Cartridge device for a measurement system for measuring the viscoelastic properties of a sample solution, 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, particularly a blood sample. The present invention also relates to a corresponding measurement system and method.

Background Art

[0002] The ability of a wound to stop bleeding, i.e., the body having an appropriate hemostatic mechanism, is essential for survival. In the case of a wound or inflammation, the process of blood coagulation can be activated by either exogenous or endogenous factors, such as tissue factor (TF) or Hageman factor (FXII), respectively. Both activation channels are continued at a common branch of the cascade, and as a result, thrombin is formed. Thrombin itself ultimately initiates the formation of fibrin fibers, which represent the protein framework of blood coagulation.

[0003] Another major component of final blood coagulation is platelets, which are interconnected by fibrin fibers during the process of coagulation and undergo many physiological changes. Within limits, a lack of platelets can be replaced by an increased amount of fibrin, or vice versa. This is reflected in observations that platelet counts and fibrinogen concentrations vary even within a healthy population.

[0004] To evaluate the potential of blood, various methods have been introduced to form appropriate coagulation to determine the stability of blood coagulation. Common clinical tests such as determination of platelet count or fibrin concentration provide information on whether the tested component is available in sufficient quantity, but lack the ability to answer the question of whether the tested component functions properly under physiological conditions (for example, the polymerization activity of fibrinogen under physiological conditions cannot be evaluated by common optical methods). In addition, most clinical tests function in plasma, so they require additional steps for preparation and, particularly under point-of-care (POC) conditions, additional time that is not desirable.

[0005] Other groups of tests that overcome these problems are summarized by the term "viscoelastic methods." A common feature of these methods is that the stiffness of the coagulation (or other parameters on which it depends) is determined sequentially, from the formation of the initial fibrin fibers to the breakdown of the coagulation by fibrinolysis. Coagulation stiffness is a crucial functional parameter for hemostasis in vivo, as coagulation must resist blood pressure and shear stress at the site of injury within the blood vessels. Coagulation stiffness is the result of numerous interconnected processes, namely coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activity, and fibrin-platelet interactions, which can be impaired by fibrinolysis. Therefore, all these mechanisms of the coagulation system are evaluated by using viscoelastic monitoring.

[0006] A common feature of all these methods used for coagulation diagnosis is that the ability of the blood clot to bind its two bodies together is determined by placing the clot in the space between a cylindrical pin and an axially symmetric cup.

[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 Figure 1, in thromboelastography, the sample, as sample fluid 1, is placed in a cup 2 that is periodically rotated approximately 5° to the left and right. A probe pin 3 is freely supported by a torsion wire 4. When a clot forms, the movement of cup 2 begins to transmit 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 stiffness of the clot, is continuously recorded and plotted against time. For historical reasons, stiffness is measured in millimeters.

[0008] A typical result of this type of measurement is illustrated in Figure 2. One of the most important parameters is the time between the onset of the activated coagulation cascade and the formation of the first long fibrin fibers, indicated by a firmness signal exceeding a predetermined value. This parameter is called coagulation time or simply CT, as follows. Another important parameter is the clot formation time (CFT), which indicates the rate of coagulation progression. CFT is defined as the time it takes for the coagulation firmness to increase from 2 mm to 20 mm. Furthermore, the maximum firmness that the coagulation reaches during the measurement, also called maximum coagulation firmness or simply MCF, is also very important in the primary diagnosis.

[0009] Improvements to the original thromboelastography technique (Hartert et al. (U.S. Patent No. 3,714,815)) are described by Cavallari et al. (U.S. Patent No. 4,193,293), Do et al. (U.S. Patent No. 4,148,216), and Cohen (U.S. Patent No. 6,537,819). Further improvements by Calatzis et al. (U.S. Patent No. 5,777,215), illustrated in Figure 3, are known under the term thromboelastometry.

[0010] Unlike the above modification, thromboelastometry is based on the cup 2 being fixed in the 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. The oscillating motion 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 the connected cup 2 about 5° in each direction around a rotation axis 5. When the sample liquid 1 begins to solidify, the amplitude of the movement of the shaft 6, detected by the detection means 10 and mirror 9 by the displacement of the light ray, begins to decrease.

[0011] During coagulation, the fibrin skeleton creates a mechanical elastic linkage mechanism between the surface of the blood-retaining cup 2 and the probe pin 3 pressed into it. Therefore, the progression of the coagulation process, induced by the addition of one or more activators, is observed. In this method, various deficiencies in the patient's hemostatic state are revealed and interpreted for appropriate medical intervention.

[0012] In this field, a general advantage of viscoelastic techniques, such as thromboelastometry, compared to other clinical methods is that the coagulation 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 shows whether all components of the coagulation pathway are available in sufficient quantities, but also whether each component is functioning properly.

[0013] To obtain detailed information about the correct amounts and functions of platelets, fibrinogen, and specific factors, there is now an increasing number of components available to activate or inhibit specific components of the coagulation system. This makes it possible to determine problematic points in the coagulation system. For practical reasons, these components are usually injected into disposable plastic cups used for measurement, later using a pipette (manual or automatic). In the final preparation step, after the blood or plasma sample is added, the entire volume of the sample (blood / plasma and any additional chemicals) is mixed by drawing it into the tip of the pipette and redistributing it into the cup.

[0014] The ability to activate or inhibit specific components of the coagulation system is particularly useful for modern thromboelastometers such as ROTEM (Pentapharm GmbH, Munich, Germany), which allows for the simultaneous performance of four measurements. This enables the acquisition of detailed information about the patient's current coagulation state, and therefore allows for appropriate treatment within minutes.

[0015] This is particularly important in patients who suffer massive blood loss, which often occurs in situations involving multiple traumas or major surgical procedures. The blood of such patients is often diluted by intravenous infusions administered to replace the volume loss. This leads to a decrease in the concentration of platelets and clotting factors, including fibrinogen.

[0016] The main advantages of thromboelastometry and thromboelastography are that they allow for the simultaneous performance of multiple different tests to accurately determine which type of blood product is the appropriate drug, that measurements can be performed at or near the point of care (POC), and that the time to obtain valid results is relatively short compared to other methods.

[0017] On the other hand, especially when surgical procedures are performed, operators must perform a considerable number of steps (preparing reagents, attaching probe pins and cups to the instrument, pipetting and mixing blood samples and reagents, adjusting computer settings, etc.) before measurements can begin, which takes a significant amount of time.

[0018] Furthermore, this not only complicates preparation but also increases the risk of operational errors. Several attempts have been made to simplify the use of thromboestrometers. For example, supplying automated pipettes to the Rotem system (Pentapharm GmbH, Munich, Germany) greatly simplifies handling and thereby reduces the risk of operational errors.

[0019] International Publication No. 2008093216 describes an attempt to provide the appropriate amounts of each reagent required for a specific test in a ready-to-use mixture. To prevent the reagents from reacting before measurement, they are supplied in lyophilized form. This is an additional advantage as the reagents can be stored at room temperature. Using this attempt, preparation is reduced to the steps of adding the blood sample to the reagent container, mixing the blood with the reagent, and transferring the mixture to the instrument.

[0020] U.S. Patent Application Publication No. 2007 / 0059840 describes a hemostatic analysis apparatus and method. The apparatus includes a container for holding a sample to be examined and a float supported so as to float above the sample. A magnet is fixed to the float. The container may be driven to oscillate. An external magnetic field is generated in close 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 the oscillation of the container and the coagulation of the sample. [Overview of the project] [Problems that the invention aims to solve]

[0021] Such new measurement systems present problems of user acceptance and uncertainty. Furthermore, their analytical instruments are incompatible with existing measurement systems. Therefore, the new systems must be completely redesigned.

[0022] All of these modifications lead to important improvements in the operation of modern thromboelastometers and thromboelastographs. However, attempts to develop widely automated techniques have been unsuccessful since 60 years before Hartert's invention. One of the two main reasons is that two disposable parts (cup and pin), which must be moved relative to each other and thus must be reversely attached to different parts of the measuring device, are required for measurement. For example, in Figure 3, the probe pin 3 is attached to the shaft 6, and the cup 2 is attached to the cup holder 12, respectively. Another main reason is that various tests are required to obtain comprehensive information on the patient's current bleeding state. These various tests require various reagents that must be mixed into the blood sample.

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

[0024] Directly related to the present invention is the problem of providing a corresponding measurement system for measuring the viscoelastic properties of a sample liquid, particularly the coagulation properties of a blood sample liquid.

[0025] A further problem inherent in the present invention is to provide a method for measuring the viscoelastic properties of a sample liquid using the measurement system. [[ID=十三]]

Means for Solving the Problems

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

[0027] In a first embodiment, the present invention provides a cartridge device relating to a measuring system for measuring the viscoelastic properties of a sample solution, particularly a blood sample, comprising: a cartridge body having at least one measuring cavity configured inside the cartridge device and having at least one probe element disposed within the at least one measuring cavity for performing a test on the sample solution; and a cover that can be attached to the cartridge body, the cover at least partially covering the at least one measuring cavity and constituting a retaining element for holding the probe element at a predetermined position within the at least one measuring cavity.

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

[0029] In a third aspect, the present invention provides a method for measuring the viscoelastic properties of a sample liquid by the measurement system, comprising the following steps: a) providing at least one probe element disposed inside the cartridge device in a cartridge device having at least one measurement cavity; b) attaching the cartridge device to the interface element, wherein the shaft is inserted into the probe element; c) filling the measurement cavity of the cartridge device with a sample liquid; d) rotating the shaft by an oscillatory movement about the axis of rotation; 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 cooperating with the sample liquid and a connector portion for connection to the measurement system. The connector portion is configured, for example, as a hole extending within the probe element and comprises friction connection means which can be, for example, clip means or screws. An insertion guide facilitates the insertion of components of the measurement system, particularly the shaft. Thereby, the shaft can be firmly connected to the probe element.

[0031] The at least one measurement cavity may comprise holding or supporting means for the probe element for arranging or holding the probe element before 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 the operating position.

[0033] In another preferred embodiment, the probe element is configured as a component of a cover that is removably fixed. The operator only has to attach the cartridge device to the measurement system, and the shaft inserted into the probe element removes the probe element from the cover and firmly holds it in a position where measurements can be performed. Therefore, the probe element comprises a fixing portion for removably fixing the probe element at the position of the fixing means of the cover.

[0034] After measurement, the cartridge device can be removed from the measuring device. Here, the shaft is removed from the probe element. The probe element then seals the measuring cavity against the cover, for example, by a flange adapted to form a seal. The cover holds the probe element within the measuring cavity.

[0035] The means for securing the cover preferably includes a clipping means that cooperates with the clipping means of the fixing portion of the corresponding probe element.

[0036] In another embodiment, the fixing portion of the probe element is integrally formed with the cover, and the fixing means of the cover is provided with holes (perforations).

[0037] The cover may be fixed to the cartridge body by either adhesive or welding. In other embodiments, the cover is integrally formed with the cartridge body, which is manufactured from, for example, a plastic material. The cover may also be manufactured from a different material than the cartridge body. This may be done, for example, by molding two or more components.

[0038] In a further preferred embodiment, the cartridge device further comprises: at least one receiving cavity configured therein for receiving a sample solution; at least one reagent cavity for holding at least one reagent; piping connecting the cavity and the at least one measuring cavity; and at least one pumping means connected to the piping for transferring the sample solution from the at least one receiving cavity to the at least one measuring cavity, wherein the cover covers the cavity and the piping, and at least partially constitutes the cavity and the piping, and at least partially constitutes the pumping means.

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

[0040] The pumping mechanism includes at least one valve for the flow of the sample liquid to guide the pumped liquid into the measuring cavity.

[0041] In another embodiment, the reagent or additional reagent may be stored in at least one reagent container that can be opened by external means.

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

[0043] In other embodiments, at least one reagent container has a bottom that can be opened by external means to discharge the reagent into the tubing and / or into one of the cavities. The container may be adapted as, for example, a blister container. At least one reagent may be stored in the cartridge device in a crushed form, a solid form or a liquid form.

[0044] The cartridge device may be further supplied with at least one reagent to be stored inside. If a receiving cavity is not provided, filling the liquid may be done directly into the measurement cavity. To achieve this, the sample liquid may be injected into the interface element through a cover, through an opening or through hole, or injected by an operator through piping, or injected by a control device.

[0045] In the case of a receiving cavity, the sample solution can be filled into the receiving cavity and also pumped into the measurement cavity by a pumping device.

[0046] To fill the sample solution, operate the pumping mechanism, add reagents, and / or open the reagent container, the measurement system is equipped with a control device. The control device has means for accessing the pumping mechanism through a pump access configured as a passage in the interface element. Furthermore, the control device can inject the sample solution into the receiving cavity through an inlet in the interface element. The control device also includes operating means for injecting or adding reagents into the cartridge device, as well as for opening the reagent container. [Brief explanation of the drawing]

[0047] [Figure 1] Figure 1 is a schematic diagram of the principle of thromboelastography by Hartert. [Figure 2] Figure 2 is a similar diagram illustrating a typical thromboelastic measurement. [Figure 3] Figure 3 is a schematic diagram of thromboelastometry. [Figure 4] Figure 4 is a schematic diagram of a first embodiment of the cartridge device according to the present invention. [Figure 5] Figure 5 is a schematic diagram of a modification of the first embodiment of the cartridge device according to the present invention. [Figure 6] Figure 6 is a schematic diagram of another variation of the first embodiment of the cartridge device according to the present invention. [Figure 7a] Figure 7a is a schematic diagram of the first embodiment of the probe element. [Figure 7b] Figure 7b is a schematic diagram of the first embodiment of the probe element of Figure 7a in the measurement cavity of the first or second embodiment of the cartridge device according to the present invention before use. [Figure 7c] Figure 7c is a schematic diagram of the first embodiment of the probe element of Figure 7a in the measurement cavity of the first or second embodiment of the cartridge device according to the present invention in use. [Figure 8a] Figure 8a is a technical diagram of the preferred probe element in Figure 7a. [Figure 8b] Figure 8b is a technical diagram of the preferred probe element in Figure 7a. [Figure 8c] Figure 8c is a technical diagram of the preferred probe element in Figure 7a. [Figure 9a] Figure 9a is a side view of a third embodiment of the cartridge device according to the present invention. [Figure 9b] Figure 9b is a cross-sectional view of the cartridge device BB in Figure 9a. Figure 9c is a cross-sectional view of the cartridge device CC in Figure 9a. Figure 9d is a cross-sectional view of the cartridge device DD in Figure 9a. [Figure 9c] Figure 9c is a cross-sectional view of the cartridge device shown in Figure 9a. [Figure 9d] Figure 9d is a cross-sectional view of the DD cartridge device shown in Figure 9a. [Figure 10a] Figure 10a is a top view of the cartridge device shown in Figure 9a. [Figure 10b] Figure 10b is a cross-sectional view of the EE section of the cartridge device shown in Figure 10a. [Figure 11a] Figure 11a is a cross-sectional view of the pumping mechanism of the cartridge device shown in Figure 9a. [Figure 11b] Figure 11b is a cross-sectional view of the pumping mechanism in Figure 11a at the operating position. [Figure 12] Figure 12 is a schematic top view of the pumping mechanism shown in Figure 11a. [Figure 13a] Figure 13a is a side view of an embodiment of the measurement system according to the present invention. [Figure 13b] Figure 13b is a top view of the measurement system shown in Figure 13a. [Figure 13c] Figure 13c is a cross-sectional view of the measurement system shown in Figure 13b. [Figure 14] Figure 14 is a cross-sectional view of a reagent container according to a third embodiment of the cartridge device according to the present invention. [Figure 15] Figure 15 is a schematic diagram of a second embodiment of the probe element. [Modes for carrying out the invention]

[0048] Further features and advantages of the present invention will become apparent from the description of the embodiments, along with reference to the drawings.

[0049] Parts and elements with the same function are indicated by the same reference number.

[0050] Prior to a detailed description of preferred embodiments, the basic features and basic practical examples are described below. All embodiments refer to a cartridge device 50 (see Figure 13c) which may be configured in the first embodiment (see Figures 4, 5, and 6), the second embodiment (see Figures 7b, 7c, and 15), or the third embodiment (see Figures 9 and 10). The cartridge device 50 includes all components that come into contact with the sample solution to be tested. These may also be reagents to which the sample solution must be mixed for measurement. The cartridge device 50 is a component of a measurement system 40 (see Figure 13c) to which the cartridge device 50 is mounted before measurement. The measurement system 40 also includes a control device (not shown) adapted to interact with the cartridge device 50 by electrical and / or mechanical means to control the flow of the sample solution and measurement, as well as to collect data. Furthermore, the device includes mechanical and electrical components required for measurement, data analysis, and user interaction. The present invention is suitable not only for thromboelastometry, thromboelastography, and platelet aggregation measurement, but also for other blood tests commonly performed in relation to surgical procedures.

[0051] A first embodiment of the cartridge device 50 of the present invention will be described with reference to Figures 4 and 5. The cartridge device 50 for a measuring system 40 for measuring medical-related properties, such as viscoelastic properties, such as coagulation or platelet function of a sample solution 1, particularly a blood sample, comprises a receiving cavity 16 for receiving the sample solution 1, a pumping means 18 for pumping the sample solution, a reagent cavity 19 for storing reagents 21, a measuring cavity 20 for measuring the sample solution 1, and piping for connecting the respective 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 measuring cavity 20. In a modified form, the cavities and ducts are arranged in different ways, one of which is shown in Figure 5, in which the pumping means 18 and the reagent cavity 19 are changed.

[0052] In this embodiment, the receiving cavity 16 consists of a cavity within the cartridge device 50. The sample solution 1 can be used by a syringe, pipette, etc., via a self-sealing cap, for example, shown as the receiving cavity cover 33a in Figure 10b. For example, by operating the pump means 18 by the control device described above, the sample solution is transferred to the reagent cavity 19, where the reagents 21 required for measurement are mixed with the sample solution 1. Furthermore, the pumping of the sample solution 1 transfers it into the measurement cavity 20 where the measurement (described below) is performed.

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

[0054] Figure 6 shows another variation of the first embodiment. Two arrangements of Figure 4, each with only one receiving cavity 16, are arranged in parallel, with the first inlet duct 13 communicating with a second inlet duct 13' which is connected to a second pumping means 18'. The second intermediate duct 14' connects to a second reagent cavity 19' which stores a second reagent 21'. The second outlet duct 15' connects the second reagent cavity 19' to a second measuring cavity 20'. Figure 6 shows only one of several easily conceivable different arrangeable variations. The sample solution 1 is shared simultaneously between the arrangements. Controlled by an external control device, the shared portion of the sample solution 1 is mixed with different reagents 21, 21' during transfer. It will be apparent to those skilled in the art that different types of tests can be combined in a single cartridge device 50 to achieve the greatest benefit to the user.

[0055] In a preferred embodiment, the cartridge device 50 comprises four arrangements as shown in Figure 4 or 5, each having four measuring cavities 20, 20'. Therefore, measurements can be performed with different reagents or similarly with the same reagents in the same sample solution to check validity.

[0056] For example, regarding blood clotting, there are various useful reagents that activate or inhibit different parts of the coagulation cascade. Pentapharm GmbH (Munich, Germany) offers, among many, tests for the activation of endogenous and exogenous blood samples (INTEM or EXTEM, respectively), as well as tests for exogenous activation where platelet function is inhibited by the administration of cytochalasin D (FIBTEM). The latest technology allows for a very accurate determination of the point in the coagulation cascade where the problem occurs through a clever combination of such tests. This is crucial for determining appropriate drug treatment. By comparing the results of EXTEM testing of a pathological sample with the results of FIBTEM testing of the same sample, it becomes possible to accurately determine, for example, whether a coagulation disorder is due to fibrinogen deficiency or platelet dysfunction. In general, there are different typical medical situations in which coagulation disorders are very likely to occur. For example, coagulation disorders during cardiac surgery are most likely to be due to the effects of heparin, while coagulation disorders occurring during liver transplant surgery are simply caused by a deficiency of specific coagulation factors, etc. This basically means that different medical institutions will require different coagulation tests. Referring to Figure 6, it is possible and valuable to provide different cartridge devices 50 for different typical surgeries. Furthermore, it is also possible, for example, to combine INTEM, EXTEM, and FIBTEM coagulation tests into a platelet aggregation test within a single cartridge. Using such a cartridge, preparing a measurement that provides almost all information about a patient's coagulation state requires only two steps: attaching the cartridge device 50 to a measurement system 40 with an external control device, and injecting a blood sample as a single sample solution 1. Given the importance of the more complex 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 point-of-care (POC) testing.

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

[0058] Figure 7a is a schematic diagram of a first embodiment of a probe element 22 located within a measuring 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 the measuring cavity 20. In the example shown, the cavity 20 is accessible through the cavity wall via piping 15, 15'. Alternatively, the cavity 20 may be filled through a cover 31, for example, by a syringe needle.

[0059] The probe element 22 includes a probe pin 3 (see Figure 1) that is connected to the flange 24 and the fixing part 25 via an intermediate part 23. The probe element 22 is configured as a rotating part and further includes a connector part 26 which is configured as a hole extending into the probe element 22 along its longitudinal axis (which is also the rotation axis 5 (see Figure 3)).

[0060] The probe element 22 is located in the measuring cavity 20 of the cartridge body 30 of the cartridge device 50, as shown in Figure 7b. The measuring cavity 20 is covered by a cover 31 (see Figures 10b and 13c). The cover 31 has an opening above the measuring cavity 20, with a fixing means 32. The probe element 22 is positioned such that a fixing portion 25 of the probe element 22, corresponding to the fixing means 32, engages with the fixing means 32. In this configuration, the probe element 22 is removably fixed to the cover 31. In this example, the fixing means 32 is equipped with a circular nose corresponding to a circular notch in the fixing portion 25 of the probe element 22. A flange 24 contacts the inside of the cover 31.

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

[0062] The insertion portion 6a of the shaft 6 is inserted into the connector portion 26 of the probe element 22, and the probe element 22 is pushed down until its bottom contacts the bottom of the measuring cavities 20, 20', thereby ensuring that the insertion portion 6a is fully inserted into the connector portion 26. The shaft 6 is then moved to the respective measuring and operating positions 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 shown in Figure 7a. Figure 8a shows a side view, and Figure 8b shows a plan view of the components of the probe element 22 described above with respect to Figure 7a. Finally, Figure 8c illustrates a cross-sectional view along the rotation axis 5. The connector portion 26 extends beyond 75% of the length of the probe element 22.

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

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

[0066] The cartridge device 50 in this example is equipped with piping 13 and 15. The duct in this embodiment is made up of a diameter of approximately 1 mm. The piping requires the cartridge device 50 to be equipped with two parts, namely the cartridge body 30 and the cover 31, which are bonded or welded together to obtain a leak-proof device. The cartridge body 30 is made of a relatively rigid material, and the cover 31 is made of an elastic material. This makes it possible to integrate the pumping means 18 into the cover. Furthermore, the cover 31 covers the receiving cavity 16 with a receiving cavity cover 33a, which constitutes a kind of liner wall 33 and a separation wall 34 which constitutes an inlet for the inlet duct 13 within the receiving cavity 16. The receiving cavity cover 33a can act as a self-seal for injecting the sample liquid 1, for example, by syringe. The cover 31 constitutes the top part of the piping 13 and 15, as well as the cover of the measuring cavity 20 (see again Figures 7b, 7c). In this example, the pumping means 18 includes a pump membrane 35 formed by a cover 31. The pump membrane 35 cooperates with the pump cavity 36, which is formed together with the pump cavity bottom 36a in the cartridge body 30, beneath the pump membrane 35.

[0067] In this embodiment, the reagent cavities 19,19' are comprised of, for example, portions of piping and / or pumping means 18,18 from which reagents can be stored and discharged, particularly, for example, the portion of the bottom 36a of the pump cavity.

[0068] Here, the pumping mechanism 18 will 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 in Figure 11a at the operating position, and Figure 12 is a schematic plan view of the pumping means 18 in Figure 11a.

[0070] In this example, the pump cavity 36 is connected to the inlet duct 13 via the inlet valve 37 and to the outlet valve via the outlet valve 38. The operation of the pump membrane 35 by appropriate actuators (not shown) of the control device (shown in Figure 11b during the work cycle) creates an guided flow of the sample liquid 1 in the flow direction 39 indicated by the arrow. The pump membrane 35, which is an integrated part of the cover 31, may be manufactured from the material of the cover or from other materials manufactured integrally with the cover 31, for example, a part manufactured from two components. The valves 37 and 38 may be of the check valve type. Figure 12 shows a plan view of the pump mechanism in a schematic manner.

[0071] The 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. By releasing the external force, the elastic pump membrane 35 returns to the position shown in Figure 11a, thereby closing the outlet valve 38 and opening the inlet valve 37, allowing the sample liquid 1 to enter the pump cavity 36. This mechanism is the latest technology according to German Patent No. 10135569. In the context of the present invention, the actuation means of the control device that operates the pump membrane 35 from the outside has the advantage that the control device is strictly separated from the parts that come into contact with the sample liquid 1. At the same time, the total number of parts required in the cartridge device 50, and furthermore the total number of disposable parts, is kept to a minimum.

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

[0073] The measurement system 40 includes an interface element 41 to which a cartridge device 50 is attached and fixed. The interface element 41 is shown in Figures 13a to 13c as an example of a substrate. The function of the interface element 41 is to support the shaft 6 and to maintain the position of the shaft 6 and, therefore, the position of the probe element 22 fixed to the insertion part 6a at the measurement position. The interface element 41 can be connected to the entire cover 31, or to only parts of the cover 31, for example, surrounding the rotating shaft 5, as shown in Figures 13a to 13c. The shaft 6 is rotatably supported in a bearing 7 within a shaft passage 44 (Figure 13c) and can rotate around the rotating shaft 5 (see Figure 3) by driving a spring 9 via a drive means (not shown). The detection means 10 cooperates with a mirror 8 fixed on the shaft 6, as also shown in Figure 3. The control device described above is also not shown but can be easily conceived. The operating and / or manipulating means can access the pumping means 18 through an open pump access 42 within the interface element 41. The receiving cavity 16 can access another inlet opening 43. These and other different passages of the interface element 41 having access to the cartridge device 50 and / or its cover 31 are illustrated by Figure 13b as a plan view of the measuring system 40 in Figure 13a. For example, a passage hole 44a is provided near the pivot axis to constitute access to the cover 31 on the measuring cavity 20, 20' for injection of sample liquid or reagent. Additional access passage holes may be provided within the interface element 41, for example, on the piping to access the piping.

[0074] Figure 13c illustrates an HH cross-sectional view of Figure 13b showing the mounted cartridge device 50 and measuring system 40. The shaft 6 with its insertion portion 6a is inserted into the probe element 22 and maintained in the measuring position as described above. Although this embodiment has only one measuring cavity 20, it will be apparent to those skilled in the art that improvements and combinations of the present invention can be carried out in different ways.

[0075] Therefore, for example, as shown in Figure 14, a cross-sectional view of the reagent container 19b of a third embodiment of the cartridge device 50 according to the present invention, it is possible to provide the reagent container 19b within a blister container. The container 19b contains a reagent 21 held within a chamber defined by a blister cover 49, a bottom 48 and a frame 47, which is held within a retaining ring 46 in a reagent cover opening 45 of a cover 31 on reagent cavities 19, 19' with reagent cavity bottoms 19a, 19a'. The bottom 48 opens when a force is applied to the blister cover 49 by a control device, and the reagent is discharged into the reagent cavities 19, 19'. The container 19b can be secured to the cover by clipping means as shown, for example. The frame 47 may be a reinforcing ring. The blister cover 49 is reinforced so as not to be damaged when force is applied. The airtightness of the cartridge device 50 is guaranteed. In this method, the structural system to be used is constructed so that each reagent can be easily integrated into the cartridge device 50. It is also advantageous that the reagents can be cooled and designed as small components that are easily transported and supplied.

[0076] It is also possible to insert reagent containers into a provided cavity connected to the piping. The reagents may be designed as spherical containers of appropriate diameter so that they cannot flow into the piping through the opening before being dissolved by the sample solution.

[0077] Figure 15 is a schematic diagram of a second embodiment of the probe element 22'. The probe element 22' is housed within the measuring cavity 20. The probe pin 3 is provided with a dimple 29 at its base. The dimple 29, 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 in Figure 7a, but lacks the fixing portion 25 and has only the flange 24. The connector portion 26 has a top portion consisting of an insertion guide 27 for the shaft insertion portion 6a. The probe element 22' is held within the measuring cavity 20 in a specific manner so that the insertion portion 6a of the shaft 6 can be easily inserted through the opening 32a of the cover 31, which has no fixing means. The insertion portion 6a can engage with a groove 28 inside the connector portion 26 of the probe element 22'. After engagement supported by the tip bearing, the shaft 6 is pulled up together with the probe element 22' in the measuring position. In practice, other engagement means are available. [Explanation of Symbols]

[0078] 1...Sample liquid, 2...Cup, 3...Probe pin, 4...Torsion wire, 5...Rotation 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'...Bottom of reagent cavity, 19b...Reagent container, 20,20'...Measurement cavity, 21,21'...Reagent, 22,22'...Probe element, 23...Intermediate part, 24...Flange, 25...Fixing part, 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…Measurement 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 be coupled to a system, the system being configured to determine at least one viscoelastic property related to a portion of a test sample, A plurality of measurement cavities including a first measurement cavity and a second measurement cavity, A plurality of receiving cavities, including a first receiving cavity for receiving a first portion of the test sample, which is empty before receiving the first portion of the test sample, and a second receiving cavity for receiving a second portion of the test sample, which is empty before receiving the second portion of the test sample. A first fluid channel that is in fluid communication with the first measurement cavity and the first receiving cavity, the first fluid channel for transferring 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 channel in fluid communication with the second measuring cavity and the second receiving cavity, the second fluid channel for transferring the second portion of the test sample from the second receiving cavity for mixing with the second reagent or combination of reagents, 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, and the first measurement cavity is configured to enable the system to determine at least one first viscoelastic property based on the first mixture. A cartridge wherein the second measuring 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 measuring cavity is configured to enable the system to determine at least one second viscoelastic property based on the second mixture.

2. The cartridge according to claim 1, wherein the first receiving cavity is associated with a single measuring cavity which is the first measuring cavity, and the second receiving cavity is associated with a single measuring cavity which is the second measuring cavity.

3. The first fluid channel is configured such that the first portion of the test sample is mixed with the first reagent or combination of reagents during transfer. The cartridge according to claim 1, wherein the second fluid channel is configured such that the second portion of the test sample is mixed with the second reagent or combination of reagents during transport.

4. A first reagent cavity that holds the first reagent or combination of reagents, The present invention further comprises a second reagent cavity that holds the second reagent or combination of reagents, The first fluid passage and the second fluid passage include piping, and the piping is 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; Includes, The cartridge according to claim 1, wherein the reagents contained in the first reagent cavity and the second reagent cavity are in the form of solids having dimensions larger than the corresponding dimensions of the ducts in the piping.

5. The first fluid passage and the second fluid passage are configured to be connected to at least one pump. The pressure change provided in the first fluid passage by the at least one pump enables mixing of the first portion of the test sample with the first reagent or combination of reagents. The cartridge according to claim 1, wherein the pressure change provided in the second fluid passage by the at least one pump enables mixing of the second portion of the test sample with the second reagent or combination of reagents.

6. A first reagent cavity that holds the first reagent or combination of reagents, The present invention further comprises a second reagent cavity that holds the second reagent or combination of reagents, The mixing of the first portion of the test sample and the first reagent or combination of reagents occurs, at least partially, within the first reagent cavity. The cartridge according to claim 1, wherein mixing of the second portion of the test sample and the second reagent or combination of reagents occurs, at least partially, within the second reagent cavity.

7. The first measurement cavity is positioned to allow a first test on the first mixture within the first measurement cavity, the first test being for measuring a first viscoelastic property based on the first mixture, The second measurement cavity is positioned to allow a second test on the second mixture within the second measurement cavity, the second test being for measuring a second viscoelastic property based on the second mixture, The cartridge according to claim 1, wherein the first test and the second test are different tests using different reagents.

8. The cartridge according to claim 1, comprising a sphere configured such that the first reagent or combination of reagents and the second reagent or combination of reagents each dissolve in the first or second portion of the test sample.

9. The first fluid flow path includes a first curved section prior to the first measurement cavity, The cartridge according to claim 1, wherein the second fluid passage includes a second curved section prior to the second measuring cavity.

10. The first fluid channel is configured to transport the first portion of the test sample from the bottom of the first receiving cavity, The cartridge according to claim 1, wherein the second fluid channel is configured to transport the second portion of the test sample from the bottom of the second receiving cavity.

11. A system comprising a cartridge and first and second probes, The aforementioned cartridge A plurality of measurement cavities including a first measurement cavity and a second measurement cavity, A plurality of receiving cavities, including a first receiving cavity for receiving a first portion of the test sample, which is empty before receiving the first portion of the test sample, and a second receiving cavity for receiving a second portion of the test sample, which is empty before receiving the second portion of the test sample. A first fluid channel that is in fluid communication with the first measurement cavity and the first receiving cavity, the first fluid channel for transferring 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 channel that is in fluid communication with the second measurement cavity and the second receiving cavity, the second fluid channel for transferring the second portion of the test sample from the second receiving cavity to mix it with the second reagent or combination of reagents. Includes, 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, and the first measurement cavity is configured to enable the system to determine at least one first viscoelastic property based on the first mixture. 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 second viscoelastic property based on the second mixture. A system in which the first and second probes are associated with the first and second measurement cavities, respectively, and are configured to measure the viscoelastic properties based on the first and second mixtures within the first and second measurement cavities, respectively.

12. A method for performing a viscoelasticity test using a cartridge coupled to a measurement system, The first operation is, A step of receiving a first portion of a test sample into a first receiving cavity on the cartridge, wherein the first receiving cavity is empty before receiving the first portion of the test sample. A step of transferring the first portion of the test sample from the first receiving cavity along a first fluid channel to a location containing a first reagent or combination of reagents, wherein during the transfer, the first portion of the test sample is mixed with the first reagent or combination of reagents. The steps include transferring 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, The steps include performing a first viscoelasticity test on the first mixture in the first measurement cavity, Performing a first operation which includes, The second operation is, A step of receiving a second portion of the test sample into a second receiving cavity on the cartridge, wherein the second receiving cavity is empty before receiving the second portion of the test sample. A step of transferring the second portion of the test sample from the second receiving cavity along the second fluid channel to a location containing the second reagent or reagent combination, wherein during the transfer, the second portion of the test sample is mixed with the second reagent or reagent combination. The steps include transferring a second mixture, based on the second portion of the test sample and the second reagent or combination of reagents, along the second fluid channel to a second measurement cavity, The steps include performing a second viscoelastic test on the second mixture in the second measurement cavity, A method comprising performing a second operation which includes the following.

13. The method according to claim 12, wherein the first receiving cavity is associated with a single measuring cavity which is the first measuring cavity, and the second receiving cavity is associated with a single measuring cavity which is the second measuring cavity.

14. The method according to claim 12, further comprising the step of operating a pump to transfer the first portion of the test sample from the first receiving cavity.

15. The mixing of the first portion of the test sample and the first reagent or combination of reagents occurs, at least partially, within the first reagent cavity on the cartridge. The method according to claim 12, wherein the mixing of the second portion of the test sample and the second reagent or combination of reagents occurs, at least partially, in the second reagent cavity on the cartridge.

16. The first mixture is transferred to the first measuring cavity through the curve in the first fluid channel. The method according to claim 12, wherein the second mixture is transferred to the second measuring cavity through a curve in the second fluid channel.

17. The method according to claim 12, comprising a sphere configured such that the first reagent or combination of reagents and the second reagent or combination of reagents dissolve in the first or second portion of the test sample, respectively, during mixing.

18. The step of transferring the first portion of the test sample from the first receiving cavity includes applying pressure along the first fluid passage, The method according to claim 12, wherein the step of transferring the second portion of the test sample from the second receiving cavity includes applying pressure along the second fluid passage.

19. The first portion of the test sample is transferred from the bottom of the first receiving cavity. The method according to claim 12, wherein the second portion of the test sample is transported from the bottom of the second receiving cavity.

20. The method according to claim 12, wherein at least one step of the first operation is performed simultaneously with at least one step of the second operation.

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