Coagulation test device, system and method of use

Abstract

A coagulation test device for measuring clot time and clot characteristics of whole blood samples under different hemostatic conditions. The test results are used as an aid in the management of patients with unexplained coagulopathy for the purpose of helping the physician to determine appropriate clinical measures to hemostasis in the patient.

Description

Background Technology

[0001] Most existing coagulation tests (including both point-of-care (POC) and laboratory tests) diagnose bleeding abnormalities, but provide insufficient information about the underlying causes of bleeding. Current management of bleeding patients typically involves the use of the "mass transfusion protocol" (MTP). This protocol guides a strategy that manages all patients using a one-size-fits-all approach, without considering the underlying causes of the coagulation disorder in each individual patient. Laboratory tests for factor levels or viscoelasticity testing require time and skilled technicians to perform. Summary of the Invention

[0002] The coagulation testing device described in this article requires minimal laboratory skills to operate and delivers personalized, evidence-based results, which can aid in treatment decisions within 15 minutes of sample tube insertion and result acquisition. Furthermore, there have been reports of thromboembolic events resulting from treatment selection and administration. This device allows for in vitro testing of potential therapeutic agents, which can help identify underlying causes of coagulation disorders and prevent the administration of drugs that may induce thromboembolic events.

[0003] The coagulation testing device described in this article is an in vitro diagnostic field device used to measure the clot time and clot characteristics of whole blood samples under different hemostatic conditions. The test results are used as an adjunct management tool in the treatment of patients with unexplained coagulopathy to help physicians determine appropriate clinical interventions for hemostasis. Furthermore, this device addresses a key issue in perioperative medicine by testing the effect of specific hemostatic agents on the whole blood clot time in bleeding patients.

[0004] In the current state of clinical practice, abnormal test results are often resolved through empirical, educated guesswork regarding the course of drug administration. The coagulation testing device described in this article provides physicians with personalized clinical guidance regarding the specific etiology of a patient's coagulation disorder. This device simultaneously compares the effects of several hemostatic agents on whole blood clot time and derives potential causes based on the measured responses to these agents.

[0005] In one embodiment, an apparatus for processing a container containing a whole blood sample is disclosed herein. The apparatus includes: a recess for receiving the container; a vacuum source coupled to the container; an actuator coupled to the container to agitate the container; and a controller. The controller is configured to: activate the vacuum source to move the whole blood sample from the container into multiple channels within the container, and subsequently into multiple reagent chambers where the blood is mixed with reagents, and then through multiple meandering channels to multiple test chambers; activate the actuator to agitate the container; receive signals from multiple sensors, each sensor associated with one of the test chambers, wherein the signals determine the presence of coagulopathy in the whole blood of each test chamber based on the presence of a spherical member within a magnetic field generated by a magnet positioned adjacent to each of the test chambers; and output an indicator on a display indicating the presence of coagulopathy in the whole blood of each test chamber.

[0006] In another embodiment, a system is disclosed herein comprising: a container containing a whole blood sample, the container including a plurality of test chambers and a metal ball in each test chamber, and means configured to receive the container. The means includes: a plurality of sensors, each sensor positioned adjacent to each of the test chambers; and a controller configured to activate a vacuum source to move a portion of the whole blood sample into each of the test chambers, move the container, receive signals from each of the sensors during container movement, determine whether the metal ball has moved within the test chambers, determine whether the whole blood sample in each test chamber exhibits coagulopathy, and output an indicator on a display indicating the presence of coagulopathy in the whole blood of each test chamber.

[0007] In another embodiment, a method for determining the clot characteristics of a whole blood sample is disclosed herein. The method includes: introducing a whole blood sample into a chamber having multiple test channels, each test channel comprising a reagent chamber, a test chamber, and a metal ball in each test chamber; mixing the whole blood sample with reagents in each of the reagent chambers; agitating the chamber; detecting movement of the metal ball in each of the test chambers using two sensors positioned adjacent to each of the test chambers; determining one or more clot characteristics of the whole blood sample using a controller based on the detection of the movement of the metal ball; and generating an indicator of the clot characteristics for display to a user.

[0008] Other aspects of the invention will become clear by taking into account the specific embodiments and the accompanying drawings. Attached Figure Description

[0009] Figure 1 This is a perspective view of the coagulation test apparatus according to an embodiment.

[0010] Figure 2 yes Figure 1 The diagram shows a block diagram of a coagulation test apparatus.

[0011] Figure 3 yes Figure 1 The diagram shows a three-dimensional view of the coagulation test apparatus, in which the test chamber and protective cover have been removed.

[0012] Figure 4 Is with Figure 1 A perspective top view of a test chamber with an inserted sample tube used in conjunction with the coagulation test apparatus shown.

[0013] Figure 5A yes Figure 4 A three-dimensional diagram of the fluid pathway of the test chamber shown.

[0014] Figure 5B yes Figure 4 The rear perspective view of the test chamber shown is illustrated, along with the hydrophobic membrane.

[0015] Figure 6 This is a three-dimensional diagram of a coagulation test apparatus, in which the test chamber is in the appropriate position before the test.

[0016] Figure 7 yes Figure 4 The enlarged cross-sectional view of the test chamber and spherical component in the test chamber shown.

[0017] Figure 8 The relationship between the travel velocity of the spherical component in the test chamber and the resulting shear rate of the blood sample applied to the test chamber is illustrated graphically.

[0018] Figure 9 The diagram illustrates the differences in the magnetic field lines.

[0019] Figure 10 The sensor detection of the spherical component inside the test chamber is illustrated graphically.

[0020] Figure 11 yes Figure 1 The flowchart shown illustrates the operation method of the coagulation test apparatus.

[0021] Figure 12 It is a decision tree used to determine the cause of coagulopathy based on the response to hemostatic agents.

[0022] Figure 13 The sensor signals during the initial stage of clot formation are illustrated graphically.

[0023] Figure 14 The movement of the spherical component within the test chamber is illustrated graphically when weak agglomerates are present in the test chamber. Detailed Implementation

[0024] Before explaining any embodiments of the invention in detail, it should be understood that the application of the invention is not limited to the details of the construction and arrangement of the components set forth in the following description or illustrated in the accompanying drawings. The invention can have other embodiments and can be practiced or implemented in a variety of different ways.

[0025] One or more embodiments are described and illustrated in the following description and accompanying drawings. These embodiments are not limited to the specific details provided herein and can be modified in various ways. Furthermore, other embodiments not described herein may exist. Also, functionality described herein as being performed by a single component may be performed by multiple components in a distributed manner. Similarly, functionality performed by multiple components may be combined and performed by a single component. Likewise, a component described as performing a particular function may also perform additional functionality not listed herein. For example, an apparatus or structure “configured” in a certain way is configured at least in this manner, but may also be configured in a manner not listed. Furthermore, some embodiments described herein may include one or more electronic processors configured to perform the described functions by executing instructions stored in a non-transitory computer-readable medium. Similarly, embodiments described herein may be implemented as non-transitory computer-readable media storing instructions executable by one or more electronic processors to perform the described functionality. As used herein, “non-transitory computer-readable medium” includes all computer-readable media but does not consist of non-transitory propagated signals. Therefore, non-transitory computer-readable media may include, for example, hard disks, CD-ROMs, optical storage devices, magnetic storage devices, read-only memory (ROM), random access memory (RAM), SIM cards, register memory, processor caches, or any combination thereof.

[0026] Furthermore, the terms and terminology used herein are for descriptive purposes and should not be considered restrictive. For example, the use of “comprising,” “containing,” “including,” “having,” and variations thereof is intended to cover the items listed thereafter and their equivalents, as well as other items. The terms “connection” and “linkage” are used extensively and include both direct and indirect connections and links. Moreover, “connection” and “linkage” are not limited to physical or mechanical connections or links, but may include direct or indirect electrical connections or links. Furthermore, electronic communication and notification may be performed using wired connections, wireless connections, or combinations thereof, and may be transmitted directly or through one or more intermediate means via various types of networks, communication channels, and connections. Furthermore, relational terms such as first and second, top and bottom may be used herein only to distinguish one entity or action from another entity or action, without necessarily requiring or implying any actual such relationship or order between these entities or actions. The word “a” is used herein to indicate one or more (at least one) grammatical objects. For example, “an element” means at least one element and may include more than one element. Unless otherwise specified, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0027] Embodiments are described herein with reference to flowchart illustrations and / or block diagrams and / or accompanying drawings. The flowcharts, block diagrams, and other figures in this disclosure illustrate the architecture, functionality, and operation of possible implementations of systems, methods, computer program products (non-transitory computer-readable media storing instructions executable by an electronic processor, such as a microprocessor, to perform a set of functions) according to various embodiments of the invention. In this regard, each block in a flowchart, block diagram, or accompanying drawing may represent a module, segment, or instruction portion, which includes one or more executable instructions for implementing a specified logical function. In some alternative embodiments, the functions labeled in the blocks or drawings may not appear in the order indicated in the drawings. For example, two blocks shown consecutively may actually be executed substantially simultaneously, or these blocks may sometimes be executed in reverse order, depending on the functionality involved. It should also be noted that each block in the block diagrams and / or flowchart illustrations and / or accompanying drawings, and combinations of blocks in the block diagrams and / or flowchart illustrations and / or accompanying drawings, may be implemented by dedicated hardware-based systems that perform the specified functions or actions or execute combinations of dedicated hardware and computer instructions.

[0028] This document uses various terms familiar to those skilled in the art. The intended meaning of these terms does not deviate from their generally accepted meaning.

[0029] The terms anticoagulant or anticoagulant are used interchangeably and refer to compositions added to or present in a biological sample that inhibit natural or artificial clotting and prolong clotting time. Examples of anticoagulants include, but are not limited to, sodium citrate, hirudin, chelating agents such as ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), 1,2-diaminocyclohexanetetraacetic acid (DCTA), ethylenebis(oxoethylenenitrile)tetraacetic acid (EGTA), or complexing agents such as heparin and heparin-like substances, such as heparin sulfate and low molecular weight heparin, as well as coumarins and indandiones, factor Xa inhibitors, and thrombin inhibitors.

[0030] As used herein, the term coagulopathy refers to any bleeding disorder that affects the way a patient's blood clots. As used herein, the term "hypercoagulability" refers to an abnormally increased state toward blood clot formation. As used herein, the term "hypocoagulability" refers to an abnormally decreased state away from blood clot formation.

[0031] Examples of excitation sources used in this paper include magnetic fields, electromagnetic fields, light, or ultrasonic energy. Excitation sensors used in this paper are devices capable of detecting the presence, absence, or alteration of excitation sources affected or disrupted by test elements in the test sample.

[0032] The terms clot dissolution and fibrinolysis are used interchangeably, and as used herein, refer to the breakdown of fibrin (usually occurring via the enzymatic action of plasmin). The terms clot integrity and clot strength are used interchangeably, and as used herein, refer to the strength of the clot formed due to fibrin and platelet network. The term “premature thrombolysis” as used herein refers to the premature dissolution of the clot after its formation and indicates a defect in hemostasis.

[0033] Figures 1 to 2 The illustration shows a coagulation testing apparatus 10 according to some embodiments. According to some embodiments, the coagulation testing apparatus 10 provides the ability to simultaneously assess clot time and determine the clot characteristics of whole blood under various hemostatic conditions. For example... Figure 1 As illustrated, the coagulation testing device 10 includes a housing 14, a recessed area 18 configured to receive a receiving compartment 30, and a display 26. As shown, the recessed area 18 and the display 26 are positioned adjacent to each other within the housing 14; however, other configurations and orientations between the recessed area 18 and the display 26 are also possible.

[0034] refer to Figure 2The coagulation testing apparatus 10 also includes a vacuum source 12 supported by a housing 14 and a heater 16 supported by a housing 14. The coagulation testing apparatus 10 also includes a controller 20, which includes an electronic processor 24 and a computer-readable non-transitory memory 28. The memory 28 stores instructions executed by the electronic processor 24 to provide the functionality of the controller 20 as discussed herein. The controller 20 is also coupled to a display 26 and configured to output graphical information and data. For example, in some embodiments, the apparatus 10 is configured to output specific data related to the tested hemostatic agent and the whole blood clot time for each channel on the display 26 during the test. The hemostatic agent may include fibrinogen, factor VIII, factor IX, cryoprecipitate, human plasma, factor VIII and von Willebrand factor, factor 3 prothrombin complex concentrate (PCC), factor 4 prothrombin complex concentrate (PCC), protamine sulfate, platelets, heparinase, factor VII, factor VIIa, and factor XIII; however, other suitable hemostatic agents may also be used. When the test is completed, the display 26 can also show diagnostics and other test characteristics derived from the analysis of the test channel data. The controller 20 is also connected to the vacuum source 12 and the heater 16 to control activation and deactivation.

[0035] refer to Figure 3 The recessed area 18 is configured to receive the cassette 30, which allows for up to 18 channels of clot time testing within a single cassette 30. In one configuration, the cassette 30 is approximately the size of a microtiter plate (e.g., 9.7 mm × 11.8 mm) and performs 18 individual coagulation tests. More or fewer channels can be utilized within the envelope of the cassette 30. For example, for illustrative purposes, Figures 4 to 5B The diagram shows 18 channels in container 30; however, container 30 may contain more or fewer than 18 channels. In one embodiment, device 10 accepts a sample tube containing 4.5 ml of whole blood. For an 18-channel coagulation test, this embodiment creates approximately 150 μL of 18 aliquots for the test. The structure and dimensions of container 30 can be modified to reduce the sample volume to 2.7 ml by decreasing the size of the reagent chamber and subsequent test chamber.

[0036] Continue to refer to Figure 3The recessed area 18 is mechanically connected to a gear drive 38 for agitating the chamber 30 and the sample therein. The gear drive 38 is communicated with the controller 20 via an actuator 32 (e.g., a motor, pump, etc.). In one example, the actuator provides an agitation / rocking speed between 90 and 180 degrees per second, with a rocking angle between 10 and 75 degrees. The duration of one cycle is between 1 and 5 seconds. In other examples, the actuator can provide suitable rocking speeds and angles, which may be less than or greater than the parameters provided herein. Similarly, the cycle duration can be appropriately adjusted within the operating range of the device 10.

[0037] The recessed area 18 also includes one or more vacuum ports 42 that dock with the chamber 30, one or more heater areas 46 for incubation and testing, multiple magnets 50, and multiple sensors 54 that communicate with the controller 20.

[0038] Figure 4 An embodiment of the container 30 is illustrated. The container 30 includes a housing 58, a waste collection area 62, and one or more vacuum ports 66 configured to mate with one or more vacuum ports 42 on a recessed area 18. The container 30 also includes a reagent vacuum area 70, a sample tube interface 74, and a sample tube housing 78 configured to receive sample tubes 82 (e.g., ...). Figure 4 The sample tube housing 78 (shown in the image) and the vacuum area 84 of the test channel.

[0039] The container 30 is designed for injection molding and secondary assembly operations. The container 30 is sealed with a blood-compatible membrane that does not affect clotting. The container 30 contains multiple compartments isolated from each other. Blood samples are introduced into the container 30 via a vacuum source 12. A hydrophobic filter 34 ( Figure 5B This is used to stop blood flow when the blood has been completely aspirated. When the chamber 30 is outside the device 10, the vacuum port 66 is at atmospheric pressure. Because no pressure is applied to the sample, the sample remains in the sample tube 82 until it is loaded onto the device 10 and the sample sequencing has begun.

[0040] Box 30 includes a public supply channel X (such as...) Figure 5A (As shown), the common supply channel connects the sample input to a chamber containing individual hemostatic reagents. Each reagent chamber is connected to one of the vacuum ports 66 via a series of hydrophobic filters 34 for each channel. As the sample is aspirated into the chamber 30, each channel is sequentially filled at a rate established by a predetermined vacuum pressure from the vacuum source 12. When a single channel is fully filled, Figure 5BThe hydrophobic filter 34 shown for this channel becomes clogged, and the channel stops filling beyond its capacity. The remaining channels fill until each of the filters is clogged. The controller 20 monitors the duration of the applied vacuum and can also monitor the pressure drop across the filters to determine when all channels are filled.

[0041] According to some embodiments, in Figures 5A to 5B The fluid dynamics of the container 30 are also described and illustrated. The container 30 includes a waste region 86, a sample supply channel 90 communicating with the waste region 86, and one or more hemostatic reagent chambers 94 communicating with the sample supply channel 90 via corresponding channels 98. The container 30 also includes one or more meandering mixing channels 102 at the outlet of each of the respective hemostatic reagent chambers 94. The meandering mixing channels 102 are in fluid communication with one or more anticoagulant reversal chambers 106 (if the anticoagulant is used for anticoagulated whole blood samples), which in turn are each in communication with one or more clot test chambers 110. As described above and illustrated herein, the container 30 is shown as having 18 individual test channels 112, each channel containing a reagent chamber 94, a meandering fluid path 102, and a test chamber 110; however, in other configurations, the container 30 may contain more or fewer than 18 test channels 112.

[0042] Figure 6 The diagram illustrates a system for determining the clot characteristics of a whole blood sample 100, comprising a device 10 and a container 30. Specifically, the container 30 is shown positioned within a recessed region 18 of the device 10. A vacuum port 42 in the recessed region 18 communicates with a vacuum port 66 on the container 30.

[0043] Clot formation in whole blood or plasma can be measured using many different methods. Conductivity requires contact with whole blood. Capacitance measurements do not require contact and can be performed using a barrier membrane; however, these techniques require some type of electrical connection to the test apparatus to carry signals in and out of the apparatus. The coagulation test apparatus 10 described herein utilizes a non-contact measurement method in which a ball 114 made of magnetic material is located within each of 18 test chambers 110 and is used to determine the viscosity of whole blood in each test chamber 110. Figure 7The illustration shows an enlarged cross-section of the test chamber 110 and the spherical member 114 located therein. Agitation of the test chamber 110 causes the spherical member 114 to roll through the whole blood in each test chamber 110. A sensor 54 is positioned close to the test chamber 110 to measure the presence of the spherical member 114 in the test chamber 110 while the test chamber is agitated by the device 10. In one configuration, the test chamber 110 has a width of 3.0 mm and a length of 18 mm to accommodate a sample aliquot volume of approximately 150 μL. In other configurations, the test chamber 110 may have a width of 1.5 mm and a length of 10 mm to reduce the sample aliquot volume to approximately 70 μL. In one example configuration, the test chambers 110 are spaced 4.5 mm apart, which allows 18 channels for the clot time test to be incorporated into the envelope of the cassette 30. Other suitable dimensions are also possible within the scope of the device described herein.

[0044] The velocity of travel within the test chamber 110 is sensed by measuring changes in magnetic flux near sensors 54 positioned along the path of each test chamber 110 as the spherical member 114 passes. Sensors 54 do not need to contact the test chamber 110 and can be positioned 0.8 mm away from the test chamber surface. Sensors 54 sense signals generated within their respective test chambers 110 within the housing 58 of the cassette 30. This non-contact measurement method achieves complete separation between the cassette 30 and the device 10, thereby eliminating the need for contact between the device 10 and the whole blood sample. This configuration also eliminates any device cleaning or maintenance steps between test samples. It further eliminates the possibility of the device losing functionality due to clots in the device's fluid channels.

[0045] Each test chamber 110 is associated with two sensors 54, which are linearly positioned within the test chamber along the travel path of the spherical member 114 and spaced apart by a certain distance (e.g., 9.5 mm). Reference Figure 9Each sensor 54 consists of a magnetic component 118 (e.g., made of one or more rare-earth metals) with sufficient magnetic field strength (thus extending the magnetic field into the test chamber region) and a Hall effect sensor 122 located between the magnetic component 118 and the test chamber 110. The Hall effect sensor 122 generates a voltage signal proportional to the magnetic field, which is between 8 and 10 millivolts per gauss. At the start of the agitation cycle, the controller 20 records a baseline static reading of the magnetic field for each sensor 54. This baseline measurement is used to determine the amount of disturbance in the field as the spherical component 114 passes over the sensor 54. As the spherical component 114 passes over the sensor 54, it induces a disturbance in the static magnetic field, which is detected by the sensor 54. This disturbance of the magnetic flux is detected by the Hall effect sensor 122 and converted into a voltage. The voltage signal from each sensor 54 is then transmitted to the controller 20. A signal threshold is established to eliminate signal artifacts. The voltage signal from the sensor 54 can be converted into a digital signal via a series of analog-to-digital converters. Because two sensors 54 are positioned for each test chamber 110, the time between the disturbance peaks of the two sensors 54 is directly related to the travel time of the spherical member 114 within the test chamber 110. In this way, the viscosity of the fluid in the test chamber 110 can be tracked as the device 10 agitates the test chamber 110 over a period of time, causing the spherical member 114 to pass the sensors 54. Figure 9 The diagram illustrates the magnetic field interaction between the test chamber 110 and the spherical member 114. (See diagram for reference.) Figure 9 As shown, the left-hand diagram illustrates how the spherical component induces more field lines compared to the right-hand diagram without the spherical component.

[0046] Test chamber 110, sensor 54, and controller 20 determine the travel time of the spherical member 114 in each test chamber at a predetermined and programmable agitation rate. The viscosity of the fluid in each test chamber 110 is proportional to the travel time within the chamber. Therefore, the coagulation process can be viewed as an increase in liquid viscosity over time. The coagulation cascade is indeed a series of events and is therefore nonlinear. The trajectory of the travel time of device 10 can detect and monitor the state of quiescent blood as it approaches coagulation. Shortly after coagulation begins, such as... Figure 13 As shown, fluids rapidly approach high viscosity by forming clots. The trajectory angle from the fluid state to clot formation was also measured and used as a basis for diagnosing epigenetic factors or platelet dysfunction.

[0047] In addition to the clot formation time, the device 10 can determine the integrity or strength of the clot forming. Each test chamber 110 within the device 10 has two independent sensors 54 (as described above), and the travel time is calculated by these sensors. When the spherical member 114 fails to pass through both sensors 54 within the test chamber, the travel time cannot be calculated. This indicates a clot that prevents the spherical member 114 from fully traveling within the test chamber 110. However, because the weight on the spherical member 114 within the test chamber is less than 1G, the spherical member 114 may be held in place by a weak clot, where the spherical member 114 will continue to move within a limited range of the chamber length. The device 10 monitors signals from the two sensors 54 and can detect if one of the two sensors 54 is continuously providing a signal. This signal indicates a weak clot that prevents the spherical member 114 from fully traveling the length of the test chamber 110, but still allows the spherical member 114 to move. Figure 14 As shown, only one of the two sensors continues to show the movement of the spherical member 114.

[0048] Figure 14 The diagram illustrates a situation where the spherical member 114 transitions only across one of the sensors 54 with each agitation of the bin or duty cycle, thus indicating weak clumping. The frequency detected by a single sensor of the two sensors 54 indicates clumping integrity, with high frequencies indicating weak clumping. As the number of signals from a single sensor decreases, this indicates increasing clumping strength. Any movement of the spherical member 114 does not indicate strong clumping after clumping has formed, resulting in zero frequencies or frequencies below a threshold set by the device 10. The device 10 establishes a cutoff value for clumping integrity.

[0049] In one example, the duty cycle of the spherical member 114 is proportional to the integrity of the aggregate, wherein a duty cycle greater than 40% indicates severely weak aggregate, a duty cycle between 25% and 40% indicates moderately weak aggregate, a duty cycle between 10% and 25% indicates moderately strong aggregate, and a duty cycle between 0% and 10% indicates strong aggregate.

[0050] The relative size of the spherical component 114 within the test chamber and the diameter of the test chamber help induce coagulation in a manner similar to the physiological coagulation mechanism. It is well known that shear stress within the human vascular system promotes coagulation. Many coagulation testing systems require the addition of high-surface-area coagulants (such as diatomaceous earth or kaolin) to reduce normal clot time to a level that meets the requirements for rapid clot time. The method and apparatus described herein induce coagulation in 500 to 4,000 seconds within each test channel. -1 The physiological shear rate and shear stress between 100 and 1,000 dynes / second eliminate the need for coagulants. Figure 8The diagram illustrates the relationship between the travel velocity of the spherical member 114 within the test chamber 110 and the resulting shear rate, based on the diameter of the test chamber and the relative size of the spherical member 114 within the chamber. The shear rate can be adjusted by changing the agitation angle, the diameter of the test chamber, and the relative diameter of the spherical member. However, if a faster test result time is required, the system can also be used with a coagulant (such as kaolin, citrate, tissue factor, phospholipid, or other suitable activator).

[0051] refer to Figure 11 Sample processing begins with the power-on of device 10 (in 200). Device 10 undergoes quality control testing (in 204). Device 10 performs quality checks to ensure all electromechanical systems are in proper working order. Subsystems (such as the vacuum system, temperature element, and magnetic sensor) are all checked before allowing the user to initiate a sample test. Furthermore, the device is equipped with a reusable QC compartment, which is agitated in a manner similar to sample testing to ensure all electromechanical systems are functioning correctly. The results of the reusable compartment test are recorded in the controller or memory. The QC compartment is removed, and the device is then ready to receive patient samples. The sample tube (filled with whole blood from the patient; the sample tube contains a unique barcode) is then identified by device 10 (in 208). Device 10 allows the input of all the information required to run the test without operator input. Device 10 may include a barcode scanner 40 that communicates with controller 20. The operator places the sample tube barcode in front of scanner 40. Scanner 40 records the barcode and sample information into memory 28 or other storage device (e.g., a database local or remotely on device 10). Device 10 has an override function that allows manual input of patient information via display 26 (e.g., a touchscreen). The patient sample must also be associated with test tube 30. The operator places the barcode affixed to the test tube in front of scanner 40. Scanner 40 records the information from test tube 30 into memory 28 or other storage device (e.g., a database local or remotely on device 10). If the sample tube does not have a barcode, the operator may be prompted to enter information via the on-screen keyboard on display 26.

[0052] The sample and bin 30 are loaded onto device 10 (in 212), and the operator confirms the sample and bin 30 via a user interface on display 26 (in 216). A lid 130 on the device is lowered onto recessed area 18. Lid 130 includes vacuum connectors that connect to vacuum ports 66 on bin 30, necessary for moving fluid through bin 30 during sample handling and prior to the initiation of the clot time test. Vacuum ports 66 on bin 30 connect to vacuum ports 42 in device 10 by closing lid 130. Lid 130 also applies pressure to bin 30 to maintain a uniform distance between bin 30 and the sensor 54 within device 10. The operator initiates the test sequence via the user interface on display 26.

[0053] Samples provided to device 10 are typically anticoagulated to allow time between sample collection and sample testing. This is common practice in most blood testing procedures. Device 10 can also test non-anticoagulated samples in a chamber that does not contain an anticoagulation reversal agent (e.g., calcium); however, there are time limitations on placing non-anticoagulated samples in chamber 30 and on device 10.

[0054] The container 30 is configured to receive a sample vacuum extraction tube (e.g., a vacuum container with a flexible cap) within the sample tube housing 78 as a sample input device. This eliminates the need to move the sample into the container 30, a common procedure in laboratory instruments but not required by device 10. The operator inserts the sample extraction tube directly into the container 30 (in the sample tube housing 78) and places the container 30 onto the recessed area 18 in device 10. The container 30 prevents blood samples from moving into the container by controlling that any ventilation paths are not opened before placement on device 10. The sample in the tube is obtained by piercing the flexible cap with one or more needles (e.g., two needles). The operator inserts the sample tube into the sample tube receiver on the container. A gentle insertion force causes the needle assembly to pierce the sample tube cap. One needle is used to aspirate the sample, and the other needle serves as an vent so that blood can flow out of the extraction tube when a vacuum is applied.

[0055] Device 10 processes the sample (in 220) using a set of known programmed parameters. The first step is to puncture the flexible cap to draw blood from the sample tube and fill the sample supply channel 90 and the connected reagent-containing chamber 94. Blood is drawn at point X (e.g., Figure 5AThe sample travels from the sample tube to the container 30 (shown), fills the sample supply channel 90, and begins filling the reagent-containing chamber 94. The controller 20 activates the vacuum source 12 in the housing 14 to apply a vacuum to the blood sample in the container. A pressure regulator aligned linearly with the vacuum pump is read by the device 10 to control the pressure to a preset value. Typical vacuum levels for sample aspiration are between 50 and 100 millibars (mb). In this sequence, the initial sample is now divided into 18 equal and separate blood sample aliquots.

[0056] Controller 20 selects certain valves in vacuum port 66 to control the direction of vacuum. The blood sample continues to move through various channels in chamber 30. Reagent chamber 94 contains individual doses of various hemostatic agents. As part of the manufacturing process, these reagents are dried and retained in reagent chamber 94. The drying method can be lyophilization or air drying, depending on the nature of the reagent. The chamber is designed such that the blood sample is drawn from the bottom of the chamber into reagent chamber 94 and then drawn to the top of the chamber via vacuum source 12. The dried reagents are rehydrated (in 224) by the volume of the input blood sample. Each reagent chamber 94 contains a hydrophobic filter that prevents overfilling. Device 10 applies vacuum for a preset duration or monitors the pressure drop across the hydrophobic filters until all filters are clogged.

[0057] Each sample-reagent complex must be separated from its nearest neighboring sample-reagent complex to avoid cross-contamination. After filling a single reagent chamber 94, the device 10 empties the sample supply channel 90 connecting the reagent chamber 94 by closing the valve for directing the sample into the reagent chamber 94 and opening the valve for directing the contents of the sample supply channel 90 into the waste area 62 in the cassette 30. Absorbent material collects the waste from the supply channel 90. Each sample aliquot is now isolated from its neighboring reagent chamber 94 by a large air gap created by the empty supply channel 90.

[0058] Hemostasis is a temperature-dependent phenomenon. Controller 20 activates heater 16 to provide heat to chamber 30 (via heater area 36 on recessed area 18) and brings the sample aliquots within reagent chamber 94 to a programmable temperature between 25 and 40 degrees Celsius, with a normal test temperature of 37 degrees Celsius. This range allows for testing samples under normal, low-temperature, and high-temperature conditions. The sample aliquots are incubated with a hemostatic agent for a programmable time, typically between 1 and 10 minutes. In other embodiments, the sample aliquots are incubated with a hemostatic agent for between 3 and 5 minutes. This allows the temperature of the sample aliquots to equilibrate to the appropriate temperature and allows the hemostatic agent to completely dissolve and diffuse into the sample aliquots.

[0059] Prior to this, the blood samples and reagents are anticoagulant to prevent the blood samples from clotting until all sample aliquots are ready for testing. The anticoagulant must be reversed before initiating the clot time test in each test channel. A meandering channel 102 connects the reagent chamber 94 and the test chamber 110. The narrow diameter of the meandering section increases the velocity of the fluid traveling from the reagent area to the test area. A precise amount of dried or lyophilized calcium is present in line with the flow rate in each channel. The traveling fluid rehydrates the calcium and mixes it with the sample aliquots upon transfer. The chamber 30 contains an individual amount of calcium in each channel directly before the samples enter the test area. The calcium mixes with the aliquots upon entering the test area. The anticoagulant in each aliquot has now been reversed, and the clot cascade reaction can begin.

[0060] The controller 20 transmits a signal via a valve to change the direction of the vacuum source 12 and guides the sample stream, aliquoted from the reagent chamber 94, to the test chamber 110 (in 228). Typical vacuum levels are between 50 mB and 100 mB. When placed on the apparatus, the chamber 30 and the test chamber 110 are positioned at a predetermined angle between 10 and 40 degrees relative to the horizontal position of the chamber to facilitate channel filling and minimize the possibility of air bubbles being trapped in the test chamber 110. Each test chamber 110 has a hydrophobic filter aligned with the vacuum source 12 to prevent overfilling of the test chamber and to prevent blood from being drawn into the apparatus's vacuum system.

[0061] With all (or some) of the test chambers 110 filled and the anticoagulation state of the aliquots reversed, controller 20 activates actuator 32 to begin (in 232) agitation of the chamber 30 around a central axis centered on the test channel 110, initiating the clot test. This action causes the spherical members 114 within the chamber 30 to roll uniformly from one end of the test channel to the other. With each agitation cycle, the spherical members 114 in each test channel pass through a sensor 54 associated with each channel 110 to generate a signal proportional to the viscosity of the blood sample within each test channel 110. Sensor 54 transmits the generated signal to controller 20.

[0062] As described above, device 10 uses a non-contact method to detect the movement and travel time of the spherical member 114 within the compartment channel. The current method utilizes the magnetism of the 400 series stainless steel ball; however, other non-contact detection methods, such as ultrasonic, electromagnetic, and optical methods, can be used.

[0063] For each channel 110, each sensor 54 comprises a pair of neodymium iron boron rare-earth magnets 118 and two Hall effect sensors 122. Each magnet 118, spaced approximately 9.5 mm apart along a linear path in each test channel, generates a localized magnetic field that passes through the Hall effect sensors 122 and enters a specific region of the chamber 30. As the magnetic stainless steel ball passes through the magnetic field, the Hall effect sensors 122 detect a flux change above the static baseline signal caused by the presence of the magnetic ball and generate a voltage. The device measures the baseline (static) magnetic signal at the beginning of each cycle. The voltage from each sensor 54 (if a voltage is detected) is transmitted to the controller 20 for further processing.

[0064] Other excitation sources and sensor techniques can be used to measure the coagulation effect in each channel; however, they may be affected by inter-channel crosstalk. Ultrasonic sensors can also be used for each channel. In this case, the spherical member 114 in each channel does not need to be magnetic, but rather has a much higher density than whole blood to ensure that the ultrasonic waves reflect sufficiently to receive the signal. Electromagnetic sensors, similar to miniature metal detectors, can also be used. In this case, the spherical member needs to be conductive, not magnetic. Optical detection of the spherical member can be used. In this case, a reflective sensor element providing the excitation source and a proximity photodetector will detect the reflections of the spherical member as it passes through the optical sensor. The advantage of using magnetic sensing is that the magnetic fields between channels are self-isolated due to their identical polarity and do not interfere with adjacent channels spaced 4 mm apart.

[0065] In the first few minutes of the test, the baseline or normal viscosity of the sample aliquots is determined. As fibrin begins to form in each of the test channels, a viscosity increase between 10% and 20% is observed and recorded by controller 20. Shortly after this increase, the coagulation cascade rapidly progresses to the point where the viscosity of the sample in a given channel exceeds the ability of the spherical component to travel through the sample. Sensor 54, aligned with the specific channel 110, senses that no voltage is being generated. Controller 20 interprets this as clot formation and records the clot duration. The test continues until all channels have clotted or the pre-programmed maximum test time has been reached (e.g., the test is completed in 236).

[0066] As previously mentioned, clot integrity or strength should be considered when taking into account clot time and determining complete clots. When determining the source of coagulopathy, only those clot times associated with strong clots are considered. Physical observation of weak clots shows that small fibers form around the spherical component, inhibiting the ball from traveling the entire length of the test channel; however, the spherical component is able to move short distances within the test channel and cross one of the two sensors. In contrast, high-integrity clots completely capture the spherical component and allow little or no movement after clot formation.

[0067] After clot formation, sensor signals can be used to assess clot integrity. Clot formation is determined when sensor 54 no longer observes two sensor peaks during each device agitation cycle. In high-integrity / strength clots, sensor 54 does not generate a signal after clot formation. In low-integrity, weak clots, one of sensor 54 continues to generate a signal, indicating that the clot allows the spherical member 114 to travel a limited distance. Clot integrity is quantified by observing the average signal in the channels, a process that continues from the initial clot formation time (when at least one sensor reports no signal) until the end of a programmable test cycle between 300 and 1,800 seconds. The lower the number, the higher the clot integrity. High-integrity clots give values ​​between 0 and 100. Medium-integrity clots give values ​​between 101 and 400. Low-integrity clots produce clot strength values ​​greater than 401 and up to 2,000.

[0068] Device 10 compares the clot time and clot integrity of two (2) untreated or reference channels within chamber 30 with that of a channel containing treatment. Other coagulation tests determine clot time in seconds and compare it to an established range of clot time. Device 10 views the clot time relative to a reference sample channel as a way of determining the response to various hemostatic agents. A value of 1.0 indicates no difference between the hemostatic agent and the reference sample channel. Values ​​below 1.0 indicate a reduction in clot time compared to the reference channel, and values ​​above 1.0 indicate a prolonged clot time. The coefficient of variation (CV) of clot time can be as high as 12%, so the threshold for a “response” to a reagent is based on a reduction greater than the CV. For high integrity (equal to or less than 100) clots, a reduction in clot time normalized relative to a reference channel of more than 20% is considered a valid response to a reagent within the specific channel. If the clot time in the test chamber is below the lower limit of the established normal range (typically between 120 and 270 seconds), the chamber result is labeled as potentially hypercoagulable. If the clot time is higher than the upper limit of the established normal range, the test chamber is marked as hypocoagulable.

[0069] The etiology of coagulopathy is determined by the described clot time ratio and the coagulation strength of each test chamber 110 compared to an aliquot of a reference sample contained in the cassette 30. Information on hemostatic agents that reduce clot time and those that do not is combined to isolate a specific etiology or a group of possible, defective factors that contribute to coagulopathy. For example, the reference... Figure 12In the decision tree, if bin 30 and the sample respond with a reduced clot time in the cryoprecipitate channel (indicated by a ratio <0.8) but not in the factor VIII channel (indicated by a ratio >0.8), then the defect is most likely von Willebrand factor or fibrinogen, since cryoprecipitate contains all three clotting factors. Similarly, if the sample responds to the fibrinogen and cryoprecipitate channels but not to the factor VIII or factor VIII / vWF complex channel, then the result is likely a fibrinogen defect.

[0070] These responses to various hemostatic agents produce patterns or stamps indicating the specific situation to be reported at the end of the test sequence. Display 26 can provide a visual indication of the clot time for each channel and its ratio to an untreated reference channel. Display 26 can also provide the resulting defect or diagnosis of coagulopathy based on the clot time, clot ratio, and clot strength of all test channels, which is interpreted by a physician. The analysis performed by the controller is inherently multivariate, thus allowing all channel data to be viewed when determining the cause of the coagulopathy. Device 10 may also include a printer to print the information and data provided on display 26. The response to treatment is determined by a threshold of the ratio to a reference channel. Because there is an inherent difference of up to 12% between channels, a threshold is established to account for this. The response to a hemostatic agent is defined as a ratio greater than a predetermined threshold (e.g., a change of 20% or more compared to a reference channel).

[0071] Device 10 can also be used to test how a clot breaks down after it has formed. Normally, a process called fibrinolysis occurs, in which the blood clot dissolves naturally. In the device 10 described herein, the chamber 30 can continue to be agitated for approximately 30 to 60 minutes while monitoring the spherical member 114 to resume movement. While this should not occur in normal samples, some patients (e.g., trauma patients) may experience hyperfibrinolysis, where the clot dissolves too rapidly and bleeding resumes.

[0072] The initial agitation cycle between 1 and 2 seconds allows the spherical component 114 sufficient time to move from one end of the bin 30 to the other. As agglomerates begin to form, the viscosity of the sample aliquots increases, resulting in an increased travel time. The device has the ability to apply adaptive practices to the agitation cycle parameters.

[0073] For the sake of completeness, various aspects of the invention are set forth in the following numbered clauses:

[0074] Clause 1. A system comprising:

[0075] A container for whole blood samples, the container comprising multiple test chambers and a metal ball in each test chamber;

[0076] A device configured to receive the compartment, the device comprising

[0077] Multiple sensors, each positioned adjacent to one of the test chambers, and

[0078] The controller is configured as follows:

[0079] Activate the vacuum source to move a portion of the whole blood sample into each of the test chambers.

[0080] Move the compartment box.

[0081] The sensor receives a signal from each of the sensors as the bin moves.

[0082] To determine whether the metal ball moves within the test chamber, and to determine whether the whole blood sample in each test chamber exhibits coagulopathy, and

[0083] The display shows an indicator for the presence of coagulopathy in the whole blood for each test chamber.

[0084] Clause 2. The system as described in Clause 1, wherein each sensor comprises a magnet and a Hall effect sensor.

[0085] Clause 3. The system according to Clause 2, wherein the magnet generates a magnetic field near its associated test chamber, and wherein the metal ball in the test chamber is disturbed in the magnetic field, and wherein the sensor detects the disturbance and transmits a signal to the controller to determine whether the ball is moving in the test chamber.

[0086] Clause 4. The system according to Clause 1 further includes a plurality of vacuum ports in the chamber selectively coupled to the vacuum source, and a plurality of hydrophobic filters aligned in a straight line with each of the vacuum ports.

[0087] Clause 5. The system according to Clause 4, wherein the cassette comprises a plurality of reagent chambers, one reagent chamber being associated with one of the test chambers, and wherein the hydrophobic filter is configured to stop blood flow when each of the reagent chambers is filled.

[0088] Clause 6. The system according to Clause 5, wherein the device further includes a heating element configured to apply heat to the bin and the whole blood sample.

[0089] Clause 7. The system according to Clause 6, wherein the heating element heats the whole blood sample to a temperature between 34 degrees Celsius and 37 degrees Celsius.

[0090] Clause 8. The system according to Clause 6, wherein the heating element heats the whole blood sample to a temperature between 30 degrees Celsius and 33 degrees Celsius.

[0091] Clause 9. The system according to Clause 7, wherein the whole blood sample is mixed with reagents in each of the reagent chambers and incubated between 1 minute and 10 minutes.

[0092] Clause 10. The system according to Clause 9, wherein the reagent in each of the reagent chambers is isolated from its adjacent reagent chamber.

[0093] Clause 11. The system according to Clause 1, wherein the controller is further configured to determine the length of time for clot formation in each of the test chambers.

[0094] Clause 12. The system according to Clause 11, wherein the duration of time is based on how long the movement of the metal ball has been detected by the sensor associated with one of the test chambers.

[0095] Clause 13. The system according to Clause 1, wherein each test chamber contains two of the sensors.

[0096] Clause 14. The system according to Clause 13, wherein the controller is further configured to determine clot formation.

[0097] Clause 15. The system according to Clause 14, wherein clot formation is determined when the controller detects that there are no two peaks in each agitation cycle and indicates that the metal ball has stopped moving within the test chamber.

[0098] Clause 16. The system according to Clause 14, wherein the controller is further configured to determine clot integrity.

[0099] Clause 17. The system according to Clause 16, wherein a high-integrity clot is determined when neither of the two sensors generates a signal after the clot has formed.

[0100] Clause 18. The system according to Clause 16, wherein a low-integrity clot is determined if one of the two sensors continues to generate a signal indicative that the clot allows the metal ball to move a finite distance.

[0101] Clause 19. The system according to Clause 16, wherein the clot integrity is based on the average signal generated in the test chamber by the two sensors from the time the clot forms until the end of the test.

[0102] Clause 20. The system according to Clause 5, wherein the chamber contains 18 test chambers.

[0103] Clause 21. The system according to Clause 20, wherein each of the 18 test chambers is associated with one of the reagent chambers, and wherein each of the 18 test chambers receives a whole blood-reagent complex from the associated reagent chamber.

[0104] Clause 22. The system according to Clause 1, wherein the metal ball in each test chamber passes through the sensor associated with each test chamber to generate a signal proportional to the viscosity of the whole blood sample in each test chamber.

[0105] Clause 23. The system according to Clause 1, wherein the controller is further configured to determine a diagnosis based on the outcome of the coagulopathy.

[0106] Clause 24. The system according to Clause 23, wherein the controller is further configured to output the diagnostics on the display.

[0107] Clause 25. An apparatus for processing a container containing whole blood samples, the apparatus comprising:

[0108] The recessed portion is used to receive the compartment box.

[0109] A vacuum source connected to the chamber.

[0110] An actuator connected to the bin to agitate the bin; and

[0111] The controller is configured as follows:

[0112] The vacuum source is activated to move the whole blood sample from the container into multiple channels within the chamber, and subsequently into multiple reagent chambers where the blood is mixed with reagents, and then through multiple meandering channels to multiple test chambers.

[0113] Activate the actuator to agitate the bin.

[0114] Signals are received from multiple sensors, each associated with one of the test chambers, wherein the signals are based on the presence of a spherical member within a magnetic field generated by a magnet positioned adjacent to each of the test chambers.

[0115] Determine whether coagulopathy is present in the whole blood of each test chamber, and output an indicator on the display for the presence of coagulopathy in the whole blood of each test chamber.

[0116] Clause 26. The apparatus of Clause 25 further includes a plurality of vacuum ports selectively coupled to the vacuum source in the chamber, and a plurality of hydrophobic filters aligned in line with each of the vacuum ports, the hydrophobic filters being configured to stop blood flow when each of the reagent chambers is filled.

[0117] Clause 27. The apparatus according to Clause 25 further includes a heating element configured to apply heat to the cassette and the whole blood sample.

[0118] Clause 28. The apparatus of Clause 27, wherein the heating element heats the whole blood sample to a temperature between 34 degrees Celsius and 37 degrees Celsius.

[0119] Clause 29. The apparatus of Clause 27, wherein the heating element heats the whole blood sample to a temperature between 30 degrees Celsius and 33 degrees Celsius.

[0120] Clause 30. The apparatus of Clause 28, wherein the whole blood sample is mixed with reagents in each of the reagent chambers and incubated between 1 minute and 10 minutes.

[0121] Clause 31. The apparatus according to Clause 30, wherein the reagent in each of the reagent chambers is isolated from its adjacent reagent chamber.

[0122] Clause 32. The apparatus of Clause 25, wherein the controller is further configured to determine the length of time for clot formation in each of the test chambers.

[0123] Clause 33. The apparatus according to Clause 32, wherein the duration of time is based on how long the movement of the spherical member has been detected by the sensor associated with one of the test chambers.

[0124] Clause 34. The apparatus according to Clause 25, wherein each test channel comprises two of the sensors.

[0125] Clause 35. The apparatus according to Clause 34, wherein the controller is further configured to determine clot formation.

[0126] Clause 36. The apparatus according to Clause 35, wherein clot formation is determined when the controller detects that there are no two peaks in each agitation cycle and indicates that the spherical member has stopped moving within the test chamber.

[0127] Clause 37. The apparatus of Clause 35, wherein the controller is further configured to determine clot integrity.

[0128] Clause 38. The apparatus according to Clause 37, wherein a highly intact agglomerate is determined when neither of the two sensors generates a signal after the agglomerate has formed.

[0129] Clause 39. The apparatus of Clause 37, wherein a low-integrity agglomerate is determined if one of the two sensors continues to generate a signal indicative that the agglomerate allows the spherical member to move a finite distance.

[0130] Clause 40. The apparatus according to Clause 37, wherein the clot integrity is based on the average signal generated in the test chamber by the two sensors from the time the clot forms until the end of the test.

[0131] Clause 41. The apparatus according to Clause 25, wherein the chamber contains 18 test chambers.

[0132] Clause 42. The apparatus of Clause 41, wherein each of the 18 test chambers is associated with one of the reagent chambers, and wherein each of the 18 test chambers receives a whole blood-reagent complex from the associated reagent chamber.

[0133] Clause 43. The apparatus of Clause 25, wherein the spherical member in each test chamber passes through the sensor associated with each test chamber to generate a signal proportional to the viscosity of the whole blood sample in each test chamber.

[0134] Clause 44. The apparatus according to Clause 25, wherein the controller is further configured to determine a diagnosis based on the outcome of the coagulopathy.

[0135] Clause 45. The apparatus according to Clause 25, wherein the controller is further configured to output the diagnostics on the display.

[0136] Clause 46. A method for determining the clot characteristics of a whole blood sample, the method comprising:

[0137] The whole blood sample is introduced into a container with multiple test channels, each test channel containing a reagent chamber, a test chamber, and a metal ball in each test chamber;

[0138] The whole blood sample is mixed with reagents in each of the reagent chambers;

[0139] Stir the container;

[0140] The movement of the metal ball in each of the test chambers is detected by two sensors positioned adjacent to each of the test chambers;

[0141] Based on the detection of the movement of the metal ball, a controller determines one or more clot characteristics of the whole blood sample; and

[0142] An indicator of the clot characteristics is generated to be displayed to the user.

[0143] Clause 47. The method of claim 46 further comprises reversing the anticoagulant in the whole blood sample before the whole blood sample enters the test chamber.

[0144] Clause 48. The method of claim 47, wherein the chamber contains calcium, and further wherein the whole blood sample is in contact with the calcium between the outlet of the reagent chamber and the inlet of the test chamber.

[0145] Clause 49. The method of claim 46, wherein determining the one or more clot characteristics comprises determining clot formation of the whole blood sample.

[0146] Clause 50. The method of claim 49, wherein determining clot formation comprises the controller detecting that there are no two peaks in each agitation cycle, indicating that the metal ball has stopped moving within the test chamber.

[0147] Clause 51. The method of claim 50, wherein one of the clot characteristics is clot integrity.

[0148] Clause 52. The method of claim 51, wherein a highly intact clot is determined when neither of the two sensors generates a signal after the clot has formed.

[0149] Clause 53. The method of claim 51, wherein a low-integrity agglomerate is determined if one of the two sensors continues to generate a signal indicating that the agglomerate allows the metal ball to move a finite distance.

[0150] Clause 54. The method of claim 51, wherein clot integrity is based on the average signal generated in the test chamber by the two sensors from the time the clot forms until the end of the test.

[0151] Clause 55. The method of claim 51, wherein agitating the bin comprises oscillating the bin at a predetermined duty cycle, and wherein the duty cycle of the metal ball is based on the detection of movement of the metal ball.

[0152] Clause 56. The method of claim 55, wherein the duty cycle of the metal ball is proportional to the integrity of the aggregate.

[0153] Clause 57. The method of claim 56, wherein the agglomerate integrity is low when the duty cycle of the metal sphere is greater than 40%.

[0154] Clause 58. The method of claim 56, wherein the agglomerate integrity is moderate when the duty cycle of the metal sphere is between 25% and 40%.

[0155] Clause 59. The method of claim 56, wherein the agglomerate integrity is high when the duty cycle of the metal sphere is between 10% and 25%.

[0156] Clause 60. The method of claim 56, wherein the agglomerate integrity is very high when the duty cycle of the metal sphere is between 0% and 10%.

[0157] Clause 61. The method of claim 46, wherein determining the one or more clot characteristics comprises determining the viscosity of the whole blood sample.

[0158] Clause 62. The method of claim 61, wherein the viscosity is based on the travel time of the metal ball between the two sensors.

[0159] Clause 63. The method of claim 62, wherein the viscosity increases as a clot forms in the whole blood sample.

[0160] Clause 64. The method of claim 63, wherein clot formation begins when the viscosity is between 10% and 20% of a predetermined baseline.

[0161] It should be understood that the foregoing detailed description is merely illustrative and should not be considered as a limitation on the scope of the invention, which is defined only by the appended claims and their equivalents.

[0162] Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Various features and advantages of the invention are set forth in the appended claims.

Claims

1. A system comprising: A container for whole blood samples, the container comprising multiple test chambers and a metal ball in each test chamber; A means configured to receive the compartment, the means comprising: Multiple sensors, each positioned adjacent to one of the test chambers, and The controller is configured to: Activate the vacuum source to move a portion of the whole blood sample into each of the test chambers. Move the compartment box. The sensor receives a signal from each of the sensors as the bin moves. Based on the received signal, it is determined whether the metal ball is moving within the test chamber, and To determine whether the whole blood sample in each test chamber exhibits coagulopathy, and The display shows an indicator for the presence of coagulopathy in the whole blood sample for each test chamber.

2. The system according to claim 1, wherein, Each sensor contains a magnet and a Hall effect sensor.

3. The system according to claim 2, wherein, The magnet generates a magnetic field near its associated test chamber, and wherein the metal ball in the test chamber is disturbed in the magnetic field, and wherein the sensor detects the disturbance and transmits a signal to the controller to determine whether the metal ball is moving in the test chamber.

4. The system of claim 1 further includes a plurality of vacuum ports in the chamber connected to the vacuum source, and a plurality of hydrophobic filters aligned with each of the vacuum ports.

5. The system according to claim 4, wherein, The cassette contains multiple reagent chambers, one of which is associated with one of the test chambers, and wherein the hydrophobic filter is configured to stop blood flow when each of the reagent chambers is filled.

6. The system according to claim 5, wherein, The device also includes a heating element configured to apply heat to the cassette and the whole blood sample.

7. The system according to claim 6, wherein, The heating element heats the whole blood sample to a temperature between 34 and 37 degrees Celsius.

8. The system according to claim 6, wherein, The heating element heats the whole blood sample to a temperature between 30 and 33 degrees Celsius.

9. The system according to claim 7, wherein, The whole blood sample is mixed with reagents in each of the reagent chambers and incubated for between 1 minute and 10 minutes.

10. The system according to claim 9, wherein, The reagents in each of the reagent chambers are isolated from their neighboring reagent chambers.

11. The system according to claim 1, wherein, The controller is also configured to determine the length of time it takes for clots to form in each of the test chambers.

12. The system according to claim 11, wherein, The duration of the time is based on how long the metal ball has been moving, as detected by a sensor associated with one of the test chambers.

13. The system according to claim 1, wherein, Each test chamber contains two of the sensors described in the sensor suite.

14. The system according to claim 13, wherein, The controller is also configured to determine clot formation.

15. The system according to claim 14, wherein, Clumping is determined when the controller detects that there are no two peaks in each agitation cycle and indicates that the metal ball has stopped moving in the test chamber.

16. The system according to claim 14, wherein, The controller is also configured to determine clot integrity.

17. The system according to claim 16, wherein, A highly intact agglomerate is determined when neither of the two sensors generates a signal after the agglomerate has formed.

18. The system according to claim 16, wherein, Low-integrity clumps are determined when one of the two sensors continues to generate a signal indicating that the clump allows the metal ball to move a limited distance.

19. The system according to claim 16, wherein, Clot integrity is based on the average signal generated by the two sensors in the test chamber from the time the clot forms until the end of the test.

20. The system according to claim 5, wherein, The chamber contains 18 test chambers.

21. The system according to claim 20, wherein, Each of the 18 test chambers is associated with one of the reagent chambers, and each of the 18 test chambers receives a whole blood-reagent complex from the associated reagent chamber.

22. The system according to claim 1, wherein, The metal ball in each test chamber passes through a sensor associated with each test chamber to generate a signal proportional to the viscosity of the whole blood sample in each test chamber.

23. The system according to claim 1, wherein, The controller is also configured to determine a diagnosis based on the outcome of the coagulopathy.

24. The system according to claim 23, wherein, The controller is also configured to output the diagnostics on the display.

25. An apparatus for processing a container containing whole blood samples, the apparatus comprising: The recessed portion is used to receive the compartment box. A vacuum source connected to the chamber. An actuator connected to the bin to agitate the bin; as well as The controller is configured to: The vacuum source is activated to move the whole blood sample from the container into multiple channels within the chamber, and subsequently into multiple reagent chambers where the whole blood sample is mixed with reagents, and then through multiple meandering channels to multiple test chambers. Activate the actuator to agitate the bin. When the chamber is agitated, signals are received from multiple sensors, each sensor associated with one of the test chambers, wherein the signals are based on the presence of a spherical member within a magnetic field generated by magnets positioned adjacent to each of the test chambers. To determine whether coagulopathy is present in the whole blood sample from each test chamber, and The display shows an indicator for the presence of coagulopathy in the whole blood sample for each test chamber.

26. The apparatus of claim 25, further comprising a plurality of vacuum ports in the chamber coupled to the vacuum source, and further comprising a plurality of hydrophobic filters aligned with each of the vacuum ports, the hydrophobic filters being configured to stop blood flow when each of the reagent chambers is filled.

27. The apparatus of claim 25 further includes a heating element configured to apply heat to the cassette and the whole blood sample.

28. The apparatus according to claim 27, wherein, The heating element heats the whole blood sample to a temperature between 34 and 37 degrees Celsius.

29. The apparatus according to claim 27, wherein, The heating element heats the whole blood sample to a temperature between 30 and 33 degrees Celsius.

30. The apparatus according to claim 28, wherein, The whole blood sample is mixed with reagents in each of the reagent chambers and incubated between 1 minute and 10 minutes.

31. The apparatus according to claim 30, wherein, The reagents in each of the reagent chambers are isolated from their neighboring reagent chambers.

32. The apparatus according to claim 25, wherein, The controller is also configured to determine the length of time it takes for clots to form in each of the test chambers.

33. The apparatus according to claim 32, wherein, The duration of the time is based on how long the movement of the spherical component has been detected by the sensor associated with one of the test chambers.

34. The apparatus according to claim 25, wherein, Each test chamber contains two of the sensors described in the sensor suite.

35. The apparatus according to claim 34, wherein, The controller is also configured to determine clot formation.

36. The apparatus according to claim 35, wherein, Clot formation is determined when the controller detects that there are no two peaks in each agitation cycle and indicates that the spherical component has stopped moving within the test chamber.

37. The apparatus according to claim 35, wherein, The controller is also configured to determine clot integrity.

38. The apparatus according to claim 37, wherein, A highly intact agglomerate is determined when neither of the two sensors generates a signal after the agglomerate has formed.

39. The apparatus according to claim 37, wherein, Low-integrity clumps are determined when one of the two sensors continues to generate a signal indicating that the clump allows the spherical member to move a limited distance.

40. The apparatus according to claim 37, wherein, Clot integrity is based on the average signal generated by the two sensors in the test chamber from the time the clot forms until the end of the test.

41. The apparatus according to claim 25, wherein, The chamber contains 18 test chambers.

42. The apparatus according to claim 41, wherein, Each of the 18 test chambers is associated with one of the reagent chambers, and each of the 18 test chambers receives a whole blood-reagent complex from the associated reagent chamber.

43. The apparatus according to claim 25, wherein, The spherical member in each test chamber passes through a sensor associated with each test chamber to generate a signal proportional to the viscosity of the whole blood sample in each test chamber.

44. The apparatus according to claim 25, wherein, The controller is also configured to determine a diagnosis based on the outcome of the coagulopathy.

45. The apparatus according to claim 44, wherein, The controller is also configured to output the diagnostics on the display.

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