NMR measurement sample holder in a spatially limited NMR spectrometer

Abstract

The invention relates to a NMR spectrometer (10) comprising a permanent magnet arrangement (11) which comprises a measurement volume (12) and a bore (13) for introducing a NMR measurement sample in a sample cuvette (14) and a HF coil (15) outside a cylindrical temperature regulation tube (16) which comprises a continuous annular gap (17) through which a temperature regulation gas can be conducted through a gas inlet (18), characterized in that on the end opposite to the gas inlet a movable holding device (19) is mounted which in a first operating position does not touch the sample cuvette, in a second operating position holds the sample cuvette force-locked and / or form-locked on the outer circumference of the sample cuvette with an axially acting force or static friction F f in its measurement position and in a third operating position releases the sample cuvette for removal and in the second operating position applies F f >F Stau -F Gewicht , wherein F Stau denotes the buoyancy force generated by the dynamic pressure of the temperature regulation gas flowing onto the sample cuvette and F Gewicht denotes the gravitational force of the sample cuvette. By this it is possible to avoid the problems of the known generic arrangement by the dynamic pressure of the temperature regulation gas.

Description

TECHNICAL FIELD

[0001] The invention relates to an NMR spectrometer comprising an NMR magnet system with a permanent magnet arrangement for generating a B0 field in a measurement volume and a bore through the magnet center for introducing an NMR measurement sample in a substantially cylindrical, at least on its lower side closed sample tube; and comprising an HF coil for exciting nuclear spins in the NMR measurement sample, and comprising a temperature regulation system, wherein the HF coil is arranged outside a cylindrical temperature regulation tube, which extends through the measurement volume, and the sample tube can be introduced into the temperature regulation tube for NMR measurement in such a way that a continuous annular gap between the inner circumference of the cylindrical temperature regulation tube and the outer circumference of the sample tube exists, through which gap a temperature regulation gas for temperature regulating the NMR measurement sample in the sample tube can be introduced from the temperature regulation system through a gas inlet at least during an NMR measurement run. BACKGROUND

[0002] Such an NMR spectrometer comprising a permanent magnet arrangement and a device for temperature regulating an NMR measurement sample by means of a temperature regulation gas is known from DE 10 2019 212 508 Al (= reference [1]).

[0003] DE 10 2004 029 633 B4 (= reference [2]) has described an NMR device comprising an NMR spectrometer for sequentially investigating a plurality of NMR measurement samples pneumatically transported from a magazine in a refrigerated cabinet to a measurement position in the spectrometer, which NMR measurement samples are just placed at a desired higher measurement temperature during transport in a transport conduit.

[0004] In DE 10 2018 205 535 B3 (= reference [3]) a transport device is described for pneumatically transporting an NMR measurement sample, which is temperature regulated during the measurement, from an area outside an NMR spectrometer through a tubular transport channel into the NMR spectrometer and from there - after an NMR measurement carried out on the NMR measurement sample - again pneumatically outside the NMR spectrometer.

[0005] An NMR spectrometer comprising a rapid exchange system for NMR measurement samples is known from EP 3715 893 B1 (= reference [4]).

[0006] In US 10,436,859 B2 (= reference [5]) a device and a method are described for introducing an NMR measurement sample into an NMR spectrometer by means of compressed gas and for its extraction from the spectrometer.

[0007] EP 3 561 533 B1 (= reference [6]) discloses an NMR measuring sample which is conveyed into an NMR spectrometer for an NMR measurement and is thereafter conveyed out again. During the measurement, the measuring sample is held at the desired temperature by means of different thermal shields and with the aid of a temperature-regulated gas.

[0008] Background of the invention

[0009] The present invention relates generally to the temperature regulation of an NMR measuring sample in operation, in particular for a benchtop NMR instrument comprising a permanent magnet system. In permanent magnets, the generated magnetic field depends on the ferromagnetic properties of the permanent magnet material used. These properties are in turn strongly temperature-dependent. For high-resolution NMR with linewidths in the sub-hertz range, it is important to adjust the permanent magnet arrangement very precisely in terms of temperature in order to avoid drifts or fluctuations in the B0 field which would lead to a broadening of the resonance line or a distortion of the line shape in the course of the acquisition when accumulating spectra for an improved signal-to-noise ratio (S / N) or when the magnetic field strength changes.

[0010] The temperature regulation of an NMR measuring sample in NMR benchtop spectrometers by means of gas flow is therefore currently between 25°C and 60°C. This function is referred to in the instrument as "adjustable temperature" (= "AT or AT gas flow").

[0011] The core problem in this benchtop implementation comprising a permanent magnet is the very small construction space available for automation. It is therefore necessary to guide all input lines for high frequency (HF), shimming systems and locking samples into the gap between the magnetic poles. The gap is implemented relatively tightly, however, based on the requirements for the homogeneity of the NMR magnetic field.

[0012] In addition, the use of permanent magnets in NMR spectrometers requires a very precise temperature regulation of the NMR magnet, since even the smallest temperature fluctuations lead to field drifts and the spectrometer changes the resonance frequency (see also reference [1], for example). This means that a distance of only 6 mm is given between an NMR measuring sample which is measured at, for example, 60°C and a B0 magnet which is ideally kept at room temperature typically with a few millikelvins, in which there is a temperature gradient of > 30 K.

[0013] The temperature regulation of the NMR measuring sample is achieved by means of so-called "direct flow". This means that the AT gas flow, which is adjusted to the desired temperature, directly circulates around the NMR measuring sample. In the "direct flow" principle, the temperature-regulated gas is guided here directly between the NMR measuring sample and the smallest tubing from bottom to top.

[0014] The air channel is very finely structured by a very small gap size of 0.1-0.3 mm between the NMR measuring sample and the smallest tube. Through this fine channel, a dynamic pressure is generated based on the tempering air below the NMR measuring sample. This dynamic pressure causes the NMR measuring sample to lift from its measuring position in the NMR spectrometer.

[0015] The arrangement of the generic type having the features stated at the outset and the method for generating a homogeneous magnetic field are described in the reference [1] cited at the outset. Of course, reference [1] does not mention the above-described problem of the dynamic pressure formed by the tempering gas and also does not provide a remedy for this. SUMMARY

[0016] Task of the invention

[0017] In contrast, the task of the present invention is to improve the tempering system for NMR magnet systems of the type stated at the outset by means of as little expenditure as possible in such a way that the above-discussed problems of the known arrangement of the generic type including the dynamic pressure formed by the AT tempering gas are avoided.

[0018] Short description of the invention

[0019] This task is solved by the invention in equally surprisingly simple and effect- evident manner in that in an NMR spectrometer of the type defined at the outset, in which the sample tube is introduced into its measuring position in the NMR spectrometer, a holding device is mounted on the end of the sample tube opposite the gas inlet in the NMR measuring operation, which is movable relative to the sample tube into the measuring position of the sample tube, which holding device is designed in such a way that it does not contact the sample tube in a first operating position in order to enable the introduction of the sample tube into its measuring position in the NMR spectrometer, the holding device axially acts onto the sample tube with a force or static friction F f holding the sample tube in its measuring position in the second operating position and the holding device releases the sample tube again for its removal from the NMR spectrometer in a third operating position, and the holding device is designed in such a way that in the second operating position applies F f >F Stau -F Gewicht where F Stau denotes the buoyancy force onto the sample tube generated by the dynamic pressure of the tempering gas flowing onto the sample tube in the NMR measuring operation and F Gewicht denotes the gravitational force of the sample tube.

[0020] In the present case, it is particularly considered to ensure the reliable spatial fixing of the NMR measuring sample in its measuring position during the NMR measuring operation in the simplest possible manner.

[0021] This object is achieved according to the application in particular by a very particularly embodied movable holding element, which holds the NMR measuring sample on its circumference in position by means of a force- or form-lock.

[0022] Particularly advantageously, the application can be used in NMR spectrometers comprising a permanent magnet arrangement for generating a B0 field in the measuring volume. Such spectrometers usually have a temperature regulation device in order to blow an AT gas stream onto the NMR measuring sample to be measured from below at a sufficient flow rate, so that no temperature gradient is created in the NMR measuring sample.

[0023] The AT gas stream is guided into the spectrometer via a hose or tube connection and is built up to the desired temperature inside the spectrometer. In the spectrometer itself, the AT gas stream is guided through a dewar, which is a temperature-sensitive electronic system and isolates the components generating the magnetic field from the AT gas stream. The AT gas stream is guided into the tube or coil glass, which surrounds the NMR measuring sample and on which the coil generating the B1 field is arranged.

[0024] On the basis of the defined installation space, there is only a small distance (0.1 mm - 0.5 mm) between the NMR measuring sample and the coil glass. There, a holding device for the NMR measuring sample is arranged, which holds the NMR measuring sample in the measuring position despite the strong AT temperature regulation gas flow. The holding device clamps the NMR measuring sample, usually an NMR tube, and more precisely clamps it in such a way that the dynamic pressure F Stau The NMR measuring sample can reliably not be moved axially or even thrown out.

[0025] Preferred embodiments and further configurations of the application

[0026] The third operating position of the sample tube coincides in one particularly advantageous embodiment of the application with the first operating position, which then makes the NMR device even more compact, further simplifies it and thus reduces the manufacturing costs.

[0027] Very particularly preferably, one embodiment of the NMR spectrometer according to the application is characterized in that the holding device is designed in such a way that the contact surface between the sample tube and the holding device has a friction coefficient of μ > 0.3 and the following applies F f = μ * F klemm where F klemmis the clamping force acting radially onto the sample tube and μ is the friction coefficient.

[0028] The friction coefficient must be sufficiently high, whereby a significant axial force is generated. The higher the friction coefficient, the smaller the clamping force can be. As suitable material pairs, for example, glass comprising rubber or silicone elastomers can be mentioned.

[0029] It is also advantageous for the invention to be embodied in such a way that the continuous annular gap between the inner circumference of the cylindrical tempering tube and the outer circumference of the sample tube has a radial opening width of between 0.1 mm and 1 mm, preferably between 0.15 mm and 0.3 mm, in the measurement position of the sample tube. The NMR coil must be as close as possible to the sample. Every tenth of a millimeter changes the sensitivity of the spectrometer.

[0030] A further advantageous embodiment of the invention is characterized in that the tempering gas has a volume flow of at least 1 1 / min and at most 20 1 / min, preferably 3.5 1 / min to 12 1 / min, during the NMR measurement operation of the NMR spectrometer.

[0031] A large volume flow leads to the sample tube being conveyed by dynamic pressure. But a minimum volume flow is required in order to reduce the tempering time of the NMR sample and to avoid or at least minimize temperature gradients in the measurement sample.

[0032] A class of embodiments of the invention is characterized in that there is a sample changer for automated loading of the NMR spectrometer with sample tubes, which has a storage container for storing a plurality of sample tubes and means for transferring a sample tube into the measurement volume and removing the sample tube from the measurement volume.

[0033] This serves for unmonitored automated operation, if necessary also for high throughput.

[0034] In a preferred further configuration of this class of embodiments, the holding means simultaneously function as means for transferring and removing sample tubes, and the NMR spectrometer and the sample changer are preferably components of an automated device system comprising a robot gripper arm.

[0035] A separate holding means is then not required, since the gripper arm is simultaneously the holding means.

[0036] It is also advantageous for the NMR spectrometer according to the invention to be embodied in such a way that there is a dewar which at least partially encloses the conduit leading from the tempering system to the gas inlet.

[0037] The dewar is important, since the spectrometer reacts highly sensitively to temperature changes. In particular the permanent magnets should not deviate from the operating temperature. But also the electronic components and the shimming system are temperature-regulated and are temperature-regulated in very small construction spaces.

[0038] The entire electronics system must be isolated as far as possible from temperature fluctuations. Ideally, the dewar extends to the sample, whereby the AT gas flow is isolated from the electronics system. Preferably, heating is effected in the dewar itself, for example with a heating spiral. In combination with the cooled air (N2) delivered from the outside, the temperature of the AT gas flow can be adjusted.

[0039] A further embodiment of the invention is characterized in that there is a first sensor element for determining the presence of a sample tube in the NMR spectrometer.

[0040] Preferably, the sensor element checks the correct occupation of the measuring position by the sample tube, perhaps in combination with a marking on the sample tube.

[0041] The feature serves the repeatability of the measurements in automated operation, since the correct positioning of the sample in the measuring region is critical in NMR measurements. It is also important to detect the absence of a measuring sample before a new measuring sample is loaded, whereby collisions of sample tubes in the spectrometer and thus breakages are not caused.

[0042] In a preferred further configuration of this embodiment, there is a further sensor element for determining the current operating position of the holding device.

[0043] The further sensor element must register that the sample is fixed in its measuring position. In addition, the sensor shows that the holding pin is currently pulled back in order not to prevent the loading of a measuring sample.

[0044] Alternatively or additionally, in other embodiments of the invention, the holding device can have a holding piston, which can be loaded with force by means of compressed air or a motor drive, which force then moves the holding piston against a spring force of a return spring, in particular a return spring, towards the sample tube.

[0045] By means of the return spring, the holding device is in a preferred position when there is no compressed air loading. The position can be chosen: in the clamping position or pulled back.

[0046] A favorable further configuration of these embodiments is characterized in that the holding piston has a holding pin, which can enter into direct mechanical contact with the outer circumference of the sample tube.

[0047] By using the retaining pin, the material (usually an elastomer) that holds the sample tube can be freely chosen. The retaining piston, which is loaded by compressed air, must itself be solid in terms of material, i.e. have a large modulus of elasticity.

[0048] The first group of embodiments of the application is completely particularly simply constructed, wherein the retaining device has retaining arms that can at least clamp the sample tube in a pincer-like manner on a portion of the outer circumference of the sample tube, wherein the retaining arms are preferably constructed as clamping pincers or as two half-shells, which can fix the sample tube on the outer circumference of the sample tube from both sides.

[0049] By this, a symmetrical pressing force in the retaining arms is produced and the sample tube is well centered.

[0050] The second group of embodiments of the NMR spectrometer according to the application is characterized in that the retaining device has an iris diaphragm.

[0051] Advantageously, the same symmetrical pressing force by the iris diaphragm. The sample tube is even better centered than with the retaining arms.

[0052] In the third group of embodiments, the retaining device has a feed element that in the second operating position axially blocks the sample tube over the end of the sample tube that is opposite the gas inlet from moving out of the measurement position.

[0053] For example, the feed element can be extended and retracted in a radial direction with respect to the z-axis of the NMR device.

[0054] The actuating force onto the feed element is small, since it only acts in the axial direction. Furthermore, it is independent of the dynamic pressure due to the form fit.

[0055] Finally, the fourth group of embodiments is characterized in that the retaining device has a pneumatically actuable, in particular inflatable, element that can load the sample tube in the measurement position of the sample tube with a radial pressure.

[0056] This variant is realized in principle without moving parts. The balloon clamps the sample tube itself. Compared to the above variants, only a very small number of components is required.

[0057] A particularly simple further construction of this group of embodiments is characterized in that the retaining device has a highly elastic hose, for example made of silicone or another elastomer, which is arranged in the measurement position of the sample tube in an arm-like or ring-like manner around the sample tube or has an inflatable O-ring that is arranged radially around the outer circumference of the sample tube.

[0058] It is advantageous here that a good friction coefficient is achieved with glass. The hose is placed uniformly on the test tube. A large contact surface of the sample test tube and particularly good centering result therefrom.

[0059] The HF coil is usually simply applied on the outer surface of the cylindrical temperature regulation tube, where it requires almost no additional space.

[0060] Preferably, at least one shim coil for generating the Ho field is present in the NMR spectrometer according to the application, which surrounds the HF coil at a radial distance and is temperature-regulated in particular with its own temperature regulation system.

[0061] Also falling within the scope of the application is a method for operating an NMR spectrometer according to the application of the above type comprising a sample changer, characterized by the following steps:

[0062] (a) the transfer of the holding device into a first operating position;

[0063] (b) the introduction of a sample test tube comprising an NMR measurement sample through the aperture into a measurement position of the sample test tube in the measurement volume;

[0064] (c) the detection of the presence of the sample test tube in the measurement position by means of a first sensor element;

[0065] (d) the fixation of the sample test tube by means of the holding device;

[0066] (e) the checking of the current presence of the second operating position of the holding device by means of the further sensor element;

[0067] (f) the release of a temperature regulation gas flow for the temperature regulation of the NMR measurement sample;

[0068] (g) the carrying out of an NMR measurement on the NMR measurement sample;

[0069] (h) the transfer of the holding device into a third operating position and the removal of the sample test tube from the spectrometer.

[0070] This allows an error-free and reliable automation without the presence of a measurement person. Traceability of the measurement is given, since by means of the positioning sensor mechanism and the correct temperature regulation, the same measurement conditions are possible for each sample in the measurement sequence. This is important for measurements in certified methods (GXP) and prevents incorrect handling.

[0071] Further advantages of the present application result from the description and the drawings. Likewise, the above-mentioned and further features and the features still to be explained below can be used not only in the respective combinations indicated, but also in other combinations or in isolation, without departing from the scope of the present application. The illustrated and described embodiments are not to be understood as final enumeration, but rather more precisely as exemplary features for describing the present application. BRIEF DESCRIPTION OF DRAWINGS

[0072] Detailed description of the application and drawings

[0073] The application is illustrated in the drawings and explained further by way of example.

[0074] wherein:

[0075] Figure 1 schematic vertical sectional view of an embodiment of an NMR spectrometer according to the application;

[0076] Figure 2a schematic vertical sectional view through a lower partial region of a sample tube in a temperature regulation tube for illustrating dynamic pressure and conditions F according to the application f F Stau F Gewicht ;

[0077] Figure 2b schematic vertical sectional view through a - shortened - sample tube in a temperature regulation tube for illustrating radial clamping of the sample tube on the contact surface of the holding device based on sliding friction;

[0078] Figure 3a schematic vertical sectional view through an upper partial region of a sample tube in a temperature regulation tube including an embodiment of a holding device according to the application, the holding device including a holding piston, a return spring and a holding pin;

[0079] Figure 3b as Figure 3a is shown, however, without a sample tube for visualizing the first and the further sensor element;

[0080] Figure 4a as Figure 3b is shown, however, with less detail and including the holding piston in a retracted operating position for sample tube passage;

[0081] Figure 4b as Figure 4a is shown, however, with less detail and including the holding piston in an extended operating position for holding a - here not shown - sample tube in the temperature regulation tube;

[0082] Figure 5A vertical section through an upper partial region of the tempering tube is shown without an introduced sample tube, including an embodiment of a holding device, which here has a pneumatic inflatable O-ring;

[0083] Figure 6a A schematic vertical section through a sample tube, which is shown shortened in the tempering tube, is shown, including another embodiment of a holding device, which includes an inflatable O-ring, which here is in an inflated operating state for the passage of the sample tube;

[0084] Figure 6b As Figure 6a is shown, however, including the O-ring in the inflated operating state for holding a sample tube in the tempering tube; and

[0085] Figure 7 As Figure 1 is shown, however, including an NMR spectrometer according to the application as well as a sample changer and a robot gripper arm as a component of an automated device system. DETAILED DESCRIPTION

[0086] The figures Figures 1 to 7 A preferred embodiment of an NMR spectrometer 10 according to the application is shown in different detail in schematic views, respectively.

[0087] Such an NMR spectrometer 10 has a permanent magnet arrangement 11 for generating a B0 field in a measurement volume 12, including a bore 13 through the magnet center for introducing an NMR measurement sample in a substantially cylindrical, at least on its lower side closed sample tube 14, including a shimming system 26 and including an HF coil 15 for exciting nuclear spins in the NMR measurement sample, wherein the HF coil 15 is arranged outside a cylindrical tempering tube 16, which extends through the measurement volume 12, and the sample tube 14 can be introduced in the tempering tube for NMR measurement such that a continuous annular gap 17 exists between the inner circumference of the cylindrical tempering tube 16 and the outer circumference of the sample tube 14, through which gap a tempering gas for tempering the NMR measurement sample in the sample tube 14 can be guided from a tempering system through a gas inlet 18 at least in an NMR measurement operation. A fluid conduit 22 to the gas inlet 18 guides the tempering gas through a dewar 21. The tempering gas is driven by a pump device of the NMR spectrometer 10, which is not specifically shown in the figures.

[0088] The application improves this per se known NMR device and extends it with elements important for the application:

[0089] The NMR spectrometer 10 according to the application is characterized in that, on the end of the sample tube 14 which, in the NMR measurement run, is opposite the gas inlet 18, a holding device 19 is installed in the NMR spectrometer 10 which is movable relative to the sample tube 14 into the measurement position of the sample tube, the holding device 19 being designed in such a way that it does not contact the sample tube 14 in a first operating position in order to enable the sample tube to be introduced into its measurement position in the NMR spectrometer 10, the holding device in a second operating position axially acting onto the sample tube 14 with a force or static friction F which is force-locked and / or form-locked on the outer circumference of the sample tube for carrying out the NMR measurement f is held in the measurement position of the sample tube and the holding device in a third operating position releases the sample tube 14 again for removal from the NMR spectrometer 10, and the holding device 19 is designed in such a way that, in the second operating position, applies F f Stau Gewicht where F Stau denotes the buoyancy force onto the sample tube 14 which is generated by the dynamic pressure of the tempering gas flowing onto the sample tube 14 in the NMR measurement run and F Gewicht denotes the gravitational force of the sample tube 14.

[0090] is shown in strongly schematic representation in Figure 1 a first, particularly simple embodiment of the application:

[0091] The reliable spatial fixation of the sample tube 14 during the NMR measurement is achieved with the movable element of the holding device 19 which is developed specifically for this purpose and is designed according to the principles according to the application. Preferably, the fixation takes place on the upper end of the sample tube 14, in any case not in the measurement region, i.e. not in the measurement volume 12. That is, the holding device 19 has a movable element which can be extended into and from the sample channel through which the sample tube 14 for the NMR measurement is introduced into the measurement volume 12 and is thus removed therefrom again. If the sample tube 14 is in the sample head of the NMR spectrometer 10, by the extension of the movable element the sample tube 14 is clamped and thus held in its measurement position.

[0092] A sufficiently large holding force is achieved by the corresponding extension force of the movable element and the friction surface (with as high a static friction coefficient as possible).

[0093] Figure 2a ​​The temperature control gas flowing in from below into the sample tube 14 is shown in a strongly diagrammatic vertical section through the lower section region of the sample tube 14 in the temperature control tube 16. This temperature control gas causes a dynamic pressure on the sample tube 14 accordingly. But in order that the sample tube 14 is not pressed out of the measuring volume 12 upwards during the NMR measurement by this permanently present dynamic pressure, in the NMR spectrometer according to the prior art the gravitational force F Gewicht of the sample tube 14 should not be smaller than the pressure F Stau acting on the sample tube 14 from below by the dynamic pressure. However, on the other hand, the gravitational force F Gewicht should also not be greater than the pressure F Stau , because otherwise - in any case without further measures - the sample tube 14 would fall out of the measuring volume 12 downwards. Therefore, in the prior art, the dynamic pressure is usually adjusted just so by adjusting the volume flow of the temperature control gas that the sample tube 14 is just held in suspension in its measuring position, i.e. F Stau ≈ F Gewicht . But with this the parameter of the optimised temperature control gas volume flow for the temperature control of the sample tube 14 is cancelled again.

[0094] By the design of the new holding device 19 according to the application, in contrast, the important process parameter of the temperature control gas volume flow can be varied in a large range in the case of the condition F f > F Stau - F Gewicht prescribed according to the application for the holding force or static friction Ft acting on the sample tube 14, in order to optimise the temperature control of the sample tube 14. The volume flow of the temperature control gas can thus now in practice be freely adjusted in a wide range between approximately 1 1 / min and up to 20 1 / min, preferably between 3.5 1 / min and 12 1 / min, during the NMR measurement operation of the NMR spectrometer 10.

[0095] The radial opening width of the continuous annular gap 17 between the inner circumference of the cylindrical temperature control tube 16 and the outer circumference of the sample tube 14 is usually selected in the NMR spectrometer 10 according to the application in the measuring position of the sample tube 14 to be between 0.1 mm and 1 mm, preferably between 0.15 mm and 0.3 mm.

[0096] Figure 2b The radial clamping of the sample tube 14 on the contact surface 20 of the holding device 19 on the basis of the sliding friction is illustrated figuratively in a further strongly diagrammatic vertical section through the sample tube 14 in the temperature control tube 16, which is shortened here. Here, the clamping force F klemm acts radially on the sample tube 14. Therefore, in terms of the friction coefficient μ, it must apply for the arrangement according to the application: F f=μ*F klemm .

[0097] The holding device 19 according to the invention is preferably constructed such that the contact surface 20 between the sample tube 14 and the holding device 19 has a coefficient of friction μ>0.3.

[0098] exist Figure 3a Another design of the holding device 19 according to the invention is shown in a vertical cross-section of a portion of the sample tube 14 above the temperature control tube 16. This embodiment of the holding device 19 according to the invention includes a holding piston 19a, a return spring 19b, and a holding pin 19c.

[0099] The piston 19a can be held in place by means of compressed air or an engine drive force, which moves the piston toward the sample tube 14 opposite to the spring force of the return spring 19b and presses the retaining pin 19c toward it.

[0100] To detect the correct positioning of the sample tube 14 in the measurement space, a first sensing element 23 is provided for determining the presence of the sample tube 14 within the NMR spectrometer 10, such as in Figure 3b This can be seen from the text. Figure 3b As shown Figure 3a This is the same part of an NMR device, however, without a sample tube for better visualization of the sensing elements. Preferably, the first sensor is mounted in such a way that the loading status of the sample tube 14 can be reliably and without doubt determined. For example, the sensor may have a grating.

[0101] Also in Figure 3b Another sensing element 24 is depicted for determining the current operating position of the holding device 19. This second sensor indicates that the holding pin 19c is fully extended and in an operating position where it presses against the sample tube 14 and holds the sample tube in place by clamping. The AT gas flow can only be released when this positioning is confirmed by the second sensor, otherwise the sample tube 14 cannot be correctly positioned.

[0102] exist Figure 4a The middle shows with Figure 3b The same situation, however with less detail, includes a retaining piston 19a in the extended running position for the passage of the sample tube 14 (again not depicted here).

[0103] Figure 4b Showing with Figure 4a The same equipment components, however, include a retaining piston 19a in the extended operating position for holding the sample tube 14 in the temperature control tube 16 - which is not shown here for better visibility.

[0104] In another embodiment of the application, which is not shown in the drawing, the holding device 19 can have holding arms which can clamp the outer circumference of the sample tube 14 at least in a pincer-like manner, wherein the holding arms are preferably formed as clamping pincers or as two half-shells which can fix the sample tube 14 on the outer circumference of the sample tube from both sides.

[0105] In these embodiments of the holding device it is advantageous that the sample tube 14 can be held well centered in the center of the coil glass. Mechanical means for pincers, however, require somewhat more construction space.

[0106] In another embodiment, which is not shown, the holding device 19 has an iris diaphragm.

[0107] Furthermore, the holding device 19 can also have a feed element which in the second operating position axially blocks the sample tube 14 from moving out of the measuring position by means of the end of the sample tube 14 which is opposite the gas inlet 18 in a lid-like manner.

[0108] In another alternative design, the holding device 19 can have - as shown in Figure 5 a vertically sectioned area through the part region above the temperature regulation tube 16 without an introduced sample tube 14, a pneumatically actuable element 25 which can be inflated, among other things, and which loads the sample tube 14 in its measuring position with a radial pressure.

[0109] The holding element is formed as a hose, in particular as a pneumatically inflatable O-ring, which is guided around the sample tube. For clamping, the hose is loaded with compressed air. The hose thereby expands and fixes the sample tube in its measuring position.

[0110] Figure 6a and 6b each show a schematic vertical section through a sample tube 14 in a temperature regulation tube 16, including another embodiment of a holding device according to the application, including an inflatable O-ring 25' in an uninflated operating state here for sample tube passage.

[0111] Figure 6a show the pneumatically actuable element 25' in an uninflated operating state for sample tube passage, while in Figure 6b the O-ring 25' is shown in an inflated operating state for holding the sample tube 14 in the temperature regulation tube 16. That is, the inflatable hose is not loaded with compressed air relative to the ambient pressure in Figure 6a the inflated operating state.relativ = 0) and in Figure 6b pneumatic loading (p relativ > 0) can be seen. By the enlargement of the hose arranged annularly around the sample tube 14, a holding force is generated on the sample tube 14, which holds the NMR tube position fixedly in the AT temperature-control flow.

[0112] In all above-mentioned variants of the application, the holding device 19 can be driven manually, electromechanically, magnetically or pneumatically.

[0113] Figure 7 Finally, a sample changer 32 for automated loading of the NMR spectrometer 10 with sample tubes 14 is shown (in addition to Figure 1 ), which has a reservoir container for storing a plurality of sample tubes and means for transferring and removing the sample tubes 14 into or from the measuring volume 12. The sample changer is generally arranged on the upper side of the NMR spectrometer 10 in the sense of the application and is equipped for loading the spectrometer with different NMR tubes from the reservoir container and removing the NMR tubes from the measuring volume 12 again after the measurement.

[0114] In the shown embodiment, the holding device 19 simultaneously functions as means for transferring and removing the sample tubes 14. The NMR spectrometer 10 and the sample changer 32 are here components of an automated device system 30 comprising a robot gripper arm 31.

[0115] The features of all above-mentioned embodiments of the application can in each case also be combined with one another to a large extent.

[0116] List of references:

[0117] For the evaluation of the examined literature

[0118] [1] DE 10 2019 212 508 A1

[0119] [2] DE 10 2004 029 633 B4

[0120] [3] DE 10 2018 205 535 B3 = EP 3 561 533 B1 = US 10,782,369 B2

[0121] [4] EP 3 715 893 B1 = ZL 202010210645.3 = US 11,073,583 B2

[0122] [5] US 10,436,859 B2

[0123] [6] EP 3 561 533 B1

[0124] [7] DE 10 2016 203891 A1

[0125] List of reference signs

[0126] 10 NMR spectrometer

[0127] 11 Permanent magnet arrangement

[0128] 12 Measuring volume

[0129] 13 Magnet bore

[0130] 14 Sample cuvette

[0131] 15 HF coil

[0132] 16 Temperature regulation tube

[0133] 17 Annular gap

[0134] 18 Gas inlet

[0135] 19 Retaining device

[0136] 19a Retaining piston

[0137] 19b Return spring

[0138] 19c Retaining pin

[0139] 20 Contact surface

[0140] 21 Duvet

[0141] 22 Conduit to gas inlet

[0142] 23 First sensor element

[0143] 24 Further sensor element

[0144] 25; 25' Pneumatically actuatable element

[0145] 26 Shimming system

[0146] 30 Automation system

[0147] 31 Robot gripper

[0148] 32 Sample changer

Claims

1. An NMR spectrometer (10) comprising an NMR magnet system having a permanent magnet device (11) for generating a B0 field in a measurement volume (12) and an aperture (13) through the center of the magnet for introducing an NMR measurement sample into a substantially cylindrical sample tube (14) closed at least on its lower side; and including an HF coil (15) for exciting nuclear spins in the NMR measurement sample, and including a temperature control system, wherein, The HF coil (15) is disposed outside a cylindrical temperature-regulating tube (16) that extends through the measurement volume (12), and the sample tube (14) is introduced into the temperature-regulating tube for NMR measurement, such that a continuous annular gap (17) exists between the inner circumference of the cylindrical temperature-regulating tube (16) and the outer circumference of the sample tube (14), through which temperature-regulating gas for temperature regulation of the NMR measurement sample in the sample tube (14) can be guided from the temperature-regulating system through a gas inlet (18), at least during NMR measurement operation; characterized in that, during NMR measurement operation, the sample tube (14) is in contact with the gas... At the opposite end of the inlet (18), a holding device (19) is installed in the NMR spectrometer (10) that is movable relative to the sample tube (14) to the measurement position of the sample tube. The holding device (19) is designed such that it does not contact the sample tube (14) in a first operating position, so that the sample tube can be introduced into the measurement position of the sample tube in the NMR spectrometer (10). In a second operating position, the holding device forces and / or forms-locks the sample tube (14) on the outer circumference of the sample tube for NMR measurement, and applies a force or static friction F to the sample tube (14) axially. f The sample tube is held in the measurement position, and the holding device releases the sample tube (14) again in the third operating position for removal from the NMR spectrometer (10), and the holding device (19) is designed to be suitable for use in the second operating position. F f >F Stau -F Gewicht , Among them, F Stau This represents the buoyancy force on the sample tube (14) generated by the dynamic pressure of the temperature-controlled gas flowing onto the sample tube (14) during the NMR measurement operation, and F Gewicht This indicates the gravity of the sample tube (14).

2. The NMR spectrometer according to claim 1, characterized in that, The holding device (19) is configured such that the contact surface (20) between the sample tube (14) and the holding device (19) has a coefficient of friction μ>0.3, and is suitable for F f =μ*F klemm , of which F klemm μ is the clamping force acting radially on the sample tube (14) and μ is the coefficient of friction.

3. The NMR spectrometer according to claim 1, characterized in that, A continuous annular gap (17) between the inner circumference of the cylindrical temperature control tube (16) and the outer circumference of the sample tube (14) has a radial opening width between 0.1 mm and 1 mm at the measurement position of the sample tube (14).

4. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The temperature-regulating gas has a volumetric flow rate of at least 1 l / min and a maximum of 20 l / min during NMR measurement operation of the NMR spectrometer (10).

5. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, A sample changer (32) is provided for automatically loading the NMR spectrometer (10) with sample tubes (14). The sample changer has a storage container for storing a plurality of sample tubes (14) and means for transferring the sample tubes into the measurement volume (12) and removing the sample tubes (14) from the measurement volume (12).

6. The NMR spectrometer according to claim 5, characterized in that, The holding device (19) also functions as a device for transferring and removing the sample tube (14).

7. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, A dewar (21) is present, which at least partially surrounds the conduit (22) leading from the temperature control system to the gas inlet (18).

8. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, A first sensing element (23) is present for determining the presence of the sample tube (14) within the NMR spectrometer (10).

9. The NMR spectrometer according to claim 8, characterized in that, There is another sensing element (24) for determining the current operating position of the holding device (19).

10. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The holding device (19) has a holding piston (19a) which can be loaded with force by means of compressed air or an engine drive, the force of which moves the holding piston (19a) toward the sample tube (14) opposite to the return force.

11. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The holding device (19) has a holding arm that is capable of clamping at least a portion of the outer circumference of the sample tube (14) in a clamping manner.

12. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The holding device (19) has an iris-type aperture.

13. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The holding device (19) has a feeding element that, in the second operating position, covers the sample tube (14) above the end opposite the gas inlet (18) and blocks the sample tube (14) from moving out of the measuring position in the axial direction.

14. The NMR spectrometer according to any one of claims 1 to 3, characterized in that, The holding device (19) has pneumatically operable elements (25; 25') that can apply radial pressure to the sample tube (14) at the measurement position of the sample tube.

15. The NMR spectrometer according to claim 3, characterized in that, The radial opening width is between 0.15 mm and 0.3 mm.

16. The NMR spectrometer according to claim 4, characterized in that, The temperature-regulating gas has a volumetric flow rate of 3.5 l / min to 12 l / min during NMR measurement operation of the NMR spectrometer (10).

17. The NMR spectrometer according to claim 6, characterized in that, The NMR spectrometer (10) and the sample changer (32) are components of an automated device system (30) including a robotic gripper (31).

18. The NMR spectrometer according to claim 10, characterized in that, The force then moves the holding piston (19a) toward the sample tube (14) opposite to the spring force of the return spring (19b).

19. The NMR spectrometer according to claim 11, characterized in that, The retaining arm is configured as a clamping clamp or as two half-shells, which can fix the sample tube (14) from both sides on the outer circumference of the sample tube.

20. The NMR spectrometer according to claim 14, characterized in that, The pneumatically operated element is an inflatable element.

21. A method for operating an NMR spectrometer (10) according to any one of claims 9 to 14, comprising a sample changer (32), characterized in that... The following steps: (a) The holding device (19) is moved to the first operating position; (b) The sample tube (14) containing the NMR measurement sample is introduced through the hole (13) to the measurement position of the sample tube in the measurement volume (12); (c) The presence of the sample tube (14) at the measurement position is detected by means of the first sensing element (23); (d) The sample tube (14) is fixed by means of the holding device (19); (e) Check the current presence of the second operating position of the holding device (19) by means of another sensing element (24); (f) Release a temperature-regulating gas flow for temperature regulation of the NMR measurement sample; (g) Perform NMR measurements on the NMR measurement sample; (h) Move the holding device (19) to the third operating position and remove the sample tube (14) from the spectrometer (10).

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