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 system comprising: a cartridge comprising: receiving cavities, a receiving cavity for receiving a portion of a test sample; reagent cavities, a reagent cavity for receiving the portion of the test sample; testing cavities; and ductwork for interconnecting at least the receiving cavity, the reagent cavity, and a testing cavity, the reagent cavity being configured to receive the portion of the test sample via the ductwork, the ductwork having a different three-dimensional shape than each of the receiving cavities, the reagent cavities, and the testing cavities, and the receiving cavity, the reagent cavity, and the testing cavity being separate cavities; and wherein each of the reagent cavities comprises a reagent or combination of reagents, the reagent cavities comprising at least: a first cavity comprising a first reagent to activate coagulation; and a second cavity comprising a second reagent to activate coagulation; wherein the testing cavity is configured for use in measuring a viscoelastic characteristic associated with a liquid in the testing cavity, the liquid comprising a mixture of the portion of the test sample and the reagent in the reagent cavity; and wherein the ductwork is configured to receive pressure, the pressure to move the portion of the sample into the reagent cavity.

2. The system of claim 1, wherein the ductwork is configured to receive negative pressure, the negative pressure to move the portion of the sample into the reagent by drawing the portion of the sample out from a bottom of the receiving cavity and upwards into the reagent cavity.

3. The system of claim 1, wherein the ductwork comprises a duct between the reagent cavity and the testing cavity, the duct comprising a first part and a second part; and wherein the first part is in a generally downward direction relative to a side of the cartridge and the second part is in a different direction than the first part.

4. The system of claim 2, wherein the second part is in a direction that is generally parallel to the side of the cartridge.

5. The system of claim 1, wherein the first reagent and the second reagent activate different parts of a coagulation cascade.

6. The system of claim 1, wherein: the first reagent is for extrinsic activation of a portion of the test sample; and the second reagent is for intrinsic activation of a portion of the test sample.

7. The system of claim 1, where at least one of the first reagent or the second reagent comprises globules have a dimension that inhibits movement through the first liquid transport path or the second liquid transport path absent at least some dissolution of the globules.

8. A system comprising: a cartridge comprising: a first liquid transport path configured to receive a first portion of a blood sample via a first cavity, the first liquid transport path comprising a first reagent cavity containing a first reagent, a first testing cavity that is usable to measure a viscoelastic characteristic associated with a first liquid formed by mixing the first portion of the blood sample and the first reagent, and a first pathway from the first cavity to the first liquid transport path, the first pathway being configured to move the first portion of the blood sample from a bottom of the first cavity upwards and into the first liquid transport path, the first reagent cavity having a different three-dimensional shape than another part of the first liquid transport path, and the first cavity, the first reagent cavity, and the first testing cavity being separate cavities; and a second liquid transport path configured to receive a second portion of a blood sample, the second liquid transport path comprising a second reagent cavity containing a second reagent, a second testing cavity that is usable to measure a viscoelastic characteristic associated with a second liquid formed by mixing the second portion of the blood sample and the second reagent, the second reagent cavity having a different three-dimensional shape than another part of the second liquid transport path; and a control apparatus configured to control flow of liquid through the first liquid transport path and through the second liquid transport path, and to obtain data based on the first and second liquid.

9. The system of claim 8, wherein the first liquid transport path comprises a first duct between the first reagent cavity and the first testing cavity, the first duct comprising a first part and a second part, the first part being in a generally downward direction relative to a side of the cartridge and the second part being in a different direction than the first part; and wherein the second liquid transport path comprises a second duct between the second reagent cavity and the second testing cavity, the second duct comprising a third part and a fourth part, the third part being in a generally downward direction relative to a side of the cartridge and the fourth part being in a different direction than the third part.

10. The system of claim 9, wherein the second part is in a direction that is generally parallel to the side of the cartridge; and wherein the fourth part is in a direction that is generally parallel to the side of the cartridge.

11. The system of claim 8, wherein the control apparatus is configured to interact at least one of electrically or mechanically with the cartridge to control the flow of liquid.

12. The system of claim 8, where at least one of the first reagent or the second reagent comprises globules having diameters that inhibit movement through the first liquid transport path or the second liquid transport path absent at least some dissolution of the globules.

13. The system of claim 8, further comprising one or more pumps to implement positive and negative pressure changes to control flow of fluids along the first liquid transport path and the second liquid transport path.

14. The system of claim 8, wherein the second liquid transport path comprises a second pathway to receive the second portion of the blood sample; and wherein the first pathway is different from the second pathway.

15. A cartridge comprising: multiple fluid channels, a fluid channel among the multiple fluid channels comprising ductwork configured to enable fluid flow among multiple cavities along the fluid channel, each of the multiple cavities having a different three-dimensional shape than the ductwork, the multiple cavities comprising: a reagent cavity for holding at least one reagent and for receiving a test sample comprised of blood; and a testing cavity for receiving a liquid that is based on a mixture of the test sample and the at least one reagent, the testing cavity being in fluid communication with the reagent cavity via part of the ductwork; wherein the testing cavity is configured to enable a test on the liquid received in the testing cavity, the test for measuring a viscoelastic characteristic associated with the liquid; and wherein the cartridge is configured to enable movement of the test sample upwards from a bottom of an additional cavity holding blood and into the fluid channel, the additional cavity, the reagent cavity, and the testing cavity being different cavities.

16. The system of claim 15, wherein the part of the ductwork comprises a first part and a second part; and wherein the first part is in a generally downward direction relative to a side of the cartridge and the second part is in a different direction than the first part.

17. The system of claim 16, wherein the second part is in a direction that is generally parallel to the side of the cartridge.

18. The cartridge of claim 16, wherein the cartridge comprises a pressure port; and wherein flow of the test sample into the reagent cavity is implemented by applying pressure to the pressure port.

19. The cartridge of claim 16, wherein the multiple fluid channels comprise four fluid channels comprising four reagent cavities including the reagent cavity and four testing cavities including the testing cavity; wherein each testing cavity is for receiving a liquid that is based on a mixture of a test sample and a reagent from a reagent cavity in a same fluid flow path; and wherein each testing cavity is configured to enable a test on the liquid received in the testing cavity.

20. The cartridge of claim 16, wherein the at least one reagent comprises globules having a dimension that inhibits movement through the first liquid transport path or the second liquid transport path absent at least some dissolution of the globules.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0061] The figures are showing the following:

[0062] FIG. 1 is a schematic drawing of the principle of thromboelastography according to Hartert.

[0063] FIG. 2 is an exemplary diagram showing a typical thromboelastometric measurement.

[0064] FIG. 3 is a schematic drawing of the thromboelastometry.

[0065] FIG. 4 is a schematic drawing of a first embodiment of a cartridge device according to the invention.

[0066] FIG. 5 is a schematic drawing of a variation of the first embodiment of the cartridge device according to the invention.

[0067] FIG. 6 is a schematic drawing of another variation of the first embodiment of the cartridge device according to the invention.

[0068] FIG. 7a is a schematic drawing of a first embodiment of a probe element.

[0069] 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.

[0070] 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.

[0071] FIGS. 8a-c are technical drawings of the preferred probe element of FIG. 7a.

[0072] FIG. 9a is a side view of a third embodiment of a cartridge device according to the invention.

[0073] FIG. 9b is a sectional view B-B of the cartridge device of FIG. 9a.

[0074] FIG. 9c is a sectional view C-C of the cartridge device of FIG. 9a.

[0075] FIG. 9d is a sectional view D-D of the cartridge device of FIG. 9a.

[0076] FIG. 10a is a top view of the cartridge device of FIG. 9a.

[0077] FIG. 10b is a sectional view E-E of the cartridge device of FIG. 10a.

[0078] FIG. 11a is a sectional view of a pump means of the cartridge device of FIG. 9a.

[0079] FIG. 11b is a sectional view of the pump means of FIG. 11a in operated position.

[0080] FIG. 12 is a schematic top view of the pump means of FIG. 11a.

[0081] FIG. 13a is a side view of an embodiment of a measuring system according to the invention.

[0082] FIG. 13b is a top view of the measuring system of FIG. 13a.

[0083] FIG. 13c is a sectional view H-H of the measuring system of FIG. 13b.

[0084] FIG. 14 is a sectional view of a reagent receptacle of a third embodiment of the cartridge device according to the invention.

[0085] FIG. 15 is a schematic drawing of a second embodiment of the probe element.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0086] Parts and components having same functions are depicted with same references.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] 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.

[0095] 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.

[0096] 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).

[0097] 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.

[0098] 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 26 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.

[0099] 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.

[0100] 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.

[0101] Now a third embodiment of the cartridge device 50 will be described with reference to FIGS. 9a, . . . d and FIGS. 10a . . . b.

[0102] 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.

[0103] 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 formed with a pump cavity bottom 36a in the cartridge body 30 below the pump membrane 35.

[0104] 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.

[0105] The pump means 18 will now be described with reference to FIGS. 1a . . . b and FIG. 12. 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 18 of FIG. 11a In operated position, and FIG. 12 is a schematic top view of the pump means 18 of FIG. 11a.

[0106] 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.

[0107] An external force exerted on the pump membrane 35 increase the pressure within the pump cavity 36 and opens outlet valve 38 and closes 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.

[0108] Now the measuring system 40 according to the invention is described in an embodiment with reference to FIGS. 13a . . . c.

[0109] FIG. 13a, 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.

[0110] 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.

[0111] 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.

[0112] 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 blister 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 resp. transported and supplied easily.

[0113] 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.

[0114] 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

[0115] 1 Sample liquid [0116] 2 Cup [0117] 3 Probe pin [0118] 4 Torsion wire [0119] 5 Rotation axis [0120] 6 Shaft [0121] 6a Insert section [0122] 7 Bearing [0123] 8 Mirror [0124] 9 Spring [0125] 10 Detecting means [0126] 11 Base plate [0127] 12 Cup holder [0128] 13, 13′ Inlet duct [0129] 14, 14 Intermediate duct [0130] 15, 15′ Outlet duct [0131] 16, 16′ Receiving cavity [0132] 17 Branch duct [0133] 18, 18′ Pump means [0134] 19, 19′ Reagent cavity [0135] 19a, 19′a Regent cavity bottom [0136] 19b Reagent receptacle [0137] 20, 20′ Measurement cavity [0138] 21, 21′ Reagent [0139] 22, 22′ Probe element [0140] 23 Intermediate section [0141] 24 Flange [0142] 25 Fixing section [0143] 26 Connector section [0144] 27 Insertion guide [0145] 28 Groove [0146] 29 Dimple [0147] 29a Nose [0148] 30 Cartridge body [0149] 31 Cover [0150] 32 Fixing means [0151] 32a Opening [0152] 33 Wall [0153] 33a Receiving cavity cover [0154] 34 Separation wall [0155] 35 Pump membrane [0156] 36 Pump cavity [0157] 36a Pump cavity bottom [0158] 37 Inlet valve [0159] 38 Outlet valve [0160] 39 Flow direction [0161] 40 Measuring system [0162] 41 Interface element [0163] 42 Pump access [0164] 43 inlet opening [0165] 44 Shaft passage [0166] 44a Passage hole [0167] 45 Reagent cover opening [0168] 46 Retaining ring [0169] 47 Frame [0170] 48 Bottom foil [0171] 49 Blister cover [0172] 50 Cartridge device