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    • 专利摘要:
    The invention relates to a DNP device with a cryostat (7) having an opening (8) and a loading path for a measuring sample (1) which extends straight down from the opening to a sample receptacle (29) with a cryomagnet and a microwave source (2) and an arrangement for supplying microwave radiation from the microwave source to the location of the measurement sample, which comprises a microwave path running rectilinearly to the measurement sample. According to the invention, it is provided that the microwave path runs spatially separated from the loading path for loading the cryostat with a measuring sample, that the arrangement for supplying microwave radiation comprises at least one microwave passage through one or more walls of the cryostat, and that the microwave path in opposite direction to the loading path or with respect to the axis of the loading path at right angles or obliquely from the side to the location of the measuring sample hits. This allows a simple and efficient polarization of the electron spins in the sample to be achieved.
    公开号:CH708630B1
    申请号:CH01402/14
    申请日:2014-09-17
    公开日:2018-08-15
    发明作者:Wilhelm Dirk；Lohman Joost；Hinderer Joerg；Grubinger Hannes
    申请人:Bruker Biospin Ag；
    IPC主号:
    专利说明:

    Description: [0001] The invention relates to a DNP (= Dynamic Nuclear Polarization) device having at least one cryostat which has an opening and a loading path for loading the cryostat with a measurement sample, the loading path from the opening to a sample receptacle in place the measuring sample in the cryostat is rectilinear, wherein in the cryostat a magnetic coil for generating a homogeneous magnetic field at the location of the measuring sample is arranged during the measurement, wherein a microwave source for generating microwave radiation is provided, and wherein an arrangement for supplying Microwave radiation is arranged from the microwave source to the location of the measuring sample in the cryostat, which comprises a straight line to the location of the measuring sample in the cryostat extending microwave path.
    Such an arrangement is known for example from WO 08/121 458 A1 (= reference [6]).
    Background of the invention
    Nuclear Magnetic Resonance (= NMR) Nuclear magnetic resonance (NMR) spectroscopy is a commercially widely used method for characterizing the chemical composition of substances. The magnetic resonance imaging (MRI) method is based on the same basic physical principles as NMR spectroscopy. Both methods have the disadvantage that they are very less sensitive, since the polarization of the atomic nuclei is only weak in strong magnetic fields. Therefore, increasing the signal-to-noise ratio (SNR) is one of the most important goals in the development of NMR and MRI devices. The SNR can be increased either by reducing the noise component or by increasing the signal level. The reduction of noise has been achieved very successfully in recent years by cooled NMR and MRI coils.
    The desired increase of the NMR signal can be done for example by the use of stronger NMR magnets, but this causes a considerable overhead in terms of costs and usually also an increased space requirement for the apparatus.
    Dynamic nuclear polarization (= DNP) [0005] Alternatively, so-called "Dynamic Nuclear Polarization" (DNP) methods can be used: [0006] In the field of nuclear magnetic resonance spectroscopy, there are various experimental methods that allow nuclear magnetic resonance spectroscopy to be performed. Polarization significantly, thereby increasing the detection sensitivity of the experiment. One of these methods is dynamic nuclear polarization (= DNP). This technique requires the simultaneous irradiation of a microwave magnetic field at a frequency 660 times higher than the nuclear Larmor frequency of the 1H nuclei.
    Dynamic nuclear polarization requires that polarizing agents, e.g. free radicals with unpaired electron spins, located in the sample. Furthermore, it is exploited that electrons reach a high polarization at low temperatures in a strong magnetic field. By irradiation of a microwave field at a suitable frequency, a transfer of the electron polarization to the atomic nuclei of the sample is caused due to interactions. After the nuclear spins in the sample have reached a sufficiently high polarization, the sample may be incubated with a dissolution fluid, e.g. hot water, quickly warmed to room temperature. This process must be sufficiently fast because the nuclear spins lose their polarization rapidly at higher temperatures. The methods for polarization and subsequent heating and dissolution of the sample are e.g. from references [1], [2], [6] and [7].
    Further Related Art In Reference [1], the magnetic coil is cooled in a magnetic cryostat to temperatures in the range of 4K to 4.5K. The sample is introduced directly into the same magnetic cryostat and cooled to 1 K to 5 K in a separate helium space within this cryostat. Then the electron spins are excited by means of suitable microwave radiation. The frequency of the microwave radiation depends on the strength of the magnetic field in which the sample is located. It is in the range of 50 GHz to 1000 GHz.
    The microwave is introduced by means of a waveguide through the same opening through which the sample is introduced in the magnetic cryostat. The sample is introduced with a sample holder from above in the magnetic cryostat. Furthermore, sample lines for the dissolution of the sample are introduced from above into the cryostat. Since the space available in the cryostat is relatively narrow, the microwave can not be routed straight to the sample, but must be redirected to the radiation with the help of mirrors. The microwave is attenuated and thus there are power losses.
    Reference [3] discloses a DNP method in which, unlike reference [1], a sample cryostat is used as an insert in the magnetic cryostat. The sample is placed in the sample cryostat and cooled to temperatures in the sample cryostat
    Range of 1 K to 5 K cooled. The cold sample is then irradiated with a high-frequency microwave to stimulate the electron spin. In this arrangement, the sample is first irradiated via a microwave conductor inserted just from above. When the electron spins are sufficiently polarized, the microwave conductor from the sample cryostat is directed upwards and a device for dissolving the sample is introduced from above and sampled. This arrangement has the advantage that the microwave conductor can be guided straight, but it has the disadvantage of the costly change of microwave conductor and sample dissolution device. This change is very difficult to automate.
    In a refinement of reference [3] described in reference [4], several samples are simultaneously cooled in a sample cryostat. The samples are located in a sample changer, which is designed as a turntable. The samples can be polarized in this device at a circumferential position by means of the microwave, and at another circumferential position, the resolution of the sample can be carried out. Therefore, in this arrangement, even guidance of the microwave is possible. The disadvantage of this arrangement is that the changing device is located in the very cold region of the sample cryostat. Performing the mechanical movements at temperatures below 5 K is very demanding and error-prone.
    In reference [6], the microwave conductor is guided either straight from the top to the location of the measurement sample within the loading path, or in another embodiment described in reference [6] the microwave conductor encloses the straight loading path from the outside. Thus, the microwave conductor is led straight from the top to the sample. The coupling of the microwave in the outer microwave conductor is a complex and complicated process that is associated with microwave losses. However, if the microwave is guided within the loading path, then the microwave conductor must be removed from the loading path to load the sample. This process, which is also described in reference [6], has the disadvantage that it is difficult to automate.
    In reference [7], a magnet having two homogeneous magnetic field regions is used. In the first region, the irradiation with the microwave and in the second, the resolution and the NMR measurement. In reference [7] the loading path is combined with a movable microwave conductor. Here, the sample is filled in a small sample holder, and the sample holder is directly connected to the long movable microwave conductor. The sample located in the sample holder is irradiated with the microwave in the first homogeneous magnetic field region. After sufficient polarization is present, the sample is transferred to the second homogeneous magnetic field region.
    The arrangements of the prior art have in common that the microwave is introduced through the same opening of the cryostat as the samples.
    Disadvantages of the Prior Art The arrangements described in references [1], [3] and [7] are primarily designed for manual DNP operation. Although in reference [1] the sample holder and the waveguide are horizontally offset from one another, this is only possible by a deflection of the waveguide, e.g. with mirrors, possible. This diversion dampens the microwave and therefore reduces the efficiency of the system.
    In reference [3] and [6], the microwave is rectilinear and thus introduced low loss from above. However, this has the disadvantage that the waveguide must be removed before the dissolution step. It is then replaced by the Dissoluti-ons device consisting of a solvent supply line and an outlet line. This process has the disadvantage that it is difficult to automate.
    In reference [7], although the dissolution device comes from below, but it must be removed for each load of the sample, the microwave line. This is very complex and not automatable. Furthermore, a special cryostat design is required for this construction, in which sample loading and microwave from one side and the dissolution device from the other side can be introduced. To make this possible, the cryostat has two openings, which makes the structure complicated and expensive.
    The arrangement in reference [4] has the disadvantage that it has a mechanical sample changer, which, however, must be operated at a temperature of less than 5 K. This mechanism is very expensive and error prone.
    OBJECT OF THE INVENTION The present invention is based on the object of presenting a DNP device of the type defined at the outset, with which a simple and efficient polarization of the electron spins in the sample can be achieved. The microwave should be guided so that the losses on the way to the sample are as small as possible. As a result, high efficiency can be achieved. In addition, the microwave conductor should be permanently installed so that the sample does not have to be removed when changing samples or during the dissolution step. Furthermore, the invention should allow a very reliable possibility of automation. Complicated mechanical devices at very low temperatures of less than 5 K should be avoided at all costs. The space within the loading path in the cryostat should be used optimally for the loading and dissolution of the sample.
    BRIEF DESCRIPTION OF THE INVENTION This object is achieved in a surprisingly simple manner and with readily available technical means by a DNP device with the features mentioned in the introduction, which is characterized in that the microwave path from the loading path to the Loading the cryostat with a measuring sample spatially separated runs, that the arrangement for supplying microwave radiation comprises at least one microwave passage through one or more walls of the cryostat, and that the microwave path in the opposite direction to the loading path or with respect to the axis of the loading path at right angles or obliquely from the side on the place of the measuring sample meets.
    The leadership of the microwave is done so from the outside through the cryostat through with the help of suitable feedthroughs, and not - as usual in the prior art - through the opening for loading the sample. Microwell feedthroughs by cryostats per se are known in the literature, for example from reference [5], but not in use for cryostats used in DNP systems.
    With the help of the modified according to the invention DNP device also the microwave can be very energy efficient and performed in a simple technical way directly to the sample.
    Operation of the Invention and Other Advantages over the Prior Art The spatial separation of the microwave guide from the sample introduction has two major advantages: firstly, the microwave can be guided straight to the sample, so there are no lossy baffles, e.g. through mirror, necessary. Thus, a high efficiency of the microwave irradiation can be achieved on the sample. Secondly, said separation provides more space in the cryostat for sample introduction and the dissolution process. This space can be used very meaningfully to automate the entire DNP process.
    Essentially three alternatives are available for the microwave path according to the present invention: it can strike the location of the measuring sample at right angles or obliquely from the side in the opposite direction to the loading path or with respect to the axis of the loading path.
    In the first alternative, the sample is e.g. introduced from above into the cryostat, and the microwave is introduced through the opposite bottom in the cryostat and irradiated from below to the sample. However, it is equally possible for the sample to be introduced from the bottom and the microwave from the top into the cryostat. The introduction path and the arrangement for irradiation of the microwave are in this case on the same axis. Since the microwave path is completely independent of the sample introduction path, the sample introduction from above can be easily automated. This has significant advantages for using the DNP system in combination with an additional NMR or MRI system. Because automation allows the entire measuring process to be carried out quickly, efficiently and reproducibly.
    In the second alternative, the sample is e.g. again introduced from the top into the cryostat and the microwave irradiated from the side. The introduction path of the sample is again straight and is formed by the opening for loading the sample in the cryostat and receiving the sample located in the high magnetic region of the cryostat. With respect to the axis of the loading path, the microwave path is now arranged at right angles to the loading path. This arrangement again has the advantage over the prior art that it is not necessary to use the same narrow opening for the microwave irradiation and the sample loading.
    In the third alternative, the microwave path is oblique, that is at an angle deviating from 90 ° to the loading path. It may be advantageous for the construction of the kryomagnet if the microwave path is arranged in a straight line, but at an angle to the loading path which deviates from 90 °. This arrangement also has the advantage over the prior art that it is not necessary to use the same narrow opening for the microwave irradiation and the sample loading.
    In contrast to the standard DNP device can be easily replaced by the modified device according to the invention also in the marked by a magnetic cryostat and a Probenkryostaten embodiment of the sample cryostat, without the microwave guide must be removed. The microwave source including microwave guide can thus be permanently installed.
    PREFERRED EMBODIMENTS OF THE INVENTION In a preferred embodiment of the DNP device according to the invention, the microwave feed-through effects an attenuation of the microwave radiation of less than 6 dB, preferably less than 2 dB, particularly preferably less than 0.5 dB.
    The microwave is passed through a Kryostatwand and damped as little as possible. The attenuation of the microwave in the microwave feedthrough results in a reduction of the microwave energy available for the irradiation of the sample. For reasons of efficiency, this reduction should be kept as small as possible. Compared to the prior art, in which deflections of the microwave are necessary, the losses in the feedthroughs can be kept very small in the invention according to the rectilinear leadership of the microwave.
    Further preferred embodiments of the invention are those in which the material in the region of the passage through the walls of the cryostat comprises polytetrafluoroethylene (PTFE) and / or sapphire and / or aluminum oxide and / or quartz. These feedthrough materials have low attenuation values for microwaves in the intended frequency range and are therefore advantageous.
    Embodiments of the inventive DNP device in which the heat output caused by the microwave feedthrough on the cryostat is less than 200 mW, preferably less than 100 mW, even more preferably less than 50 mW, are particularly advantageous. Since heat is generated by the attenuation of the microwave, which in turn leads to heating of the cryostat, a low-loss as possible microwave feedthrough is preferred. Because the heat input generated by the microwave must be compensated by introduced into the cryostat cooling performance. This additional cooling capacity should be kept as small as possible for efficiency reasons.
    In further advantageous embodiments of the inventive DNP device, the arrangement for supplying microwave radiation ends at a distance d of less than 10 mm, preferably less than 5 mm, more preferably less than 1 mm to the sample at the sample site in the cryostat. This results in a guide of the shaft to the sample, the radiation along the transport path is largely prevented in this way. Due to the very low radiation, the microwave energy density in the sample is significantly higher than in the prior art, the efficiency of the overall system increases accordingly significantly.
    Embodiments of the invention in which the arrangement for supplying microwave radiation comprises a dielectric waveguide are also particularly preferred. The transmission losses are in this no longer dependent on the quality of the metallic surfaces and the materials, but on the dielectric properties of the material used. The frequencies used in the 100 GHz range result in similarly low losses. The main advantage of this implementation variant is that due to the low thermal conductivity of a dielectric waveguide, the heat input of the waveguide is substantially lower. A direct guidance of the waveguide by the cryostat is possible, which greatly simplifies the design and favors.
    Even more advantageous are developments of these embodiments, which at the end of the dielectric waveguide an antenna, e.g. a horn antenna, or a coupler to spatially concentrate the microwave on the region of the sample. This additionally increases the efficiency. Other particularly preferred developments of these embodiments are characterized in that the dielectric waveguide is constructed of a dielectric with dielectric constant ε of 1 <ε <15, in particular of polytetrafluoroethylene (PTFE) and / or sapphire and / or alumina and / or quartz.
    Embodiments of the inventive DNP device in which the microwave bushing has at least one dielectric lens are also particularly preferred. In this case, the dielectric lens is used for focusing the microwave energy. The waveguide ends in comparison to the previously mentioned embodiments at a greater distance from the sample. In the space between the end of the waveguide and sample, dielectric lenses are inserted, which are dimensioned so that a maximum focusing of the microwave energy to the sample takes place. This can significantly increase the efficiency. Preferably, an antenna or a coupler is provided at the end of the waveguide. As a result, the losses at the transition can be reduced and a further increase in efficiency can be achieved.
    Advantageous developments of these embodiments are characterized in that the dielectric lens has an insertion loss of 5 dB, preferably of 2 dB, in particular of 1 dB, particularly preferably of 0.5 dB. The insertion loss of the dielectric lens is directly related to the microwave losses in this area. These losses are in turn converted directly into heat energy that pollutes the cryostat. Therefore, the lowest possible insertion loss is advantageous.
    The dielectric lens will usually be constructed of a dielectric with dielectric constant ε with 1 <ε <15, in particular polytetrafluoroethylene (PTFE) and / or sapphire and / or alumina and / or quartz. The dielectric lenses focus the microwave in the area of the passage through the cryostat. As a result, only a small part of the microwave energy is radiated laterally when passing through the cryostat. This is important, because the laterally radiated microwave energy can not be used for the irradiation of the sample, on the one hand, and on the other hand, this energy causes a warming of the cryostat and must therefore be compensated by higher cooling capacity.
    In a still more preferred variant, the lens system is additionally shielded. The shielding is achieved by a metallic structure that resembles a waveguide. Since the lenses have to fit into it, a large cross-section may have to be chosen compared to a waveguide. The shield has the additional advantage that edge fields can also be guided to the sample, which results in an increase in efficiency. By keeping a much larger part of the microwave energy, the heat input to the cryostat is also reduced, resulting in a higher temperature stability and lower cooling performance.
    In another preferred embodiment, an antenna is mounted at the end of the waveguide or dielectric waveguide to optimize the radiation. This results in lower adaptation losses and a better concentration of microwave power on the sample. Efficiency can be significantly increased by better pooling of energy. Instead of the antenna, capacitive or inductive couplers can also be used.
    A particularly preferred class of embodiments of the inventive DNP device is characterized in that an arrangement for supplying a dissolving liquid, which enables a resolution of the measuring sample and the generation of a hyperpolarized sample liquid, is provided.
    The polarized sample is washed with a dissolving liquid, e.g. hot water, quickly warmed to temperatures ranging from 5 ° C to 70 ° C. The dissolution of the sample can be done directly in the strong magnetic field in which the sample was polarized with the microwave. The warm and liquid sample has a very high nuclear spin polarization after dissolution.
    Very particular preference is further developments of the class of embodiments, in which the supply of the solution liquid to the measuring sample from above and the supply of microwave radiation to the measuring sample are provided from below. At this time, the solution liquid becomes out of the direction opposite to the microwave, i. from above, led to the sample. The sample was previously irradiated from below. The reverse arrangement, in which the microwave from above and the solution liquid is guided from below to the sample, is advantageous. Important for both arrangements is that the microwave path is separated from the loading path of the sample. Because thus the microwave conductor can be permanently installed without having to be removed for each sample loading.
    Also within the scope of the present invention is the use of a DNP device of the above-described embodiments for generating hyperpolarized liquid for NMR and / or MRI measurements. Here, polarization agents, e.g. Free radicals with unpaired electron spins, used. The sample is cooled to a low temperature less than 5 K in a strong magnetic field. The polarization of the electron spin increases strongly. The sample is then irradiated with a microwave and interaction processes cause polarization transfer to the nuclear spins of the sample. This considerably increases the polarization of the nuclear spins. Compared to the prior art, the guidance of the microwave is very low loss, resulting in an efficient polarization of the sample.
    For applications in NMR spectroscopy, the irradiated and dissolved sample is transported directly into a probe head, which is located in another HUR system. In this sample head, a spectroscopic NMR measurement is then performed. Due to the high polarization of the nuclear spins, a more than 10 000-fold higher SNR is achieved in this NMR experiment. Particularly suitable for NMR measurements are nuclei with a long relaxation time T1, such as e.g. 13C or 15N.
    In MRI applications, the irradiated and dissolved sample is collected with a syringe. Subsequently, it is injected directly to a person to be examined or an animal to be examined. Again, due to the high polarization of the nuclear spins, a more than 10 000-fold higher SNR is achieved in this NMR experiment. Cores with a long relaxation time T1, such as, for example, are suitable for these MRI measurements. 13C or 15N, since the relaxation time is directly related to the decrease in nuclear spin polarization. Proton measurements (1H) are also possible, but due to the short relaxation time of 1H less suitable in the present case.
    Further advantages of the invention will become apparent from the description and the drawings. The embodiments shown and described are not to be understood as exhaustive enumeration, but rather have exemplary character for the description of the invention.
    DETAILED DESCRIPTION OF THE INVENTION AND DRAWING [0048] The invention is illustrated in the drawing and will be explained in more detail by means of exemplary embodiments. Show it:
    1 shows an embodiment of the inventive DNP arrangement for guiding the microwave from below in a schematic vertical section;
    Fig. 2 shows an embodiment of the novel DNP arrangement for guiding the microwave of the
    Page;
    3 shows a schematic vertical section of a prior art DNP arrangement with guidance of the microwave through the sample opening of the cryostat;
    4 shows an embodiment of the prior art DNP arrangement, wherein a common cryostat is used for magnet and sample, but which has two separate helium spaces, which are operated at different temperatures;
    Fig. 5 shows an embodiment of the inventive DNP arrangement for guiding the microwave from un th in a schematic vertical section, wherein the sample cryostat and the magnetic cryostat are not separated;
    Fig. 6 shows an embodiment of the sample cryostat with inventive microwave guide and guides through the cryostat;
    FIG. 7 shows an embodiment of the sample cryostat as in FIG. 6, but with a flange on the waveguide; FIG.
    8 shows an embodiment of the sample cryostat with inventive microwave guide and guides through the cryostat with horn antenna:
    9 shows an embodiment of the sample cryostat with microwave guide according to the invention, which takes place through a dielectric waveguide;
    10 shows an embodiment of the sample cryostat with microwave guide according to the invention, which takes place through two dielectric lenses;
    11 shows an embodiment of the sample cryostat with microwave guidance according to the invention, which is effected by two dielectric lenses and waveguides in the cryostat;
    FIG. 12 shows an embodiment of the inventive DNP arrangement with a microwave introduced from below, a dissolution device and a second NMR measuring system; FIG.
    FIG. 13 shows an embodiment of the DNP arrangement according to the invention with the microwave introduced from below, the dissolution device and the MRI system; FIG. The present invention relates to the optimization of DNP devices for use in NMR and MRI devices.
    NMR spectroscopy and magnetic resonance imaging (MRI) method suffer from the low number of polarized nuclear spins. This nuclear spin polarization can be increased by so-called "Dynamic Nuclear Polarization" (DNP) methods. One of these DNP methods is the dissolution DNP method. In this case, a sample containing a polarization promoter and is in a strong magnetic field, irradiated at low temperatures (less than 5 K) with a microwave. Due to interactions, the electron spins are transferred to the nuclear spins of the sample. If a sufficiently high polarization of the nuclear spins is achieved, the sample is dissolved in a very rapid process, the so-called dissolution step, and at the same time heated up. The now liquid sample has a very high nuclear spin polarization. It can now be measured with NMR or MRI systems. In this way, an increase in the signal-to-noise ratio of factors well in excess of 10,000 can be achieved over conventional methods. Therefore, these dissolution-DNP methods are particularly advantageous for increasing the contrast in MRI measurements. In order to be able to use this method in the clinical area and also in the preclinical area, a largely automated procedure is very advantageous.
    The sample is brought to its desired temperature in a cryostat. For this purpose, two types of systems are common, either the sample is introduced directly into the magnetic cryostat, in this device only one cryostat is needed. Or in the cryomagnet is another cryostat, which receives the sample.
    In both cases, in the prior art, the waveguide for transporting the microwave through the same opening as the sample is introduced into the cryostat. This has the significant disadvantage that the area in which the sample is located, is relatively filled. Therefore, with the arrangements of the prior art reliable automation of the sample polarization with microwave irradiation and dissolution of the sample (= dissolution) is difficult.
    The present invention is characterized in that the microwave conductor follows a path independent of the sample introduction port. It is guided in a straight path with suitable feedthroughs through the cryostat. Due to the straight guide, distractions, e.g. in the form of mirrors, be omitted, resulting in an efficient and low-loss transmission of the microwave. As a considerable advantage over the prior art, the space gain in the cryostat can be seen. This makes it possible with the inventive arrangement to achieve an automated sample handling. The possibility of automation is of considerable advantage for the clinical and preclinical use of the method.
    Fig. 1 schematically illustrates the inventive arrangement for carrying out DNP experiments. The sample 1 is held by the sample holder 3 and is located in the sample holder 29. Sample holder, sample and sample holders are again in the sample cryostat 7, which has an opening 8. This opening is used to introduce the sample holder including sample.
    The cryostat is located inside the strong cryomagnet 9. The cryomagnet in turn has a magnetic cryostat 12 and a magnetic coil 6. The sample 1 is irradiated with microwaves in the frequency range of 50 GHz to 1000 GHz, typical values are 100 GHz. The microwave is generated in the microwave source 2 and introduced via the waveguide 5 from below. Here, the microwave source 2 is either directly under the cryomagnet 9 or e.g. laterally from the cryomagnet, which causes a deflection of the microwave with suitable devices, e.g. Mirrors, necessary. The microwave exits the waveguide 5, passes through the passage 4 through the sample cryostat and then enters the sample receptacle 29, in which the sample 1 is located. In contrast to the prior art according to
    Reference [1] takes the sample holder 29 here only the sample, but it does not have resonant for the microwave structures, since the microwave is irradiated directly from below onto the sample. The microwave feedthrough 4 is designed so that thermal losses and the attenuation of the microwave can be minimized.
    Fig. 2 shows an inventive arrangement in which the microwave is passed through the cryostat. This structure is of interest for so-called split magnets 6 ', 6 ", in which the kryomagnet coils are subdivided into different regions (cf., for example, references [8], [9].) The microwave is passed through the cryostat 17 with the aid of two feedthroughs 4'. and 4 ", and then guided with the waveguide 10 through the sample receptacle 29 'to the sample 1. This construction is more complex than that in Fig. 1, since a further feed-through 4 "is required, but it is also possible for the two split-magnet coils 6 'and 6" to be completely separate and each surrounded by separate cryostat. Then, in the located between the two split magnet coils 6 ', 6 "opening of the waveguide 10 are introduced, in this case, the implementation of 4" is not necessary, which greatly simplifies the structure for the microwave transmission.
    Fig. 3 shows the prior art, wherein the microwave from the microwave source 2 'via the waveguide 5' through the opening 8b in the sample cryostat to the microwave chamber 11 and finally to the sample 1 is performed. The sample cryostat is located in the cryomagnet 9, which in turn has a cryostat 12 and a magnetic coil 6. In this arrangement, therefore, the two cryostats 12 and 7 are separated. The arrangement is designed for dissolution DNP measurements. In this case, the sample 1 is first irradiated with microwave beams in the range of 50 GHz to 1000 GHz, which are polarized due to interactions of nuclear spins in the sample. When sufficient polarization is achieved, the sample is rapidly warmed to room temperature using a dissolution liquid (e.g., hot water). For this purpose, the dissolution liquid is introduced from the solvent container 55 via the solvent feed line 54 into the microwave chamber 11. The dissolution liquid dissolves the frozen sample and the dissolved sample then flows through the outlet conduit 50 and the dissolution controller 51 from the DNP apparatus. It can be collected and used for NMR or MRI experiments.
    Fig. 4 shows an analogous to Fig. 1 DNP arrangement according to the prior art, wherein the magnetic cryostat and the sample cryostat are not separated, but for the cooling of the magnetic coil and the sample only a cryostat 17 is used.
    Fig. 5 shows the inventive arrangement with microwave feed from below, as in Fig. 1, but here only a cryostat 17 is used for the cooling of the magnetic coil and the sample.
    Fig. 6 illustrates the inventive implementation of the waveguide by the cryostat. The microwave is guided here by the waveguide 5 "in the outer space 16 to the sample 1, which is located in the sample holder 29". All waveguides shown and described below can also be dimensioned "overmoded". That is, it may also be used a waveguide whose cross-sections is substantially larger than that of a standard waveguide of the corresponding frequency. This results in additional freedom of design due to the possibility of using larger waveguides, but the energy transport then takes place in different modes capable of propagation.
    In order to prevent a thermal short circuit between sample cryostat inner tube 13, thermal radiation shield 21 and sample cryostat outer tube 20 when passing through the cryostat, the waveguide is interrupted. The interruption gives rise to the first 23 and third waveguide section 27. Both waveguides have identical cross section. The break between the two waveguides is short. In order to reduce the radiation around this gap and to increase the efficiency, the second waveguide piece 24 is arranged around the interruption. The second waveguide piece encloses the first and third waveguide pieces, which is why it has a larger cross section. The spacers 25 and 26 ensure the mechanical stability of the small distance between the three waveguide pieces. The spacers consist e.g. made of nylon, potetetrafluoroethylene (PTFE) or fiberglass reinforced carbon fiber (GRP).
    The microwave feedthroughs 22 and 28 ensure on the one hand the vacuum-tightness of the cryostat and on the other hand the microwave permeability. Between waveguide 5 "in the outer space and the microwave feedthrough 22 is also a small gap to prevent thermal contact.
    Fig. 7 shows in comparison to Fig. 6, the additional flange 30. The flange reduces the microwave radiation at the gap, thus the propagation losses are reduced in the waveguide and the efficiency is additionally increased.
    Fig. 8 illustrates the additional horn antenna 31 which widens the cross section of the third waveguide piece 27 '. The expansion has two main advantages; On the one hand, this can improve the adaptation to the sample, which leads to lower reflection losses and thus to a further increase in efficiency. On the other hand, by this arrangement, the irradiated cross-section can be adjusted, whereby a better field homogeneity of the microwave is achieved in the sample.
    Fig. 9 shows the inventive arrangement in which a dielectric waveguide 33 for guiding the microwave is used. The dielectric waveguide consists of an electrical insulator with the lowest possible dielectric losses, which enables a low-loss transport of the microwave energy. The thermal conductivity of the material is also low, which is why the dielectric waveguide can be guided from the outer space 16 through the sample cryostat outer tube 20 and the thermal radiation shield 21. At the end of the dielectric waveguide is the antenna 32, which ensures the most homogeneous field in the sample.
    The antenna can be designed as a simple antenna, but also as an antenna array. If the antenna is located between thermal radiation shield 21 and sample cryostat inner tube 13, a microwave feedthrough 28 "is required in the sample cryostat inner tube Alternatively, the antenna may be mounted within the sample cryostat inner tube, in which case the dielectric waveguide will pass through the sample cryostat inner tube 13. The microwave feedthrough 28 "is omitted in this case.
    Fig. 10 shows the inventive arrangement in which the microwave is focused by two dielectric lenses 34 and 35. In the outer space 16, the microwave is guided through the waveguide 5 to the first dielectric lens 34. The gap between sample cryostat outer tube 20 and waveguide 5 '' may be varied to optimize matching and emissivity characteristics The lenses shown here are spatially arranged to simultaneously pass through sample cryostat outer tube 20 (first dielectric lens 34) and sample cryostat inner tube In this case, the lenses also achieve the vacuum tightness If the lenses are not arranged in the area of the sample cryostat outer tube and sample cryostat inner tube or if a different lens configuration is used, a microwave feedthrough (shown) is additionally provided as 22 and 28 in Fig. 6) is necessary.
    Fig. 11 shows an extension to the arrangement Fig. 10. Here is the area in which the microwave energy is guided, additionally shielded by a Weitenleiter. The waveguide is subdivided into a first 23 ', second 24' and third waveguide piece 27 "to ensure thermal isolation (as in Fig. 6) .Focusing of the microwave is accomplished as in Fig. 10 by the lenses 34 and 35. The shield improves the efficiency of the microwave line and reduces the heat input in the cryostat caused by the microwave energy.
    Fig. 12 shows an example of the inventive arrangement for carrying out the dissolution-DNP process for high-resolution NMR measurements. Here, the sample 1 is irradiated in the sample holder 29 with microwaves. The microwaves are generated in the microwave source 2, introduced through the waveguide 5 and the microwave feedthrough 4 in the sample holder 29. If the sample is sufficiently polarized due to the microwave irradiation, the dissolution liquid from the solvent container 55! introduced via the solvent supply line 54 'in the sample holder. The dissolution liquid now dissolves the sample and the sample liquid flows via the outlet line 50 'through the dissolution controller 51' and the sample line 52 into the NMR probe head 53. The NMR probe head is located in the second cryomagnet 9 "in the now significantly increased NMR measurements SNR can be performed.
    13 shows, by way of example, the arrangement according to the invention for carrying out the dissolution-DNP process for magnetic resonance imaging (MRO measurements), in which the microwave is guided from below through the microwave feedthrough 4 into the sample receptacle 29, as in FIG. The sample is irradiated and dissolved as indicated in Figure 12. The sample liquid now flows through the outlet conduit 50 "and the dissolution controller 51" and is then collected with the syringe 58. The sample liquid is then collected into the MRI system 56 The increased polarization rapidly decreases with time after dissolution of the sample, therefore the processes up to the injection of the sample liquid into the patient are extremely time-critical.
    List of Reference Numerals: (1) Sample (2) Microwave Source (3) Sample Holder (4, 4 ', 4 ") Microwave Feedthrough (5, 5', 5") Waveguides (6, 6 ', 6 ", 6') ") Magnetic coil (7) Sample cryostat (8, 8a-e) Sample cryostat opening (9, 9, 9") Cryomagnet (10) Waveguide in cryostat (11) Microwave chamber (12) Magnetic cryostat (13) Sample cryostat inner tube (14) Cryogenic space (15) Sample cryostat vacuum chamber (16) External space (17) Cryostat (20) Sample cryostat outer tube (21) Thermal radiation shield (22) Microwave passage from the outside to the sample cryostat vacuum chamber (15) (23, 23 ') First waveguide piece in the sample cryostat (24, 24 ') second waveguide piece in the sample cryostat (25, 25') spacer (26, 26 ') spacer (27, 27', 27 ") third waveguide piece in the sample cryostat (28, 28 ', 286") microwave feedthrough the sample cryostat vacuum chamber to the cryogenic space (29, 29 ', 29 ") Sample holder (30) Flange (31) Horn antenna (32) Antenna including Ant network (33) dielectric waveguide (34) first dielectric lens (35) second dielectric lens (50, 50 ', 50 ") outlet conduit (51, 51', 51") dissolution control (52, 52 ') sample conduit (53) NMR Sample Head (54,54 ') Solvent Supply Line (55,55') Solvent Container (56) Magnetic Resonance Imaging System (57) Subject to be Examined (58) Syringe d Distance from the sample to the array for guiding and irradiating microwaves
    Reference List [1] Ardenkje-Larsen, J.H. et al: WO 02/37132 A1
    权利要求:
    Claims (14)
    [1]
    [2] Ardenkjasr-Larsen, JH et al: "Increase in signal-to-noise ratio of> 10,000 times in liquid-state NMR", PNAS, Vol. 100, 10 158-10 163 (2003) [3] Comment, A. et al .: "Design and Performance of a DNP Prepolarizer Coupled to a Rodent MRI Scanner", Concepts in Magnetic Resonance Part B, Vol. 31B (4) 255-269 (2007) [4] Batel, M. et al .: "A multi-sample 94 GHz dissolution dynamic-nuclear-polarization system", Journal of Magnetic Resonance, Vol. 214, 166-174 (2012) [5] Gregory, WD et al .: DE 1 949 160 A1 [6 Urban, J. et al .: WO 08/121 458 A1 [7] Leggett, J. et al .: A dedicated spectrometer for dissolution DNP NMR spectroscopy, Phys. Chem. Chem. Phys., Vol. 12, 5883-5892 (2010) [8] Dempsey, J. et al .: WO 2011/106 524 A1 [9] Saitoh, K. et al .: EP 1 643 261 A1 Claims
    1. DNP device, i. Dynamic nuclear polarization apparatus, comprising at least one cryostat (7; 12; 17) having an opening (8; 8a; 8b; 8c; 8d; 8e) and a loading path for loading the cryostat (7; 12; 17) with a measuring sample (1), the loading path from the opening (8; 8a; 8b; 8c; 8d; 8e) to a sample receptacle (29) at the location of the measuring sample (1) in the cryostat (7) being rectilinear wherein a magnetic coil (6; 6 '; 6 ") for generating a homogeneous magnetic field at the location of the measuring sample (1) is arranged in the cryostat (7; 12; 17) during the measurement, wherein a microwave source (2 2) is provided for generating microwave radiation, and wherein an arrangement for supplying microwave radiation from the microwave source (2; 2) to the location of the measuring sample (1) in the cryostat (7; 12; 17) is arranged, which comprises a microwave path running rectilinearly to the location of the measuring sample (1) in the cryostat (7; 12; 17), characterized in that the microwave path from the loading path d for loading the cryostat (7; 12; 17) with a measuring sample (1) is spatially separated, that the arrangement for supplying microwave radiation comprises at least one microwave passage through one or more walls of the cryostat (7; 12; 17), and that the microwave path in the opposite direction to Loading path or with respect to the axis of the loading path at right angles or obliquely from the side to the location of the measuring sample (1).
    [2]
    2. DNP device according to claim 1, characterized in that the Mikrowellendurchführung causes an attenuation of the microwave radiation of less than 6 dB, preferably less than 2 dB, more preferably less than 0.5 dB.
    [3]
    3. DNP device according to one of the preceding claims, characterized in that the material in the region of the passage through the Kryostatwände polytetrafluoroethylene and / or sapphire and / or alumina and / or quartz comprises.
    [4]
    4. DNP device according to one of the preceding claims, characterized in that the introduced from the microwave feedthrough on the cryostat heat output is less than 200 mW, preferably less than 100 mW, more preferably less than 50 mW.
    [5]
    5. DNP device according to one of the preceding claims, characterized in that the microwave feedthrough comprises at least one dielectric lens.
    [6]
    6. DNP device according to claim 5, characterized in that the dielectric lens has an insertion loss of 5 dB, preferably of 2 dB, in particular of 1 dB, particularly preferably of 0.5 dB.
    [7]
    7. DNP device according to claim 5 or 6, characterized in that the dielectric lens of a dielectric with dielectric constant ε with 1 <ε <15, in particular polytetrafluoroethylene and / or sapphire and / or alumina and / or quartz, is constructed.
    [8]
    8. DNP device according to one of the preceding claims, characterized in that the arrangement for supplying microwave radiation at a distance d of less than 10 mm, preferably less than 5 mm, more preferably less than 1 mm to the sample sample at the sample location in Cryostat ends.
    [9]
    9. DNP device according to one of the preceding claims, characterized in that the arrangement for supplying microwave radiation comprises a dielectric waveguide.
    [10]
    10. DNP device according to claim 9, characterized in that the dielectric waveguide of a dielectric with dielectric constant ε with 1 <ε <15, in particular of polytetrafluoroethylene and / or sapphire and / or alumina and / or quartz is constructed.
    [11]
    11. DNP device according to one of the preceding claims, characterized in that the arrangement for supplying microwave radiation comprises at least one antenna, in particular a horn antenna or a Antennenar-ray, and / or a coupler and / or a power divider.
    [12]
    12. DNP device according to one of the preceding claims, characterized in that an arrangement for supplying a dissolving liquid, which enables a resolution of the measuring sample and the generation of a hyperpolarized sample liquid, is provided.
    [13]
    13. DNP device according to claim 12, characterized in that the supply of the solution liquid to the measuring sample from above and the supply of microwave radiation to the measuring sample are provided from below or vice versa.
    [14]
    14. Use of a DNP device according to any one of claims 12 or 13 for the production of hyperpolarized liquid for NMR and / or MRI measurements.
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    同族专利:
    公开号 | 公开日
    GB2520159B|2020-09-30|
    GB201416758D0|2014-11-05|
    DE102013219453B8|2014-10-02|
    US9739862B2|2017-08-22|
    GB2520159A|2015-05-13|
    CH708630A2|2015-03-31|
    US20150084632A1|2015-03-26|
    DE102013219453B3|2014-08-07|
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    法律状态:
    2019-10-31| PFA| Name/firm changed|Owner name: BRUKER SWITZERLAND AG, CH Free format text: FORMER OWNER: BRUKER BIOSPIN AG, CH |
    优先权:
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    DE102013219453.6A|DE102013219453B8|2013-09-26|2013-09-26|DNP device|
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