Cartridge device for measurement system for measuring viscoelastic property of sample liquid, corresponding measurement system, and corresponding method

Abstract

To provide a cartridge device for a measurement system for measuring the viscoelastic properties of a sample liquid, especially a blood sample.SOLUTION: A cartridge device 50 for a measurement system for measuring the viscoelastic properties of a sample liquid, in particular a blood sample, includes a cartridge body 30 and a cover 31. The cartridge body 30 has at least one measurement cavity 20 configured inside the cartridge device and has at least one probe element 22 disposed in the measurement cavity 20 for making an inspection of the sample liquid. The cover 31 can be attached to the cartridge body 30. The cover 31 covers at least a part of the measurement cavity 20 and constitutes a holding element for holding the probe element 22 in a predetermined position within the measurement cavity 20.SELECTED DRAWING: Figure 13c

Description

[Technical field]

[0001] The present invention relates to a cartridge device for a measurement system for measuring the viscoelastic properties of a sample liquid, in particular a blood sample.The present invention also relates to a corresponding measurement system and method. [Background technology]

[0002] It is essential for survival that wounds stop bleeding, i.e. that the body has adequate hemostatic mechanisms. In case of injury or inflammation, the process of blood clotting can be activated by either extrinsic or intrinsic factors, such as tissue factor (TF) or Hageman factor (FXII), respectively. Both activation channels continue in a common branch of the cascade, resulting in the formation of thrombin, which itself finally initiates the formation of fibrin fibers that represent the protein backbone of the blood clot.

[0003] The other main components of the final blood clot are platelets, which are interconnected by fibrin fibers during the coagulation process and undergo many physiological changes. Within limits, a deficiency in platelets can be replaced by an increased amount of fibrin, or vice versa. This is reflected in the observation that even within healthy populations, platelet counts and fibrinogen concentrations vary.

[0004] To evaluate the potential of blood, various methods have been introduced to form a proper clot and to determine the stability of the clot. Common laboratory tests such as platelet counting or determination of fibrin concentration provide information whether the tested component is available in sufficient amounts, but they lack the ability to answer the question of whether the tested component functions properly under physiological conditions (e.g., the polymerization activity of fibrinogen under physiological conditions cannot be evaluated by common optical methods). Most other laboratory tests work in plasma, which requires additional steps for preparation and additional time that is unfavorable, especially under point of care conditions.

[0005] Another group of tests that overcome these problems are summarized by the term "viscoelastic methods". The common feature of these methods is that the firmness of the clot (or other parameters on which it depends) is determined continuously, from the formation of the first fibrin fibers to the degradation of the clot by fibrinolysis. The firmness of the clot is an important functional parameter for hemostasis in vivo, since the clot must resist the blood pressure and shear stress at the site of injury in the blood vessel. The firmness of the clot is the result of a number of interlinked processes, namely, coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activation, and fibrin-platelet interactions, which can be impaired by fibrinolysis. Therefore, by using viscoelastic monitoring, all these mechanisms of the coagulation system are evaluated.

[0006] A common feature of all these methods used for coagulation diagnosis is that a blood clot is placed in the space between a cylindrical pin and an axisymmetric cup, and the ability of the blood clot to bind these two bodies is determined.

[0007] The first viscoelastic method is called "Thromboelastography" (Hartert H: Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren Klin Wochenschrift 26:577-583, 1948). As illustrated in FIG. 1, in thromboelastography, a sample as sample liquid 1 is placed in a cup 2 that is periodically rotated by about 5° to the left and right, respectively. A probe pin 3 is freely supported by a torsion wire 4. When a clot forms, the movement of the cup 2 starts to be transmitted to the probe pin 3 against the opposite momentum of the torsion wire 4. The movement of the probe pin 3 as a measure of the firmness of the clot is continuously recorded and plotted against time. For historical reasons, firmness is measured in millimeters.

[0008] The result of a typical measurement of this kind is illustrated in FIG. 2. One of the most important parameters is the time between the initiation of the coagulation cascade, with the induction of an activator, and the time until the first long fibrin fibers are generated, indicated by a firmness signal exceeding a certain value. This parameter is called the clotting time or, in the following, simply CT. Another important parameter is the clot formation time (CFT), which gives a measure of the speed of the development of the clot. CFT is defined as the time it takes for the firmness of the clot to increase from 2 mm to 20 mm. Furthermore, the maximum firmness reached by the clot during the measurement, also called maximum clot firmness or simply MCF, is also of great importance in the primary diagnosis.

[0009] Improvements on the original thromboelastography technique (Hartert et al. (U.S. Pat. No. 3,714,815)) have been described by Cavallari et al. (U.S. Pat. No. 4,193,293), by Do et al. (U.S. Pat. No. 4,148,216), and by Cohen (U.S. Pat. No. 6,537,819). A further improvement by Calatzis et al. (U.S. Pat. No. 5,777,215), illustrated in FIG. 3, is known under the term thromboelastometry.

[0010] Different from the above mentioned modifications, thromboelastometry is based on the cup 2 being fixed in a cup holder 12 while the probe pin 3 is actively rotated. For this purpose, the probe pin 3 is mounted on a shaft 6 supported by a ball bearing 7 in a base plate 11 and has a spring 9 connected to it. A rocking movement perpendicular to the plane of the drawing induced at the opposite end of the spring is converted into a periodic rotation of the shaft 6 and of the connected cup 2 about the rotation axis 5 of about 5° in each direction. When the sample liquid 1 starts to coagulate, the amplitude of the movement of the shaft 6, detected by the detection means 10 and the mirror 9 due to the displacement of the light beam, starts to decrease.

[0011] During clotting, the fibrin skeleton creates a mechanical elastic linkage between the surface of the blood receiving cup 2 and the probe pin 3 pressed into it. The progression of the clotting process, triggered by the addition of one or more activating factors, is therefore observed. In this way, various defects in the patient's hemostatic status become apparent and are interpreted for appropriate medical intervention.

[0012] A general advantage of viscoelastic, e.g. thromboelastometry, techniques compared to other clinical methods in the field is that the clotting process and changes in the mechanical properties of the sample are monitored as a whole. This means that, unlike the other clinical methods mentioned above, thromboelastometry not only indicates whether all components of the clotting pathway are available in sufficient amounts, but also whether each component is functioning properly.

[0013] In order to obtain detailed information about the exact amount and function of platelets as well as fibrinogen and certain factors, today an increasing number of components are available to activate or inhibit certain components of the coagulation system. This makes it possible to determine the point in the coagulation system that is problematic. For practical reasons, these components are usually injected by using a pipette (manual or automatic) into a disposable plastic cup that is subsequently used for the measurement. In the final preparation step, after the blood or plasma sample has been added, the entire amount of the sample (blood / plasma and additional chemicals) is mixed by drawing it into the tip of the pipette and dispensing it again into the cup.

[0014] The ability to activate or inhibit specific components of the coagulation system is particularly useful in the context of modern thromboelastometers such as ROTEM (Pentapharm GmbH, Munich, Germany), which allows four measurements to be performed in parallel. This allows detailed information on the current status of the patient's coagulation state to be achieved, thus enabling appropriate treatment within minutes.

[0015] This is particularly important in the case of patients who suffer from large amounts of blood loss, which often occurs in the setting of multiple trauma or major surgical procedures. Such patients' blood is often diluted by the infusions administered to replace the loss in volume. This leads to reduced concentrations of clotting factors, including platelets and fibrinogen.

[0016] The main advantages of thromboelastometry and thromboelastography are the ability to perform several different tests simultaneously to accurately determine which blood products are appropriate medications, the ability to perform measurements at or near the point of care (POC), and the relatively short time to useful results compared to other methods.

[0017] On the other hand, the operator must perform a significant number of steps to start a measurement (preparing reagents, attaching the probe pin and cup to the instrument, pipetting and mixing the blood sample and reagents, adjusting computer settings, etc.), which takes a significant amount of time, especially when a surgical procedure is being performed.

[0018] Moreover, this not only complicates the preparation but also increases the risk of operating errors. There have been some attempts to simplify the use of thromboelastometers. For example, the provision of an automatic pipette on the Rotem system (Pentapharm GmbH, Munich, Germany) greatly simplifies the handling and thereby reduces the risk of operating errors.

[0019] WO2008093216 describes an approach to provide the appropriate amount of each of the reagents required for one particular test in a ready-to-use mixture. To prevent reaction of the reagents prior to measurement, they are supplied in lyophilisate form. This has the added advantage that the reagents can be stored at room temperature. With this approach, the preparation is reduced to the steps of adding the blood sample to a reagent container, mixing the blood with the reagent, and transporting the mixture to the instrument.

[0020] US 2007 / 0059840 describes a hemostasis analysis device and method. The device includes a container for holding a sample to be tested and a float floatably supported above the sample. A magnet is affixed to the float. The container can be driven in an oscillating motion. An external magnetic field is generated in proximity to the float. A magnetic field strength detector detects changes in the magnetic field as a result of the movement of the float and magnet in response to oscillating the container and clotting of the sample. Summary of the Invention [Problem to be solved by the invention]

[0021] Such a new measurement system entails acceptance problems and uncertainties for users. Moreover, the analyzer does not fit into the existing measurement system. Therefore, a new system must be completely designed.

[0022] All these modifications lead to important improvements in the operation of modern thromboelastometers and thromboelastographs, however, there have been no successful attempts to develop a widely automated technique since the 60 years before Hartert's invention. One of the two main reasons is that the measurement requires two disposable parts (cup and pin) that are moved relative to each other and therefore must be attached in reverse to different parts of the measurement device. For example, in Figure 3, the probe pin 3 is attached to the shaft 6 and the cup 2 to the cup holder 12. The other main reason is that various tests are required to obtain comprehensive information of the patient's current bleeding status. These various tests require various reagents that must be mixed into the blood sample.

[0023] The problem underlying the present invention is to provide a cartridge device for a measurement system for measuring the viscoelastic properties of a sample liquid, in particular a blood sample.

[0024] Directly relevant to the present invention is the problem of providing a corresponding measurement system for determining the viscoelastic properties of a sample liquid, in particular the coagulation properties of a blood sample liquid.

[0025] A further problem inherent to the present invention is to provide a method for measuring the viscoelastic properties of a sample liquid using said measurement system. [Means for solving the problem]

[0026] These problems are solved by the subject matter of the independent claims, in which preferred embodiments are described.

[0027] In a first aspect, the present invention provides a cartridge device for a measurement system for measuring viscoelastic properties of a sample liquid, in particular a blood sample, comprising a cartridge body having at least one measurement cavity configured inside the cartridge device and having at least one probe element arranged in the at least one measurement cavity for performing a test on the sample liquid, and a cover that can be attached to the cartridge body, the cover at least partially covering the at least one measurement cavity and constituting a holding element for holding the probe element in a predetermined position within the at least one measurement cavity.

[0028] In a second aspect, the present invention provides a measurement system for measuring the viscoelastic properties of a sample liquid, in particular a blood sample, comprising at least one interface element, at least one shaft rotatably supported by said interface element so as to be rotated by a drive means, at least one cartridge device fixed to said interface element and for holding said sample liquid, comprising a cartridge body with a cover and at least one probe element provided in a measurement cavity configured in said cartridge body for cooperating with said at least one shaft, at least one detection means cooperating with said shaft for measuring the viscoelastic properties of the sample liquid, and control means for controlling the measurement system.

[0029] In a third aspect, the present invention provides a method for measuring viscoelastic properties of a sample liquid by means of the measurement system, comprising the following steps: a) providing a cartridge device having at least one measurement cavity with at least one probe element arranged inside the cartridge device; b) attaching the cartridge device to the interface element, the shaft being inserted into the probe element; c) filling the measurement cavity of the cartridge device with sample liquid; d) rotating the shaft in an oscillating motion about the rotation axis; and e) measuring the viscoelastic properties of the sample liquid by detecting the rotation of the shaft by the detection means.

[0030] In a preferred embodiment, the probe element comprises a probe pin for cooperating with the sample liquid and a connector part for connection to a measurement system. The connector part is for example configured as a hole extending in the probe element and is provided with frictional connection means, which can for example be a clip means or a screw. An insertion guide facilitates the insertion of the parts of the measurement system, in particular the shaft, whereby the shaft can be securely connected to the probe element.

[0031] At least one measurement cavity may comprise holding or supporting means for the probe element, for aligning or holding the probe element prior to insertion of the shaft.

[0032] After the shaft is inserted into the connector portion, the shaft can be lifted to place the probe element in an operative position.

[0033] In another preferred embodiment, the probe element is configured as a component part of the cover which is removably fixed. The operator only has to mount the cartridge device on the measurement system and a shaft inserted in the probe element removes the probe element from the cover and holds it firmly in a position where a measurement can be performed. The probe element is therefore provided with a fixing part which removably fixes the probe element at the fixing means of the cover.

[0034] After the measurement, the cartridge device can be removed from the measurement device, where the shaft is removed from the probe element, which then seals the measurement cavity against the cover, for example by means of a flange adapted to form a seal, which holds the probe element in the measurement cavity.

[0035] The fastening means of the cover preferably comprise clipping means which cooperate with clipping means of the fastening portion of the corresponding probe element.

[0036] In another embodiment, the fixing parts of the probe elements are integrally arranged on the cover, the fixing means of the cover comprising perforations.

[0037] The cover may be fixed to the cartridge body either by gluing or welding. In other embodiments, the cover is integrally configured with the cartridge body, for example made of a plastic material. It is also possible that the cover is made of a different material than the cartridge body. This may be done, for example, by moulding of two or more components.

[0038] In a further preferred embodiment, the cartridge device further comprises at least one receiving cavity configured therein for receiving sample liquid, at least one reagent cavity for holding at least one reagent, piping connecting said cavities and said at least one measuring cavity, and at least one pump means connected to the piping for transporting sample liquid from the at least one receiving cavity to the at least one measuring cavity by means of the piping, wherein a cover covers said cavity and said piping and at least partially constitutes said cavity and said piping and at least partially constitutes the pump means.

[0039] In a further embodiment, at least one reagent cavity is configured integrally with the pump means and / or with the at least one measurement cavity and / or with one or more tubings. The reagent cavity may be configured as a deep cavity or simply a small place where a reagent can be stored. Thus, the sample liquid being pumped into the measurement cavity through the tubing and pump means can be mixed with the reagent.

[0040] The pump means comprises at least one valve for directing flow of the sample liquid to direct the pumped liquid into the measurement cavity.

[0041] In other embodiments, the reagents or additional reagents may be stored in at least one reagent container that may be opened by external means.

[0042] In a further embodiment, at least one reagent container for storing a reagent is integrated within the cover.

[0043] In another embodiment, the at least one reagent container comprises a bottom that can be opened by external means in order to eject the reagent into the tubing and / or into one of the cavities. The container can be adapted, for example, as a blister container. The at least one reagent can be stored in the cartridge device in crushed, solid or liquid form.

[0044] The cartridge device may further be provided with at least one reagent stored therein. If no receiving cavity is provided, the filling of the liquid may be performed directly into the measurement cavity. To this end, the sample liquid may be injected through the cover, via an opening or through hole, into the interface element, or injected by the operator through a tube, or injected by the control device.

[0045] In the case of a receiving cavity, the sample liquid may be filled into the receiving cavity and pumped by pump means to the measuring cavity.

[0046] For filling the sample liquid, operating the pump means, adding reagents and / or opening the reagent containers, the measurement system is equipped with a control device. The control device has means for accessing the pump means through a pump access configured as a passage in the interface element. Furthermore, the control device can inject the sample liquid into the receiving cavity through an inlet in the interface element. The control device also comprises operating means for injecting or adding reagents to the cartridge device as well as opening the reagent containers. [Brief description of the drawings]

[0047] [Figure 1] FIG. 1 is a schematic diagram of the principle of thromboelastography according to Hartert. [Diagram 2] FIG. 2 is an exemplary diagram showing a typical thromboelastographic measurement. [Diagram 3] FIG. 3 is a schematic diagram of thromboelastometry. [Figure 4] FIG. 4 is a schematic diagram of a first embodiment of a cartridge device according to the present invention. [Diagram 5] FIG. 5 is a schematic diagram of a variant of the first embodiment of the cartridge device according to the invention. [Figure 6] FIG. 6 is a schematic diagram of another variant of the first embodiment of the cartridge device according to the invention. [Figure 7a] FIG. 7a is a schematic diagram of a first embodiment of a probe element. [Figure 7b] Figure 7b is a schematic illustration of a first embodiment of the probe element of figure 7a in a measurement cavity of the first or second embodiment of a cartridge device according to the invention before use. [Figure 7c] Figure 7c is a schematic illustration of the first embodiment of the probe element of figure 7a in a measurement cavity of the first or second embodiment of a cartridge device according to the invention in use. [Figure 8a] FIG. 8a is a technical diagram of the preferred probe element of FIG. 7a. [Figure 8b] FIG. 8b is a technical diagram of the preferred probe element of FIG. 7a. [Figure 8c] FIG. 8c is a technical diagram of the preferred probe element of FIG. 7a. [Figure 9a] Figure 9a is a side view of a third embodiment of a cartridge device according to the present invention. [Figure 9b] Figure 9b is a BB cross-sectional view of the cartridge device of Figure 9a, Figure 9c is a CC cross-sectional view of the cartridge device of Figure 9a, and Figure 9d is a DD cross-sectional view of the cartridge device of Figure 9a. [Figure 9c] FIG. 9c is a cross-sectional view taken along line CC of the cartridge device of FIG. 9a. [Figure 9d] FIG. 9d is a DD cross-sectional view of the cartridge device of FIG. 9a. [Figure 10a] FIG. 10a is a top view of the cartridge device of FIG. 9a. [Figure 10b] FIG. 10b is an E-E cross-sectional view of the cartridge device of FIG. 10a. [Figure 11a] Figure 11a is a cross-sectional view of the pump means of the cartridge device of Figure 9a. [Figure 11b] Figure 11b is a cross-sectional view of the pump means of Figure 11a in an operated position. [Figure 12] FIG. 12 is a schematic top view of the pump means of FIG. 11a. [Figure 13a] FIG. 13a is a side view of an embodiment of a measurement system according to the present invention. [Figure 13b] FIG. 13b is a top view of the measurement system of FIG. 13a. [Figure 13c] FIG. 13c is a HH cross-sectional view of the measurement system of FIG. 13b. [Figure 14] FIG. 14 is a cross-sectional view of a reagent container of a cartridge device according to a third embodiment of the present invention. [Figure 15] FIG. 15 is a schematic diagram of a second embodiment of a probe element. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] Further features and advantages of the present invention will become apparent from the following detailed description of the embodiments taken in conjunction with the drawings.

[0049] Parts and elements having the same function are designated with the same reference numbers.

[0050] Before proceeding to a detailed description of the preferred embodiments, the basic features and a basic practical example are described below. All embodiments refer to a cartridge device 50 (see FIG. 13c) which can be configured in the first embodiment (see FIGS. 4, 5 and 6), the second embodiment (see FIGS. 7b, 7c and 15) or the third embodiment (see FIGS. 9, 10). The cartridge device 50 includes all the parts that come into contact with the sample liquid to be tested. These may also be reagents with which the sample liquid must be mixed for the measurement. The cartridge device 50 is part of a measurement system 40 (see FIG. 13c) to which the cartridge device 50 is attached before the measurement. The measurement system 40 also comprises a control device (not shown) adapted to interact with the cartridge device 50 by electrical and / or mechanical means to control the flow and measurement of the sample liquid and to collect data. Furthermore, the device includes mechanical and electrical parts required for the measurement, data analysis and user interaction. The invention is suitable for thromboelastometry, thromboelastography and platelet aggregation measurements, but also for other blood tests that are usually performed in conjunction with surgical procedures.

[0051] A first embodiment of a cartridge device 50 according to the invention will now be described with reference to figures 4 and 5. The cartridge device 50 for a measurement system 40 for measuring medically relevant, for example viscoelastic, properties, such as the coagulation or platelet function of a sample liquid 1, in particular a blood sample, comprises a receiving cavity 16 for receiving the sample liquid 1, a pumping 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 piping for connecting said cavities. The piping comprises an inlet duct 13 from the receiving cavity 16 to the pumping means 18, an intermediate duct from the pumping means 18 to the reagent cavity 19, and an outlet duct 15 from the reagent cavity 19 to the measurement cavity 20. In variants, said cavities and ducts are arranged in a different way, one of which is shown in figure 5, in which the pumping means 18 and the reagent cavity 19 are altered.

[0052] In this embodiment, the receiving cavity 16 comprises a cavity within the cartridge device 50. The sample liquid 1 may be applied by means of a syringe, pipette or the like, for example via a self-sealing cap, shown as receiving cavity cover 33a in Fig. 10b. By operating the pumping means 18, for example by the control device described above, the sample liquid is transferred to the reagent cavity 19, where the reagents 21 required for the measurement are mixed with the sample liquid 1. The pumping of the sample liquid 1 further results in transferring it into the measurement cavity 20, where the measurement (described below) is performed.

[0053] In other embodiments the reagent cavity 19 is integrated into the pumping means 18 and / or into the measuring cavity 20 and / or into the piping. The transfer of the sample liquid 1 can be controlled by said control device.

[0054] FIG. 6 shows another variant of the first embodiment. Two arrangements of FIG. 4 with only one receiving cavity 16 are arranged in parallel, the first inlet duct 13 communicates with a second inlet duct 13' connected to a second pumping 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 a second measuring cavity 20'. FIG. 6 shows only one possible variant of several different arrangements that can be easily conceived. The sample liquid 1 is shared simultaneously between the arrangements. Controlled by an external control device, the shared portion of the sample liquid 1 is mixed into the different reagents 21, 21' during the transfer. It is clear to the skilled person that different types of tests can be combined in one cartridge device 50 to achieve maximum benefits for the user.

[0055] In a preferred embodiment, the cartridge device 50 comprises the four arrangements of Figures 4 or 5 with four measurement cavities 20, 20'. Measurements can therefore be performed with different reagents in the same sample liquid or equally with the same reagents for plausibility checks.

[0056] For example, with regard to blood clotting, there are different reagents available that activate or inhibit different parts of the clotting cascade. Pentapharm GmbH (Munich, Germany) offers, among other things, tests for activation of endogenous and exogenous blood samples (INTEM or EXTEM, respectively) and also a test for extrinsic activation, where platelet function is inhibited by administration of cytochalasin D (FIBTEM). It is state of the art that by a judicious combination of such tests it is possible to determine very precisely at what point in the clotting cascade a problem occurs. This is very important for determining the appropriate drug treatment. By comparing the results of an EXTEM test of a pathological sample with the results of a FIBTEM test of the same sample it is possible to determine precisely whether, for example, a clotting disorder is due to a deficiency of fibrinogen or a dysfunction of platelets. In general, there are different typical medical situations in which clotting disorders are highly likely to occur. For example, clotting disorders during open heart surgery are most likely due to the effects of heparin, whereas clotting disorders occurring during liver transplant surgery are simply caused by a deficiency of a particular clotting factor, etc. This basically means that different medical institutions will require different clotting tests. With reference to FIG. 6, it is possible and worthwhile to provide different cartridge devices 50 for different typical procedures. It is also possible, for example, to combine INTEM, EXTEM and FIBTEM coagulation tests with a platelet aggregation test in one cartridge. Using such a cartridge, the preparation of a measurement that provides almost all the information about the patient's coagulation status requires only two steps: mounting the cartridge device 50 on the measurement system 40 with an external control device and injecting a blood sample as one sample liquid 1. Considering the importance of the more complicated and time-consuming preparation in some thromboelastography or thromboelastometry tests, it is clear that the present invention is highly advantageous for easier, safer and more accurate POC testing.

[0057] It is important to note that the cartridge device 50 of the described embodiment is suitable for a variety of different diagnostic tests, such as thromboelastometry, thromboelastography, platelet aggregometry, etc. Depending on the type of test for which the cartridge device 50 is designed, there will be different additional components that interact with the sample during the measurement and / or external controls. Possible adaptations for thromboelastometry and platelet aggregometry are described below.

[0058] Figure 7a is a schematic diagram of a first embodiment of a probe element 22 provided in a measurement cavity 20 (see also Figures 10b and 13c). Figures 7b and 7c show a second embodiment of a cartridge device 50 in the form of a cartridge body 30 comprising only a measurement cavity 20. In the example shown, this cavity 20 is accessible through the cavity wall via tubing 15, 15'. Alternatively, the cavity 20 can be filled through the cover 31, for example by means of a syringe needle or the like.

[0059] The probe element 22 comprises a probe pin 3 (see FIG. 1) which is connected via an intermediate portion 23 to a flange 24 and to a fixed portion 25. The probe element 22 is configured as a rotating part and further comprises a connector portion 26 configured as a hole extending within the probe element 22 along its longitudinal axis, which is also the axis of rotation 5 (see FIG. 3).

[0060] 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 a cover 31 (see Figs. 10b and 13c). The cover 31 comprises an opening with a fastening means 32 above the measurement cavity 20. The probe element 22 is arranged such that the fastening part 25 of the probe element 22 corresponding to the fastening means 32 engages with the fastening means 32. In this way the probe element 22 is removably fixed to the cover 31. The fastening means 32 in this example is equipped with a circular nose that corresponds to the circular notch of the fastening part 25 of the probe element 22. The flange 24 contacts the inside of the cover 31.

[0061] During mounting of the cartridge device 50 to the measuring system 40 (see also FIG. 13c), the shaft 6 (see FIG. 3 and FIG. 13a-13c) of the measuring system 40 is inserted by its lower part, the insert part 6a, into the connector part 26. By inserting the probe element 22 into the connector part 26, the probe element 22 is removed from the cover 31 after the insert part 6a is fully inserted into the connector part 26. The probe element 22 is then placed in the measuring position as shown in FIG. 7c and is maintained in this position. The insert part 6a of the shaft 6 engages with the connector part 26 of the probe element 22, for example by friction, clip means, screw, etc. In the case of a screw, the probe element 22 is held by engagement with the cover 31 or by holes (perforations) in the cover 31. The shaft 6, which has a thread corresponding to the insert part 6a of the shaft 6, is inserted into the connector part of the probe element 22 by rotating it until the insert part 6a is fully inserted into the connector part 26. The shaft 6 can be pushed down and / or rotated with the probe element 22 fully engaged until the probe element 22 is removed from the cover 31. FIG. 7c shows the sample liquid 1 pumped into the measurement cavity 20. The probe pin 3 of the probe element 22 is immersed in the sample liquid 1. The measurement described above can be performed. After the measurement, the cartridge device 50 is removed from the measurement system 40 and the shaft 6 together with the probe element 22 is lifted against the cover 31. The insert 6a of the shaft 6 is withdrawn from the connector part 26 of the probe element 22 and the flange 24 of the probe element 22 contacts and seals against the opening in the cover 31. Instead of the flange 24, the upper end of the probe element 22 may have a larger diameter than the opening in the cover 31. The insert 6a of the shaft 6 and the measurement cavities 20, 20' are preferably configured symmetrically.

[0062] It is also possible to insert the insert portion 6a of the shaft 6 into the connector portion 26 of the probe element 22 and press the probe element 22 down until its bottom contacts the bottom of the measurement cavity 20, 20', thereby ensuring that the insert portion 6a is fully inserted into the connector portion 26. The shaft 6 is then moved into the respective measurement, operative position of the probe element 22, as shown in Figure 7c.

[0063] Figures 8a-8c are technical diagrams of a preferred embodiment of the probe element 22 of Figure 7a. Figure 8a shows a side view and Figure 8b shows a top view of the parts of the probe element 22 described with respect to Figure 7a above. Finally, Figure 8c illustrates a cross-sectional view along the axis of rotation 5. The connector portion 26 extends over 75% of the length of the probe element 22.

[0064] A third embodiment of the cartridge device 50 will now be described with reference to Figures 9a-9d and 10a-10b.

[0065] Figure 9a is a side view of a second embodiment of the third embodiment of the cartridge device 50 according to the present invention. Figure 9b is a BB cross-sectional view of the cartridge device 50 of Figure 9a. Figure 9c is a CC cross-sectional view of the cartridge device of Figure 9a. Figure 9b is a DD cross-sectional view of the cartridge device of Figure 9a. Figure 10a is a plan view of the cartridge device of Figure 9a. Figure 10b is an EE cross-sectional view of the cartridge device of Figure 10a.

[0066] The cartridge device 50 in this example is equipped with the ducts 13 and 15. The ducts are constructed in this embodiment with a diameter of about 1 mm. The ducts require that the cartridge device 50 comprises two parts, namely 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 relatively rigid and the cover 31 is constructed as an elastic part. It is then possible to integrate the pump means 18 in the cover. Furthermore, the cover 31 covers the receiving cavity 16 with a receiving cavity cover 33a, constituting a kind of liner wall 33 and a separating wall 34 constituting an inlet for the inlet duct 13 in the receiving cavity 16. The receiving cavity cover 33a can act as a self-seal for the injection of the sample liquid 1, for example by a syringe. The cover 31 constitutes the top part of the ducts 13 and 15 and also constitutes the cover of the measuring cavity 20 (see again Figs. 7b, 7c). In this example, the pump means 18 comprises a pump membrane 35 defined by the cover 31. The pump membrane 35 cooperates with a pump cavity 36 defined below the pump membrane 35 and with a pump cavity bottom 36a in the cartridge body 30.

[0067] In this embodiment the reagent cavity 19, 19' is constituted for example by the tubing and / or by the part of the pump means 18, 18 in which the reagent can be stored and discharged, in particular for example the pump cavity bottom 36a.

[0068] The pump means 18 will now be described with reference to Figures 11a, 11b and 12.

[0069] Figure 11a is a cross-sectional view of the pumping means 18, 18' of the cartridge device 50, Figure 11b is a cross-sectional view of the pumping means 18 of Figure 11a in an operative position, and Figure 12 is a schematic plan view of the pumping means 18 of Figure 11a.

[0070] In this example, the pump cavity 36 is connected to the inlet duct 13 via an inlet valve 37 and to the outlet valve 18 via an outlet valve 38. Actuation of the pump membrane 35 (shown in Fig. 11b in a working cycle) by suitable actuation means (not shown) of the control device creates a directed flow of the sample liquid 1 in the flow direction 39 indicated by the arrow. The pump membrane 35, being an integral part of the cover 31, may be a part made of the material of the cover or made of another material integrally manufactured to the cover 31, for example a part by two-component manufacture. The valves 37, 38 may be of the check valve type. Fig. 12 shows a plan view of the pump means in a schematic way.

[0071] An external force applied to the pump membrane 35 increases the pressure in the pump cavity 36, opening the outlet valve 38 and closing the inlet valve 37. Releasing the external force causes the elastic pump membrane 35 to return to the position shown in FIG. 11a, thereby closing the outlet valve 38 and opening the inlet valve 37, thereby directing the sample liquid 1 into the pump cavity 36. This mechanism is state of the art according to DE 10135569. In the context of the present invention, the actuation means of the control device, which actuate the pump membrane 35 from the outside, has the advantage that there is a strict separation between those parts in contact with the sample liquid 1 and the control device. At the same time, the total number of parts required for the cartridge device 50, and also the total number of disposable parts, is kept to a minimum.

[0072] A measurement system 40 according to the present invention will now be described in an embodiment with reference to Figures 13a to 13c, where Figure 13a is a side view of an embodiment of the measurement system 40, Figure 13b is a plan view of the measurement system 40 of Figure 13a and Figure 13c is a HH cross-sectional view of the measurement system 40 of Figure 13b.

[0073] The measuring system 40 comprises an interface element 41 on which the cartridge device 50 is attached and fixed. The interface element 41 is shown by way of example as a substrate in Figs. 13a-13c. The function of the interface element 41 is to support the shaft 6 and to maintain the position of the shaft 6 and therefore of the probe element 22 fixed in the insert 6a in the measuring position. The interface element 41 can be connected to the entire cover 31 as shown in Figs. 13a-13c or to only parts of the cover 31, for example surrounding the axis of rotation 5. The shaft 6 is rotatably supported in a bearing 7 in a shaft passage 44 (Fig. 13c) and can be rotated about the axis of rotation 5 (see Fig. 3) by driving a spring 9 via a drive means (not shown). The detection means 10 cooperate with a mirror 8 fixed on the shaft 6, as also shown in Fig. 3. The control device is likewise not shown but can be easily imagined. The actuation means and / or the manipulation means have access to the pump means 18 through an open pump access 42 in the interface element 41. The receiving cavity 16 has access to another inlet opening 43. These and other different passages of the interface element 41 with access to the cartridge device 50 and / or its cover 31 are illustrated by Fig. 13b as a top view of the measurement system 40 of Fig. 13a. For example, a passage hole 44a is provided near the axis of rotation so as to constitute an access to the cover 31 on the measurement cavity 20, 20' for the injection of sample liquid or reagents. Additional access passage holes can be provided in the interface element 41, for example on the tubing for accessing said tubing.

[0074] Figure 13c illustrates a HH section of figure 13b showing the mounted cartridge device 50 and the measurement system 40. The shaft 6 with its insert 6a is inserted into the probe element 22 and maintains it in the measurement position as described above. This embodiment comprises only one measurement cavity 20, but it is clear to those skilled in the art that improvements and combinations of the invention can be made in different ways.

[0075] Thus, for example, it is possible to provide a reagent container 19b in a blister container, as shown in FIG. 14, which is a cross-sectional view of a reagent container 19b of a third embodiment of a cartridge device 50 according to the invention. The container 19b comprises a blister cover 49 held in a retaining ring 46 in a reagent cover opening 45 of the cover 31 over the reagent cavity 19, 19' with the reagent cavity bottom 19a, 19a', a reagent 21 held in a chamber defined by a bottom 48 and a frame 47. The application of a force on the blister cover 49 by the control device opens the bottom 48 and the reagent is discharged into the reagent cavity 19, 19'. The container 19b can be fixed to the cover by clip means, for example as shown. The frame 47 can be a reinforcing ring. The blister cover 49 is reinforced so that it is not damaged when a force is applied. The tightness of the cartridge device 50 is guaranteed. In this way, a structural system is created that is utilized and the respective reagent can be easily integrated into the cartridge device 50. It is also advantageous that the reagents can be designed as small elements that are cooled and easily transported and dispensed.

[0076] It is also possible to insert a reagent container into a provided cavity that is connected to a tubing. The reagent can be designed as a sphere of suitable diameter so that it cannot flow through the opening into the tubing before being dissolved by the sample liquid.

[0077] FIG. 15 is a schematic diagram of a second embodiment of a probe element 22'. The probe element 22' is provided in the measurement cavity 20. The probe pin 3 is provided with a dimple 29 at its bottom, which, together with the nose 29a, constitutes a tip bearing that supports the probe element 22'. The probe element 22' is similar to the probe element 22 of FIG. 7a, but does not have a fixing part 25, but only a flange 24. The connector part 26 has a top part that is constituted by an insertion guide 27 for the insertion part 6a of the shaft. The probe element 22' is held in the measurement cavity 20 in a specific manner so that the insertion part 6a of the shaft 6 can be easily inserted through the opening 32a of the cover 31, which does not have a fixing means. The insertion part 6a can engage in a groove 28 inside the connector part 26 of the probe element 22'. After the engagement supported by the tip bearing, the shaft 6 is raised together with the probe element 22' in the measurement position. In practice, other engagement means can be used. [Explanation of symbols]

[0078] 1 ... sample liquid, 2 ... cup, 3 ... probe pin, 4 ... torsion wire, 5 ... rotating axis, 6 ... shaft, 6a ... insertion part, 7 ... bearing, 8 ... mirror, 9 ... spring, 10 ... detection means, 11 ... substrate, 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' ... reagent cavity bottom, 19b ... reagent container, 20, 20' ... measurement cavity, 21, 21' ... reagent, 22, 22' ... probe element, 23 ... intermediate part, 24 ... flange, 25 ... fixing part, 26 ...connector part, 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

Claims

1. a cartridge configured to couple to a system configured to determine at least one viscoelastic property associated with a portion of a test sample; a plurality of measurement cavities including a first measurement cavity and a second measurement cavity; a plurality of reagent cavities including a first reagent cavity containing a first reagent or combination of reagents and a second reagent cavity containing a second reagent or combination of reagents; a plurality of receiving cavities including a first receiving cavity for receiving a first portion of the test sample and a second receiving cavity for receiving a second portion of the test sample; a first fluid flow path in fluid communication with the first measurement cavity, the first reagent cavity, and the first receiving cavity, the first fluid flow path for transporting the first portion of the test sample from the first receiving cavity for mixing with the first reagent or combination of reagents; a second fluid flow path in fluid communication with the second measurement cavity, the second reagent cavity, and the second receiving cavity, the second fluid flow path for transporting the second portion of the test sample from the second receiving cavity for mixing with the second reagent or combination of reagents; a resilient element associated with a portion of the cartridge; the first measurement cavity is configured to receive a first mixture based on the first portion of the test sample and the first reagent or combination of reagents, the first measurement cavity being configured to enable the system to determine at least one viscoelastic property based on the first mixture; A cartridge, wherein the second measurement cavity is configured to receive a second mixture based on the second portion of the test sample and the second reagent or combination of reagents, and the second measurement cavity is configured to enable the system to determine at least one viscoelastic property based on the second mixture.

2. The cartridge of claim 1 , wherein the elastic element is at least partially arranged in the first measurement cavity or the second measurement cavity.

3. 3. The cartridge of claim 1 or 2, wherein the elastic element is configured to interface with a first probe for the first measurement cavity or configured to interface with a second probe for the second measurement cavity.

4. 3. The cartridge of claim 1, wherein the first receiving cavity is associated with a single measurement cavity that is the first measurement cavity, and the second receiving cavity is associated with a single measurement cavity that is the second measurement cavity.

5. The method further includes piping including the first fluid flow path and the second fluid flow path, the piping comprising: a first duct between the first reagent cavity and the first measurement cavity, through which the first mixture passes; a second duct between the second reagent cavity and the second measurement cavity, through which the second mixture passes; Including, 3. A cartridge according to claim 1 or 2, wherein the reagents contained in the first and second reagent cavities are in the form of solids having dimensions larger than corresponding dimensions of the tubing.

6. The method further includes piping including the first fluid flow path and the second fluid flow path, the piping comprising: a first duct between the first reagent cavity and the first measurement cavity, through which the first mixture passes; a second duct between the second reagent cavity and the second measurement cavity, through which the second mixture passes; Including, a change in pressure in the first duct allows mixing of the first portion of the test sample with the first reagent or combination of reagents; 3. A cartridge according to claim 1 or 2, wherein a change in pressure in the second duct enables mixing of the second portion of the test sample with the second reagent or combination of reagents.

7. mixing of the first portion of the test sample with the first reagent or combination of reagents occurs at least partially within the first reagent cavity; The cartridge of claim 6 , wherein mixing of the second portion of the test sample with the second reagent or combination of reagents occurs at least partially within the second reagent cavity.

8. the first measurement cavity is arranged to enable a first test on the first mixture in the first measurement cavity, the first test being to measure a first viscoelastic property based on the first mixture; the second measurement cavity is arranged to enable a second test on the second mixture in the second measurement cavity, the second test being to measure a second viscoelastic property based on the second mixture; 3. The cartridge of claim 1 or 2, wherein the first test and the second test are different.

9. 3. The cartridge of claim 1 or 2, wherein the first reagent or combination of reagents and the second reagent or combination of reagents comprise spheres configured to dissolve in the first or second portion of the test sample, respectively.

10. the first fluid flow path includes a first bend between the first reagent cavity and the first measurement cavity; The cartridge of claim 1 or 2, wherein the second fluid flow path includes a second bend between the second reagent cavity and the second measurement cavity.

11. the first fluid flow path is configured to transport the first portion of the test sample from a bottom of the first receiving cavity; The cartridge of claim 1 or 2, wherein the second fluid flow path is configured to transport the second portion of the test sample from a bottom of the second receiving cavity.

12. 3. A system configured to receive the cartridge of claim 1 or 2, the system comprising first and second probes associated with the first and second measurement cavities, respectively, the first and second probes configured to measure viscoelastic properties based on the first and second mixtures in the first and second measurement cavities, respectively.

13. 1. A method for performing a viscoelastic test using a cartridge coupled to a measurement system, comprising: A first operation, comprising: receiving a first portion of a test sample into a first receiving cavity on the cartridge; transferring the first portion of the test sample from the first receiving cavity along a first fluid flow path to a first reagent cavity, the first reagent cavity containing a first reagent or combination of reagents on the cartridge, and during transfer, the first portion of the test sample is mixed with the first reagent or combination of reagents; transporting a first mixture based on the first portion of the test sample and the first reagent or combination of reagents along the first fluid flow path to a first measurement cavity; performing a first viscoelastic test on the first mixture in the first measurement cavity through an elastic portion arranged in the first measurement cavity; performing a first operation including: A second operation, receiving a second portion of the test sample into a second receiving cavity on the cartridge; transferring the second portion of the test sample from the second receiving cavity along a second fluid flow path to a second reagent cavity, the second reagent cavity containing a second reagent or combination of reagents on the cartridge, wherein the second portion of the test sample is mixed with the second reagent or combination of reagents during transfer; transporting a second mixture based on the second portion of the test sample and the second reagent or combination of reagents along the second fluid flow path to a second measurement cavity; performing a second viscoelastic test on the second mixture in the second measurement cavity through an elastic portion arranged in the second measurement cavity; and performing a second operation including: A method, wherein at least one step of the first operation is performed simultaneously with at least one step of the second operation.

14. The method of claim 13 , further comprising the step of operating a pump to transfer the first portion of the test sample from the first receiving cavity.

15. mixing of the first portion of the test sample with the first reagent or combination of reagents occurs at least partially within the first reagent cavity; 15. The method of claim 13 or 14, wherein mixing of the second portion of the test sample with the second reagent or combination of reagents occurs at least in part within the second reagent cavity.

16. 15. The method of claim 13 or 14, wherein the first reagent or combination of reagents and the second reagent or combination of reagents comprise spheres configured to dissolve into the first or second portion, respectively, of the test sample during mixing.

17. transferring the first portion of the test sample from the first receiving cavity includes applying pressure along the first fluid flow path; 15. The method of claim 13 or 14, wherein transferring the second portion of the test sample from the second receiving cavity comprises applying pressure along the second fluid flow path.

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