Device for holding NMR measurement sample in spatially limited NMR spectrometer

Abstract

The invention relates to an NMR spectrometer (10), comprising a permanent magnet arrangement (11), which comprises a measurement volume (12) and a bore (13) for introducing an NMR measurement sample in a sample cuvette (14), and an HF coil (15) outside a cylindrical temperature control tube (16), which comprises a continuous annular recess (17) through which a temperature control gas can be conducted via a gas inlet (18), the device is characterized in that a movable holding device (19) is mounted at the end opposite the gas inlet, and the holding device does not contact the sample test tube in a first operating position; the holding device holds the sample cuvette on the outer circumference of the sample cuvette in a force-fitting and / or form-fitting manner in its measuring position with an axially acting force or static friction Ff in a second operating position, and the holding device releases the sample cuvette for removal in a third operating position and applies Ffgt in the second operating position; fStau-FGewicht, where FStau represents the buoyancy generated by the dynamic pressure of the temperature control gas flowing onto the sample cuvette and FGewicht represents the gravity of the sample cuvette. In this way, the problem of a known generic arrangement of the dynamic pressure caused by the temperature control gas can be avoided.

Description

Technical Field

[0001] The invention relates to an NMR spectrometer, comprising an NMR magnet system having a permanent magnet arrangement for generating a B0 field in a measurement volume and a hole through the center of the magnet for introducing an NMR measurement sample in a substantially cylindrical sample tube which is closed at least on its underside; and an HF coil for exciting nuclear spins in the NMR measurement sample, wherein the HF coil is arranged outside a cylindrical temperature control tube which extends through the measurement volume and into which the sample tube can be introduced for NMR measurement in such a way that a continuous annular gap is present between the inner circumference of the cylindrical temperature control tube and the outer circumference of the sample tube, through which gap a temperature control gas for temperature control of the NMR measurement sample in the sample tube can be introduced from the temperature control system via a gas inlet at least during NMR measurement operation. Background Art

[0002] Such an NMR spectrometer comprising a permanent magnet arrangement and a device for temperature control of an NMR measurement sample by means of a temperature control gas is known from DE 10 2019 212 508 A1 (=reference [1]).

[0003] DE 10 2004 029 633 B4 (=reference [2]) describes an NMR device comprising an NMR spectrometer for sequentially studying a plurality of NMR measurement samples which are pneumatically transported from a chamber in a refrigerated cabinet to a measurement position in the spectrometer and which are brought to the desired higher measurement temperature during transport in the transport conduit.

[0004] DE 10 2018 205 535 B3 (= reference [3]) describes a transport device for pneumatically transporting an NMR measurement sample, which is temperature-controlled during the measurement, from an area outside the NMR spectrometer via a tubular transport channel into the NMR spectrometer and from there - after carrying out the NMR measurement on the NMR measurement sample - pneumatically transporting it back out of the NMR spectrometer.

[0005] An NMR spectrometer comprising a rapid-change system for NMR measurement samples is known from EP 3 715 893 B1 (=reference [4]).

[0006] US Pat. No. 10,436,859 B2 (ref. [5]) describes a device and a method for introducing an NMR measurement sample into an NMR spectrometer and for removing it from the spectrometer by means of compressed gas.

[0007] EP 3 561 533 B1 (ref. [6]) discloses an NMR measurement sample which is fed into an NMR spectrometer for NMR measurement and then fed out again. During the measurement, the measurement sample is kept at the desired temperature by means of different heat shields and a temperature-controlled gas.

[0008] Background of the Invention

[0009] The present invention generally relates to the temperature control of samples for NMR measurements in operation, in particular for tabletop NMR instruments comprising a permanent magnet system. In a permanent magnet, the magnetic field generated depends on the ferromagnetic properties of the permanent magnet material used. These properties are in turn strongly temperature-dependent. For high-resolution NMR with sub-Hertz line widths, it is important to adjust the permanent magnet arrangement very precisely in terms of heat in order to avoid drifts or fluctuations of the B0 field, which over the duration of the acquisition can lead to broadening of the resonance lines when accumulating spectra for improving the signal-to-noise ratio (S / N) or distortion of the line shape when the magnetic field strength changes.

[0010] In NMR tabletop spectrometers, the NMR measurement sample is therefore temperature-controlled by means of a gas flow, currently between 25° C. and 60° C. This function is referred to in these instruments as “adjustable temperature” (= “AT or AT gas flow”).

[0011] The core problem in this tabletop embodiment with permanent magnets is the very small installation space available for automation. As a result, all the input lines for the high frequency (HF), the shim system and the locking sample must be routed into the gap between the magnetic poles. However, the gap must be designed relatively tightly due to the homogeneity requirements for the NMR magnetic field.

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

[0013] The temperature of the NMR measurement sample is controlled by so-called "direct flow". This means that an AT gas flow adjusted to the desired temperature flows directly around the NMR measurement sample. In the "direct flow" principle, the temperature control gas is guided directly between the NMR measurement sample and the smallest tube from bottom to top.

[0014] Due to the very small gap size of 0.1-0.3 mm between the NMR measurement sample and the smallest tube, the air channel is designed to be very thin. Through this thin channel, a dynamic pressure is generated due to the temperature-controlled air under the NMR measurement sample. This dynamic pressure causes the NMR measurement sample to be lifted from its measurement position in the NMR spectrometer.

[0015] The reference [1] cited at the outset describes a generic arrangement having the features described at the outset and a method for generating a uniform magnetic field. Of course, reference [1] does not mention the above-described problem of the dynamic pressure generated by the temperature-controlled gas and does not provide a remedy for this. Summary of the invention

[0016] Mission of the present invention

[0017] In contrast, the object of the present invention is to improve a temperature control system for an NMR magnet system of the type mentioned at the outset by means of technical means which are as economical as possible in such a way that the above-discussed problems of known generic arrangements involving the dynamic pressure generated by the AT temperature control gas are avoided.

[0018] A short description of the invention

[0019] This object is achieved by the invention in an equally surprisingly simple and effective manner in that, in an NMR spectrometer of the type defined in the introduction, a holding device is mounted at the end of the sample tube which is opposite the gas inlet in the NMR measuring operation and which is movable relative to the sample tube into a measuring position of the sample tube, the holding device being designed such that in a first operating position it does not contact the sample tube in order to enable the sample tube to be introduced into the measuring position of the sample tube in the NMR spectrometer, and in a second operating position the holding device holds the sample tube in a force-locking and / or form-locking manner on the outer circumference of the sample tube for carrying out the NMR measurement with a force or static friction F acting axially on the sample tube. f The holding device holds the sample tube in the measuring position, and the holding device releases the sample tube again in the third operating position for removal from the NMR spectrometer, and the holding device is designed such that in the second operating position the F f >F Stau -F Gewicht , where F Stau represents the buoyancy force on the sample tube generated by the dynamic pressure of the temperature control gas flowing onto the sample tube during the NMR measurement operation, and F Gewicht represents the gravity of the sample tube.

[0020] In particular, the invention provides for ensuring a reliable spatial fixation of the NMR measurement sample in its measurement position during the NMR measurement operation in the simplest possible manner.

[0021] This object is achieved according to the invention in particular by a very specially designed movable holding element which holds the NMR measurement sample in position over its circumference by force-locking or form-locking.

[0022] The invention can be used particularly advantageously in an NMR spectrometer comprising a permanent magnet arrangement for generating a B0 field in a measurement volume. Such a spectrometer usually has a temperature control device in order to control the NMR measurement sample to be measured by means of an AT gas flow which is blown in from below with a sufficient flow rate to the respective NMR measurement sample so that no temperature gradient is formed in the NMR measurement sample.

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

[0024] Due to the limited installation space, there is only a small distance (0.1 mm-0.5 mm) between the NMR measurement sample and the coil glass. A holding device for the NMR measurement sample is provided there, which holds the NMR measurement sample in the measurement position despite the strong AT temperature control gas flow. The holding device clamps the NMR measurement sample, usually an NMR test tube, and more precisely clamps it in such a way that the dynamic pressure F Stau It is reliably not possible to displace the NMR measurement sample axially or even eject it.

[0025] Preferred embodiments and further developments of the present invention

[0026] In a particularly advantageous embodiment of the invention, the third operating position of the sample tube coincides identically with the first operating position, which then makes the NMR device even more compact, further simplifies it and thus reduces the production costs.

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

[0028] The friction coefficient must be high enough to generate a significant axial force. The higher the friction coefficient, the smaller the clamping force can be. As a suitable material pair, for example, glass including rubber or silicone elastomer can be mentioned.

[0029] Also advantageous is an embodiment of the invention in which the continuous annular gap between the inner circumference of the cylindrical temperature control 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 measuring position of the sample tube. The NMR coil must be as close as possible to the sample. The sensitivity of the spectrometer changes with every tenth of a millimeter.

[0030] Further advantageous embodiments of the invention are characterized in that the temperature control gas has a volume flow of at least 1 l / min and a maximum of 20 l / min, preferably 3.5 l / min to 12 l / min, during NMR measurement operation of the NMR spectrometer.

[0031] A large volume flow leads to a transport of the sample tube by dynamic pressure. However, a minimum volume flow is necessary in order to reduce the temperature conditioning time of the NMR sample and to avoid or at least minimize temperature gradients in the measurement sample.

[0032] One embodiment of the invention is characterized in that a sample changer is provided for the automated charging of the NMR spectrometer with sample tubes, the sample changer having a storage container for storing a plurality of sample tubes and a device for transferring sample tubes into the measurement volume and removing the sample tubes from the measurement volume.

[0033] This is used for unmonitored automated operation and, if necessary, also for high transmission rates.

[0034] In a preferred refinement of this type of embodiment, the holding device simultaneously functions as a device for transferring and removing sample tubes, and the NMR spectrometer and the sample changer are preferably components of a robotic system including a robot gripper arm.

[0035] A separate holding device is then not necessary, since the gripping arm is simultaneously the holding device.

[0036] An embodiment of the NMR spectrometer according to the invention is also advantageous, which is characterized in that a dewar is provided which at least partially surrounds a line leading from the temperature control system to the gas inlet.

[0037] The dewar is important because spectrometers react very sensitively to temperature changes. In particular, the permanent magnets should not deviate from the operating temperature. However, the electronic components and the shim system are also temperature-controlled and do so in a very small installation space.

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

[0039] Another embodiment of the invention is characterized in that a first sensor element is present for determining the presence of a sample cuvette in the NMR spectrometer.

[0040] Preferably, the sensor element serves to check the correct occupation of the measuring position by the sample cuvette, possibly in conjunction with a marking on the sample cuvette.

[0041] This feature serves to ensure the repeatability of the measurement in automated operation, since the correct positioning of the sample in the measurement region is crucial in NMR measurements. It is also important to detect the absence of a measurement sample before charging with a new measurement sample, so that the sample tube does not collide in the spectrometer and thus break.

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

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

[0044] Alternatively or additionally, in other embodiments of the present invention, the retaining device may have a retaining piston which may be loaded with a force by means of compressed air or a motor drive, which force then moves the retaining piston toward the sample tube in opposition to a return force, in particular a spring force of a return spring.

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

[0046] An advantageous further development of these embodiments is characterized in that the retaining piston has retaining pins which can come into direct mechanical contact with the outer circumference of the sample tube.

[0047] By using a retaining pin, the material (usually an elastomer) of the sample tube can be freely selected. Due to the compressed air loading, the retaining piston itself must be strong in terms of material, ie have a high modulus of elasticity.

[0048] A first group of embodiments of the present invention is of particularly simple construction, wherein the holding device has holding arms which can clamp at least part of the outer circumference of the sample tube in a clamp-like manner, wherein the holding arms are preferably designed as clamping pliers or as two half shells which can fix the sample tube on the outer circumference of the sample tube from both sides.

[0049] This results in a symmetrical pressing force in the holding arm and the sample tube is well centered.

[0050] A second group of embodiments of the NMR spectrometer according to the invention is characterized in that the holding device has an iris diaphragm.

[0051] Advantageously, the symmetrical pressing force by the iris diaphragm is also achieved. The sample tube can be centered even better than with a holding arm.

[0052] In a third group of embodiments, the holding device has an advance element which, in the second operating position, blocks a movement of the sample tube out of the measuring position in a cap-like manner over the end of the sample tube opposite the gas inlet in the axial direction.

[0053] For example, the feed element can extend in and out in a radial direction relative to the z-axis of the NMR device.

[0054] The actuating force on the feed element is small, because it is only held in the axial direction. In addition, it is independent of the dynamic pressure due to the form-locking connection.

[0055] Finally, a fourth group of embodiments is characterized in that the holding device has a pneumatically actuatable, in particular inflatable, element which can act upon the sample tube with a radial pressure force in its measuring position.

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

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

[0058] The good coefficient of friction achieved with glass is advantageous here. The hose rests evenly on the test tube. This results in a large contact surface and particularly good centering of the sample tube.

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

[0060] Preferably, in the NMR spectrometer according to the invention, at least one shim coil for generating the H0 field is present, which surrounds the HF coil at a radial distance and is temperature-controlled, in particular, by means of a separate temperature control system.

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

[0062] (a) transferring the holding device to a first operating position;

[0063] (b) introducing a sample tube including a sample for NMR measurement through the hole into a measurement position of the sample tube in the measurement volume;

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

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

[0066] (e) checking, by means of the further sensor element, whether a second operating position of the holding device is currently present;

[0067] (f) releasing a temperature-controlled gas flow for temperature control of the NMR measurement sample;

[0068] (g) performing NMR measurement on the NMR measurement sample;

[0069] (h) Transferring the holding device into a third operating position and removing the sample cuvette from the spectrometer.

[0070] This allows error-free and reliable automation without the presence of a measuring technician. The measurement is traceable because, through positioning of the sensor system and correct temperature control, the same measuring conditions are possible for each sample in the measurement series. This is important for measurements in certified methods (GXP) and prevents incorrect operation.

[0071] Further advantages of the present invention are apparent from the description and the drawings. Likewise, the above-mentioned features and those to be further implemented can be used according to the present invention individually or in any combination. The embodiments shown and described are not to be understood as a final enumeration, but rather have exemplary features for describing the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0072] DETAILED DESCRIPTION AND APPENDED DRAWINGS OF THE PRESENT INVENTION

[0073] The invention is illustrated in the drawings and explained in more detail with reference to exemplary embodiments.

[0074] in:

[0075] Figure 1 A schematic vertical sectional view of an embodiment of an NMR spectrometer according to the invention is shown;

[0076] Figure 2a A schematic vertical section through the lower part of the sample tube in the temperature control tube is shown to illustrate the dynamic pressure and the condition F according to the invention. f >F Stau -F Gewicht ;

[0077] Figure 2b A schematic vertical section through a sample tube, shown shortened in a temperature control tube, is shown in order to illustrate the radial clamping of the sample tube on the contact surface of the holding device based on sliding friction;

[0078] Figure 3a A vertical section through the upper partial region of a sample tube in a temperature control tube is shown, including an embodiment of a holding device according to the invention, which comprises a holding piston, a return spring and a holding pin;

[0079] Figure 3b like Figure 3a Shown, however, without a sample tube in order to visualize the first and further sensing elements;

[0080] Figure 4a like Figure 3b Shown, however, with fewer details and including a retaining piston in an extended operating position for the passage of a sample tube;

[0081] Figure 4b like Figure 4a is shown, however, with fewer details and includes a retaining piston in an extended operating position for retaining a sample tube—not shown here—in a temperature control tube;

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

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

[0084] Figure 6b like Figure 6a It is shown, however, including an O-ring for holding a sample tube in the temperature control tube in the gas-filled operating state; and

[0085] Figure 7 like Figure 1 However, the illustration includes an NMR spectrometer according to the invention as well as a sample changer and a robot gripper as components of a robotic system. DETAILED DESCRIPTION

[0086] Figure Figures 1 to 7 A preferred embodiment of an NMR spectrometer 10 according to the invention is shown in various details in each of the schematic illustrations.

[0087] Such an NMR spectrometer 10 has a permanent magnet arrangement 11 for generating a B0 field in a measurement volume 12, a hole 13 through the center of the magnet for introducing an NMR measurement sample in a substantially cylindrical sample cuvette 14 which is closed at least on its underside, a shim system 26 and an HF coil 15 for exciting nuclear spins in the NMR measurement sample, wherein the HF coil 15 is arranged outside a cylindrical temperature control tube 16 which extends through the measurement volume 12 and into which the sample cuvette 14 can be introduced for NMR measurement in such a way that a continuous annular gap 17 is present between the inner circumference of the cylindrical temperature control tube 16 and the outer circumference of the sample cuvette 14, through which a temperature control gas for temperature control of the NMR measurement sample in the sample cuvette 14 can be guided from the temperature control system via a gas inlet 18, at least in NMR measurement operation. A fluid line 22 to the gas inlet 18 guides the temperature control gas through a dewar 21. The temperature-controlled gas is driven by a pump device of the NMR spectrometer 10 —not specifically shown in the drawing.

[0088] The present invention improves this NMR apparatus known per se and expands it with elements that are essential to the present invention:

[0089] The NMR spectrometer 10 according to the present invention is characterized in that, at the end of the sample tube 14 which is opposite the gas inlet 18 in NMR measurement operation, a holding device 19 is installed in the NMR spectrometer 10 and can be moved relative to the sample tube 14 into a measuring position of the sample tube. The holding device 19 is designed so that in a first operating position it does not contact the sample tube 14 so as to enable the sample tube to be introduced into its measuring position in the NMR spectrometer 10. In a second operating position, the holding device holds the sample tube 14 on its outer circumference in a force-locking and / or form-locking manner for carrying out the NMR measurement, with a force or static friction F acting axially on the sample tube 14. f The holding device 19 is designed so that in the second operating position the sample tube 14 is held in the measuring 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 so that in the second operating position the F f >F Stau -F Gewicht , where F Stau represents the buoyancy force on the sample tube 14 generated by the dynamic pressure of the temperature control gas flowing onto the sample tube 14 during NMR measurement operation, and F Gewicht represents the gravity of the sample tube 14 .

[0090] Strongly indicating Figure 1 A particularly simple first embodiment of the invention is shown in FIG.

[0091] Reliable spatial fixation of the sample tube 14 during the NMR measurement is achieved by means of a movable element of the holding device 19 which is specially developed for this purpose and is designed according to the principle of the invention. Preferably, the fixation takes place at the upper end of the sample tube 14, but in any case not in the measurement region, that is, not in the measurement volume 12. That is, the holding device 19 has a movable element which can be inserted into and extended from the sampling channel through which the sample tube 14 for the NMR measurement is introduced into the measurement volume 12 and is then removed again. If the sample tube 14 is in the sample head of the NMR spectrometer 10, the sample tube 14 is clamped and thus held in its measurement position by the insertion of the movable element.

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

[0093] Figure 2aThe highly schematic vertical section through the lower part of the sample tube 14 in the temperature control tube 16 shows the temperature control gas flowing from below into the sample tube 14. The temperature control gas correspondingly generates a dynamic pressure on the sample tube 14. However, in order to prevent the sample tube 14 from being pushed upward out of the measurement volume 12 by this permanently existing dynamic pressure during the NMR measurement, in NMR spectrometers according to the prior art, the weight F of the sample tube 14 is Gewicht It should not be less than the pressure F acting on the sample tube 14 from below by the dynamic pressure. Stau On the other hand, gravity F Gewicht It should not be greater than the pressure F Stau , because otherwise - in any case without further measures - the sample tube 14 would fall downwards out of the measurement volume 12. Therefore, in the prior art, the dynamic pressure is usually adjusted by adjusting the volume flow of the temperature control gas in such a way that the sample tube 14 remains suspended in its measurement position, i.e. F Stau ≈F Gewicht However, this then again obviates the parameter of the optimized temperature control gas volume flow rate for temperature control of the sample tube 14 .

[0094] By means of the design according to the invention of the novel holding device 19, the conditions F specified according to the invention for the holding force or static friction Ft acting on the sample tube 14 are maintained. f >F Stau -F Gewicht In the case of the NMR spectrometer 10, the important process parameter of the temperature control gas volume flow rate can be varied within a wide range in order to optimize the temperature control of the sample tube 14. In practice, the temperature control gas volume flow rate can thus now be freely adjusted within a wide range between approximately 1 l / min and up to 20 l / min, preferably between 3.5 l / min and 12 l / 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 in the measuring position of the sample tube 14 in the NMR spectrometer 10 according to the invention is usually selected 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 due to sliding friction is graphically illustrated in a highly schematic vertical section through the sample tube 14 in the temperature control tube 16, which is shown shortened here. klemm The radial action is on the sample tube 14. Therefore, with regard to the friction coefficient μ, the following must apply for the arrangement according to the invention:f =μ*F klemm .

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

[0098] exist Figure 3a 1 shows another design of a holding device 19 according to the invention in a vertical section through the upper partial area of ​​the sample tube 14 in the temperature control tube 16. This embodiment of the holding device 19 according to the invention has a holding piston 19a, a return spring 19b and a holding pin 19c.

[0099] The holding piston 19 a can be acted upon by means of compressed air or a motor drive, which force moves the piston in the direction of the sample tube 14 counter to the spring force of the return spring 19 b and presses the holding pin 19 c against it.

[0100] In order to detect the correct positioning of the sample cuvette 14 in the measurement space, a first sensor element 23 is provided for determining the presence of the sample cuvette 14 within the NMR spectrometer 10, such as in Figure 3b It can be seen in. Figure 3b Shown as Figure 3a The first sensor is preferably installed in such a way that the filling of the sample tube 14 can be reliably and unambiguously determined. For example, the sensor can have a grating.

[0101] Also in Figure 3b , another sensor element 24 for determining the current operating position of the holding device 19 is depicted. The second sensor displays when the holding pins 19 c are fully extended and are in an operating position in which they press against the sample tube 14 and hold it in position by clamping. The AT gas flow can only be released when this positioning confirmation is displayed by the second sensor, because otherwise the sample tube 14 cannot be positioned correctly.

[0102] exist Figure 4a Shown in Figure 3b The same situation, however with fewer details and including the retaining piston 19 a in the extended operating position for the passage of the sample tube 14 (again not shown here).

[0103] Figure 4b Shown with Figure 4aThe same device components, however, include a holding piston 19 a in an extended operating position for holding a sample tube 14 in a temperature control tube 16 —again not shown here for better visibility.

[0104] In other embodiments of the present invention - not shown in the drawings - the holding device 19 can have holding arms which can clamp at least part of the outer circumference of the sample tube 14 in a clamp-like manner, wherein the holding arms are preferably designed as clamping pliers or as two half shells which can fix the sample tube 14 on its outer circumference from both sides.

[0105] The advantage of these embodiments of the holding device is that the sample tube 14 can be held better centered in the center of the coil glass. However, the mechanism for the clamp requires somewhat more installation space.

[0106] In another group of embodiments (not shown), the holding device 19 has an iris diaphragm.

[0107] Furthermore, the holding device 19 can also have an advance element which, in the second operating position, blocks a movement of the sample tube 14 out of the measuring position in a cap-like manner via the end of the sample tube 14 opposite the gas inlet 18 in the axial direction.

[0108] In another set of alternative designs, the retaining device 19 can be - as in Figure 5 The vertical section through the upper partial region of the temperature control tube 16 without an introduced sample tube 14 has a pneumatically actuatable element 25 which can be inflated, in particular, and which applies radial pressure to the sample tube 14 in its measuring position.

[0109] The holding element is designed as a hose (here specifically as a pneumatically inflatable O-ring), which is guided around the sample tube. For clamping, the hose is loaded with compressed air. As a result, the hose expands and fixes the sample tube in its measuring position.

[0110] Figure 6a and 6b A schematic vertical section through a sample tube 14 - shown shortened here - in a temperature control tube 16 is shown in each case including a further embodiment of a holding device according to the invention, including an inflatable O-ring 25 ′ for passing the sample tube through it, here in a non-inflated operating state.

[0111] Figure 6a The pneumatically actuatable element 25 ′ is shown in an unfilled operating state for the passage of a sample tube 14 , whereas Figure 6bIn the figure, an O-ring 25' is shown in the inflated operating state for holding the sample tube 14 in the temperature control tube 16. That is, the inflatable hose is Figure 6a There is no compressed air loading relative to the ambient pressure (p relativ =0) and Figure 6b Compressed air loading (p relativ By widening the hose arranged annularly around the sample tube 14 , a holding force is generated on the sample tube 14 , which holds the NMR tube in a fixed position in the AT temperature control flow.

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

[0113] Figure 7 Finally, it is shown (attached to Figure 1 ) A sample changer 32 for the automated charging of the NMR spectrometer 10 with sample tubes 14, the sample changer having a storage container for storing a plurality of sample tubes and a device for transferring and removing the sample tubes 14 into or from the measurement volume 12. The sample changer within the meaning of the present invention is usually arranged on the top side of the NMR spectrometer 10 and is equipped for charging the spectrometer with different NMR tubes from the storage container and for removing the NMR tubes from the measurement volume 12 again after the measurement.

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

[0115] The features of all of the above-described embodiments of the invention can—in any case also mostly—be combined with one another.

[0116] References

[0117] Literature review for patentability assessment

[0118] [1] DE10 2019 212 508 A1

[0119] [2] DE10 2004 029 633 B4

[0120] [3] DE10 2018 205 535 B3 =EP3 561533B1 = US 10,782,369 B2

[0121] [4] EP3 715 893 B1 = ZL202010210645.3= US11,073,583 B2

[0122] [5] US10,436,859 B2

[0123] [6] EP3 561 533 B1

[0124] Reference numerals list

[0125] 10 NMR spectrometer

[0126] 11Permanent magnet device

[0127] 12. Measuring Volume

[0128] 13 magnet holes

[0129] 14 sample tubes

[0130] 15 HF Coil

[0131] 16 Thermostatic tube

[0132] 17 Ring-shaped gap

[0133] 18 Gas inlet

[0134] 19 Holding device

[0135] 19a Holding piston

[0136] 19b return spring

[0137] 19c retaining pin

[0138] 20 contact surface

[0139] 21 Dewar

[0140] 22 Conduit to gas inlet

[0141] 23 First sensing element

[0142] 24 Another sensing element

[0143] 25; 25' Pneumatically operated components

[0144] 26 Shimming System

[0145] 30Automatic device system

[0146] 31Robot gripper arm

[0147] 32 Sample Changer

Claims

1. An NMR spectrometer (10) comprising an NMR magnet system having a permanent magnet arrangement (11) for generating a B0 field in a measurement volume (12) and a hole (13) through the center of the magnet for introducing an NMR measurement sample in a substantially cylindrical sample tube (14) which is closed at least on its underside; and an HF coil (15) for exciting nuclear spins in the NMR measurement sample, wherein: The HF coil (15) is arranged outside a cylindrical temperature control tube (16), which extends through the measurement volume (12), and the sample tube (14) can be introduced into the temperature control tube for NMR measurement, so that a continuous annular gap (17) is present between the inner circumference of the cylindrical temperature control tube (16) and the outer circumference of the sample tube (14), through which a temperature control gas for temperature control of the NMR measurement sample in the sample tube (14) can be introduced from the temperature control system via a gas inlet (18) at least during NMR measurement operation. The invention is characterized in that the sample tube (14) is in contact with the gas inlet (18) during NMR measurement operation. A holding device (19) is installed in the NMR spectrometer (10) at the end opposite to the body inlet (18) and can be moved relative to the sample tube (14) to a measuring position of the sample tube. The holding device (19) is designed so that in a first operating position, the holding device does not contact the sample tube (14) so ​​as to enable the sample tube to be introduced into the measuring position of the sample tube in the NMR spectrometer (10). In a second operating position, the holding device locks the sample tube (14) on the outer circumference of the sample tube in a force-locking and / or form-locking manner for NMR measurement, with a force or static friction F acting axially on the sample tube (14). f The holding device (19) is designed to hold the sample tube in the measuring position and to release the sample tube (14) again in the third operating position for removal from the NMR spectrometer (10), and the holding device (19) is designed so that in the second operating position the sample tube (14) is held in the measuring position and the holding device (19) is designed to hold the sample tube (14) in the measuring position and to release the sample tube (14) again in the third operating position for removal from the NMR spectrometer (10). F f >F Stau -F Gewicht , Among them, F Stau 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 NMR measurement operation, and F Gewicht represents the gravity of the sample tube (14).

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

3. The NMR spectrometer according to any one of the preceding claims, characterized in that 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) has a radial opening width of between 0.1 mm and 1 mm, preferably between 0.15 mm and 0.3 mm, in the measuring position of the sample tube (14).

4. The NMR spectrometer according to any one of the preceding claims, characterized in that During NMR measurement operation of the NMR spectrometer (10), the temperature control gas has a volume flow of at least 1 l / min and a maximum of 20 l / min, preferably 3.5 l / min to 12 l / min.

5. The NMR spectrometer according to any one of the preceding claims, characterized in that A sample changer (32) is provided for automatically charging the NMR spectrometer (10) with sample tubes (14), the sample changer having a storage container for storing a plurality of sample tubes (14) and a device for transferring 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) simultaneously functions as a device for transferring and removing sample tubes (14), and the NMR spectrometer (10) and the sample changer (32) are preferably components of a robotic system (30) comprising a robot gripper arm (31).

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

8. The NMR spectrometer according to any one of the preceding claims, characterized in that There is a first sensing element (23) for determining the presence of the sample cuvette (14) within the NMR spectrometer (10).

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

10. The NMR spectrometer according to any one of claims 1 to 5 and 7 to 9, characterized in that The holding device (19) has a holding piston (19a) which can be acted upon by compressed air or a motor drive with a force which then moves the holding piston (19a) toward the sample tube (14) counter to a restoring force, in particular a spring force of a restoring spring (19b).

11. The NMR spectrometer according to any one of claims 1 to 10, characterized in that The holding device (19) has holding arms which are capable of clamping at least a portion of the outer circumference of the sample tube (14) in a clamp-like manner, wherein the holding arms are preferably designed as clamping pliers or as two half shells which are capable of fixing the sample tube (14) on its outer circumference from both sides.

12. The NMR spectrometer according to any one of claims 1 to 9, characterized in that The holding device (19) has an iris diaphragm.

13. The NMR spectrometer according to any one of claims 1 to 5 and 7 to 9, characterized in that The holding device (19) has an advance element which, in a second operating position, blocks a movement of the sample tube (14) out of the measuring position in a cover-like manner over an end of the sample tube (14) opposite the gas inlet (18) in an axial direction.

14. The NMR spectrometer according to any one of claims 1 to 9, characterized in that The holding device (19) has a pneumatically actuatable, in particular inflatable, element (25; 25') which can act upon the sample tube (14) with a radial pressure in its measuring position.

15. Method for operating an NMR spectrometer (10) according to one of claims 9 to 14 comprising a sample changer (32) according to claim 5, characterized in that Here are the steps: (a) transferring the holding device (19) into a first operating position; (b) introducing a sample tube (14) containing a sample for NMR measurement through the hole (13) into a measurement position of the sample tube in the measurement volume (12); (c) detecting the presence of the sample tube (14) in the measuring position by means of a first sensor element (23); (d) fixing the sample tube (14) by means of the holding device (19); (e) checking the current presence of the second operating position of the holding device (19) by means of a further sensor element (24); (f) releasing a temperature-controlled gas flow for temperature control of the NMR measurement sample; (g) performing NMR measurement on the NMR measurement sample; (h) The holding device (19) is transferred into a third operating position and the sample cuvette (14) is removed from the spectrometer (10).

Images