Patent Description:
It is essential for survival that a wound stops bleeding, i.e. that the body possesses an adequate mechanism for haemostasis. The process of blood clotting can be activated in the case of injuries or inflammations by either extrinsic or intrinsic factors, e.g. tissue factor (TF) or Hagemann factor (F XII), respectively. Both activation channels are continued in a common branch of the cascade resulting in thrombin formation. The thrombin itself finally initiates the formation of fibrin fibres which represent the protein backbone of blood clots.

The other main constituent of the final blood clot are the thrombocytes which are interconnected by the fibrin fibres and undergo a number of physiological changes during the process of coagulation. Within limits a lack of thrombocytes can be substituted by an increased amount of fibrin or vice versa. This is reflected in the observation that the thrombocyte counts as well as the fibrinogen concentration varies even within a healthy population.

Various methods have been introduced to assess the potential of blood to form an adequate clot and to determine the blood clots stability. Common laboratory tests such as thrombocyte counts or the determination of fibrin concentration provide information on whether the tested component is available in sufficient amount but lack in answering the question whether the tested component works properly under physiological conditions (e.g. the polymerisation activity of fibrinogen under physiological conditions can not be assessed by common optical methods). Besides that, most laboratory tests work on blood-plasma and therefore require an additional step for preparation and additional time which is unfavourable especially under POC (point of care) conditions.

Another group of tests which overcomes these problems is summarized by the term "viscoelastic methods". The common feature of these methods is that the blood clot firmness (or other parameters dependent thereon) is continuously determined, from the formation of the first fibrin fibres until the dissolution of the blood clot by fibrinolysis. Blood clot firmness is a functional parameter, which is important for haemostasis in vivo, as a clot must resist blood pressure and shear stress at the site of vascular injury. Clot firmness results from multiple interlinked processes: coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activation and fibrin-platelet interaction and can be compromised by fibrinolysis. Thus, by the use of viscoelastic monitoring all these mechanisms of the coagulation system can be assessed.

A common feature of all these methods used for coagulation diagnosis is that the blood clot is placed in the space between a cylindrical pin and an axially symmetric cup and the ability of the blood clot to couple those two bodies is determined.

The first viscoelastometric method was called "thrombelastography" (<NPL>). As illustrated in <FIG>, in the thromboelastography, the sample as a sample liquid <NUM> is placed in a cup <NUM> that is periodically rotated to the left and to the right by about <NUM>°, respectively. A probe pin <NUM> is freely suspended by a torsion wire <NUM>. When a clot is formed it starts to transfer the movement of the cup <NUM> to the probe pin <NUM> against the reverse momentum of the torsion wire <NUM>. The movement of the probe pin <NUM> as a measure for the clot firmness is continuously recorded and plotted against time. For historical reasons the firmness is measured in millimetres.

The result of a typical measurement of this kind is illustrated in <FIG>. One of the most important parameters is the time between the activator induced start of the coagulation cascade and the time until the first long fibrin fibres have been build up which is indicated by the firmness signal exceeding a defined value. This parameter will be called clotting time or just CT in the following. Another important parameter is the clot formation time (CFT) which gives a measure for the velocity of the development of a clot. The CFT is defined as the time it takes for the clot firmness to increase from <NUM> to <NUM>. The maximum firmness a clot reaches during a measurement, further on referred to as maximum clot firmness or just MCF, is also of great diagnostic importance.

Modifications of the original thromboelastography technique (<CIT>) have been described by <CIT>), by <CIT>), by <CIT>). A further modification by <CIT>) illustrated in <FIG> is known under the term thromboelastometry.

Contrary to the modifications mentioned above, thromboelastometry is based on a cup <NUM> fixed in a cup holder <NUM> while the probe pin <NUM> is actively rotated. For this purpose the probe pin <NUM> is attached to a shaft <NUM> which is suspended by a ball bearing <NUM> in a base plate <NUM> and has a spring <NUM> connected to it. An oscillating motion perpendicular to the drawing plane induced at the opposite end of the spring is transformed into a periodically rotation of the shaft <NUM> and the connected cup <NUM> around a rotation axis <NUM> by about <NUM>° in each direction. As the sample liquid <NUM> begins to coagulate the motion amplitude of the shaft <NUM> which is detected by the deflection of a light beam from detecting means <NUM> and a mirror <NUM> starts to decrease.

During coagulation the fibrin backbone creates a mechanical elastic linkage between the surfaces of the blood-containing cup <NUM> and a probe pin <NUM> plunged therein. A proceeding coagulation process induced by adding one or more activating factor(s) can thus be observed. In this way, various deficiencies of a patient's haemostatic status can be revealed and can be interpreted for proper medical intervention.

A general advantage of viscoelastometric, e.g. thromboelastometric, techniques compared to other laboratory methods in this field therefore is that the coagulation process and the change of mechanical properties of the sample are monitored as a whole. This means that - in contrary to other laboratory methods mentioned above - thromboelastometry does not only indicate if all components of the coagulation pathways are available in sufficient amounts but also if each component works properly.

To obtain detailed information on the correct amount and function of the thrombocytes as well as the fibrinogen and certain factors nowadays there is an increasing amount of compounds available which activate or inhibit certain components of the coagulation system. This allows determining at which point of the coagulation system a problem is located.

For practical reasons theses compounds are usually injected into the disposable plastic cup which later on is used for the measurement by using a pipette (either a manual or an automatic one). In the last preparation step, after the blood or plasma sample has been added, the whole amount of sample (blood/plasma and the additional chemicals) is mixed by drawing it into the pipette tip and dispensing it into the cup again.

The possibility to activate or to inhibit certain components of the coagulation system is especially useful in conjunction with state-of-the-art thromboelastometers such as the ROTEM (Pentapharm GmbH, Munich, Germany) which allows conducting four measurements in parallel. This allows detailed information on the current status of the coagulation-situation of a patient to be achieved and therefore allows an appropriate therapy within several minutes.

This is of particular importance in case of patients struck by massive blood loss as it often occurs in context with multiple traumata or major surgery. The blood of such patients often is diluted due to infusions which are administered to replace the loss in volume. This leads to a decrease of the concentration of thrombocytes as well as coagulation factors including fibrinogen.

Main advantages of thromboelastometry and thromboelastography are the possibility to perform several differential tests in parallel in order to precisely determine which kinds of blood products are the appropriate medication, the possibility to perform the measurement at or close to the point of care (POC) and - compared to other methods - the relatively small amount of time until valid results are available.

On the other hand the operator has to perform a significant number of steps in order to start the measurement (preparation of the reagents, attachment of the probe pin and the cup to the instrument, pipeting and mixing the blood sample and the reagents, adjustment of computer settings, etc.) on which the time spent is considerable, especially in the case of surgery being performed.

Furthermore this rather complex preparation also increases the risk of operating errors. There have been several approaches to simplify the usage of thromboelastometers. The Rotem-System (Pentapharm GmbH, Munich, Germany) e.g. is supplied with an automatic pipette which simplifies the handling to a large degree and thereby decreases the risk of operating errors.

<CIT> describes the approach to provide the adequate amount of each of the reagents needed for one specific test in a ready-to-use mixture. In order to prevent the reaction of the reagents prior to the measurement, they are supplied in a lyophilisate state. This is additionally advantageous as the reagents can be stored at room temperature. Using this approach the preparation is reduced to the steps of adding the blood sample into the reagent container, mixing of blood with the reagent and transferring the mixture to the instrument.

<CIT> describes a hemostasis analysis device and method. The device includes a container for holding a sample to be tested and a bobber configured to be buoyantly suspended on the sample. A magnet is secured to the bobber. The container can be driven in an oscillating motion. An external magnetic field is generated adjacent to the bobber. A magnetic field strength detector detects changes in the magnetic field as a result of movement of the bobber and magnet responsive to the oscillating motion of the container and clotting of the sample.

Such a new measuring system entails acceptability problems and uncertainties for a user. Moreover, that analysis device does not fit in existing measuring systems. Therefore new systems have to be completely designed.

All these modifications lead to a significant improvement of handling of modern thromboelastometers and thromboelastographs, however, no successful approach to develop a widely automated technique has been made since Hartert's invention <NUM> years ago. One of the two main reasons of that is the fact that the measurement requires two disposable parts (cup and pin) being moved in relation to each other and thus have to be reversibly attached to different parts of the measurement device. in <FIG>, the probe pin <NUM> is attached to the shaft <NUM> and the cup <NUM> to the cup holder <NUM>, respectively. The other main reason is that different tests are required to get comprehensive information of a current bleeding status of a patient. These different tests require different reagents which have to be mixed with the blood sample.

<CIT> describes a system and a method for determining a coagulation time, e.g., TT, PT, aPTT, and ACT, of a blood test sample deposited in a test cartridge. A cartridge housing having upper and lower major sides and a minor sidewall encloses a test chamber having a test chamber pivot element and is provided with a cartridge port for introducing a test sample into the test chamber. Ferromagnetic agitator vane leaflets extend from an agitator pivot element supported by the test chamber pivot element intermediate the upper and lower major sides for rotational motion. The agitator vane leaflets can be swept, in response to an external magnetic field, through the test sample in the absence of coagulation. A timer is started when the agitator movement is commenced whereupon the agitator moves freely. Resistance to agitator movement due to coagulation is detected, and the coagulation time is measured.

It is a problem underlying the presented invention to provide a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample.

Directly connected to this invention is the problem to provide a corresponding measuring system for measuring viscoelastic characteristics of a sample liquid, in particular the coagulation characteristics of a blood sample liquid.

It is a further problem underlying the invention to provide a method for measuring viscoelastic characteristics of a sample liquid using said measuring system. These problems are solved by the subject-matter of independent claim <NUM>.

In a preferred embodiment the probe element comprises a probe pin to cooperate with the sample liquid and a connector section for a connection to the measuring system. The connector section is formed e.g. as a bore extending within the probe element and comprises frictional connection means which can be e.g. clip means or a thread. An insertion guide facilitates an insertion of a part, in particular a shaft, of a measuring system. Thereby the shaft can be connected securely to the probe element.

The measurement cavities can comprise bearing or supporting means for the probe element to align or hold the probe element prior to insertion of the shaft.

After the shaft has been inserted into the connector section, the shaft can be lifted to position the probe element at a working position.

In an alternative preferred embodiment the probe element is formed as a detachably fixed component part of the cover. An operator only has to attach the cartridge device to the measuring system the shaft being inserted into the probe element will detach the probe element from the cover and hold it securely in a position ready to carry out a measurement. Therefore the probe element comprises a fixing section for detachably fixing the probe element at fixing means of the cover.

After a measurement the cartridge device can be detached from the measuring system wherein the shaft is removed from the probe element. Then the probe element will seal the measurement cavity against the cover by means of e.g. a flange adapted to form a sealing. The cover retains the probe element within the measurement cavity.

It is preferred that the fixing means of the cover comprises clip means cooperating with corresponding clip means of the fixing section of the probe element.

In an alternative embodiment the fixing section of the probe element is integrally formed with the cover, the fixing means of the cover comprising a perforation.

The cover can be fixed on the cartridge body either by bonding or welding. In an alternative embodiment the cover is integrally formed with the cartridge body, e.g. made of a plastic material. It is also possible that the cover is made of a material which is different from the cartridge body. That can be done for example by two- or more-component-moulding.

The cartridge device further comprises receiving cavities formed therein for receiving the blood sample; reagent cavities for holding reagents; a ductwork connecting said cavities and the measurement cavities; and at least one pump means connected to the ductwork for transporting the sample liquid from the receiving cavities to the measurement cavities by means of the ductwork, wherein the cover covers and at least partially forms said cavities and said ductwork and forms at least partially the pump means.

In a further embodiment the reagent cavities are integrally formed with the pump means or/and with the measurement cavities or/and with one or more of the ductworks. The reagent cavity can be formed as a deep cavity or just a small place where reagent can be deposited. Thus the sample liquid being pumped through the ductwork and the pump means into the measurement cavity can be mixed with the reagent.

The pump means comprise at least one valve for a directed flow of the sample liquid in order to direct the pumped liquid into the measurement cavity.

The reagent or an additional reagent are stored in reagent receptacles which can be opened by external means.

In a further embodiment the reagent receptacles storing a reagent are integrated in the cover.

In another embodiment the reagent receptacles comprise a bottom part which can be opened by external means to discharge the reagent into the ductwork and/or into one of the cavities. The receptacle can be adapted as a blister receptacle, for example.

The reagents can be stored within the cartridge device in pulverized, solid or liquid form.

The cartridge device is further provided with reagents stored therein.

Filling in sample liquid, namely blood sample, can be done directly into the measurement cavity if no receiving cavity is provided. To this end the sample liquid can be injected through the cover via an opening or passage hole in the interface element or through a ductwork by an operator or by a control apparatus.

In case of a receiving cavity the sample liquid, namely blood sample, can be filled into the receiving cavity and be pumped by the pump means to the measuring cavity.

To fill in sample liquid, operate the pump means, add reagents and/or open the reagent receptacle the measuring system is equipped with a control apparatus. The control apparatus has means to access the pump means through a pump access formed as a passage of the interface element. Further the control apparatus can inject sample liquid through an inlet opening in the interface element into the receiving cavity. The control apparatus comprises also operating means to inject or to add reagents into the cartridge device as well as to open reagent receptacles.

Further features and advantages of the present invention will be evident from a description of embodiments with reference to the figures.

Parts and components having same functions are depicted with same references.

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

A first cartridge device <NUM> will be described with reference to <FIG>. The cartridge device <NUM> for the measuring system <NUM> for measuring medical relevant, e.g. viscoelastic, characteristics like coagulation or platelet function of a sample liquid <NUM>, namely a blood sample, comprises a receiving cavity <NUM> for receiving the sample liquid <NUM>, pump means <NUM> for pumping the sample liquid, a reagent cavity <NUM> for storing a reagent <NUM>, a measurement cavity <NUM> for measuring the sample liquid <NUM> and a ductwork connecting said cavities. The ductwork comprises an inlet duct <NUM> from the receiving cavity <NUM> to the pump means <NUM>, an intermediate duct from the pump means <NUM> to the reagent cavity <NUM> and an outlet duct <NUM> from the reagent cavity <NUM> to the measurement cavity <NUM>. In a variation said cavities and ducts can be arranged in different ways one of which is shown in <FIG>, wherein pump means <NUM> and reagent cavity <NUM> are changed.

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

In an alternative, the reagent cavity <NUM> is integral formed with the pump means <NUM> and/or with the measurement cavity <NUM> and/or with the ductwork. The transport of the sample liquid <NUM> can be controlled by said control apparatus.

<FIG> shows another variation. Two arrangements of <FIG> with only one receiving cavity <NUM> are arranged in parallel, wherein a first inlet duct <NUM> communicates with a second inlet duct <NUM>' connected to second pump means <NUM>'. A second intermediate duct <NUM>' leads to a second reagent cavity <NUM>' storing a second reagent <NUM>'. A second outlet duct <NUM>' connects the second reagent cavity <NUM>' to the second measurement cavity <NUM>'. <FIG> shows only one possible variation of a plurality of different arrangements easily imagined. The sample liquid <NUM> is shared among the arrangements in parallel. Controlled by the external control apparatus the shared portions of the sample liquid <NUM> are mixed with different reagents <NUM>, <NUM>' during transport. It is apparent to a person skilled in the art that in order to achieve a maximum benefit for a user different types of tests can be combined in one cartridge device <NUM>.

In a preferred embodiment the cartridge device <NUM> comprises four arrangements of <FIG> having <NUM> measurement cavities <NUM>, <NUM>'. Thus measurements can be done with different reagents on the same liquid sample or with same reagents as well to check plausibility.

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

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

<FIG> is a schematic drawing of a first embodiment of a probe element <NUM> arranged in the measurement cavity <NUM> (see also <FIG> and <FIG>). <FIG> show a second cartridge device <NUM> in form of a cartridge body <NUM> which comprises only the measurement cavity <NUM>. In the shown example this cavity <NUM> is accessible via a ductwork <NUM>, <NUM>' through a cavity wall. Alternatively the cavity <NUM> can be filled through a cover <NUM>, e.g. by injection needles or the like.

The probe element <NUM> comprises the probe pin <NUM> (see <FIG>) which is connected to a flange <NUM> and a fixing section <NUM> via an intermediate section <NUM>. The probe element <NUM> is formed as a rotational part and further comprises a connector section <NUM> formed as a bore extending within the probe element <NUM> along its longitudinal axis, which is the rotational axis <NUM> as well (see <FIG>).

The probe element <NUM> is arranged in the measurement cavity <NUM> of the cartridge body <NUM> of the cartridge device <NUM> as shown in <FIG>. The measurement cavity <NUM> is covered by the cover <NUM> (see also <FIG> and <FIG>). The cover <NUM> comprises an opening with fixing means <NUM> above the measurement cavity <NUM>. The probe element <NUM> is arranged such that its fixing section <NUM> corresponding to the fixing means <NUM> engage with them. In this manner the probe element <NUM> is detachably fixed to the cover <NUM>. The fixing means <NUM> in this example are equipped with a circular nose corresponding to a circular notch of the fixing section <NUM> of the probe element <NUM>. Other fixing means e.g. clip means or the like are possible. The flange <NUM> is in contact to the inner side of the cover <NUM>.

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

It is also possible to insert the insert section 6a of the shaft <NUM> into the connector section <NUM> of the probe element <NUM> and push the probe element <NUM> down until its bottom contacts the bottom of the measurement cavity <NUM>, <NUM>' ensuring that the insert section 6a is completely inserted into the connector section <NUM>. Then the shaft <NUM> will be moved up into the measuring resp. working position of the probe element <NUM> as shown in <FIG>.

c are technical drawings of a preferred embodiment of the probe element <NUM> of <FIG>. <FIG> shows a side view and <FIG> shows a top view of the probe element <NUM> parts of which have been described above regarding <FIG>. Finally, <FIG> illustrates a sectional view along rotational axis <NUM>. The connector section <NUM> extends over more than about <NUM>% of the length of the probe element <NUM>.

Now a third cartridge device <NUM> will be described with reference to <FIG>. d and <FIG>.

<FIG> is a side view of a second one of a third cartridge device <NUM>. <FIG> is a sectional view B-B of the cartridge device <NUM> of <FIG> is a sectional view C-C of the cartridge device of <FIG> is a sectional view D-D of the cartridge device of <FIG> is a top view of the cartridge device of <FIG> is a sectional view E-E of the cartridge device of <FIG>.

The cartridge device <NUM> of this example is equipped with the ductwork <NUM> and <NUM>. The ducts are formed with a diameter of approximately <NUM>. The ductwork requires that the cartridge device <NUM> comprises two parts: the cartridge body <NUM> and the cover <NUM>, which are glued or welded together to obtain a leak-proof device. The cartridge body <NUM> is relative rigid and the cover <NUM> is formed as an elastic part. So it is possible to integrate the pump means <NUM> into the cover <NUM>. Moreover, the cover <NUM> covers the receiving cavity <NUM> with the receiving cavity cover 33a and forms a type of liner wall <NUM> and a separation wall <NUM> forming an inlet for the inlet duct <NUM> within the receiving cavity <NUM>. The receiving cavity cover 33a might act as a self seal for injection of a sample liquid <NUM> by a syringe for example. The cover <NUM> forms top parts of the ductwork <NUM> and <NUM> and a cover of the measurement cavity <NUM> (see also <FIG>). In this example the pump means <NUM> comprises a pump membrane <NUM> formed by the cover <NUM>. The pump membrane <NUM> cooperates with a pump cavity <NUM> formed with a pump cavity bottom 36a in the cartridge body <NUM> below the pump membrane <NUM>.

A reagent cavity <NUM>, <NUM>' is formed, e.g. by sections of the ductwork or/and the pump means <NUM>, <NUM>' in which the reagents can be stored resp. deposited, especially on the pump cavity bottom 36a, for example.

The pump means <NUM> will now be described with reference to <FIG>. b and <FIG>.

<FIG> is a sectional view of the pump means <NUM>, <NUM>' of the cartridge device <NUM>, <FIG> is a sectional view of the pump means <NUM> of <FIG> in operated position, and <FIG> is a schematic top view of the pump means <NUM> of <FIG>.

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

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

Now the measuring system <NUM> according to the invention is described in an embodiment with reference to <FIG>.

<FIG> is a side view of an embodiment of the measuring system <NUM>, <FIG> is a top view of the measuring system <NUM> of <FIG>, and <FIG> is a sectional view H-H of the measuring system <NUM> of <FIG>.

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

<FIG> illustrates a sectional view H-H of <FIG> showing the mounted cartridge device <NUM> and the measuring system <NUM>. The shaft <NUM> with its insert section 6a is inserted into the probe element <NUM> and keeps it in a measurement position as mentioned above. It comprises only one measurement cavity <NUM>, but it is apparent to a person skilled in the art that modifications and combinations can be carried out in different ways.

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

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

Claim 1:
A system for measuring viscoelastic characteristics of a blood sample (<NUM>), the system comprising:
a cartridge device (<NUM>) which comprises:
a plurality of receiving cavities (<NUM>, <NUM>') for receiving blood sample (<NUM>);
a plurality of reagent cavities (<NUM>, <NUM>') each configured to store a reagent (<NUM>, <NUM>') to be mixed with blood sample (<NUM>) for measurement; and
a plurality of measurement cavities (<NUM>, <NUM>'), wherein there is one probe for each measurement cavity (<NUM>, <NUM>');
at least one pump means (<NUM>, <NUM>') for transporting blood sample (<NUM>);
ductwork (<NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>) for connecting the plurality of receiving cavities (<NUM>, <NUM>'), the plurality of reagent cavities (<NUM>, <NUM>'), the at least one pump means (<NUM>, <NUM>'), and the plurality of measurement cavities (<NUM>, <NUM>'), wherein the ductwork (<NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>) comprises inlet ducts (<NUM>, <NUM>') connecting the receiving cavities (<NUM>, <NUM>') to the at least one pump means (<NUM>, <NUM>'), ducts (<NUM>, <NUM>', <NUM>, <NUM>') connecting the at least one pump means (<NUM>, <NUM>') to the reagent cavities (<NUM>, <NUM>') and connecting the reagent cavities (<NUM>, <NUM>') to the measurement cavities (<NUM>, <NUM>'), wherein by operating the at least one pump means (<NUM>, <NUM>'), blood sample (<NUM>) is transported to the reagent cavities (<NUM>, <NUM>'), where the reagent (<NUM>, <NUM>') is to be mixed with blood sample (<NUM>); and
a cover (<NUM>), wherein the cover (<NUM>) covers and at least partially forms said cavities (<NUM>, <NUM>'; <NUM>, <NUM>', <NUM>, <NUM>') and said ductwork (<NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>, <NUM>'; <NUM>) and forms at least partially the at least one pump means (<NUM>, <NUM>');
wherein the reagent (<NUM>, <NUM>') to be stored in each of the plurality of reagent cavities (<NUM>, <NUM>') comprises a reagent or combination of reagents, the plurality of reagent cavities (<NUM>, <NUM>') including at least:
a first cavity comprising a reagent to activate coagulation; and
a second cavity comprising a reagent to activate coagulation and one or more reagents configured for suppressing thrombocyte function; and
wherein a respective probe is configured to measure a viscoelastic characteristic of a mixture of blood sample and reagent in a respective measurement cavity (<NUM>, <NUM>').