CARTRIDGE DEVICE FOR A MEASURING SYSTEM FOR MEASURING VISCOELASTIC CHARACTERISTICS OF A SAMPLE LIQUID, A CORRESPONDING MEASURING SYSTEM, AND A CORRESPONDING METHOD
20230349932 · 2023-11-02
Assignee
Inventors
Cpc classification
B01L2300/0636
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0627
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/10
PERFORMING OPERATIONS; TRANSPORTING
G01N11/00
PHYSICS
B01L3/502
PERFORMING OPERATIONS; TRANSPORTING
G01N33/86
PHYSICS
B01L2400/0475
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0861
PERFORMING OPERATIONS; TRANSPORTING
B01L3/52
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/087
PERFORMING OPERATIONS; TRANSPORTING
International classification
G01N33/86
PHYSICS
B01L3/00
PERFORMING OPERATIONS; TRANSPORTING
G01N11/00
PHYSICS
Abstract
The present invention is directed to a cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, in particular a blood sample, comprising a cartridge body having at least one measurement cavity formed therein and having at least one probe element arranged in said at least one measurement cavity for performing a test on said sample liquid; and a cover being attachable on said cartridge body; wherein said cover covers at least partially said at least one measurement cavity and forms a retaining element for retaining said probe element in a predetermined position within said at least one measurement cavity. The invention is directed to a measurement system and a method for measuring viscoelastic characteristics of a sample liquid.
Claims
1-18. (canceled)
19. A cartridge for a measuring system, the cartridge comprising: at least two testing cavities, each testing cavity of the at least two testing cavities being configured to perform a respective test to determine a respective viscoelastic characteristic associated with a respective liquid, each respective test comprising an independent test to determine the respective viscoelastic characteristic associated with the respective liquid; at least two receiving cavities, each receiving cavity of the at least two receiving cavities being configured to receive a respective component used to produce the respective liquid, each receiving cavity being a different structure and being configured to hold at least an amount of the respective component that enables determination of the respective viscoelastic characteristic by testing performed in a respective testing cavity; at least two reagent cavities, each reagent cavity of the at least two reagent cavities being configured to hold at least one respective reagent, each receiving cavity being devoid of reagent prior to receiving the respective component used to produce the respective liquid; and ductwork connecting each respective receiving cavity, each respective reagent cavity, and each respective testing cavity, each of the at least two receiving cavities and each of the at least two reagent cavities being different from the ductwork; wherein: each respective reagent cavity has a larger volume than a portion of the ductwork that has a length equivalent to a length of each respective reagent cavity, the length of each respective reagent cavity being measured along a respective first axis connecting an inlet and an outlet of each respective reagent cavity, each respective receiving cavity has a larger volume than a portion of the ductwork that has a length equivalent to a length of each respective receiving cavity, the length of each respective receiving cavity being measured along a respective second axis that is parallel to the respective first axis, and each respective reagent cavity is between each respective receiving cavity and each respective testing cavity in a respective fluid flow path; wherein each respective reagent cavity is configured to receive the respective component from each respective receiving cavity and to enable mixing of the respective component and the at least one respective reagent to produce the respective liquid; wherein the ductwork comprises (i) first ducts, each respective first duct being fluidically connected between each respective receiving cavity and each respective reagent cavity and (ii) second ducts, each respective second duct being fluidically connected between each respective reagent cavity and each respective testing cavity, the first ducts and the second ducts being parts of respective fluid flow paths from each respective receiving cavity to and through each respective reagent cavity and subsequently to each respective testing cavity; and wherein each receiving cavity is associated with a single testing cavity.
20. The cartridge of claim 19, wherein the ductwork is configured so that, in response to pressure, the respective component and the at least one respective reagent mix to form the respective liquid during transport.
21. The cartridge of claim 19, wherein the at least two receiving cavities comprise a first receiving cavity and a second receiving cavity, wherein the at least two testing cavities comprise a first testing cavity and a second testing cavity, and wherein the at least two reagent cavities comprise a first reagent cavity and a second reagent cavity; and wherein respective first ducts are fluidically connected between the first receiving cavity and the first reagent cavity and between the second receiving cavity and the second reagent cavity, and respective second ducts are fluidically connected between the first reagent cavity and the first testing cavity and between the second reagent cavity and the second testing cavity so as to create a single first fluid flow path of the respective fluid flow paths from the first receiving cavity through the first reagent cavity to the first testing cavity and a single second fluid flow path of the respective fluid flow paths from the second receiving cavity through the second reagent cavity to the second testing cavity.
22. The cartridge of claim 21, wherein different reagents of the at least one respective reagent are positioned in each of the first reagent cavity and the second reagent cavity such that a reagent in the first reagent cavity is different from a reagent in the second reagent cavity.
23. The cartridge of claim 19, wherein each respective first duct, each respective second duct, each respective receiving cavity, each respective reagent cavity, and each respective testing cavity is part of a single respective fluid flow path configured to transport liquids between each respective receiving cavity and each respective testing cavity.
24. A system configured to measure viscoelastic characteristics associated with a blood sample, the system comprising: a cartridge comprising: a first receiving cavity configured to receive a first part of the blood sample; a second receiving cavity configured to receive a second part of the blood sample; the second receiving cavity being separate from the first receiving cavity; a first reagent cavity configured to hold at least one first reagent; a second reagent cavity configured to hold at least one second reagent; a first testing cavity configured to hold a first liquid that is based on the first part of the blood sample and the at least one first reagent, the first testing cavity being configured to enable performance of a first viscoelastic test based on the first liquid in the first testing cavity; a second testing cavity configured to hold a second liquid that is based on the second part of the blood sample and the at least one second reagent, the second testing cavity being configured to enable performance of a second viscoelastic test based on the second liquid in the second testing cavity; ductwork comprising: a first duct fluidically connected between the first reagent cavity and the first receiving cavity; a second duct fluidically connected between the first reagent cavity and the first testing cavity; a third duct fluidically connected between the second reagent cavity and the second receiving cavity; a fourth duct fluidically connected between the second reagent cavity and the second testing cavity; the first receiving cavity being associated with a single testing cavity which is the first testing cavity, the first receiving cavity being devoid of reagent prior to receiving the first part of the blood sample, and the first receiving cavity having a larger volume than a portion of the ductwork that has a length equivalent to a length of the first receiving cavity; the first reagent cavity having a larger volume than a portion of the ductwork that has a length equivalent to a length of the first reagent cavity, the length of the first reagent cavity comprising a dimension along a first axis connecting an inlet and an outlet of the first reagent cavity, and the length of the first receiving cavity comprising a dimension that is parallel to the first axis; the second receiving cavity being associated with a single testing cavity which is the second testing cavity, the second receiving cavity being devoid of reagent prior to receiving the second part of the blood sample, and the second receiving cavity having a larger volume than a portion of the ductwork that has a length equivalent to a length of the second receiving cavity; and the second reagent cavity having a larger volume than a portion of the ductwork that has a length equivalent to a length of the second reagent cavity, the length of the second reagent cavity comprising a dimension along a second axis connecting an inlet and an outlet of the second reagent cavity, and the length of the second receiving cavity comprising a dimension that is parallel to the second axis; the at least one first reagent comprising a reagent that is in the first reagent cavity for mixing with the first part of the blood sample; and the at least one second reagent comprising a reagent that is different than the at least one first reagent and that is in the second reagent cavity for mixing with the second part of the blood sample, the first viscoelastic test being independent of the second viscoelastic test.
25. The system of claim 24, wherein the at least one first reagent and the at least one second reagent comprise reagent globules configured to dissolve in respective parts of the blood sample.
26. The system of claim 24, where the at least one first reagent comprises one of: a reagent that interacts with the first part of the blood sample and that is configured to activate coagulation via an intrinsic pathway; a reagent that interacts with the first part of the blood sample and that comprises (i) a reagent or a combination of reagents configured to activate coagulation or (ii) a reagent or a combination of reagents configured to suppress thrombocyte contraction; or a reagent that interacts with the first part of the blood sample and that is configured to activate coagulation via an extrinsic pathway.
27. The system of claim 24, further comprising: a first pressure-controlled stop to inhibit entry of the first part of the blood sample into the first reagent cavity; and a second pressure-controlled stop to inhibit entry of the second part of the blood sample into the second reagent cavity.
28. The system of claim 27, wherein the first pressure-controlled stop comprises a first valve and the second-pressure controlled stop comprise a second valve.
29. The system of claim 24, wherein the first receiving cavity, the first reagent cavity, the first testing cavity, the first duct, and the second duct are parts of a first fluid flow path; and wherein the second receiving cavity, the second reagent cavity, the second testing cavity, the third duct, and the fourth duct are parts of a second fluid flow path, the first fluid flow path being arranged in parallel to the second fluid flow path.
30. The system of claim 24, wherein a first fluid flow path through the cartridge comprises a single first fluid flow path associated with both the first receiving cavity and the first testing cavity, the first fluid flow path being configured to transport liquids between the first receiving cavity and the first testing cavity; and wherein a second fluid flow path through the cartridge comprises a single second fluid flow path associated with both the second receiving cavity and the second testing cavity, the second fluid flow path being configured to transport liquids between the second receiving cavity and the second testing cavity.
31. The system of claim 24, further comprising: a first element arranged relative to the first testing cavity, the first element being configured to measure a viscoelastic characteristic based on the first liquid; and a second element arranged relative to the second testing cavity, the second element being configured to measure a viscoelastic characteristic based on the second liquid.
32. The system of claim 31, wherein the first element comprises means for measuring the viscoelastic characteristic based on the first liquid; and wherein the second element comprises means for measuring the viscoelastic characteristic based on the second liquid.
33. A cartridge for a measuring system, the cartridge comprising: testing cavities comprising at least (i) a first testing cavity configured to hold a first liquid that is based on a mixture of first blood and at least one first reagent, the first testing cavity being configured to enable a first viscoelastic test based on the first liquid, and (ii) a second testing cavity configured to hold a second liquid that is based on a mixture of second blood and at least one second reagent, the second testing cavity being configured to enable a second viscoelastic test based on the second liquid, the first viscoelastic test being independent of the second viscoelastic test; flow paths comprising at least (i) a first flow path configured to transport the first liquid to the first testing cavity, the first flow path comprising first ductwork that at least partly enables mixing of the first blood and the at least one first reagent to produce the first liquid, the first ductwork comprising a first duct, and (ii) a second flow path configured to transport the second liquid to the second testing cavity, the second flow path comprising second ductwork that at least partly enables mixing of the second blood and the at least one second reagent to produce the second liquid, the second ductwork comprising a second duct that is separate from the first duct; and wherein the first flow path comprises a first reagent cavity, the first reagent cavity comprising a cavity along the first flow path where the at least one first reagent is deposited, the first reagent being larger in volume than a first portion of the first duct in the first flow path, the first portion having a length equivalent to a length of the first reagent cavity, and the length of the first reagent cavity being measured along a first axis connecting an inlet and an outlet of the first reagent cavity; wherein the second flow path comprises a second reagent cavity, the second reagent cavity comprising a cavity along the second flow path where the at least one second reagent is deposited, the second reagent cavity being larger in volume than a second portion of the second duct in the second flow path, the second portion having a length equivalent to a length of the second reagent cavity, and the length of the second reagent cavity being measured along a second axis connecting an inlet and an outlet of the second reagent cavity; a first receiving cavity configured to receive the first blood, the first receiving cavity being associated with a single testing cavity which is the first testing cavity and the first receiving cavity being devoid of reagent prior to receiving the first blood, the first reagent cavity being configured to receive the first blood from the first receiving cavity, the first receiving cavity having a larger volume than a portion of the first duct that has a length equivalent to a length of the first receiving cavity, and the length of the first receiving cavity being measured along a third axis that is parallel to the first axis; and a second receiving cavity configured to receive the second blood, the second receiving cavity being associated with a single testing cavity which is the second testing cavity and the second receiving cavity being devoid of reagent prior to receiving the second blood, the second reagent cavity being configured to receive the second blood from the second receiving cavity, the second receiving cavity being separate from the first receiving cavity, the second receiving cavity having a larger volume than a portion of the second duct that has a length equivalent to a length of the second receiving cavity, and the length of the second receiving cavity being measured along a fourth axis that is parallel to the second axis.
34. The cartridge of claim 33, wherein the at least one first reagent comprises one of the following: a reagent that interacts with the first blood and that is configured to activate coagulation via an intrinsic pathway; a reagent that interacts with the first blood and that comprises at least one of (i) a reagent configured to activate coagulation or (ii) a reagent configured to suppress thrombocyte function; or a reagent that interacts with the first blood and that is configured to activate coagulation via an extrinsic pathway, and wherein the at least one second reagent comprises one of the following: a reagent that interacts with the second blood and that is configured to activate coagulation via an intrinsic pathway; a reagent that interacts with the second blood and that comprises at least one of (i) a reagent configured to activate coagulation or (ii) a reagent configured to suppress thrombocyte function; or a reagent that interacts with the second blood and that is configured to activate coagulation via an extrinsic pathway.
35. The cartridge of claim 33, wherein the first receiving cavity is fluidically connected to a single flow path over which the first liquid is transported to the first testing cavity, the single flow path to which the first receiving cavity is fluidically connected being the first flow path; and wherein the second receiving cavity is fluidically connected to a single flow path over which the second liquid is transported to the second testing cavity, the single flow path to which the second receiving cavity is fluidically connected being the second flow path.
36. The cartridge of claim 33, wherein the first flow path is configured for connection to a pump to implement pressure changes to control flow of fluids along the first flow path using positive and negative pressure.
37. The cartridge of claim 33, further comprising: a first pressure-controlled stop to control entry of the first blood from the first ductwork into the first reagent cavity; and a second pressure-controlled stop to control entry of the second blood from the second ductwork into the second reagent cavity.
38. The cartridge of claim 33, wherein the first flow path is configured so that, in response to pressure, the first blood and the at least one first reagent mix to form the first liquid during transport; and wherein the second flow path is configured so that, in response to pressure, the second blood and the at least one second reagent mix to form the second liquid during transport.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0059] The figures are showing the following:
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DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0084] Parts and components having same functions are depicted with same references.
[0085] Prior to a detailed description of the preferred embodiments the basic features and a basic practical implementation are summoned as follows. All embodiments refer to a cartridge device 50 (see
[0086] A first embodiment of a cartridge device 50 of the invention will be described with reference to
[0087] In this embodiment the receiving cavity 16 consists of a cavity within the cartridge device 50. The sample liquid 1 can be applied by means of a syringe, pipette etc, e.g. through a self sealing cap shown as a receiving cavity cover 33a in
[0088] In an alternative embodiment the reagent cavity 19 is integral formed with the pump means 18 and/or with the measurement cavity 20 and/or with the ductwork. The transport of the sample liquid 1 can be controlled by said control apparatus.
[0089]
[0090] In a preferred embodiment the cartridge device 50 comprises four arrangements of
[0091] 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
[0092] It is important to note that the cartridge devices 50 of the described embodiments are suitable for different diagnostic tests like thromboelastometry, thromboelastography, platelet aggregometry and others. Depending on which type of test or tests the cartridge device 50 is designed for, there are different additional parts required which interact with the sample during measurement and/or an external control apparatus. Possible adaptations for thromboelastometry and platelet aggregometry are described below.
[0093]
[0094] The probe element 22 comprises the probe pin 3 (see
[0095] The probe element 22 is arranged in the measurement cavity 20 of the cartridge body 30 of the cartridge device 50 as shown in
[0096] During attaching the cartridge device 50 to the measuring system 40 (see also
[0097] It is also possible to insert the insert section 6a of the shaft 6 into the connector section 26 of the probe element 22 and push the probe element 22 down until its bottom contacts the bottom of the measurement cavity 20, 20′ ensuring that the insert section 6a is completely inserted into the connector section 26. Then the shaft 6 will be moved up into the measuring resp. working position of the probe element 22 as shown in
[0098]
[0099] Now a third embodiment of the cartridge device 50 will be described with reference to
[0100]
[0101] The cartridge device 50 of this example is equipped with the ductwork 13 and 15. The ducts are formed with an diameter of approximately 1 mm in this embodiment. The ductwork requires that the cartridge device 50 comprises two parts: the cartridge body 30 and the cover 31, which are glued or welded together to obtain a leak-proof device. The cartridge body 30 is relative rigid and the cover 31 is formed as an elastic part. So it is possible to integrate the pump means 18 into the cover 31. Moreover, the cover 31 covers the receiving cavity 16 with the receiving cavity cover 33a and forms a type of liner wall 33 and a separation wall 34 forming an inlet for the inlet duct 13 within the receiving cavity 16. The receiving cavity cover 33a might act as a self seal for injection of a sample liquid 1 by a syringe for example. The cover 31 forms top parts of the ductwork 13 an 15 and a cover of the measurement cavity 20 (see also
[0102] In this embodiment a reagent cavity 19, 19′ Is formed, e.g. by sections of the ductwork or/and the pump means 18, 18′ In which the reagents can be stored resp. deposited, especially on the pump cavity bottom 36a, for example.
[0103] The pump means 18 will now be described with reference to
[0104]
[0105] In this example the pump cavity 36 is connected to the inlet duct 13 via an inlet valve 37 and to the outlet valve via an outlet valve 38. Actuation of the pump membrane 35 (shown in
[0106] An external force exerted on the pump membrane 35 increase the pressure within the pump cavity 36 and opens outlet valve 38 and closes inlet valve 37. Releasing the external force the elastic pump membrane 35 returns into the position shown in
[0107] Now the measuring system 40 according to the invention is described in an embodiment with reference to
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[0109] The measuring system 40 comprises an interface element 41 to which the cartridge device 50 is attached and fixed. The interface element 41 is shown in
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[0111] Thus it is possible to e.g. arrange a reagent receptacle 19b in a blister receptacle e.g. as shown in
[0112] 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.
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[0114] The insertion section Ba can engage with a groove 28 inside the connector section 26 of the probe element 22′. After that engagement which is supported by the toe bearing the shaft 6 will be drawn up together with the probe element 22′ in the measuring position. It is a matter of fact that other engagement means can be used.
LIST OF REFERENCE NUMERALS
[0115] 1 Sample liquid [0116] 2 Cup [0117] 3 Probe pin [0118] 4 Torsion wire [0119] 5 Rotation axis [0120] 6 Shaft [0121] 6a Insert section [0122] 7 Bearing [0123] 8 Mirror [0124] 9 Spring [0125] 10 Detecting means [0126] 11 Base plate [0127] 12 Cup holder [0128] 13, 13′ Inlet duct [0129] 14, 14′ Intermediate duct [0130] 15, 15′ Outlet duct [0131] 16, 16′ Receiving cavity [0132] 17 Branch duct [0133] 18, 18′ Pump means [0134] 19, 19′ Reagent cavity [0135] 19a, 19′a Reagent cavity bottom [0136] 19b Reagent receptacle [0137] 20, 20′ Measurement cavity [0138] 21, 21′ Reagent [0139] 22, 22′ Probe element [0140] 23 Intermediate section [0141] 24 Flange [0142] 25 Fixing section [0143] 26 Connector section [0144] 27 Insertion guide [0145] 28 Groove [0146] 29 Dimple [0147] 29a Nose [0148] 30 Cartridge body [0149] 31 Cover [0150] 32 Fixing means [0151] 32a Opening [0152] 33 Wall [0153] 33a Receiving cavity cover [0154] 34 Separation wall [0155] 35 Pump membrane [0156] 36 Pump cavity [0157] 36a Pump cavity bottom [0158] 37 Inlet valve [0159] 38 Outlet valve [0160] 39 Flow direction [0161] 40 Measuring system [0162] 41 Interface element [0163] 42 Pump access [0164] 43 Inlet opening [0165] 44 Shaft passage [0166] 44a Passage hole [0167] 45 Reagent cover opening [0168] 46 Retaining ring [0169] 47 Frame [0170] 48 Bottom foil [0171] 49 Blister cover [0172] 50 Cartridge device