Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method

Abstract

The present invention is directed to a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample, comprising a cartridge body having at least one measurement cavity formed therein and having at least one probe element arranged in said at least one measurement cavity for performing a test on said sample liquid; and a cover being attachable on said cartridge body; wherein said cover covers at least partially said at least one measurement cavity and forms a retaining element for retaining said probe element in a predetermined position within said at least one measurement cavity. The invention is directed to a measurement system and a method for measuring viscoelastic characteristics of a sample liquid.

Claims

1. A device for evaluation of hemostasis, comprising: a plurality of cavities, including a first cavity, a second cavity and a third cavity, wherein each of the plurality of cavities comprises one or more reagents therein; ductwork, including an inlet for receiving a test sample, wherein the ductwork is in communication with each of the plurality of cavities, whereby each of the plurality of cavities is configured to receive, via the ductwork, a portion of the test sample, wherein the first cavity comprises one or more reagents configured for extrinsic activation of the coagulation cascade; wherein the second cavity comprises (i) one or more reagents configured for extrinsic activation of the coagulation cascade and (ii) one or more reagents configured for suppressing thrombocyte function; and wherein the third cavity comprises one or more reagents configured for intrinsic activation of the coagulation cascade.

2. The device of claim 1, wherein the one or more reagents configured for suppressing thrombocyte function include cytochalasin D.

3. The device of claim 1, wherein the one or more reagents configured for extrinsic activation of the coagulation cascade include tissue factor.

4. The device of claim 3, wherein the one or more reagents configured for suppressing thrombocyte function include cytochalasin D.

5. The device of claim 1, wherein the one or more reagents configured for intrinsic activation of the coagulation cascade include a Hagemann factor.

6. The device of claim 1, wherein the plurality of cavities further comprises a fourth cavity.

7. The device of claim 6, wherein the fourth cavity comprises one or more reagents configured for testing platelet aggregometry.

8. The device of claim 1, wherein the device is a cartridge configured for use in conjunction with a measuring system.

9. The device of claim 8, wherein the measuring system is configured to measure over time changes in viscoelastic properties of the portion of the test sample in each of the cavities.

10. The device of claim 9, wherein the measuring system is configured to receive the cartridge in a pre-determined orientation whereby the cartridge in the pre-determined orientation is aligned with a plurality of detectors, each of the plurality of detectors associated with a respective cavity.

11. The device of claim 9, wherein the changes in viscoelastic properties of the portion of the test sample are measured by the measuring system detecting changes in amplitude of an oscillating motion excitation of the portion of the test sample.

12. The device of claim 11, wherein the oscillating motion excitation of the portion of the test sample is achieved mechanically via a plurality of probes interfaced with the measuring system.

13. The device of claim 9, wherein the measuring system is configured to measure clotting time for the portion of the test sample in each of the cavities.

14. The device of claim 9, wherein the measuring system is configured to measure clot formation time for the portion of the test sample in each of the cavities.

15. The device of claim 9, wherein the measuring system is configured to measure a maximum clot firmness for the portion of the test sample in each of the cavities.

16. The device of claim 9 wherein the measuring system includes a light beam detector.

17. The device of claim 16, wherein the light beam detector is used to detect changes in amplitude of an oscillating motion excitation of the portion of the test sample.

18. The device of claim 9, wherein the measurement system is configured to measure changes in viscoelastic properties of the portions of the test samples based on a periodic induced motion in the portions of the test sample.

19. The device of claim 18, wherein the periodic induced motion is a periodic rotational motion by a shaft.

20. A method for using the device of claim 9, the method comprising measuring over time changes in viscoelastic properties of the portion of the test sample in each of the cavities and comparing the measured changes in viscoelastic properties of the portion of the test sample in the first chamber with the measured changes in viscoelastic properties of the portion of the test sample in the second chamber.

21. The method of claim 20, further comprising assessing a fibrinogen deficiency on the basis of the comparison.

22. A method for using the device of claim 9, the method comprising measuring over time changes in viscoelastic properties of the portion of the test sample in each of the cavities and assessing a fibrinogen deficiency on the basis of such measurements.

23. A method for using the device of claim 9, the method comprising performing at least three measurements in parallel within the plurality of cavities using a combination of agonists and antagonists of different parts of the coagulation cascade.

24. The device of claim 8, wherein the measuring system includes control apparatus configured for interacting with the cartridge to move the test sample through the cartridge.

25. The device of claim 8, wherein the measuring system includes control apparatus for measurement, data analysis and user interaction.

26. The device of claim 8, wherein the measuring system is configured for receiving and securing the cartridge.

27. The device of claim 1, wherein the one or more reagents within each of the plurality of cavities are in a solid form.

28. The device of claim 1, wherein each of the plurality of cavities is a measurement cavity integrally formed with a reagent cavity.

29. The device of claim 28, wherein each measurement cavity is configured for measuring viscoelastic characteristics of the portion of the test sample.

30. The device of claim 1, further comprising a housing.

31. The device of claim 30, wherein the housing defines the inlet.

32. The device of claim 30, wherein each of the plurality of cavities are at least partially defined by the housing.

33. The device of claim 30, wherein the housing includes a housing body and a cover, wherein the housing body and the cover cooperate to define and enclose the ductwork and cavities.

34. The device of claim 30, wherein the housing defines a unitary cartridge comprising the plurality of cavities and the ductwork.

35. The device of claim 34, wherein the cartridge is disposable.

36. The device of claim 1, wherein the device is configured for measuring viscoelastic characteristics of each of the portion of the test sample based on detecting changes in clot firmness.

37. The device of claim 36, wherein clot firmness is continuously determined from formation of fibrin fibres through dissolution by fibrinolysis.

38. The device of claim 1, wherein the device is configured for performing at least three measurements in parallel within the plurality of cavities using a combination of agonists and antagonists of different parts of the coagulation cascade.

39. The device of claim 1, wherein the device is configured such that the one or more reagents within each of the cavities are mixed with the portion test sample in a portion of the fluid pathway prior to being delivered to the cavities.

40. A method for using the device of claim 1, comprising mixing the one or more reagents in each of the cavities with the portion test sample in a portion of the fluid pathway prior to being delivered to the cavities.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The figures are showing the following:

(2) FIG. 1 is a schematic drawing of the principle of thromboelastography according to Hartert.

(3) FIG. 2 is an exemplary diagram showing a typical thromboelastometric measurement.

(4) FIG. 3 is a schematic drawing of the thromboelastometry.

(5) FIG. 4 is a schematic drawing of a first embodiment of a cartridge device according to the invention.

(6) FIG. 5 is a schematic drawing of a variation of the first embodiment of the cartridge device according to the invention.

(7) FIG. 6 is a schematic drawing of another variation of the first embodiment of the cartridge device according to the invention.

(8) FIG. 7a is a schematic drawing of a first embodiment of a probe element.

(9) FIG. 7b is a schematic drawing of the first embodiment of the probe element of FIG. 7a within a measuring cavity of the first or a second embodiment of the cartridge device according to the invention before use.

(10) FIG. 7c is a schematic drawing of the first embodiment of the probe element of FIG. 7a within a measuring cavity of the first or the second embodiment of the cartridge device according to the invention in use.

(11) FIGS. 8a-c are technical drawings of the preferred probe element of FIG. 7a.

(12) FIG. 9a is a side view of a third embodiment of a cartridge device according to the invention.

(13) FIG. 9b is a sectional view B-B of the cartridge device of FIG. 9a.

(14) FIG. 9c is a sectional view C-C of the cartridge device of FIG. 9a.

(15) FIG. 9d is a sectional view D-D of the cartridge device of FIG. 9a.

(16) FIG. 10a is a top view of the cartridge device of FIG. 9a.

(17) FIG. 10b is a sectional view E-E of the cartridge device of FIG. 10a.

(18) FIG. 11a is a sectional view of a pump means of the cartridge device of FIG. 9a.

(19) FIG. 11b is a sectional view of the pump means of FIG. 11a in operated position.

(20) FIG. 12 is a schematic top view of the pump means of FIG. 11a.

(21) FIG. 13a is a side view of an embodiment of a measuring system according to the invention.

(22) FIG. 13b is a top view of the measuring system of FIG. 13a.

(23) FIG. 13c is a sectional view H-H of the measuring system of FIG. 13b.

(24) FIG. 14 is a sectional view of a reagent receptacle of a third embodiment of the cartridge device according to the invention.

(25) FIG. 15 is a schematic drawing of a second embodiment of the probe element.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

(26) Parts and components having same functions are depicted with same references.

(27) Prior to a detailed description of the preferred embodiments the basic features and a basic practical implementation are summoned as follows. All embodiments refer to a cartridge device 50 (see FIG. 13c) which can be formed in a first embodiment (see FIGS. 4, 5 and 6), in a second embodiment (see FIGS. 7b, 7c and 15) or in a third embodiment (see FIGS. 9 to 10). The cartridge device 50 contains all parts coming into contact with a sample liquid 1 to be tested. These can be also reagents the sample liquid has to be mixed with for a measurement. The cartridge device 50 is part of a measuring system 40 (see FIG. 13c) to which the cartridge device 50 is attached before measurement. The measuring system 40 also comprises a control apparatus (not shown) which has been adapted to interact with the cartridge device 50 by electrical and/or mechanical means to control flow of sample liquid 1 (see FIG. 7c) and measurements as well as collect data. Furthermore this apparatus contains mechanical and electronic parts required for measurement, data analysis and user interaction. The present invention is not only suitable for thromboelastometry, thromboelastography and platelet aggregometry but also for other blood tests usually performed regarding surgery.

(28) A first embodiment of a cartridge device 50 of the invention will be described with reference to FIGS. 4 and 5. The cartridge device 50 for the measuring system 40 for measuring medical relevant, e.g. viscoelastic, characteristics like coagulation or platelet function of a sample liquid 1, particularly a blood sample, comprises a receiving cavity 16 for receiving the sample liquid 1, pump means 18 for pumping the sample liquid, a reagent cavity 19 for storing a reagent 21, a measurement cavity 20 for measuring the sample liquid 1 and a ductwork connecting said cavities. The ductwork comprises an inlet duct 13 from the receiving cavity 16 to the pump means 18, an intermediate duct from the pump means 18 to the reagent cavity 19 and an outlet duct 15 from the reagent cavity 19 to the measurement cavity 20. In a variation said cavities and ducts can be arranged in different ways one of which is shown in FIG. 5, wherein pump means 18 and reagent cavity 19 are changed.

(29) In this embodiment the receiving cavity 16 consists of a cavity within the cartridge device 50. The sample liquid 1 can be applied by means of a syringe, pipette etc, e.g. through a self sealing cap shown as a receiving cavity cover 33a in FIG. 10b. By operating the pump means 18, e.g. by means of the control apparatus mentioned above, the sample liquid is transported to the reagent cavity 19, where the reagent 21 required for measurement is mixed with the sample liquid 1. Further pumping the sample liquid 1 will transfer it into the measurement cavity 20 in which the measurement (described below) is carried out.

(30) In an alternative embodiment the reagent cavity 19 is integral formed with the pump means 18 and/or with the measurement cavity 20 and/or with the ductwork. The transport of the sample liquid 1 can be controlled by said control apparatus.

(31) FIG. 6 shows another variation of the first embodiment. Two arrangements of FIG. 4 with only one receiving cavity 16 are arranged in parallel, wherein a first inlet duct 13 communicates with a second inlet duct 13 connected to second pump means 18. A second intermediate duct 14 leads to a second reagent cavity 19 storing a second reagent 21. A second outlet duct 15 connects the second reagent cavity 19 to the second measurement cavity 20. FIG. 6 shows only one possible variation of a plurality of different arrangements easily imagined. The sample liquid 1 is shared among the arrangements in parallel. Controlled by the external control apparatus the shared portions of the sample liquid 1 are mixed with different reagents 21, 21 during transport. It is apparent to a person skilled in the art that in order to achieve a maximum benefit for a user different types of tests can be combined in one cartridge device 50.

(32) In a preferred embodiment the cartridge device 50 comprises four arrangements of FIG. 4 or 5 having 4 measurement cavities 20, 20. Thus measurements can be done with different reagents on the same liquid sample or with same reagents as well to check plausibility.

(33) Regarding e.g. blood coagulation there are different reagents available which activate or suppress different parts of the coagulation cascade. Pentapharm GmbH (Munich, Germany) for example amongst others provide tests for intrinsic and extrinsic activation of a blood sample (INTEM or EXTEM respectively), and also a test for extrinsic activation in which the thrombocyte function is suppressed by administration of cytochalasin D (FIBTEM). It is state of the art that it is possible by wise combination of such tests to be able to determine very precisely at which point within the coagulation cascade a problem occurs. This is of great importance in order to determine a proper medication. By comparison of the results on an EXTEM test of a pathologic sample to those of a FIBTEM test of the same sample it is possible to e.g. precisely determine if a coagulation disorder results from lack of fibrinogen or a malfunction of platelets. Generally, there are different typical medical scenarios in which coagulation disorders are very likely to occur. For example coagulation disorders occurring during liver transplantation are merely caused by lack of certain coagulation factors etc., while coagulation disorders during open heart surgery are most likely due to the influence of heparin. This means basically that different medical settings require different coagulation tests. Referring to FIG. 6 it is possible and worthwhile to provide different cartridge devices 50 for different typical operations. It is also possible to combine e.g. an INTEM, an EXTEM and a FIBTEM coagulation test with a platelet aggregometry test within one cartridge. Using such a cartridge the preparation of a measurement which provides almost overall information about the coagulation status of a patient merely requires the two steps of attaching the cartridge device 50 to the measuring system 40 with the external control apparatus and injecting the blood sample as one sample liquid 1. Considering the significance of more complex and time consuming preparation of several thromboelastography or thromboelastometry tests, it is evident that the invention is of great advantage for easier, safer and more accurate POC-tests.

(34) It is important to note that the cartridge devices 50 of the described embodiments are suitable for different diagnostic tests like thromboelastometry, thromboelastography, platelet aggregometry and others. Depending on which type of test or tests the cartridge device 50 is designed for, there are different additional parts required which interact with the sample during measurement and/or an external control apparatus. Possible adaptations for thromboelastometry and platelet aggregometry are described below.

(35) FIG. 7a is a schematic drawing of a first embodiment of a probe element 22 arranged in the measurement cavity 20 (see also FIGS. 10b and 13c). FIGS. 7b and 7c show a second embodiment of the cartridge device 50 in form of a cartridge body 30 which comprises only the measurement cavity 20. In the shown example this cavity 20 is accessible via a ductwork 15, 15 through a cavity wall. Alternatively the cavity 20 can be filled through a cover 31, e.g. by injection needles or the like.

(36) The probe element 22 comprises the probe pin 3 (see FIG. 1) which is connected to a flange 24 and a fixing section 25 via an intermediate section 23. The probe element 22 is formed as a rotational part and further comprises a connector section 26 formed as a bore extending within the probe element 22 along its longitudinal axis, which is the rotational axis 5 as well (see FIG. 3).

(37) The probe element 22 is arranged in the measurement cavity 20 of the cartridge body 30 of the cartridge device 50 as shown in FIG. 7b. The measurement cavity 20 is covered by the cover 31 (see also FIGS. 10b and 13c). The cover 31 comprises an opening with fixing means 32 above the measurement cavity 20. The probe element 22 is arranged such that its fixing section 25 corresponding to the fixing means 32 engage with them. In this manner the probe element 22 is detachably fixed to the cover 31. The fixing means 32 in this example are equipped with a circular nose corresponding to a circular notch of the fixing section 25 of the probe element 22. Other fixing means e.g. clip means or the like are possible. The flange 24 is in contact to the inner side of the cover 31.

(38) During attaching the cartridge device 50 to the measuring system 40 (see also FIG. 13c) the shaft 6 of the measuring system 40 (see FIG. 3 and FIGS. 13a . . . c) is inserted with its bottom portion, an insert section 6a, into the connector section 26. By insertion into the connector section 26 of the probe element 22 the probe element 22 will be detached from the cover 31 not before the insert section 6a is completely inserted in the connector section 26. Then the probe element 22 will be put into in a measuring position as shown in FIG. 7c and kept there. The insert section 6a of the shaft 6 is engaged with the connector section 26 of the probe element 22 e.g. by friction, clip means, thread or the like. In case of a thread the probe element 22 will be hold by the engagement with or perforation of the cover 31. The shaft 6 having a corresponding thread on its insert section 6a will be inserted into the connector section of the probe element 22 by rotation until the insert section 6a will be completely inserted into the connector section 26. Then the shaft 6 can be pushed down and/or rotated together with the fully engaged probe element 22 until the probe element 22 will be detached from the cover 31. FIG. 7c shows the sample liquid 1, which has been pumped into the measurement cavity 20. The probe pin 3 of the probe element 22 is immersed in the sample liquid 1. A measurement as described above can be carried out. After the measurement the cartridge device 50 is detached from the measuring system 40, wherein the shaft 6 is drawn up together with the probe element 22 against the cover 31. The insert section 6a of the shaft 6 will be drawn out of the connector section 25 of the probe element 22 the flange 24 thereof contacting and sealing the opening of the cover 31. Instead of a flange 24 the upper end of the probe element 22 can have a larger diameter than the opening in the cover 31. It is preferred that the insert section 6a of the shaft 6 and the measurement cavity 20, 20 are formed symmetrically.

(39) It is also possible to insert the insert section 6a of the shaft 6 into the connector section 26 of the probe element 22 and push the probe element 22 down until its bottom contacts the bottom of the measurement cavity 20, 20 ensuring that the insert section 6a is completely inserted into the connector section 26. Then the shaft 6 will be moved up into the measuring resp. working position of the probe element 22 as shown in FIG. 7c.

(40) FIGS. 8a . . . c are technical drawings of a preferred embodiment of the probe element 22 of FIG. 7a FIG. 8a shows a side view and FIG. 8b shows a top view of the probe element 22 parts of which have been described above regarding FIG. 7a. Finally, FIG. 8c illustrates a sectional view along rotational axis 5. The connector section 26 extends over more than about 75% of the length of the probe element 22.

(41) Now a third embodiment of the cartridge device 50 will be described with reference to FIGS. 9a, . . . , d and FIGS. 10a, . . . b.

(42) FIG. 9a is a side view of a second embodiment of a third embodiment of the cartridge device 50 according to the invention. FIG. 9b is a sectional view B-B of the cartridge device 50 of FIG. 9a. FIG. 9c is a sectional view C-C of the cartridge device of FIG. 9a. FIG. 9b is a sectional view D-D of the cartridge device of FIG. 9a. FIG. 10a is a top view of the cartridge device of FIG. 9a. FIG. 10b is a sectional view E-E of the cartridge device of FIG. 10a.

(43) The cartridge device 50 of this example is equipped with the ductwork 13 and 15. The ducts are formed with an diameter of approximately 1 mm in this embodiment. The ductwork requires that the cartridge device 50 comprises two parts: the cartridge body 30 and the cover 31, which are glued or welded together to obtain a leak-proof device. The cartridge body 30 is relative rigid and the cover 31 is formed as an elastic part. So it is possible to integrate the pump means 18 into the cover 31. Moreover, the cover 31 covers the receiving cavity 16 with the receiving cavity cover 33a and forms a type of liner wall 33 and a separation wall 34 forming an inlet for the inlet duct 13 within the receiving cavity 16. The receiving cavity cover 33a might act as a self seal for injection of a sample liquid 1 by a syringe for example. The cover 31 forms top parts of the ductwork 13 an 15 and a cover of the measurement cavity 20 (see also FIGS. 7b . . . c). In this example the pump means 18 comprises a pump membrane 35 formed by the cover 31. The pump membrane 35 cooperates with a pump cavity 36 termed with a pump cavity bottom 36a in the cartridge body 30 below the pump membrane 35.

(44) In this embodiment a reagent cavity 19, 19 is formed, e.g. by sections of the ductwork or/and the pump means 18, 18 in which the reagents can be stored resp. deposited, especially on the pump cavity bottom 36a, for example.

(45) The pump means 18 will now be described with reference to FIGS. 11a . . . b and FIG. 12.

(46) FIG. 11a is a sectional view of the pump means 18, 18 of the cartridge device 50, FIG. 11b is a sectional view of the pump means 16 of FIG. 11a In operated position, and FIG. 12 is a schematic top view of the pump means 18 of FIG. 11a.

(47) In this example the pump cavity 36 is connected to the inlet duct 13 via an inlet valve 37 and to the outlet valve via an outlet valve 38. Actuation of the pump membrane 35 (shown in FIG. 11b in a working cycle) by an appropriate actuating means (not shown) of the control apparatus the pump means 18 will create a directed flow of the sample liquid 1 in a flow direction 39 depicted by the arrows. The pump membrane 35 being an integrated part of the cover 31 can be made of the cover material or a part made of another material integrally manufactured with the cover 31, e.g. two components manufacturing. The valves 37, 36 can be a type of non-return valve. FIG. 12 shows a top view of the pump means in a schematic way.

(48) An external force exerted on the pump membrane 35 increase the pressure within the pump cavity 36 and opens outlet valve 38 and doses inlet valve 37. Releasing the external force the elastic pump membrane 35 returns into the position shown in FIG. 11a whereby outlet valve 38 will be closed and inlet valve 37 opened to let sample liquid 1 into the pump cavity 36. This mechanism is state of the art according to DE10135569. In context with the present invention the actuation means of the control apparatus activating the pump membrane 35 from outside has the advantage of strict separation between those parts coming into contact with the sample liquid 1 and the control apparatus. At the same time the total number of parts required for the cartridge device 50 being a disposable part as well is kept on a minimum.

(49) Now the measuring system 40 according to the invention is described in an embodiment with reference to FIGS. 13a . . . c.

(50) FIG. 13e, is a side view of an embodiment of the measuring system 40, FIG. 13b is a top view of the measuring system 40 of FIG. 13a, and FIG. 13c is a sectional view H-H of the measuring system 40 of FIG. 13b.

(51) The measuring system 40 comprises an interface element 41 to which the cartridge device 50 is attached and fixed. The interface element 41 is shown in FIGS. 13a to 13c in way of example as a base plate. The function of the interface element 41 is to support the shaft 6 and to maintain its position and thus the position of the probe element 22 fixed to the insert section 6a in a measurement position. The interface element 41 can be connected to the whole cover 31 as shown in FIGS. 13a to 13c or only to parts of the cover 31, e.g. surrounding the rotation axis 5. The shaft 6 is rotatable supported in a bearing 7 within a shaft passage 44 (FIG. 13c) and can be rotated around the rotation axis 5 (see also FIG. 3) by driving the spring 9 via driving means (not shown). The detecting means 10 cooperate with the mirror 8 fixed on the shaft 3, also shown in FIG. 3. The control apparatus mentioned above is not shown as well, but easy to imagine. Its actuation and/or operating means can access the pump means 18 through an opening pump access 42 in the interface element 41. The receiving cavity 16 is accessible through another inlet opening 43. These and other different passages or passage ways of the interface element 41 to have access to the cartridge device 50 and/or its cover 31 are illustrated by FIG. 13b as a top view of the measuring system 40 of FIG. 13a. Passage holes 44a are arranged next to the rotational axis 5 to form an access to the cover 31 above the measurement cavity 20, 20, e.g. for injection of liquid sample or reagents. Additional access passage holes can be arranged in the interface element 41, e.g. above the ductwork to access said ductwork.

(52) FIG. 13c illustrates a sectional view H-H of FIG. 13b showing the mounted cartridge device 50 and the measuring system 40. The shaft 6 with its insert section 6a is inserted into the probe element 22 and keeps it in a measurement position as mentioned above. This embodiment comprises only one measurement cavity 20, but it is apparent to a person skilled in the art that modifications and combinations of the invention can be carried out in different ways.

(53) Thus it is possible to e.g. arrange a reagent receptacle 19b in a blister receptacle e.g. as shown in FIG. 14 which is a sectional view of the reagent receptacle 19b of a third embodiment of the cartridge device 50 according to the invention. The receptacle 19b contains reagent 21 hold within a chamber defined by a buster cover 49, a bottom part 48 and a frame 47 hold in a retaining ring 46 within an reagent cover opening 45 in the cover 31 above the reagent cavity 19, 19 with a reagent cavity bottom 19a, 19a. Upon exertion of a force by the control apparatus onto the blister cover 49 the bottom part 48 will open and discharge the reagent 21 into the reagent cavity 19, 19. The receptacle 19b can be fixed to the cover by e.g. clip means as depicted. The frame 47 can be a reinforced ring. The blister cover 49 is reinforced so that it will not break when a force is exerted on it. Thus the leak-tightness of the cartridge device 50 will be ensured. In this way a unitized construction system can be made, wherein the respective reagents can be easily integrated into the cartridge device 50. It is also advantageous that the reagents can be designed as a small component being cooled reap, transported and supplied easily.

(54) It is also possible to insert reagent receptacles into provided cavities being connected to the ductwork. The reagents can be designed as globules with an appropriate diameter so that they cannot flow through openings into the ductwork before being dissolved by the sample liquid.

(55) FIG. 15 is a schematic drawing of a second embodiment of a probe element 22. The probe element 22 is arranged in the measurement cavity 20. The probe pin 3 is provided with a dimple 29 at its bottom side. The dimple 29 forms with a nose 29a a toe bearing to support the probe element 22. The probe element 22 is similar to the probe element 22 of FIG. 7a, but has no fixing section 25, only the flange 24. The connector section 26 comprises a top end formed with an insertion guide 27 for the insertion section 6a of the shaft. The probe element 22 is hold in the measurement cavity 20 in a specific manner so that the insertion section 6a of the shaft 6 can be inserted easily through an opening 32a of the cover 31 which has no fixing means. The insertion section 6a can engage with a groove 28 inside the connector section 26 of the probe element 22. After that engagement which is supported by the toe bearing the shaft 6 will be drawn up together with the probe element 22 in the measuring position. It is a matter of fact that other engagement means can be used.

LIST OF REFERENCE NUMERALS

(56) 1 Sample liquid 2 Cup 3 Probe pin 4 Torsion wire 5 Rotation axis 6 Shaft 6a Insert section 7 Bearing 8 Mirror 9 Spring 10 Detecting means 11 Base plate 12 Cup holder 13, 13 Inlet duct 14, 14 Intermediate duct 15, 15 Outlet duct 16, 16 Receiving cavity 17 Branch duct 18, 18 Pump means 19,19 Reagent cavity 19a, 19a Regents cavity bottom 19b Reagent receptacle 20, 20 Measurement cavity 21, 21 Reagent 22, 22 Probe element 23 Intermediate section 24 Flange 25 Fixing section 26 Connector section 27 Insertion guide 28 Groove 29 Dimple 29a Nose 30 Cartridge body 31 Cover 32 Fixing means 32a Opening 33 Wall 33a Receiving cavity cover 34 Separation wall 35 Pump membrane 36 Pump cavity 36a Pump cavity bottom 37 Inlet valve 38 Outlet valve 39 Flow direction 40 Measuring system 41 Interface element 42 Pump access 43 inlet opening 44 Shaft passage 44a Passage hole 45 Reagent cover opening 46 Retaining ring 47 Frame 48 Bottom foil 49 Blister cover 50 Cartridge device