High-speed switch-field coupled NMR spectrometer for 2F NMR

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 two-field nuclear magnetic resonance spectrometer adapted to perform magnetic field cycling technology NMR relaxation measurement experiments. For the polarization of an NMR sample and the detection of an NMR signal, a high-field superconducting NMR magnet system for generating a uniform magnetic field parallel to the z-axis in the central region of the two-field NMR spectrometer, a low-field magnet system for 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 reciprocate an NMR sample between the high-field superconducting NMR magnet system and the low-field permanent magnet system, and includes. A magnetic field cycling NMR spectrometer including a high-field superconducting NMR magnet, a low-field magnet system, and a shuttle system is known from European Patent No. 4071492 (= reference [1]). [Background Art]

[0002] Generally, 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 is a commercially widespread method for analyzing and characterizing the chemical composition of substances. In an NMR experiment, a sample is exposed to a strong static magnetic field and interacts with the spins of the nuclei contained in the sample. High-frequency (= "RF") pulses are sent to the sample to manipulate the spins, and the response of the sample, i.e., the RF signal (also called the "NMR signal"), is measured. The response of the sample depends on the environment of the nuclei in the sample, particularly the bonding electrons. Therefore, by analyzing the measured NMR signal, information regarding the chemical structure of the sample can be obtained.

[0003] Improvements in NMR methods such as magnetic field cycling enable the utilization of the interaction of nuclear spins with magnetic fields of different intensities, thereby making more spectroscopic information regarding the sample available.

[0004] Magnetic field cycling techniques in NMR have been applied to various magnetic field-dependent studies. The main idea is to measure relaxation on a frequency basis. Applications include materials science such as polymer dynamics, structural biology such as membrane dynamics and protein dynamics, and relaxation measurement of contrast agents in the field of 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 additional measurement dimensions, which can be used to improve resolution, and in particular to more reliably identify the maximum value of the spectrum.

[0006] In the first workspace equipped with the first NMR probe, a first magnetic field strength ("high field") with high uniformity is present, enabling strong initial polarization and signal detection with particularly high resolution and sensitivity. Furthermore, nuclear spin manipulation can be performed in the first workspace. In the second workspace equipped with the second NMR probe, a second magnetic field strength ("low field") with at least fairly good uniformity is present, which also enables nuclear spin manipulation, particularly band-selective manipulation of spins.

[0007] In many nuclear spin systems, coupling characteristics and / or relaxation times depend on the present magnetic field strength. Therefore, since two different magnetic field strengths are available, a 2F-NMR instrument can perform experiments that utilize different coupling characteristics and / or relaxation times in the same single measurement.

[0008] This provides additional information about the sample for spectroscopic applications. In particular, it allows us to obtain dynamic information (movement information) about nuclei or molecules containing such nuclei within the sample.

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

[0010] Temporary exposure of a sample to a variable relaxation magnetic field can be achieved by electronically switching the current in a magnetic coil or by mechanically moving the sample between locations with different magnetic flux densities. The latter magnetic field cycling variant is also called the “sample shuttle technique” used in this invention. A good electronically switchable relaxation meter has magnetic field switching and settling times to the required precision and stability in milliseconds, while the sample shuttle time 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] provides a general overview of the FFC NMR principle.

[0012] In a typical two-field NMR experiment, the sample is first exposed to a first strong magnetic field at a first position (first magnetic center, first sample space), then moved to a second position (second magnetic center, second sample space) with a second weaker magnetic field where nuclear spins are relaxed and / or manipulated, and finally the sample is returned to the first strong magnetic field position where the actual NMR measurement takes place.

[0013] At the first position, the sample is polarized in a magnetic field with the highest magnetic flux density technically feasible. The relaxation process takes place in low-field intervals that vary in length and with respect to lower magnetic flux densities. The signal remaining after this relaxation interval is detected again in a further magnetic field with the highest possible fixed magnetic flux density.

[0014] At the second position, the polarization can be transferred to a desired atomic nucleus, and as a result, the NMR signal of this nucleus can be amplified in subsequent NMR measurements. In order to preserve as much of the polarization transferred as possible when the sample is transported between the second and first positions, this transport should be rapid, and for this purpose, a short path between the second and first positions is desirable.

[0015] European Patent No. 3081954 (reference [3]) describes in detail a 2F-NMR measurement comprising a sample in a first workspace having a very uniform magnetic field with a first magnetic field strength, and transferring the sample to a second workspace having a lower uniform magnetic field with a second magnetic field strength. A sample carrier is provided for transporting the sample between the first workspace and the second workspace.

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

[0017] U.S. Patent Application Publication No. 2016 / 0076924 (Reference [4]) describes a magnetic field cycling magnetic resonance-based method and apparatus for measuring and analyzing the fluid properties in a fluid composite. The pre-polarized magnet is a Halbach magnet through which the fluid flows. Magnetization relaxation is performed in a second magnetic field region of variable intensity, and the measurement step is performed in a third magnetic field region on an NMR measurement module. Due to the flow nature of this experiment, the apparatus does not include a shuttle system.

[0018] International Publication No. 2011 / 151049 (=Reference [5]) describes a method and apparatus for performing a nuclear spin relaxation method to determine the longitudinal relaxation behavior of nuclear spins of a sample. This method includes pre-polarization, development, and detection steps. Pre-polarization of the nuclear spins of the sample occurs in a large magnetic field up to 1 Tesla. When the nuclear spin magnetization reaches saturation, a sufficiently fast (non-adiabatic) switching occurs to a smaller, tunable developmental magnetic field so that the nuclear spins cannot follow. At the end of the development period, the magnetic field is switched again to a detection magnetic field, and the z component of the magnetization is recorded in the detection field. Switching between different magnetic fields is achieved by a suitable coil arrangement and their rapid switching. Sample transport is omitted from the description. Thus, this known two-field NMR experiment is also performed without a shuttle. Furthermore, very different magnetic fields of extremely variable intensity 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]) studied relaxation and polarization transfer phenomena by using a shuttle system and measuring the magnetic field dependence of T1 relaxation time over a magnetic field range of 10 nT to 9.4 T in heteronuclear spin systems. 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 seconds. This slow transfer time results in polarization loss. To go to magnetic fields below 2 mT, a magnetic shield is mounted on top of the NMR spectrometer, with a lower magnetic field inside the shield. To vary the magnetic field in the range of less than 2 mT, the current in a magnetic coil located inside the shield is adjusted. Additional shim coils are used to compensate for linear and secondary magnetic field gradients.

[0020] U.S. Patent No. 11,579,224 (reference [7]) describes a magnet system for a two-field NMR experiment, comprising a superconducting main magnetic field magnet for generating a first magnetic field in a first sample space, a superconducting additional magnetic 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 magnetic field magnet and the additional magnetic field magnet. The magnet system includes a cooled additional coil vessel in vacuum.

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

[0022] Reference [1] cited on the top page describes a general two-field NMR spectrometer including a high-field superconducting NMR magnet system bridged by a magnetic tunnel having a low-field magnet system that generates a variable uniform magnetic field, and a shuttle system designed to reciprocate an NMR sample between the high-field superconducting NMR magnet system and the low-field permanent magnet system. In particular, Reference [1] details a transfer device that is part of the shuttle assembly.

Prior Art Documents

Patent Documents

[0023]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Non-Patent Documents

[0024]

Non-Patent Document 1

Non-Patent Document 2

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

[0026] In particular, the present invention aims to achieve the following: - Very uniform low magnetic field - Excellent resolution of the spectrum detected in high magnetic fields - High detection sensitivity - To maintain the lifespan of the manipulated spin for as long as possible. One problem with the present invention is to overcome the polarization loss caused by spin-spin relaxation during shuttle operation. Furthermore, it is necessary to minimize the mutual influence between the two magnetic systems, namely the polarized high-field magnet and the low-field magnet. Another object of the present invention is to provide a system that enables relaxation measurements with higher sensitivity than the prior art by providing a developing magnetic field magnet that exhibits high uniformity at very low magnetic fields. It will be apparent to those skilled in the art that the arrangement of low-magnetic-field magnets and their shielding from both the Earth's magnetic field and high-magnetic-field magnets represent significant technical challenges. [Means for solving the problem]

[0027] This objective is achieved by a two-field NMR spectrometer in a remarkably simple and effective manner, according to the present invention, where a further magnetic system is provided in the magnetic tunnel, and the high-field superconducting NMR magnet system, the magnetic tunnel, and the low-field magnet system are arranged coaxially around the z-axis along the bore of the high-field superconducting NMR magnet system.

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

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

[0030] This system can be adapted to existing or commercially available NMR spectrometers without changing the magnet bore.

[0031] Preferred embodiments and further developments of the present invention In a particularly preferred class of embodiments of the present invention, the further magnet system of the magnetic tunnel preferably includes permanent magnets arranged in a Halbach dipole configuration of k=2. The Halbach configuration 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 embodiments of this class, the magnetic field generated by the additional magnet system of the magnetic tunnel is directed perpendicular to the uniform magnetic field parallel to the z axis generated by the high-field superconducting NMR magnet system. Generating a magnetic field perpendicular to the tunnel axis is the most efficient orientation for the Halbach configuration. This minimizes the amount of permanent magnets required for a given magnetic field strength.

[0033] In another advantageous embodiment, a further magnet system in the magnetic tunnel is designed to generate an adiabatic magnetic field having 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 polarization spins during rapid sample transfer between two magnetic fields, namely a high-field superconducting magnet and a low-field magnet system (= magnetic field cycling coil).

[0034] The solution according to the present invention makes it possible to use magnetic field coils in relaxation or magnetic field cycling magnets that are not actively shielded, i.e., do not require additional shielding coils. Therefore, the relaxation magnets are more efficient, so that higher magnetic fields can be achieved with the same current.

[0035] By using a magnetic tunnel, the magnetic field cycling coil can be positioned outside the superconducting magnet. Being unconstrained by the superconducting magnet bore allows for larger coils within the relaxation magnet, eliminating the need for active shielding.

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

[0037] A preferred embodiment of the present invention is characterized in that the high-field superconducting NMR magnet system is designed to generate a uniform magnetic field in the range of 5T to 30T, particularly 7.3T to 29.3T. In this embodiment, a superconducting magnet with 600.13 MHz = 14.65 Tesla / 700.13 MHz = 17.09 Tesla is used, but theoretically, this technology can extend to a 1.2 GHz Bruker superhigh field magnet, which corresponds to 29.29 Tesla. The higher the magnetic field, the higher the resolution. By adjusting the ring-shaped permanent magnet (shimming ring) to the magnet, the system can be adapted to any superconducting magnet. Theoretically, 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 resistance coil-based electromagnet device for magnetic field cycling, designed to generate a uniform magnetic field with a variable magnetic flux density in the range of 100 μT to 1 T. This means that the low-field magnet system can generate a much lower magnetic field compared to conventional unshielded magnets with a lower limit of 200 μT. Therefore, the low-field range of the device is significantly expanded by this innovation.

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

[0040] A further embodiment is advantageous in which the low-field magnet system for magnetic field cycling is positioned directly above the high-field superconducting NMR magnet system. The magnetic field cycling coil is positioned far enough away from the superconducting high-field magnet to avoid magnetic coupling with the SC magnet. The power required for the same magnetic field is significantly reduced. Furthermore, water cooling of the relaxation magnets is more efficient because there is more space for the cooling system. The additional radial space allows for 12 coils and 6 water jackets, thus enabling the achievement of a maximum magnetic field of 0.8T and a high duty cycle.

[0041] In another preferred embodiment, the low-field magnet system includes a ring-shaped permanent magnet having radial magnetization with respect to the z-axis, which is designed to counteract the magnetic levitation field generated particularly from a high-field superconducting NMR magnet system. Using permanent magnets is a passive solution, so no additional power or cooling is required. Adding axial adjustment of the ring is easy. This allows for addressing fluctuations in the stray magnetic field of the superconducting magnet by simply changing the axial position of the magnet ring.

[0042] In the present invention, low magnetic magnetic field Stone systems shield against external magnetic disturbances with low magnetic flux density and non-uniformity. It includes a cylindrical ferromagnetic portion. The cylindrical ferromagnetic portion is A class of embodiments characterized in that it includes a cylindrical ferromagnetic portion containing a μ-metal is particularly preferred. Ferromagnetic μ-metal components are used in magnetic field cycling coils to maintain the same magnetic field uniformity over a range of 100 μT to 0.8 T. The shape and thickness of the component are optimized as follows: At high magnetic fields, the ferromagnetic portion is magnetically saturated, but external non-uniform disturbances (such as the earth magnetic field, leakage magnetic fields from superconducting magnets and magnetic tunnels) are weaker compared to the magnetic field from the zero coil, thus achieving the expected magnetic field uniformity. At low magnetic fields, non-uniform disturbances (such as the earth field, leakage fields from superconducting magnets and magnetic tunnels) are greater than the magnetic field of the zero coil. However, because the magnetic field is weak, the ferromagnetic portion guides the non-uniform disturbances and the coil's magnetic field, while uniformity is maintained at very low magnetic field strengths, optimizing the first two coils (inside the μ metal portion) for low magnetic field strengths. Using μ-metal components is a passive solution for attenuating and shielding the remaining low external magnetic fields. In principle, μ-metal components function independently of the orientation of low residual magnetic fields. Therefore, additional shimming coils and power amplifiers are not required.

[0043] In embodiments of this class, the low-field magnet system preferably includes at least one low-field coil positioned inside a cylindrical ferromagnetic portion designed to generate a magnetic field at 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 several 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 modification of embodiments of this class is characterized in that the low-field magnet system includes at least one high-field coil positioned outside the cylindrical ferromagnetic portion to generate a magnetic field with a magnetic flux density exceeding the magnetic saturation of the ferromagnetic portion. These coils must be positioned radially outward from the μ-metal shield so that their magnetic fields are shielded by the μ-metal when the magnetic field falls below the saturation point of the μ-metal.

[0045] In a preferred embodiment of the present invention, the shuttle system is designed to move an NMR sample back and forth 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 conserved by its very rapid reciprocating motion through the adiabatic magnetic field of the magnetic tunnel.

[0046] Further advantages can be extracted from the description and accompanying drawings. The features described above and below can be used individually or collectively in any combination according to the present invention. The embodiments mentioned should not be understood as an exhaustive list, but rather as illustrative features for the purpose of describing the present invention. The present invention will be illustrated in the drawings and described in more detail based on exemplary embodiments. [Brief explanation of the drawing]

[0047] [Figure 1] This is a schematic vertical cross-sectional view of an NMR spectrometer equipped with a modified magnetic tunnel according to the present invention. [Figure 2]This is a schematic diagram of a preferred method of magnetic field cycling using a two-field NMR spectrometer according to the present invention, in which a magnetic field cycling coil is positioned at the upper end of a magnetic tunnel. [Figure 3] This is a cross-sectional view through a magnetic tunnel, showing arrows indicating the direction of magnetic flux within the hollow magnetic tunnel and the magnetic material establishing the tunnel. [Figure 4] This is a schematic three-dimensional diagram of a resistance coil-based electromagnet device for magnetic field cycling, which includes a low-field coil system located inside a cylindrical ferromagnetic portion surrounded by a high-field coil system designed to generate a uniform magnetic field with variable magnetic flux density and to generate a magnetic field with a magnetic flux density exceeding the magnetic saturation of the ferromagnetic portion. [Figure 5] Figure 4 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, which includes a resistance coil-based electromagnet device for magnetic field cycling, a further magnet system for a magnetic tunnel, and a ring-shaped permanent magnet radially surrounding the further magnet system. [Modes for carrying out the invention]

[0048] Figure 1 is a schematic diagram of the dual-field NMR spectrometer 10 used for conducting magnetic field cycling NMR relaxation measurement experiments. For the detection of polarization and NMR signals of the NMR sample 12, a high-field superconducting NMR magnet system 11' is used to generate a uniform magnetic field parallel to the z-axis in the central region of the dual-field NMR spectrometer 10, A low-field magnet system 11'' that generates a variable uniform magnetic field, A shuttle system 13 is designed to move the NMR sample 12 back and forth between a high-field superconducting NMR magnet system 11' and a low-field permanent magnet system 11'', A magnetic tunnel 14 connects 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 present invention is characterized by the provision of a further magnetic system 14' in the magnetic tunnel 14 and a high-field superconducting NMR magnetic system 11', wherein the magnetic tunnel 14 and the low-field magnetic system 11'' are coaxially arranged around the z-axis along the bore 15 of the high-field superconducting NMR magnetic system 11' contained in the cryostat 20.

[0050] The low-field magnet system 11'' for magnetic field cycling is positioned directly above the high-field superconducting NMR magnet system 11'' to avoid a long sample transport path. Therefore, the magnetic 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 move the NMR sample 12 back and forth 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 shuttle technique and improves signal (polarization) loss during shuttle. The low-field magnet is located very close to the high-field magnet but outside the cryostat 20 of the high-field magnet, which enables a short round-trip distance.

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

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

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

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

[0056] This solution involves extending the average magnetic field range outward from 0.5T to 1T by adding a magnetic tunnel (typically 0.7T to 1T) beyond the cryogenic magnet. This solution allows the use of magnetic field cycling coils (relaxing magnets) without additional shielding coils, i.e., more efficient ones (more magnetic field for the same current). The power required for the same magnetic field is significantly reduced, and water cooling is also more efficient (more space for the cooling system).

[0057] The schematic diagram in Figure 2 shows a preferred operating mode in which the relaxation field coil is moved outside the magnet and a magnetic tunnel is added. A) The magnetic field expansion in the z-direction of the bore is shown. This represents the magnetic field strength to which the sample is exposed. The dotted line indicates the lower end of the magnetic tunnel where the magnetic field strength is maintained during the transfer of the sample from this separate level (approximately 1 T). B) In the first step of this method, the sample is polarized in a high-field magnet for a predetermined 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 quickly (1 ms) switched to a pre-selected magnetic field for relaxation (here, 100 μT - 0.8 T). E) The sample is exposed to a relaxation magnetic field for a specified period of time. F) Optionally, the magnetic field for the FCC sample can be changed to a moderate level. G) Next, return the sample to the high-field magnet. H) Spectrum acquisition is performed inside a high-magnetic field magnet.

[0058] In a cross-sectional view of the magnetic tunnel 14, Figure 3 shows one embodiment of a further magnet system 14' of the magnetic tunnel 14, which includes 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 establishing the tunnel.

[0059] The magnetic field generated by the additional magnet system 14' of the magnetic tunnel 14, which is designed to generate an adiabatic magnetic field with a magnetic flux density in the range of 0.7T to 1T, is directed 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 positioned in a region of bore 15 where the magnetic flux density of the uniform magnetic field generated by the high-field superconducting NMR magnet system 11' is reduced to about 1T.

[0061] Inside the 14' ring of additional magnet systems, 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, which has a magnetic resilience 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 exceeds 1 T.

[0063] In this example, the magnetic tunnel 14 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. This creates magnetic field inhomogeneity at the magnetic center of the cryogenic magnet, which can be easily compensated for by a room temperature shim system.

[0064] To resume, the 2F NMR apparatus according to the present invention includes three different main magnetic elements: a. High-field magnet for polarization b. Magnetic tunnel c. Magnetic field cycling coil ("FCC") for relaxation

[0065] a) High-field polarization magnets are generally superconducting NMR magnets, which can be selected from, for example, 7.3T to 29.3T. b) The magnetic tunnel is composed of permanent magnets in a Halbach configuration. It generates an adiabatic magnetic field with a magnetic field strength of 0.5T to 1.5T depending on the nucleus. The magnetic tunnel is important for maintaining spin polarization during movement between magnets a) and c). The magnetic tunnel is placed within the bore of the superconducting magnet, and the magnetic field strength is reduced to approximately 1T, so the sample is never in a non-magnetic environment, and preferably the magnetic field does not fall below 0.7T. The direction of the magnetic field is not important; both the superconducting magnet and the FCC generate a magnetic field in the z direction along the common bore, while the magnetic tunnel generates a magnetic field perpendicular to the x direction due to the Halbach configuration. c) A magnetic field cycling coil or fast magnetic field cycling magnet (FCC) is an electromagnet that can change 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's magnetic field. The FFC magnet must have at least 10% uniformity along the sample.

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

[0067] The low-field permanent magnet system 11" includes a cylindrical ferromagnetic portion 16' containing a μ-metal in particular to shield against non-uniform disturbance magnetic fields at low magnetic flux density.

[0068] Furthermore, the low-field permanent magnet system 11'' includes at least one low-field coil 18 located inside the cylindrical ferromagnetic portion 16'', which is designed to generate a magnetic field at a magnetic flux density below the magnetic saturation of the ferromagnetic portion 16''.

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

[0070] Figure 5 shows a schematic three-dimensional sub-diagram of one embodiment of a low-field permanent magnet system in a two-field NMR spectrometer 10 according to the present invention, which includes a resistance coil-based electromagnet device 16 for magnetic field cycling shown in Figure 4, a further magnet system 14' of the magnetic tunnel 14, and a ring-shaped permanent magnet 17 radially surrounding the further magnet system 14' with radial magnetization with respect to the z axis.

[0071] This additional system of ring-shaped permanent magnets 17 is designed to counteract the magnetic stray field generated from the high-field superconducting NMR magnet system 11' in order to achieve a very low magnetic field of approximately 100 μT. The amplitude of the superconducting magnetic stray field of the high-field superconducting NMR magnet system 11' is approximately 10 mT at the center of the coil of the low-field permanent magnet system 11''. The ring is magnetized radially in the opposite direction, generating a constant magnetic field with a gradient along the z-axis.

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

[0073] A preferred concept of the dual-field NMR according to the present invention is to add a low-field magnet on top of a high-field magnet. In the path between the two magnetic centers, a magnetic tunnel made with 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 samples 13 Shuttle System 14 Magnetic tunnels 14' Further Magnetic System 15 Bore of high-field superconducting NMR magnet system 16. Resistance coil-based electromagnet device for magnetic field cycling 16' Cylindrical ferromagnetic portion, especially containing μ metal 17 Ring-shaped permanent magnets 18 Low-field coils placed inside the cylindrical ferromagnetic section 19. High-field coils positioned on the outside of the cylindrical ferromagnetic section. 20 NMR cryostat

[0075] List of prior art documents: Publications to be considered when evaluating the patentability of the present 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 magnetic field cycling NMR relaxation measurement experiments, For the detection of polarization and NMR signals of the NMR sample (12), a high-field superconducting NMR magnet system (11') is provided to generate a uniform magnetic field parallel to the z-axis in the central region of the dual-field NMR spectrometer (10), A low-field magnet system (11") that generates a variable uniform magnetic field, A magnetic tunnel (14) connects the center of the high-field superconducting NMR magnet system (11') to the low-field magnet system (11"), A shuttle system (13) designed to move the NMR sample (12) back and forth between the high-field superconducting NMR magnet system (11') and the low-field magnet system (11''), Includes, A further magnet system (14') is provided in the magnetic tunnel (14), The high-field superconducting NMR magnet system (11'), the magnetic tunnel (14), and the low-field magnet system (11") are, The high-field superconducting NMR magnet system (11') is coaxially arranged along the bore (15) around the z-axis, The low-field magnet system (11") includes a cylindrical ferromagnetic portion (16') for shielding from external magnetic disturbances with low magnetic flux density and non-uniformity. A dual-field NMR spectrometer (10) characterized by the above.

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

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

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

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

6. The high-field superconducting NMR magnet system (11') is designed to generate a uniform magnetic field in the range of 5T to 50T, particularly 7.3T to 29.3T. The NMR spectrometer according to claim 1, characterized in that...

7. The low-field magnet system (11") includes a resistance coil-based electromagnet device (16) for magnetic field cycling, designed to generate a uniform magnetic field with a variable magnetic flux density in the range of 100 μT to 1 T. The NMR spectrometer according to claim 1, characterized in that...

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

9. The low-field magnet system (11") for magnetic field cycling is positioned directly above the high-field superconducting NMR magnet system (11'). The NMR spectrometer according to claim 1, characterized in that...

10. The low-field magnet system (11") includes a ring-shaped permanent magnet (17) having radial magnetization with respect to the z-axis, which is designed to cancel out the stray magnetic field generated in particular from the high-field superconducting NMR magnet system (11'). The NMR spectrometer according to claim 1, characterized in that...

11. The cylindrical ferromagnetic portion (16') of the low-field magnet system (11") contains a μ-metal. The NMR spectrometer according to claim 1, characterized in that...

12. The low-field magnet system (11") includes at least one low-field coil (18) located inside the cylindrical ferromagnetic portion (16'), which is designed to generate a magnetic field at a magnetic flux density below the magnetic saturation of the ferromagnetic portion (16'). The NMR spectrometer according to claim 11, characterized in that...

13. The low-field magnet system (11") includes at least one high-field coil (19) positioned outside the cylindrical ferromagnetic portion (16') to generate a magnetic field with a magnetic flux density exceeding the magnetic saturation of the ferromagnetic portion (16'). An NMR spectrometer according to claim 11 or 12, characterized in that...

14. The shuttle system (13) is designed to move the NMR sample (12) back and forth between the high-field superconducting NMR magnet system (11') and the low-field magnet system (11'') in less than 100 ms. The NMR spectrometer according to claim 1, characterized in that...

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