive testing of artworks with stray-field NMR thus offers many opportunities for research innovation and further development.

Mobile sensor for high resolution NMR spectroscopy and imaging

In this work we describe the construction of a mobile NMR tomograph with a highly homogeneous magnetic field. Fast MRI techniques as well as NMR spectroscopy measurements were carried out. The magnet is based on a Halbach array built from identical permanent magnet blocks generating a magnetic field of 0.22T. To shim the field inhomogeneities inherent to magnet arrays constructed from these materials, a shim strategy based on the use of movable magnet blocks is employed. With this approach a reduction of the line-width from approximately 20kHz to less than 0.1kHz was achieved, that is by more than two orders of magnitude, in a volume of 21cm(3). Implementing a RARE sequence, 3D images of different objects placed in this volume were obtained in short experimental times. Moreover, by reducing the sample size to 1cm(3), sub ppm resolution is obtained in (1)H NMR spectra.

Analysis of historical porous building materials by the NMR-MOUSE®

Samples of sandstone with and without deposits of silicon oxide stone strengthener as well as samples of historical brick material were analyzed by transverse NMR relaxation and mercury intrusion porosimetry. Relaxation times and relaxation time distributions of the protons from the water saturated samples were measured by low-field NMR using homogeneous and inhomogeneous fields. The measurements in inhomogeneous fields were performed with two different NMR-MOUSE sensors, one with a field gradient of 2 T/m and the other with an average field gradient of about 20 T/m. In the sandstone samples the application of stone strengtheners was shown to result in a confinement of the large pores within the outer layer of a few millimeters depth. Depending on the ferromagnetic contamination of the brick samples, the relaxation time distributions can be affected. The agreement of T2 relaxation time distributions and pore size distributions from mercury intrusion porosimetry was found to be better for the NMR-MOUSE sensors than for the homogeneous field measurements. This is true even for different brick samples, unless the content in ferromagnetic particles is very strong.

Single-Sided NMR

Since its discovery in 1945 [1, 2], nuclear magnetic resonance (NMR) has developed into an inexhaustible research field. It is exploited in several areas in physics, chemistry, biology, and medicine to extract unique information at the molecular level [3–8]. In chemistry, for example, it is considered to be one of the most powerful analytical tools to elucidate molecular structure, and in medicine it is routinely used for diagnostic imaging. Driven by the fact that sensitivity and spectral resolution increase with the magnetic field strength and homogeneity, magnets are built larger and larger over the years. Today, magnets are heavy and static devices installed in special NMR laboratories designed to shield electromagnetic interference and reduce magnetic field distortions in order to provide ideal experimental conditions (Fig. 1.1a). Besides the fact that samples of interest must be taken to the magnet, they must fit into the limited space available in the bore of the magnet. These issues are certainly a limitation when arbitrarily large samples require non-destructive analysis.

Noninvasive nuclear magnetic resonance profiling of painting layers

In this work we demonstrate the potential of single-sided nuclear magnetic resonance (NMR) sensors to access deeper layers of paintings noninvasively by means of high-resolution depth profiles spanning several millimeters. The performance of the sensor in resolving painting structures was tested on models for which excellent agreement with microscopy techniques was obtained. The depth profiling NMR technique was used in situ to investigate old master paintings. The observation of differences in NMR relaxation times of tempera binders from these paintings and from artificially aged panels raises the possibility to differentiate between original and recently restored areas.

High-resolution NMR spectroscopy under the fume hood.

This work reports the possibility to acquire high-resolution (1)H NMR spectra with a fist-sized NMR magnet directly installed under the fume hood. The small NMR sensor based on permanent magnets was used to monitor the trimerization of propionaldehyde catalyzed by indium trichloride in real time by continuously circulating the reaction mixture through the magnet bore in a closed loop with the help of a peristaltic pump. Thanks to the chemical selectivity of NMR spectroscopy the progress of the reaction can be monitored on-line by determining the concentrations of both reactant and product from the area under their respective lines in the NMR spectra as a function of time. This in situ measurement demonstrates that NMR probes can be used in chemistry laboratories, e.g. for reaction optimization, or installed at specific points of interest along industrial process lines. Therefore, it will open the door for the implementation of feedback control based on spectroscopic NMR data.

Low-gradient single-sided NMR sensor for one-shot profiling of human skin.

This paper describes a shimming approach useful to reduce the gradient strength of the magnetic field generated by single-sided sensors simultaneously maximizing its uniformity along the lateral directions of the magnet. In this way, the thickness of the excited sensitive volume can be increased without compromising the depth resolution of the sensor. By implementing this method on a standard U-shaped magnet, the gradient strength was reduced one order of magnitude. In the presence of a gradient of about 2 T/m, slices of 2mm could be profiled with a resolution that ranges from 25 μm at the center of the slice to 50 μm at the borders. This sensor is of particular advantage for applications, where the scanning range is of the order of the excited slice. In those cases, the full profile is measured in a single excitation experiment, eliminating the need for repositioning the excited slice across the depth range to complete the profile as occurs with standard high gradient sensors. Besides simplifying the experimental setup, the possibility to move from a point-by-point measurement to the simultaneous acquisition of the full profile led to the shortening of the experimental time. A further advantage of performing the experiment under a smaller static gradient is a reduction of the diffusion attenuation affecting the signal decay measured with a CPMG sequence, making it possible to measure the T(2) of samples with high diffusivity (comparable to the water diffusivity). The performance of the sensor in terms of resolution and sensitivity is first evaluated and compared with conventional singled-sided sensors of higher gradient strength using phantoms of known geometry and relaxation times. Then, the device is used to profile the structure of human skin in vivo. To understand the contrast between the different skin layers, the distribution of relaxation times T(2) and diffusion coefficients is spatially resolved along the depth direction.