Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
  • G01R33/00—Arrangements or instruments for measuring magnetic variables
  • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
  • G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
  • G01R33/30—Sample handling arrangements, e.g. sample cells, spinning mechanisms
  • G01R33/307—Sample handling arrangements, e.g. sample cells, spinning mechanisms specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer

Definitions

• the present invention concerns an apparatus and a method for liquid or solid state Nuclear Magnetic Resonance (NMR) spectroscopy and/or NMR imaging (MRI) of at least one animate or inanimate sample, which allows improving both the filling factor and the radio-frequency field amplitude in at least one detection coil surrounding said at least one sample.
• NMR Nuclear Magnetic Resonance
• MRI NMR imaging
• a NMR apparatus contains in a statoric frame magnetic means, radio frequency (RF) means comprising excitation circuits, an emitting coil and RF receiving means. Located in a central hole of this statoric frame, this apparatus contains positioning means for holding the sample or an object to analyse. In some cases, especially in solid state NMR, the means for holding the sample have means for spinning it, and sometimes extra means for tilting the spinning axis.
• the spinning part is called the rotor. It has a cylindrical shape and wears at one end tiny turbo blades driven by air jets.
• the rotor is made of a material transparent for magnetic fields, generally made of ceramics.
• sample container It may be filled with the sample to analyse, but when this sample is small, it wears an internal sample container, mechanically centred and whose axis is parallel to the mechanical axis of the rotor.
• the invention concerns small sized samples, so the rotor always contains a sample container whose diameter is smaller than the rotor diameter. It is necessary to underline that frequently, in NMR literature, the sample container is abusively called in short “sample” instead of "sample container”.
• the sample - be it an object or a subject - is placed inside a strong static and very homogeneous magnetic field BQ.
• S 0 static magnetic field
• Each of these two states has a different energy in the presence of S 0 .
• These energy levels are named Zeeman energy levels, and the spins can absorb energy in the radio-frequency range, to undergo transitions between their two states.
• the magnetic moments of the nuclear spins precess around the static magnetic field.
• the frequency ⁇ of the precession (called “Larmor precession") is roughly proportional to the static magnetic field, also depending on the local chemical environment and can be used to probe molecular structure and dynamics.
• an oscillating magnetic field B 1 needs to be applied.
• This field is produced by antennas (i.e. coils) surrounding the object or subject.
• This field is oscillating at the Larmor frequency (resonance condition) and can be applied for time delays long enough to perturb the magnetization and rotate it at various angles.
• the typical NMR experiment consists of the application of this Bi field for a time delay ⁇ , long enough to place the equilibrium magnetization M in the transverse plane xy.
• the length of this time delay is defined by the relation:
• ⁇ is the gyromagnetic ratio of the nucleus.
• the spins After application of this radiofrequency field (called ⁇ /2 pulse), the spins return to equilibrium. During this time, the magnetization still precesses around the static magnetic field and its trajectory is detected using antennas (i.e. tuned circuits) at the Larmor frequency.
• antennas i.e. tuned circuits
• the same antenna is used to perturb the nuclear magnetization (i.e. excitation) and then record (i.e. acquire) its response (namely free induction decay, also called "FID") during its return to equilibrium.
• FID free induction decay
• This signal contains the information about the frequencies of precession and a Fourier analysis of the FID gives the NMR spectrum. On the spectrum one can identify resonances based on their frequency differences.
• S/N signal to noise
• the reciprocity theorem states that the signal coming from a small volume of sample dV detected by a coil is proportional to the strength of the radio-frequency field Bi that this coil can generate per unit current in the same point of space [1].
• improved sensitivity can be obtained by rendering the strength of Bi field maximum for the volume of interest and this is typically performed by optimizing the filling factor of the coil.
• This filling factor may be defined as the ratio between the volume of the sample and the volume of the coil, which means that the best sensitivity is obtained for coil sizes comparable to the sample size.
• the chemical environment manifests through various interactions, which are anisotropic (i.e. different interactions for different directions in space) and often lead to a continuous distribution of resonant frequencies.
• anisotropic i.e. different interactions for different directions in space
• the anisotropic parts of the interactions are averaged to zero due to free molecular tumbling and translation, thus the NMR spectra are narrow and the chemical information can be easily retrieved.
• the chemical shift anisotropy, the dipolar interactions, the quadrupolar interaction and sometimes the scalar couplings and the magnetic susceptibility broaden the spectrum and account for the loss in spectral resolution.
• Magnetic Angle Sample Spinning is one of the cornerstones of high-resolution solid-state NMR, and most solid-state NMR probes are currently able to spin small sample holders (i.e. rotors) from 1000 Hz to 35000 Hz or even more.
• sample holders i.e. rotors
• DOR Double Rotation
• DAS Double Angle Spinning
• liquid samples are studied using ordinary macroscopic size saddle type coils (i.e. macro-coils having a diameter ranging from 1 mm to 10 mm) or more recently micro solenoidal type coils have been designed to closely fit to horizontally disposed capillary tubes (100 - 1000 ⁇ m diameter), as shown in the drawings of [5-7] references.
• a drawback of these apparatuses is that they can only work with the coils being electrically connected and mechanically linked to the static part of the probe: this means that specific probes need to be constructed in each case.
• the sample holder needs to withstand high gas pressures and mechanical stress, and thus to have a non-negligible wall thickness.
• Common rotors have wall thicknesses ranging from about 0.5 mm to 0.75 mm, and scaling down to smaller sizes would compromise their mechanical stability. Machining hard materials with precision gets also very demanding for sub-millimeter sizes. Thus, it is very difficult to develop micro-rotors that rotate fast inside static RF micro-coils.
• RF antennas have been used in the past in NMR and MRI. They generally comprise an electronic part consisting of the tuning and matching elements necessary to produce a tuned circuit and a coil close to, or inside which, the animate or inanimate sample under study is placed. This circuit can be tuned at the same time to many frequencies, allowing for multinuclear studies. Inductive coupling between two circuits can be performed through physical proximity between them.
• the mutual inductance M between two coils is equal to the flux that crosses one coil when a current unity flows into the other one: it depends upon the geometrical characteristics of the coils and upon the distance between them.
• inductive coupling between two or more coils is commonly used in order to acquire images [9, 10], with the purpose to optimize the detection and the tuning bandwidth of the coil over a region of interest [11].
• a secondary coil can be implanted [12] into the subject and allows for continuous monitoring.
• the sample under study typically a patient, is static and motion can induce variations in the coupling between the primary and the secondary circuits, leading to signal and B 1 amplitude variations.
• the nature of the interactions is such that no spatial averaging is required by rotating the sample. The interactions are isotropic for MRI and thus no MAS technique is applied, leading to a completely different and independent development of the techniques than for NMR spectroscopy.
• sample containers In solid state and liquid state NMR spectroscopy, the sample containers have standardized size that cannot suit to any sample, especially very small sized samples. Hence, using commercially available probes to study very small sized samples corresponds to a poor filling factor, resulting in a poor signal sensitivity.
• One purpose of the present invention is to overcome the above-exposed drawbacks and, in particular, those relating to the filling factor and the sensitivity of the NMR probe especially for small solid fast spinning samples. This is achieved by the apparatus for liquid or solid state NMR spectroscopy and/or NMR imaging of at least one animate or inanimate sample according to the invention, which comprises :
• At least one sample container comprising a sampling volume which is designed to be filled by said at least one sample and to be subjected to an electromagnetic radio frequency field
• a static probe comprising an energizing circuit for excitation of nuclei of said at least one sample by generating an incident radio frequency field at the Larmor frequency of said nuclei, and for reception of a return radio frequency field emitted by said at least one sample
• said apparatus comprises at least one sensitive coil which is mounted closely around or in contact with said sample container and which is coupled to said static probe by an electromagnetic radio frequency field, and wherein said sensitive coil defines a sensing volume which is substantially equal to said sampling volume.
• the apparatus of the invention is characterized in that said sensitive coil is embedded in an inner spinning rotor which is rotatively mounted inside said static probe and which is integral with said sample container, so that both the filling factor and the radio frequency field amplitude in said sensitive coil are maximized.
• electromagnetic radio frequency field it is meant a coupling without any electrical contacts (i.e. a coupling which is devoid of any galvanic contacts), be it either a radio frequency electric field (transmitted through a capacitor) or a radio frequency magnetic field (transmitted through inductively coupled coils).
• sensing volume of said sensitive coil it is meant in the present description the inner space of this sensitive coil, which is submitted to said electromagnetic field.
• spinning rotor it is meant by definition a rotor which is able to continuously rotate according to more than 360 degrees, for instance at a spinning frequency of at least a few Hz
• integral with it is meant in the present description an assembly where both related parts may not move relative to one another (i.e. no relative motion between the rotor, the sensitive coil and the sample container).
• said sensitive coil is preferably mounted in contact with by any lithography process (e.g. etching process), micromachining process (e.g. laser micromachining), any microfabrication process (e.g. laser polymerization and metallization) or any wire winding technology, said sample container, although it may be also mounted a few millimeters or a fraction of millimeter around the latter, preferably at a distance less than or equal to 2 mm, in order to obtain a satisfactory filling factor.
• lithography process e.g. etching process
• micromachining process e.g. laser micromachining
• any microfabrication process e.g. laser polymerization and metallization
• wire winding technology any wire winding technology
• said electromagnetic radio frequency field is performed through a radio frequency magnetic field.
• said apparatus also comprises at least one resonant circuit for detection of precession frequencies of said nuclei, which is electromagnetically coupled to said static probe so as to be tunable thereto substantially at the Larmor frequency of said nuclei, and which comprises said sensitive coil mounted within the emitting coil of said energizing circuit.
• said apparatus comprises a static probe which is, according to this preferred embodiment, electromagnetically coupled to said at least one resonant circuit which is tuned substantially at the Larmor frequency of said nuclei.
• This apparatus according to the invention is particularly - but not only - suitable for high-resolution NMR spectroscopy of small solid samples, and also for NMR imaging thereof.
• said apparatus according to the invention may also be used to study small static liquid-state samples, in combination with an existing commercially available NMR probe.
• the increase in RF field amplitude will be particularly useful in the case of very broad spectra, typical of paramagnetic proteins.
• the electromagnetic radio frequency field is a magnetic field, applied through magnetic induction between the probe emitting coil and the sensitive coil therein, this sensitive coil being mounted on or closely around said at least one sample container.
• this sensitive coil being mounted on or closely around said at least one sample container.
• the sensitive coil acts both as a magnetic field concentrator for the excitation field, and as a signal enhancer for the response signal thanks to the reciprocity theorem.
• the coil must be connected to a net that further comprises at least one capacitor, and eventually a set of capacitors and/or inductors which is connected to the terminals of said sensitive coil.
• the sensitive micro-coils (inductors) according to the invention can be manufactured according to standard techniques, and they may surround either the sample containers, such as small capillaries [15-20].
• These sensitive micro-coils may either be of a solenoidal coil type (generally used for solid state NMR), of a saddle coil type (generally used for liquid state
• NMR nuclear magnetic resonance
• surface coils conical coils
• Litz coils etc.
• conducting coating directly deposited on the sample container itself.
• saddle type embodiment is not preferred.
• the coil type (solenoidal or saddle type) of the sensitive coil is chosen of the same type than the emitting coil. That is to say, with a solenoidal emitting probe, the sensitive coil is advantageously solenoidal, and in the case of a saddle type emitting probe, the sensitive coil would be advantageously of a saddle type, which implies that the sensitive coil would not spin.
• the shapes of said at least one emitting coil and said at least one sensitive coil both have a cylindrical symmetry, and then they each define a revolution surface.
• the size of the conductor used for the fabrication of the micro-coil must carefully be chosen in order to minimize
• Wire diameters varying from 5 to 150 micrometers are advantageously used and the number of turns is optimized to keep thermal effects as low as possible.
• the windings may be irregular, either to improve field homogeneity or to reach a specific magnetic field pattern.
• each dimension determined by V 2 i.e. diameter or length
• said static or rotating sensitive coil is a micro-coil having a diameter preferably between 100 ⁇ m and 1500 ⁇ m.
• said resonant circuit is inductively coupled to said energizing circuit.
• said resonant circuit may further comprise at least one capacitor which is connected to the terminals of said at least one sensitive coil and which may comprise a thin cylindrical film surrounding said sensitive coil.
• said capacitor may either have:
• said resonant circuit may consist of said sensitive coil (i.e. being then devoid of any capacitor), which is made in this case of one or several self-resonant micro-coil(s), advantageously for spectroscopy of high gamma nuclei, such as tritium, hydrogen of fluorine.
• said sensitive coil may be made either of one self-resonant solenoidal micro-coil, or of a self-resonant plurality of concentric metal rings (R) which are axially spaced around said capillary (3) along the axis thereof.
• said resonant circuit may comprise a plurality of sensitive coils arranged to define at least one tank circuit, so that said resonant circuit is tunable to said static probe at multiple Larmor frequencies for the analysis of multiple types of nuclei at the same time.
• said resonant circuit may advantageously be a double frequency-tunable one comprising two sensitive coils, one of which is series connected to said tank circuit including the other one.
• Such double and multiple resonance systems allow to study multiple types of nuclei at the same time (either in liquid and solid state NMR or MRI), particularly on the low frequency channel (dedicated for the low frequency nucleus, typically carbon-13, nitrogen-15, silicon-29, etc.), while applying a radio-frequency irradiation on the high frequency channel (typically hydrogen, fluorine, tritium).
• the low frequency channel typically carbon-13, nitrogen-15, silicon-29, etc.
• a radio-frequency irradiation on the high frequency channel typically hydrogen, fluorine, tritium
• the electromagnetic radio frequency field is a radio frequency electrical field.
• this electrical field coupling is advantageously performed through capacitors, two input and output capacitors being series connected with said sensitive coil, so that said radio frequency electrical field passes through said capacitors.
• each of said input and output capacitors is made of a static cylindrical plate which is mechanically linked to said static probe and of a rotating cylindrical plate which is mechanically linked to said sensitive coil and embedded in said sample container, those two cylindrical plates facing each other and having the same symmetry axis than that of the rotor and that of said sample container.
• said input and output capacitors are advantageously both embedded at each end of the rotor, close to the respective ends thereof.
• the self inductance L of the coil and the value of the two coupling capacitors C are chosen to maximize the power transmitted by the probe to the radio frequency field applied to the sample.
• they are comprised in an adapting network, consisting of a set of capacitors and/or inductors, which is connected to the terminals of said sensitive coil.
• the two plates of each input and output capacitor may either be:
• said at least one sensitive coil may advantageously be rotatively mounted inside said static probe, being embedded in said inner rotor which is integral with said sample container and said sensitive coil. It is thus to be noted that such an apparatus of the invention allows for the use of either static or rotating sensitive coils, depending upon the samples to be analyzed.
• said at least one sample container is a capillary on the surface of which said at least one sensitive coil is mounted.
• said at least one static or rotating sensitive micro-coil has a length preferably of between 1 mm and 20 mm and a number of turns preferably ranging from 1 to 20, which combination has experimentally proved to provide a maximization of the radio frequency field amplitude in said sensitive coil.
• rotating micro-coils provides a unique means to perform a NMR analysis (for instance a high- resolution NMR analysis).
• the first case is where the sample quantity is limited (a few micrograms), and placing it inside commercially available NMR rotors would not be advantageous because of the small filling factor.
• One could design smaller rotors in order to enhance the filling factor in practice the smallest rotors are 2 mm outer diameter [21]), but the challenge becomes insurmountable when sub-millimetre scale rotors need to be machined.
• the wall thickness together with the required strength for the material renders this task extremely difficult.
• Using rotating micro-coils according to the invention allows achieving higher filling factors, without the restrictions linked to the small size sample spinning.
• the invention is well suited for any sample that requires a shielding, provided that shielding allows the transfer of magnetic fields, and in the case of an electric field coupling, provided that shielding also allows the transfer of electric fields.
• the sensitive coil is advantageously placed inside the shielding, next to the sample.
• shielding allowed by the invention is of biological type, when a "sensitive" product must be protected from contamination, or the environment must be protected from the contamination by this product.
• the sensitive coil is advantageously placed inside the shielding, next to the sample. So, the benefits of the invention are not significantly affected by the presence of one or several shieldings. As far as the sample container remains unchanged, and the shieldings do not alter the magnetic field, the sensitivity is the same with or without shieldings. In the case of a sample whose contamination is prohibited
• said inner rotor of the NMR apparatus- which is integral with both said at least one sample container and said resonant circuit, as above indicated - may include a plurality of shieldings barrier layers which are provided around said at least one sample container and which form the outer wall of this inner rotor. If the sample is a radioactive material, said shieldings are radioactive barrier layers.
• sample holders i.e. rotors
• the sample holders may be designed to have protective barriers against sample or probe damage, since the sensitivity of the experiment depends less crucially on the size of the rotor. This may have a particular importance in the study of size-limited samples, sensible, hazardous or even fragile samples, such as biological substances, radioactive materials, or studies under very high pressure and/or temperature.
• said apparatus may further comprise an outer rotor which surrounds said inner rotor and which is adapted to rotate at a slower frequency than that of the latter, so as to allow a simultaneous double rotation according to the "DOR"
• said apparatus may have several detection coils (i.e. sensitive coils), each one tuned on a different Larmor frequency corresponding to a different nucleus, in such a way that only one micro-coil can be excited by the RF field of an excitation coil.
• detection coils i.e. sensitive coils
• the emitting coil of the probe is thus sequentially excited close to any of the resonant frequencies of the different detection coils, each one surrounding one sample.
• samples may be either in different sample containers placed with their axis parallel to the mechanical axis of the rotor, and parallel one to the other and at a distance great enough to prevent the interference from one sample to the other, or at different distances along the same sample container, those distances being large enough to prevent the interference from one sample to the other.
• a method according to the present invention for solid or liquid state NMR spectroscopy and/or NMR imaging of at least one animate or inanimate sample which uses an apparatus comprising at least one sensitive coil which is mounted closely around said sample and defines a sensing volume being substantially filled by said sample, said method comprising :
• said electromagnetic radio frequency field is a radio frequency magnetic field.
• this RF field induces an electromagnetic coupling to said energizing circuit of at least one resonant circuit comprising said at least one sensitive coil within an emitting coil of said energizing circuit, said at least one resonant circuit detecting the precession frequencies of said nuclei and being tuned to said energizing circuit substantially at the Larmor frequency of said nuclei.
• said electromagnetic radio frequency field is a radio frequency electrical field, as explained above for said apparatus.
• said at least one sample is a solid one, and may be used either in a static or a rotating way at any spinning frequency, while implementing said method.
• said at least one sensitive coil may spin in a continuous way at a spinning frequency of at least 1 Hz.
• This method of the invention may advantageously be used in either liquid or solid state NMR, and said resonant circuit may be designed according to the expected spectral resolution.
• said at least one resonant circuit is advantageously rotated inside said static probe at a spinning frequency greater than 1 kHz and, more advantageously, at a spinning frequency ranging from 3 kHz to 35 kHz.
• said method comprises rotating said resonant circuit by means of an inner rotor which is integral with both said at least one sample container and said resonant circuit, using a technique selected from the group consisting of the Magic Angle Sample Spinning technique ("MAS”), the Double Rotation technique (“DOR”) and the Double Angle Spinning technique (“DAS").
• MAS Magic Angle Sample Spinning technique
• DOR Double Rotation technique
• DAS Double Angle Spinning technique
• MAS tunable energizing circuit
• the invention may use several detection coils (i.e. sensitive coils), tuned on different frequencies, different enough not to interfere with one another.
• the emitting coil of the probe is sequentially excited close to any of the resonant frequencies of the different detection coils, each one surrounding one sample,
• the invention is particularly advantageous for any nuclei whose excitation and manipulation require a large amplitude radio frequency field (e.g. protons and even more oxygen-17).
• a large amplitude radio frequency field e.g. protons and even more oxygen-17.
• static liquid samples e.g. paramagnetic proteins
• Bi field offers the possibility to excite quantitatively over a wide range of frequencies, may further be carried out.
• Figure 1a is a partial and schematic longitudinal sectional view of a NMR apparatus according to the invention, with coupling by an electric field
• Figure 1b is a partial and schematic longitudinal sectional view of another NMR apparatus according to the invention, with coupling by a magnetic field
• Figure 1c is a partial and schematic longitudinal sectional view of a variant according to the invention of the NMR apparatus of figure 1 a, with coupling by an electric field,
• Figures 1d and 1 e are respective schematic variants according to the invention of the NMR apparatus of figure 1b, both with coupling by a magnetic field to a self-resonant sensitive micro-coil,
• Figures 1f and 1 g schematically show a specific embodiment of the invention with a plurality of micro-coils, figure 1f with magnetic coupling and figure 1g with capacitive coupling.
• Figure 2a is a schematic view of the electronic components of the apparatus according to figure 1 a, showing an electric field coupling
• Figure 2b is a schematic view of the electronic components of the apparatus according to figure 1 b, showing a magnetic field (inductive) coupling
• Figure 2c is a variant according to the invention of the apparatus of figure 2b showing a multiple-tuned inductive coupling
• Figure 3 is a schematic longitudinal sectional view of a rotor containing a resonant tunable circuit according to figures 1 b and 2b,
• Figure 3' is a variant according to the invention of the rotor of figure 3
• Figures 3a and 3b are respectively schematic longitudinal and transversal sectional views of a variant according to the invention of the rotor of figure 3
• Figures 3c and 3d are respectively schematic longitudinal and transversal sectional views of another variant according to the invention of the rotor of figure 3,
• Figure 4a is a schematic longitudinal sectional view of a rotor according to figure 3, whose extremities are respectively provided with two outer loops for spectrum analysis,
• Figure 4b is a graph showing the evolution of the response voltage V of tuned resonant circuit according to the invention, measured by a spectrum analyzer on a reduced frequency scale with set up of figure 4a,
• Figures 5a and 5b are respectively two exemplary schematic longitudinal sectional views of a double rotor structure relating to the "DOR" probe design, figure 5a relating to the prior state of the art and figure 5b relating to an inner tuned resonant coil according to the invention,
• Figure 6 is a multiple plot graph showing the evolution of the RF field amplitude in the resonant circuit as a function of its resonance frequency ⁇ 0 , according to various sensitive coil geometries,
• Figure 7 is a multiple plot graph showing the evolution of the RF power dissipated in the resonant circuit over the power provided by the amplifier of the NMR probe, as a function of its resonance frequency ⁇ 0 , and according to various sensitive coil geometries, 9
• Figure 8 illustrates a sensitivity enhancement of a liquid sample-containing capillary surrounded by said sensitive tuned coil in a static operating mode, compared to a "control" capillary being devoid thereof, by means of two respective spectra (a) and (b) plotted as a function of chemical shift,
• Figure 9 illustrates a sensitivity enhancement of a solid sample-containing capillary surrounded by a sensitive tuned coil in a rotating operating mode, compared to a "control" capillary being devoid thereof, by means of two respective spectra (a) and (b) plotted as a function of chemical shift,
• Figure 10a is a pulse sequence which was applied to the solid state NMR apparatus including the same tuned rotating sensitive coil as used for figure 9, and
• Figure 10b is a spectrum obtained from a capillary surrounded by this tuned rotating sensitive coil.
• Figure 11 a is a static proton spectrum obtained inside a capillary surrounded by the self-resonant sensitive coil of an apparatus according to figure 1d,
• Figure 11 b is a high resolution "MAS" spectrum of the same capillary and apparatus according to figure 1d, obtained using a spinning of said capillary at 300 Hz,
• a static probe comprising a usual antenna-containing energizing circuit for excitation of nuclei of the sample 4 (the static probe and its energizing circuit are not shown in their entirety), the energizing circuit (not shown on these drawings) surrounding the rotor 2 and being designed to generate the RF field, and
• this circuit 6, 6' being electromagnetically coupled (i.e. by a wireless connection) to the energizing circuit so as to be tunable thereto substantially at the Larmor frequency of the nuclei, and comprising a small sensitive micro-coil 6a or 6a' mounted around the capillary 3 and within the static probe.
• the sensitive micro-coil As may be seen in figures 1 a and 1b, the sensitive micro-coil
• 6a or 6a' defines an inner sensing volume which is substantially equal to the sampling volume 3a of the capillary 3.
• the apparatus 1 of figures 1 a and 2a shows a capacitive (i.e. electric) coupling between the sensitive micro-coil 6a, which is mounted around the capillary 3 and forms a detection/excitation coil, and the rest of the apparatus 1 including a static probe P, shown in figure 2a, which comprises the energizing circuit.
• the micro-coil 6a is physically connected at each end to a metal ring 6b (preferably made of copper) covering the rotor lateral surface between two parallel circles.
• the capacitive coupling occurs between these rings 6b and two statoric cylindrical surfaces facing them, forming external concentric metal rings 7 (preferably also made of copper) that are fixed in the housing (not shown) of the probe P.
• the width of the air gaps between the rings 6b and 7 determines the values of the capacitance of the resonant circuit 6, such rings 6b and 7 respectively forming the capacitor plates of two capacitors. This arrangement allows the electrical connection during the free rotation of the sample 4. The distance between these metal rings 6b and 7 has thus to remain constant during the spinning of the rotor 2.
• the apparatus 1 ' of figures 1 b and 2b shows an inductive (i.e. magnetic) coupling between the two tuned circuits, i.e. the resonant one 6' and the energizing one.
• the sensitive micro-coil 6a' surrounds the capillary 3 and is tuned to the resonance frequency using a small capacitor 6b', schematically drawn aside the coil, but which is generally settled on the rotation axis.
• the energizing circuit of the static probe P' contains an emitting macro-coil 5, which surrounds the rotor 2 and which is fixed to the housing of the probe.
• FIG 1c which is a variant of figure 1a
• another embodiment for capacitive coupling between the static probe P and a possibly rotating micro-coil 106a is such that the rotating plates 106b and the static plates 107 replacing the afore-mentioned rotating plates 6b and static plates 7 are kept at a fixed distance during sample spinning, being axially spaced along the symmetry axis of the capillary 3.
• This wireless coupling between the static part P and the potentially rotating part containing the micro-coil 106a is thus also performed by means of two air capacitors.
• the rotor's upper and bottom parts are electroplated and tethered to the micro-coil 106a.
• the static part P has also these two metallic plates 107 positioned at the right distance from the rotor's plates 106b (this distance is kept constant during the static of spinning experiment).
• the corresponding resonant circuit 306' or 406' exclusively consists of a solenoidal self-resonant micro-coil 306a' in figure 1d or a self- resonant micro-coil 406a' made of concentric metal rings R which are axially spaced around the capillary 3 axis in figure 1g.
• Both types of micro-coils are specially advantageous for spectroscopy of high gamma nuclei, such as tritium, hydrogen of fluorine.
• figure 1d shows a solenoidal shape self- resonant micro-coil 306a' which is wrapped around the sample containing capillary 3.
• the winding of the self-resonant micro-coil is not equidistant in order to maximize the radio-frequency field homogeneity at the volume of the sample.
• the capillary 3 is centred inside the rotor 2 and spun with it.
• Figure 1e shows the concentric rings R which form a resonator close to the Larmor frequency of the spins.
• the homogeneity of the radio-frequency field can be optimized by the changing the gap between the rings R.
• both self-resonant micro-coils 306a' and 406a' of figures 1d and 1e allow to improve the spinning stability of the assembly in the rotor 2.
• micro-coils 506a' or 606a' can be included in the same rotor, either along the same sample container 3 or around one or several sample containers 3' and 3" as schematised in figures 1f and 1g, figure 1f , with magnetic coupling and figure 1g with capacitive coupling (each micro-coil 606a' being combined with a capacitor 606b').
• a micro-coil 506a', 606a' is around a single sample container 3 or 3', 3" to maximize the filling factor; but putting a micro-coil around several sample containers is still in the scope of this invention.
• Figure 2c is a variant of figure 2b, wherein the resonant circuit 706' is a double frequency-tunable one which comprises two sensitive coils 706a' and 706a" arranged to define at least one tank circuit TC, so that this resonant circuit 706' is tunable to the double resonance static probe P' at two Larmor frequencies for the analysis of two types of nuclei at the same time.
• figure 2c shows how to doubly tune a micro-coil 706a' which is inductively coupled to a double resonance NMR probe.
• the coupling by electric field of figure 2a essentially differs from the coupling by magnetic field of figure 2b or 2c, in that the corresponding static probe P includes the capacitor plates 7 in place of the emitting macro-coil 5 of the static probe P' of figure 2b or 2c.
• the angle between the axis of the coils 5, 6a or 6a' and the static magnetic field is preferably set to be equal to the magic angle, according to figures 1a and 1 b, but it can generally be arbitrary. Now, this inductive coupling will be discussed with reference to figure 2b.
• the energizing circuit corresponds to the circuit of a commercial NMR probe, while the resonant circuit 6' includes a coil 6a' - preferably a micro-coii- placed inside the emitting coil 5.
• the coupling M between both circuits depends on the geometric characteristics of the coils.
• the inductance of the sensitive coil 6a' of figure 1b be L.
• a small capacitor 6b' of capacitance C (of either fixed or variable type) is connected, for instance by soldering or through a micro connector that, together with the inductor, makes the tuned LC resonant circuit 6' tuned at the Larmor frequency of the observed nuclei.
• the value of the capacitance C is chosen in the vicinity of the theoretical value Q . from the formula :
• FIG. 3 shows in longitudinal section the structure of the rotor 2 containing the sensitive tuned micro-coil 6a'. It is generally used for solid state NMR.
• This rotor 2 comprises an outer cylindrical rotor body 2a which is provided at one end with a rotor cap 2b and, radially to the inside thereof, with a plurality of stabilization inserts 2c surrounding the capillary 3.
• the latter is provided on its cylindrical outer surface with the tuned micro-coil 6a' and, at one end, with the tuning capacitor 6b' which is connected thereto, its mass centre being on the symmetry axis and the plates of the capacitor 6b' being perpendicular to the cylindrical surface of the capillary 3.
• the assembly of the capillary 3, the micro- coil 6a' and the capacitor 6b', which is placed inside the rotor 2 is well maintained along its symmetry axis thanks to the inserts 2c, which may be plastic or preferentially ceramic plugs, having the right dimensions to fit tightly these components and having high thermal conductivity. Tight fitting is indeed necessary for the stable spinning of this rotor assembly at high frequencies.
• the rotor may be positioned inside a "MAS" probe and spun as any commercial rotor.
• the macro-coil 5 of the "MAS" probe surrounds the rotor 2 and constitutes the energizing circuit which provides the energy for the excitation of the nuclei.
• a coupling constant k characterizes the strength of the coupling, or in other words the influence that each circuit has to the other one.
• Figure 3' shows in longitudinal section the structure of a rotor 2 which contains a sensitive tuned micro-coil 6a" and which only differs from that of figure 3 in that the capillary 3 is provided on its cylindrical outer surface with the micro-coil 6a" and, at one end, with a tuning capacitor 6b" which is connected thereto in such a manner that the plates of the capacitor 6b" are cylindrical and coaxial with the capillary 3.
• Figures 3a and 3b, on the one hand, and figures 3c and 3d, on the other hand, are each a variant of the rotor 2 shown in figure 3 for an inductively coupled micro-coil 106a' or 206a'.
• the capacitor 106b' or 206b' is made of a thin cylindrical film which surrounds the sensitive micro-coil 106a' or 206a'.
• the capacitor 106b' has two concentric cylindrical plates P1 and P2 which extend parallel to the axis of the micro-coil 106a', so as to define respective inner and outer axial faces of this cylindrical film.
• the capacitor 106b' is cylindrical and surrounds the capillary 3.
• the leads connecting the micro-coil 106a' to the capacitor 106b' are shorter than in figure 3.
• the micro-coil 106a' is stabilized inside a solid cylinder 2a which can be a plastic insert as in figure 3.
• the thin film capacitor 106b' can be lithographied on the outer surface of this insert or on a thin surface that can be glued onto this surface.
• the plates P1 and P2 are slit along a generatrix by a slot S, to avoid circular Eddy currents at the radio-frequency of excitation.
• all modern micro- fabrication techniques such as lithography, can be used to produce such capacitors 106b' and 206b'.
• Another preferred example is "Capton capacitors", in which a Capton thin film which is covered on both surfaces by copper.
• the capacitor 206b' has two slit parallel annular plane plates PT and P2' (by a slot S' along a generatrix) which extend perpendicularly to the axis of the rotor 202, so as to define respective end radial bases of this cylindrical film. This configuration allows for less metallic surfaces, less heating and smaller capacitances.
• the typical size of the micro-coils 106a' or 206a' is between 10 and 1000 micrometers in diameter, while the capacitance values may vary from 0.1 to hundreds of picoFarads.
• the film capacitor 106b' of figures 3a and 3b allows for small capacitors having large critical voltage (useful for high- frequency nuclei), while the capacitor 206b' of figures 3c and 3d allows for larger capacitors since the distance between the metal layers can be very small (a couple of micrometers).
• the tuning of the resonant circuit 6' was checked using a spectrum analyzer in the configuration shown on figure 4a, which shows that two outer loop coils 8 and 9 located at the respective ends of the rotor 2 were connected to a spectrum analyzer, and a dispersive Lorenzian was obtained on the screen.
• the frequency difference between the two extreme points is equal to: ⁇ / ⁇ - 1/Q and allows to measure the quality factor of the circuit.
• the coupling between the two energizing and resonant circuits depends on the geometrical characteristics of the coils 5 and 6a' and remains constant, since the axis of the rotation is stable throughout the motion.
• the Bi field is stable and no phase distortions are expected during the signal recording.
• the excitation and detection performances depend upon the characteristics of this resonant tuned circuit 6, 6'.
• the RF amplitude can be enhanced if a much smaller coil 6a or 6a' than that of the energizing circuit is used in the resonant circuit 6 or 6'. This means that one may obtain a higher Bi field in the sampling volume 3a for the same radio-frequency power. It also means that the sensitivity for the detection is higher.
• the noise level is the same as having a single coil, since the set of energizing and resonant circuit 6 or 6' is tuned on resonance and matched to 50 Ohms.
• the signal to noise is enhanced with respect to the ordinary single coil NMR detection.
• artefact signals coming from the rotation of the coil are modulated at harmonics of the spinning frequency (0-30 kHz) and are filtered electronically being very distant from the NMR frequencies (hundreds of MHz). It appears that such signals have never been observed in experiments.
• Figures 5a and 5b show two exemplary schematic views of a double rotor structure, according to the "DOR" NMR probe design.
• Figure 6 shows the plots of the RF field amplitude in the resonant circuit 6' as a function of its resonance frequency ⁇ 0 , in order to calculate the optimum RF field produced by the sensitive coil 6a' as a function of its resonance frequency.
• a 'MAS" apparatus 1 ' as shown in figure 1b was used in the calculations of these graphs.
• Various geometries were tested for the sensitive micro-coil 6a' and the quality factors Q ? and Q 2 for both energizing and resonant circuits 6' were assumed equal to 100.
• the primary circuit is specified by solenoidal coil 7 mm in diameter, 15 mm in length having 5 turns and a quality factor of 100.
• the secondary circuit is characterized by a solenoidal coil 1.65 mm in diameter having a quality factor of 100.
• the length and the number of turns in the secondary coil are varied in the simulation and specified in the inset of figures 6 and 7.
• the blue triangles represent the field generated by the probe coil in the absence of any micro-coil.
• the down-pointed triangles plot correspond to the field produced by the main coil 5 of the energizing circuit, in the absence of any resonant circuit 6', and serves to set reference (i.e. "control") for comparison.
• the three other plots correspond to various sensitive micro- coil 6a' geometries.
• the resonance frequency of the sensitive micro-coil 6a' was fixed at a certain value, and then the tuning and matching capacitors C M and C ⁇ (see figure 2 again) of the energizing circuit were varied, in order to maximize the RF field produced in the sensitive micro- coil 6a'. This corresponds to the procedure followed in the experiments as well.
• Figure 7 shows the plots of the ratio RF power dissipated in the resonant circuit 6' and the power provided by the amplifier, as a function of resonance frequencies for various geometries as in figure 6.
• a "MAS" apparatus 1' as shown in figure 1 b was used in the calculations of these graphs.
• This graph establishes that the power is mainly dissipated in the sensitive micro-coil 6a' on resonance, and this acts as an amplifier (i.e. a concentrator) for the RF field.
• the filling factor was optimized by wrapping the micro-coil 6a' of the resonant circuit 6' manually around the cylindrical wail of the capillary 3. All experiments we performed using a commercial "Bruker” rotor 2 with an outer diameter of 7 mm and a "BL MAS” probe as the source of the energizing circuit, and the capillary 3 had an outer diameter of 1.4 mm.
• the experiments were performed on static samples 4 and also on samples 4 rotating at 5000 Hz (within ⁇ 5 Hz accuracy).
• the automatic spinning module was used for the rotor 2 takeoff and spinning stabilization and landing, proving that the rotor 2 mass was correctly balanced.
• Figure 8 illustrates the sensitivity enhancement of a liquid sample-containing capillary 3 surrounded by the resonant tuned micro-coil 6a' in a static operating mode, compared to a "control" capillary 3 being devoid thereof.
• the "control" spectrum of this sample is shown on the (a) plot. Then, the resonant tuned circuit was placed around the capillary 3 and the RF amplitude was calibrated. Two non-magnetic capacitors from ATC, each having a capacitance of 33 pF, were connected in parallel and to the macro-coil. The new ⁇ /2 length was 2.6 ⁇ s and corresponded to a RF amplitude of 96 kHz, and the S/N was equal to 230. The tuning and matching of the assembly was optimized to an impedance of 50, using the wobbling utility of the "Bruker" spectrometer.
• Figure 9 illustrates the sensitivity enhancement of a solid sample-containing capillary 3 surrounded by a sensitive tuned coil 6a' in a rotating operating mode, compared to a "control" sample 3 being devoid thereof.
• 23 Na NMR spectra of powder samples of Na 2 C 2 O 4 are presented.
• the spectrum in (b) was recorded from the capillary 3 having an outer diameter of 1.4 mm containing a powder sample 4 of Na 2 C 2 O 4 of about 800 ⁇ g.
• a solenoidal coil 6a' having 13 turns and a chip capacitor of 27 pF connected thereto were used.
• Chip capacitors from Rodenstein were used, having a size of 2 mmx 1.3 mm * 0.6 mm.
• the Q value of the resonant circuit 6' was measured to be of 79.
• the capacitor terminations were magnetic and the tuning (i.e. resonance) frequency measured on the spectrum analyzer was of 74 MHz.
• the sample 4 and the resonant circuit 6' were tightly fitted using the inserts 2c of figure 3, inside a 7 mm rotor 2 and spun at 5 kHz.
• the rotation frequency was stable (within 5 Hz) over a period of 4 - 5 days.
• the tuning curve at the wobbling utility of the spectrometer was tuned and matched near to 50 Ohm at the resonance frequency of 23Na, i.e. 79.3 MHz, using the probes tuning and matching knobs.
• the Q value of the probe in the absence of the resonant circuit 6' was measured to be of 128 and, in the presence of the latter, to be of 85.
• Figure 10 is a spectrum obtained from a capillary 3 surrounded by this tuned rotating resonant micro-coil 6a', it being a 23 Na "MQ MAS" experiment.
• the same rotor 2-micro-coil 6a' system was used as for figure 9.
• the pulse sequence shown in figure 10(a) was applied and the spectrum (b) was obtained.
• the increment in t1 was set to 100 ⁇ s.
• Figures 11a and 11b respectively correspond to a static proton spectrum of water and alcohol inside a capillary surrounded by the solenoidal self-resonant coil 306a' of figure 1d and to a high-resolution "MAS" spectrum of the same capillary and micro-coil 306a' under 300 Hz of spinning.
• MAS high-resolution "MAS" spectrum of the same capillary and micro-coil 306a' under 300 Hz of spinning.
• FIG 11 b shows the high-resolution spectrum obtained using only a self-resonant micro-coil 306a ⁇ and a moderate spinning frequency (300 Hz).
• the line-width is less than 2.5 Hz.
• the radio-frequency amplitude is of the order of 350 kHz, greatly enhanced with respect to the one delivered by the surrounding primary coil 5 (25 kHz).
• the signal to noise is by consequence also improved.
• the correct length of the micro-coil 360a' which gives the self-resonance condition, was determined experimentally. It is also to be noted that the amplitude of the radio-frequency field was a factor 14 higher than that delivered by the probe's coil 5, and that only 50 W of power from the high-power amplifier was used in this experiment.

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• 2006
  • 2006-07-05 EP EP06809256A patent/EP1910859A2/de not_active Ceased

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