A thromboelastogram detection device and method based on magnetic beads

Abstract

The present invention provides a thromboelastometry detection device and method based on magnetic beads, which drives a detection cup (1) containing a blood sample to perform periodic reciprocating rotation at a predetermined amplitude and frequency; causes magnetic beads (4) immersed in the blood sample to move in the blood sample as the detection cup periodically reciprocates, and the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood; detects the movement amplitude of the magnetic beads (4) moving in the blood sample by an angular displacement sensor (3); establishes a dynamic peak curve of the movement amplitude of the magnetic beads in the blood sample by a signal processing circuit, and analyzes the dynamic peak curve by the signal processing circuit. The detection device and method of the present invention are combined with conventional magnetic bead coagulation detection and thromboelastometry detection technologies, and proposes detection of the whole blood coagulation process, reflecting the direct influence of the whole blood flowing in layers during the blood coagulation process on the movement trajectory of the magnetic beads.

Description

Technical Field

[0001] The present invention relates to the technical field of blood detection and analysis, and in particular to a thromboelastogram detection device and method based on magnetic beads. Background Art

[0002] The whole blood coagulation analyzer can perform simple and rapid coagulation analysis using a small amount of whole blood. At present, the thromboelastometry method is mainly used for coagulation analysis, which produces a graph by measuring the changes in blood viscoelasticity caused by fibrin polymerization. It was first invented by Hartert in 1948 and can detect various dynamic changes in the coagulation process of whole blood, such as the formation dynamics of blood clots, the contraction of blood clots, viscosity, fibrin elasticity and fibrinolysis. According to its detection principle, it is mainly divided into four categories, namely photoelectric detection, electromechanical detection, pressure analysis and impedance analysis; the rotational thromboelastometry (ROTEM), thromboelastograph (TEG) and coagulation and platelet function analyzer (SONOCLOT) belong to the first three categories respectively.

[0003] The dual-magnetic-circuit magnetic bead method for coagulation detection and analysis has the advantages of requiring a small amount of sample and being less affected by interference such as bubbles. Traditionally, the magnetic beads of the dual-magnetic-circuit magnetic bead method (STAGO) are driven by electromagnets to move back and forth. This form of movement will cause fibrin in the blood to break, so a magnetic bead with a limited length of reciprocating motion is used to reflect the entire blood coagulation process, and as time changes, the trajectory of the reciprocating magnetic beads will change with the coagulation of the blood. In conventional coagulation testing, the dual-magnetic-circuit magnetic bead method is mainly used to detect part of the in vitro plasma in the coagulation chain reaction; it is driven by an alternating magnetic field to oscillate the magnetic beads, and the detection coil measures the trajectory of the magnetic beads that changes in the coagulation viscosity of the plasma. Summary of the invention

[0004] In view of the above problems, the purpose of the present invention is to provide a thromboelastometry detection device and method based on magnetic beads. The detection device and method of the present invention combines conventional magnetic bead coagulation detection and thromboelastometry detection technology, proposes to detect the coagulation process of whole blood, and reflects the direct influence of the whole blood flowing in the stratified flow of blood coagulation process on the movement trajectory of magnetic beads.

[0005] The present invention provides a thromboelastogram detection device based on magnetic beads, comprising: a detection cup (1), a rotating component (2), an angular displacement sensor (3), magnetic beads (4) and a magnet (5);

[0006] The test cup (1) is used to hold a blood sample;

[0007] The rotating component (2) is used to drive the detection cup (1) to perform periodic reciprocating rotation at a predetermined amplitude and frequency;

[0008] The magnetic beads (4) are placed in the detection cup (1), and the blood sample in the detection cup (1) can immerse the magnetic beads (4); the magnetic beads (4) move in the blood sample with periodic reciprocating rotation, and the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

[0009] The angular displacement sensor (3) is used to detect the movement amplitude of the magnetic beads (4) in the blood, and the angular displacement sensor (3) is located below the detection cup (1);

[0010] The magnet (5) is installed on the side of the detection cup, and is used to provide magnetic force to the magnetic beads (4) to overcome the viscoelasticity of blood and the static friction of the magnetic beads in the early stage of coagulation, and to maintain the movement amplitude of the magnetic beads during the detection process.

[0011] Preferably, the detection cup (1) has a protrusion in the middle, and a channel is left around the protrusion for the magnetic beads to move periodically.

[0012] Preferably, the rotating component (2) comprises a stepping motor (2a) or a cam, and a connector (2b), and the stepping motor (2a) or the cam is connected to the detection cup (1) via the connector (2b).

[0013] Preferably, the magnet (5) is a permanent magnet, or an electromagnet with controllable magnetic force.

[0014] Preferably, the amplitude angle of the reciprocating rotation of the detection cup (1) ranges from ±2 degrees to ±20 degrees.

[0015] Preferably, the period of the reciprocating rotation of the detection cup (1) is 3 seconds to 30 seconds.

[0016] Preferably, the diameter of the magnetic beads (4) is 1 mm to 5 mm.

[0017] Preferably, the inclination angle of the bottom surface of the detection cup relative to the horizontal plane ranges from 0 to 90 degrees.

[0018] Preferably, the magnet (5) is located between the end of the detection cup and the surface of the magnetic beads inside the detection cup (1) closest to the end of the magnet.

[0019] Preferably, the detection device further comprises a signal processing circuit, wherein the signal processing circuit is used to obtain a reading representing the amplitude of movement of the magnetic beads from the angular displacement sensor (3), and to establish a dynamic peak curve of the amplitude of movement of the magnetic beads, and to analyze the dynamic peak curve.

[0020] Preferably, the reading of the angular displacement sensor (3) is used to reflect the torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process, and the reading is positively correlated with the viscosity η of the blood, the rotation speed ω of the detection cup, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the center O of the detection cup.

[0021] Preferably, the angular velocity ω of the rotation of the detection cup (1) has the following relationship: Where Φ is the angle of rotation of the test cup; t is the time taken by the test cup to rotate Φ; ω ​​is the angular velocity of the test cup; when the test cup just starts to rotate, the velocity of the blood layer at a distance b from the center of the test cup O is V b , the blood layer at a distance from the center of the detection cup O is in a static state, that is, the velocity of the liquid layer at a is V a =0; the linear velocity of the liquid layer on both sides of the magnetic bead satisfies the following relationship: V a =0, V b =ωb; where a and b represent the distance from the two sides of the magnetic bead to the center O of the detection cup; V a 、V b Respectively represent the linear velocity of the liquid layer on both sides of the magnetic bead; the shear rate of the liquid layer on both sides of the magnetic bead is equal to the velocity gradient of the liquid layer: In the formula Represents the velocity gradient on the liquid layer on both sides of the magnetic bead; a small annular surface element is taken at a distance x from the center of the magnetic bead on the magnetic bead, and the area S of the annular surface element is approximately S = 2πRd x , where R represents the radius of the magnetic bead; the tangential force between two adjacent blood flow layers acting on the surface element of the magnetic bead is: F 切向力 =2πτRd x The moment of the tangential force on the center O of the test cup is: M′=2πτRd x a; then the moment M of the blood flow layer acting on the entire force-bearing spherical surface of the magnetic bead is in In the formula, η represents the viscosity of the blood to be tested, then M=πηωabR. The torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process is positively correlated with the blood viscosity η, the detection cup rotation speed ω, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the detection cup center O.

[0022] The present invention provides a thromboelastogram detection method based on magnetic beads, which is characterized by comprising the following steps:

[0023] Driving a test cup (1) containing a blood sample to perform periodic reciprocating rotation at a predetermined amplitude and frequency;

[0024] The magnetic beads (4) immersed in the blood sample are moved in the blood sample as the detection cup periodically reciprocates, and the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

[0025] detecting the movement amplitude of magnetic beads (4) moving in the blood sample by an angular displacement sensor (3);

[0026] A dynamic peak curve of the movement amplitude of the magnetic beads in the blood sample is established by the signal processing circuit, and the dynamic peak curve is analyzed by the signal processing circuit.

[0027] Preferably, the amplitude angle of the reciprocating rotation of the detection cup (1) ranges from ±2 degrees to ±20 degrees.

[0028] Preferably, the period of the reciprocating rotation of the detection cup (1) is 3 seconds to 30 seconds.

[0029] Preferably, the diameter of the magnetic beads (4) is 1 mm to 5 mm.

[0030] Preferably, the inclination angle of the bottom surface of the detection cup relative to the horizontal plane ranges from 0 to 90 degrees.

[0031] Preferably, a magnet (5) is installed on the side of the detection cup to provide magnetic force to the magnetic beads (4) to overcome the viscoelasticity of blood and the static friction of the magnetic beads in the early stage of coagulation, and to maintain the movement amplitude of the magnetic beads during the detection process.

[0032] Preferably, the reading of the angular displacement sensor (3) is used to reflect the torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process, and the reading is positively correlated with the viscosity η of the blood, the rotation speed ω of the detection cup, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the center O of the detection cup.

[0033] Preferably, the angular velocity ω of the rotation of the detection cup (1) has the following relationship: Where Φ is the angle of rotation of the test cup; t is the time taken by the test cup to rotate Φ; ω ​​is the angular velocity of the test cup; when the test cup just starts to rotate, the velocity of the blood layer at a distance b from the center of the test cup O is V b , the blood layer at a distance from the center of the detection cup O is in a static state, that is, the velocity of the liquid layer at a is V a =0; the linear velocity of the liquid layer on both sides of the magnetic bead satisfies the following relationship: V a =0, V b =ωb; where a and b represent the distance from the two sides of the magnetic bead to the center O of the detection cup; V a 、V b Respectively represent the linear velocity of the liquid layer on both sides of the magnetic bead; the shear rate of the liquid layer on both sides of the magnetic bead is equal to the velocity gradient of the liquid layer: ; In the formula Represents the velocity gradient on the liquid layer on both sides of the magnetic bead; a small annular surface element is taken at a distance x from the center of the magnetic bead on the magnetic bead, and the area S of the annular surface element is approximately S = 2πRd x , where R represents the radius of the magnetic bead; the tangential force between two adjacent blood flow layers acting on the surface element of the magnetic bead is: F 切向力 =2πτRd x The moment of the tangential force on the center O of the test cup is: M′=2πτRd x a; then the moment M of the blood flow layer acting on the entire force-bearing spherical surface of the magnetic bead is in In the formula, η represents the viscosity of the blood to be tested, then M=πηωabR. The torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process is positively correlated with the blood viscosity η, the detection cup rotation speed ω, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the detection cup center O.

[0034] It can be seen that the detection device and detection method of the present invention measure the reading of the angular displacement sensor to indicate the change amplitude of the magnetic bead position, and use the positive correlation between the position change and the change of the torque M generated by the stratified flowing blood on the magnetic bead during the blood coagulation process to reflect the blood coagulation change, thereby realizing the detection of TEG thromboelastogram during the blood coagulation process through the dynamic peak curve of the magnetic bead movement amplitude. The present invention breaks through the traditional measurement method of the dual magnetic circuit magnetic bead method and realizes the combination of magnetic bead coagulation detection and thromboelastography detection.

[0035] Other features and advantages of the present invention will be described in the following description, and partly become apparent from the description, or understood by practicing the present invention. The purpose and other advantages of the present invention can be realized and obtained by the structures particularly pointed out in the written description, claims, and drawings.

[0036] The technical solution of the present invention is further described in detail below through the drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0038] Figure 1 This is a schematic diagram of the structure of a magnetic bead-based thromboelastography detection device;

[0039] Figure 2 The figure is a flow chart of the magnetic bead-based thromboelastography detection method;

[0040] Figure 3Schematic diagram of the dynamic peak curve of the magnetic bead movement amplitude;

[0041] Figure 4 This is a force analysis diagram of the magnetic beads in the detection cup;

[0042] Figure 5 This is a diagram of the movement trajectory of the magnetic beads in the blood in the detection cup;

[0043] Figure 6 Schematic diagram of the magnetic bead surface element and the magnetic bead movement section in the magnetic bead torque analysis. DETAILED DESCRIPTION

[0044] The exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although the exemplary embodiments of the present disclosure are shown in the accompanying drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present disclosure and to fully convey the scope of the present disclosure to those skilled in the art.

[0045] The embodiment of the present invention provides a magnetic bead-based thromboelastometry detection device and method. The detection device and method of the present invention combines conventional magnetic bead coagulation detection and thromboelastometry detection technology, proposes to detect the coagulation process of whole blood, and reflects the direct impact of the stratified flow of whole blood on the movement trajectory of magnetic beads during the blood coagulation process.

[0046] Figure 1It is a structural principle diagram of the thromboelastogram detection device based on magnetic beads. The detection device of the present invention comprises: a detection cup 1, a rotating part 2, an angular displacement sensor 3, magnetic beads 4 and a magnet 5. The detection cup 1 is used to hold a blood sample, and the magnetic beads 4 are placed in the detection cup 1. The blood sample in the detection cup 1 can immerse the magnetic beads 4, and there is a protrusion in the middle of the detection cup 1, and a channel is left around the protrusion for the periodic movement of the magnetic beads. The rotating part 2 comprises a stepper motor 2a or a cam, and a connector 2b, and the stepper motor 2a or the cam is connected to the detection cup 1 through the connector 2b; the detection cup 1 is driven by the stepper motor 2a to perform periodic reciprocating rotation at a predetermined amplitude and frequency; the magnetic beads 4 immersed in the blood sample move in the blood sample with the periodic reciprocating rotation. In the process of blood coagulation, the changing torque M generated by the blood will drive the magnetic beads to move, so the movement amplitude of the magnetic beads 4 is directly related to the coagulation strength of the blood. Therefore, the blood coagulation changes can be reflected by detecting the movement amplitude of the magnetic beads 4 immersed in the blood sample. The angular displacement sensor 3 is used to detect the movement amplitude of the magnetic beads 4. The sensor can be a differential inductive angular displacement sensor, which is located below the detection cup 1. The test surface of the differential inductive angular displacement sensor 3 is parallel to the bottom surface of the detection cup 1, and the bottom surface of the detection cup 1 and the horizontal plane (that is, the test surface of the angular displacement sensor 3 and the horizontal plane) are at a certain tilt angle α, as shown in the figure. The magnet 5 is a permanent magnet, or an electromagnet with controllable magnetic force, installed on the side of the detection cup, and is used to provide a magnetic force to the magnetic beads 4. The magnetic force is used to overcome the static friction between the magnetic beads and the test cup in the early stage of coagulation and the initial adhesion between the blood sample and the magnetic beads. When the detection cup starts to rotate, the initial static friction and blood sample adhesion are eliminated to keep the magnetic beads in a static state; and the magnetic force generated by the magnet 5 is a constant force, which can reduce the movement amplitude of the magnetic beads in the subsequent test process and keep the movement amplitude of the magnetic beads always within the detection range.

[0047] Among them, the stepper motor 2a drives the detection cup 1 to rotate back and forth periodically, and the amplitude angle of the rotation ranges from ±2 degrees to ±20 degrees, preferably ±10 degrees; the reciprocating period is 3 seconds to 30 seconds, preferably 15 seconds. The diameter of the magnetic bead 4 is 1mm to 5mm, preferably 3mm. The inclination angle α of the bottom surface of the detection cup relative to the horizontal plane ranges from 0-90 degrees (i.e. horizontal or vertical), preferably 15 degrees. The distance between the end of the magnet 5 close to the detection cup and the nearest surface of the magnetic bead inside the detection cup 1 to the end of the magnet is 1mm-30mm, preferably 18.4mm.

[0048] The detection device also includes a signal processing circuit, which obtains a reading representing the movement amplitude of the magnetic beads from the angular displacement sensor 3. The reading is related to the torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process, reflecting the change of blood viscosity during the blood coagulation process. Thus, the signal processing circuit dynamically detects the change of the position of the magnetic beads with periodic rotation, and establishes a dynamic peak curve of the movement amplitude of the magnetic beads, such as Figure 3 In addition, the signal processing circuit analyzes the dynamic peak curve, and the analysis process includes extracting the envelope signal of the original signal to form an envelope curve, thereby obtaining relevant results, and the test results are correlated with the TEG thromboelastogram to achieve the unification of the results of different methodologies.

[0049] Figure 2 It is a flow chart of the thromboelastogram detection method based on magnetic beads of the present invention. The detection method comprises the following steps: the detection cup 1 containing the blood sample is driven by the stepper motor 2a to perform periodic reciprocating rotation at a predetermined amplitude and frequency. The magnetic beads 4 immersed in the blood sample are moved in the blood sample as the detection cup rotates periodically and reciprocatingly. The movement amplitude of the magnetic beads 4 moving in the blood sample is detected by the angular displacement sensor 3. The dynamic peak curve of the movement amplitude of the magnetic beads in the blood sample is established by the signal processing circuit according to the change of the position of the magnetic beads, and the dynamic peak curve is analyzed by the signal processing circuit. The analysis process includes extracting the envelope signal of the original signal to form an envelope curve, thereby obtaining relevant results, and the test results are correlated with the TEG thromboelastogram. Among them, the stepper motor 2a drives the detection cup 1 to perform periodic reciprocating rotation, and the amplitude angle of the rotation ranges from ±2 degrees to ±20 degrees, preferably ±10 degrees; the reciprocating period is 3 seconds to 30 seconds, preferably 15 seconds. The diameter of the magnetic beads 4 is 1mm to 5mm, preferably 3mm. The tilt angle α of the bottom surface of the detection cup relative to the horizontal plane ranges from 0 to 90 degrees (i.e. horizontal or vertical), preferably 15 degrees. The distance between the end of the magnet 5 close to the detection cup and the closest surface of the magnetic bead inside the detection cup 1 to the end of the magnet is 1 mm to 30 mm, preferably 18.4 mm.

[0050] Combine the following Figure 4-6 , specifically analyze the magnetic bead torque during the above detection process. Figure 4 This is a force analysis diagram of the magnetic beads in the test cup. The shaded part in the figure is the distribution of the blood sample in the test cup. The blood in the test cup will just cover the magnetic beads. The forces on the magnetic beads include the gravity of the magnetic beads themselves G and the magnetic force F of the magnet on the magnetic beads. 磁 , the buoyancy of blood on magnetic beads F 浮 , the support force of the test cup on the magnetic beads N, the rolling friction force of the test cup on the magnetic beads F 摩擦力The tangential force F of the blood layer on the magnetic beads is the pressure exerted on the magnetic beads by the laminar blood, which changes with the changes in the viscoelasticity of the blood. 磁 It is used to overcome the viscoelasticity of blood in the early stage of coagulation. Figure 4 Left), the magnetic beads will be stationary at the bottom of the test cup, and the above-mentioned multiple forces on the magnetic beads are in a balanced state; as the test cup reciprocates (such as Figure 4 Right), the rolling friction force F of the test cup on the magnetic beads 摩擦力 and the buoyancy F of blood on magnetic beads 浮 Ignore. 磁 Since the movement amplitude of the magnetic beads is small, it is considered to be a constant force, which is balanced with the force components in the same direction as the gravity G and the support force N. In the movement direction of the magnetic beads, the tangential force F, i.e., the pressure exerted by the blood on the magnetic beads, will push the magnetic beads to roll, and as the blood coagulates, the tangential force F gradually increases, and the movement amplitude of the magnetic beads will also become larger and larger.

[0051] According to Newton's law of viscosity, when blood moves in laminar flow in the test cup, each layer of blood will exert pressure on the magnetic beads, causing them to rotate. Figure 5 As shown in the top view of the detection cup, the shaded part is the movement trajectory of the magnetic beads in the blood in the detection cup when viewed from above. Driven by the stepper motor, the detection cup rotates at an angular velocity ω, driving the liquid to flow in layers, so that the magnetic beads are affected by the pressure of the blood liquid layer, generating a torque M to rotate the magnetic beads. Figure 5 Where a and b are the distances from the two sides of the magnetic bead to the center O of the detection cup, and b=a+2R (R is the radius of the magnetic bead).

[0052] The angular velocity ω of the detection cup rotation has the following relationship:

[0053]

[0054] Where Φ is the angle of rotation of the detection cup (°); t is the time taken by the detection cup to rotate Φ (s); ω is the angular velocity of the detection cup (rad / s).

[0055] When the test cup just starts to rotate, the velocity of the liquid layer at a distance b from the center O of the test cup (i.e., the liquid layer in direct contact with the test cup) is V b , the liquid layer at a distance from the center of the detection cup O is in a static state, that is, the velocity of the liquid layer at a is V a Equal to 0. The linear velocity of the liquid layer on both sides of the magnetic bead satisfies the following relationship:

[0056] V a =0 Formula 2

[0057] V b =ωb Formula 3

[0058] Where a and b represent the distances (cm) from the two sides of the magnetic bead to the center of the detection cup O. a 、V b Respectively represent the linear velocity of the liquid layer on both sides of the magnetic bead.

[0059] The shear rate of the liquid layer on both sides of the magnetic bead is equal to the velocity gradient of the liquid layer:

[0060]

[0061] In the formula Represents the velocity gradient on the liquid layer on both sides of the magnetic bead.

[0062] At the distance x from the center of the magnetic bead, take a tiny circular surface element, such as Figure 6 The area S of the circular ring-shaped surface element shown by the diagonal line is:

[0063]

[0064] get

[0065]

[0066] Where y′ is dy / dx;

[0067] There are higher-order infinitesimals in the above formula, which can be approximated to 0;

[0068] S=2πRd x Formula 7

[0069] Where R represents the radius of the magnetic bead (cm).

[0070] Assume that τ is the shear stress per unit surface element, and the magnitude of the internal friction force between two adjacent flow layers acting on any layer is proportional to the contact area of ​​the two adjacent layers, i.e., S. Then the tangential force acting on it is:

[0071] F 切向力 =2πτRd x Formula 8

[0072] The moment of this force on the center O of the test cup is:

[0073] M′=2πτRd x a Formula 9

[0074] Then the moment M of the liquid acting on the entire force-bearing spherical surface of the magnetic bead (the hemispherical surface is affected by the viscous force) is:

[0075]

[0076] According to Newton's law of viscosity:

[0077]

[0078] Where η represents the viscosity of the blood to be tested. Substituting into formula 10, we get:

[0079]

[0080] M=πηωabR Formula 13

[0081] Right now:

[0082] M∝ηωabR Formula 14

[0083] Here ∝ indicates positive correlation.

[0084] The torque M is the internal friction torque acting on the spherical surface of the magnetic bead. When in equilibrium, this torque is related to the position where the magnetic bead is balanced. The position of the magnetic bead is reflected by the reading of the differential inductive angular displacement sensor. Therefore, the reading of the differential inductive angular displacement sensor also reflects the torque of the magnetic bead when in equilibrium. It can be seen from formula 14 that the reading of the differential inductive angular displacement sensor is positively correlated with the viscosity of blood η, the rotation speed of the detection cup ω, the radius R of the magnetic bead, and the product of the distance a and b from the magnetic bead to the center of the detection cup O. Among them, the rotation speed ω of the detection cup is related to the angle Φ of the detection cup and the time t used by the detection cup to rotate Φ, that is, the torque M is also related to the rotation angle and rotation time of the detection cup.

[0085] It can be seen that the detection device and detection method of the present invention measure the reading of the angular displacement sensor to indicate the change amplitude of the magnetic bead position, and use the positive correlation between the position change and the change of the torque M generated by the stratified flowing blood on the magnetic bead during the blood coagulation process to reflect the blood coagulation change, thereby realizing the detection of TEG thromboelastogram during the blood coagulation process through the dynamic peak curve of the magnetic bead movement amplitude. The present invention breaks through the traditional measurement method of the dual magnetic circuit magnetic bead method and realizes the combination of magnetic bead coagulation detection and thromboelastography detection.

[0086] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprises" or any other variants are intended to cover non-other inclusions, so that a process, method, article or device that includes a series of elements includes not only those elements, but also other elements that are not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the term "includes an element defined by..." does not exclude the existence of other identical elements in the process, method, article or device that includes the element.

[0087] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A magnetic bead-based thromboelastography detection method, characterized in that: The following steps are involved: Driving the test cup (1) containing the blood sample to perform periodic reciprocating rotation at a predetermined amplitude and frequency; The magnetic beads (4) immersed in the blood sample are caused to move in the blood sample as the detection cup periodically reciprocates, and the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood; detecting the movement amplitude of magnetic beads (4) moving in the blood sample by an angular displacement sensor (3); A dynamic peak curve of the movement amplitude of the magnetic beads in the blood sample is established by a signal processing circuit, and the dynamic peak curve is analyzed by the signal processing circuit; The magnet (5) is a permanent magnet or an electromagnet with controllable magnetic force, which is installed on the side of the test cup and is used to provide a magnetic force to the magnetic beads (4). The magnetic force is used to overcome the static friction between the magnetic beads and the test cup in the early stage of coagulation and the initial adhesion between the blood sample and the magnetic beads. When the test cup starts to rotate, the initial static friction and blood sample adhesion are eliminated to keep the magnetic beads in a static state. The magnetic force generated by the magnet (5) is a constant force. The reading of the angular displacement sensor (3) is used to reflect the torque M generated by the stratified flowing blood on the magnetic beads during the blood coagulation process, and the reading is positively correlated with the viscosity η of the blood, the rotation speed ω of the detection cup, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the center O of the detection cup; The detection cup speed ω has the following relationship: ; where Φ is the angle of rotation of the test cup; t is the time taken for the test cup to rotate Φ; ω ​​is the rotation speed of the test cup; when the test cup just starts to rotate, the speed of the blood layer at a distance b from the center of the test cup O is , the blood layer at a point O from the center of the detection cup is in a static state, that is, the velocity of the liquid layer at a point =0; the linear velocity of the liquid layer on both sides of the magnetic bead satisfies the following relationship: , ; In the formula, a and b represent the distance from the two sides of the magnetic bead to the center O of the detection cup; , Respectively represent the linear velocity of the liquid layer on both sides of the magnetic bead; the shear rate of the liquid layer on both sides of the magnetic bead is equal to the velocity gradient of the liquid layer: ; In the formula Represents the velocity gradient on the liquid layer on both sides of the magnetic bead; a small annular surface element is taken at a distance x from the center of the magnetic bead on the magnetic bead. The area of ​​the annular surface element is Approximately , where R represents the radius R of the magnetic bead; the tangential force between two adjacent blood flow layers acting on the surface element of the magnetic bead is: , the moment of the tangential force on the center O of the test cup is: ; Then the moment M of the blood flow layer acting on the entire force-bearing spherical surface of the magnetic bead is ,in , where η represents the viscosity of the blood to be tested, then During the blood coagulation process, the torque M generated by the stratified flowing blood on the magnetic beads is positively correlated with the blood viscosity η, the detection cup rotation speed ω, the radius R of the magnetic beads, and the product of the distance a and b from the magnetic beads to the detection cup center O.

2. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The detection cup (1) has a protrusion in the middle, and a channel is left around the protrusion for the magnetic beads to move periodically.

3. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The rotating component (2) comprises a stepping motor (2a) or a cam, and a connector (2b), and the stepping motor (2a) or the cam is connected to the detection cup (1) via the connector (2b).

4. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The amplitude angle of the reciprocating rotation of the detection cup (1) ranges from ±2 degrees to ±20 degrees.

5. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The cycle of the reciprocating rotation of the detection cup (1) is 3 seconds to 30 seconds.

6. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The diameter of the magnetic beads (4) is 1 mm to 5 mm.

7. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The range of the tilt angle of the bottom surface of the detection cup relative to the horizontal plane is 0-90 degrees.

8. The magnetic bead-based thromboelastography detection method according to claim 1, characterized in that: The distance between the end of the magnet (5) close to the detection cup and the closest surface of the magnetic beads inside the detection cup (1) to the end of the magnet is 1 mm to 30 mm.

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