WO2022188189A1 - Magnetic bead based thrombelastogram detection device and method - Google Patents

Abstract

A magnetic bead (4) based thrombelastogram detection device and method. A detection cup (1) containing a blood sample is driven to periodically rotate back and forth at predetermined amplitude and frequency; a magnetic bead (4) immersed in the blood sample is enabled to move in the blood sample along with the periodically back-and-forth rotation of the detection cup (1), and the movement amplitude of the magnetic bead (4) is positively correlated to the coagulation intensity of blood; the movement amplitude of the magnetic bead (4) moving in the blood sample is measured by means of an angular displacement sensor (3); and a dynamic peak curve of the movement amplitude of the magnetic bead (4) in the blood sample is established by means of a signal processing circuit, and the dynamic peak curve is analyzed by means of the signal processing circuit. The magnetic bead (4) based thrombelastogram detection device and method are combined with conventional magnetic bead (4) blood coagulation detection and thrombelastography detection technologies, detection of a whole blood coagulation process is proposed, and the direct effect of whole blood flowing in a layered manner in the blood coagulation process on a movement path of the magnetic bead (4) is reflected.

Description

A magnetic bead-based thromboelastography detection device and method technical field

The invention relates to the technical field of blood detection and analysis, in particular to a magnetic bead-based thromboelastography detection device and method.

Background technique

The Whole Blood Coagulation Analyzer performs simple and rapid coagulation analysis using trace amounts of whole blood. At present, thromboelastometry is mainly used for coagulation analysis, which is a graph produced by measuring the viscoelastic changes of blood caused by fibrin polymerization. It was first invented by Hartert in 1948 and can detect various dynamic changes during whole blood coagulation, such as clot formation kinetics, clot contraction, 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; rotary thromboelastometer (ROTEM), thromboelastography (TEG) and coagulation and platelet function analyzer (SONOCLOT) ) belong to the first three categories, respectively.

The dual-magnetic-circuit magnetic bead method for coagulation detection and analysis has the advantages of requiring less sample volume and less influence by interference such as air bubbles. In the traditional sense, the magnetic beads of the double 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. Therefore, a magnetic bead with a limited length of reciprocating motion is used to reflect The entire blood coagulation process, and with the change of time, the reciprocating magnetic beads track will change with the blood coagulation. In conventional coagulation detection, the dual magnetic circuit magnetic bead method is mainly for the detection of a part of the isolated plasma in the coagulation chain reaction; it is driven by an alternating magnetic field to make the magnetic beads do oscillating motion, and the detection coil measures the change of plasma coagulation viscosity. Motion trajectory of the magnetic beads.

SUMMARY OF THE INVENTION

In view of the above problems, the purpose of the present invention is to provide a magnetic bead-based thromboelastometry detection device and method. The detection device and method of the present invention combine the conventional magnetic bead coagulation detection and thromboelastometry detection technology, and propose the detection of the whole blood coagulation process, reflecting the direct influence of the whole blood flowing in layers in the blood coagulation process on the movement track of the magnetic bead.

The invention provides a magnetic bead-based thromboelastometry detection device, comprising: a detection cup (1), a rotating part (2), an angular displacement sensor (3), a magnetic bead (4) and a magnet (5);

The detection cup (1) is used for holding blood samples;

The rotating component (2) is used to drive the detection cup (1) to periodically reciprocate with a predetermined amplitude and frequency;

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) reciprocate periodically Rotating and moving in the blood sample, the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

The angular displacement sensor (3) is used for detecting the movement amplitude of the magnetic beads (4) in the blood, and the angular displacement sensor (3) is located below the detection cup (1);

The magnet (5) is installed on the side of the detection cup for providing magnetic force to the magnetic beads (4) to overcome the viscoelasticity of blood and the static friction force of the magnetic beads in the early stage of coagulation, and to maintain the movement range of the magnetic beads during the detection process.

Preferably, there is a bulge in the middle of the detection cup (1), and a channel for the periodic movement of the magnetic beads is left around the bulge.

Preferably, the rotating part (2) comprises a stepper motor (2a) or a cam, and a connector (2b), through which the stepper motor (2a) or the cam is connected to the detection cup. (1) Connection.

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

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

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

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

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

Preferably, the magnet (5) is close to the end of the detection cup and between the inner magnetic bead of the detection cup (1) which is closest to the end of the magnet.

Preferably, the detection device further comprises a signal processing circuit, which is used for obtaining a reading representing the movement amplitude of the magnetic bead from the angular displacement sensor (3), and establishing a dynamic peak curve of the movement amplitude of the magnetic bead, The dynamic peak curve is analyzed.

Preferably, the reading of the angular displacement sensor (3) is used to reflect the moment M generated by the stratified flow of blood on the magnetic beads during the blood coagulation process, and the reading is related to the viscosity η of the blood, the rotational speed of the detection cup ω, and the magnetic bead. The radius R and the product of the distance a and b from the magnetic bead to the center O of the detection cup are positively correlated.

Preferably, the angular velocity ω of the rotation of the detection cup (1) has the following relationship:

In the formula, Φ is the rotation angle of the detection cup; t is the time it takes for the detection cup to rotate the Φ angle; ω is the angular velocity of the detection cup; The velocity of the liquid layer is V _b , and the blood liquid layer at a distance from the center O of the detection cup is in a static state, that is, the velocity V _a of the liquid layer at a is equal to 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; in the formula, a and _{b respectively represent the distance from both sides of the magnetic bead to the center O of the detection cup; Va and V b respectively} represent the linear velocity of the liquid layer on both sides of the magnetic bead; The shear rate 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; at the distance x from the magnetic bead center on the magnetic bead, take a tiny annular surface element, the area S of the annular surface element is approximately S=2πRd _x , where R represents the radius R of the magnetic bead; the tangential force acting on the surface of the magnetic bead between two adjacent blood flow layers is: F _{tangential force} = 2πτRd _x , the tangential force on the detection cup center O The moment is: M′=2πτRd _x a; then the moment M of the blood flow layer acting on the entire force 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 moment M generated by the stratified flow of blood to the magnetic beads during the blood coagulation process and the viscosity η of the blood, the rotation speed of the detection cup ω, the radius of the magnetic beads R and the magnetic beads The product of the distance a and b from the center O of the detection cup is positively correlated.

The present invention provides a magnetic bead-based detection method for thromboelastometry, which is characterized by comprising the following steps:

Drive the detection cup (1) containing the blood sample to periodically reciprocate with a predetermined amplitude and frequency;

The magnetic beads (4) immersed in the blood sample are moved in the blood sample along with the periodic reciprocating rotation of the detection cup, and the motion amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

The motion 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 motion 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.

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

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

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

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

Preferably, a magnet (5) is installed on the side of the detection cup to provide magnetic force to the magnetic beads (4) so as 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 of the magnetic beads during the detection process. magnitude.

Preferably, the reading of the angular displacement sensor (3) is used to reflect the moment M generated by the stratified flow of blood on the magnetic beads during the blood coagulation process, and the reading is related to the viscosity η of the blood, the rotational speed of the detection cup ω, and the magnetic bead. The radius R and the product of the distance a and b from the magnetic bead to the center O of the detection cup are positively correlated.

Preferably, the angular velocity ω of the rotation of the detection cup (1) has the following relationship:

In the formula, Φ is the rotation angle of the detection cup; t is the time it takes for the detection cup to rotate the Φ angle; ω is the angular velocity of the detection cup; The velocity of the liquid layer is V _b , and the blood liquid layer at a distance from the center O of the detection cup is in a static state, that is, the velocity V _a of the liquid layer at a is equal to 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; in the formula, a and _{b respectively represent the distance from both sides of the magnetic bead to the center O of the detection cup; Va and V b respectively} represent the linear velocity of the liquid layer on both sides of the magnetic bead; The shear rate 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; at the distance x from the magnetic bead center on the magnetic bead, take a tiny annular surface element, the area S of the annular surface element is approximately S=2πRd _x , where R represents the radius R of the magnetic bead; the tangential force acting on the surface element of the magnetic bead between two adjacent blood flow layers is: F _{tangential force} = 2πτRd _x , the tangential force on the detection cup center O The moment is: M′=2πτRd _x a; then the moment M of the blood flow layer acting on the entire force 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 moment M generated by the stratified flow of blood to the magnetic beads during the blood coagulation process and the viscosity η of the blood, the rotation speed of the detection cup ω, the radius of the magnetic beads R and the magnetic beads The product of the distance a and b from the center O of the detection cup is positively correlated.

Thus, it can be seen that the detection device and detection method of the present invention represent the change range of the position of the magnetic beads by measuring the reading of the angular displacement sensor, and use the position change and the change of the torque M generated by the blood flowing in layers during the blood coagulation process to the magnetic beads. The positive correlation reflects the changes of blood coagulation, so that the detection of TEG thrombelastogram in the process of blood coagulation can be realized through the dynamic peak curve of the motion amplitude of the magnetic beads. The invention breaks through the traditional double magnetic circuit magnetic bead method for measurement, and realizes the combination of magnetic bead coagulation detection and thromboelastometry detection.

Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention may be realized and attained by the structure particularly pointed out in the written description, claims, and drawings.

The technical solutions of the present invention will be described in further detail below through the accompanying drawings and embodiments.

Description of drawings

The accompanying drawings are used to provide a further understanding of the present invention, and constitute a part of the specification, and are used to explain the present invention together with the embodiments of the present invention, and do not constitute a limitation to the present invention. In the attached image:

Fig. 1 is a schematic diagram of the structure of a magnetic bead-based thromboelastography detection device;

Fig. 2 is the flow chart of the detection method of thrombelastography based on magnetic beads;

Fig. 3 is the schematic diagram of the dynamic peak curve of magnetic bead motion amplitude;

Fig. 4 is the force analysis diagram of magnetic beads in the detection cup;

Fig. 5 is the movement track diagram of magnetic beads in blood in the detection cup;

FIG. 6 is a schematic diagram of the surface element of the magnetic bead and the cross-section of the movement of the magnetic bead in the analysis of the magnetic bead moment.

Detailed ways

Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited by the embodiments set forth herein. Rather, these embodiments are provided so that the present disclosure will be more thoroughly understood, and will fully convey the scope of the present disclosure to those skilled in the art.

The embodiments of the present invention provide a magnetic bead-based thromboelastometry detection device and method. The detection device and method of the present invention combine the conventional magnetic bead coagulation detection and thromboelastometry detection technology, and propose the detection of the whole blood coagulation process, reflecting the direct influence of the stratified flow of whole blood in the blood coagulation process on the movement track of the magnetic beads.

FIG. 1 is a schematic structural diagram of the magnetic bead-based thromboelastography detection device. The detection device of the present invention includes: a detection cup 1 , a rotating part 2 , an angular displacement sensor 3 , a magnetic bead 4 and a magnet 5 . The detection cup 1 is used for holding blood samples, the magnetic beads 4 are placed in the detection cup 1, the blood sample in the detection cup 1 can be submerged in the magnetic beads 4, and the detection cup 1 has a convex in the middle From the beginning, a channel for the periodic movement of the magnetic beads is left around the protrusion. The rotating part 2 includes a stepping motor 2a or a cam, and a connector 2b, through which the stepping motor 2a or the cam is connected to the detection cup 1; the detection cup 1 is driven by the stepping motor 2a , perform periodic reciprocating rotation with 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 push the magnetic beads to move. Therefore, the movement range of the magnetic beads 4 is directly related to the coagulation strength of the blood. Therefore, changes in blood coagulation 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 , and 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) form a certain inclination angle α, as shown in the figure shown. The magnet 5 is a permanent magnet, or an electromagnet with a controllable magnetic force, and is installed on the side of the detection cup to provide a magnetic force to the magnetic bead 4, which is used to overcome the static friction between the magnetic bead and the test cup in the early stage of coagulation. force and the initial adhesion force between the blood sample and the magnetic beads, when the detection cup starts to rotate, by eliminating the initial static friction force and the blood sample adhesion force, the magnetic beads are kept 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 testing process and keep the movement amplitude of the magnetic beads within the detection range.

Wherein, 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 and 30 seconds, Among them, 15 seconds is preferable. The diameter of the magnetic beads 4 is 1 mm˜5 mm, preferably 3 mm. The range of the inclination angle α of the bottom surface of the detection cup relative to the horizontal plane is 0-90 degrees (that is, 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 beads inside the detection cup 1 to the end of the magnet is 1 mm-30 mm, preferably 18.4 mm.

The detection device also includes a signal processing circuit, which obtains a reading representing the movement amplitude of the magnetic bead from the angular displacement sensor 3, and the reading is related to the torque generated by the blood flowing in layers during the blood coagulation process to the magnetic bead. M is correlated, reflecting changes in blood viscosity during blood coagulation. Therefore, the signal processing circuit dynamically detects the change of the position of the magnetic bead with the periodic rotation, and establishes a dynamic peak curve of the movement amplitude of the magnetic bead, as shown in FIG. 3 . In addition, the signal processing circuit analyzes the dynamic peak curve. The analysis process includes extracting the envelope signal of the original signal to form an envelope curve, so as to obtain relevant results. The test results are correlated with the TEG thromboelastometry to achieve Harmonization of results from different methodologies.

FIG. 2 is a flow chart of the magnetic bead-based thromboelastometry detection method of the present invention. The detection method includes the following steps: the detection cup 1 containing the blood sample is driven by the stepping motor 2a to periodically reciprocate at a predetermined amplitude and frequency. The magnetic beads 4 immersed in the blood sample are moved in the blood sample with the periodic reciprocating rotation of the detection cup. The motion 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 motion amplitude of the magnetic bead in the blood sample is established by the signal processing circuit according to the change of the position of the magnetic bead, and the dynamic peak curve is analyzed by the signal processing circuit. The analysis process includes the envelope signal extraction of the original signal, An envelope curve is formed, resulting in relevant results, the test results of which are correlated with TEG thromboelastometry. Wherein, 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 and 30 seconds, Among them, 15 seconds is preferable. The diameter of the magnetic beads 4 is 1 mm˜5 mm, preferably 3 mm. The range of the inclination angle α of the bottom surface of the detection cup relative to the horizontal plane is 0-90 degrees (that is, 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 beads inside the detection cup 1 to the end of the magnet is 1 mm-30 mm, preferably 18.4 mm.

In the following, with reference to Figs. 4-6, the analysis of the magnetic bead torque in the above detection process is specifically carried out. Figure 4 is the force analysis diagram of the magnetic beads in the detection cup. The shaded part in the figure is the distribution of the blood sample in the test cup, and the blood in the test cup will just cover the magnetic beads. The force of the magnetic beads specifically includes the gravity of the magnetic beads G, the magnetic force F of the magnet to the _magnetic beads, the buoyancy of the blood to the magnetic beads F _float , the support force N of the detection cup to the magnetic beads, and the rolling friction force of the detection cup to the magnetic beads. The effect of F _{friction force} and the tangential force F of the blood liquid layer on the magnetic beads F tangential force and other forces. The F tangential force is the pressure exerted on the magnetic beads by the blood in laminar flow, which is changed by the change of blood viscoelasticity. F _magnetism is used to overcome the viscoelasticity of blood in the non-coagulated state at the initial stage of coagulation. When the detection cup does not rotate (as shown in the left picture of Figure 4), the magnetic beads will be stationary at the bottom of the test cup, and the above-mentioned forces on the magnetic beads are in a balanced state; with the reciprocating rotation of the detection cup (as shown in the right picture of Figure 4) , the rolling _friction force F of the detection cup to the magnetic beads and the _buoyant force F of the blood to the magnetic beads are ignored. _Magnetic F is considered to be a constant force due to the small movement range of the magnetic beads, which is balanced with the component forces of gravity G and supporting force N in the same direction. In the movement direction of the magnetic beads, the F tangential force, that is, the pressure exerted by the blood on the magnetic beads, will push the magnetic beads to roll, and as the blood coagulates, the F tangential force gradually increases, and the movement amplitude of the magnetic beads will also become larger and larger. .

According to Newton's law of viscosity, when the blood moves in laminar flow in the test cup, each liquid layer of the blood will exert pressure on the magnetic beads to make the magnetic beads rotate. As shown in the top view of the detection cup in Figure 5, the shaded part is the trajectory of the magnetic beads in the blood in the detection cup from the top view. Driven by the stepping motor, the detection cup rotates at an angular velocity ω, which drives the liquid to flow in layers. , so that the magnetic beads are subjected to the pressure of the blood layer, and a torque M is generated to make the magnetic beads rotate. In Figure 5, a and b are the distances from both sides of the magnetic bead to the center O of the detection cup, and satisfy b=a+2R (R is the radius of the magnetic bead).

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

In the formula, Φ is the rotation angle of the detection cup (°); t is the time it takes for the detection cup to rotate the Φ angle (s); ω is the angular velocity of the detection cup (rad/s).

When the test cup just starts to rotate, the speed of the liquid layer at the distance b from the center O of the test cup (that is, the liquid layer in direct contact with the test cup) is V _b , and the liquid layer at a distance from the center O of the test cup is in a static state, That is, the velocity Va of the liquid layer at _a is equal to 0. The linear velocity of the liquid layer on both sides of the magnetic bead satisfies the following relationship:

Va ₌ 0 Equation 2

V _b =ωb Equation 3

In the formula, a and b respectively represent the distance (cm) from both sides of the magnetic bead to the center O of the detection cup. V _a and V _b represent the linear velocity of the liquid layer on both sides of the magnetic bead, respectively.

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 across the liquid layer on both sides of the magnetic bead.

At the distance x from the center of the magnetic bead, take a tiny annular surface element, as shown in Figure 6. The area S of the annular surface element shown by the oblique line is:

get

where y' is dy/dx;

The above formula has high-order infinitesimals, which can be approximated to 0;

S=2πRd _x Formula 7

In the formula, R represents the radius R (cm) of the magnetic bead.

Let τ be the shear stress on the unit surface element, and the internal friction force acting on any layer between two adjacent flow layers is proportional to the contact area of the two adjacent layers, namely S, then the tangential force acting on it is :

F _{tangential force} = 2πτRd _x formula 8

The moment of this force on the center O of the detection cup is:

M'=2πτRd _x a Equation 9

Then the moment M of the liquid acting on the entire force spherical surface of the magnetic bead (the hemisphere is affected by the viscous force) is:

According to Newton's Viscosity Law:

where η represents the viscosity of the blood to be tested. Substitute into Equation 10 to get:

M=πηωabR Equation 13

which is:

M∝ηωabR Equation 14

where ∝ represents a positive correlation.

The torque M is the internal friction torque acting on the spherical surface of the magnetic bead. At equilibrium, this torque is related to the position where the force of the magnetic bead is balanced. The position of the magnetic bead is reflected by the reading of the differential inductance angular displacement sensor. Therefore, the differential inductance The reading of the angular displacement sensor also reflects the moment of the magnetic bead at equilibrium. It can be seen from Equation 14 that the reading of the differential inductive angular displacement sensor is the product of the blood viscosity η, the detection cup rotation speed ω, the radius R of the magnetic bead and the distance a and b from the magnetic bead to the detection cup center O. The parameters are positively correlated. The rotation speed ω of the detection cup is related to the rotation angle Φ of the detection cup and the time t used to detect the rotation angle Φ of the detection cup, that is, the torque M is also related to the rotation angle and rotation time of the detection cup.

Thus, it can be seen that the detection device and detection method of the present invention represent the change range of the position of the magnetic beads by measuring the reading of the angular displacement sensor, and use the position change and the change of the torque M generated by the blood flowing in layers during the blood coagulation process to the magnetic beads. The positive correlation reflects the changes of blood coagulation, so that the detection of TEG thrombelastogram in the process of blood coagulation can be realized through the dynamic peak curve of the motion amplitude of the magnetic beads. The invention breaks through the traditional double magnetic circuit magnetic bead method for measurement, and realizes the combination of magnetic bead coagulation detection and thromboelastometry detection.

It should be noted that, in this document, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply that these entities or operations are the same. any such actual relationship or sequence exists. Also, reference to "comprising", "comprising" or any other variation is intended to cover non-exclusive inclusion, whereby a process, method, article or device that includes a list of elements includes not only which elements but also not explicitly listed or other elements inherent to such a process, method, article or apparatus. Without further limitation, the term "comprising an element defined does not preclude the presence of additional identical elements in a process, method, article or apparatus comprising said element".

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the invention. Thus, provided that 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 (20)

1. A magnetic bead-based thromboelastometry detection device, characterized by comprising: a detection cup (1), a rotating part (2), an angular displacement sensor (3), a magnetic bead (4) and a magnet (5);

   The detection cup (1) is used for holding blood samples;

   The rotating component (2) is used to drive the detection cup (1) to periodically reciprocate with a predetermined amplitude and frequency;

   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) reciprocate periodically Rotating and moving in the blood sample, the movement amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

   The angular displacement sensor (3) is used for detecting the movement amplitude of the magnetic beads (4) in the blood, and the angular displacement sensor (3) is located below the detection cup (1);

   The magnet (5) is installed on the side of the detection cup for providing magnetic force to the magnetic beads (4) to overcome the viscoelasticity of blood and the static friction force of the magnetic beads in the early stage of coagulation, and to maintain the movement range of the magnetic beads during the detection process.
2. The magnetic bead-based thromboelastometry detection device according to claim 1, wherein the detection cup (1) has a protrusion in the middle, and a channel for the periodic movement of the magnetic beads is left around the protrusion.
3. The magnetic bead-based thromboelastometry detection device according to claim 1, characterized in that, the rotating part (2) comprises a stepper motor (2a) or a cam, and a connector (2b), through which the connector (2b) ) to connect the stepper motor (2a) or the cam with the detection cup (1).
4. The magnetic bead-based thromboelastometry detection device according to claim 1, wherein the magnet (5) is a permanent magnet or an electromagnet with a controllable magnetic force.
5. The magnetic bead-based thromboelastometry detection device 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.
6. The magnetic bead-based thromboelastometry detection device according to claim 1, characterized in that the period of the reciprocating rotation of the detection cup (1) is 3 seconds to 30 seconds.
7. The magnetic bead-based thromboelastography detection device according to claim 1, characterized in that, the diameter of the magnetic bead (4) is 1 mm to 5 mm.
8. The magnetic bead-based thromboelastometry detection device according to claim 1, wherein the inclination angle of the bottom surface of the detection cup relative to the horizontal plane ranges from 0 to 90 degrees.
9. The magnetic bead-based thromboelastometry detection device according to claim 1, characterized in that, the distance between the end of the magnet (5) close to the detection cup and the surface of the inner magnetic bead in the detection cup (1) closest to the end of the magnet The distance is 1mm to 30mm.
10. The magnetic bead-based thromboelastography detection device according to claim 1, characterized in that, the detection device further comprises a signal processing circuit, and the signal processing circuit is used to obtain a magnetic representation from the angular displacement sensor (3) The readings of the bead movement amplitude are established, and the dynamic peak curve of the magnetic bead movement amplitude is established, and the dynamic peak curve is analyzed.
11. The magnetic bead-based thromboelastometry detection device according to claim 1, wherein the reading of the angular displacement sensor (3) is used to reflect the torque M generated by the stratified blood flowing in the blood coagulation process to the magnetic beads , the reading is positively correlated with the blood viscosity η, the detection cup rotation speed ω, the magnetic bead radius R and the product of the distance a and b from the magnetic bead to the detection cup center O.
12. The magnetic bead-based thromboelastometry detection device according to claim 9, wherein the angular velocity ω of the rotation of the detection cup (1) has the following relationship:

    

    In the formula, Φ is the rotation angle of the detection cup; t is the time it takes for the detection cup to rotate the Φ angle; ω is the angular velocity of the detection cup; The velocity of the liquid layer is V _b , and the blood liquid layer at a distance from the center O of the detection cup is in a static state, that is, the velocity V _a of the liquid layer at a is equal to 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; in the formula, a and _{b respectively represent the distance from both sides of the magnetic bead to the center O of the detection cup; Va and V b respectively} represent the linear velocity of the liquid layer on both sides of the magnetic bead; The shear rate 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; at the distance x from the magnetic bead center on the magnetic bead, take a tiny annular surface element, the area S of the annular surface element is approximately S=2πRd _x , where R represents the radius R of the magnetic bead; the tangential force acting on the surface element of the magnetic bead between two adjacent blood flow layers is: F _{tangential force} =2πτRd _x , the tangential force on the detection cup center O The moment is: M′=2πτRd _x a; then the moment M of the blood flow layer acting on the entire force 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 moment M generated by the stratified flow of blood to the magnetic beads during the blood coagulation process and the viscosity η of the blood, the rotation speed of the detection cup ω, the radius of the magnetic beads R and the magnetic beads The product of the distance a and b from the center O of the detection cup is positively correlated.
13. A magnetic bead-based method for detecting thromboelastography, comprising the following steps:

    Drive the detection cup (1) containing the blood sample to periodically reciprocate with a predetermined amplitude and frequency;

    The magnetic beads (4) immersed in the blood sample are moved in the blood sample along with the periodic reciprocating rotation of the detection cup, and the motion amplitude of the magnetic beads (4) is positively correlated with the coagulation strength of the blood;

    The motion 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 motion 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.
14. The magnetic bead-based thromboelastometry detection method according to claim 13, characterized in that the amplitude and angle of the reciprocating rotation of the detection cup (1) ranges from ±2 degrees to ±20 degrees.
15. The magnetic bead-based thromboelastometry detection method according to claim 13, characterized in that, the period of the reciprocating rotation of the detection cup (1) is 3 seconds to 30 seconds.
16. The magnetic bead-based thromboelastometry detection method according to claim 13, wherein the magnetic bead (4) has a diameter of 1 mm to 5 mm.
17. The magnetic bead-based thromboelastometry detection method according to claim 13, wherein the range of the inclination angle of the bottom surface of the detection cup relative to the horizontal plane is 0-90 degrees.
18. The method for detecting thromboelastography based on magnetic beads according to claim 13, characterized in that a magnet (5) is installed on the side of the detection cup to provide magnetic force to the magnetic beads (4) to overcome the viscosity of blood in the initial stage of coagulation. Elasticity and static friction of magnetic beads, as well as maintaining the range of motion of magnetic beads during detection.
19. The magnetic bead-based thromboelastometry detection method according to claim 13, characterized in that, the reading of the angular displacement sensor (3) is used to reflect the torque M generated by the stratified blood flowing in the blood coagulation process to the magnetic beads , the reading is positively correlated with the blood viscosity η, the detection cup rotation speed ω, the magnetic bead radius R and the product of the distance a and b from the magnetic bead to the detection cup center O.
20. The magnetic bead-based thromboelastometry detection method according to claim 19, wherein the angular velocity ω of the rotation of the detection cup (1) has the following relationship:

    

    In the formula, Φ is the rotation angle of the detection cup; t is the time it takes for the detection cup to rotate the Φ angle; ω is the angular velocity of the detection cup; The velocity of the liquid layer is V _b , and the blood liquid layer at a distance from the center O of the detection cup is in a static state, that is, the velocity V _a of the liquid layer at a is equal to 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; in the formula, a and _{b respectively represent the distance from both sides of the magnetic bead to the center O of the detection cup; Va and V b respectively} represent the linear velocity of the liquid layer on both sides of the magnetic bead; The shear rate 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; at the distance x from the magnetic bead center on the magnetic bead, take a tiny annular surface element, the area S of the annular surface element is approximately S=2πRd _x , where R represents the radius R of the magnetic bead; the tangential force acting on the surface of the magnetic bead between two adjacent blood flow layers is: F _{tangential force} = 2πτRd _x , the tangential force on the detection cup center O The moment is: M′=2πτRd _x a; then the moment M of the blood flow layer acting on the entire force 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 moment M generated by the stratified flow of blood to the magnetic beads during the blood coagulation process and the viscosity η of the blood, the rotation speed of the detection cup ω, the radius of the magnetic beads R and the magnetic beads The product of the distance a and b from the center O of the detection cup is positively correlated.

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