WO2005095945A2

WO2005095945A2 - Sample container for ultrasound measurements

Info

Publication number: WO2005095945A2
Application number: PCT/EP2005/003182
Authority: WO
Inventors: Theodor Funck; Daniel Gau
Original assignee: Tf Instruments Gmbh
Priority date: 2004-03-31
Filing date: 2005-03-24
Publication date: 2005-10-13
Also published as: KR20060130217A; CA2561176A1; DE102004015830A1; WO2005095945A3; EP1733221A2; JP2007530961A

Abstract

The invention relates to a sample container (10) for ultrasound measurements, which comprises a container component (20) forming a sample receiver. Said container component (20) comprises a wall material (21) the composition and/or thickness of which is selected such that ultrasound waves can be coupled from the outside through the wall material (21) into the sample container (10) with maximum transmission. The invention also relates to methods for the ultrasound measurement on a sample using such a sample container, to methods for producing the sample container and to an assembly including the sample container and a resonator chamber.

Description

Sample holder for ultrasonic measurements

The invention relates to sample containers for ultrasound measurements with the features according to the preamble of claim 1, methods for ultrasound measurement on flowable samples with the features of the preamble of claim 16 and methods for the production of said sample containers.

It is known to detect material properties of flowable samples by high-resolution measurements of the ultrasound speed and / or the ultrasound absorption in the sample. The measurement is typically carried out in a resonator chamber for receiving the sample. US Pat. No. 5,983,723 proposes to excite the walls of the resonator chamber with ultrasonic transducers attached to the outside to produce ultrasonic vibrations. However, this technique can have disadvantages due to the complicated structure of the resonator chamber and the adjustment of the ultrasonic transducers. For a trouble-free measurement of only the sample arranged in the resonator chamber, it has also proven to be advantageous if the sample is in direct contact with the surface of the ultrasonic transducer, which usually consists of a metal. For example, ultrasound transducers in resonator chambers according to DE 101 37 679 are located on the inner walls of the resonator chamber and in direct contact with the sample.

However, ultrasonic measurement with direct transducer contact through the sample has a number of disadvantages. In many cases, an interaction of the sample with the metal surface of the ultrasonic transducer cannot be ruled out. For example, substances from the sample can be adsorbed on the transducer surface or a corrosive flow of the sample onto the transducer surface. In both cases, the transducer surface is changed so that the measurement results can be falsified. This is particularly disadvantageous for the desired high-resolution measurement of the sound properties. Another problem is that adsorbed substances are often difficult to remove from the metal surfaces of the transducers. This is particularly critical in the case of measurements on biological samples, since the measurement must not lead to undesired carryover of biological material between different samples.

For some substances, the high-resolution measurement of the ultrasound speed in the solid phase is important. The tracking of phase transitions solid / liquid or vice versa also provides important information about the physical properties of a substance by measuring the ultrasound speed. So far, such measurements have only been possible using ultrasound pulse measurement methods. However, the resolution of these methods is very limited for small sample dimensions.

As a further disadvantage of conventional ultrasound measurements, it is known in practice that considerable measurement errors can be caused if gas residues are also enclosed in the resonator chamber in addition to the sample. For example, when filling in liquid samples, air can be trapped, particularly on the ultrasonic transducers. To avoid air pockets, the sample can be filled into the resonator chamber particularly slowly and gently. However, this is disadvantageous because of the large amount of time required under practical conditions.

The object of the invention is to provide an improved technique for ultrasonic measurements on fluid samples, with which the disadvantages of the conventional resonator chambers are overcome. In particular, undesired interactions between the sample and the transducer surface are to be avoided, the filling of the sample into the resonator chamber without gas inclusions is facilitated and accelerated, and contamination of the chamber by the sample is to be avoided.

This object is achieved by a sample holder, a combination of a sample holder and a resonator chamber, a method for ultrasound measurement and a method for producing the sample holder with the features of claims 1, 16, 18 or 23. Advantageous embodiments and applications of the invention result from the dependent claims.

In terms of the device, the invention is based on the general technical teaching of providing a sample container for samples which is intended to be arranged with the sample in a resonator chamber and its wall material at least in partial areas which are arranged in the resonator chamber adjacent to the ultrasonic transducers when the sample container is used , is designed for transmission of ultrasound with minimal loss. The inventors have found that when using a wall material optimized in terms of its composition and / or thickness for maximum transmission (eg greater than 99%), a falsification of the measurement results is surprisingly avoided, even though the ultrasonic transducer and the sample are separated from each other by an additional foreign material (wall material). The provision of a sample container according to the invention, which can be inserted into the resonator chamber, advantageously provides the solution to all of the problems mentioned above. By separating the sample and transducer surface, contamination or changes in the wall Interface excluded. Adhesion of harmful or dangerous substances on the transducers or transfer of substances to follow-up samples is excluded. Limitations with regard to the accuracy of the ultrasound measurement are avoided. The sample container can be filled outside the resonator chamber. A large number of samples can be prepared, for example, in a large number of sample containers, while the measurements are carried out in parallel in the resonator chamber. Time losses due to the bubble-free filling of samples into the chamber are avoided.

A particular advantage lies in overcoming the above-mentioned problem when measuring on solid samples or samples containing solid-liquid phase transitions.

The inclusion of a solid, which is smaller than the dimension of the ultrasonic resonator measuring cell, in the sample holder allows the coupling to the transducers of the resonator measuring cell, even with solid samples. This solid can be located within the sample container in a coupling medium that differs from the coupling substance outside the sample container. In this way, phase transitions can also be examined with the involvement of liquid phases. By coordinating the various coupling media, it is possible to optimize the impedance ratios while reducing the reflection losses and thus to improve the coupling of the sound field into the sample. The sample container according to the invention is therefore suitable both for fluid, flowable samples and for samples which contain a fluid and a solid component.

If, according to a preferred embodiment of the invention, a container part of the sample container according to the invention is made entirely of the maximum sound-permeable wall material stands, there may be advantages for the handling of the sample container when inserted into a resonator chamber.

According to a further preferred embodiment of the invention, the wall material consists at least partially of a flexible material. The wall material is flexible and pliable and can therefore advantageously be optimally adapted to the inner walls of the resonator chamber of a measuring arrangement. If the container part forms a flexible bag according to a preferred variant, an adaptation of the wall material to the inner wall of the resonator chamber and in particular to the ultrasound transducers in the resonator chamber can be simplified. According to a further variant, the flexible wall material has its own dimensional stability. The container part advantageously has an inherent shape in the emptied and in the filled state, which can facilitate the handling of the sample container (in particular the insertion into a resonator chamber).

According to a further preferred embodiment of the invention, the sample container is equipped with a holder to which the container part made of the preferably flexible wall material is attached. The holder can be advantageous for handling the sample container z. B. have during transport from a filling device into the resonator chamber and take on additional functions. The holder can be formed in one piece with the container part. However, it is preferred to provide the holder as a separate component. If, for example, the holder comprises a stopper which projects into the container part of the sample holder, the holder also forms a closure of the sample holder.

If the plug is provided with a through opening according to a further modification of the invention, the Loading the sample container with a liquid sample can be advantageously simplified.

According to a further embodiment of the invention, the holder can be equipped with a closure element which fits in a form-fitting manner in the through opening of the stopper and can be inserted or screwed into it. In the case of a completely filled sample container, by pushing the closing element forward, the closure element can advantageously exert an overpressure on the sample in the sample container, under the effect of which the container part is stretched out and unfolds completely. The closure part is, for example, a screw which interacts with a suitable internal thread in the through opening.

Further advantages for flexible use and quick assembly of the sample container can result if the container part is detachably attached to the holder. Particular advantages result from the use of a fixing ring with which the container part is attached to the stopper.

For the desired ultrasound transmission, the wall material of the container part of a sample container according to the invention preferably has a predetermined acoustic impedance, which is selected as a function of the acoustic impedance of the sample to be measured. Since the sample container has a simple structure and the container part can be produced inexpensively as a disposable item, appropriately adapted container parts or sample containers can be prepared for measurements on different samples. For numerous practical applications, it is particularly advantageous if the acoustic impedance of the transducer material equals the acoustic impedance of the sample and the impedance of the coupling substance (e.g. 1.5 x 10 ⁶ kg m ^"2 s ^_1 ). The acoustic impedance is preferably selected in the range from approximately 1.0 to 2.0 x 10 ⁶ kg m ^{~ 2} s ^_1 .

According to a modified embodiment of the invention, it is not absolutely necessary to select the wall material in relation to a specific acoustic impedance. As an alternative or in addition to the impedance matching, it is possible to choose the thickness of the wall material in such a way that a minimum reflection and a maximum transmission are formed by the wall material. It is known from the monograph by L. Bergmann ("The Ultrasound", S. Hürzel Verlag, Stuttgart, 1954, page 15 ff.) That the permeability of the wall material is a function of the wall thickness and the speed of sound in the wall Depending on the operating conditions, when there are several wall thicknesses, maxima of permeability occur, so that the wall thickness can advantageously be chosen according to acoustic and design considerations.

For practical applications, a wall thickness in the range from 10 μm to 1 mm, in particular less than 100 μm, for. B. 10 microns to 20 microns. According to an advantageous variant of the invention, it can in particular be provided that the wall thickness is less than or equal to 1/10 of the wavelength used for the ultrasound measurement. The inventors have found that, even with small wall thicknesses, sample containers can be formed which, surprisingly, are sufficiently stable for use under practical conditions, in particular for filling, a possible transport and / or measurement.

The wall material preferably consists of a polymer film, such as. B. from acetate, polypropylene or polyethylene base. The polymer films used preferably have an op- table transparency, so that the sample can be observed while it is being filled.

According to a further, particularly advantageous embodiment of the invention, a coupling substance is provided on the outside of the container part. This improves the acoustic coupling of the sample container to the surface of the ultrasonic transducer. The coupling substance can comprise, for example, water or an ultrasound contact gel known per se.

The above-mentioned is device-related. The object is further achieved by providing a combination of a sample container with the features described here and a resonator chamber known per se. The sample container can be firmly connected to the resonator chamber or, for example, be detachably fixed at the upper edge thereof, in order to ensure, for example, the desired protection of the ultrasonic transducers against the sample for a whole series of measurements.

In relation to the method, the above-mentioned object is achieved by the provision of a method for ultrasound measurement, in which the sample to be measured is filled into the sample container with the features described here and in a resonator chamber in which the sample from the ultrasound transducers, in particular through the wall material with the maximum Transmission is separated, subjected to a known ultrasound measurement. According to a first variant of the method according to the invention, the sample container can be loaded with the sample if the sample container has not yet been arranged in the resonator chamber. In this case, there may be advantages in terms of avoiding gas influences in the sample container. Alternatively, it can be provided that the sample container is not loaded until it is arranged in the resonator chamber. In this case, you can lower requirements are placed on the stability of the wall material of the container part.

Preferred embodiments of the method according to the invention are directed to the measurement on fluid, flowable samples or on samples which contain a fluid, flowable and a solid component.

Another independent object of the invention described here is a manufacturing method for producing the sample holder with the properties described here from a polymer film. According to a first embodiment of the manufacturing method according to the invention, an immersion method is provided in which a temperature-controllable stamp is immersed in a polymer solution, so that a polymer layer forms on the stamp surface, which is then subjected to drying. The temperature of the stamp is set according to the invention to a predetermined drying temperature at which the wall material is in the flowable state. As a stamp is preferably a body with an outer shape that corresponds to the desired inner shape of the container part and a polished surface, for. B. made of stainless steel, used internally by an electric heater or externally, for. B. is heated by warm air. According to a modified embodiment of the production process, an extrusion or drawing process is provided in which a film made of the desired wall material is spread out on a perforated die. A stamp is passed through the hole in the perforated die and the surface of the film is arranged in accordance with the shape of the container part. In this case too, the desired drying temperature of the stamp is set. Further details and advantages of the invention will become apparent from the following description of the accompanying drawings. Show it:

1 shows a schematic sectional illustration of an embodiment of a sample container according to the invention,

FIGS. 2, 3: schematic sectional representations of sample containers according to the invention in resonator chambers (without a representation of the coupling substance), and

FIGS. 4 and 5: schematic sectional representations of devices for producing sample containers according to the invention.

The invention is described below by way of example with reference to preferred embodiments of sample containers according to the invention with a round or substantially rectangular cross section, which are equipped for resonator chambers with two flat or curved ultrasound transducers. It is emphasized that the implementation of the invention is not limited to these designs, but that other geometric shapes and / or sizes can generally also be implemented.

According to FIG. 1, the sample container 10, which is illustrated schematically in a sectional view, comprises a container part 20 and a holder 30. The container part 20, which is illustrated with a thick solid line for reasons of clarity, but in practice consists of an extremely thin-walled wall material 21 the bag-shaped wall material 21 and a collar 22 formed in one piece with the wall material.

The wall material consists, for example, of cellulose acetate film, polyvinyl acetate, polypropylene or polyethylene. The thickness of the wall material 21 is selected, for example, in the range from 10 μm to 20 μm. The volume of the container part 20 is 170 μl in the example shown.

The bracket 30 is a stopper made of a thermoplastic material (e.g. PVC). The plug 31 projects into the container part 20 on its underside. On its lower side facing the container part 20, the stopper 31 has a circumferential projection on which the outside diameter of the stopper 31 increases from a value corresponding to the inside diameter of the container part 20 to the desired outside dimension of the upper side of the holder 30. The container part 20 is fastened to the projection 31 with a circumferential O-ring 34.

The plug 31 has an axial bore 32, on the upper part of which a thread 33 is provided and which widens towards the container part 20 in accordance with a conical surface 35.

A method according to the invention for ultrasound measurement on a sample with the illustrated sample holder 10 comprises the following steps. First the sample container is filled with the liquid sample. For this purpose, for example, the sample is filled into the container part 20 through the through opening 32 using a pipette or a syringe. The injection takes place up to a fill level that falls in the area of the thread 32. A screw (not shown) is then screwed into the thread 33 as a closure element. Under the effect of doing so on the liquid Applied pressure, the wall material 21 of the container part 20 is tightened. When this pressure is exerted, the tightness of the sample container 10 can also be visually observed. If undesired pores or cracks should appear, they are immediately recognizable by an escaping liquid. The corresponding sample is discarded. After the sample container has been successfully loaded, it is inserted into a resonator chamber. Since the outer shape of the container part 21 is selected to be essentially the same as the inner shape of the resonator chamber, can. the sample container 10 are simply inserted into a resonator chamber.

A coupling substance is located in the resonator chamber for coupling between the ultrasonic transducers 41 of the resonator chamber 40 (see FIGS. 2, 3) and the sample container 20. Alternatively, this is provided in the resonator chamber 40 before the sample container 20 is inserted. Then the actual ultrasound measurement follows. Details of the ultrasound measurement and the sound parameters used are not described here, since these are known per se. For example, resonance frequencies are recorded in the liquid-filled resonator chamber.

FIGS. 2 and 3 show a schematic sectional view of the combination of the sample container 20 with the sample 1 (shown in broken lines) and the resonator chamber 40 with the ultrasound transducers 41. For example, flat ultrasound transducers 41 (FIG. 2) or curved ultrasound transducers 41 (FIG 3) be provided.

FIGS. 4 and 5 schematically illustrate a dipping device 50 and a pulling device 60 for producing the container parts 20 of the sample containers 10 according to the invention. The dipping device 50 provides that a temperature-controlled rer stamp 51 is immersed one or more times in a liquid polymer solution 52 and finally withdrawn. The polymer layer remaining on the stamp surface is dried at the predetermined drying temperature. Depending on the polymer material and the layer thickness formed (polymer concentration in solution 52), the drying temperature is empirically determined in a material-specific manner by means of test series.

In the pulling device 60 (FIG. 5) it is provided that the temperature-controlled stamp 61 is pushed through a perforated die on which the film 63 of the polymer material for forming the container part 20 is located.

After the wall material 21 has been formed on the stamp 51 or 61, the wall material as the container part 20 is stripped off from the stamp 51 or 61 and connected to the holder 30 with the O-ring 34 (see FIG. 1).

The features of the invention disclosed in the above description, the drawings and the claims can be of importance both individually and in combination for the implementation of the invention in its various configurations.

Claims

claims

1. Sample container (10) for ultrasonic measurements, with a container part (20) which forms a sample holder, characterized in that the container part (20) has a wall material (21), the composition and / or thickness of which is selected such that ultra- Sound waves with maximum transmission from the outside through the wall material (21) can be coupled inwards into the sample container (10).

2. Sample container according to claim 1, wherein the container part (20) consists entirely of the wall material (21).

3. Sample holder according to claim 1 or 2, wherein the wall material (21) is flexible.

4. Sample container according to claim 3, wherein the wall material (21) forms a flexible bag.

5. Sample container according to claim 3, wherein the wall material (21) is dimensionally stable in the emptied state of the container part (20).

6. Sample holder according to at least one of the preceding claims, wherein the container part (20) has a holder (30).

7. Sample holder according to claim 6, wherein the holder (30) has a plug (31) projecting into the container part (20).

8. A sample container according to claim 7, wherein the stopper (31) has a passage opening (32).

9. Sample holder according to claim 8, wherein the through opening (32) has an internal thread (33).

10. sample container according to claim 7, 8 or 9, wherein the container part (20) with a fixing ring (34) on the stopper (31) is releasably attached.

11. Sample container according to at least one of the preceding claims, in which the wall material (21) of the container part

(20) has an acoustic impedance which is chosen equal to the acoustic impedance of a sample in the sample container (10).

12. Sample container according to claim 10, in which the acoustic properties of the wall material (21) of the container part (20) are matched to the properties of the coupling substance and to the content of the container.

13. Sample container according to at least one of the preceding claims, wherein the wall material (21) of the container part (20) has a thickness which is less than or equal to 1/10 of the wavelength of the ultrasonic waves.

14. Sample holder according to claim 12, wherein the thickness of the wall material (21) is selected in the range 1 μm to 1 mm.

15. Sample container according to at least one of the preceding claims, in which the wall material (21) consists of polymer film.

16. resonator chamber (40) for ultrasonic measurements, in which a sample container (10) is arranged according to at least one of the preceding claims.

17. resonator chamber according to claim 16, wherein a coupling substance is arranged between the container part (20) of the sample container (10) and the inner wall of the resonator chamber (40).

18. A method for ultrasound measurement on a sample, comprising the steps of: filling the sample (1) into a sample container (10) according to at least one of the preceding claims 1 to 14, and - ultrasound measurement of the sample in a resonator chamber (40), the sample (1) is separated from the surfaces of the ultrasonic transducers (41) by the wall of the sample container and the coupling substance.

19. The method according to claim 18, wherein the sample container (10) with the filled sample (1) is inserted into the resonator chamber (40).

20. The method according to claim 19, in which the sample (1) is filled into the sample container (10) inserted into the resonator chamber (40).

21. The method according to any one of claims 18 to 20, wherein a fluid, flowable sample is filled into the sample container (10).

22. The method according to any one of claims 18 to 20, wherein a sample is filled into the sample container (10), which consists of at least one fluid, flowable component and at least one solid component is composed.

23. A method for producing a sample container according to at least one of the preceding claims 1 to 16, in which the container part (20) is formed on a stamp (51, 61) by dipping or pulling, the stamp being heated to a predetermined drying temperature ,