WO2011124339A1

WO2011124339A1 - Device for generating pressures in sample containers

Info

Publication number: WO2011124339A1
Application number: PCT/EP2011/001546
Authority: WO
Inventors: Jürgen Kempf; Hans Robert Kalbitzer; Alexander Meier
Original assignee: Universität Regensburg
Priority date: 2010-03-31
Filing date: 2011-03-28
Publication date: 2011-10-13
Also published as: DE102010017279A1

Abstract

The invention relates to a device for generating pressures in a fluid in a sample container 12, in particular a sample container 12 for use in high-pressure spectroscopy. The device comprises a sample container 12 for receiving the fluid and a piston 18 displaceably supported relative to the sample container 12, such that the volume enclosed in the sample container 12 changes as the piston 18 is displaced. The piston is non-positively connected to a magnetic or magnetizable element 34. The device further comprises an electromagnet 36 disposed near the magnetic or magnetizable element 34, so that a force can be applied to the piston 18 by the magnetic field thereof by means of the magnetic or magnetizable element 34, by which force the piston 18 can be displaced relative to the sample container 12 in order to generate a pressure in the sample container 12. Finally, the device comprises a control device 42 for actuating the electromagnet 36, such that a prescribed pressure curve over time is generated in the sample container 12.

Description

Device for generating pressures in sample containers

FIELD OF THE INVENTION

The present invention relates to a device for generating pressures in a fluid in a sample container, in particular a sample container for use in high-pressure spectroscopy. Furthermore, the invention relates to a device for examining sample fluids by means of high-pressure spectroscopy and a method for spectroscopic examination see, in particular NMR spectroscopy examination of a sample.

BACKGROUND OF THE INVENTION In many biology, medicine, chemistry and physical chemistry processes fluid samples are being tested under high pressures. An example of such a method is high-resolution, high-pressure NMR spectroscopy. High-pressure NMR spectroscopy makes it possible to characterize conformational states of biomedically interesting macromolecules at high pressure with high resolution, which occur only in low concentrations under normal pressure and therefore not or at most difficult to detect. An example of such states are intermediate states in protein folding and misfolding, which are also commonly referred to as folding "intermediates" in German literature, and which play a major role in enzymatic catalysis For example, with the co-operation of one of the inventors with high-pressure NMR investigations, it was possible to identify rare intermediates for the prion protein which is responsible for the development of BSE (see Kremer, W., Kachel, N., Kuwata, K., Akasaka, K., & Kalbitzer, HR (2007): Species specific differences in the intermediate states of human and Syrian hamster prion protein detected by high press NMR spectroscopy, J. Biol. Chem., 282, 22689-22698 ).

In principle, variable fluid pressures in the range from 0.1 MPa to over 100 MPa, in some cases up to 600 MPa, are required for such investigations. In addition to the generation of high fluid pressures and the generation of rapid pressure jumps is of great interest. As shown in the dissertation by Martin Reinhard Arnold, "Hochdruck Hochdruck NMR", University of Regensburg (2002), rapid pressure jumps allow kinetic processes to be measured and traced at atomic resolution.

However, in addition to high-pressure NMR spectroscopy, high pressures are also required in other analysis or spectroscopy methods. Examples include Fourier transform infrared spectroscopy or UV spectroscopy. High-pressure liquid chromatography (HPLC) also requires pressures in the range of a few 10 MPa and currently up to 100 MPa. Here, however, the generation of pressures of over 100 MPa and their temporal stabilization would be of great interest. Further applications of sample fluids under high pressures are conceivable, for example in chemistry (eg reaction kinetics), in materials science (eg surface treatment, investigation of alloys and mixed fluids) and in physics (eg investigation of dynamic processes at high pressures, etc.). US 6,507,101 B 1 discloses an NMR cell system for NMR spectroscopy on supercritical fluids. The NMR cell system includes an external pumping system that can be used to generate hydraulic pressure in the cell. In the cell, pressures of up to 30 MPa are produced at temperatures of up to 400 ° C to produce pressure and temperature conditions beyond the critical point to produce a supercritical fluid.

Another high-pressure cell for NMR measurements is disclosed in US 6,486,672 Bl. Usually, high pressures are generated hydraulically in NMR cells. The NMR cells are closed by a membrane on which the hydraulic medium acts from outside. The resistance of the membrane is usually the upper limit for the pressures that can be generated.

To generate the hydraulic pressure usually spindle presses or piston pumps are used. With screw presses, hydraulic pressures can be controlled with sufficient accuracy. however, they do not allow rapid dynamic pressure changes and, in particular, do not allow for rapid pressure jumps of the order of 10 MPa / ms. For pressure jump applications, a pre-pressure is usually generated and then modulated by rapid opening and closing of high-pressure valves. However, this requires a relatively large amount of equipment. In addition, spindle presses are not suitable for rapidly repeating pressure jumps, as they are necessary in spectroscopy, because of the too slow Druckauf construction. With piston presses, the desired pressures can be quickly produced, but not sufficiently precise control.

An alternative to piston pumps or screw presses is the generation of pressure with piezoelectric elements, which can basically be controlled precisely and quickly, but the problem here is the relatively low stroke of piezoelectric elements. This has the consequence that, due to the compressibility of the hydraulic medium and the sample fluid within the available stroke hardly pressures of more than a few 10 MPa can be generated.

From WO 2009/010971 A2 a piezo-hydraulic compressor is known in which a hydraulic power transmission is used to increase the working stroke of the piezoelectric element. The compressor is designed to generate pressure oscillations in a working medium that are used in a Sterling process for cold generation. Nevertheless, even in this pressure generator, the maximum pressure is limited by the maximum stroke of the piezoelectric element, the compressibility of the pressure medium and not least by the durability of the membrane. In addition, piezoelectric elements with a, despite hydraulic translation, large required stroke are relatively expensive.

DE 10 2007 053 549 discloses an electromagnetic hydraulic pump in which an armature is mounted axially displaceable radially within a coil. The anchor has a diameter which is greater than the diameter of an axially fixedly connected to this anchor

Piston, which projects axially into a central recess of a pole core. On the inner wall of the recess is a sealing ring, so that in the fluid-filled centric recess, a hydraulic pressure can be produced. In the hydraulic pump, a compression device for leakage losses of hydraulic fluid is provided. For applying a hydraulic Pressure, the armature is pulled by a magnetic coil in the direction pointing to the pole core.

SUMMARY OF THE INVENTION

The invention has for its object to provide an apparatus and method for generating pressures in a fluid in a sample container, in particular a sample container for use in high-pressure spectroscopy, which allow the generation of high pressures and pressure jumps with high pressure change rates by simple means.

This object is achieved by a device according to claim 1 and a method according to claim 23. Advantageous developments are specified in the dependent claims.

According to the invention, the device comprises a sample container for receiving the fluid with a piston which is mounted so displaceable relative to the sample container that changes the volume enclosed in the sample container during displacement of the piston. The piston is non-positively connected to a magnetic or magnetizable element. The device further comprises an electromagnet which is arranged in the vicinity of the magnetic or magnetizable element such that a force can be exerted on the piston by means of its magnetic field via the magnetic or magnetizable element, by means of which the piston is movable relative to the sample container in order to move to generate a pressure to the sample container. Finally, the device comprises a control device for actuating the electromagnet such that a predetermined temporal pressure profile is generated in the sample container.

According to the invention, the piston is driven by the frictional connection with the magnetic or magnetizable element directly from the electromagnet. The frictional connection between the piston and the magnetic or magnetizable element may be a simple mechanical coupling, which is formed for example via a push rod, but unlike the prior art requires no interposition of a hydraulic medium. This can avoid problems with the compressibility of the hydraulic medium. In addition, the design is extremely simple, robust and compact enough to be ideally combined with a variety of analytical equipment. By actuating the piston via the magnetic or magnetizable section and the electromagnet, the force with which the piston is pushed in the direction of the sample container can be directly controlled by the coil current in the electromagnet. Since movement of the piston changes the volume of the fluid trapped in the sample container, the pushing force of the piston corresponds to a pressure within that fluid. In other words, the pressure in the sample container can be controlled simply and directly via a simple control of the coil current. According to a first embodiment of the invention, the force required for pressure generation is exerted on the fluid via an axially displaceable piston which at the same time closes the sample container in cooperation with the sealing means. Therefore, unlike in the prior art, the sample container does not have to be closed by a membrane, which usually can be a weak point in the generation of high pressures. In an advantageous development of the first embodiment, the sealing means are formed by a sealing ring, which is arranged between a portion of the piston and a portion of the sample container. In this case, the sealing ring preferably has an oblong-oval cross section whose diameter is greater in a first direction than in a second direction, the first direction being parallel to the displacement direction of the piston. Such a cross-sectionally oval configuration of the sealing ring is particularly suitable for sealing the piston against the sample container over the entire required stroke of the piston.

In an advantageous development of the first embodiment, the sample container on an annular support on which the sealing ring rests with its side facing the sample container, and a radially inwardly facing peripheral surface adjacent to the annular bearing surface and on which the sealing ring with its radially outer Side is present. Further, the sealing ring preferably surrounds a portion of the piston, so that the sealing ring rests with its radially inner side on the portion of the piston. In this case, on the piston one of said annular bearing surface opposite surface is formed, against which the sealing ring abuts with its side facing away from the sample container.

In this embodiment, the sealing ring between two radially spaced circumferential surfaces and two axially spaced surfaces is constrained and thus ensures a secure sealing between piston and sample container. It should be noted that the further the piston is displaced in the direction of the sample container, the more the sealing ring is compressed, so that the sealing effect is expediently increased with increasing pressures in the sample container.

In the region of the section surrounded by the sealing ring, the piston preferably comprises a radially acting piezo element, by the actuation of which at least a portion of the sealing ring can be pressed against the peripheral surface of the sample container facing radially inward. By controlling this radially acting piezoelectric element, therefore, the sealing effect of the sealing element can be selectively further enhanced, for example, in situations in which particularly high pressures are to be generated in the sample container. The notion of a "radially acting piezoelectric element" merely indicates that the piezoelectric element has at least one expansion component in the radial direction and, above all, serves to delimit the term from an axial piezoelectric element described below.

According to a second embodiment, the sample body is closed by an elastic membrane and the piston has a radially acting piezoelectric element, by the actuation of a portion of the membrane, which is located between an inserted into the sample container portion of the piston and a wall of the sample container, against the Wall of the sample container can be pressed. In the activated state of the piezoelectric element, the membrane is effectively relieved by being wedged between the piston and the sample container wall. In this way, high pressures can be combined with a sufficient lifetime of the membrane. It is important, however, that the radially acting piezoelectric element is driven synchronously with the piston movement. However, this is technically feasible down to the microsecond range.

In an alternative embodiment, instead of the radially acting piezoelectric element for sealing, an annular, axially acting piezoelectric element may be provided which surrounds the opening of the interior of the sample container covered by the membrane radially on the outside and by the actuation of which the membrane is pressed against the sample container. As a result, the membrane is pressed firmly against the sample container in an annular area surrounding the opening of the sample container and thus sealed against it. Preferably, the control means is programmed to drive the electromagnet to produce pressure jumps of 10 MPa / ms or more and / or maximum pressures of 100 MPa or more, preferably 400 MPa or more in the fluid, the control being simply controlled by the controller Coil current can be done. As will be explained in more detail below with reference to an exemplary embodiment, it is possible with the device according to the invention to generate such pressures and pressure change rates.

Preferably, the cross-sectional area of an opening of the sample container closed by the piston is less than 3 mm ^2, and more preferably less than 1.5 mm. With such a small cross-sectional area, the desired pressures beyond 100 MPa can be produced with very moderate forces, which can be readily produced with an electromagnet. The volume of the sample container is preferably less than 5 ml, more preferably less than 3 ml. Preferably, the force which can be exerted by the electromagnet via the magnetic or magnetizable element on the piston is more than 100 N, preferably more than 170 N. Preferably applies to the force F, which is exercisable by the electromagnet via the magnetic or magnetizable element, and the cross-sectional area A _{q of} the opening of the

F

Sample container, which is closed by the piston-> 1 OOMPa, preferably -> 400MPa.

Preferably, the piston has an axially acting piezoelectric element, by the actuation of which the piston can be extended or shortened in the axial direction. An extension or shortening of the piston in the axial direction has a similar effect as the axial displacement of the piston, so that the pressure in the sample container can be modulated by controlling the axial piezoelectric element. For example, this structure allows to preset a certain pressure by moving the piston and then to modulate it by the operation of the axial piezoelectric element. Since in this case the piezoelectric element is not responsible for the complete pressure build-up, the initially mentioned limited stroke of a piezoelectric element in combination with the displaceable piston is unproblematic. The combination of a piston individually controllable for displacement and an individual one controllable axial piezoelectric element allows both the generation of very fast pressure jumps as well as a very precise adjustment of pressures.

In a particularly preferred embodiment, the axially acting piezoelectric element can be used to generate ultrasonic waves, for example with frequencies in the 100 kHz range. As a result, in addition to the high pressures set by the electromagnet, ultrasonic waves can be generated in the sample liquid, opening up a new and promising field of application. For example, the chemical reaction kinetics in liquids can be influenced by ultrasound. In the context of the invention, this can be combined in combination with the very high pressures and pressure jumps that can be generated.

A particularly interesting use of the axially acting piezoelectric element as an ultrasonic source results in connection with high-pressure NMR spectroscopy. The inventors suggest that excitation with ultrasound waves can induce a change in the topology or the conformational equilibrium of proteins, which can be detected directly by NMR spectroscopy. With the topology (eg, the secondary, tertiary, and quaternary structures of the proteins), physical and chemical properties of the proteins, such as hydrophobic properties, solubility, and the like, also change. In this context, it can be expected that the use of the piezo element as an ultrasound source opens up completely new possibilities for investigating the behavior and properties of proteins in NMR spectroscopy.

Another application for ultrasonic waves relates to an alternative type of pressure measurement in which the pressure dependence of the propagation velocity of sound waves in liquids is utilized.

Specifically, the propagation velocity of sound waves is inversely proportional to the root of the liquid density, which in turn increases with pressure. For this reason, it is possible to draw conclusions about the fluid pressure via transit time measurements of ultrasonic waves. Instead of explicitly measuring transit times, the inventors further propose to determine the propagation velocity (and via this the pressure) over the resonant frequency. For this purpose, the end of the sample vessel opposite the piezoelectric element can be designed so that it efficiently reflects the sound waves. Depending on the pressure or density of the sample medium would then result in a slightly different resonant frequency, which are detected can. A standing wave can be obtained at an excitation frequency of 100 kHz in a sample container having a length of at least about 7 mm, and at a resonance frequency of 1 MHz with a sample container length of at least about 0.7 mm. Thus, ultrasonic waves in the 100 kHz range are suitable for the formation of standing waves in sample containers of a typical size. In addition, the sample containers can be specially designed for the formation of desired ultrasonic resonant modes.

Although the aforementioned ultrasonic range is of particular interest, other periodic excitations in the range of 0.1 Hz to 10 THz are also of interest for the investigation of proteins.

Preferably, the axially acting piezoelectric element is actuated by the same control device as the above-mentioned electromagnet in order to modulate the pressure preset by means of the electromagnet to a desired total pressure.

In an advantageous development, means are furthermore provided in order to transmit the voltage applied to the axially acting piezoelectric element as current pressure value to the control device. In this embodiment, the axially acting piezoelectric element is used not only as an additional pressure generator, but at the same time as a pressure sensor. For example, with the aid of the axially acting piezoelectric element, the pre-pressure generated with the aid of the electromagnet can be measured and thereby precisely adjusted. Moreover, with the aid of the inverse piezoelectric effect, i. the deformation due to an applied electrical voltage, an additional pressure modulation are generated. The piezoelectric pressure modulation can be performed in the microsecond range. Alternatively, the actual pressure in the liquid can also be measured directly at the piezoelectric element by causing its deformation, which is caused by the electromagnetically generated pre-pressure and the piezoelectric pressure modulation, to be contactless, e.g. is detected by optical distance sensors. Alternatively, an additional piezoelectric sensor element may be provided in the sample container, which is designed EMC compatible.

Preferably, the electromagnet comprises a rod-shaped ferromagnetic coil core, which is arranged coaxially with the magnetic or magnetizable element. Furthermore, the electromagnet is preferably bipolar controllable. As a result, the piston can not only be pushed in the direction of the sample container to generate a pressure, but also actively retracted to produce a very rapid pressure drop in the sample container. As a result, both positive and negative pressure jumps can be generated with large increase or decrease rates. Preferably, for the time constant τ of the electromagnet: r = μμ ₀ η ² -R <50 ms, particularly preferably <10 ms.

Here is / the length of the coil, A is the pole face of the coil core and μ its permeability. R denotes the electrical resistance of the coil and n its number of turns. With such a choice of the coil and core parameters, desired time constants can be obtained which allow pressure jumps in the millisecond range.

In an advantageous embodiment, the non-positively connected to the piston magnetizable element is formed by a ferromagnetic core, which is surrounded by a coil.

Alternatively, however, a magnetic element may be provided in the form of a permanent magnet.

Preferably, the magnetic or magnetizable element is connected to the piston via a non-magnetic guide element. Due to the non-magnetic guide element, the location of the force generation, d. H. the electromagnet is located some distance from the sample container. In practice, the guide element requires little more space than a hydraulic line, but avoids the problems described above in terms of the compressibility of the working medium and the need to provide a membrane. By the guide member, the solenoid can also be accommodated in a place where there is enough space available. For example, in applications involving samples subject to static or alternating electromagnetic fields, such as in NMR applications, the electromagnet may be located sufficiently far from these electromagnetic fields to avoid field disturbance.

Preferably, the electromagnet and the magnetic or magnetizable portion are surrounded by an electromagnetic shield, in particular a shield comprising a shielding fleece, shielding foils, or shielding composite plates of a Ni-Fe alloy or a functionally similar alloy. The Ni-Fe alloy may contain other components in lower concentrations, such as Cu and Mo. This can avoid EMC problems. By means of such a shield, it can be achieved, for example, that the electromagnet and the magnetic or magnetizable section do not disturb the NMR magnetic field in the region of the sample in a function-impairing manner.

BRIEF DESCRIPTION OF THE FIGURES FIG. 1 shows a schematic representation of a high-pressure NMR spectrometer with a device for generating pressures according to a development of the invention.

Fig. 2 shows a schematic longitudinal sectional view of a portion of a sample container, which is closed by a piston and a sealing ring.

Fig. 3 shows a similar longitudinal sectional view as Fig. 2, but in which, in addition, an axially acting and a radially acting piezoelectric element is provided.

FIG. 4 shows an electromagnet and a magnetizable element for use in the pressure generating device of FIG. 1. FIG.

Fig. 5 shows an electromagnet and a magnetic element for use in the pressure generating device of Fig. 1. Fig. 6 shows an alternative sealing of the sample container by means of a membrane which is supported by piezoelectric activation.

Fig. 7 shows a further alternative sealing of the sample container by means of a membrane which is supported by piezoelectric activation

DESCRIPTION OF A PREFERRED EMBODIMENT

FIG. 1 shows a schematic representation of components of a high-pressure NMR spectrometer 10. The NMR spectrometer 10 comprises a sample container 12 with an interior space 14 which can be filled with a sample fluid. The sample container is in a strong static magnetic field, which is generated by schematically illustrated NMR coils 16. The sample container is closed by a piston 18, which cooperates with a sealing ring 20. As shown in the enlarged and somewhat more detailed illustration of FIG. 2, the piston 18 has an elongated portion 22 which projects into the interior 14 of the sample container 12. The piston 18 is displaceable in the axial direction of the sample container 12, so that it protrudes different distances in the interior 14 of the sample container 12 and thereby changes the volume enclosed in the sample container 12 when moving the piston. The axial displacement direction is indicated by an arrow 25 in FIG.

2, the sealing ring 20 has an elongate oval cross-section, the diameter of which is greater in the direction parallel to the displacement direction 25 than in the direction transverse thereto. The piston 18, the sealing ring 20 and the sample container 12 cooperate in such a way that the gap between the piston 18 and the container 12 is sealed over the entire stroke length of the piston 18, which is required for pressure generation. This is favored by the oval cross section of the sealing ring 20.

As can be seen in more detail in FIG. 2, the interior 14 of the sample container 12 has a step-shaped enlargement, which in the representation of FIG. 2 comprises a horizontal annular support surface 24 and a vertical peripheral surface 26. The sealing ring 20 rests with its side facing the sample container 12 on the annular bearing surface 24 and is located with its radially outer side of the radially inwardly facing peripheral surface 26 at. Furthermore, the sealing ring 20 lies with its radially inner side on the elongated piston portion 22 and with its side facing away from the sample container 12 at one of the annular bearing surface 24 opposite surface 28 of the piston 18 at. The sealing ring 20 is constrained more strongly between the four surfaces mentioned, the further the piston 18 is displaced in the direction of the sample container 12. This means that the sealing effect expediently increases, the higher the pressure generated by the piston 18 in the inner space 14 of the sample container 12.

Referring again to Fig. 2, the piston 18 is followed by a non-magnetic guide rod 30 formed of plastic, for example. The guide rod 30 is mounted axially displaceably in schematically illustrated guides 32. At the 1, a magnetizable or magnetic section 34, which is marked in the schematic view of FIG. 1 by dotted filling, is arranged in the FIG. 1 end of the guide rod 30. In the vicinity of the magnetic or magnetizable portion 34, an electromagnet 36 is arranged. The electromagnet 36 comprises a rod-shaped ferromagnetic core 38, which is surrounded by a coil 40. The ferromagnetic core 38 is disposed coaxially with the magnetic or magnetizable portion 34. The coil 40 or its power supply (not shown) can be controlled bipolar via a control device 42. The control device 42 may be, for example, a PC on which a corresponding control program is stored.

4 shows by way of example a schematic structure of the electromagnet 36 and the section 34, which in this case is a magnetizable section. 4 shows a schematic representation of the coil 40 surrounding the ferromagnetic coil core 38. The magnetizable section 34 is also here formed by a ferromagnetic core, which is arranged at the end of the non-magnetic guide rod 30 remote from the sample container 12 (see FIG. 1). In Fig. 4, a housing 44 made of plastic or other solid, non-magnetic material is shown, in which the spool core 38 fixed and the guide rod 30 is slidably mounted with the magnetizable portion 34, as indicated by the arrow 46. The magnetizable portion 34 is magnetized by a coil 48 having a polarization opposite to that of the electromagnet 36.

Instead of a magnetizable portion 34, however, a permanent magnet 50 may be provided as a magnetic element, as shown in Fig. 5. In this case, the coil 48 of Fig. 4 can be omitted. The remainder of FIG. 5 is consistent with FIG. 4 and will therefore not be described again.

The electromagnet 36 and the magnetizable portion 34 and permanent magnet 50 are surrounded in the illustration of Fig. 4 and Fig. 5 by an electromagnetic shield 52, which is represented by a dashed line. This shield consists of a nickel-iron alloy, also known as mu-metal. In addition to the main components Nickel and iron may also be other constituents such as Cu and Mo. Mu metal has a high permeability which causes the magnetic flux of low frequency magnetic fields to concentrate in the material. The shield 52 may be in the form of a Abschirmvlieses, shielding or Abschirmverbundplatten. The shield 52 is important so that the magnetic field in the NMR spectrometer 10 is not disturbed by the electromagnet 36 and the magnetizable portion 34 and the permanent magnet 50.

The following describes the operation of the pressure generating device. By applying a suitable current to the coil 40 of the electromagnet 36, an axial force is exerted on the magnetized portion 34 and the permanent magnet 50, respectively, by which the piston 18 is pushed over the guide rod 30 in the direction of the sample container 12. In this case, the elongated portion 22 of the piston 18 penetrates into the interior 14 of the sample container 12 and thus reduces the volume of the inner space 14, whereby the pressure is increased therein. The pressure is proportional to the thrust, d. H. proportional to the current in the coil 40 of the electromagnet 36 and to the magnetic flux density in the section 34 which, in the case of the embodiment of FIG. 4, is in turn proportional to the flow of current through the coil 48. By controlling the current in the coil 40 of the electromagnet 36 and optionally in the coil 48 for magnetizing the magnetizable element 34, therefore, the pressure generated in the sample container 12 can be easily controlled.

The control is done via the control unit 42, which is shown schematically in Fig. 1. A special feature of the invention is that can be generated by a simple control of the coil current or the coil currents a virtually arbitrary predetermined time pressure curve. This predetermined temporal pressure curve may comprise both a constant pressure maintained at a precise value and the generation of predetermined pressure jumps in the millisecond range. The limiting factor for the shortness of the pressure jumps is the time constant τ of the electromagnet, which corresponds to the quotient of the self-inductance and the resistance R of the coil, ie τ = μμ ₀ η ² -,

IR

where μ is the permeability and A is the pole face of the spool core 38, n corresponds to the number of turns and / of the coil length. With a coil length / = 10 cm, a core radius r of 3 cm, n = 1000 turns and a permeability μ = 1000, time constants of less than 50 ms, preferably less than 10 ms, can easily be generated. Preferred values for the resistance of the coil are 500 to 1000 Ω.

Furthermore, with the construction of FIG. 4, currents of less than 1 A can readily produce thrust forces of 200 N or more. This means that with a cross-sectional area of the opening of the sample container 12 closed by the piston 18, for example 1 mm, pressures of 200 MPa or more can be produced. When using a ferromagnetic higher-permeability coil core or a more-coil coil, the pressure in the sample container 12 may also be 400 MPa or even more than 600 MPa. In this case, pressure jumps at a rate of 10 MPa / ms and at higher currents rates of over 50 MPa / ms can be achieved, both positive pressure jumps and negative, for which the polarity is reversed at the coil 40 of the electromagnet 36, so the piston 18 is actively retracted.

The device described has a number of particular advantages. The pressure generator formed by the device is extremely small and compact and therefore can be easily integrated into spectroscopy devices or other testing or analysis devices. It allows the production of electronically controlled pressure profiles of almost arbitrary shape, limited only by maximum pressures in the range of several 100 MPa and pressure change rates in the range of several 10 MPa / ms. As a result, the pressure generating device is particularly ideally suited for high pressure NMR spectroscopy. Due to the spatial separation of solenoid 36 and piston 18 EMC problems in the sample area can be largely avoided, especially when the shield 52 described is used. Unlike a conventional arrangement with a hydraulic medium, the force of the electromagnetic actuator can be mechanically transferred to the sample fluid, and the stroke of the actuator is therefore not limited by the compressibility of a hydraulic medium. Another advantage is that the membranes commonly used in hydraulic applications can be dispensed with. Since the membranes usually represent a weak point, especially at high pressures, this represents a significant design advantage with regard to the generation of very high pressures. With the device, a stroke of the piston 18 of several millimeters can be achieved, with which it is possible to produce pressures of several 100 MPa for samples with liquid volumes of one or a few milliliters, even if the sample has, for example, the compressibility of water. The arrangement of the sealing ring 20 between the surfaces 24, 26, 28 and the outer periphery of the elongated portion 22 of the piston 18 allows a secure seal over the entire stroke of the piston 18. Of particular advantage is that the sealing effect increases, the deeper the elongated Section 22 of the piston 18 is inserted into the interior 14 of the sample container 12, that is, the higher the pressure in the sample container 12.

The pressure generating device described can be used especially for high-pressure NMR spectroscopy and optical analysis methods such as Fourier transform infrared spectroscopy or UV spectroscopy. A further advantageous use is in the field of high-pressure liquid chromatography. However, the use of the device is not limited to these applications, but a variety of applications are conceivable in which the production of precisely controlled pressure profiles is of importance. An example would be a mobile pressure generator with adjustable pressure for calibration of pressure sensors. In addition to a calibration with a constant output pressure as possible, the pressure generator allows to generate predetermined pressure profiles or pressure jumps, whereby the dynamic characteristics of pressure sensors could be checked.

An advantageous development of the invention is shown in FIG. Fig. 3 shows a similar sectional view of the piston 18 and a portion of the sample container 12 as in Fig. 2, and the corresponding components are denoted by the same reference numerals. The essential difference from the embodiment of FIG. 2 is that the elongate portion 22 of the piston 18 is formed of a radially acting piezoelectric element 54 and an axially acting piezoelectric element 56. The radially acting piezoelectric element 54 can be controlled via a schematically illustrated control line 58 by the control device 42 so that it expands in a direction transverse to the piston axis and thereby a portion of the sealing ring 20 radially outward against the radially inwardly facing circumferential surface 26th suppressed. As a result, the sealing effect of the sealing ring 20 is further enhanced. The term "radially acting" piezoelectric element 54 is intended to indicate that the expansion direction of the piezoelectric element 54 has at least one radial component, but that this expansion would take place only in the radial direction. and this radial component is effective in the additional sealing effect.

The axially acting piezoelectric element 56 causes the piston 18, namely its elongated section 22, to be lengthened or shortened in the axial direction, as a result of which the pressure in the interior 14 of the sample container 12 can additionally be modulated. As a result, with the same mechanical stroke (essentially limited by the sealing effect of the sealing ring 20), a greater effective stroke can be generated. It is also possible to modulate a pre-set by the solenoid 36 pressure with the axially acting piezoelectric element 56, for example, to fine tune a pressure or to produce even greater pressure jumps and modulation frequencies than are possible with the solenoid 36 alone.

A signal line 60 for driving the axially acting piezoelectric element 56 is shown schematically under reference numeral 60. It should be noted that the axially acting piezoelectric element 56 can be used not only to generate a pressure but also to measure the applied pressure. Therefore, it is advantageous if, via the signal line 60, the electrical voltage or piezoelectric charge applied to the axially acting piezoelectric element 56 can also be transmitted to the control device 42 as the current pressure value. Thus, a pre-pressure generated by means of the electromagnet 36 can be measured by means of the axially acting piezo element 56 and precisely adjusted in response to the measurement. After that, the axially acting piezo element 56 can be switched as an actuator in order to use the inverse piezo effect, i. H. a deformation due to an applied electrical voltage to generate a modulation of the form. This piezoelectric pressure modulation can be performed in the microsecond range.

As mentioned above, the current pressure in the liquid can be measured directly on the basis of the mechanical deformation of the piezoelectric element, in particular contactless, z. B. via optical distance sensors. Alternatively, an additional piezoelectric element or another pressure-sensitive element could be provided as a pressure sensor in the sample container. In the embodiment of FIG. 3, the control device 42 is expediently the same control device as that for controlling the electromagnet 36. However, this is not absolutely necessary. Fig. 6 shows a schematic representation of a part of a device according to the above-mentioned second embodiment, in which the sample container 12 is sealed by a membrane 62. In FIG. 6, the same or corresponding components are denoted by the same reference numerals as in the previous FIGS. 1 to 5.

As can be seen in Fig. 6, the sample container 12 is closed at its upper end by a membrane 62. 6 shows in solid lines the piston 18 in a retracted position in which it exerts no pressure on the membrane and the fluid in the interior of the sample container 12. The piston 18 comprises, as described above, both an axially acting piezoelectric element 56 for pressure modulation and a radially acting piezoelectric element 54, the function of which in connection with the diaphragm 62 will be described below.

Fig. 6 also shows in a dashed line in a schematic manner a state in which the piston 18 has been displaced in the direction of the sample container 12 and penetrated into the inner space thereof to generate a pressure in the interior. As can be seen in the dashed representation, in this case, the membrane 62 is stretched. In this case, considerable tensile loads and loads due to the fluid pressure in the gap between the piston 18 and the wall of the sample container 12 would usually occur - in particular on the vertical sections of the diaphragm 62 in the illustration of FIG. 6. However, according to the embodiment of FIG. 6, the radially acting piezoelectric element 54 is activated in the state of maximum advancement of the piston 18 so as to expand radially, thereby pressing the vertical portion of the diaphragm 62 against the inner wall of the sample container 12. This relieves the diaphragm, and in particular its vertical sections in the illustration of FIG. 6, and improves the seal. This piezoelectrically assisted sealing makes higher pressures and pressure rates achievable than with a simple membrane.

It is of course essential in this embodiment that the radially acting piezoelectric element 54 is driven at the right time for crimping the membrane. These Control is also preferably adopted by the same controller 52 shown in the previous drawings. This allows the feed of the piston, the axial modulation of the piston length over the axially acting piezoelectric element 56 and the pinching of the membrane between the radially acting piezoelectric element 54 and the sample container 12 can be easily synchronized.

Another embodiment with a membrane 62 for sealing the sample volume 14 is shown in FIG. The membrane 62 is clamped with a mounting ring 66 on the sample container 12. The diaphragm is pushed down by operation of the piston 18 to thereby pressurize the sample fluid. For better sealing of the interior 14 of the sample container 12, an annular, axially acting piezoelectric element 64 is provided, which is arranged on the side facing away from the sample of the membrane 62. The radially inner edge of the annular piezoelectric element 64 approximately coincides with the radially outer edge of the inner space 14 of the sample container 12. When the plunger 18 is pushed down to pressurize, the annular piezoelectric element 64 is actuated to expand in the axial direction, to support the attachment ring 66, thereby ensuring a tight connection between the sample container 12 and the membrane 62 around the sample liquid , By the annular piezoelectric element 64, a very good seal between the membrane 62 and the sample container 12 can be ensured even if adjacent surfaces of the membrane 62 on the one hand and the sample container 12 on the other hand are not perfectly flat or the mounting ring 66 is not perfectly parallel to the surface of the sample container 12 is arranged. It should be noted that upon actuation of the piston 18 extremely high pressures are produced which would cause escape of the sample liquid even through the smallest gaps or passages. Due to the local pressure force along the annular piezoelectric element 64, however, a secure seal is ensured. As further shown in FIG. 7, a flange 68 is provided, on which a spring 70, which is shown only symbolically, is supported, with which the piston 18 is biased in the direction of the sample container 12. The bias causes the force applied to the piston 18 by the solenoid 36 (not shown in FIG. 7) to produce a predetermined pressure. bring to the biasing force of the spring 70 is reduced. In this way, larger pressure peaks can be achieved with the same power of the electromagnet.

Further, an optical distance sensor 72 is provided on the flange 68, with which the distance between the flange 68 and the piston 18 can be measured. As a result, the deflection of the piston 18 can be determined, from which in turn, if necessary with reference to reference measurements, the pressure in the sample container 12 can be determined. The distance sensor 72 can therefore be used as a simple and precise means for determining the pressure in the interior 14 of the sample container 12.

Although preferred embodiments have been shown and described in detail in the drawings and foregoing description, this should be considered as illustrative and not restrictive of the invention. It should be understood that only the preferred embodiments are shown and described and all changes and modifications that are presently and in the future within the scope of the invention should be protected.

LIST OF REFERENCE NUMBERS

10 high-pressure NMR spectrometers

12 sample containers

14 Interior of the sample container 12

16 coils for generating the NMR magnetic field

18 pistons

20 sealing ring

22 elongated portion of the piston 18th

24 annular bearing surface

25 displacement direction

26 radially inwardly facing peripheral surface

28 of the annular surface 24 opposite surface

30 guide bar

32 Guide for guide rod 30

34 magnetic or magnetizable section

36 electromagnet

38 spool core

40 coil

42 control device

44 leadership

46 Displacement direction of the piston

48 coil

50 permanent magnet

52 shielding

54 radially acting piezoelectric element

56 axially acting piezoelectric element

58 signal line

60 signal line

62 membrane

64 annular, axially acting piezoelectric element

66 fixing ring

68 flange

70 spring

72 distance sensor

Claims

claims

Device for generating pressures in a fluid in a sample container (12), in particular a sample container (12) for use in high-pressure spectroscopy, comprising:

a sample container (12) for receiving the fluid,

a piston (18) slidably mounted relative to the sample container (12) such that the volume trapped in the sample container (12) changes upon displacement of the piston (18);

the piston (18) is non-positively connected to a magnetic or magnetizable element (34, 50),

an electromagnet (36) which is arranged in the vicinity of the magnetic or magnetizable element (34, 50) such that a force can be exerted on the piston (18) through its magnetic field via the magnetic or magnetizable element (34, 50), by which the piston is movable relative to the sample container (12) to generate pressure in the sample container (12), and

a control device (42) for activating the electromagnet (36) in such a way that a predetermined chronological pressure profile is generated in the sample container (12).

Apparatus according to claim 1, wherein the sample container (12) by a piston (18) and a cooperating with the piston (18) sealing means (20) is closable.

Apparatus according to any one of the preceding claims, wherein the sealing means is formed by a sealing ring (20) disposed between a portion of the piston (18) and a portion of the sample container (12).

Apparatus according to claim 3, wherein the sealing ring (20) has an elongated oval cross-section whose diameter is greater in a first direction than in a second direction, the first direction being parallel to the direction of displacement of the piston (18).

Apparatus according to claim 3 or 4, wherein the sample container (12) has an annular bearing surface (24) on which the sealing ring (20) with its the sample container (12) facing side rests, and having a radially inwardly facing peripheral surface (26) adjacent to the annular bearing surface (24) and against which the sealing ring (20) bears with its radially outer side.

Apparatus according to claim 5, wherein the sealing ring (20) surrounds a portion (22) of the piston (18), so that the sealing ring rests with its radially inner side on the portion (22) of the piston 18,

wherein on the piston (18) one of the annular bearing surface (24) opposite surface (28) is formed, against which the sealing ring (20) abuts with its side facing away from the sample container (12).

Device according to one of Claims 3 to 6, in which the piston (18) has a radially acting piezoelement (54) in the region of the section surrounded by the sealing ring (22), by the actuation of which at least a portion of the sealing ring (20) is in contact with the radially inwardly facing peripheral surface of the sample container (12) can be pressed.

Apparatus according to claim 1, wherein the sample container (12) by an elastic

Membrane (62) is closed and

the piston has a radially acting piezoelectric element (54), by the actuation of which a portion of the membrane (62) located between a portion of the piston (18) inserted into the sample container (12) and a wall of the sample container (12) abuts the wall of the sample container (12) can be pressed, or

an annular, axially acting piezoelectric element (64) is provided which surrounds the opening of the inner space (14) of the sample container (12) covered by the membrane (62) radially on the outside and by actuation of which the membrane can be pressed against the sample container (12) ,

Device according to one of the preceding claims, wherein the frictional connection between the piston (18) and the magnetic or magnetizable element (34, 50) is a mechanical coupling without the interposition of a hydraulic medium.

10. Device according to one of the preceding claims, wherein the control means (42) is programmed to control the electromagnet (36) that in the fluid pressure jumps by 10 MPa / ms or more and / or maximum pressures of 100 MPa or more, preferably 400 MPa or more are generated.

11. Device according to one of the preceding claims, wherein the cross-sectional area of an opening of the sample container (12), which is closed by the piston (18), or into which the piston penetrates, less than 3 mm 2, preferably LESS than 1 5 mm 2 and / or the volume of the sample container is less than 5 ml, preferably less than 3 ml.

12. Device according to one of the preceding claims, wherein the force exerted by the electromagnet (36) via the magnetic or magnetizable element (34, 50) on the piston (18), more than 100 N, preferably more than 400 N is.

13. Device according to one of the preceding claims, in which for the force F from the electromagnet 36 via the magnetic or magnetizable element (34, 50) on the piston (18) is exercisable, and the cross-sectional area A _{q of} an opening of Pro

F

container (12), which is closed by the piston (18) applies: -> \ 00MPa,

F

preferably-> 400 Pa.

14. Device according to one of the preceding claims, wherein the piston (18) has an axially acting piezoelectric element (56), by the actuation of the piston (18) in the axial direction can be extended or shortened.

15. The apparatus of claim 14, wherein the axially acting piezoelectric element (56) from the control device (42) is controllable to modulate a by means of the electromagnet (36) preset pressure, and in particular such that ultrasonic waves are generated in the sample medium ,

16. The apparatus of claim 15, wherein means are provided to transmit the applied voltage to the axially acting piezoelectric element (56) as the current pressure value to the control device (42).

17. Device according to one of the preceding claims, wherein the electromagnet (36) comprises a stabfbrmigen ferromagnetic coil core (38) which is arranged coaxially with the magnetic or magnetizable element (34, 50).

18. Device according to one of the preceding claims, wherein the electromagnet (36) is bipolar actuated.

19. The apparatus of claim 17 or 18, wherein the coil core (38) has a pole face A and a magnetic permeability μ and is surrounded by a coil having a length 1, n turns and with an electrical resistance R, wherein for the time

7 A

constant τ of the electromagnet applies: τ - μμ ₀ η - 100ms, preferably <50ms.

1R

20. Device according to one of the preceding claims, wherein the magnetizable element (34) is formed by a ferromagnetic core, which is surrounded by a coil (48).

21. Device according to one of the preceding claims, wherein the magnetic element is formed by a permanent magnet (50).

22. Device according to one of the preceding claims, wherein the magnetic or magnetizable element (34, 50) via a non-magnetic guide element (30) with the piston (18) is connected.

23. Device according to one of the preceding claims, wherein the electromagnet (36) and the magnetic or magnetizable portion (34, 50) of an electromagnetic shield (52) is surrounded, in particular a shield (52) comprising a Abschirmvlies, Abschirmfolien or Shielding composite plates of a Ni-Fe alloy or a function-like alloy comprises.

24. Device according to one of the preceding claims, wherein a spring element (70) is provided, which biases the piston (18) in the direction of the sample container (12).

25. Device (10) for the examination of sample fluids by high-pressure spectroscopy, in particular by high-pressure NMR spectroscopy at pressures above 100 MPa, preferably above 400 MPa, comprising

a spectroscopic device, in particular an NMR spectrometer, which is suitable for receiving a sample container (12), and

a device for generating pressures in a fluid in the sample container (12) according to one of claims 1 to 23.

26. A method for spectroscopic examination, in particular NMR spectroscopy examination of a sample, comprising the following steps:

Filling a sample fluid into a sample container (12),

- Closing of the sample container (12) having a piston (18) and a sealing means (20) which cooperates with the piston (18), wherein the piston (18) relative to the sample container (12) is mounted so displaceable that in Sample container enclosed volume during displacement of the piston (18) while maintaining the seal by the sealant (20) changes,

- Controlling an electromagnet (36) which is arranged in the vicinity of a non-positively connected to the piston (18) magnetic or magnetizable element (34, 50) to move the piston (18) relative to the sample container (12), so in the sample container (12) a pressure is generated, which corresponds to a predetermined temporal pressure curve, and

- Determining spectra, in particular NMR spectra, while the sample fluid is exposed to the predetermined temporal pressure curve.

27. The method of claim 26, wherein the solenoid is controlled so that in the fluid pressure jumps by 10 MPa / ms or more and / or maximum pressures of 100 MPa or more, preferably 400 MPa or more are generated.

28. The method of claim 26 or 27, wherein by means of a piezoelectric element, which is arranged in the region of the sample-side end of the piston, ultrasonic waves in the sample medium are generated, in particular ultrasonic waves in the frequency range of 10 kHz to 1 MHz.