Fast switch field combined NMR device for 2fnmr

Abstract

To provide an improved generic two-field NMR spectrometer allowing fast field-cycling NMR experiments.SOLUTION: A central region of a two-field-NMR spectrometer 10 for polarization of an NMR sample 12 and for detection of NMR signals, includes a high field superconducting NMR magnet system 11'; a low field magnet system 11" for generating a variable homogenous magnetic field; a magnetic tunnel 14 for connecting the center of the high field magnet system with the low field magnet system; and a shuttle system 13 designed for shuttling the NMR sample between the high field magnet system and the low field magnet system. The magnetic tunnel is provided with a further magnet system 14', and the high field magnet system, the magnetic tunnel and the low field magnet system are arranged coaxially about the z-axis along a bore 15 of the high field magnet system.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a dual-field nuclear magnetic resonance spectrometer adapted to perform field cycling technique NMR relaxometry experiments, a high-field superconducting NMR magnet system for generating a uniform magnetic field parallel to the z-axis in a central region of the dual-field NMR spectrometer for polarization of the NMR sample and detection of the NMR signal; a low field magnet system generating a variable uniform magnetic field; a magnetic tunnel connecting the center of the high-field superconducting NMR magnet system and the low-field magnet system; a shuttle system designed to shuttle an NMR sample between a high field superconducting NMR magnet system and a low field permanent magnet system; Includes. A field-cycling NMR spectrometer comprising a high-field superconducting NMR magnet, a low-field magnet system and a shuttle system is known from EP 4071492 (=reference [1]). [Background technology]

[0002] In general, the present invention relates to the technical field of magnetic resonance. Nuclear magnetic resonance (="NMR") spectroscopy is a powerful tool in instrumental chemical analysis and a commercially widespread method for analyzing and characterizing the chemical composition of substances. In an NMR experiment, a sample is subjected to a strong static magnetic field, which interacts with the spins of the nuclei contained in the sample. Radio frequency (="RF") pulses are sent to the sample to manipulate the spins, and the reaction of the sample, i.e. the RF signal (also called the "NMR signal"), is measured. The reaction of the sample depends on the environment of the nuclei in the sample, in particular on the bound electrons. Thus, by analyzing the measured NMR signal, information about the chemical structure of the sample can be obtained.

[0003] Improvements in NMR methods, such as field cycling, make it possible to exploit the interaction of nuclear spins with magnetic fields of different strengths, thereby making more spectroscopic information available about the sample.

[0004] Field cycling techniques in NMR have been applied to a variety of field-dependent studies. The main idea is to measure relaxation on a frequency basis. Applications include materials science (e.g. polymer dynamics), structural biology (e.g. membrane dynamics and protein dynamics), and relaxation measurements of contrast agents in MRI.

[0005] In particular, in dual-field NMR (= "2F-NMR") experiments, nuclear spins can be exposed to and manipulated by RF pulses of two different magnetic field strengths. This makes it possible to obtain additional spectroscopic information about the sample, especially dynamic information, or an additional measurement dimension, which can be used to improve the resolution, in particular to more reliably identify spectral maxima.

[0006] In the first working space with the first NMR probe, a first magnetic field strength with high homogeneity ("high magnetic field") is present, which allows for strong initial polarization and signal detection with particularly high resolution and high sensitivity. Furthermore, nuclear spin manipulations can be performed in the first working space. In the second working space with the second NMR probe, a second magnetic field strength with at least fairly good homogeneity ("low magnetic field") is present, which also allows for nuclear spin manipulations, in particular band-selective manipulations of the spins.

[0007] For many nuclear spin systems, the coupling properties and / or relaxation times depend on the magnetic field strength present. Thus, because there are two different magnetic field strengths available, 2F NMR instruments can perform experiments that exploit different coupling properties and / or relaxation times in the same single measurement.

[0008] This provides additional information about the sample in spectroscopic applications: in particular, dynamic information (mobility information) about the nuclei in the sample or molecules containing said nuclei can be obtained.

[0009] Thus, an additional dimension of the NMR measurement of the sample becomes available. This additional dimension is based on a different second magnetic field strength, and therefore a different physical behavior, compared to the physical behavior at the first magnetic field strength. In other words, the evolution of the spin system in the sample is different at the first and second magnetic field strengths.

[0010] The temporal exposure of the sample to a variable relaxation field can be performed by electronically switching the current in the magnet coils or by mechanically moving the sample between positions of different magnetic flux density. The latter field cycling variant is also called the "sample shuttle technique" used in the present invention. A good electronically switched relaxometer has field switching and settling times to the required precision and stability on the order of milliseconds, while sample shuttling times can be achieved in less than 100 ms (see, for example, reference [1]).

[0011] Special conventional technology Rainer Kimmich and Esteban Anoardo, “Field-cycling NMR relaxometry”, Progress in Nuclear Magnetic Resonance Spectroscopy 44 (2004) 257-320 (=Reference [2]) gives a general overview of the FFC NMR principles.

[0012] In a typical two-field NMR experiment, the sample is first exposed to a first strong magnetic field at a first location (first magnetic center, first sample space), then moved to a second location (second magnetic center, second sample space) in a second, weaker magnetic field where the nuclear spins are relaxed and / or manipulated, and finally the sample is moved back to the first strong magnetic field location where the actual NMR measurements are performed.

[0013] In the first position, the sample is polarized in a magnetic field with a flux density as high as technically feasible. A relaxation process takes place in a low magnetic field interval that varies in length and with a lower flux density. The signal remaining after this relaxation interval is detected again in a further magnetic field of fixed flux density as high as possible.

[0014] At the second location, the polarization can be transferred to the desired nuclei, so that the NMR signal of these nuclei can be amplified in the subsequent NMR measurement. In order to preserve as much as possible the polarization transferred when the sample is transported between the second and first locations, this transport should be rapid, which is why a short path between the second and first locations is desirable.

[0015] EP 3081954 (=reference [3]) describes in detail a 2F-NMR measurement comprising a sample in a first working space with a highly homogeneous magnetic field having a first magnetic field strength and transferring the sample to a second working space with a magnetic field having a less homogeneous magnetic field at a second magnetic field strength. A sample carrier is provided for transporting the sample between the first and second working spaces.

[0016] The usual structure of the magnet system of a two-field NMR spectrometer includes a superconducting magnet (magnetic coil) in a cryostat. A first sample space (first magnetic center) is formed in the magnetic center of the superconducting magnet located in the room temperature bore of the cryostat. A second sample space (second magnetic center) is located in the room temperature bore in the stray magnetic field of the superconducting magnet, where a nearly uniform magnetic field is generated locally by a ferromagnetic shim. This magnet structure can be manufactured using a standard NMR system by placing a ferromagnetic shim in the room temperature bore. A disadvantage of this magnet structure is that the magnetic field strength in the second sample space is limited to about 0.5 Tesla or less. Furthermore, the magnetic field strength in the second sample space is not freely adjustable. If the ferromagnetic shim is placed in the room temperature bore, the installation space is also quite limited.

[0017] US 2016 / 0076924 (= Reference [4]) describes a field-cycling magnetic resonance-based method and apparatus for measuring and analyzing flow properties in flowing composites. The pre-polarizing magnet is a Halbach magnet through which the fluid flows. Relaxation of the magnetization is performed in a second magnetic field region of variable strength, and the measurement step is performed in a third magnetic field region on the NMR measurement module. Due to the flow nature of this experiment, the apparatus does not include a shuttle system.

[0018] WO 2011 / 151049 (=reference [5]) describes a method and an apparatus for carrying out the nuclear spin relaxation method to determine the longitudinal relaxation behavior of the nuclear spins of a sample. The method comprises the steps of prepolarization, evolution and detection. Prepolarization of the nuclear spins of the sample occurs in a large magnetic field with a magnitude of up to 1 Tesla. When the nuclear spin magnetization reaches a saturation state, a sufficiently fast (non-adiabatic) switching of the magnetic field to a small adjustable evolutionary field occurs so that the nuclear spins cannot follow. At the end of the evolution period, a switching of the magnetic field to a detection field is performed again and the z-component of the magnetization is recorded in the detection field. The switching between the different magnetic fields is achieved by suitable coil arrangements and their rapid switching. The transport of the sample will not be described. Thus, this known two-field NMR experiment is also performed without a shuttle. Moreover, the very different magnetic fields of highly variable strength are generated by only a single magnet system.

[0019] Zhoukov et al., “Field-cycling NMR experiments in an ultra-wide magnetic field range: relaxation and coherent polarization transfer”, Phys.Chem.Chem.Phys., 2018, 20, 12396-12405 (= Reference [6]) used a shuttle system to study the relaxation and polarization transfer phenomena by measuring the magnetic field dependence of the T1 relaxation time over a magnetic field range of 10 nT to 9.4 T in a heteronuclear spin system. The shuttle system includes a carriage that is mechanically moved by a rack-and-gear system with a relatively slow transfer time of about 0.5 s. This slow transfer time results in a loss of polarization. To go to magnetic fields below 2 mT, a magnetic shield is attached to the top of the NMR spectrometer, and inside the shield, the magnetic field is low. To vary the magnetic field in the range below 2 mT, the currents in the magnetic coils located inside the shield are adjusted. Additional shim coils are used to compensate for linear and quadratic magnetic field gradients.

[0020] US Patent No. 11,579,224 (=Reference [7]) describes a magnet system for a two-field NMR experiment, including a superconducting main field magnet for generating a first magnetic field in a first sample space, a superconducting additional field magnet for generating a second magnetic field in a second sample space, and a cryostat having a cooled main coil vessel, an evacuated room temperature cover, and an RT bore extending through the main field magnet and the additional field magnet. The magnet system includes a cooled additional coil vessel in vacuum.

[0021] The RT cover has a flange connection with an opening through which the RT bore extends. The front end of the additional coil container protrudes into the RT cover through the flange opening so that the additional field magnet also protrudes at least partially into the RT cover through the flange opening. A closure structure is installed at the flange connection, sealing the RT cover between the flange connection and the RT bore. This allows for flexible use and two-field NMR spectroscopy with good signal strength.

[0022] Reference [1] cited on the front page describes a general dual-field NMR spectrometer that includes a high-field superconducting NMR magnet system bridged by a magnetic tunnel with a low-field magnet system that generates a variable uniform magnetic field, and a shuttle system designed to shuttle an NMR sample between the high-field superconducting NMR magnet system and the low-field permanent magnet system. In particular, reference [1] describes in detail the transport device that is part of the shuttle assembly. [Prior art documents] [Patent documents]

[0023] [Patent Document 1] European Patent No. 4071492 [Patent Document 2] European Patent No. 3081954 [Patent Document 3] US Patent Application Publication No. 2016 / 0076924 [Patent Document 4] International Publication No. 2011 / 151049 [Patent Document 5] U.S. Pat. No. 11,579,224 [Non-patent literature]

[0024] [Non-Patent Document 1] R. Kimmich et al., “Field-cycling NMR relaxometry”, Progress in Nuclear Magnetic Resonance Spectroscopy 44 (2004) 257-320 [Non-Patent Document 2] Zhoukov et al., “Field-cycling NMR experiments in an ultra-wide magnetic field range:relaxation and coherent polarization transfer”,Phys.Chem.Chem.Phys.,2018,20,12396-12405 Summary of the Invention [Problem to be solved by the invention]

[0025] The aim of the present invention is to present an improved versatile dual-field NMR spectrometer that enables fast field cycling NMR experiments over a wide range of magnetic fields, preferably from the very low 100 µT to the very high 29.3 T.

[0026] In particular, the present invention aims to: -Very uniform low magnetic field -Excellent resolution of detected spectra at high magnetic fields -High detection sensitivity -Maintain the longevity of the manipulated spins as much as possible. One problem with the present invention is to overcome the loss of polarization due to spin-spin relaxation during shuttling. Also, the influence of the two magnet systems, the polarizing high field magnet and the low field magnet, on each other needs to be minimized. Another object of the present invention is to provide a system that allows relaxation measurements with greater sensitivity than the prior art by providing an advanced field magnet with high homogeneity at very low magnetic fields. It will be apparent to those skilled in the art that the placement of the low field magnet and its shielding against both the earth's magnetic field and high field magnets represents a major technical challenge. [Means for solving the problem]

[0027] This object is achieved according to the invention in a surprisingly simple and effective manner by a dual-field NMR spectrometer, whereby the magnetic tunnel is provided with a further magnet system, the high-field superconducting NMR magnet system, the magnetic tunnel and the low-field magnet system being arranged coaxially around the z-axis along the bore of the high-field superconducting NMR magnet system.

[0028] In the framework of the present invention the terms low field magnet system, field cycling coil and relaxation magnet are used synonymously.

[0029] The transport system according to the present invention is space-saving, can be easily integrated into a commercially available NMR spectrometer, and can precisely move an NMR sample container fixed to a shuttle assembly between at least two adjustable measurement positions in less than 100 ms.

[0030] The system can be adapted to existing or commercially available NMR spectrometers without modification of the magnet bore.

[0031] Preferred embodiments and further developments of the invention In a particularly preferred class of embodiments of the present invention, the further magnet system of the magnetic tunnel comprises permanent magnets preferably arranged in a Halbach dipole configuration with k=2. The Halbach arrangement allows for a strong magnetic field inside the tunnel and a very low stray magnetic field outside the tunnel.

[0032] Preferably, in a further development of this class of embodiments, the magnetic field generated by the further magnet system of the magnetic tunnel is oriented perpendicular to the homogeneous magnetic field parallel to the z-axis generated by the high-field superconducting NMR magnet system. Creating a magnetic field perpendicular to the tunnel axis is the most efficient orientation for the Halbach arrangement, which minimizes the amount of permanent magnets required for a given magnetic field strength.

[0033] In another advantageous embodiment, the further magnet system of the magnetic tunnel is designed to generate an adiabatic magnetic field with a magnetic flux density in the range of 0.5T to 1T. The principle of magnetic tunneling makes it possible to maintain the lifetime of polarized spins during rapid sample transfer between two magnetic fields, i.e. a high-field superconducting magnet and a low-field magnet system (=field cycling coils).

[0034] The solution according to the invention allows the use of field coils for relaxation or field cycling magnets that are not actively shielded, i.e. no additional shielding coils are required. The relaxation magnets are therefore more efficient, as higher magnetic fields can be achieved with the same current.

[0035] The use of a magnetic tunnel allows the field-cycling coils to be located outside the superconducting magnet. Not being restricted by the superconducting magnet bore allows for larger coils in the relaxation magnet and does not require active shielding.

[0036] In a preferred further development of this embodiment, one end of the further magnet system of the magnetic tunnel is placed in a region of the bore where the flux density of the homogeneous magnetic field generated by the high-field superconducting NMR magnet system is reduced to about 1 T, ensuring that the sample is never in a non-magnetic environment. The direction of the magnetic field is not important: the sample is always exposed to a magnetic field of at least 1 T before entering the field cycling coil. This ensures that the polarization is not lost during the transfer process.

[0037] A preferred embodiment of the invention is characterized in that the high field superconducting NMR magnet system is designed to generate a homogeneous magnetic field in the range of 5T to 30T, in particular 7.3T to 29.3T. In the present embodiment, 600.13Mhz=14.65 Tesla / 700.13Mhz=17.09 Tesla superconducting magnets are used, but theoretically the technology can be extended up to 1.2GHz Bruker ultra-high field magnets, equivalent to 29.29 Tesla. The higher the magnetic field, the higher the resolution. The system can be adapted to any superconducting magnet by adjusting the ring-shaped permanent magnet (shimming ring) to the magnet. In theory, the system can even be improved by using a superconducting magnet with a higher magnetic field. For example, if a customer wants to use a stronger magnet, it is possible to adapt the existing system to the new magnet.

[0038] In an advantageous embodiment, the low field magnet system includes a resistive coil-based electromagnet device for field cycling designed to generate a uniform magnetic field with variable magnetic flux density in the range of 100 μT to 1 T. This means that the low-field magnet system can generate much lower magnetic fields compared to the prior art unshielded magnets, which have a lower limit of 200 μT. The low-field range of the device is therefore significantly extended by this innovation.

[0039] Preferably, in this embodiment variation, the magnetic field generated by the electromagnet arrangement for field cycling has a homogeneity of at least 10% along the NMR sample, preferably within a switching time of about 1 ms or less. Exposure of the sample to a uniform and temporally stable magnetic field is important for signal quality.

[0040] A further embodiment is advantageous in which the low field magnet system for field cycling is arranged directly above the high field superconducting NMR magnet system. The field cycling coils are far enough away from the superconducting high field magnets that they can avoid magnetic coupling with the SC magnets. The power required for the same magnetic field is greatly reduced. Furthermore, the water cooling of the relaxation magnets is more efficient since there is more space for the cooling system. The additional radial space makes it possible to have 12 coils and 6 water jackets, thus allowing a maximum magnetic field of 0.8 T to be reached as well as a high duty cycle.

[0041] In another preferred embodiment, the low field magnet system comprises a ring-shaped permanent magnet with a radial magnetization relative to the z-axis, specifically designed to cancel the magnetic stray fields arising from high field superconducting NMR magnet systems. Using permanent magnets is a passive solution, so no additional power or cooling is required. It is easy to add axial adjustment of the ring. This makes it possible to deal with variations in the stray field of a superconducting magnet by simply changing the axial position of the magnet ring.

[0042] A preferred class of embodiments is characterized in that the low-field permanent magnet system comprises a cylindrical ferromagnetic part, in particular comprising μ-metal, for shielding inhomogeneous external magnetic disturbance fields with low magnetic flux density. Ferromagnetic μ-metal components are used in the field cycling coils to maintain the same magnetic field homogeneity over the range from 100 μT to 0.8 T. The shape of the part and its thickness are optimized as follows. At high magnetic fields, the ferromagnetic parts are magnetically saturated, but the expected magnetic field uniformity is achieved because the external non-uniform disturbance magnetic fields (earth magnetic field, leakage magnetic fields from superconducting magnets and magnetic tunnels, etc.) are weak compared to the magnetic field from the zero coil. At low fields, the inhomogeneous disturbance fields (earth field, leakage fields from superconducting magnets and magnetic tunnels, etc.) are larger than the field of the zero coil. However, since the field is weak, the ferromagnetic part guides the inhomogeneous disturbance fields as well as the field of the coils, and homogeneity is maintained at very low field strengths, optimizing the first two coils (inside the μ-metal part) for low field strengths. The use of μ-metal components is a passive solution for attenuating and shielding the residual low external magnetic field. In principle, μ-metal components work independently of the orientation of the low residual magnetic field. Therefore, no additional shimming coils and power amplifiers are required.

[0043] In this class of embodiments, the low field magnet system preferably includes at least one low field coil disposed inside a cylindrical ferromagnetic portion designed to generate a magnetic field with a magnetic flux density below the magnetic saturation of the ferromagnetic portion. This coil is necessary to generate a magnetic field in the range of 100 μT to a few mT. Otherwise, the magnetic field generated by the coil will be shielded and the magnetic field at the center of the coil will be 0 T.

[0044] Another preferred variant of this class of embodiments is characterized in that the low field magnet system includes at least one high field coil arranged outside the cylindrical ferromagnetic portion to generate a magnetic field with a magnetic flux density above the magnetic saturation of the ferromagnetic portion. These coils must be placed radially outside the μ-metal shield so that their magnetic fields are shielded by the μ-metal when the magnetic fields are below the saturation of the μ-metal.

[0045] In a preferred embodiment of the present invention, the shuttle system is designed to shuttle an NMR sample between a high field superconducting NMR magnet system and a low field magnet system in less than 100 ms. The polarization of the sample is ideally preserved by very rapid shuttling through the adiabatic magnetic field of a magnetic tunnel.

[0046] Further advantages can be extracted from the description and the attached drawings. The above and following features can be used individually or collectively in any combination according to the invention. The mentioned embodiments should not be understood as an exhaustive enumeration, but rather have exemplary features for the explanation of the invention. The invention is illustrated in the drawings and will be explained in more detail on the basis of exemplary embodiments. [Brief description of the drawings]

[0047] [Figure 1] 1 is a schematic vertical cross-sectional view of an NMR spectrometer with a modified magnetic tunnel according to the invention; [Diagram 2] FIG. 2 is a schematic diagram of a preferred method of field cycling by using a dual-field NMR spectrometer according to the present invention, in which a field-cycling coil is placed at the top end of the magnetic tunnel. [Diagram 3]FIG. 2 is a cross-sectional view through a magnetic tunnel with arrows indicating the direction of magnetic flux within the hollow magnetic tunnel and within the magnetic material that establishes the tunnel. [Figure 4] FIG. 1 is a schematic three-dimensional diagram of a resistive coil-based electromagnetic device for magnetic field cycling, designed to generate a uniform magnetic field with variable magnetic flux density, including a low magnetic field coil system disposed inside a cylindrical ferromagnetic portion surrounded by a high magnetic field coil system for generating a magnetic field with a magnetic flux density above the magnetic saturation of the ferromagnetic portion. [Diagram 5] FIG. 5 is a schematic three-dimensional partial view of one embodiment of a low-field permanent magnet system in an NMR spectrometer according to the present invention, comprising a resistive coil-based electromagnet device for magnetic field cycling as shown in FIG. 4, an additional magnet system in a magnetic tunnel, and a ring-shaped permanent magnet radially surrounding the additional magnet system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] FIG. 1 is a schematic diagram of a dual-field NMR spectrometer 10 for performing field-cycling NMR relaxometry experiments; a high-field superconducting NMR magnet system 11' for generating a uniform magnetic field parallel to the z-axis in a central region of the dual-field NMR spectrometer 10 for polarizing the NMR sample 12 and detecting the NMR signal; A low-field magnet system 11 ″ that generates a variable uniform magnetic field; a shuttle system 13 designed to shuttle the NMR sample 12 between the high field superconducting NMR magnet system 11' and the low field permanent magnet system 11"; a magnetic tunnel 14 connecting the center of the high-field superconducting NMR magnet system 11' to the low-field magnet system 11"; Includes.

[0049] The dual-field NMR spectrometer 10 according to the invention is characterized by the provision of a further magnet system 14' in the magnetic tunnel 14 and by a high-field superconducting NMR magnet system 11', the magnetic tunnel 14 and the low-field magnet system 11'' being arranged coaxially around the z-axis along the bore 15 of the high-field superconducting NMR magnet system 11' contained in a cryostat 20.

[0050] The low field magnet system 11″ for field cycling is placed directly above the high field superconducting NMR magnet system 11′ to avoid a long sample transport path. Therefore, the field cycling magnet must eliminate the residual magnetic fields of the high field magnet and the tunnel magnet.

[0051] The shuttle system 13 is designed to shuttle the NMR sample 12 between the high field superconducting NMR magnet system 11' and the low field magnet system 11" in less than 100 ms. Thus, the present invention uses a relatively fast sample shuttling technique and improves signal (polarization) loss during shuttling. The low field magnet is located in close proximity to the high field magnet, but outside the high field magnet cryostat 20, which allows for short shuttle distances.

[0052] The basic idea of ​​the present invention was to design an improved dual-field NMR spectrometer 10 for performing field-cycling NMR, which has excellent resolution in the high-field part with magnetic fields of up to 30 T flux density and is adapted to reach very low magnetic fields of up to 100 μT flux density in the low-field part of the device.

[0053] The system according to the invention can be easily adapted to existing NMR spectrometers without modification of the magnet bore.

[0054] The schematic diagram in Figure 2 shows a preferred method of field cycling by using a dual-field NMR spectrometer according to the present invention in which the field cycling coil is positioned above the superconducting high-field magnet. The sample is shuttled between the high-field superconducting NMR magnet system 11' and the low-field NMR magnet system 11" via a magnetic tunnel 14.

[0055] Said method corresponds to the prior art method of reference [6] with the difference that the spectrometer uses a high-speed shuttle for very fast transport of the sample tube from the polarizing magnet to the relaxation magnet, as disclosed in reference [1]. Moreover, reference [6] does not use a magnetic tunnel, which loses polarization and therefore signal during the transfer.

[0056] The solution is to expand the average magnetic field area towards the outside of the cryogenic magnet from 0.5T to 1T by adding a magnetic tunnel (typically 0.7T to 1T). This solution makes it possible to use field cycling coils (relaxation magnets) without additional shielding coils, i.e. more efficient (more magnetic field at the same current). The power required for the same magnetic field is significantly reduced and the water cooling is also more efficient (more space for the cooling system).

[0057] The schematic in Figure 2 shows the preferred mode of operation, in which the relaxation field coils are moved to the outside of the magnet and a magnetic tunnel is added. A) The evolution of the magnetic field in the z-direction of the bore is shown, which represents the magnetic field strength to which the sample is exposed. The dotted line indicates the bottom end of the magnetic tunnel where the magnetic field strength is maintained during the transfer of the sample from this discrete level (approximately 1 T). B) In the first step of the method, the sample is polarized in a high field magnet for a defined exposure time. C) The second step is the rapid transfer of the sample to the FCC via an adiabatic magnetic tunnel. D) The FCC can be rapidly (1 ms) switched to a preselected magnetic field (here, 100 μT-0.8 T) for relaxation. E) The sample is exposed to a relaxation magnetic field for a defined period of time. F) Optionally, the FCC sample can be subjected to a moderate magnetic field. G) The sample is then returned to the high field magnet. H) Spectral acquisition is performed in a high-field magnet.

[0058] In a cross-sectional view of the magnetic tunnel 14, Figure 3 shows an embodiment of a further magnet system 14' of the magnetic tunnel 14 including permanent magnets arranged in a Halbach dipole configuration with k = 2. The arrows indicate the direction of magnetic flux inside the hollow magnetic tunnel and inside the magnetic material that establishes the tunnel.

[0059] The magnetic field generated by the further magnet system 14' in the magnetic tunnel 14, which is designed to generate an adiabatic magnetic field with a flux density in the range of 0.7 T to 1 T, is oriented perpendicular to the uniform magnetic field parallel to the z-axis generated by the high-field superconducting NMR magnet system 11'.

[0060] One end of the further magnet system 14' of the magnetic tunnel 14 is arranged in the region of the bore 15 where the flux density of the homogeneous magnetic field generated by the high-field superconducting NMR magnet system 11' is reduced to approximately 1T.

[0061] Inside the ring of the further magnet system 14' a strong horizontal magnetic field is generated. By stacking many such rings a long tunnel with a constant horizontal magnetic field can be achieved.

[0062] The following assumptions were made: The permanent magnet material used is NdFeB with a magnetic remanence of 1.39T. The inner radius of the ring is 8.5 mm and the outer radius is 20 mm. The resulting magnetic field inside the ring is greater than 1 T.

[0063] The magnetic tunnel 14 in this example has a length of 600 mm and starts axially 400 mm from the magnetic center of the 600 MHz magnet and 500 mm from the magnetic center of the 700 MHz magnet, which creates a magnetic field inhomogeneity in the magnetic center of the cryogenic magnets that can be easily compensated for with a room temperature shim system.

[0064] To resume, the 2F NMR device according to the invention comprises three different main magnetic elements: a. High-field magnet for polarization b. Magnetic tunnel c. Field Cycling Coil for Mitigation ("FCC")

[0065] a) The high field polarizing magnet is generally a superconducting NMR magnet, which may be selected from, for example, 7.3 T to 29.3 T. b) The magnetic tunnel consists of permanent magnets in a Halbach configuration. It generates an adiabatic magnetic field with a field strength of 0.5T to 1.5T depending on the nucleus. The magnetic tunnel is important to maintain the spin polarization during the transfer between the magnets a) and c). The magnetic tunnel is placed inside the bore of the superconducting magnet and the magnetic field strength is reduced to about 1 T so that the sample is never in a non-magnetic environment, preferably never below a magnetic field of 0.7 T. The direction of the magnetic field is not important: the superconducting magnet and the FCC both generate a magnetic field in the z direction along the common bore, while the magnetic tunnel generates a perpendicular magnetic field in the x direction due to the Halbach configuration. c) The field cycling coil or fast field cycling magnet (FCC) is an electromagnet that can be varied from 100 μT to 1 T in a very short time of 1 ms. This magnet is not actively shielded, but its design allows it to be independent of the magnetic field of the high field magnet in the Z direction, the magnetic field of the magnetic tunnel in the x direction, and the earth magnetic field. FFC magnets must have a homogeneity of at least 10% along the sample.

[0066] FIG. 4 shows in a schematic three-dimensional view important details of a preferred embodiment of a dual-field NMR spectrometer 10 according to the present invention. Here, the low-field magnet system 11″ includes a resistive coil-based electromagnet device 16 for field cycling, designed to generate a uniform magnetic field with variable flux density in the range of 100 μT to 1 T and homogeneity of at least 10% along the NMR sample 12, preferably within a switching time of about 1 ms or less.

[0067] The low-field permanent magnet system 11'' comprises a cylindrical ferromagnetic part 16', which contains, inter alia, μ-metal, for shielding inhomogeneous disturbing magnetic fields with low magnetic flux density.

[0068] Furthermore, the low field permanent magnet system 11″ includes at least one low field coil 18 disposed inside the cylindrical ferromagnetic portion 16′ designed to generate a magnetic field with a magnetic flux density below the magnetic saturation of the ferromagnetic portion 16′.

[0069] Additionally, the low field permanent magnet system 11'' includes at least one high field coil 19 disposed outside the cylindrical ferromagnetic portion 16' to generate a magnetic field with a magnetic flux density above the magnetic saturation of the ferromagnetic portion 16'.

[0070] FIG. 5 shows in a schematic three-dimensional partial view one embodiment of a low-field permanent magnet system in a dual-field NMR spectrometer 10 according to the invention, comprising a resistive coil-based electromagnet arrangement 16 for magnetic field cycling as shown in FIG. 4, a further magnet system 14′ in the magnetic tunnel 14, and a ring-shaped permanent magnet 17 radially surrounding the further magnet system 14′ with radial magnetization relative to the z-axis.

[0071] This additional system of ring-shaped permanent magnets 17 is designed to cancel the magnetic stray field arising from the high-field superconducting NMR magnet system 11' to achieve a very low magnetic field of about 100 μT. The amplitude of the superconducting magnetic stray field of the high-field superconducting NMR magnet system 11' is about 10 mT at the center of the coils of the low-field permanent magnet system 11". The rings are radially magnetized in opposite directions to generate a constant magnetic field with a gradient along the z-axis.

[0072] Preferred embodiments of the magnetic tunnel: In high-resolution dual-field NMR, the NMR sample is shuttled between a high magnetic field (e.g. 14 T) and a low magnetic field (e.g. 3 T). The path between the high and low fields must be within as high a background field as possible, because the sample cannot lose its polarization. The magnetic field direction is not important.

[0073] The preferred concept of dual-field NMR according to the present invention is to add a low-field magnet on top of the high-field magnet. In the path between the two magnetic centers, a magnetic tunnel made of a Halbach array can maintain a minimum magnetic flux density. [Explanation of symbols]

[0074] 10 Dual field NMR spectrometer 11' High-field superconducting NMR magnet system 11” low field NMR magnet system 12 NMR sample 13 Shuttle System 14 Magnetic Tunnel 14' Further magnet systems 15. Bore of high-field superconducting NMR magnet system 16 Resistive coil-based electromagnetic device for field cycling 16' Cylindrical ferromagnetic parts, especially those containing μ metals 17 Ring-shaped permanent magnet 18. Low-field coil placed inside the cylindrical ferromagnetic section 19 High magnetic field coils arranged on the outside of the cylindrical ferromagnetic part 20 NMR Cryostat

[0075] List of prior art documents: Publications to be considered for assessing the patentability of the invention: [1] European Patent No. 4071492 ≒ Chinese Patent No. 115201728 ≒ U.S. Patent No. 11,474,172 [2] R. Kimmich et al., “Field-cycling NMR relaxometry”, Progress in Nuclear Magnetic Resonance Spectroscopy 44(2004)257-320 [3] European Patent No. 3081954 [4] U.S. Patent Application Publication No. 2016 / 0076924 [5] International Publication No. 2011 / 151049 [6] IVZhoukov et al., "Field-cycling NMR experiments in an ultra-wide magnetic field range: relaxation and coherent polarization transfer", Phys.Chem.Chem.Phys., 2018, 20, 12396-12405 [7] U.S. Patent No. 11,579,224 Specifications ≒ European Patent No. 4006567 Specifications ≒ Dokko Patent No. 102020214887 Specifications

Claims

1. A dual-field NMR spectrometer (10) for performing field cycling NMR relaxometry experiments, comprising: a high-field superconducting NMR magnet system (11') for generating a uniform magnetic field parallel to the z-axis in a central region of said dual-field NMR spectrometer (10) for polarizing an NMR sample (12) and detecting NMR signals; a low field magnet system (11″) generating a variable homogeneous magnetic field; a magnetic tunnel (14) connecting the centre of said high field superconducting NMR magnet system (11') to said low field magnet system (11"); a shuttle system (13) designed to shuttle the NMR sample (12) between the high field superconducting NMR magnet system (11') and the low field magnet system (11"); Including, The magnetic tunnel (14) is provided with a further magnet system (14'), The high field superconducting NMR magnet system (11'), the magnetic tunnel (14) and the low field magnet system (11"), arranged coaxially around the z-axis along the bore (15) of the high-field superconducting NMR magnet system (11′), Dual field NMR spectrometer (10).

2. NMR spectrometer according to claim 1, characterized in that the further magnet system (14') of the magnetic tunnel (14) comprises permanent magnets preferably arranged in a Halbach dipole configuration with k=2.

3. 3. The NMR spectrometer according to claim 2, characterized in that the magnetic field generated by the further magnet system (14') of the magnetic tunnel (14) is oriented perpendicular to the uniform magnetic field parallel to the z-axis generated by the high-field superconducting NMR magnet system (11').

4. NMR spectrometer according to any one of claims 1 to 3, characterized in that the further magnet system (14') of the magnetic tunnel (14) is designed to generate an adiabatic magnetic field with a magnetic flux density in the range of 0.7 T to 1 T.

5. 5. An NMR spectrometer according to claim 1, characterized in that one end of the further magnet system (14') of the magnetic tunnel (14) is arranged in a region of the bore (15) in which the magnetic flux density of the homogeneous magnetic field generated by the high-field superconducting NMR magnet system (11') is reduced to about 1 T.

6. NMR spectrometer according to any one of claims 1 to 5, characterized in that the high-field superconducting NMR magnet system (11') is designed to generate a homogeneous magnetic field in the range of 5T to 50T, in particular 7.3T to 29.3T.

7. NMR spectrometer according to any one of claims 1 to 6, characterized in that the low-field magnet system (11'') comprises a resistive coil-based electromagnet arrangement (16) for field cycling, designed to generate a homogeneous magnetic field with a variable magnetic flux density in the range of 100 μT to 1 T.

8. 8. The NMR spectrometer according to claim 7, characterized in that the magnetic field generated by the electromagnet arrangement (16) for field cycling has a homogeneity of at least 10% along the NMR sample (12) within a switching time, preferably of about 1 ms or less.

9. 9. NMR spectrometer according to any one of claims 1 to 8, characterized in that the low field magnet system (11") for field cycling is placed directly above the high field superconducting NMR magnet system (11').

10. 10. NMR spectrometer according to any one of claims 1 to 9, characterized in that the low field magnet system (11") comprises a ring-shaped permanent magnet (17) with a radial magnetization with respect to the z-axis, in particular designed to cancel stray fields arising from the high field superconducting NMR magnet system (11').

11. NMR spectrometer according to any one of claims 1 to 10, characterized in that the low-field permanent magnet system (11'') comprises a cylindrical ferromagnetic part (16') containing in particular a μ-metal for shielding external magnetic disturbance fields of low magnetic flux density and inhomogeneity.

12. NMR spectrometer according to claim 11, characterized in that the low-field permanent magnet system (11'') comprises at least one low-field coil (18) arranged inside the cylindrical ferromagnetic part (16') designed to generate a magnetic field with a magnetic flux density below the magnetic saturation of the ferromagnetic part (16').

13. NMR spectrometer according to claim 11 or 12, characterized in that the low-field permanent magnet system (11") comprises at least one high-field coil (19) arranged outside the cylindrical ferromagnetic part (16') for generating a magnetic field with a magnetic flux density above the magnetic saturation of the ferromagnetic part (16').

14. NMR spectrometer according to any one of claims 1 to 13, characterized in that the shuttle system (13) is designed to shuttle the NMR sample (12) between the high field superconducting NMR magnet system (11') and the low field magnet system (11") in less than 100 ms.

Images