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 8A

Description

[Technical Field]

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

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Patent Application No. 14 / 958,890, filed December 3, 2015, which is a continuation-in-part of U.S. Patent Application No. 14 / 500,248, filed September 29, 2014, which is incorporated herein by reference in its entirety for all purposes.

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

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

[0005] Another group of tests that assess the potential of blood to form a sufficient clot is known as "viscoelastic methods." In at least some viscoelastic methods, clot firmness (or other parameters dependent thereon) is determined over a predetermined period of time, e.g., from the formation of the first fibrin fibers to clot dissolution by fibrinolysis. Clot firmness is a functional parameter that contributes to hemostasis in vivo because the clot must resist blood pressure and shear stress at the site of vascular injury or incision. In many cases, clot firmness 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 [Problem to be solved by the invention]

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

[0007] Some embodiments of a system for testing the characteristics of a blood sample (which, as used herein, should be understood to include blood or blood products such as plasma) can include a cartridge configured to mate with a control console and configured to accept a blood sample for point-of-care whole blood coagulation analysis. In certain circumstances, the cartridge is configured to interact with the control console to perform multiple automated transport and testing operations on a portion of the blood sample to provide reliable, rapid results indicative of a patient's blood characteristics at the point of care (e.g., while the patient is undergoing surgery in a surgical suite). 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 the cartridge (and the blood sample therein) and an indication from an operator to begin the automated testing process.

[0008] In some embodiments, the 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 is then prompted by the analyzer console's user interface to initiate multiple automated blood transfer and testing operations. The analyzer console then 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 graphical 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 the blood sample using a single cartridge device. Such assays provide information about 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 indicating a patient's blood characteristics at the point of care (e.g., while the patient is undergoing surgery in the 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 receive a portion of the blood sample and can include a blood sample volume measuring chamber, a mixing chamber, and a viscoelastic blood testing chamber. The blood sample volume measuring chamber can be in fluid communication with the blood sample receiver, and the blood sample volume measuring chamber can have an internal volume selected to contain a predetermined volume of blood sample from a blood sample container. The mixing chamber can be in fluid communication with the blood sample volume measuring chamber and can also be in fluid communication with a reagent, and the mixing chamber can be configured to receive the blood sample from the blood sample volume measuring chamber and mix the received blood with the reagent. The viscoelastic blood testing chamber is configured to receive the mixed blood and reagent from the mixing chamber, and a viscoelastic test is 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 multiple blood sample paths in selective fluid communication with the blood sample receiver. Each blood sample path can include a blood measurement chamber for receiving a predetermined volume of the blood sample via the blood sample receiver, a reagent mixing chamber for receiving the predetermined volume of the blood sample and mixing it with one or more reagents, and a blood coagulation blood testing chamber for receiving the blood sample from the reagent mixing chamber with the one or more reagents mixed therewith. Optionally, the blood coagulation blood testing chamber can have a movable probe therein for measuring blood coagulation characteristics.

[0011] 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 pathway in selective fluid communication with the blood sample receiver. The blood sample pathway can include a blood measurement chamber configured to be filled with a predetermined volume of blood sample via the blood sample receiver, a reagent mixing chamber for receiving the predetermined volume of blood sample from the blood measurement chamber and mixing the predetermined volume of blood sample with one or more reagents, a blood coagulation blood test chamber for receiving the blood sample from the reagent mixing chamber with the one or more reagents mixed therewith, and an overflow chamber in fluid communication with the blood sample pathway to collect excess blood 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 viscoelastic properties of a blood sample. The system can include a control unit housing the viscoelastic measurement components. The control unit can define an external port. The system can also include at least one disposable cartridge, the at least one disposable cartridge including a blood sample inlet accessible along an exterior of the cartridge and multiple blood test chambers positioned along an interior of the cartridge. Optionally, the control unit is configured to removably mate with the disposable cartridge when inserted into the external port, such that the blood sample inlet of the cartridge remains external to the control unit while the multiple blood test chambers are positioned in the control unit.

[0013] Some embodiments described herein include a method of using a system for measuring 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 exterior. The method can also include attaching a blood sample reservoir to the blood sample inlet. The method can further include providing a user input via a user interface of the blood test control console to initiate automated transport of blood in the blood sample reservoir to multiple 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 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 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 can be in selective fluid communication with the blood sample receiver structure.

[0015] In some embodiments described herein, a cartridge device for a measurement system for measuring viscoelastic properties of a blood sample can include multiple blood test chambers for measuring blood coagulation properties. Each of the blood test chambers can be exposed to the atmosphere and have a sample input port positioned along a sidewall 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 in 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 viscoelastic properties of a blood sample may include multiple reagent mixing chambers for receiving a predetermined volume of blood sample and mixing it with one or more reagent beads. The cartridge device may also include multiple retaining elements extending into the reagent mixing chambers to maintain predetermined vertical positions of the reagent mixing beads within the mixing chambers. At least one retaining element of the reagent mixing chambers can engage with the multiple reagent mixing beads to maintain the multiple reagent mixing beads spaced apart from one another.

[0017] In certain embodiments described herein, a cartridge device for a measurement system for measuring viscoelastic properties of a blood sample can include multiple reagent mixing chambers for receiving and mixing a predetermined volume of blood sample with one or more reagent beads. The cartridge device can also include a movable mixing element carried by the reagent mixing chambers. The movable mixing element can include a material inert to the blood sample. The cartridge device can further include multiple retention elements extending into the reagent mixing chambers to maintain the reagent mixing beads in a spaced-apart position from the movable mixing elements.

[0018] Some embodiments described herein may include a method for measuring clotting characteristics of a blood sample. The method may include detecting insertion of a blood test cartridge into a receiver portion of a blood test control unit. The method may also include displaying a prompt to a user for input via a user interface of the blood test control unit to initiate automated transport of blood in a blood sample reservoir 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 may further include automatically transporting a predetermined volume of blood sample from a blood sample receiver of the blood test cartridge to each of the one or more blood test chambers in the cartridge. Optionally, the method may also include moving a probe in each blood test chamber of the cartridge to measure the blood clotting characteristics. The method may further include displaying the blood clotting characteristic measurement results via the user interface.

[0019] Other embodiments described herein include a control console for measuring clotting characteristics of a blood sample. The control console can include a control unit housing containing at least one interface element configured to removably receive a disposable cartridge (which can optionally have multiple blood test chambers therein and can have multiple measurement components configured to measure clotting characteristics of a blood sample in the multiple 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., in some embodiments, 37°C). 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 multiple blood test chambers of the disposable cartridge after the temperature sensor indicates that the multiple blood test chambers of the disposable cartridge have reached a predetermined temperature.

[0020] Some or all of the embodiments described herein may 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 may be utilized more efficiently, particularly in point-of-care contexts such as operating rooms. Reduced user interaction also reduces the opportunity for manual operator error, such as measurement inaccuracies and reagent mixing errors. Thus, more accurate thromboelastometry results may be obtained in some situations.

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

[0022] Third, in some embodiments, the analyzer console is configured to perform multiple quality control operations / checks to ensure that blood test results are not compromised. For example, the analyzer console may be configured to verify that a blood test cartridge is heated to a target temperature (e.g., approximately 37°C) before a blood sample is dispensed into the cartridge's test chamber. Because the temperature of a blood sample can, in some circumstances, affect clotting characteristics, the accuracy of thromboelastometry results may be enhanced as a result of such temperature control operations / checks.

[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 likelihood of disturbing the blood (e.g., causing bubble formation) and / or damaging the blood in a manner that may adversely affect the accuracy of 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 to rapidly transfer relevant information to the analyzer console regarding each blood sample testing cycle. For example, each cartridge can be labeled with a barcode, a near-field communication tag, an RFID tag, or the like, which includes 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, or the like) that scans the barcode upon insertion of the cartridge into the analyzer console. The analyzer console automatically performs appropriate actions in response to 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, or the like, which includes information such as, but not limited to, patient information, clinician information, or calibration information (e.g., that is readable by a corresponding reader device on the analyzer console).

[0025] Sixth, each fluid path of the cartridge can include a mixing chamber, the mixing chamber comprising 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 the one or more reagent beads from each other and to prevent the mixing element from direct contact with the reagent beads. Further advantages associated with the thromboelastometry systems provided herein are also contemplated, as will become apparent from the disclosure below.

[0026] The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. [Brief explanation of the drawings]

[0027] [Figure 1A] FIG. 1 is a perspective view illustrating components and use of an exemplary thromboelastometry system, according to some embodiments. [Figure 1B] FIG. 1 is a perspective view illustrating components and use of an exemplary thromboelastometry system, according to some embodiments. [Figure 2] FIG. 1 is a perspective view illustrating components and use of an exemplary thromboelastometry system, according to some embodiments. [Figure 3] FIG. 1 is a perspective view illustrating components and use of an exemplary thromboelastometry system, according to some embodiments. [Figure 4] FIG. 4 is a perspective view of an exemplary cartridge component of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3. [Figure 5] FIG. 5 is an exploded view of the cartridge components of FIG. 4. [Figure 6] FIG. 5 is a partial cutaway view of the right side of the cartridge component of FIG. 4. [Figure 7] FIG. 5 is a left side view of the cartridge component of FIG. 4. [Figure 8A] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8B] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8C]4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8D] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8E] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8F] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8G] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 8H] 4 is a series of schematic diagrams illustrating the operation of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordance with some embodiments. [Figure 9] 1 is a schematic diagram of another exemplary thromboelastometry system, according to some embodiments. [Figure 10A] FIG. 5 is a top view of the cartridge component of FIG. 4. [Figure 10B] FIG. 10B is a partial cross-sectional view of the cartridge component of FIG. 10A. [Figure 10C] 10B is a schematic diagram showing a partial cross-sectional view of the cartridge component of FIG. 10B along with associated components of the analyzer console of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3. [Figure 11] FIG. 4 is an exploded perspective view of a thromboelastometry analyzer console of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3. [Figure 12]FIG. 4 is a block diagram that schematically illustrates the subsystems of the thromboelastometry analyzer console of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3. [Figure 13] 1 is a flowchart of a method of using a thromboelastometry system, according to some embodiments. [Figure 14A] 1 is a flowchart of a method for controlling a thromboelastometry system, according to some embodiments. [Figure 14B] 1 is a flowchart of a method for controlling a thromboelastometry system, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

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

[0029] 1A-3 , some embodiments of blood testing system 100 include an analyzer console 140 and one or more cartridges 120 configured to removably mate with analyzer console 140. In this embodiment, blood testing system 100 is a thromboelastometry system configured to determine multiple blood clotting characteristics of a blood sample deposited into cartridge 120. For example, cartridge 120 may be configured as a disposable cartridge including 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 may be used to connect other types of blood sample reservoirs 10 with cartridge 120 (e.g., tubing may be used through which blood may be injected into cartridge 120, etc.). Thromboelastometry system 100 may be used as a particularly advantageous whole blood coagulation analysis system at the point-of-care site (e.g., in an operating room while a patient is undergoing or being prepared for surgery, etc.) Additionally, thromboelastometry system 100 may be used as a whole blood coagulation analysis system in a laboratory setting.

[0030] The analyzer console 140 includes a user interface 142 (which in this embodiment includes a touchscreen display) and a main chassis 144. The user interface display 142 may be configured to output one or more graphical results 143 from the blood test assays performed via the cartridge 120 and console 140 (e.g., one or more plots, e.g., sometimes referred to as a TEMogram, numerical data or measurements, or a combination thereof). In some embodiments, the user interface display 142 is rigidly attached to the analyzer console 140. In certain embodiments, the user interface display 142 is pivotable and / or otherwise positionally adjustable relative to the main chassis 144. A main power switch 148 may be located in a convenient location other than a protected location on the main chassis 144.

[0031] In the illustrated embodiment, the touchscreen display 142 is configured to receive user input and display output information to the user. For example, a user can input information into the thromboelastometry system 100 by making selections from various soft buttons that may be displayed on the touchscreen display 142 at times during the beginning, middle, and end of the testing process. In some embodiments, other selections, such as, for example, but not limited to, soft keyboard input, may be provided via the touchscreen display 142. In some embodiments, data entry may additionally or alternatively be performed by voice input. In other embodiments, the user interface may include other peripheral devices (e.g., a mouse, keyboard, additional display devices, etc.) that may be included as part of the thromboelastometry system 100. In some embodiments, a computer data network (e.g., an intranet, the Internet, a LAN, etc.) may be used to allow remote devices to receive and / or input information from the system 100. For example, in some embodiments, one or more remote displays may 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 entry 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 near-field communication tags or RFID tags, or the like.

[0032] In the illustrated embodiment, the main chassis 144 houses various internal subsystems (as described further below) and includes various electronic connection receptacles (not shown), as well as a cartridge port 150. The various electronic connection receptacles may include network and device connectors, such as, but not limited to, one or more USB ports, an Ethernet port (e.g., RJ45), a VGA connector, and a Sub-D9 connector (RS232). Such connection receptacles may be located on the rear 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 may be located on or near the front of the main chassis 144. A USB port so positioned may provide a user convenience for recording data, for example, 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] 1A-3 , the cartridge port 150 is positioned in an easily accessible location on the main chassis 144. In the embodiment shown, the cartridge port 150 is positioned on the front of the main chassis 144 so that it is conveniently accessible by a user at the point-of-care site. The cartridge port 150 defines an opening and an interior space shaped complementarily to the exterior dimensions of the disposable cartridge 120. To insert the disposable cartridge 120 into the cartridge port 150, a user can grasp the end of the cartridge 120, including the blood sample receiver 122, and slide the opposite end (front end) into the cartridge port 150. The sliding insertion can continue until a hard stop is reached, defining the fully inserted position. 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 the main chassis 144. The portion of cartridge 120 received into cartridge port 150 can include an exterior surface feature (e.g., a tapered angle on the rear end portion shown in FIG. 1B ) that mates with at least one internal interface element inside console 140 to ensure proper positioning of cartridge 120. To that end, at least blood sample receiver 122 remains outside main chassis 144 throughout the duration of a blood sample test. In this configuration, blood sample receiver 122 serves as a blood sample well that is accessible so that blood sample reservoir 10 can be inserted into receiver 122 while disposable cartridge 120 is mated with console 140 in the fully inserted position. In some embodiments, cartridge port 150 and main chassis 144 are configured to protect exposed portions of cartridge 120 from accidental contact.As further described below, an internal sensor (eg, 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 is fully inserted, in some embodiments, the analyzer console 140 initiates one or more of the following actions: An internal cartridge clamping mechanism, including a locating pin, can be activated to precisely 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. A 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 check the cartridge 120 for the presence of blood (which should not be present at this point). A rotational thromboelastometry measuring subsystem can be engaged with the cartridge 120, and optionally, rotation of the rotational thromboelastometry measuring subsystem can begin (without the presence of blood). The cartridge 120 can be leak tested using 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 may additionally or alternatively be activated when the analyzer console 140 detects that the cartridge 120 is fully inserted. After such an action is completed, in some embodiments, an indication of the result of the action (e.g., pass or fail) may be displayed on the touchscreen display 142. If the analyzer console 140 determines that the action was successfully completed, a prompt is provided on the touchscreen display 142 informing the user that the thromboelastometry system 100 is ready to accept the blood sample reservoir 10.

[0035] Briefly, in some embodiments, a user can operate the illustrated embodiment of thromboelastometry system 100 as follows. First, a user can insert disposable cartridge 120 into cartridge port 150, allowing cartridge 120 to be seated in the fully inserted position. Completion of that step will automatically initiate a series of actions by thromboelastometry system 100, as described below. Successful completion of such actions will display a notification on touchscreen display 142 that blood collection tube 10 may be inserted into sample well 122. After the user has mated blood collection tube 10 into sample well 122, the user initiates the test by pressing a "Start" button (or the like) on touchscreen display 142. At least a blood measurement, reagent mixing, and thromboelastometry test are then performed automatically by system 100 (e.g., in this embodiment, without requiring manual intervention from the user). Once the test is complete, the results are displayed on the touchscreen display 142 in the form of qualitative graphical representations and quantitative parameters (e.g., as shown in FIG. 1A ). Also, when the test is complete, the cartridge 120 may be removed from the console 140 and discarded (e.g., in such an embodiment, 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 portion of the clotted blood sample).

[0036] Alternatively, in some embodiments, the blood collection tube 10 may 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 after the console 140 acts on the cartridge 120 (again, as described below). With the blood collection tube 10 pre-coupled with the cartridge 120, the combination of the blood collection tube 10 and cartridge 120 may then be inserted into the cartridge port 150.

[0037] 4 and 5, the illustrated embodiment of the disposable cartridge 120 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 enclose the cavity and flow channel of the main body portion 124 and define the blood flow path, as described further below. The sample well 122, as described above, is part of the main body portion 124. However, other configurations of the disposable cartridge 120 are also contemplated.

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

[0039] In some embodiments, overmolding, such as by insert molding or multi-shot molding techniques, may be used to construct some aspects of the main body portion 124, right cover 126, and / or left cover 128 (i.e., device components). For example, an elastomeric valve element (as described further below) may be overmolded into 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 insertion of the valve. A polymer is poured into the first mask to form a hard plastic device component. A second mask is then provided, having the inverse of the shape of the device component with the valve. The hardened plastic device component is placed into the mask, and an elastomeric material is injected into the open space formed in the device component by the first mask, thereby forming an elastomeric valve in the device component. In some embodiments, the device component is the main body portion 124, right cover 126, and / or left cover 128. Exemplary valves 160a-e, 168, and 170 in overmolded left cover 128 are shown in Figure 7. In some embodiments, the valves comprise an elastomeric material that is deformable under application of pressure. Deformation of the valves by application of external pressure forces the elastomeric material into the duct, thereby fluid-tightly sealing the duct and preventing the flow of sample liquid therethrough.

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

[0041] The disposable cartridge 120 also includes five pins 138a, 138b, 138c, 138d, and 138e. The pins 138a-e are individual component parts (see, e.g., FIG. 10B ) that are held within openings in the main body portion 124 (e.g., within test chambers 136a-e (sometimes referred to as “cups”), as further described below with reference to FIGS. 8A-10B ). Tabs 129 located on the right cover 126 and left cover 128 mechanically hold the pins 138a-e within the main body portion 124. However, the pins 138a-e are free to move within the main body portion 124 to a limited extent. For example, the pins 139a-e are free to rotate unconstrained within the main body portion 124 and are free to translate vertically by a few millimeters. This configuration of the pins 138a-e relative to the other components of the cartridge 120 can be generated as follows. Prior to affixing the right and left covers 126, 128 to the main body portion 124, the pins 138a-e may 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 and left covers 126, 128 may then be affixed to the main body portion 124. With the right and left covers 126, 128 affixed to the main body portion and the pins 138a-e positioned within the main body portion 124, the pins are secured in place vertically by tabs 129 that cover the tops of the pins 138a-e, so that they cannot fall out or be removed from the cups 136a-e without removing the right and left covers 126, 128 from the main body portion 124. Tab 129 allows free rotational movement of pins 138a-e, as well as sufficient vertical movement to allow pins 138a-e to interact with a fluid sample and perform measurements of the viscoelastic properties of the fluid sample in cups 136a-e (e.g., rotational thromboelastometry). Additionally, tab 129 provides an opening for shaft 310b to couple with pin 138b, as shown in FIG. 10C.In one example, right cover 126 and left cover 128 are affixed to main body portion 124, after which pins 138a-e are pressed over tabs 129 into main body portion 122. Tabs 129 on right cover 126 and left cover 128 prevent pins 138a-e from falling out of main body portion 122, even if cartridge 120 is turned upside down. In some embodiments, the pins and tabs are positioned to prevent a semi-solidified fluid sample in the test chamber from escaping the test chamber, even if cartridge 120 is turned upside down.

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

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

[0044] 4, 5, and 6, generally, disposable cartridge 120 is configured to (i) draw blood from a blood collection tube (e.g., blood collection tube 10 of FIGS. 1-3) and measure a precise volume of the drawn blood, (ii) mix a precise amount of blood with a reagent, and (iii) deliver the mixture to multiple cup and pin locations in cartridge 120 where a thromboelastometry test is performed. These steps are described in more detail below.

[0045] In the illustrated embodiment, 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 reagents and mixing elements, and (iii) a blood coagulation test chamber (e.g., in this embodiment, a cup with a movable probe / pin therein). For example, channel 130a includes measurement chamber 132a, mixing chamber 134a, and test chamber 136a (see examples of test chambers shown in detail in Figures 10A-B). Similarly, channel 130b includes measurement chamber 132b, mixing chamber 134b, and test chamber 136b. Channel 130c includes measurement chamber 132c, mixing chamber 134c, and testing chamber 136a. Channel 130d includes measurement chamber 132d, mixing chamber 134d, and testing chamber 136d. Channel 130e includes measurement chamber 132e, mixing chamber 134e, and testing chamber 136e.

[0046] In some embodiments, sample well 122 includes needles 123a and 123b configured to pierce a septum of a blood collection tube when the blood collection tube is inserted into sample well 122. Needle 123a is in fluid communication with channels 130a-e, while needle 123b is a vent that facilitates rapid blood flow 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; and 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. Measuring chambers 132a-e may also be referred to as metering chambers 132a-e. Each measuring chamber 132a-e has an inlet port and an outlet port. The inlet ports are positioned near the top of measuring chamber 132a-e. For example, measuring chamber inlet port 132ai is positioned near the top of measuring chamber 132a. This configuration can be advantageous when blood contains gas bubbles because such gases are allowed to escape from the blood as it enters measuring chamber 132a-e. Additionally, this configuration can advantageously minimize turbulence in the fluid flow as the blood flows into measuring chamber 132a-e, thereby reducing the potential for damage to blood cells.

[0048] Outlet ports 134ao-eo for transferring blood from measurement chambers 132a-e to mixing chambers 134a-e are located at the bottom of the measurement chambers. For example, measurement chamber outlet port 132ao is located at the bottom of measurement chamber 132a. In some embodiments, the bottom of measurement chamber 132a is angled downward toward outlet port 132ao. In some embodiments, the bottom of measurement chamber 132a is angled 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 angled 2° to 15° from a plane perpendicular to the direction of the force applied to move the blood sample through outlet port 132ao. In one embodiment, the above-described angle 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 would also be effective. This configuration can help promote complete filling of measuring chambers 132a-e with blood. It can also minimize the transfer of bubbles into outlet port 132ao because more blood is transferred to outlet port 132ao before the surface of the volume of blood contained in measuring chamber 132a (which may contain bubbles) contacts outlet port 132ao. As such, the correct volume of blood is contained in measuring chamber 132a-e.

[0049] In some embodiments, the top of measurement chamber 132a is angled to cause air to escape measurement chamber 132a through a transfer port located at the top of the measurement chamber opposite 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 upward from a low 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° relative to a plane parallel to the bottom or top of the device or relative to a plane perpendicular to the primary gravitational field applied to the blood sample while in 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 also effective. In devices including an angled top of measuring chamber 132a, air and bubbles are transferred from measuring chamber 132a before the blood, providing a measured blood sample with a reduced amount of air, which can affect the accuracy of the blood measurement and can also interfere with other downstream applications. In some embodiments, both the top and bottom of measuring chamber 132a are angled as described above.

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

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

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

[0053] As described above, each individual channel 130a-e has a respective measuring chamber 132a-e. In some embodiments, the fluid flow path within each individual channel 130a-e is as follows: From measuring chamber 132a-e, blood can flow to a respective mixing chamber 134a-e. For example, blood from measuring chamber 132a can flow to mixing chamber 134a. Similarly, blood from measuring chamber 132b can flow to mixing chamber 134b. Blood from measuring chamber 132c can flow to mixing chamber 134c. Blood from measuring chamber 132d can flow to mixing chamber 134d. Blood from measuring chamber 132e can flow to mixing chamber 134e. From mixing chamber 132a-e (after mixing is complete), blood can flow to a respective testing chamber 136a-e (having a corresponding probe / pin 138a-e therein; see FIGS. 10A-b below). For example, blood from mixing chamber 134a can flow to testing chamber 136a. Similarly, blood from mixing chamber 134b can flow to testing chamber 136b. Blood from mixing chamber 134c can flow to testing chamber 136c. Blood from mixing chamber 134d can flow to testing chamber 136d. Blood from mixing chamber 134e can flow to testing chamber 136e. Various valves and vents controllable by analyzer console 140 are interspersed among the fluid flow paths of the individual channels 130a-e. Using such valves and vents, blood flow within the individual channels 130a-e can be controlled by analyzer console 140 according to a predetermined scheme.

[0054] Referring now to FIGS. 6 and 7, additional features of cartridge 120 will now be described. FIG. 6 provides a side view of certain chambers of cartridge 120 (measuring chambers 132a-e, reagent mixing chambers 134a-e, and blood coagulation test chambers 136a-e). FIG. 7 provides a left side view of cartridge 120 and individual channels 130a-e. In this view, test chamber inlet ports 136ai, 136bi, 136ci, 136di, and 136ei for each test chamber 136a-e are visible. Inlet ports 136ai-e are positioned near the top of test chambers 136a-e, e.g., along the sidewalls of chambers 136a-e, and at a height above the distal heads of pins 138a-e that interact with the blood sample, but below the proximal ends of pins 138a-e (see FIG. 10B). This configuration may be advantageous when the blood contains air bubbles. This is because such gases may be allowed to escape from the blood as it enters the cups 136a-e. In viscous solutions, if the solution enters through the bottom, bubbles will be retained at the bottom of the cups 136a-e, adversely affecting thromboelastometry measurements by the pins 138a-e in the cups 136a-e. Additionally, this configuration advantageously minimizes fluid flow disturbances as the blood flows into the testing chambers 136a-e. Fluid flow disturbances and bubble mixing are also minimized by having a small diameter or blood flow area of ​​the sample inlet ports 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 top surface of the blood in the cups 136a-e by using the smaller diameter of the sample inlet ports 136bi in combination with the location of the inlet ports 136bi along the sidewalls 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 embodiment shown, cartridge 120 includes two locator pin receivers 140a and 140b, which are used to mate with locator pins of analyzer console 140 (as described further below). In this manner, cartridge 120 can be precisely positioned relative to analyzer console 140.

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

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

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

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

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

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

[0062] As described further below, in some embodiments, valves 160a-e are individually actuated by pins that are translated toward and away from valves 160a-e. To close a valve 160a-e, the pins can engage and expand an elastomeric member of valve 160a-e so that the elastomeric member contacts the valve seat of valve 160a-e. When such pins are retracted away from the elastomeric member of valve 160a-e, the elastomeric member rebounds so that the elastomeric member no longer expands, and the valve is then opened. The pins, in some embodiments, are translated by a solenoid.

[0063] Other mechanisms for regulating fluid flow within cartridge 120 may also be present. For example, stop junctions may be located between measurement chambers 132a-e and mixing chambers 134a-e to control the flow of blood from measurement chambers 132a-e to mixing chambers 134a-e. In some embodiments, the stop junctions are barriers that can be opened when a sufficient amount of pressure is applied to the barrier. In some embodiments, the stop junctions include a narrow area for sample fluid flow such that if sufficient pressure is not applied, the surface tension of the sample fluid prevents flow through the stop junction. If sufficient pressure is applied, the flow of 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. The one or more reagent beads 180 are disposed within and retained within the plurality of retaining elements 182. The mixing element 184 is disposed within the bottom portion of the mixing chambers 134a-e and is free to move 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 element 182 extends into each mixing chamber 134a-e and is adapted to maintain a predetermined vertical position of each of the reagent beads 180 within the mixing chamber (e.g., a vertical position below the height of the portion of blood being passed into the mixing chamber 134a-e), thereby ensuring that each of the beads 180 will be submerged when a predetermined volume of blood is directed into the respective mixing chamber 134a-e. In certain embodiments, the height of the liquid filling the mixing chamber 134a-e from the measurement chamber 132a-e (i.e., the fill level) is above the retaining element 182 within the mixing chamber. In some embodiments, the retaining element 182 is above the height of the fill level of the mixing chamber. In these embodiments, the retaining element is configured to position the reagent within the fluid path such that the reagent is dissolved by the liquid upon entry into the mixing chamber. In some embodiments, a flow path is defined as the path that a liquid travels from one chamber to another, including within the chamber itself after entering through an inlet or duct.

[0065] Also, in some embodiments, a plurality of retaining elements 182 in each mixing chamber 134a-e maintain each of the reagent beads 180 in each mixing chamber 134a-e spaced apart from one another. In such embodiments, each of the reagent beads 180 is not contacted by other beads 180 in each mixing chamber 134a-e, is not contacted by the mixing elements 184 in each mixing chamber 134a-e, and is maintained at a vertical height in each mixing chamber 134a-e that is less than the height of the blood portion being transported into each mixing chamber 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. In some embodiments, the retaining element 182 prevents contact between different reagent beads 180, between the reagent beads 180 and the mixing element 184, and / or 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 movement of the reagent beads 180 within the mixing chambers 134a-e and to allow the sample liquid or blood sample to dissolve the reagent beads 180. In some embodiments, the retaining element 182 includes a barrier. The retaining element 182 can include inward or outward protrusions in the walls of the mixing chambers 134a-e, on the surface of the right cover 126 or left cover 128, or on other surfaces of the device. In some embodiments, the retaining element 182 includes a channel, post, or divot. The retaining element 182 may include an array of posts or an array of divots. In some embodiments, the array of posts includes posts of different diameters to retain reagent beads of different diameters. In some embodiments, the retaining element 182 includes a compartment or series of compartments for retaining the reagent beads. The retaining element 182 may also be configured to limit the movement of the reagent beads within the mixing chambers 134a-e while allowing blood to flow in a manner that contacts 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 secure the reagent beads 180 below a predetermined blood sample fill level in the mixing chambers 134a-e. This fill 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 filled. This fill level can be predetermined based on the factors described above. Thus, the retaining element 182 can be specifically designed to maintain the position of the reagent beads 180 below this predetermined fill level.

[0068] Additionally, the retaining element 182 can limit the movement of the mixing element 184 within the mixing chambers 134a-e. In some embodiments, the stationary element 182 used to limit the movement of the mixing element 184 within the mixing chambers 134a-e includes an array or compartment of posts that allows the sample fluid or blood sample within the mixing chambers 134a-e to contact the mixing element 184, agitating the sample fluid or blood sample and facilitating dissolution of the reagents within the mixing chambers 134a-e.

[0069] In the illustrated embodiment, the one or more soluble reagent beads 180 are spherical and of two different sizes (e.g., approximately 2 mm diameter and approximately 3 mm diameter). However, other shapes and / or sizes of reagent beads 180 are also contemplated. In some embodiments, the reagent beads 180 are lyophilized materials, although other forms of materials are also contemplated. The reagent beads 180 can include materials such as, but not limited to, CaCl2, ellagic acid / phospholipids, 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 a different reagent composition (from one or more reagent beads 180 therein) for the purpose of performing five different assays. In this example, the first mixing chamber 134e can include a plurality of reagent beads 180, which provide CaCl and ellagic acid / phospholipids for mixing with a predetermined volume of blood (from the corresponding measuring 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 include a plurality of reagent beads 180, which provide CaCl, ellagic acid / phospholipids, and heparinase for mixing with a predetermined volume of blood (from the corresponding measuring chamber 132d), such that a second sample portion can be used in a second type of assay. Furthermore, in this example, the third mixing chamber 134c can include a plurality of reagent beads 180, which provide CaCl, tissue factor, and polybrene for mixing with a predetermined volume of blood (from the corresponding measuring 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 include a plurality of reagent beads 180, which provide CaCl, tissue factor, polybrene, and cytochalasin D for mixing with a predetermined volume of blood (from the corresponding measuring 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, which provide CaCl, tissue factor, polybrene, and tranexamic acid for mixing with a predetermined volume of blood (from the corresponding measuring chamber 132a), such that a 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 rest of the beads 180 in each mixing chamber 134a-e to first allow mixing and then activation / clotting of the citrated blood sample. Such separation of the reagent beads 180 carrying the CaCl2 reagent may be achieved using a retaining element 182 (as described above). Alternatively, such separation may be achieved by retaining the reagent beads 180 carrying the CaCl2 reagent in separate channels or separate mixing chambers, separated from the other beads 180 in each chamber 134a-e (so that the blood portion reaches the CaCl2 reagent after mixing with the other beads 180 in the respective mixing chamber 134a-e). Alternatively, such separation may be achieved by positioning CaCl2 reagent liquid or dry film CaCl2 reagent in separate channels, so that the blood portion reaches the CaCl2 reagent after mixing with the other beads 180 in the respective mixing chamber 134a-e. Alternatively, the reagent beads 180 carrying the CaCl2 reagent may be coated with an additional layer (which is then retained by the retaining element 182 as described above) so that the blood portion begins to dissolve the reagent beads 180 carrying the CaCl2 reagent after the blood portion has first mixed with the other beads 180 in the respective mixing chambers 134a-e.

[0071] Other configurations for providing reagent to the blood sample may also be used. In some embodiments, the reagent is coated on the walls 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 may be coated in such a way that it is at least partially or entirely contained within the mixing chambers 134a-e. In some embodiments, the reagent is coated so that it remains below the fill level of the mixing chambers 134a-e (the fill level is related to the height of blood in the mixing chamber, as determined in part by a predetermined volume of blood as measured in the measurement chamber). In some embodiments, the coated reagent is a film layer, i.e., a reagent film. A reagent film is a layer of reagent coated on or near a surface. The reagent film can be liquid or may be dried. The liquid reagent may be retained as a film layer by a soluble layer of material placed on top of the liquid reagent. Alternatively, the liquid reagent layer may be applied to a surface and then dried. Alternatively, pre-dried or solid film reagents can be applied to a surface to form a film layer. In some embodiments, the film layer is in the form of a dissolvable film strip. In some embodiments, it is preferred that certain reagents be delivered in a reagent film as opposed to reagent beads 180. For example, certain reagents that are difficult to lyophilize within reagent beads 180 can instead be applied as a film layer on or near a surface within the device.

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

[0073] Alternatively, a reagent film may 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 a 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 an area that at least partially covers or forms the walls of the mixing chambers 134a-e. The reagent film may be used alone or in addition to one or more reagent beads 180 disposed 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 comprises a lyophilized material, although other forms of material are contemplated. The reagent film can include materials such as, but not limited to, CaCl, ellagic acid / phospholipids, 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 each measurement chamber 132a-e) with a different reagent composition (from one or more reagent beads 180 and / or one or more reagent films therein). In this example, the first mixing chamber 134e can include multiple reagent beads 180 and at least one reagent film to provide CaCl and ellagic acid / phospholipids for mixing with the predetermined volume of blood (from the corresponding measurement chamber 132e) so that a first sample portion can be used in a first type of assay. Also in this example, second mixing chamber 134d can include a plurality of reagent beads 180 and at least one reagent film to provide CaCl, ellagic acid / phospholipids, and heparinase for mixing with a predetermined volume of blood (from corresponding measurement chamber 132d), such that a second sample portion can be used in a second type of assay. Also in this example, third mixing chamber 134c can include a plurality of reagent beads 180 and at least one reagent film to provide CaCl, tissue factor, and polybrene for mixing with a predetermined volume of blood (from corresponding measurement chamber 132c), such that a third sample portion can be used in a third type of assay. Also in this example, fourth mixing chamber 134b can include a plurality of reagent beads 180 and at least one reagent film to provide CaCl, tissue factor, polybrene, and cytochalasin D for mixing with a predetermined volume of blood (from 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 contain a plurality of reagent beads 180 and at least one reagent film to provide CaCl2, tissue factor, polybrene, and tranexamic acid for mixing with a predetermined volume of blood (from the corresponding measuring chamber 132a), such that a fifth sample portion can be used in a fifth type of assay.

[0075] Additionally, a reagent film can be deposited on a surface upstream or downstream from the mixing chamber and mixed 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 separate mixing chamber, which is separated from the other reagent beads 180 or reagent film in each chamber 134a-e (e.g., so that the blood portion reaches the CaCl2 reagent film after mixing with the other reagent beads 180 and / or reagent film in each mixing chamber 134a-e). Alternatively, the CaCl2 reagent film is deposited in the mixing chamber 134a-e and coated with an additional soluble film layer, so that the blood portion begins to dissolve the other reagent film carrying the CaCl2 reagent after first mixing with the other reagent beads 180 or reagent film in each mixing chamber 134a-e.

[0076] In some embodiments, the reagent beads 180 or reagent film are separated from the rest of the reagent beads 180 or reagent film in each mixing chamber 134a-e to allow mixing with different reagents in a suitable sequence. In one embodiment, such separation of the reagent beads 180 can be achieved using a retaining element 182 (as described above). Alternatively, such separation can be achieved by retaining the reagent beads 180 or reagent film in separate channels or separate mixing chambers, separated from the other beads 180 or reagent films in each chamber 134a-e (so that portions of the blood reach and mix with the loaded reagents in a suitable sequence). In one embodiment, such separation is achieved by positioning the reagent liquid, reagent beads 180, or dry film reagent in separate channels, so that portions of the blood reach the reagent before or after mixing with the other reagent beads 180 or reagent films in each mixing chamber 134a-e. In some embodiments, the reagent beads 180 or reagent film are located along the duct 134ad fluidly connecting the mixing chambers 134a-e and the test chambers 136a-e. Alternatively, the reagent beads 180 or reagent film are coated with an additional layer (which is then held by the holding element 182, as described above) so that the blood portions begin to dissolve the reagent in the reagent beads 180 or reagent film containing the additional soluble layer after first mixing with the other reagent beads 180 or reagent film in the respective mixing chambers 134a-e. In some embodiments, the coated reagent layer is a soluble film layer made from a substrate containing a polymer composition and a reagent. The polymer composition forms a soluble barrier, maintaining the coating of the reagent on or near surfaces within the device. Upon contact with a blood sample, the polymer composition dissolves, allowing the blood sample to mix with the reagent.

[0077] The mixing element 184 comprises a ferromagnetic material, including, but not limited to, nickel, cobalt, chromium (IV) oxide, gadolinium, permalloy, and alnico (aluminum-nickel-cobalt alloy), and the like, as well as combinations thereof. In the embodiment shown, the mixing element 184 is spherical and solid. In other embodiments, the mixing element 184 can have shapes, including, but not limited to, cubic, conical, cylindrical, sector-shaped, elongated, and prismatic shapes, as well as irregular shapes. In some embodiments, the mixing element 184 can include one or more surface features, such as protrusions, depressions, or holes.

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

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

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

[0081] While the exemplary fluid control process 200 includes five blood flow channels (each including a measuring chamber 132a-e, a mixing chamber 134a-e, and a cup 136a-e, respectively), 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 are included, or three blood flow channels are included, or four blood flow channels are included, or six blood flow channels are included, or seven or more blood flow channels are included. Referring to FIG. 8B, measuring chambers 132a-e have been filled with blood, and a small amount of blood is contained in overflow chamber 139. To reach this state, the following changes (compared to FIG. 8A) were made and / or the following conditions existed: (i) valves 168 and 170 were open, (ii) valves 160a-e were closed, (iii) vents 166a-e were closed, (iv) negative pressure was applied to vacuum application port 162, and (v) pressure application port 164 was not pressurized. Thus, blood flowed (i) from blood collection tube 10, (ii) through valve 168, (iii) through 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 blood detection location 127b, (x) through valve 170, and (xi) into overflow chamber 139. When blood was detected in blood detection location 127b, the application of negative pressure was discontinued, thereby stopping further blood flow.

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

[0083] In some embodiments, the exemplary fluid control process 200 includes stop valves instead of or in addition to stop junctions between one, some, or each of the measuring chambers 132a-e and the mixing chambers 134a-e. In some embodiments, the stop valves are snap-action valves that snap open when a set pressure is reached, or modulating valves that open proportionally to the pressure differential. Other cartridge embodiments can include pressure-controlled valves in other fluid paths.

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

[0085] Referring to FIG. 8C , measuring chambers 132a-d are still filling with blood, but blood from measuring chamber 132e has been transferred to mixing chamber 134e. To reach this state (compared to FIG. 8B ), the following changes were made and / or 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 pressure application port 164. Thus, blood flowed (i) from measuring chamber 132e and (ii) into mixing chamber 134e. Because vents 166a-d and valves 160a-d remained closed, blood in measuring chambers 132a-d did not flow into 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 to promote dissolution of the reagent beads therein.

[0086] In some embodiments, fluid control process 200 shown in FIG. 8C includes stop junctions (not shown) between measuring chambers 132a-e and mixing chambers 134a-e to prevent blood from flowing from the measuring chambers 132a-e to the mixing chambers 134a-e unless a sufficient pressure differential is applied between them. In this embodiment, the stop junctions prevent blood from leaking from measuring chambers 132a-d into mixing chambers 166a-d unless vents 166a-d are opened or sufficient pressure is applied to pressure application port 164 to cause blood to flow through the stop junction. To fill measuring chamber 132e with blood from mixing chamber 134e, the following changes were made and / or the following conditions existed (compared to FIG. 8B): (i) valves 168 and 170 are closed, (ii) valves 160a-e remain closed, (iii) vents 166a-d remain closed, (iv) vent 166e is opened, and (v) air pressure source is applied to pressure application port 164, causing blood to flow from measurement chamber 132e into mixing chamber 134e through the stop junction, but the stop junction between measurement chamber 132a-d and mixing chamber 134a-d prevents blood from flowing from measurement chamber 132a-d into mixing chamber 134a-d. With blood in mixing chamber 134e, the mixing element in mixing chamber 134e can move and agitate the blood to promote dissolution of the reagent beads therein.

[0087] Referring to Figure 8D, measuring chambers 132a-d are still filled with blood, and the blood / reagent mixture that was in mixing chamber 134e (see Figure 8C) has been transferred to cup 136e. To reach this state, the following changes were made and / or conditions existed (compared to Figure 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 source was applied to pressure application port 164. Thus, the blood / reagent mixture flowed (i) from mixing chamber 134e and (ii) into cup 136e. Vents 166a-d and valves 160a-d remained closed so that blood did not flow from measuring chambers 132a-d toward mixing chambers 134a-d. With the blood / reagent mixture positioned in cup 136e, rotational thromboelastometry can begin within cup 136e.

[0088] Referring to Figure 8E, measuring chambers 132a-c are still filled with blood, cup 136e is still filled with blood / reagent mixture, and the blood that was in measuring chamber 132d (see Figure 8D) has been transferred to mixing chamber 134d. To reach this state, the following changes (compared to Figure 8D) were made and / or the following conditions existed: (i) valves 168 and 170 remained closed, (ii) valve 160e was closed, (iii) valves 160a-d remained closed, (iv) vent 166d was opened, (v) vents 166a-c and 166e remained closed, and (vi) 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, application of a pressure differential between measurement chamber 132d and mixing chamber 134d causes blood to travel through the stop junction, while the stop junction between measurement chambers 132a-c and mixing chambers 134a-c prevents flow. Thus, blood flowed (i) from measurement chamber 132d and (ii) into mixing chamber 134d. Because vents 166a-c and valves 160a-c remained closed, blood did not flow from measurement chamber 132a-c toward mixing chambers 134a-c. With blood in mixing chamber 134d, a mixing element in mixing chamber 134d can agitate the blood and promote dissolution of the reagent beads therein.

[0089] Referring to FIG. 8F, measuring chambers 132a-c are still filled with blood, cup 136e is still filled with the blood / reagent mixture, and the blood / reagent mixture that was in mixing chamber 134d (see FIG. 8E) has been transferred to cup 136d. To reach this state, the following changes (compared to FIG. 8E) were made and / or the following conditions existed: (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 pressure application port 164. Thus, the blood / reagent mixture flowed (i) from mixing chamber 134d and (ii) into cup 136d. Vents 166a-c and valves 160a-c remained closed so that blood did not flow from measuring chambers 132a-c toward mixing chambers 134a-c. With the blood / reagent mixture positioned in cup 136d, rotational thromboelastometry can begin within cup 136d.

[0090] Referring to Figure 8G, measuring chambers 132a-b are still filled with blood, cups 136d-e are still filled with the blood / reagent mixture, and the blood that was in measuring chamber 132c (see Figure 8F) has been transferred to mixing chamber 134c. To reach this state, the following changes (compared to Figure 8F) 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, and (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, application of a pressure differential between measurement chamber 132c and mixing chamber 134c causes blood to travel through the stop junction, 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. Because vents 166a-b and valves 160a-b remained closed, blood did not flow from measurement chambers 132a-b toward mixing chambers 134a-b. With blood in mixing chamber 134c, a mixing element in mixing chamber 134c can agitate the blood and promote dissolution of the reagent beads therein.

[0091] 8H, process 200 is shown completed. That is, cups 136a-c all contain blood / reagent mixture, and rotational thromboelastometry can occur within cups 136a-e. This state can be achieved by actuating valves 168, 170, and 160a-e, and vents 166a-e, along with applying a vacuum to vacuum application port 162 or pressure to pressure application port 164, as described above.

[0092] 9, in some alternative embodiments, one or more of the individual blood flow channels or pathways may include multiple mixing chambers arranged in series. For example, exemplary fluid control process 280 includes five blood flow channels (similar to the number of channels in the embodiment 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 mixing chamber as in the embodiment of FIGS. 8A-H). That is, mixing chambers 137a and 137f are arranged in series between measuring chamber 132a and cup 136a. Mixing chambers 137b and 137g are arranged in series between measuring chamber 132b and cup 136b. Mixing chambers 137c and 137h are arranged in series between measuring chamber 132c and cup 136c. Mixing chambers 137d and 137i are arranged in series between measuring chamber 132d and cup 136d. Mixing chambers 137e and 137j are disposed in series between measuring chamber 132e and cup 136e.

[0093] In some embodiments, reagent beads carrying 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 initiating activation / clotting of the blood sample at a controlled time point.

[0094] Although the exemplary fluid control process 280 includes five blood flow channels, each including two mixing chambers arranged in series, 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 it can be combined in the cartridge with one or more other blood flow channels that also include 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] Looking now at the blood coagulation test chambers 136a-e in more detail, the chambers 136a-e are configured to provide a viscoelastic test to a blood sample portion drawn into each chamber. Referring to FIGS. 10A and 10B, pins 138a-e are positioned within the cartridge 120. The representative example showing pin 138b positioned within cup 136b illustrates the existence of a clearance space between the outer diameter of pin 138b and the inner diameter of cup 136b. The blood / reagent mixture will at least partially fill the clearance space when rotational thromboelastometry is performed therein. Pin 138b has a shoulder 138bs. The clearance space between the outer diameter of pin 138b and the inner diameter of cup 136b is smaller in the area below shoulder 138bs than in the area above shoulder 138bs. The area below shoulder 138bs between the outer diameter of pin 138b and the inner diameter of cup 136b is the area that is activated for performing rotational thromboelastometry.

[0096] Cup 136b and pin 138b are shown in cross section in FIG. 10B (according to section 10B-10B of section FIG. 10A). Additionally, sample inlet port 136bi (positioned behind pin 138b in the orientation of FIG. 10B) is provided so that the blood / reagent mixture flows into cup 136b via sample inlet port 136bi. In the illustrated embodiment, cup inlet port 136bi is positioned in the sidewall of cup 136b above the enlarged distal portion of pin 138b (see shoulder 138bs) but below the proximal end of pin 138b (see the end of pin 138b near its entry into axial bore 138bb). In this configuration, the blood / reagent mixture flows into cup 136b, reducing the possibility of bubble formation. Additionally, when cup inlet port 136bi is positioned below shoulder portion 138bs in the active space between the inner diameter of cup 136b and the outer diameter of pin 138b, positioning cup inlet port 136bi at the top of cup 136b eliminates any effect that cup inlet port 136bi might otherwise have on thromboelastometry measurements performed within cup 136b.

[0097] In certain devices, bridging or other structure formation 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) can occur. This can affect the ability of blood to flow into the cups 136a-e or can cause errors during thromboelastometry measurements performed in 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 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 test chamber fills, but the bridge will not be stable enough to last during the measurement. Typically, a 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, the stable bridge lasts for more 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, cup inlet port 136bi is positioned in the sidewall of cup 136b at a height above the enlarged distal portion of pin 138b (see shoulder 138bs) but below the proximal end of pin 138b (see the end of pin 138b near its entry into axial bore 138bb), and inlet port 136bi is at least 1.5 mm from pin 138b. In other words, the pin geometry can allow for this additional clearance. The reason is that the pin has a narrower portion where bridging could occur, thereby allowing for a larger clearance between the pin and the cup to prevent stable bridging.

[0098] In the illustrated embodiment, the top of cartridge 124 includes vent 121. Vent 121 is in fluid communication with needle 123b. Thus, when air is needed to vent a blood sample tube positioned in sample well 122, air is drawn through vent 121 and forced into the blood sample tube via needle 123b.

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

[0100] 10C , an exemplary rotary thromboelastometry assembly 300b can engage pin 138b to perform rotational thromboelastometry on a blood sample contained in cup 136b. In this particular embodiment, the exemplary rotary 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). Base plate 302 is lowered, as represented by arrow 318b, so that a distal portion of shaft 310b enters bore 138bb and is removably coupled to pin 138b. Bearing 312b is engaged with base plate 302 and shaft 310b to facilitate rotational movement of shaft 310b relative to base plate 302. Reaction spring 320b is coupled to shaft 310b, and oscillation of spring 320b can induce shaft 310b to oscillate back and forth by approximately + / - 5°, as represented by arrow 316b. Mirror 315 is coupled to shaft 310b. Light source 330b is configured to project light toward mirror 314b, which can be reflected from mirror 315 toward detector 340b (depending on the rotational orientation of shaft 310b). Thus, movement of pin 138b can be detected by an optical detection system. It should also be understood that other configurations of rotational thromboelastometry assembly 300b are contemplated within the scope of this disclosure.

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

[0102] As the blood in cup 136b begins to clot, the amplitude of movement of shaft 310b begins to decrease (as detected by the deflection of the light beam from mirror 315 toward detector 340b). During clotting, the blood's fibrin backbone (along with platelets) creates a mechanical, elastic linkage between the surfaces of cup 136b and pin 138b. Thus, the ongoing clotting process, induced by the addition of one or more of the above-mentioned activators, can be observed and quantified. In this way, various defects in the patient's hemostatic status can be revealed and interpreted for appropriate medical intervention. At the end of the testing process, base plate 302 can be elevated to decouple shaft 310b from pin 138b.

[0103] 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 computer and electronic components necessary for 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, memory devices, an operating system and other executable instructions, a power supply, user interface controls, communication devices, and circuit boards.

[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 interior space within 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 the sample handler assembly 400 can be easily removed from the analyzer console 140 for servicing. The sample handler assembly 400 is electrically interconnected with the 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 in the cartridge 120 and display the results on the touchscreen display 142.

[0105] 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 the proper orientation so 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 the mechanical frame assembly (which is stationary relative to the analyzer console 140). For example, the viscoelastic measurement system 480 can move upward and downward. As described further below, the viscoelastic measurement system 480 can move downward to engage with the cartridge 120 (see, e.g., FIG. 11 ) and can move upward to disengage from the cartridge 120. The cartridge receiver and a portion of the clamp 410 can move horizontally relative to the mechanical frame assembly. As described further below, the cartridge receiver and a portion of the clamp 410 can move horizontally to clamp or unclamp the cartridge 120 in the sample handler assembly 400.

[0107] In some embodiments, the cartridge receiver and clamp 410 includes a movable block subassembly and a stationary block subassembly. A space exists between the movable block subassembly and the stationary block subassembly within which the cartridge 120 can be received. The movable block subassembly can be translated toward or away from the stationary block subassembly. Thus, the cartridge 120 can be clamped and unclamped between the movable block subassembly and the stationary block subassembly by virtue of the relative movement therebetween. In some embodiments, the viscoelastic measurement system 480 is mounted to the movable block subassembly. Thus, when the movable block subassembly 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 particular embodiments, the motor is a stepper motor. In some embodiments, a gear reducer is coupled to the motor. Using a belt and pulley arrangement for compactness, the motor can be used to drive a lead screw. The threads of the lead screw are engaged with complementary threads on 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, a microswitch, etc.) is included to detect when the movable block subassembly has been translated horizontally to the 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, the portions of the movable block subassembly and the stationary block subassembly that contact the cartridge 120 comprise a flexible or compressible material so that the cartridge 120 is also protected from damage while it is clamped.

[0111] In certain embodiments, the movable block subassembly can include one or more features on a clamping surface of the movable block subassembly that serve to position the cartridge 120 at a desired location within the sample handler assembly 400. For example, in some embodiments, the movable block subassembly includes two locator pins that mate with locator pin receivers 140a and 140b (see FIG. 7) of the cartridge 120 to precisely 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 heating 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 independently heated in some such embodiments. Heating can be performed on one or more sides of the cartridge 120. Other types of heating modalities can also be used, including, but not limited to, IR, ultrasound, microwave, and the like.

[0113] In certain embodiments, one or more temperature sensors 414 are included that 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, infrared temperature sensors, or the like. Thus, the analyzer console 140 can control the heating of the cartridge 120 to a predetermined temperature (e.g., approximately 37° C.) using the heater 412 and the temperature sensor 414.

[0114] The movable block subassembly can include multiple solenoids, which are used to actuate the aforementioned vents and valves of cartridge 120. For example (see also FIG. 7 ), valves 168, 170, and 160a-e can be 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 comprise solenoids. Actuation of valves 168, 170, and 160a-e by valve actuator 430 is achieved by coupling a pin to valve actuator 430, which is extendable from the movable block subassembly to contact and expand the valve elastomeric members so that the elastomeric members contact valve seats within cartridge 120. Actuation of the vents 166a-e by the vent actuator 432 is achieved by coupling a pin to a resilient tip that is extendable from a movable block subassembly to obstruct the vents 166a-e. Such a pin with a resilient tip can act as a stopper to substantially prevent air flow through the vents 166a-e. In some embodiments, the valve actuator 430 and the vent actuator 432 include solenoids that include internal springs that cause the valve actuator 430 and the vent actuator 432 to be normally extended (e.g., when power is removed from the solenoids). Thus, such normally closed solenoids will close the vents and valves of the cartridge 120 as a default configuration.

[0115] The sample handler assembly 400 also includes a pressure source 436 and a vacuum source 434, which can apply air pressure and vacuum 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 contact the cartridge 120 and 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, in some embodiments, are at least partially made from a resilient material. For example, in some embodiments, the pressure source 436 and the vacuum source 434 are at least partially made from a resilient material such as, but not limited to, silicone, butyl rubber, nitrile rubber, ethylene propylene rubber, and fluoroelastomer. One or more internally housed pressure and / or vacuum pumps (not shown) may also be included within analyzer console 140. Such internally housed pressure and vacuum pumps are used to generate air pressure or vacuum that is applied to cartridge 120 to induce transport of blood through cartridge 120, as described above with reference to Figures 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 may also be used to guide the movement of the mixing elements within the mixing chambers 134a-e. The movement of the mixing elements promotes dissolution of the reagent beads in the blood contained within the mixing chambers 134a-e, as described above.

[0118] Analyzer console 140 may also include one or more sensors 448. One or more sensors 448 may be used to detect the presence of blood at specific locations within cartridge 120, such as blood detection locations 127a and 127b (see FIG. 5), as described above. In some embodiments, sensor 448 is an optical sensor, such as an IR (infrared) sensor. In some embodiments, sensor 448 may be used to detect blood in other areas of cartridge 120, such as, but not limited to, in cups 136a-e (see FIGS. 8A-8H).

[0119] The sample handler assembly 400 of the analyzer console 140 also 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. The one or more thromboelastometry assemblies may each be affixed 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 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 vertically raise or lower relative to the cartridge receiver and clamp 410, the motor rotating a threaded lead screw engaged with 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, a microswitch, etc.) is included to detect when the base plate 302 has been vertically translated to the desired end-of-travel position.

[0121] Viscoelastic measurement system 480 includes one of the additional rotating thromboelastometry assemblies (e.g., rotating thromboelastometry assembly 300b in FIG. 10C ), where the one or more rotating thromboelastometry assemblies include a shaft configured to couple with a pin (e.g., shaft 310b configured to couple with pin 138b). Because the thromboelastometry assembly is mounted to base plate 302, the shaft is raised or lowered in conjunction with raising or lowering of base plate 302. Thus, actuation of the linear actuator assembly causes the shaft to vertically raise or lower relative to cartridge receiver and clamp 410 and relative to cartridge 120 when cartridge 120 is clamped therein. Thus, from the description herein, it can be understood that actuation of the linear actuator assembly can engage the shaft with the pin of the cartridge 120 and also disengage the shaft from the pin of the cartridge 120 (see, for example, FIG. 10C, which 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 also includes one or more of the following features: The analyzer console 140 can include one or more barcode scanners 450, which can read a barcode, for example, at the barcode location 125 on the tip of the cartridge 120 (see FIG. 5 ). In some embodiments, the analyzer console 140 can include one or more devices to 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 a desired location and orientation. In some embodiments, the analyzer console 140 can include one or more auxiliary connections 460. The auxiliary connections 460 can include network and device connectors, such as, but not limited to, one or more USB ports, an Ethernet port (e.g., RJ45), a VGA connector, and a Sub-D9 connector (RS232). Such auxiliary connections 460 may be located on the rear of the main chassis 144, or may be positioned in other convenient locations on the main chassis 144. For example, in some embodiments, one or more USB ports may be positioned on or near the front of the main chassis 144.

[0123] The analyzer console 140 also includes a user interface 142 (e.g., comprising a touchscreen display in this embodiment). In the embodiment shown, the user interface 142 is configured to receive user input and display output information to the user. For example, a user can input information into the analyzer console 140 by making selections from various soft buttons that may be displayed on the user interface 142 at points during the beginning, middle, and end of the testing process. In some embodiments, other selections, such as, but not limited to, soft keyboard input, may be provided via the user interface 142. In some embodiments, data entry may additionally or alternatively be performed by voice input. In some embodiments, the user interface may include other peripheral devices (e.g., a mouse, keyboard, additional display devices, etc.) as part of the analyzer console 140. In some embodiments, a computer data network (e.g., an intranet, the Internet, a LAN, etc.) may be used to allow remote devices to receive and / or input information from the system 100. For example, in some embodiments, one or more remote displays may be utilized via the auxiliary connection 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 near field communication tags, RFID tags, or the like. The analyzer console 140 can also include one or more control systems 470, which can execute instructions embodied in a computer program. The control system 470 can include, by way of example, both general-purpose and special-purpose microprocessors, as well as any one or more processors of any type 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 otherwise mounted as needed. Control system 470 is capable of processing instructions for execution within analyzer console 140, including instructions stored in memory or on storage devices. In some implementations, multiple processors and / or multiple buses may be used, along with multiple memories and types of memory, as needed. Multiple computing devices may also be connected (e.g., as in a server bank, a group of blade servers, or a multiprocessor system), with each device providing a portion of the required operations.

[0124] The storage device can provide mass storage for the control system 470. In some implementations, the storage device can be or contain a computer-readable medium, such as a floppy disk device, a hard disk device, an optical disk device, or an array of devices, including a tape device, flash memory, or other similar solid-state memory device, or devices in a storage area network or other configuration. The computer program product can be tangibly embodied in an information carrier. The computer program product can also contain instructions that, when executed, perform one or more methods, such as those described above with reference to FIGS. 8A-8H. The computer program product can also 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 a thromboelastometry system provided herein according to an exemplary process 490. In step 492, a user can insert a cartridge into an 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 . In step 494, after a prompt is received from the analyzer console, a user can couple a blood sample container to the cartridge. As defined by step 492, step 494 can be performed with the cartridge remaining inserted into the analyzer console. In step 496, a user can press a “start” button (or equivalent) to initiate automated transport of blood in the blood sample reservoir to the blood testing chamber of the cartridge so that the viscoelastic properties of the blood can be measured. In some examples, the analyzer console provides an indication that the test is ready to be initiated, but that indication is not required as part of process 490.

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

[0127] In step 510, the presence of the cartridge is detected in a receptacle of an analyzer console of the thromboelastometry system. For example, detection can be performed by a microswitch, an optical sensor, a barcode scanner, or the like, or a combination thereof. Even if the cartridge is detected in the receptacle, at least a portion of the cartridge can be outside the analyzer console.

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

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

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

[0131] The analyzer console scans the cartridge for a barcode in step 550. For example, the analyzer console can scan the tip of the cartridge, where 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 scanning the barcode 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, coupling the shaft of the thromboelastometry subsystem to the pin can configure the thromboelastometry system to perform thromboelastometry on a blood sample contained in the cup of the cartridge. For example, referring to FIG. 10C , shaft 310b of thromboelastometry assembly 300b is lowered toward the cartridge so that shaft 310b is friction-fit and removably coupled to pin 138b of cartridge 120.

[0134] In step 580, the analyzer console can initiate a rotational reciprocating motion of the pin relative to the cup of the cartridge, for example, this step is illustrated above with reference to Figure 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 can be about 35° C. to about 40° C., preferably about 37° C.

[0136] In step 600, the analyzer console provides a prompt to couple the blood sample container to the cartridge. For example, this prompt is provided upon successful completion of one or more steps or successful verification of one or more conditions, or both. For example, this prompt can be provided upon successful achievement of a predetermined cartridge temperature according to step 590, among others. The prompt can be provided via the analyzer console's user interface. For example, the prompt can be a visual message displayed on the analyzer console's touchscreen monitor. In some implementations, an audible prompt can 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 coupled 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 successful completion of one or more steps, or based on successful verification of one or more conditions, or both. The prompt can be provided through the user interface of the analyzer console. For example, the prompt can be a visual message displayed on a touchscreen monitor of the analyzer console. In some embodiments, the touchscreen 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, a vacuum source on the analyzer console can be used to cause blood to flow into the cartridge. In some implementations, an air pressure source on the analyzer console is used to cause blood to flow into the cartridge. The analyzer console can also actuate various valves or vents to control blood flow through the cartridge (see, e.g., FIGS. 8A-8H).

[0140] In step 640, the analyzer console can induce agitation to assist in dissolving reagents in the blood contained within the cartridge. This step is illustrated above in connection with the horizontal reciprocating movement of the magnet shuttle, which includes one or more magnets magnetically coupled to the mixing elements of the cartridge 120, causing the movement of the mixing elements within the cartridge 120 to urge the reagent beads to dissolve in the blood contained within the mixing chambers 134a-e.

[0141] In step 650, the thromboelastometry test is initiated. For example, the analyzer console can begin analyzing data generated by the thromboelastometry assemblies regarding the reciprocating rotation of shafts coupled with pins 138a-e positioned in the cartridge cups 136a-e (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 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 regarding cup 136e. Subsequently, the analyzer console can begin analyzing data generated by the thromboelastometry assembly regarding cup 136d, and so on.

[0142] In step 660, the analyzer console displays the thromboelastometry results. Such results may be displayed simultaneously with the administration of the test and upon completion of the test. The results may be displayed via the analyzer console's user interface, such as on a touchscreen display. The results may be displayed using qualitative graphical representations and quantitative parameters.

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

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

Claims

1. A cartridge (120) for use with an analyzer console (140), said cartridge (120) comprising: a blood sample receiver (122) configured to receive a blood sample to be tested; blood processing and testing pathways (130a, 130b, 130c, 130d, 130e), each configured to receive a portion of the blood sample, and each configured to receive a portion of the blood sample, a measuring chamber (132a, 132b, 132c, 132d, 132e) in fluid communication with the blood sample receiver (122) and 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 measuring chambers (132a, 132b, 132c, 132d, 132e), the mixing chambers (134a, 134b, 134c, 134d, 134e) containing a reagent; a blood testing chamber (136a, 136b, 136c, 136d, 136e) configured to receive a mixture based on a portion of the blood sample and the reagent and to test the mixture within the blood testing chamber; a duct fluidly connecting the measuring chamber, the mixing chamber, and the blood testing chamber; Equipped with mixing to produce the mixture is performed in the mixing chamber (134a, 134b, 134c, 134d, 134e) and in a blood processing and testing path (130a, 130b, 130c, 130d, 130e) in a duct upstream of the mixing chamber; cartridge (120), a channel in fluid communication with a measurement chamber (132e) of the blood processing and testing pathway, the channel configured to receive a portion of the test sample from the measurement chamber (132e); and a blood detection site (127b) on the cartridge, for use with a sensor on the analyzer console to be able to determine the presence of the portion of the blood sample; A cartridge (120) comprising:

2. 2. The cartridge (120) of claim 1, further comprising a stop junction (132as) between the measuring chamber (132a, 132b, 132c, 132d, 132e) and the mixing chamber (134a, 134b, 134c, 134d, 134e) to regulate the flow of the portion of the blood sample from the measuring chamber (132a, 132b, 132c, 132d, 132e) to the mixing chamber (134a, 134b, 134c, 134d, 134e).

3. 3. The cartridge (120) of claim 2, wherein application of positive pressure causes a portion of the blood sample to flow through the stop junction in a duct connecting the measuring chamber (132a, 132b, 132c, 132d, 132e) and the mixing chamber (134a, 134b, 134c, 134d, 134e).

4. 4. The cartridge (120) of claim 1, wherein the mixing chambers (134a, 134b, 134c, 134d, 134e) and the blood testing chambers (136a, 136b, 136c, 136d, 136e) for each of the blood processing and testing paths (130a, 130b, 130c, 130d, 130e) are connected in parallel with the mixing chambers (134a, 134b, 134c, 134d, 134e) and the blood testing chambers (136a, 136b, 136c, 136d, 136e) for other blood processing and testing paths (130a, 130b, 130c, 130d, 130e).

5. The cartridge (120) of any one of claims 1 to 4, wherein the mixing chamber (134a, 134b, 134c, 134d, 134e) contains solid-state reagent beads (180) that contact a portion of the blood sample received from the measurement chamber (132a, 132b, 132c, 132d, 132e).

6. 6. The cartridge (120) of claim 5, wherein the reagent beads (180) comprise a reagent composition comprising one or more of CaCl2, ellagic acid / phospholipids, tissue factor, heparinase, polybrene, cytochalasin D, or tranexamic acid.

7. The cartridge (120) of any one of claims 1 to 6, wherein the measuring chamber (132a, 132b, 132c, 132d, 132e) comprises an outlet port at a bottom of the measuring chamber (132a, 132b, 132c, 132d, 132e).

8. The cartridge (120) of any one of claims 1 to 7, wherein the measuring chambers (132a, 132b, 132c, 132d, 132e) comprise a transfer port near a top of the measuring chambers (132a, 132b, 132c, 132d, 132e).

9. The cartridge (120) of claim 1, wherein the reagent comprises reagent beads.

10. The cartridge (120) of any one of claims 1 to 9, further comprising a pressure application port (164), said pressure application port (164) being coupled to a pressure source that applies pressure to the mixing chamber (134a).

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

12. A method for performing a viscoelastic test on a blood sample using the cartridge of claim 1 or 4.

13. a sample well (122) and needles (123a, 123b) configured to pierce a septum of a blood collection tube (10) when the blood collection tube (10) is inserted into the sample well (122); The cartridge (120) of any one of claims 1 to 10, wherein the needle (123a) is in fluid communication with the blood processing and testing path (130a, 130b, 130c, 130d, 130e) while the needle (123b) facilitates the flow of the blood sample in the blood collection tube (10).

14. 14. The cartridge (120) of claim 13, further comprising a vent (121) in fluid communication with the needle (123b), wherein when air is needed to vent the blood collection tube (10) positioned in the sample well (122), air is drawn through the vent (121) and forced into the blood collection tube via the needle (123b).

15. The cartridge (120) of any one of claims 1 to 10, 13 and 14, wherein when an air pressure vent is closed, the portion of the blood sample in the measuring chamber (132a) does not flow into the corresponding mixing chamber (134a).

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