Blood test system and method

Abstract

To provide a blood coagulation test system.SOLUTION: Some embodiments of a blood coagulation test system include an analyzer console device and a disposable cartridge component configured to be removably installed in the console device. In some embodiments, the blood coagulation test system can operate, for example, as an automated thromboelastometry system particularly useful in a point-of-care site.SELECTED DRAWING: Figure 4

Description

Technical Field

[0001] This document relates to systems and methods for examining the characteristics of blood samples, such as an automated thromboelastometry system for point-of-care whole blood coagulation analysis.

Background Art

[0002] Cross-Reference to Related Applications This application claims the benefit of U.S. Patent Application No. 14 / 958,890, filed on December 3, 2015, which is a continuation-in-part of U.S. Patent Application No. 14 / 500,248, filed on September 29, 2014, and for all purposes, the entire contents thereof are incorporated herein by reference.

[0003] Hemostasis is the body's response to vascular injury and bleeding. Hemostasis involves a coordinated effort between platelets and numerous blood coagulation proteins (or clotting factors), resulting in the formation of a blood clot and subsequent cessation of bleeding.

[0004] Various methods have been introduced to evaluate the potential of blood to form a sufficient blood clot and to determine the stability of the blood clot. Common laboratory tests, such as platelet counting or fibrin concentration determination, provide information about whether the tested components are available in sufficient quantities, but some of these tests may not answer the question of whether the tested components are functioning properly under physiological conditions. Other laboratory tests act on plasma, which may impose additional preparation steps and additional time beyond what is suitable, for example, in a point-of-care context (e.g., in the operating room during surgery).

[0005] Another group of tests that evaluate the potential of blood to form sufficient blood clots are known as "viscoelastic methods." In at least some viscoelastic methods, clot hardness (or other parameters that depend on it) is determined over a predetermined period, for example, from the formation of the first fibrin fibers to the dissolution of the clot by fibrinolysis. Since the clot must resist blood pressure and shear stress at the site of vascular injury or incision, clot hardness is a functional parameter that contributes to hemostasis in vivo. In many cases, clot hardness can result from multiple interrelated processes, including coagulation activation, thrombin formation, fibrin formation and polymerization, platelet activation, and fibrin-platelet interactions.

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] To isolate and test the specific functions of platelets, fibrinogen, and other factors in a blood sample, reagent compounds can be mixed with the blood sample and can activate or inhibit specific components in the blood sample. In some commercially available point-of-care blood testing systems, a liquid reagent is injected into a disposable plastic cup containing the blood sample, and then the cup is engaged by the control console of the blood testing system to evaluate the clotting / coagulation characteristics of the blood sample. As part of the test process, the system requires manual intervention by the operator for each assay, such as when a pipette is used by the operator, for example, to dispense and measure the reagent, blood, and mixed sample.

MEANS FOR SOLVING THE PROBLEMS

[0007] Some embodiments of a system for testing the characteristics of a blood sample (which should be understood to include blood products such as blood or plasma as used herein) can include a cartridge that is configured to mate with a control console and is further configured to receive a blood sample for point-of-care whole blood coagulation analysis. In certain situations, the cartridge is configured to interact with the control console and perform a plurality of automated transport and testing operations on a portion of the blood sample, providing reliable and rapid results indicative of the patient's blood characteristics at the point of care (e.g., while the patient is undergoing surgery in the operating room). For example, the system can serve as an automated thromboelastometry system to provide detailed and rapid results of blood coagulation characteristics in response to receiving an indication from the cartridge (and the blood sample in the cartridge) and the operator to initiate an automated testing process.

[0008] In some embodiments, a thromboelastometry system includes a reusable analyzer console and one or more disposable cartridge components configured to mate with the console. In one example, to operate the thromboelastometry system, a user inserts the cartridge into the analyzer console and, when prompted by the analyzer console, inserts a blood collection tube (containing a whole blood sample) into the receiver portion of the cartridge. The user then initiates a plurality of automated blood transfer and testing operations as prompted by the user interface of the analyzer console. Thereafter, the analyzer console automatically performs the tests (without requiring further user interaction with the cartridge or blood sample) and displays the results on a graphic display using qualitative graphic representations and quantitative parameters. In this particular example, no manual pipetting, mixing, or handling of reagents by the user is required. In some embodiments, four or more assays are automatically performed on a blood sample using a single cartridge device. Such assays provide information regarding the overall dynamics of hemostasis, such as clotting time, clot formation, clot stability, and lysis. Moreover, such information can be rapidly output from the system's user interface to provide reliable and rapid results indicative of a patient's blood characteristics at the point of care (e.g., while a patient is undergoing surgery in an operating room).

[0009] Certain embodiments described herein include a cartridge for use with a blood testing console. The cartridge can include a blood sample receiver configured to receive a blood sample to be tested. The cartridge can also include one or more blood processing and testing pathways. Each blood processing and testing pathway can be configured to receive a portion of the blood sample and can include a blood sample volume measurement chamber, a mixing chamber, and a viscoelastic blood testing chamber. The blood sample volume measurement chamber can be in fluid communication with the blood sample receiver and can have a selected internal volume to contain a predetermined volume of the blood sample from the blood sample container. The mixing chamber can be in fluid communication with the blood sample volume measurement chamber and can be in fluid communication with a reagent, and the mixing chamber can be configured to receive the blood sample from the blood sample volume measurement chamber and mix the received blood with the reagent. The viscoelastic blood testing chamber can be configured to receive the mixed blood and reagent from the mixing chamber, and a viscoelastic test can be performed on the mixed blood and reagent while the mixed blood and reagent are present in the testing chamber.

[0010] In some embodiments described herein, the cartridge device can include a blood sample receiver and a plurality of blood sample pathways selectively in fluid communication with the blood sample receiver. Each blood sample pathway can include a blood measurement chamber for receiving a predetermined amount of the blood sample via the blood sample receiver, a reagent mixing chamber for receiving the predetermined amount of the blood sample and mixing it with one or more reagents, and a blood clotting blood testing chamber for receiving the blood sample from the reagent mixing chamber with one or more reagents mixed therewith. Optionally, the blood clotting blood testing chamber can have a movable probe therein for measuring blood clotting characteristics.

[0011] The various embodiments described herein include a cartridge device for a measurement system for measuring the viscoelastic properties of a blood sample. The cartridge can include a blood sample receiver and at least one blood sample path selectively in fluid communication with the blood sample receiver. The blood sample path can include a blood measurement chamber configured to be filled by a predetermined amount of blood sample via the blood sample receiver, a reagent mixing chamber for receiving a predetermined amount of blood sample from the blood measurement chamber and for mixing the predetermined amount of blood sample with one or more reagents, a blood coagulation blood test chamber for receiving the blood sample with one or more reagents mixed therewith from the reagent mixing chamber, and an overflow chamber in fluid communication with the blood sample path for collecting excess blood in excess of a predetermined amount of blood sample from the blood measurement chamber. Optionally, the blood coagulation blood test chamber can have a movable probe therein for measuring blood coagulation properties.

[0012] Other embodiments described herein include a measurement system for measuring the viscoelastic properties of a blood sample. The system can include a control unit housing a viscoelastic measurement component. The control unit can define an external port. Also, the system can include at least one disposable cartridge, and the at least one disposable cartridge can include a blood sample inlet accessible along the outside of the cartridge and a plurality of blood test chambers positioned along the inside of the cartridge. Optionally, the control unit is configured to removably mate with the disposable cartridge when inserted into the external port, with the blood sample inlet of the cartridge remaining external to the control unit while the plurality of blood test chambers are positioned within the control unit.

[0013] Some embodiments described herein include a method of using a system for measuring the viscoelastic properties of a blood sample. The method can include inserting a disposable cartridge into a blood test control console such that a blood sample inlet remains exposed to the outside. The method can also include attaching a blood sample reservoir to the blood sample inlet. The method can further include providing user input via a user interface of the blood test control console and initiating an automated transport of blood from the blood sample reservoir into a plurality of blood test chambers in the cartridge to measure the viscoelastic properties of the blood in each of the blood test chambers.

[0014] In certain embodiments described herein, a cartridge device for a measurement system for measuring the viscoelastic properties of a blood sample can include a blood sample receiver structure defining a cavity configured to removably mate with a blood sample reservoir container. The cartridge device can also include a plurality of blood test chambers, the plurality of blood test chambers being spaced apart from the blood sample receiver structure and each having a movable probe therein for measuring blood coagulation properties. All of the blood test chambers may be selectively in fluid communication with the blood sample receiver structure.

[0015] In some embodiments described herein, a cartridge device for a measurement system for measuring the viscoelastic properties of a blood sample can include a plurality of blood test chambers for measuring blood coagulation properties. Each of the blood test chambers can be exposed to the atmosphere and can have a sample input port positioned along a side wall of the blood test chamber. Optionally, each of the blood test chambers is in fluid communication with an output port of a respective reagent mixing chamber defined within the cartridge device at a height below the sample input port of the blood test chamber.

[0016] In various embodiments described herein, a cartridge device for a measurement system for measuring the viscoelastic properties of a blood sample can include a plurality of reagent mixing chambers for receiving a predetermined amount of the blood sample and mixing it with one or more reagent beads. The cartridge device can also include a plurality of retaining elements extending into the reagent mixing chambers to maintain a respective predetermined vertical position of each of the reagent mixing beads within the mixing chambers. At least one of the retaining elements of the reagent mixing chambers can engage the plurality of reagent mixing beads to keep the plurality of reagent mixing beads spaced apart from each other.

[0017] In certain embodiments described herein, a cartridge device for a measurement system for measuring the viscoelastic properties of a blood sample can include a plurality of reagent mixing chambers for receiving a predetermined amount of the blood sample and mixing it with one or more reagent beads. The cartridge device can also include a movable mixing element retained by the reagent mixing chambers. The movable mixing element can include a material that is inert with respect to the blood sample. The cartridge device can further include a plurality of retaining elements extending into the reagent mixing chambers to maintain the reagent mixing beads at a position spaced apart from the movable mixing element.

[0018] Some embodiments described in this specification may include a method for measuring the coagulation characteristics of a blood sample. The method can include detecting that a blood test cartridge is inserted into the receiver portion of a blood test control unit. The method can also include displaying a prompt to the user for input via a user interface of the blood test control unit, and initiating automated transport of blood from a blood sample reservoir in the cartridge to one or more blood test chambers in the cartridge to measure the viscoelastic properties of the blood in each of the blood test chambers. The method can further include automatically transporting a predetermined amount of blood sample from the blood sample receiver of the blood test cartridge to each of one or more blood test chambers in the cartridge. Optionally, the method can include moving a probe in each blood test chamber of the cartridge to measure blood coagulation characteristics. The method can further include displaying the measurement results of the blood coagulation characteristics via the user interface.

[0019] Other embodiments described herein include a control console for measuring the clotting characteristics of a blood sample. The control console can include a control unit housing that houses at least one interface element configured to removably receive a disposable cartridge, which optionally can have a plurality of blood test chambers therein and can have a plurality of measurement components configured to measure the clotting characteristics of a blood sample within the plurality of blood test chambers of the disposable cartridge. The control console can also include one or more heating elements positioned proximal to the interface element and configured to heat the cartridge to a predetermined test-related temperature (e.g., 37° C. in some embodiments). The control console can further include one or more temperature sensors positioned proximal to the interface element. The control unit can be configured to transport blood to the plurality of blood test chambers of the disposable cartridge after the temperature sensors indicate that the plurality of blood test chambers of the disposable cartridge have reached a predetermined temperature.

[0020] Some or all of the embodiments described herein can provide one or more of the following advantages. First, some embodiments of the thromboelastometry system are configured to be automated, minimizing user interaction with the system. As a result, human resources can be utilized more efficiently, particularly in a point-of-care context such as an operating room. Also, the reduction in user interaction reduces the opportunity for manual operator errors such as measurement inaccuracies and reagent mixing errors. Thus, more accurate thromboelastometry results are obtained in some situations.

[0021] Second, in some embodiments, the cartridge component includes a plurality of fluid channels, each of which is individually controllable, and a plurality of different assays can be performed from a single supply of a blood sample. For example, each fluid channel includes a dedicated valve and a dedicated vent, which are controllable by an analyzer console, and the blood flow and testing of each fluid channel are individually controllable. This feature enables the thromboelastometry system to automatically perform sophisticated assay processes.

[0022] Third, in some embodiments, the analyzer console is configured to perform a plurality of quality control operations / verifications to ensure that the blood test results are not compromised. For example, the analyzer console can be configured to confirm that the blood test cartridge is heated to a target temperature (e.g., about 37°C) before the blood sample is dispensed into the test chamber of the cartridge. Since the temperature of the blood sample can affect the clotting characteristics in some situations, the accuracy of the thromboelastometry results can be enhanced as a result of such temperature control operations / verifications.

[0023] Fourth, in certain embodiments of the cartridge device, the geometry of the blood flow path through the fluid channels of the cartridge is configured to reduce the possibility of damaging the blood in a manner that could disrupt the blood (e.g., cause bubble formation) and / or negatively affect the accuracy of the blood test results.

[0024] Fifth, in some embodiments, the blood test cartridge (and optionally, the blood collection reservoir) can be equipped with one or more computer-readable components that rapidly transfer relevant information of the analyzer console for each blood sample test cycle. For example, each cartridge can be labeled with a barcode, a near-field communication tag, an RFID tag, etc., which contain information such as, but not limited to, the type of assay to be performed by the cartridge, the type of reagent container in the cartridge, manufacturer information, or expiration date. In such embodiments, the analyzer console can include a barcode reader (or a reader for a near-field communication tag or an RFID tag, etc.) that scans the barcode when the cartridge is inserted into the analyzer console. The analyzer console automatically performs appropriate actions in response to the data read from the barcode. In another example, each blood collection reservoir to be used with a corresponding cartridge can be labeled with a barcode, a near-field communication tag, an RFID tag, etc., which contain information such as, but not limited to, patient information, clinician information, or calibration information (e.g., it can be readable by a corresponding reader device of the analyzer console).

[0025] Sixth, each fluid path of the cartridge can include a mixing chamber that includes one or more reagents and a mixing element positioned therein. In some embodiments, the reagents include soluble reagent beads. The mixing chamber of the cartridge can be configured to separate one or more reagent beads from each other and can be configured to prevent the mixing element from direct contact with the reagent beads. Also, additional advantages associated with the thromboelastometry system provided herein are envisioned as will become apparent from the following disclosure.

[0026] Details of one or more embodiments of the present invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will become apparent from the description and drawings, and from the claims.

Brief Description of the Drawings

[0027]

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DETAILED DESCRIPTION OF THE INVENTION

[0028] Like reference numerals in the various drawings indicate like elements.

[0029] Referring to FIGS. 1A - 3, some embodiments of the blood testing system 100 include an analyzer console 140 and one or more cartridges 120 configured to removably mate with the analyzer console 140. In this embodiment, the blood testing system 100 is a thromboelastometry system configured to determine a plurality of blood coagulation characteristics of a blood sample placed into the cartridge 120. For example, the cartridge 120 can be configured as a disposable cartridge that includes a blood sample receiver 122 for mating with a blood sample reservoir 10 (e.g., a Vacutainer sample tube supplied by Becton, Dickinson & Company of Franklin Lakes, NJ, or another blood storage structure). In some cases, an adapter can be used to couple other types of blood sample reservoirs 10 to the cartridge 120 (e.g., tubing can be used through which blood can be injected into the cartridge 120, etc.). The thromboelastometry system 100 can be used as a particularly advantageous whole blood coagulation analysis system at the point of care (e.g., in an operating room while a patient is undergoing surgery or preparing for surgery). Additionally, the thromboelastometry system 100 can be used as a whole blood coagulation analysis system in a laboratory setting.

[0030] The analyzer console 140 includes a user interface 142 (in this embodiment, including a touch screen display) and a main chassis 144. The user interface display 142 can be configured to output one or more graphical results 143 from a blood test assay implemented via the cartridge 120 and the console 140 (e.g., one or more plots, such as those sometimes referred to as TEMograms, numerical data or measurements, or combinations thereof). In some embodiments, the user interface display 142 is firmly attached to the analyzer console 140. In certain embodiments, the user interface display 142 is pivotable and / or otherwise positionally adjustable with respect to the main chassis 144. The main power switch 148 can be located in a convenient location, except in a protected location on the main chassis 144.

[0031] In the illustrated embodiment, the touchscreen display 142 is configured to receive user input and to display display output information to the user. For example, the user can input information into the thromboelastometry system 100 by selecting various soft buttons that can be displayed on the touchscreen display 142 at points in time during the start, middle, and end of the inspection process. In some embodiments, other selections, such as but not limited to soft keyboard input, can be provided via the touchscreen display 142. In some embodiments, data input can be implemented additionally or alternatively by voice input. In other embodiments, the user interface can include other peripheral devices (such as, for example, a mouse, a keyboard, and an additional display device, etc.) that can be included as part of the thromboelastometry system 100. In some embodiments, a computer data network (such as, for example, an intranet, the Internet, a LAN, etc.) can be used to enable remote devices to receive and / or input information from the system 100. For example, in some embodiments, one or more remote displays can be utilized via a network connection. Also, in the illustrated embodiment, the thromboelastometry system 100 includes an external barcode reader 146. The external barcode reader 146 can facilitate convenient one-dimensional or two-dimensional barcode input of data, such as but not limited to blood sample data, user identification, patient identification, and normal values. Alternatively or additionally, the thromboelastometry system 100 can be equipped with a reader configured to read a near-field wireless communication tag or an RFID tag, etc.

[0032] In the illustrated embodiment, the main chassis 144 houses various internal subsystems (as further described below), includes various electronic connection receptacles (not shown), and also includes a cartridge port 150. The various electronic connection receptacles can include network and device connectors such as, but not limited to, one or more USB ports, Ethernet ports (e.g., RJ45), VGA connectors, and Sub-D9 connectors (RS232). Such connection receptacles can be positioned on the back of the main chassis 144 or in other convenient locations on the main chassis 144. For example, in some embodiments, one or more USB ports can be positioned on or near the front of the main chassis 144. USB ports so positioned can provide user convenience, for example, for recording data onto a memory stick. In some embodiments, the thromboelastometry system 100 is configured to operate using wireless communication modalities such as, but not limited to, Wi-Fi, Bluetooth, NFC, RF, and IR.

[0033] Still referring to FIGS. 1A - 3, the cartridge port 150 is positioned in an easily accessible location on the main chassis 144. In the illustrated embodiment, the cartridge port 150 is positioned on the front face of the main chassis 144, which is configured to be conveniently accessible by the user at the point - of - care site. The cartridge port 150 defines an opening and an internal space that are shaped complementary to the outer dimensions of the disposable cartridge 120. To insert the disposable cartridge 120 into the cartridge port 150, the user can grasp the end of the cartridge 120 that includes the blood sample receiver 122 and slide the opposite end (the tip) into the cartridge port 150. The slide insertion can continue until a hard stop that defines the fully inserted position is reached. In the fully inserted position, the rear - end portion of the disposable cartridge 120 (including the blood sample receiver 122 in this embodiment) remains outside of the main chassis 144. The portion of the cartridge 120 received into the cartridge port 150 can include outer - surface features (such as the tapered angle of the rear - end portion shown in FIG. 1B), and the outer - surface features mate with at least one internal interface element inside the console 140 to ensure proper positioning of the cartridge 120. For this purpose, at least the blood sample receiver 122 remains outside of the main chassis 144 throughout the period of the blood sample test. In this configuration, the blood sample receiver 122 serves as a blood sample well, and the blood sample well is accessible, and the blood sample reservoir 10 can be inserted into the receiver 122 while the disposable cartridge 120 is mated with the console 140 in the fully inserted position. In some embodiments, the cartridge port 150 and the main chassis 144 are configured such that the exposed portion of the cartridge 120 is protected from accidental contact.Furthermore, as described below, an internal sensor (e.g., a microswitch, an optical sensor, etc.) can detect when the disposable cartridge 120 is fully inserted into the main chassis 144.

[0034] When the analyzer console 140 detects that the cartridge 120 has been fully inserted, in some embodiments, the analyzer console 140 initiates one or more of the following actions. An internal cartridge clamping mechanism including positioning pins can be activated to accurately position and removably hold the disposable cartridge 120 in the fully inserted position. One or more cartridge heating elements can be activated to warm the cartridge 120. The temperature of the cartridge 120 can be monitored. The barcode on the tip of the cartridge 120 can be read and the barcode data can be stored in the memory of the analyzer console 140. One or more blood detection sensors can inspect the cartridge 120 for the presence of blood (which should not be present at this point). A rotational thromboelastometry for measuring the subsystem can be engaged with the cartridge 120 and optionally, the rotation of the rotational thromboelastometry for measuring the subsystem can begin (in the absence of blood). The cartridge 120 can be leak tested using a vacuum or air pressure delivered by the analyzer console 140. For example, a pressure / vacuum decay test can be performed. In some embodiments, other actions can be additionally or alternatively activated when the analyzer console 140 detects that the cartridge 120 has been fully inserted. After such actions are completed, in some embodiments, an indication of the result of the action can be displayed on the touch screen display 142 (e.g., pass or fail). If the analyzer console 140 determines that the action has been completed successfully, a prompt is provided on the touch screen display 142, which informs the user that the thromboelastometry system 100 is ready to receive the blood sample reservoir 10.

[0035] Briefly, in some embodiments, a user can operate the illustrated embodiments of the thromboelastometry system 100 as follows. First, the user can insert a disposable cartridge 120 into the cartridge port 150, and the cartridge 120 is adapted to be installed in a fully inserted position. As described below, completion of that step will automatically initiate a series of operations by the thromboelastometry system 100. When such operations are completed successfully, a notification that the blood collection tube 10 can be inserted into the sample well 122 will be displayed on the touch screen display 142. After the user fits the blood collection tube 10 into the sample well 122, the user starts the test by pressing a "start" button (etc.) on the touch screen display 142. At least blood measurement, reagent mixing, and thromboelastometry testing are then automatically performed by the system 100 (e.g., in this embodiment, without requiring manual intervention from the user). When the test is completed, the results are displayed on the touch screen display 142 in the form of qualitative graphic representations and quantitative parameters (e.g., as shown in FIG. 1A). Also, when the test is completed, the cartridge 120 can be removed from the console 140 and discarded (e.g., in such embodiments, the cartridge 120 is not reusable in that the reagent beads (described below) are no longer present in the cartridge and the measurement chamber contains a coagulated blood sample portion).

[0036] Alternatively, in some embodiments, the blood collection tube 10 can be inserted into the sample well 122 of the cartridge 120 before inserting the cartridge 120 into the cartridge port 150. In such a situation, blood from the collection tube 10 cannot advance to the measurement chamber (described below) of the blood cartridge 120 until (again, as described below) the console 140 acts on the cartridge 120. With the blood collection tube 10 pre-connected to the cartridge 120, the combination of the blood collection tube 10 and the cartridge 120 can then be inserted into the cartridge port 150.

[0037] Referring now to FIGS. 4 and 5, an embodiment in which a disposable cartridge 120 is shown includes a main body portion 124, a right cover 126, a left cover 128, and five pins 138a, 138b, 138c, 138d, and 138e. The right cover 126 is affixed to the right side of the main body portion 124, and the left cover 128 is affixed to the left side of the main body portion 124. As such, the right cover 126 and the left cover 128 surround the cavities and flow channels of the main body portion 124 and define a blood flow path, as further described below. The sample well 122 described above is part of the main body portion 124. However, other configurations of the disposable cartridge 120 are envisioned.

[0038] In some embodiments, the main body portion 124, the right cover 126, the left cover 128, and the pins 138a, 138b, 138c, 138d, and 138e are made by injection molding. After molding, the right cover 126 and the left cover 128 can be attached to the main body portion 124 using various techniques including, but not limited to, ultrasonic welding, laser welding, solvent bonding, adhesive bonding, and UV curable adhesive bonding. Various polymer materials can be used to form the main body portion 124, the right cover 126, the left cover 128, and the pins 138a - e. For example, such polymer materials can include, but are not limited to, acrylic, polycarbonate, polyvinyl chloride (PVC), polyethylene, polypropylene, polymethyl methacrylate, polystyrene, acrylonitrile butadiene styrene (ABS), polyethylene, and polypropylene, as well as combinations thereof. In some embodiments, materials are used to form the main body portion 124, the right cover 126, the left cover 128, and the pins 138a - e, including an acrylic - based multi - polymer compound. In some embodiments, the main body portion 124, the right cover 126, and the left cover 128 are essentially transparent or at least translucent. Thus, in FIG. 4, the features of the main body portion 124 can be seen even when the right cover 126 is attached thereto.

[0039] In some embodiments, for example, overmolding by insert molding or multi-shot molding techniques may be used to configure some aspects of the main body portion 124, the right cover 126, and / or the left cover 128 (i.e., the device components). For example, an elastomeric valve element (as described further below) may be overmolded within the left cover 128. To generate a valve by overmolding, a first mask is used to generate the device component without the valve. The mask is the inverse of the shape of the device component, and the device component includes an open space for later valve insertion. A polymer is poured into the first mask to form a rigid plastic device component. Next, a second mask having the inverse of the shape of the device component with the valve is provided. The cured plastic device component is placed within the mask, and an elastomeric material is injected into the open space formed within the device component by the first mask, thereby forming an elastomeric valve within the device component. In some embodiments, the device component is the main body portion 124, the right cover 126, and / or the left cover 128. Exemplary valves 160a - e, 168, and 170 within the left cover 128 formed by overmolding are shown in FIG. 7. In some embodiments, the valve includes an elastomeric material that is deformable when pressure is applied. Deformation of the valve by application of external pressure pushes the elastomeric material into the duct, thereby fluid-sealing the duct and preventing flow of sample liquid through the duct.

[0040] Furthermore, in some embodiments, secondary operations may be performed on the cartridge 120. For example, one or more needles 123a - b (see FIG. 6) for piercing a blood collection tube may be installed in the sample well 122 using secondary operations.

[0041] Also, the disposable cartridge 120 includes five pins 138a, 138b, 138c, 138d, and 138e. The pins 138a - e are individual component parts (see, for example, FIG. 10B), and they are held within the openings of the main body portion 124 (within inspection chambers 136a - e (sometimes referred to as "cups") as further described below with reference to FIGS. 8A - 10B). Tabs 129 positioned on the right cover 126 and the left cover 128 mechanically hold the pins 138a - e within the main body portion 124. However, the pins 138a - e can move freely to a limited extent within the scope of the main body portion 124. For example, the pins 139a - e can rotate freely without being restricted within the main body portion 124, and can translate freely vertically by a few millimeters. This configuration of the pins 138a - e relative to other components of the cartridge 120 can be produced as follows. Before attaching the right cover 126 and the left cover 128 to the main body portion 124, the pins 138a - e can be installed in their respective locations within the main body portion 124 as shown in FIG. 5. With the pins 138a - e positioned within the main body portion 124, the right cover 126 and the left cover 128 can then be attached to the main body portion 124. With the right cover 126 and the left cover 128 attached to the main body portion and the pins 138a - e positioned within the main body portion 124, the pins are fixed in place vertically by tabs 129 that cover the upper portions of the pins 138a - e such that they cannot fall out of or be removed from the cups 136a - e without removing the right cover 126 and the left cover 128 from the main body portion 124. The tabs 129 allow for free rotational movement of the pins 138a - e, as well as sufficient vertical movement, enabling the pins 138a - e to interact with the fluid sample and perform measurements of the viscoelastic properties of the fluid sample within the cups 136a - e (e.g., rotational thromboelastometry). In addition, the tab 129 provides an opening for the shaft 310b to connect with the pin 138b as shown in FIG. 10C.In one example, the right cover 126 and the left cover 128 are attached to the main body portion 124, and then the pins 138a - e are pushed into the main body portion 122 beyond the tabs 129. The tabs 129 of the right cover 126 and the left cover 128 will prevent the pins 138a - e from falling off the main body portion 122 even when the cartridge 120 is upside down. In some embodiments, the pins and tabs are positioned to prevent the semi - solidified fluid sample in the inspection chamber from escaping the inspection chamber even when the cartridge 120 is upside down.

[0042] In some embodiments, the main body portion 124 includes a barcode location 125. The barcode location 125 can be used as a location for adhering a barcode label or for printing a barcode. The barcode location 125 is above the tip of the cartridge 120 (with respect to the direction of insertion of the cartridge 120 into the analyzer console 140 as shown in FIGS. 1 - 3).

[0043] In the illustrated embodiment, the right cover 126 includes blood detection locations 127a and 127b. As will be further described below, the blood detection locations 127a and 127b are designated locations on the cartridge 120 where the sensors of the analyzer console 140 interface with the cartridge 120. The sensors inspect for the presence of blood in the cartridge 120 at the blood detection locations 127a and 127b. In some embodiments, the sensors are optical sensors (e.g., infrared sensors), and the blood detection locations 127a and 127b are polished areas with enhanced transparency and optical clarity. Thus, the right cover 126 is configured so that the optical sensors of the analyzer console 140 can easily detect the presence or absence of blood at the blood detection locations 127a and 127b.

[0044] Referring now to FIGS. 4, 5, and 6, generally speaking, the disposable cartridge 120 is configured to (i) extract blood from a blood collection tube (e.g., blood collection tube 10 of FIGS. 1-3), measure the exact volume of the extracted blood, (ii) mix an exact amount of the blood with a reagent, and (iii) deliver the mixture to a plurality of cups and pins of the cartridge 120 where a thromboelastometry test is performed. These steps are described in more detail below.

[0045] In the illustrated embodiment, the disposable cartridge 120 includes five individual blood flow channels 130a, 130b, 130c, 130d, and 130e. Alternatively, in some embodiments, the cartridge includes a single individual blood flow channel, or two individual blood flow channels, or three individual blood flow channels, or four individual blood flow channels, or six individual blood flow channels, or seven or more individual blood flow channels. Each channel 130a-e includes (i) a measurement chamber, (ii) a mixing chamber containing a reagent and a mixing element, and (iii) a blood coagulation test chamber (e.g., in this embodiment, a cup having a movable probe / pin therein). For example, channel 130a includes a measurement chamber 132a, a mixing chamber 134a, and a test chamber 136a (see the example of the test chamber shown in detail in FIGS. 10A-B). Similarly, channel 130b includes a measurement chamber 132b, a mixing chamber 134b, and a test chamber 136b. Channel 130c includes a measurement chamber 132c, a mixing chamber 134c, and a test chamber 136a. Channel 130d includes a measurement chamber 132d, a mixing chamber 134d, and a test chamber 136d. Channel 130e includes a measurement chamber 132e, a mixing chamber 134e, and a test chamber 136e.

[0046] In some embodiments, the sample well 122 includes needles 123a and 123b, which are configured to pierce the septum of the blood collection tube when the blood collection tube is inserted into the sample well 122. Needle 123a is in fluid communication with channels 130a - e, while needle 123b is a vent that facilitates the rapid flow of blood from the blood collection tube.

[0047] In the illustrated embodiment, the fluid flow path from needle 123a to channels 130a - e is as follows. Needle 123a merges with measurement chamber 132a. Measurement chamber 132a merges with measurement chamber 132b. Measurement chamber 132b merges with measurement chamber 132c. Measurement chamber 132c merges with measurement chamber 132d. Measurement chamber 132d merges with measurement chamber 132e. Thus, blood can flow from the blood collection tube through needle 123a to measurement chamber 132a, from measurement chamber 132a to measurement chamber 132b, from measurement chamber 132b to measurement chamber 132c, from measurement chamber 132c to measurement chamber 132d, and from measurement chamber 132d to measurement chamber 132e. Also, measurement chambers 132a - e can also be referred to as metering chambers 132a - e. Each of the measurement chambers 132a - e has an inlet port and an outlet port. The inlet port is positioned near the top of the measurement chambers 132a - e. For example, measurement chamber inlet port 132ai is positioned near the top of measurement chamber 132a. This configuration can be advantageous when the blood contains air bubbles. The reason is that such gas is allowed to escape from the blood when the blood enters the measurement chambers 132a - e. Additionally, this configuration can advantageously minimize fluid flow turbulence when the blood flows into the measurement chambers 132a - e, thereby reducing the possibility of damaging blood cells.

[0048] Outlet ports 134ao~eo for transferring blood from measurement chambers 132a~e to mixing chambers 134a~e are positioned at the bottom of the measurement chambers. For example, measurement chamber outlet port 132ao is positioned at the bottom of measurement chamber 132a. In some embodiments, the bottom of measurement chamber 132a is angled downwardly toward outlet port 132ao. In some embodiments, the bottom of measurement chamber 132a is at an angle of 2° to 15° from a plane parallel to the bottom or top of cartridge 120. In some embodiments, the bottom of measurement chamber 132a is at an angle of 2° to 15° from a plane orthogonal to the direction of the force applied to move the blood sample through outlet port 132ao. In one embodiment, the angles described above are approximately 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°, 14°, or 15°. In a preferred embodiment, the angle described above is 5°, although other angles will also be effective. This configuration can help to facilitate completely filling measurement chambers 132a~e with blood. Also, it can minimize the transfer of bubbles into outlet port 132ao. The reason is that more blood is transferred to outlet port 132ao before the surface of the volume of blood (which may contain bubbles) contained in measurement chamber 132a contacts outlet port 132ao. So, an accurate volume of blood is contained in measurement chambers 132a~e.

[0049] In some embodiments, the top of measurement chamber 132a is angled to cause air to escape from measurement chamber 132a through a transfer port positioned at the top of the measurement chamber on the opposite side of inlet port 132ai. The transfer port is used to transfer air and fluid from measurement chamber 132a into another measurement chamber (e.g., 132b) or into overflow chamber 139. In this embodiment, the top of measurement chamber 132a is angled upwardly from a lower point above inlet port 132ai to a higher point above the transfer port. The angle of the top of the measurement chamber is between 2° and 15° compared to a plane parallel to the bottom or top of the device, or compared to a plane orthogonal to the primary gravitational field applied to the blood sample while it is within measurement chamber 132a. In one embodiment, the angle described above is approximately 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°, 14°, or 15°. In a preferred embodiment, the angle described above is 5°, although other angles are effective. In devices that include the angled top of measurement chamber 132a, air and bubbles are transferred from measurement chamber 132a before the blood, providing a measured blood sample with a reduced amount of air, where air can affect the accuracy of blood measurements and can also interfere with other downstream applications. In some embodiments, both the top and bottom of measurement chamber 132a are angled as described above.

[0050] From the foregoing description of the fluid flow path from the needle 123a to the measurement chambers 132a-e, and from the foregoing description of the location of the measurement chamber outlet ports, it should be understood that the measurement chambers 132a-e are filled with blood in a sequential manner. That is, the first measurement chamber 132a will be filled with blood. Then, the blood from the measurement chamber 132a will flow into the measurement chamber 132b. Then, the measurement chamber 132b will be filled with blood. Then, the blood from the measurement chamber 132b will flow into the measurement chamber 132c. Then, the measurement chamber 132c will be filled with blood. Then, the blood from the measurement chamber 132c will flow into the measurement chamber 132d. Then, the measurement chamber 132d will be filled with blood. Then, the blood from the measurement chamber 132d will flow into the measurement chamber 132e. Then, the measurement chamber 132e will be filled with blood.

[0051] After the measurement chamber 132e is filled with blood, then the blood from the measurement chamber 132e will flow into the overflow chamber 139. The blood flowing from the measurement chamber 132e will enter the overflow chamber 139 at the overflow chamber inlet port 139i. As will be described further below, the overflow chamber 139 serves to ensure that the measurement chamber 132e is completely filled, while preventing blood from exiting the cartridge 120 and flowing into the vacuum supply source, which is used to draw blood into the measurement chambers 132a - e as described above. The vacuum supply source is fluidly connected to the overflow chamber 139 at the overflow chamber outlet port 139o. When a negative pressure (with respect to atmospheric pressure) from the vacuum supply source is applied at the overflow chamber outlet port 139o, the blood from the blood collection tube connected to the needle 123a will flow into the cartridge 120 so as to fill all the measurement chambers 132a - e. Also, some of the blood will exit the measurement chamber 132e and flow towards the overflow chamber 139.

[0052] Furthermore, as described below, various valves and vents are scattered in the fluid flow path, and the blood flow can be controlled by the analyzer console according to a predetermined scheme. In addition, the above-described blood detection locations 127a and 127b (see FIG. 5) are designated locations on the cartridge 120, where the sensors of the analyzer console 140 interface with the cartridge 120. The sensors inspect for the presence of blood in the cartridge 120 at the blood detection locations 127a and 127b. The blood sensor location 127a is on the fluid flow path between the needle 123a and the measurement chamber 132a. When the analyzer console detects blood at the blood sensor location 127a, the analyzer console 140 determines that blood has been drawn into the cartridge 120. The blood sensor location 127b is on the fluid flow path between the measurement chamber 132e and the overflow chamber 139. When the analyzer console detects blood at the blood sensor location 127b, the analyzer console 140 determines that blood has been drawn into and filled all of the measurement chambers 132a - e. Further, when the analyzer console 140 detects blood at the blood sensor location 127b, the analyzer console 140 can stop the further application of negative pressure at the overflow chamber outlet port 139o. In other words, by detecting blood at the blood sensor location 127b, the analyzer console 140 can determine that the application of vacuum has properly filled all of the measurement chambers 132a - e and that the application of vacuum can be stopped. Optionally, the cartridge 120 can be equipped with a blood temperature sensor at or near the location of the blood sensor location 127b to confirm that the blood sample is at a predetermined target temperature.

[0053] As described above, each of the individual channels 130a - e has its own measurement chamber 132a - e. In some embodiments, the fluid flow paths in the individual channels 130a - e are as follows. From the measurement chambers 132a - e, blood can flow to their respective mixing chambers 134a - e. For example, blood from measurement chamber 132a can flow to mixing chamber 134a. Similarly, blood from measurement chamber 32b can flow to mixing chamber 134b. Blood from measurement chamber 132c can flow to mixing chamber 134c. Blood from measurement chamber 132d can flow to mixing chamber 134d. Blood from measurement chamber 132e can flow to mixing chamber 134e. From the mixing chambers 132a - e (after mixing is complete), blood can flow to their respective test chambers 136a - e (which have corresponding probes / pins 138a - e therein. See FIGS. 10A - b below). For example, blood from mixing chamber 134a can flow to test chamber 136a. Similarly, blood from mixing chamber 134b can flow to test chamber 136b. Blood from mixing chamber 134c can flow to test chamber 136c. Blood from mixing chamber 134d can flow to test chamber 136d. Blood from mixing chamber 134e can flow to test chamber 136e. Various valves and vents controllable by the analyzer console 140 are interspersed in the fluid flow paths of the individual channels 130a - e. Using such valves and vents, the blood flow in the individual channels 130a - e can be controlled by the analyzer console 140 according to a predetermined scheme.

[0054] Referring now to FIGS. 6 and 7, additional features of the cartridge 120 are described herein. In FIG. 6, side views of specific chambers of the cartridge 120 (measurement chambers 132a-e, reagent mixing chambers 134a-e, and blood coagulation test chambers 136a-e) are provided. In FIG. 7, left side views of the cartridge 120 and the individual channels 130a-e are provided. In this figure, inspection chamber inlet ports 136ai, 136bi, 136ci, 136di, and 136ei for each of the inspection chambers 136a-e can be seen. The inlet ports 136ai-ei are positioned near the top of the inspection chambers 136a-e, for example, along the side wall portions of the chambers 136a-e and above the distal heads of the pins 138a-e that interact with the blood sample, but at a height below the proximal ends of the pins 138a-e (see FIG. 10B). This configuration can be advantageous when the blood contains air bubbles. The reason is that when the blood enters the cups 136a-e, such gas can be allowed to escape from the blood. In a viscous solution, if the solution enters through the bottom, the bubbles are retained at the bottom of the cups 136a-e, which adversely affects thromboelastometry measurements by the pins 138a-e in the cups 136a-e. In addition, this configuration can advantageously minimize fluid flow disturbance when the blood flows into the inspection chambers 136a-e. Also, fluid flow disturbance and bubble mixing are minimized by having a small diameter or blood flow area of the sample inlet port 136bi into the cups 136a-e. Bubbles present in the blood from the mixing chambers 134a-e are separated from the fluid and remain on the upper surface of the blood in the cups 136a-e by using a smaller diameter of the sample inlet port 136bi in combination with the location of the inlet port 136bi along the side wall portions of the chambers 136a-e. In some embodiments, the diameter of the sample inlet port 136bi is 1 mm. In some embodiments, the diameter of the sample inlet port 136bi is approximately 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 mm.

[0055] In the illustrated embodiment, the cartridge 120 includes two locator pin receivers 140a and 140b. The locator pin receivers 140a and 140b are used to mate with the locator pins of the analyzer console 140 (as described further below). In this way, the cartridge 120 can be accurately positioned with respect to the analyzer console 140.

[0056] Also, the cartridge 120 includes a vacuum application port 162. When a source of vacuum is applied at the vacuum application port 162 and the vents and valves of the cartridge 120 are properly configured, blood can be drawn into the measurement chambers 132a - e as described above and as described further below.

[0057] Also, the cartridge 120 includes a pressure application port 164. When a pressure source is applied at the pressure application port 164 and the vents and valves of the cartridge 120 are properly configured, blood is forced to flow from the measurement chambers 132a - e into the mixing chambers 134a - e, and subsequently from the mixing chambers 134a - e into the inspection chambers 136a - e as described above and as described further below.

[0058] Also, in the illustrated embodiment, the cartridge 120 includes vents 166a, 166b, 166c, 166d, and 166e. Other cartridge embodiments can include fewer or more vents. The vents 166a-e each communicate with a respective mixing chamber 134a-e. Thus, when the vents 166a-e are open and allow air flow therethrough, air from the mixing chambers 134a-e can be easily displaced when blood flows into the mixing chambers 134a-e. Conversely, when the vents 166a-e are closed and prevent air flow therethrough, blood is prevented from flowing into the mixing chambers 134a-e because air in the mixing chambers 134a-e is not allowed to be displaced therefrom. The vents 166a-e can be individually opened and closed by the analyzer console 140 according to a predetermined scheme, as further described below. Thus, blood flow into the mixing chambers 134a-e can be controlled as desired.

[0059] Also, in the illustrated embodiment, the cartridge 120 includes valves 168, 170, 160a, 160b, 160c, 160d, and 160e. Other cartridge embodiments can include fewer or more valves. The valves 168, 170, and 160a-e are positioned within the fluid flow paths of the cartridge 120. Thus, the valves 168, 170, and 160a-e can be actuated (opened or closed) by the analyzer console 140 to allow or prevent fluid flow through the fluid flow paths in which the valves 168, 170, and 160a-e are respectively positioned. For example, valve 168 is positioned within the fluid flow path between needle 123a and measurement chamber 132a. Thus, when valve 168 is open, blood can flow from needle 123a to measurement chamber 132a, and when valve 168 is closed, blood cannot flow from needle 123a to measurement chamber 132a.

[0060] Valve 170 is positioned in the fluid flow path between the measurement chamber 132e and the overflow chamber 139. Therefore, when valve 170 is open, blood can flow from the measurement chamber 132e to the overflow chamber 139, and when valve 170 is closed, blood cannot flow from the measurement chamber 132e to the overflow chamber 139.

[0061] Valves 160a - e are respectively positioned in the fluid flow paths between the mixing chambers 134a - e and the inspection chambers 136a - e. Therefore, when valves 160a - e are open, blood can respectively flow from the mixing chambers 134a - e to the inspection chambers 136a - e, and when valves 160a - e are closed, blood cannot flow from the mixing chambers 134a - e to the inspection chambers 136a - e.

[0062] Furthermore, as will be described below, in some embodiments, valves 160a - e are individually actuated by pins, and the pins are translated towards and away from valves 160a - e. To close valves 160a - e, the pins can engage and expand the elastomeric members of valves 160a - e, and the elastomeric members are adapted to contact the valve seats of valves 160a - e. When such pins are retracted away from the elastomeric members of valves 160a - e, the elastomeric members will rebound so that the elastomeric members can no longer expand, and then the valves are opened. The pins are translated by solenoids in some embodiments.

[0063] There may also be other mechanisms for adjusting the fluid flow within the cartridge 120. For example, a stop junction is installed between the measurement chambers 132a - e and the mixing chambers 134a - e to control the flow of blood from the measurement chambers 132a - e to the mixing chambers 134a - e. In some embodiments, the stop junction is a barrier that can be opened when a sufficient amount of pressure is applied to the barrier. In some embodiments, the stop junction includes a narrow area for the flow of the sample fluid, and when sufficient pressure is not applied, the surface tension of the sample fluid prevents the flow through the stop junction. When sufficient pressure is applied, the flow of the sample fluid through the stop junction can continue due to capillary forces.

[0064] Referring more particularly to FIG. 6, some embodiments of the mixing chambers 134a - e contain (i) one or more soluble reagent beads 180, (ii) a plurality of retaining elements 182, and (iii) a mixing element 184. One or more of the reagent beads 180 are disposed within the plurality of retaining elements 182 and are retained within the scope of the plurality of retaining elements 182. The mixing element 184 is disposed within the bottom portion of the mixing chambers 134a - e and can move freely horizontally across the bottom portion of the mixing chambers 134a - e. The plurality of retaining elements 182 separate the reagent beads 180 from the mixing element 184 and prevent the mixing element 184 from migrating upwardly away from the bottom portion of the mixing chambers 134a - e. Thus, the plurality of retaining elements 182 prevent direct contact between the mixing element 184 and the reagent beads 180 within the mixing chambers 134a - e. Preferably, the retaining elements 182 extend into each of the mixing chambers 134a - e and are adapted to maintain each of the reagent beads 180 within a respective predetermined vertical position (e.g., a vertical position below the height of the blood portion passed into the mixing chambers 134a - e) within the mixing chamber, thereby ensuring that each of the beads 180 will be submerged when a predetermined amount of blood is directed into each of the mixing chambers 134a - e. In certain embodiments, the height of the liquid (i.e., the fill level) that fills the mixing chambers 134a - e from the measurement chambers 132a - e is above the retaining elements 182 within the mixing chambers. In some embodiments, the retaining elements 182 are above the height of the fill level of the mixing chambers. In these embodiments, the retaining elements are configured to position the reagent within the fluid path such that when liquid enters the mixing chamber, the reagent is dissolved by the liquid. In some embodiments, the flow path is defined as the path traveled by the liquid as it goes from one chamber to another, including within the chamber itself after entering from an inlet or duct.

[0065] Also, in some embodiments, the plurality of retention elements 182 in each of the mixing chambers 134a - e hold respective reagent beads 180 in each of the mixing chambers 134a - e that are separated from each other. In such embodiments, each of the reagent beads 180 is not contacted by other beads 180 in each of the mixing chambers 134a - e, is not contacted by the mixing elements 184 in each of the mixing chambers 134a - e, and is maintained at a vertical height in each of the mixing chambers 134a - e that is below the height of the blood portion transported into each of the mixing chambers 134a - e.

[0066] The retaining element 182 can take the form of several unique configurations that result in control over the location of the reagent beads 180. Also, in some embodiments, the retaining element 182 prevents contact between different reagent beads 180, contact between the reagent beads 180 and the mixing element 184, and / or contact between the reagent beads 180 and other surfaces or components within the mixing chambers 134a - e. In some embodiments, the retaining element 182 is configured to limit the movement of the reagent beads 180 within the mixing chambers 134a - e and is also configured to allow a sample liquid or blood sample to dissolve the reagent beads 180. In some embodiments, the retaining element 182 includes a barrier. Also, the retaining element 182 can include inward or outward protrusions within the walls of the mixing chambers 134a - e, or on the surface of the right cover 126 or the left cover 128, or on other surfaces of the device. In some embodiments, the retaining element 182 includes channels, posts, or divots. The retaining element 182 can include an array of posts or an array of divots. In some embodiments, the array of posts includes posts of different diameters for holding reagent beads of different diameters. In some embodiments, the retaining element 182 includes a compartment or a series of compartments for holding the reagent beads. Also, the retaining element 182 can be configured to limit the movement of the reagent beads within the mixing chambers 134a - e and is configured to allow blood to flow in a manner that the blood contacts the reagent beads 180 and dissolves the reagent beads 180. In some embodiments, the retaining element 182 is configured to allow the flow of a blood sample through the mixing chambers 134a - e.

[0067] The retaining element 182 can further fix the reagent beads 180 below a predetermined blood sample filling level in the mixing chambers 134a - e. This filling level is determined by the volume of blood provided by the measurement chambers 132a - e, as well as by the dimensions of the mixing chambers 134a - e and the volume of components or reagents in the mixing chambers 134a - e when filling. This filling level can be determined in advance based on the above factors. Thus, the retaining element 182 can be specifically designed to maintain the position of the reagent beads 180 below this predetermined filling level.

[0068] Additionally, the retaining element 182 can limit the movement of the mixing element 184 in the mixing chambers 134a - e. In some embodiments, the stationary element 182 used to restrict the movement of the mixing element 184 in the mixing chambers 134a - e includes an array of posts or compartments that allow the sample fluid or blood sample in the mixing chambers 134a - e to contact the mixing element 184, and are adapted to promote agitation of the sample fluid or blood sample and dissolution of the reagents in the mixing chambers 134a - e.

[0069] In the illustrated embodiment, one or more soluble reagent beads 180 are spherical and are of two different sizes (e.g., about 2 mm in diameter and about 3 mm in diameter). However, the use of other shapes and / or sizes of reagent beads 180 is also envisioned. In some embodiments, the reagent beads 180 are lyophilized material, although other forms of material are also envisioned. The reagent beads 180 can include materials such as, but not limited to, CaCl2, ellagic acid / phospholipid, tissue factor, heparinase, polybrene, and cytochalasin D, tranexamic acid, and combinations thereof. The reagent beads 180 are soluble in blood. For example, in this particular embodiment, each of the five mixing chambers 134a - e is configured to mix a predetermined volume of blood (as defined by the respective measurement chambers 132a - e) with different reagent compositions (from one or more of the reagent beads 180 therein) for the purpose of performing five different assays. In this example, the first mixing chamber 134e can contain a plurality of reagent beads 180, and the plurality of reagent beads 180 provide CaCl2 and ellagic acid / phospholipid for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132e) such that the first sample portion can be used in the first type of assay. Also, in this example, the second mixing chamber 134d can contain a plurality of reagent beads 180, and the plurality of reagent beads 180 provide CaCl2, ellagic acid / phospholipid, and heparinase for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132d) such that the second sample portion can be used in the second type of assay. Further, in this example, the third mixing chamber 134c can contain a plurality of reagent beads 180, and the plurality of reagent beads 180 provide CaCl2, tissue factor, and polybrene for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132c) such that the third sample portion can be used in the third type of assay.Also, in this example, the fourth mixing chamber 134b can include a plurality of reagent beads 180, and the plurality of reagent beads 180 provide CaCl2, tissue factor, polybrene, and cytochalasin D for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132b), such that the fourth sample portion can be used in a fourth type of assay. Finally, in this example, the fifth mixing chamber 134a can include a plurality of reagent beads 180, and the plurality of reagent beads 180 provide CaCl2, tissue factor, polybrene, and tranexamic acid for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132a), such that the fifth sample portion can be used in a fifth type of assay.

[0070] In some embodiments, the reagent beads 180 carrying the CaCl2 reagent are separated from the remaining portions of the beads 180 in each mixing chamber 134a - e to first enable mixing and then enable activation / coagulation of the citrated blood sample. Such separation of the reagent beads 180 carrying the CaCl2 reagent can be achieved using the retaining element 182 (as described above). Alternatively, such separation can be achieved by holding the reagent beads 180 carrying the CaCl2 reagent, which are separated from the other beads 180 in each chamber 134a - e, in separate channels or separate mixing chambers (after the blood portion has been mixed with the other beads 180 in each mixing chamber 134a - e, the blood portion is adapted to reach the CaCl2 reagent). Alternatively, such separation is achieved by positioning the CaCl2 reagent liquid or the dried film CaCl2 reagent in separate channels, such that after the blood portion has been mixed with the other beads 180 in each mixing chamber 134a - e, the blood portion is adapted to reach the CaCl2 reagent. Alternatively, the reagent beads 180 carrying the CaCl2 reagent are coated with an additional layer (and then held by the retaining element 182 as described above), such that after the blood portion has been mixed with the other beads 180 in each mixing chamber 134a - e first, the blood portion is adapted to begin dissolving the reagent beads 180 carrying the CaCl2 reagent.

[0071] Also, other configurations for providing the reagent to the blood sample can be used. In some embodiments, the reagent is coated on the wall portions of the mixing chambers 134a - e. In some embodiments, the reagent is coated on the right cover 126 or the left cover 128. The reagent coated on the right cover 126 or the left cover 128 can be coated in such a manner that it will be at least partially or entirely contained within the mixing chambers 134a - e. In some embodiments, the reagent is coated such that it remains below the fill level of the mixing chambers 134a - e (the fill level is related to the height of the blood in the mixing chambers such that it is partially determined by a predetermined volume of blood as measured within the measurement chamber). In some embodiments, the reagent to be coated is a film layer, i.e., a reagent film. The reagent film is a layer of reagent coated on or near the surface. The reagent film can be liquid or can be dried. The liquid reagent can be retained as a film layer by a soluble layer of material placed on top of the liquid reagent. Also, the liquid reagent layer can be applied on the surface and then dried. Also, a pre - dried or solid film reagent can be applied to the surface to form the film layer. In some embodiments, the film layer is in the form of a soluble film strip. In some embodiments, certain reagents, as opposed to the reagent beads 180, are preferably delivered within the reagent film. For example, certain reagents that are difficult to lyophilize within the reagent beads 180 can instead be coated as a film layer on or near the surface within the device.

[0072] In some embodiments, the reagent to be coated is in the form of reagent beads 180. The reagent beads can be fixed to the wall of the chamber or to the cover using a retaining element 182. The retaining element 182 can include a series of compartments, posts, divots, inward or outward protrusions, or an array of any of the above. Other shapes or configurations of reagents that can be coated or fixed within the cover, the wall of the chamber, or the fluid passageways between chambers are also envisioned. In some embodiments, both the reagent beads 180 and the reagent film are coated on one or more surfaces of the device, for example, within the mixing chambers 134a - e.

[0073] Also, the reagent film can be provided to dissolve in the blood sample within the mixing chambers 134a - e. The reagent film is soluble in blood. The reagent film is adhered to the surface within the mixing chambers 134a - e. In some embodiments, the reagent film is deposited on the walls of the mixing chambers 134a - e. In some embodiments, the reagent film is deposited on the right cover 126 or the left cover 128 in a region that at least partially covers or forms the walls of the mixing chambers 134a - e. The reagent film can be used alone or in addition to one or more reagent beads 180 placed within the mixing chambers 134a - e. Thus, the use of one or more reagent films within the mixing chambers 134a - e provides an additional mechanism for introducing reagents into the mixing chambers 134a - e to dissolve in the blood.

[0074] In some embodiments, the reagent film contains lyophilized material, although other forms of material are envisioned. The reagent film can contain materials such as, but not limited to, CaCl2, ellagic acid / phosopholipid, tissue factor, heparinase, polybrene, cytochalasin D, and tranexamic acid, as well as combinations thereof. In one particular example, each of the five mixing chambers 134a-e is configured to mix a predetermined volume of blood (as defined by the respective measurement chambers 132a-e) with a different reagent composition (from one or more of the reagent beads 180 and / or one or more of the reagent films). In this example, the first mixing chamber 134e can contain a plurality of reagent beads 180 and at least one reagent film, and provides CaCl2 and ellagic acid / phosopholipid for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132e), such that a first sample portion can be used in a first type of assay. Also in this example, the second mixing chamber 134d can contain a plurality of reagent beads 180 and at least one reagent film, and provides CaCl2, ellagic acid / phosopholipid, and heparinase for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132d), such that a second sample portion can be used in a second type of assay. Further in this example, the third mixing chamber 134c can contain a plurality of reagent beads 180 and at least one reagent film, and provides CaCl2, tissue factor, and polybrene for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132c), such that a third sample portion can be used in a third type of assay. Also in this example, the fourth mixing chamber 134b can contain a plurality of reagent beads 180 and at least one reagent film, and provides CaCl2, tissue factor, polybrene, and cytochalasin D for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132b), such that a fourth sample portion can be used in a fourth type of assay.Finally, in this example, the fifth mixing chamber 134a can include a plurality of reagent beads 180 and at least one reagent film, and provides CaCl2, tissue factor, polybrene, and tranexamic acid for mixing with a predetermined volume of blood (from the corresponding measurement chamber 132a), such that the fifth sample portion can be used in a fifth type of assay.

[0075] Furthermore, the reagent film can be deposited on a surface upstream or downstream from the mixing chamber and can mix with the blood sample before or after the mixing chamber. In some embodiments, the reagent film carrying the CaCl2 reagent is placed in a separate channel or a separate mixing chamber, which is separated from the other reagent beads 180 or reagent films in each of the chambers 134a - e (e.g., such that after the blood portion has mixed with the other reagent beads 180 and / or reagent films in each of the mixing chambers 134a - e, the blood portion reaches the CaCl2 reagent film). Alternatively, the CaCl2 reagent film is deposited in the mixing chambers 134a - e and coated with an additional soluble film layer such that after the blood portion has first mixed with the other reagent beads 180 or reagent films in each of the mixing chambers 134a - e, the blood portion begins to dissolve the other reagent film carrying the CaCl2 reagent.

[0076] In some embodiments, the reagent beads 180 or reagent film are separated from the remaining portions of the reagent beads 180 or reagent film in their respective mixing chambers 134a - e, and are adapted to be mixed with different reagents in a suitable sequence. In one embodiment, such separation of the reagent beads 180 can be achieved using the holding element 182 (as described above). Alternatively, such separation can be achieved by holding the reagent beads 180 or reagent film, which are separated from the other beads 180 or reagent film in their respective chambers 134a - e, in separate channels or separate mixing chambers (such that the blood portion reaches and mixes with the loaded reagents in a suitable sequence). In one embodiment, such separation is achieved by positioning the reagent liquid, reagent beads 180, or dried film reagents in separate channels, such that the blood portion reaches the reagent before or after mixing with the other reagent beads 180 or reagent film in their respective mixing chambers 134a - e. In some embodiments, the reagent beads 180 or reagent film are installed along the duct 134ad that fluidly connects the mixing chambers 134a - e and the inspection chambers 136a - e. Alternatively, the reagent beads 180 or reagent film are coated by an additional layer (and then held by the holding element 182 as described above), such that after the blood portion first mixes with the other reagent beads 180 or reagent film in their respective mixing chambers 134a - e, the blood portion begins to dissolve the reagent in the reagent beads 180 or reagent film that includes the additional soluble layer. In some embodiments, the coated reagent layer is a soluble film layer made from a substrate that includes a polymer composition and a reagent. The polymer composition forms a soluble barrier and maintains the coating of the reagent on or near the surface within the device. When contacting the blood sample, the polymer composition dissolves, enabling the blood sample to mix with the reagent.

[0077] The hybrid element 184 includes ferromagnetic materials including, but not limited to, nickel, cobalt, chromium (IV) oxide, gadolinium, permalloy, and alnico (aluminum-nickel-cobalt alloy), and combinations thereof. In the illustrated embodiment, the hybrid element 184 is spherical and solid. In other embodiments, the hybrid element 184 can have a shape including, but not limited to, cube, cone, cylinder, sector, elongated shape, and prism shape, and irregular shapes. In some embodiments, the hybrid element 184 can include one or more surface features such as protrusions, depressions, or holes.

[0078] As further described below, the hybrid element 184 is movable within the mixing chambers 134a - e in response to the movement of the magnet to which the hybrid element 184 is magnetically coupled. The magnet to which the hybrid element 184 is magnetically coupled is contained within the analyzer console 140. The movement of the hybrid element 184 urges the reagent beads 180 to dissolve in the blood contained within the mixing chambers 134a - e.

[0079] Referring now to FIGS. 8A - 8H, an exemplary fluid control process 200 that can be used with the thromboelastometry system provided herein is schematically shown. The process 200 begins with blood contained only within the blood collection tube 10 and ends with a blood / reagent mixture contained within the cups 136a - e configured for rotational thromboelastometry. It should be understood that in some embodiments, the cartridge 120 (see FIGS. 1 - 7) used to implement the fluid control process 200 is heated (e.g., up to about 37°C) before having any blood therein.

[0080] Referring to FIG. 8A, an exemplary fluid control process 200 includes a blood collection tube 10, measurement chambers 132a-e, mixing chambers 134a-e, and cups 136a-e, an overflow chamber 139, blood detection locations 127a and 127b, a vacuum application port 162, a pressure application port 164, vents 166a-e, valves 168, 170, and 160a-e. In the configuration shown, valve 168 is closed, thereby substantially holding blood in blood collection tube 10.

[0081] The exemplary fluid control process 200 includes five blood flow channels (each including measurement chambers 132a - e, mixing chambers 134a - e, and cups 136a - e), but it should be understood that having five blood flow channels is not required in all embodiments. For example, in some embodiments, only a single blood flow channel is included. Alternatively, two blood flow channels may be included, or three blood flow channels may be included, or four blood flow channels may be included, or six blood flow channels may be included, or seven or more blood flow channels may be included. Referring to FIG. 8B, the measurement chambers 132a - e are filled with blood, and a small amount of blood is contained within the overflow chamber 139. To reach this state, the following changes were made and / or the following conditions existed compared to FIG. 8A: (i) valves 168 and 170 were opened, (ii) valves 160a - e were closed, (iii) vents 166a - e were closed, (iv) negative pressure was applied to the vacuum application port 162, and (v) the pressure application port 164 was not pressurized. Thus, blood flowed (i) from the blood collection tube 10, (ii) through valve 168, (iii) through the blood detection location 127a, (iv) into measurement chamber 132a to fill measurement chamber 132a, (v) into measurement chamber 132b to fill measurement chamber 132b, (vi) into measurement chamber 132c to fill measurement chamber 132c, (vii) into measurement chamber 132d to fill measurement chamber 132d, (viii) into measurement chamber 132e to fill measurement chamber 132e, (ix) through the blood detection location 127b, (x) through valve 170, and (xi) into the overflow chamber 139. When blood was detected within the blood detection location 127b, the application of negative pressure was stopped, thereby stopping further blood flow.

[0082] In some embodiments, the exemplary fluid control process 200 includes a stop junction 132as between one, several, or each of the measurement chambers 132a - e and the mixing chambers 134a - e. In some embodiments, through the application of positive pressure to the measurement chambers or negative pressure to the mixing chambers 134a - e, blood flows through the stop junction 132as in the duct 132ad connecting the measurement chambers 132a - e and the mixing chambers 134a - e. The stop junction provides a mechanism for adjusting the flow without connection to an external control device. The application of positive or negative pressure can create a pressure difference on either side of the stop junction, causing the stop junction to open or drawing blood through the stop junction by overcoming the forces due to surface tension. The desired pressure is applied via the pressure application port 164, causing blood to flow through the stop junction and / or relieving the pressure in the corresponding mixing chambers 134a - e by opening the pneumatic vents 166a - e.

[0083] In some embodiments, the exemplary fluid control process 200 includes, instead of or in addition to, a stop junction between one, several, or each of the measurement chambers 132a - e and the mixing chambers 134a - e, a stop valve. In some embodiments, the stop valve is a snap - acting valve that snaps open when a set pressure is reached or a modulating valve that opens in proportion to a pressure difference. Other cartridge embodiments can include pressure - controlled valves within other fluid paths.

[0084] In some embodiments, the stop valve can be opened and closed by the same mechanism provided by valves 168, 162, 160a - e shown in the reaction system in FIGS. 8A - 8H. In some embodiments, the stop valve can be opened and closed through a mechanism other than applying pressure to the blood. In some embodiments, the stop valve is opened based on a remote command from a control device connected to the stop valve. In some embodiments, the stop valve is actuated by the analyzer console 140 and can allow or prevent fluid flow through the fluid path from the measurement chambers 132a - e to the mixing chambers 134a - e.

[0085] Referring to FIG. 8C, the measurement chambers 132a - d are still filled with blood, but the blood from the measurement chamber 132e is being transferred to the mixing chamber 134e. To reach this state (compared to FIG. 8B), the following changes were made and / or the following conditions existed: (i) valves 168 and 170 were closed, (ii) valves 160a - e remained closed, (iii) vents 166a - d remained closed, (iv) vent 166e was opened, and (v) an air pressure source was applied to the pressure application port 164. Thus, blood flowed (i) from the measurement chamber 132e and (ii) into the mixing chamber 134e. Since vents 166a - d and valves 160a - d remained closed, the blood in the measurement chambers 132a - d did not flow into the mixing chambers 134a - d. With blood in the mixing chamber 134e, the mixing element in the mixing chamber 134e can move and agitate the blood, promoting the dissolution of the reagent beads therein.

[0086] In some embodiments, the fluid control process 200 shown in FIG. 8C includes a stop junction (not shown) between the measurement chambers 132a-e and the mixing chambers 134a-e, which prevents the flow of blood from the measurement chambers to the mixing chambers when a sufficient pressure difference is not applied between the measurement chambers 132a-e and the mixing chambers 134a-e. In this embodiment, the stop junction prevents leakage of blood from the measurement chambers 132a-d into the mixing chambers 166a-d unless the vents 166a-d are opened or sufficient pressure is applied to the pressure application port 164 to cause blood to flow through the stop junction. To fill the measurement chamber 132e with blood from the mixing chamber 134e, the following changes were made and / or the following conditions existed (compared to FIG. 8B). (i) Valves 168 and 170 were closed, (ii) valves 160a-e remained closed, (iii) vents 166a-d remained closed, (iv) vent 166e was opened, (v) an air pressure source was applied to the pressure application port 164, causing blood to flow through the stop junction from the measurement chamber 132e into the mixing chamber 134e, while the stop junction between the measurement chambers 132a-d and the mixing chambers 134a-d prevented the flow of blood from the measurement chambers 132a-d into the mixing chambers 134a-d. With blood in the mixing chamber 134e, the mixing element in the mixing chamber 134e is movable and can stir the blood and promote the dissolution of the reagent beads therein.

[0087] Referring to FIG. 8D, the measurement chambers 132a - d are still filled with blood, and the blood / reagent mixture (see FIG. 8C) that was in the mixing chamber 134e has been transferred to the cup 136e. To reach this state, the following changes were made and / or the following conditions existed (compared to FIG. 8C). (i) Valves 168 and 170 remained closed, (ii) valve 160e was opened, (iii) valves 160a - d remained closed, (iv) vent 166e was closed, (v) vents 166a - d remained closed, and (vi) an air pressure supply source was applied to the pressure application port 164. Thus, the blood / reagent mixture flowed (i) from the mixing chamber 134e and (ii) into the cup 136e. Since vents 166a - d and valves 160a - d remained closed, blood did not flow from the measurement chambers 132a - d towards the mixing chambers 134a - d. With the blood / reagent mixture positioned in the cup 136e, rotational thromboelastometry can begin within the cup 136e.

[0088] Referring to FIG. 8E, the measurement chambers 132a - c are still filled with blood, the cup 136e is still filled with the blood / reagent mixture, and the blood that was in the measurement chamber 132d (see FIG. 8D) is being transferred to the mixing chamber 134d. To reach this state, the following changes were made and / or the following conditions existed (compared to FIG. 8D). (i) Valves 168 and 170 remain closed, (ii) valve 160e is closed, (iii) valves 160a - d remain closed, (iv) vent 166d is opened, (v) vents 166a - c and 166e remain closed, (vi) an air pressure source is applied to the pressure application port 164. In embodiments including a stop junction between the measurement chamber 132d and the mixing chamber 134d, the blood travels through the stop junction due to the application of a pressure difference between the measurement chamber 132d and the mixing chamber 134d, while the stop junction between the measurement chambers 132a - c and the mixing chambers 134a - c prevents flow. Thus, (i) from the measurement chamber 132d, (ii) into the mixing chamber 134d, the blood flowed. Since vents 166a - c and valves 160a - c remained closed, the blood did not flow from the measurement chambers 132a - c towards the mixing chambers 134a - c. With the blood in the mixing chamber 134d, the mixing element in the mixing chamber 134d can agitate the blood and promote the dissolution of the reagent beads therein.

[0089] Referring to FIG. 8F, the measurement chambers 132a - c are still filled with blood, the cup 136e is still filled with the blood / reagent mixture, and the blood / reagent mixture (see FIG. 8E) that was in the mixing chamber 134d has been transferred to the cup 136d. To reach this state, the following changes were made and / or the following conditions existed (compared to FIG. 8E). (i) Valves 168 and 170 remained closed, (ii) valve 160d was opened, (iii) valves 160a - c and 160e remained closed, (iv) vent 166d was closed, (v) vents 166a - c and 166e remained closed, and (vi) an air pressure source was applied to the pressure application port 164. Thus, the blood / reagent mixture flowed (i) from the mixing chamber 134d and (ii) into the cup 136d. Since vents 166a - c and valves 160a - c remained closed, blood did not flow from the measurement chambers 132a - c towards the mixing chambers 134a - c. With the blood / reagent mixture positioned in the cup 136d, rotational thromboelastometry can begin within the cup 136d.

[0090] Referring to FIG. 8G, the measurement chambers 132a - b are still filled with blood, the cups 136d - e are still filled with the blood / reagent mixture, and the blood that was in measurement chamber 132c (see FIG. 8F) is being transferred to mixing chamber 134c. To reach this state (compared to FIG. 8F), the following changes were made and / or the following conditions existed. (i) Valves 168 and 170 remained closed, (ii) valve 160d was closed, (iii) valves 160a - c and 160e remained closed, (iv) vent 166c was opened, (iv) vents 166a - b and 166d - e remained closed, (v) an air pressure source was applied to pressure application port 164. In embodiments including a stop junction between measurement chamber 132d and mixing chamber 134d, blood travels through the stop junction due to the application of a pressure difference between measurement chamber 132c and mixing chamber 134c, while the stop junction between measurement chambers 132a - b and mixing chambers 134a - b prevents flow. Thus, blood flowed (i) from measurement chamber 132c and (ii) into mixing chamber 134c. Since vents 166a - b and valves 160a - b remained closed, blood did not flow from measurement chambers 132a - b into mixing chambers 134a - b. With the blood in mixing chamber 134c, the mixing element in mixing chamber 134c can stir the blood and promote the dissolution of the reagent beads therein.

[0091] Referring to FIG. 8H, the completion of process 200 is shown. That is, cups 136a - c all contain the blood / reagent mixture, and rotational thromboelastometry can occur within cups 136a - e. This state can be achieved according to the method of operating valves 168, 170, and 160a - e, and vents 166a - e, involving applying a vacuum to vacuum application port 162 or applying a pressure to pressure application port 164 as described above.

[0092] Referring to FIG. 9, in some alternative embodiments, one or more of the individual blood flow channels or paths can include a plurality of mixing chambers arranged in series. For example, the exemplary fluid control process 280 includes five blood flow channels (the same number as the channels in the embodiments of FIGS. 8A-H), but each of the channels includes two mixing chambers arranged in series (rather than including a single mixing chamber for each of the mixing chambers as in the embodiments of FIGS. 8A-H). That is, mixing chambers 137a and 137f are arranged in series between measurement chamber 132a and cup 136a. Mixing chambers 137b and 137g are arranged in series between measurement chamber 132b and cup 136b. Mixing chambers 137c and 137h are arranged in series between measurement chamber 132c and cup 136c. Mixing chambers 137d and 137i are arranged in series between measurement chamber 132d and cup 136d. Mixing chambers 137e and 137j are arranged in series between measurement chamber 132e and cup 136e.

[0093] In some embodiments, the reagent beads carrying the CaCl2 reagent are separated from other reagent beads by positioning the CaCl2 reagent in the second of two mixing chambers arranged in series. In that manner, the series of mixing chambers can allow the blood sample to be mixed with the reagent, followed by the activation / coagulation of the blood sample being initiated at a controlled time point.

[0094] The exemplary fluid control process 280 includes five blood flow channels, each of which includes two mixing chambers arranged in series, but it should be understood that such a configuration is not required in all embodiments. For example, in some embodiments, only a single blood flow channel including two mixing chambers arranged in series is included in the cartridge. Such a single blood flow channel with two mixing chambers can be the only blood flow channel in the cartridge, or can be combined in the cartridge with one or more other blood flow channels including a single mixing chamber. It should be understood that all combinations and permutations of multiple blood flow channels and mixing chambers are within the scope of the present disclosure.

[0095] Now, looking more specifically at the blood coagulation test chambers 136a - e, the chambers 136a - e are configured to provide a viscoelasticity test on the blood sample portion drawn into each chamber. Referring to FIGS. 10A and 10B, the pins 138a - e are positioned within the cartridge 120. A representative example showing the pin 138b positioned within the cup 136b illustrates that there is a clearance space between the outer diameter of the pin 138b and the inner diameter of the cup 136b. The blood / reagent mixture will at least partially fill the clearance space when rotational thromboelastometry is being performed therein. The pin 138b has a shoulder portion 138bs. The clearance space between the outer diameter of the pin 138b and the inner diameter of the cup 136b is smaller in the area below the shoulder portion 138bs than in the area above the shoulder portion 138bs. The area between the outer diameter of the pin 138b and the inner diameter of the cup 136b, which is below the shoulder portion 138bs, is the area activated for performing rotational thromboelastometry.

[0096] The cup 136b and the pin 138b are shown in the cross-section of FIG. 10B (in accordance with cross-section 10B-10B of section view 10A). Additionally, a sample inlet port 136bi (positioned behind the pin 138b in the orientation of FIG. 10B) is provided such that a blood / reagent mixture will flow into the cup 136b through the sample inlet port 136bi. In the illustrated embodiment, the cup inlet port 136bi is above the enlarged distal portion of the pin 138b (see shoulder portion 138bs), but at a height below the proximal end of the pin 138b (see the end near the axial bore 138bb of the pin 138b) and is positioned within the sidewall portion of the cup 136b. In this configuration, the blood / reagent mixture will flow into the cup 136b, reducing the likelihood of foam formation. Additionally, if the cup inlet port 136bi is positioned within the active space between the inner diameter of the cup 136b and the outer diameter of the pin 138b below the shoulder portion 138bs, positioning the cup inlet port 136bi at the top of the cup 136b eliminates the potential influence that the cup inlet port 136bi might otherwise have on thromboelastometry measurements performed within the cup 136b.

[0097] In certain devices, bridging or other structure formation may occur between the cup inlet port 136bi (within the inner diameter of the cup 136b) and the outer diameter of the pin 138b (i.e., the probe element). This can affect the ability of blood to flow into the cups 136a - e, or can introduce errors during thromboelastometry measurements performed within the cups 136a - e. In some embodiments, the opening of the inlet port 136bi and the outer diameter of the pin 138b are separated by at least a minimum clearance distance that prevents stable bridging or other clot structure formation of the blood sample between the pin 138b and the cup inlet port 136bi. At the minimum clearance distance, bridging between the sample inlet port and the pin can occur as the inspection chamber fills, however, the bridge will not be stable enough to persist during measurement. Typically, the bridge will form around a bubble, and the bubble will become unstable if its diameter is greater than or equal to the minimum clearance distance. In some embodiments, a stable bridge persists for longer than 1 second, 2 seconds, 3 seconds, 4 seconds, or 5 seconds. In some embodiments, the minimum clearance distance is at least 1.5 mm. In some embodiments, the minimum clearance distance is at least 1.5 mm, 2 mm, 2.5 mm, or 3 mm. In the embodiment shown in FIG. 10B, the cup inlet port 136bi is located in the sidewall of the cup 136b at a height above the enlarged distal portion of the pin 138b (see shoulder portion 138bs) but below the proximal end of the pin 138b (see the end near the axial bore 138bb of the pin 138b), and the inlet port 136bi is at least 1.5 mm from the pin 138b. In other words, the geometry of the pin can allow for this additional clearance. The reason is that at the location where bridging may occur, the pin has a narrower portion, thereby allowing a greater clearance between the pin and the cup to prevent stable bridging.

[0098] In the illustrated embodiment, the upper portion of the cartridge 124 includes a vent 121. The vent 121 is in fluid communication with the needle 123b. Thus, when air is required to vent a blood sample tube positioned in the sample well 122, air is drawn in through the vent 121 and fed into the blood sample tube through the needle 123b.

[0099] Each of the pins 138a - e includes an axial bore. For example, the pin 138b includes an axial bore 138bb. The axial bore 138bb can be used to engage a shaft (not shown in FIG. 10B) for performing rotational thromboelastometry.

[0100] Referring to FIG. 10C, an exemplary rotational thromboelastometry assembly 300b can engage with a pin 138b to perform rotational thromboelastometry on a blood sample contained within a cup 136b. In this particular embodiment, the exemplary rotational thromboelastometry assembly 300b includes a base plate 302, a shaft 310b, a bearing 312b, a mirror 314b, a reaction spring 320b, a light source 330b, and a detector 340b (e.g., a charge-coupled device, etc.). The base plate 302 is lowered as represented by arrow 318b such that the tip portion of the shaft 310b enters bore 138bb and is removably coupled to the pin 138b. The bearing 312b is engaged with the base plate 302 and the shaft 310b to facilitate rotational movement of the shaft 310b relative to the base plate 302. The reaction spring 320b is coupled to the shaft 310b, and the oscillation of the spring 320b can induce the shaft 310b to reciprocally oscillate by approximately + / -5° as represented by arrow 316b. The mirror 315 is coupled to the shaft 310b. The light source 330b is configured to project light toward the mirror 314b, and the light can be reflected from the mirror 315 toward the detector 340b (depending on the rotational orientation of the shaft 310b). Thus, the movement of the pin 138b can be detected by an optical detection system. It should also be understood that other configurations of the rotational thromboelastometry assembly 300b are envisioned within the scope of the present disclosure.

[0101] The detected motion data is analyzed by an algorithm running on an analyzer console 140 (see FIGS. 1 - 3) to process and determine thromboelastometry results. This system facilitates various thromboelastometry parameters such as, for example, but not limited to, clotting time, clot formation time, alpha angle, amplitude, maximum clot firmness, lysis start time, lysis time, lysis index (%), and maximum lysis (%).

[0102] When the blood in the cup 136b begins to coagulate, the amplitude of movement of the shaft 310b begins to decrease (as detected by the deflection of the light beam from the mirror 315 towards the detector 340b). During coagulation, the fibrin backbone of the blood (with platelets) creates a mechanical elastic linkage between the surfaces of the cup 136b and the pin 138b. Thus, the ongoing coagulation process induced by adding one or more of the above-described activating factors can be observed and quantified. In this way, various deficiencies in the patient's hemostatic situation can be revealed and interpreted for appropriate medical intervention. At the end of the test process, the base plate 302 can be raised to disconnect the shaft 310b from the pin 138b.

[0103] Referring to FIG. 11, the main chassis 144 of the analyzer console 140 can include a front portion 144f and a rear portion 144b. In some embodiments, the rear portion 144b houses at least some of the computers and electronic components necessary for the operation of the analyzer console 140. For example, the rear portion 144b can house hardware devices and software such as, but not limited to, a computer processor, a memory device, an operating system, and other executable instructions, a power supply, a user interface control, a communication device, and a circuit board.

[0104] In the illustrated embodiment, the front portion 144f includes a cover 145 and a sample handler assembly 400. The sample handler assembly 400 defines an internal space in which the cartridge 120 can be received. In some embodiments, the sample handler assembly 400 is a modular subassembly of the analyzer console 140 and can be easily removed from the analyzer console 140 for servicing. The sample handler assembly 400 is electrically interconnected with a computer and electronic components housed within the rear portion 144b. As such, the analyzer console 140 can perform rotational thromboelastometry on a blood sample positioned within the cartridge 120 and display the results on the touch screen display 142.

[0105] Referring now to FIGS. 11 and 12, the analyzer console 140 can include a cartridge receiver and clamp 410 and a viscoelastic measurement system 480. A mechanical frame assembly is used to support the cartridge receiver and clamp 410 and the viscoelastic measurement system 480 in proper orientation such that the cartridge receiver and clamp 410 and the viscoelastic measurement system 480 can function symbiotically.

[0106] The cartridge receiver and clamp 410 and a portion of the viscoelastic measurement system 480 are movable relative to a mechanical frame assembly that is stationary relative to the analyzer console 140. For example, the viscoelastic measurement system 480 can move upward and downward. As further described below, the viscoelastic measurement system 480 can move downward to engage the cartridge 120 (see, e.g., FIG. 11), and can move upward to disengage from the cartridge 120. A portion of the cartridge receiver and clamp 410 can move horizontally relative to the mechanical frame assembly. As further described below, a portion of the cartridge receiver and clamp 410 can move horizontally to clamp or unclamp the cartridge 120 into the sample handler assembly 400.

[0107] In some embodiments, the cartridge receiver and clamp 410 includes a movable block sub-assembly and a stationary block sub-assembly. A space in which the cartridge 120 can be received is present between the movable block sub-assembly and the stationary block sub-assembly. The movable block sub-assembly can be translated toward or away from the stationary block sub-assembly. Accordingly, the cartridge 120 can be clamped and unclamped between the movable block sub-assembly and the stationary block sub-assembly due to the relative movement therebetween. In some embodiments, the viscoelastic measurement system 480 is attached to the movable block sub-assembly. Accordingly, when the movable block sub-assembly is translated, the viscoelastic measurement system 480 is also translated.

[0108] In some embodiments, the movable block subassembly can be translated by an electric motor. In certain embodiments, the motor is a stepper motor. In some embodiments, a gear reducer is coupled to the motor. For miniaturization, a belt and pulley arrangement can be used such that the motor can be used to drive a lead screw. The threads of the lead screw are engaged with complementary threads of the movable block such that rotation of the lead screw results in horizontal translation of the movable block. In some embodiments, an end-of-travel detector (e.g., a proximity sensor, an optical sensor, and a microswitch, etc.) is included to detect when the movable block subassembly has been horizontally translated to a desired end-of-travel position.

[0109] In some embodiments, one or more springs can extend between the movable block subassembly and the stationary block subassembly. The springs can help facilitate an appropriate clamping force between the movable block subassembly and the stationary block subassembly. In some embodiments, the springs are adjustable.

[0110] In some embodiments, portions of the movable block subassembly and the stationary block subassembly that contact the cartridge 120 include a flexible or compressible material such that it is protected from damage while the cartridge 120 is being clamped.

[0111] In certain embodiments, the movable block subassembly can include one or more features on the clamping surface of the movable block subassembly, which serves to position the cartridge 120 in a desired location within the sample handler assembly 400. For example, in some embodiments, the movable block subassembly includes two locator pins that can engage with the locator pin receptacles 140a and 140b (see FIG. 7) of the cartridge 120 to accurately position the cartridge 120 relative to the sample handler assembly 400.

[0112] In some embodiments, one or both of the movable block subassembly and the stationary block subassembly include a heating device 412 that can warm the cartridge 120 when the cartridge 120 is clamped therebetween. For example, in some embodiments, the heater 412 is an electrical resistance heater used to heat at least a portion of the cartridge 120. In some embodiments, the heater 412 is configured to facilitate warming of individual portions of the cartridge 120 independently of other portions of the cartridge 120. For example, one or more of the individual blood flow channels 130a, 130b, 130c, 130d, and 130e (see FIGS. 4 - 7) can be warmed independently in some such embodiments. The warming can be performed on one or more sides of the cartridge 120. Other types of warming modalities can also be used, including but not limited to IR, ultrasonic, and microwave.

[0113] In certain embodiments, one or more temperature sensors 414 are included, and the one or more temperature sensors 414 can detect the temperature of the cartridge 120 at one or more locations on the cartridge 120. For example, in some embodiments, the one or more temperature sensors 414 can be thermocouples, thermistors, and infrared temperature sensors, among others. Thus, the analyzer console 140 can use the heater 412 and the temperature sensor 414 to control heating the cartridge 120 to a predetermined temperature (e.g., about 37 °C).

[0114] The movable block subassembly can include a plurality of solenoids, which are used to operate the aforementioned vents and valves of the cartridge 120. For example (see also FIG. 7), valves 168, 170, and 160a - e are actuated by valve actuator 430, and vents 166a - e can be actuated by vent actuator 432. In some embodiments, valve actuator 430 and vent actuator 432 include solenoids. Actuation of valves 168, 170, and 160a - e by valve actuator 430 is achieved by connecting pins to valve actuator 430, and valve actuator 430 is extensible from the movable block subassembly and contacts the valve elastomeric member to expand the valve elastomeric member such that the elastomeric member contacts the valve seat in cartridge 120. Actuation of vents 166a - e by vent actuator 432 is achieved by connecting pins to the elastic tip portions, and the elastic tip portions are extensible from the movable block subassembly and obstruct vents 166a - e. Such pins with elastic tip portions can act as stoppers to substantially prevent air flow through vents 166a - e. In some embodiments, valve actuator 430 and vent actuator 432 include solenoids, and the solenoids include internal springs, which cause valve actuator 430 and vent actuator 432 to be extended normally (e.g., when power is removed from the solenoids). Thus, such normally - closed solenoids will, by default configuration, close the vents and valves of cartridge 120.

[0115] Also, the sample handler assembly 400 includes a pressure source 436 and a vacuum source 434, by which air pressure and vacuum can be applied to the pressure application port 164 and the vacuum application port 162 of the cartridge 120, respectively (see FIG. 7). For example, the pressure source 436 and the vacuum source 434 can be in contact with the cartridge 120, and can transmit pressure or vacuum to the pressure application port 164 and the vacuum application port 162 when the cartridge 120 is clamped in the cartridge receiver and clamp 410. The pressure source 436 and the vacuum source 434 are at least partially made of an elastic material in some embodiments. For example, in some embodiments, the pressure source 436 and the vacuum source 434 are at least partially made of an elastic material such as, but not limited to, silicone, butyl rubber, nitrile rubber, ethylene propylene rubber, and fluoroelastomer. Also, one or more internally housed pressure pumps and / or vacuum pumps (not shown) can be included in the analyzer console 140. Such internally housed pressure pumps and vacuum pumps are used to generate air pressure or vacuum, which is applied to the cartridge 120 and induces the transport of blood in the cartridge 120 as described above with reference to FIGS. 8A-8H.

[0116] Also, as previously described, the cartridge receiver and clamp 410 includes a stationary block subassembly. In some embodiments, the stationary block subassembly does not move as a whole relative to the mechanical frame assembly and relative to the analyzer console 140.

[0117] In some embodiments, the analyzer console 140 includes a mixing unit 440. In certain embodiments, the mixing unit 440 includes a motor, a crank and connecting rod assembly, and a magnetic shuttle. These components are used to magnetically couple the mixing elements of the cartridge 120 and can also be used to induce the movement of the mixing elements within the mixing chambers 134a - e. The movement of the mixing elements, as described above, promotes the dissolution of the reagent beads in the blood contained within the mixing chambers 134a - e.

[0118] Also, the analyzer console 140 can include one or more sensors 448. The one or more sensors 448 can be used to detect the presence of blood at specific locations within the cartridge 120, such as the blood detection locations 127a and 127b (see FIG. 5), as described above. In some embodiments, the sensor 448 is an optical sensor, such as an IR (infrared) sensor. In some embodiments, the sensor 448 can be used to detect blood in other areas of the cartridge 120, such as within the cups 136a - e (see FIGS. 8A - 8H), without being limited thereto.

[0119] Also, the sample handler assembly 400 of the analyzer console 140 includes a viscoelastic measurement system 480. The viscoelastic measurement system 480 includes a base plate 302 (see, e.g., FIG. 10C), one or more thromboelastometry assemblies (e.g., thromboelastometry assembly 300b), and a linear actuator assembly. One or more thromboelastometry assemblies can each be attached to the base plate 302. In some embodiments, the linear actuator assembly is coupled to the base plate 302 and to the cartridge receiver and clamp 410, such that actuation of the linear actuator assembly can translate the base plate 302 and the cartridge receiver and clamp 410 toward or away from each other. The linear bearing assembly of the linear actuator can guide the base plate 302 in a linear path and can stabilize the base plate 302 as it translates toward or away from the cartridge receiver and clamp 410.

[0120] In some embodiments, the linear actuator assembly uses a motor (e.g., a DC motor or a stepper motor) to cause the base plate 302 to move up or down in a direction perpendicular to the cartridge receiver and clamp 410, and the motor rotates a lead screw having a thread that engages a drive nut. The drive nut is coupled to the base plate 302. In some embodiments, an end-of-travel detector (e.g., a proximity sensor, an optical sensor, and a microswitch, etc.) is included to detect when the base plate 302 has been translated vertically to a desired end-of-travel position.

[0121] The viscoelastic measurement system 480 includes one of a further rotational thromboelastometry assembly (e.g., the rotational thromboelastometry assembly 300b of FIG. 10C), and the one or more rotational thromboelastometry assemblies include a shaft configured to couple to a pin (e.g., the shaft 310b configured to couple to the pin 138b). Since the thromboelastometry assembly is mounted to the base plate 302, the shaft is raised or lowered in conjunction with the raising or lowering of the base plate 302. Thus, the operation of the linear actuator assembly causes the shaft to rise or fall vertically with respect to the cartridge receiver and clamp 410 and with respect to the cartridge 120 when the cartridge 120 is clamped in the cartridge receiver and clamp 410. Thus, from the description herein, it can be understood that the operation of the linear actuator assembly can engage the shaft with the pin of the cartridge 120 and disengage the shaft from the pin of the cartridge 120 (see, e.g., FIG. 10C. FIG. 10C shows that the base plate 302 is lowered to engage the shaft 310b with the pin 138b).

[0122] In addition to the above-described features of the analyzer console 140, in some embodiments, the analyzer console 140 may also include one or more of the following features. The analyzer console 140 can include one or more barcode scanners 450, and the one or more barcode scanners 450 can read barcodes at, for example, the barcode location 125 on the tip of the cartridge 120 (see FIG. 5). In some embodiments, the analyzer console 140 includes one or more devices that can detect the presence of the cartridge 120 in a desired insertion location and / or orientation. For example, in some embodiments, one or more microswitches can be used to detect when the cartridge 120 is inserted into the sample handler assembly 400 in the desired location and orientation. In some embodiments, the analyzer console 140 can include one or more auxiliary connectors 460. The auxiliary connectors 460 can include network and device connectors such as, but not limited to, one or more USB ports, Ethernet ports (e.g., RJ45), VGA connectors, and Sub-D9 connectors (RS232). Such auxiliary connectors 460 can be positioned on the back of the main chassis 144 or in other convenient locations on the main chassis 144. For example, in some embodiments, one or more USB ports can be positioned on or near the front of the main chassis 144.

[0123] In addition, the analyzer console 140 includes a user interface 142 (e.g., in this embodiment, a touch screen display). In the illustrated embodiment, the user interface 142 is configured to receive user input and display output information to the user. For example, the user can input information to the analyzer console 140 by selecting various soft buttons that can be displayed on the user interface 142 at points in time during the start, middle, and end of the inspection process. In some embodiments, other selections, such as, but not limited to, soft keyboard input, can be provided via the user interface 142. In some embodiments, data input can be performed additionally or alternatively by voice input. In some embodiments, the user interface can include other peripheral devices (e.g., a mouse, a keyboard, and an additional display device, etc.) as part of the analyzer console 140. In some embodiments, a computer data network (e.g., an intranet, the Internet, a LAN, etc.) can be used to enable remote devices to receive and / or input information from the system 100. For example, in some embodiments, one or more remote displays can be utilized via the auxiliary connection unit 460. Also, in the illustrated embodiment, the user interface 142 includes an external barcode reader 146 (see FIG. 1A). Alternatively or additionally, the user interface 142 of the analyzer console 140 can be equipped with a reader configured to read a short-range wireless communication tag or an RFID tag, etc. Further, the analyzer console 140 can include one or more control systems 470, and the one or more control systems 470 can execute instructions embodied in a computer program. The control system 470 can include, by way of example, both general-purpose and dedicated microprocessors, as well as any one or more processors of any kind of digital computer.In some embodiments, control system 470 includes one or more such processors, memories, storage devices, interfaces, and other types of electronic subsystems and components. Such components may be mounted on a common motherboard or, if desired, in other manners. Control system 470 is capable of processing instructions for execution within analyzer console 140, which instructions include instructions stored in memory or on a storage device. In some implementations, multiple processors and / or multiple buses may be used, along with multiple memories and types of memory, as needed. Also, multiple computing devices may be connected such that each device provides a portion of the required operations (e.g., a server bank, a group of blade servers, or a multiprocessor system).

[0124] The storage device can provide mass storage for control system 470. In some implementations, the storage device can be or include an array of devices that are computer-readable media, such as floppy (registered trademark) disk devices, hard disk devices, optical disk devices, or tape devices, flash memory, or other similar solid state memory devices, or devices in a storage area network or other configuration. A computer program product can be tangibly embodied in an information carrier. Also, the computer program product can contain instructions that, when executed, perform one or more methods, such as those described above with reference to FIGS. 8A-8H. Further, the computer program product can be tangibly embodied in a computer-readable or machine-readable medium, such as a memory, a storage device, or memory on a processor.

[0125] Referring to FIG. 13, in some implementations, a user can interact with the thromboelastometry system provided herein according to exemplary process 490. At step 492, the user can insert a cartridge into the analyzer console. In some examples, at least a portion of the cartridge remains exposed while other portions of the cartridge are hidden within the analyzer console. For example, this step is illustrated above with reference to FIG. 1A. At step 494, after a prompt is received from the analyzer console, the user can connect a blood sample container to the cartridge. Step 494 can be performed with the cartridge remaining inserted within the analyzer console as defined by step 492. At step 496, the user can press a "start" button (or equivalent) to initiate automated transport of the blood from the blood sample reservoir to the blood test chamber of the cartridge, enabling the viscoelastic properties of the blood to be measured. In some examples, the analyzer console provides an indication that it is ready to initiate the test, but that indication is not required as part of process 490.

[0126] Referring to FIGS. 14A and 14B, in some implementations, the thromboelastometry system can perform thromboelastometry according to exemplary process 500. The individual steps of process 500 need not necessarily be performed in the order listed. Further, in some implementations, some steps of process 500 can be performed in parallel. Process 500 can be performed by a thromboelastometry system such as thromboelastometry system 100 described above.

[0127] In step 510, the presence of the cartridge is detected within the receiving portion of the analyzer console of the thromboelastometry system. For example, the detection can be carried out by, such as, a microswitch, an optical sensor, and a barcode scanner, or a combination thereof. Even if the cartridge is detected in the receiving portion, at least a part of the cartridge can be outside the analyzer console.

[0128] In step 520, the analyzer console activates a clamping mechanism to clamp the cartridge at least partially into the analyzer console. For example, a cartridge receiver and clamp 410 as described above can be activated to clamp the cartridge.

[0129] In step 530, the analyzer console can optionally determine whether the cartridge has characteristics indicating that it has been previously used. For example, the analyzer console can use an optical sensor to examine the presence of blood in the cartridge. In some embodiments, if one or more characteristics indicating that the cartridge has been previously used are detected, the analyzer console can interrupt further steps of process 500 and provide an appropriate message via the user interface.

[0130] In step 540, the analyzer console can perform one or more QC tests to test the integrity of the cartridge. For example, in some embodiments, the cartridge can be tested for leaks, such as by performing a pressure / vacuum decay test.

[0131] In step 550, the analyzer console scans the cartridge with respect to the barcode. For example, the analyzer console can scan the tip of the cartridge, and at the tip of the cartridge, a 1D or 2D barcode can be present.

[0132] In step 560, the analyzer console determines the type of thromboelastometry assay to be performed based on the information obtained from the barcode scan in step 550.

[0133] In step 570, the shaft of the thromboelastometry subsystem of the analyzer console is coupled to the pin of the cartridge. The pin is positioned within the cup of the cartridge. Thus, the coupling of the shaft of the thromboelastometry subsystem to the pin can configure the thromboelastometry system to perform thromboelastometry on the blood sample contained within the cup of the cartridge. For example, referring to FIG. 10C, the shaft 310b of the thromboelastometry assembly 300b is lowered toward the cartridge such that the shaft 310b frictionally engages and is removably coupled to the pin 138b of the cartridge 120.

[0134] In step 580, the analyzer console can initiate a reciprocating rotational movement of the pin with respect to the cup of the cartridge. For example, this step is illustrated above with reference to FIG. 10C.

[0135] In step 590, the analyzer console can heat the cartridge. In some implementations, the analyzer console can heat the cartridge to a predetermined temperature. In certain implementations, the analyzer console can maintain the cartridge at a predetermined temperature. For example, in some implementations, the predetermined temperature is from about 35° C. to about 40° C., preferably about 37° C.

[0136] In step 600, the analyzer console provides a prompt to connect the blood sample container to the cartridge. For example, this prompt may be provided when one or more steps have been successfully completed and / or when one or more conditions have been successfully verified. For example, in particular, this prompt may be provided when the cartridge has been successfully reached at a predetermined temperature according to step 590. The prompt may be provided via the user interface of the analyzer console. For example, the prompt can be a visual message displayed on the touch screen monitor of the analyzer console. In some implementations, an audible prompt may be provided.

[0137] In step 610, the analyzer console can optionally detect the presence of blood in the cartridge. Such detection can be performed, for example, using one or more IR sensors of the analyzer console. Detection of blood in the cartridge in this step can indicate that the blood sample container has been successfully connected to the cartridge.

[0138] In step 620, the analyzer console can provide a prompt to "start" the test. In some implementations, the prompt to "start" the test can be provided based on the successful completion of one or more steps and / or based on the successful verification of one or more conditions. The prompt can be provided via the user interface of the analyzer console. For example, the prompt can be a visual message displayed on the touch screen monitor of the analyzer console. In some embodiments, the touch screen can receive user input to start the test.

[0139] In step 630, the analyzer console can cause blood to flow from the sample container into the cartridge. In some implementations, the vacuum source of the analyzer console can be used to cause blood to flow into the cartridge. In some implementations, the pneumatic pressure source of the analyzer console is used to cause blood to flow into the cartridge. Also, the analyzer console can operate various valves or vents to control the blood flow in the cartridge (see, for example, FIGS. 8A-8H).

[0140] In step 640, the analyzer console can induce agitation to assist in dissolving the reagents in the blood contained in the cartridge. This step is illustrated above in connection with the horizontal reciprocating motion of the magnetic shuttle, which comprises one or more magnets magnetically coupled to the mixing element of the cartridge 120, and this step causes the movement of the mixing element in the cartridge 120 to prompt the reagent beads to dissolve in the blood contained in the mixing chambers 134a-e.

[0141] In step 650, a thromboelastometry test is initiated. For example, the analyzer console can begin analyzing data that is generated by the thromboelastometry assembly with respect to the reciprocating rotation of the shaft connected to pins 138a - e positioned in cups 136a - e of the cartridge (see FIGS. 8A - 8H). In some implementations, the analyzer console can begin analyzing data generated by some of the thromboelastometry assemblies before beginning to analyze data generated by other ones of the thromboelastometry assemblies. For example, as described above with reference to FIGS. 8A - 8H, the analyzer console can first begin analyzing data generated by the thromboelastometry assembly with respect to cup 136e. Subsequently, the analyzer console can begin analyzing data generated by the thromboelastometry assembly with respect to cup 136d, and so on.

[0142] In step 660, the analyzer console displays the results of the thromboelastometry. Such results can be displayed simultaneously with the conduct of the test and upon completion of the test. The results can be displayed via the user interface of the analyzer console, for example, on a touchscreen display. The results can be displayed using qualitative graphic representations and quantitative parameters.

[0143] In step 670, the analyzer console can unclamp the cartridge upon cessation of the test. In some cases, such cessation can be initiated by user input to the analyzer console to stop the test, or by completion of the test assay, or by expiration of a time - based parameter. The unclamping can be effected, for example, by horizontal translation of the movable block sub - assembly. After unclamping, the cartridge can be removed from the analyzer console.

[0144] Multiple embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the present invention. Accordingly, other embodiments are within the scope of the appended claims.

Claims

1. A cartridge (120) for use with an analyzer console (140), the cartridge (120) comprising: A blood treatment and testing path (130a, 130b, 130c, 130d, 130e), Each of the blood treatment and testing paths (130a, 130b, 130c, 130d, 130e) is configured to receive a portion of a blood sample, and the blood treatment and testing paths (130a, 130b, 130c, 130d, 130e) include: Measurement chambers (132a, 132b, 132c, 132d, 132e) having a selected internal volume for containing the portion of the blood sample, Mixing chambers (134a, 134b, 134c, 134d, 134e) in fluid communication with the measurement chambers (132a, 132b, 132c, 132d, 132e), the mixing chambers (134a, 134b, 134c, 134d, 134e) containing a reagent and configured to receive the portion of the blood sample from the measurement chambers (132a, 132b, 132c, 132d, 132e) such that the portion of the blood sample contacts the reagent, Blood test chambers (136a, 136b, 136c, 136d, 136e) configured to receive a mixture based on the portion of the blood sample and the reagent and to test the mixture within the blood test chambers (136a, 136b, 136c, 136d, 136e), wherein mixing to produce the mixture occurs in the mixing chambers (134a, 134b, 134c, 134d, 134e) and in the blood treatment and testing paths (130a, 130b, 130c, 130d, 130e) (before and after the mixing chambers (134a, 134b, 134c, 134d, 134e)), In each of the measurement chambers (132a, 132b, 132c, 132d, 132e), a vacuum application port (162) for connection to a source of vacuum for drawing in the portion of the blood sample, The cartridge (120) includes a blood detection location (127b) where the analyzer console (140) determines that the application of vacuum to the cartridge has properly filled the measurement chamber (132e).

2. The cartridge (120) according to claim 1, wherein each of the blood treatment and inspection paths (130a, 130b, 130c, 130d, 130e) includes a stop junction (132as) between the measurement chambers (132a, 132b, 132c, 132d, 132e) and the mixing chambers (134a, 134b, 134c, 134d, 134e).

3. The cartridge (120) according to claim 2, further comprising a pressure application port (164) and an air pressure vent (166a), wherein, by applying a desired pressure, a portion of the blood sample flows through the stop junction in the blood treatment and inspection paths (130a, 130b, 130c, 130d, 130e) via the pressure application port (164) and through the air pressure vent (166a).

4. The cartridge (120) according to claim 2, wherein a negative pressure is applied to a portion of the blood sample, and the portion flows through the stop junction in the duct connecting the measurement chamber (132a) and the mixing chamber (134a) to the mixing chamber.

5. The cartridge (120) according to any one of claims 1 to 4, wherein each of the blood treatment and inspection paths (130a, 130b, 130c, 130d, 130e) is arranged in series between the measurement chambers (132a, 132b, 132c, 132d, 132e) and the blood inspection chambers (136a, 136b, 136c, 136d, 136e).

6. The cartridge (120) according to claim 5, wherein there are two mixing chambers (134a, 134b, 134c, 134d, 134e and 137a, 137b, 137c, 137d, 137e) in each of the blood treatment and inspection paths (130a, 130b, 130c, 130d, 130e).

7. The cartridge according to any one of claims 1 to 4, wherein the measurement chamber (132e) includes a transfer port used to transfer air and fluid out of the measurement chamber (132e) and into the overflow chamber (139).

8. The cartridge according to any one of claims 1 to 4, wherein the measurement chamber (132a, 132b, 132c, 132d, 132e) has an outlet port at the bottom of the measurement chamber (132a, 132b, 132c, 132d, 132e).

9. The cartridge according to any one of claims 1 to 4, wherein the measurement chamber (132a, 132b, 132c, 132d, 132e) has an inlet port at the top of the measurement chamber (132a, 132b, 132c, 132d, 132e).

10. Further comprising a sample well (122) and needles (123a, 123b) configured to pierce the septum of the blood collection tube (10) when the blood collection tube (10) is inserted into the sample well (122), The cartridge (120) according to claim 1 or 4, wherein the needle (123a) is in fluid communication with the blood treatment and inspection path (130a, 130b, 130c, 130d, 130e) while the needle (123b) facilitates the flow of the blood sample in the blood collection tube (10).

11. The cartridge (120) according to claim 10, further comprising a vent (121) through which air is drawn when air is required to vent the blood collection tube (10) positioned in the sample well (122), and the air is fed into the blood collection tube through the needle (123b).

12. The cartridge (120) according to claim 3, wherein when the pneumatic vent (166a) is closed, the portion of the blood sample in the measurement chamber (132a) does not flow into the corresponding mixing chamber (134a).

13. An analyzer console (140) comprising a cartridge receiver for receiving the cartridge according to claim 1 or 4.

14. The analyzer console (140) according to claim 13, wherein at least a part of the cartridge received in the cartridge receiver is outside the analyzer console.

15. A method for performing a viscoelastic test on the blood sample using the cartridge according to claim 1 or 4.

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