WO2020132926A1

WO2020132926A1 - Blood sample analysis method and blood coagulation analyzer

Info

Publication number: WO2020132926A1
Application number: PCT/CN2018/123800
Authority: WO
Inventors: 郭文恒; 章姚辉; 闫华文; 孙骁
Original assignee: 深圳迈瑞生物医疗电子股份有限公司; 北京深迈瑞医疗电子技术研究院有限公司
Priority date: 2018-12-26
Filing date: 2018-12-26
Publication date: 2020-07-02
Also published as: CN112955742A

Abstract

Disclosed are a blood sample analysis method and a blood coagulation analyzer. The blood sample analysis method based on the blood coagulation analyzer comprises: performing optical detection on an object to be detected contained in a reaction vessel to obtain an optical detection result, wherein the object to be detected comprises at least the plasma of a blood sample to be detected; obtaining interferent information reflecting the interferents in the object to be detected based on the optical detection result (803); determining a blood coagulation detection method for the blood sample to be detected based on the interferent information (804); when the interferents in the object to be detected do not influence a detection result of a blood coagulation detection item based on an optical method, performing a blood coagulation detection on the object to be detected based on the optical method (806); and when the interferents in the object to be detected influence the detection result of the blood coagulation detection item based on the optical method, performing the blood coagulation detection on the object to be detected based on a magnetic bead method (805).

Description

Blood sample analysis method and coagulation analyzer

Technical field

The invention relates to a medical device, in particular to a blood sample analysis method and a blood coagulation analyzer.

Background technique

The blood coagulation analyzer is used to measure the content of various components in human blood in clinical medicine and quantify the results of biochemical analysis, providing a reliable digital basis for clinical diagnosis of various diseases in patients. The measurement methods of the existing coagulation analyzer mainly include coagulation method, immunoturbidimetry method and chromogenic substrate method. Among them, the coagulation method is to detect the change of a series of physical quantities (light, electricity, mechanical motion, etc.) of plasma under the action of a triggering reagent (also called coagulation activator), and then analyze the data obtained by the computer and convert it into the final result . At present, the specific implementation of coagulation method can usually be divided into magnetic bead method and optical method, which are mainly used in prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin Time (TT) and related coagulation factor and other derivative testing.

Since the magnetic bead method and the optical method are two independent detection methods that are different in detection principle and detection components, the current mainstream instrument manufacturers either use the magnetic bead method, such as Stargo, in the choice of the coagulation method implementation method (STAGO) companies, either using optical methods, such as Wolfen (IL) and Sysmex (SYSMEX).

The magnetic bead method directly uses the coagulation reaction, and the fibrinogen in the plasma is converted into fibrin, and the viscosity in the plasma is increased. The test result is obtained by detecting the swing amplitude of the magnetic bead in the test cup.

The optical method is to use the optical principle to probe the change of the turbidity of the test sample in the test cup. Its advantage is that it can output the optical information curve in the test process, so that it can give more valuable judgments on the results and instrument status compared with the magnetic bead method. However, the disadvantage of the optical method is that it is easily interfered by the color of the sample itself, so that the correct result cannot be obtained or the result cannot be output. As shown in Figure 5 is an exemplary hemoglobin, bilirubin, chylous and other interfering substances spectral curve, the horizontal axis is the wavelength (unit nm), the vertical axis is the absorbance, through observation can be found that the three substances are different The wavelength has different absorbances, reflecting that the three interferences have different absorption capabilities for light of different wavelengths, especially chyle, which has absorbance in the visible range of 340nm-790nm, which means that when the object contains When there is a large amount of chyle, irradiating the test object with visible light will absorb a large amount of light by the chyle, which will affect the results of the optical method for blood coagulation detection.

technical problem

The invention mainly provides a blood sample analysis method and a blood coagulation analyzer. Before the blood coagulation item is detected, the blood sample analysis method based on the blood coagulation analyzer first determines whether the sample has interference, and determines whether to use the optical method or the magnetic bead method according to the judgment result Coagulation test, which solves the problem of inaccurate optical detection or inability to output test results due to interference.

Technical solution

According to a first aspect, an embodiment provides a blood sample analysis method, including:

Perform optical detection on the test object contained in the reaction vessel to obtain an optical test result. The test object contains at least the plasma of the blood sample;

Obtain interference information reflecting the situation of interfering substances in the test object according to the optical detection results, where interfering substances refer to substances that have an influence on the detection result of the blood coagulation detection item based on the optical method;

Determine the coagulation detection method for the blood sample to be tested according to the information of the interference;

When the interference in the test object does not affect the detection result of the coagulation test item based on the optical method, the processor controls the optical method detection device to perform the coagulation test on the test object based on the optical method;

When the interference in the test object will affect the detection result of the coagulation detection item based on the optical method, the processor controls the magnetic bead method detection device to perform the coagulation detection on the test object based on the magnetic bead method.

According to a second aspect, an embodiment provides a blood sample analysis method based on a coagulation analyzer, including:

Obtain the information of interfering substances reflecting the situation of interfering substances in the blood sample to be tested. Interfering substances refer to substances that have an influence on the coagulation detection based on optical method;

According to the interference information, it is determined whether the blood sample to be tested is coagulated based on the optical method or the magnetic bead method.

According to a third aspect, an embodiment provides a coagulation analyzer including a pre-judgment device, an optical method detection device, a magnetic bead method detection device, an object transport mechanism and a processor;

The pre-judgment device is used to perform optical detection on the test object before performing the coagulation test under the control of the processor to obtain an optical detection result. The test object contains at least the plasma of the blood sample;

The optical method detection device is used to perform coagulation detection on the measured object based on the optical method under the control of the processor, and output an electrical signal reflecting the coagulation situation;

The magnetic bead method detection device is used to perform coagulation detection on the measured object based on the magnetic bead method under the control of the processor, and output an electrical signal reflecting the coagulation situation;

The analyte transfer mechanism is used to transfer the reaction container containing the analyte to a preset position under the control of the processor;

The processor is used to determine whether the optical method detection device performs coagulation detection on the test object or the magnetic bead method detection device performs coagulation detection on the test object according to the optical detection result, and receives the electrical signal reflecting the coagulation condition, and obtains the test blood sample after processing Measurement parameters.

According to a fourth aspect, an embodiment provides an optical method detection device, a magnetic bead method detection device, a test object transport mechanism, and a processor;

The processor is used to obtain interference information reflecting the condition of the interference in the blood sample to be tested, and determine whether the optical method detection device performs coagulation detection on the test object or the magnetic bead method detection device performs coagulation detection on the test object according to the interference information And receive the electrical signal reflecting the coagulation situation, and obtain the measured parameters of the blood sample after processing. The interfering substance refers to the substance that has an influence on the coagulation detection based on the optical method.

According to a fifth aspect, an embodiment provides a blood coagulation analyzer including: an optical method detection device, a magnetic bead method detection device, an object transport mechanism and a processor;

The magnetic bead method detection device is used to perform coagulation detection on the object under the control of the processor based on the magnetic bead method, and output an electrical signal reflecting the coagulation condition; the detection area of the magnetic bead method detection device and the optical method detection device are The same detection area;

The test object transfer mechanism is used to transfer the reaction container containing the test object to the common detection area under the control of the processor;

The processor is used to control the coagulation detection of the test object by the optical method detection device. When the optical method detection device detects inaccuracy or fails to output an electrical signal reflecting coagulation, the magnetic bead method detection device coagulates the test object Detection.

According to a sixth aspect, an embodiment provides a computer-readable storage medium including a program, where the program can be executed by a processor to implement the above method.

Beneficial effect

According to the blood sample analysis method and the coagulation analyzer of the above embodiment, before the coagulation item test, first determine whether the sample is disturbed, and determine whether to use the optical method or the magnetic bead method to perform the coagulation item test according to the judgment result; or preferentially use the optical method Carry out blood coagulation test. When the sample does not affect the detection result of the coagulation test item based on the optical method, the optical method is used to detect the coagulation item of the sample; when the sample will affect the detection result of the coagulation test item based on the optical method, the magnetic beads are used Method for testing the blood coagulation items. This method solves the problem of inaccurate optical detection or inability to output detection results due to interference.

BRIEF DESCRIPTION

FIG. 1 is a schematic diagram of component modules of a coagulation analyzer according to an embodiment;

2 is a schematic structural diagram of a magnetic bead detection device according to an embodiment;

3a is a timing diagram of applying PWM waves to a driving coil according to an embodiment;

FIG. 3b is a schematic diagram of an electric signal of magnetic bead movement according to an embodiment;

4 is a schematic structural diagram of an optical method detection device according to an embodiment;

FIG. 5 is a spectral curve diagram of an interferer according to an embodiment;

6 is a schematic structural view of an embodiment where the optical method detection area and the magnetic bead method detection area are located in the same detection area;

7 is a schematic diagram of multi-channel detection according to an embodiment;

8 is a flowchart of a blood sample analysis method according to an embodiment;

9 is a flowchart of an optical detection method according to an embodiment.

Embodiments of the invention

detailed description

The present invention will be further described in detail below through specific embodiments and drawings. Corresponding similar element labels are used for similar elements in different embodiments. In the following embodiments, many details are described so that the present application can be better understood. However, those skilled in the art can easily recognize that some of the features may be omitted in different situations, or may be replaced by other elements, materials, and methods. In some cases, some operations related to this application are not shown or described in the specification. This is to avoid the core part of this application being overwhelmed by too many descriptions. For those skilled in the art, describe these in detail Related operations are not necessary, they can fully understand related operations according to the description in the specification and general technical knowledge in the field.

In addition, the features, operations, or characteristics described in the specification may be combined in any appropriate manner to form various embodiments. At the same time, the steps or actions in the method description can also be sequentially replaced or adjusted in a manner obvious to those skilled in the art. Therefore, the various orders in the specification and the drawings are only for clearly describing a certain embodiment, and are not meant to be a necessary order, unless otherwise stated that a certain order must be followed.

The serial numbers themselves, such as "first", "second", etc., are used to distinguish the described objects, and do not have any order or technical meaning. The "connection" and "connection" mentioned in this application, unless otherwise specified, include direct and indirect connection (connection).

A

In the embodiment of the present invention, before detecting the coagulation item, it is first determined whether the sample is disturbed, and it is determined whether to apply the optical method or the magnetic bead method to perform the coagulation item detection according to the determination result. When the sample does not affect the detection result of the coagulation test item based on the optical method, the optical method is used to detect the coagulation item of the sample; when the sample will affect the detection result of the coagulation test item based on the optical method, the magnetic beads are used Method for testing the blood coagulation items.

Please refer to FIG. 1, which shows a schematic structural diagram of a blood coagulation analyzer according to an embodiment of the present invention. The blood coagulation analyzer includes a sample placement area 11, a sample collection mechanism 12, a reagent placement area 13, a reagent collection mechanism 14, and a reaction vessel The placement area 10, the object transfer mechanism 15, the pre-judgment device 16, the optical method detection device 18, the magnetic bead method detection device 17, and the processor 19.

The sample placement area 11 is used to provide a place where the test sample 11a is placed. The test sample may be plasma after removing blood cells, for example, plasma obtained by centrifuging the blood sample. In the illustration, the sample placement area 11 is a rectangular area where multiple samples 11a can be placed. In an actual instrument, the sample placement area 11 may also be a bar-shaped or circular area, or it may be only a location where the sample is placed.

The reagent placement area 13 is used to provide a place where the test reagent 13a is placed. In the illustration, the reagent placement area 13 is a rectangular area in which multiple test reagents 13a can be placed. In an actual instrument, the reagent placement area 13 may also be a bar or circular area. The reagent includes at least one of a diluent, a mixed reagent, and a trigger reagent.

The reaction container placement area 10 is used to provide a place for placing the test reaction container 10a. In the illustration, the reaction vessel placement area 10 is a rectangular area, and a plurality of reaction vessels 10a can be placed. In an actual instrument, the reaction vessel placement area 10 may also be a bar or circular area.

The sample collection mechanism 12 is used to collect the tested sample from the sample placement area 11 and add the measured sample to the reaction container 10a placed on the reaction container placement area 10, and the reagent collection mechanism 14 is used to collect the reagent from the reagent placement area 13 And add the reagent to the reaction container 10a placed on the reaction container placement area 10. The sample to be tested and the reagent are mixed and reacted in the reaction vessel 10a to form a sample. In some embodiments, the sample collection mechanism 12 and the reagent collection mechanism 14 may also be two-dimensional moving parts with a sampler, which can be collected in the sample placement area 11 or the reagent placement area 13 by two-dimensional movement in the plane The tested sample or reagent is added to the reaction container 10a placed on the reaction container placement area 10.

In a specific embodiment, the reaction container placement area 10 also has the function of incubation. The sample to be tested and the reagent are mixed in the reaction container 10a and then placed on the reaction container placement area 10 for incubation. After the incubation is completed, the test object The transfer mechanism 15 transfers to the corresponding detection position for detection. In some embodiments, the reaction container placement area 10 does not have an incubation function. After the test sample and the reagent are mixed in the reaction container 10a, the test object transport mechanism 15 needs to be transferred to the incubation position for incubation.

The magnetic bead method detection device 17 is used to detect the coagulation item based on the magnetic bead method on the sample (analyte) mixed with the test sample and the reagent under the control of the processor, and output an electrical signal reflecting the coagulation condition to the processing器19。 19. The area where the sample is tested for coagulation based on the magnetic bead method is called the magnetic bead method detection area.

In one embodiment, the structure of the magnetic bead method detection device 17 is shown in FIG. 2, which may include a driving coil 210 and a measurement coil 220. The structure of the reaction vessel used in the magnetic bead method is shown in FIG. 2. In FIG. 2, the reaction container 200 is subjected to a cross-sectional process. A magnetic bead 201 is placed in the accommodating chamber of the reaction container 200, and the bottom of the reaction container is provided for the magnetic bead 201 to move under the drive of a magnetic field. For convenience of description, the reaction container 200 has a length direction extending along the motion track of the magnetic beads and a width direction perpendicular to the length direction. In the embodiment of the present application, the magnetic bead is made of a material that can be quickly magnetized and demagnetized. When the magnetic bead is in a magnetic field, it can be quickly magnetized by the magnetic field. When the magnetic field disappears, the magnetic bead can be quickly demagnetized. The shape of the magnetic bead may be spherical or other shapes, such as a polyhedron, which are only exemplified here and not specifically limited. Optionally, the detection device 16 may include an even array of drive coils 210, for example, there may be two sets of drive coils 210, and the two sets of drive coils 210 are located opposite each other at a certain distance, and are located on both sides of the reaction vessel 200 along the length of the reaction vessel 200, respectively. . The two driving coils 210 are applied with PWM waves of the same period but different timing. As shown in FIG. 3a, the period M1 and the period M2 are the periods during which the driving coil M1 and the driving coil M2 generate magnetic fields, respectively, thereby generating intermittent magnetic fields alternately (in During the period t1 and t2, the driving coil M1 generates a magnetic field in the illustrated period M1; during the period t3 and t4, the driving coil M2 generates a magnetic field in the illustrated period M2; and so on), the magnetization is repeated by the magnetic field The beads cause the magnetic beads 201 in the reaction container 200 to oscillate along the orbit formed by the reaction container.

Optionally, the detection device 16 may include an even-numbered array of measurement coils 220, for example, may include two sets of measurement coils 220, and the two sets of measurement coils 220 are located opposite each other at a certain distance, and are located on both sides of the reaction vessel 200 along the width direction of the reaction vessel 200, respectively. . The two sets of measuring coils 220 are divided into a transmitting coil and a receiving coil. The two ends of the transmitting coil are connected to a signal transmitting circuit (not shown in the figure), which is used to input a sine wave alternating current and used to generate a continuous magnetic field. The two ends of the receiving coil are connected A signal receiving circuit (not shown in the figure) to detect the motion electrical signal generated by the oscillating motion of the magnetic bead 201. The movement electrical signal refers to an electrical signal that can reflect the movement state of the magnetic bead 201. The transmitting coil generates a magnetic field, and the magnetic beads cut the magnetic field lines to change the path of the magnetic field lines, thereby changing the magnetic flux received by the receiving coil. The receiving coil generates the original induced electromotive force according to the received magnetic flux to generate a corresponding induced current. The induced current undergoes circuit conversion and signal Conditioning can obtain a voltage signal containing motion information of the magnetic bead 201, that is, a motion electrical signal of the magnetic bead 201. Since the motion of the magnetic bead 201 changes the characteristics of the original induced current, the motion information of the magnetic bead 201 can be extracted from the changed induced current.

As shown in FIG. 2, in one embodiment, two sets of driving coils 210 and two sets of measuring coils 220 are arranged to cross each other, and the reaction vessel 200 is between two sets of driving coils 210 and at the same time between two sets of measuring coils 220. Under the action of the driving electromagnetic field, the magnetic beads 201 can move in the sample to be tested in the reaction container 200.

When the magnetic bead 201 moves in the reaction vessel 200, the measuring coil 220 generates a corresponding induced current, which reflects the movement of the magnetic bead 201 and can be used as the motion electrical signal of the magnetic bead 201. Of course, the induced current generated by the measuring coil 220 may be converted to obtain a voltage signal, and the voltage signal may be used as the motion electrical signal of the magnetic bead 201.

The measurement coil 220 transmits the motion electric signal of the magnetic bead 201 obtained by the detection to the processor. Alternatively, the measurement coil 220 may be connected to the processor through a signal conversion circuit (not shown) and a signal conditioning circuit (not shown). For example, the signal conversion circuit can perform analog-to-digital conversion on the motion electrical signal of the magnetic bead 201 acquired by the measuring coil 220 for at least a period of time, and the signal conditioning circuit can be capable of converting the magnetic bead 201 acquired by the measurement coil 220 for at least a period of time. The motion electric signal is preprocessed such as rectification, filtering and normalization. FIG. 3b is a schematic diagram of the movement electrical signal of the magnetic bead 201 in a period of time in an embodiment, wherein the movement electrical signal of the magnetic bead 201 may be a voltage signal. In this embodiment, the magnetic bead 201 is in the reaction vessel Reciprocating motion within 200, the electric signal of the magnetic bead 201 in a period of time presents a sinusoidal distribution, as shown in the figure.

The optical method detection device 18 is used to detect the coagulation item based on the optical method of the sample (analyte) mixed with the test sample and the reagent under the control of the processor 19, and output an electrical signal reflecting the coagulation condition to the processor 19. The area where the sample is tested for coagulation based on the optical method is called the optical detection area.

In an embodiment, the structure of the optical method detection device 400 is shown in FIG. 4, and may include a light source 410 for performing optical method detection, a lens assembly 420, a filter 430 and a receiving unit 450. In the present application, a halogen lamp may be used as the light source 410. Preferably, the halogen lamp is accommodated in a lamp case having a plurality of heat sinks. The heat sinks are used to cool the heat generated by the light source 410 due to heat generation. The lens assembly 420 is composed of a plurality of condensers, and is used to converge and collimate the scattered light emitted by the light source 410. The lens assembly 420 is disposed on the optical path that guides the light irradiated by the light source 410 to the sample 440 (object to be measured).

In the embodiment of the present application, the filter 430 may be a disc shape, a polygon, etc. In a preferred embodiment, the filter 430 is a disc shape, which can be rotated around the center of the circle under the drive of a motor . The filter 430 is provided with a plurality of holes. In one embodiment of the present application, six holes are provided on the filter 430 as an example for description. For other cases, refer to this embodiment for the same or similar applications. As shown in the figure, the hole 431 is a hole to block the opaque light, and the remaining five holes 432 are used to install five filters with different transmission wavelengths. For example, the five filters only transmit 340nm, 405nm, and 575nm, respectively , 660nm and 800nm light, other wavelengths of light are not transmitted, the hole 431 can be a spare hole, only need to add an optical film before installing the optical film. The 6 holes are provided along the rotation direction of the filter 430 at a certain angular interval. With the rotation of the filter 430, the filter can be rotated to the optical path, so that the light only passes through the filter after passing through the filter Only the light with the matching wavelength of the film can pass through and illuminate the reaction container behind for optical detection.

When performing the coagulation test on the sample in the reaction container based on the optical method, different coagulation items require light irradiation of a specific wavelength. For example, the prothrombin time (PT) test item requires 405nm wavelength light to illuminate the sample, so The processor controls the motor to rotate the 405 nm wavelength filter on the filter 430 onto the optical path. The thrombin time (TT) test item requires 660nm wavelength light to illuminate the sample, so the processor controls the motor to rotate the 660nm wavelength filter on the filter 430 to the optical path.

The receiving unit 450 is connected to the processor. The receiving unit 450 is used to collect transmitted light and/or scattered light after the sample is irradiated with light of a specific wavelength, convert the optical signal into an electrical signal, and transmit the electrical signal to the processor. After the processor processes the electrical signal, the measurement parameters of the blood sample to be measured are obtained.

Of course, in other embodiments, the optical method detection device 400 may not use the above halogen lamp solution, but adopt LEDs with multiple wavelengths, and combine the beams emitted by the multiple LEDs through a dichroic mirror corresponding to the LEDs. Or, a light combining prism is used to combine multiple wavelength beams, that is, the detection structure or detection method of the optical method detection device 400 is not limited, and details are not described herein again.

As shown in Fig. 5 is an exemplary hemoglobin, bilirubin, chyle and other interfering substances spectral curve, the horizontal axis is the wavelength (unit nm), the vertical axis is the absorbance, the inventor noticed that the three substances are different The wavelength has different absorbances, reflecting that the three interferences have different absorption capabilities for light of different wavelengths, especially chyle, which has absorbance in the visible range of 340nm-790nm, which means that when the object contains When there is a large amount of chyle, irradiating the test object with visible light will absorb a large amount of light by the chyle, which will affect the results of coagulation detection based on the optical method.

Therefore, in the embodiment of the present invention, a pre-judgment link is added before the formal coagulation test is performed to determine whether the sample to be tested contains an interferer that has an effect on the coagulation detection result based on the optical method.

In this embodiment, the pre-judgment device 16 is used to perform optical detection on the test object before performing coagulation detection under the control of the processor 19 to obtain an optical detection result. The test object detected by the pre-judgment device 16 contains at least the test sample, that is, the test object may be plasma, or a mixture of plasma and reagent (sample), and the reagent includes at least the diluent, mixed reagent, and trigger reagent. One kind. The detection position where the pre-judgment device 16 optically detects the object may be a dedicated position, or may be an incubation area, an optical method detection area, or a magnetic bead method detection area.

In an embodiment of the present application, the pre-judgment device 16 includes a photodetection device, and the photodetection device includes a light emitting end and a light receiving end, wherein the light emitting end is used to adopt at least one kind of specific wavelength light or the wavelength is close to the specific wavelength The specific light refers to the wavelength of light used when the coagulation item is detected by the optical method. The light receiving end is used to detect the optical information of the light of the test object after being subjected to light, to obtain the optical detection result of the test object for light of each specific wavelength. The optical information may be the transmitted and/or scattered light intensity after the light beam passes through the measured object. The light receiving end is signally connected to the processor 19, and is used to send the obtained optical detection result to the processor 19.

In some embodiments, the light emitting end of the pre-judgment device 16 is connected to the optical method detection device, and the light beam that irradiates the object to be measured is the light beam that is filtered by the filter 430 and then split through the optical fiber; when the pre-judgment When the detection position where the device 16 optically detects the object is the optical detection area, the light filtered by the corresponding light-transmitting filter 430 can be directly irradiated to the object without a separate light source. In some embodiments, the light emitting end of the pre-judgment device 16 may also have a separate light source.

In another embodiment of the present application, the pre-judgment device 16 includes an image acquisition device, the image acquisition device is used to collect image data (such as photos) of the object to be measured, to obtain an optical detection result, and send the optical detection result to the processor 19. In a specific embodiment, the image acquisition device may be a camera for capturing image data.

The processor 19 is used to obtain the interference information reflecting the condition of the interference in the blood sample to be tested, and to determine whether the optical method detection device performs coagulation detection on the test object or the magnetic bead method detection device performs coagulation on the test object based on the interference information Detect and receive the electrical signal reflecting the coagulation situation, and then process the electrical signal to obtain the measurement parameters of the blood sample to be measured. Among them, the interfering substance refers to the substance that has an influence on the coagulation detection based on the optical method.

In an embodiment of the present application, the processor 19 obtains interference information reflecting the condition of the interference in the test object according to the optical detection result. For example, the light emitting end of the pre-judgment device 16 is irradiated with light of at least one specific wavelength The test object, the light receiving end receives the transmitted light and/or scattered light of the test object after being irradiated with light, and the processor 19 calculates the test object for each specific wavelength of light based on the optical information received from the light receiving end of the pre-judgment device 16 When the absorbance value of at least one specific wavelength light is greater than the preset threshold value, it means that the sample will absorb the specific wavelength light, and the interference in the test object will be detected by the optical method for the detection of blood coagulation. The results have an impact. Wherein, the preset threshold has different values for different specific wavelengths of light, which may be the system default setting value, or a value set by the user based on experience or experimental data. In this embodiment, when the interference in the test object does not affect the detection result of the coagulation test item based on the optical method, or the test result of the coagulation test item based on the optical method does not exist in the test object When an interferer is affected, the processor controls the optical method detection device to perform coagulation detection on the object based on the optical method; when the interference in the object will affect the detection result of the coagulation detection item based on the optical method, or When it is said that there is an interfering substance that affects the detection result of the coagulation detection item based on the optical method, the processor controls the magnetic bead method detection device to perform coagulation detection on the object based on the magnetic bead method. The interfering substance refers to a substance that absorbs light of a specific wavelength, wherein the specific wavelength refers to at least one of the wavelengths of light used when performing coagulation detection on a mixed sample of plasma and reagent by an optical method.

In another embodiment, the test object may be irradiated with light close to a specific wavelength, and it may also be determined whether there is an interfering substance that will affect the detection result of the coagulation test item based on the optical method.

In another embodiment of the present application, the processor 19 recognizes the color of the test object based on the image data (such as a photo) received from the pre-judgment device 16 and compares the color of the test object with the preset color. When the color of the object is the same as or close to the preset color, it is judged that the interference in the object will affect the detection result of the blood coagulation detection item based on the optical method. Among them, the preset color is the color of the image data obtained when there is no interference in the test object, which can be the default color set by the system or the color set by the user based on experience or experimental data. In this embodiment, when the interference in the test object does not affect the detection result of the coagulation detection item based on the optical method, the processor controls the optical method detection device to perform coagulation detection on the test object; when the test object When the interfering substance in the test will affect the detection result of the coagulation detection item based on the optical method, the processor controls the magnetic bead method detection device to perform coagulation detection on the test object.

In some embodiments, as shown in FIG. 6, the optical detection area based on the optical method for coagulation detection and the magnetic bead detection area based on the magnetic bead method are the same detection area. The reaction container used for the magnetic bead method for coagulation detection is the same device as the container for holding the sample which is used for the optical method for coagulation detection. When the magnetic bead method is used for detection, the magnetic beads need to be placed at the bottom of the reaction vessel. When the magnetic bead method is used for coagulation detection, the magnetic beads move under the drive of the driving coil, and the measurement coil obtains the movement of the magnetic beads according to the generated induced electromagnetic field. The generated electrical signals are sent to the processor; when using the optical method for coagulation detection, there is no need to place magnetic beads in the reaction vessel, and the emission fiber uses at least one light of a specific wavelength or a light pair with a wavelength close to a specific wavelength The test object in the reaction vessel is irradiated, and the receiving optical fiber transmits the received light information to the photoelectric conversion unit to obtain an electric signal. The magnetic beads can only be placed in the reaction container when the magnetic bead method is used for detection, and there are no magnetic beads in the reaction container when the optical method is used for detection. In this case, the coagulation analyzer also includes Pick-and-place device; of course, in some embodiments, the magnetic beads can always be placed in the reaction vessel. When performing optical detection, the magnetic beads will always remain at the bottom of the reaction vessel. In this case, the coagulation analyzer does not need to be used for pick-and-place Magnetic bead pick and place device.

As shown in FIG. 7, in some embodiments, the analyzer may also be provided with multiple detection areas as shown in FIG. 6 for detecting multiple samples at the same time, and each detection area may share an optical irradiation unit , The beam is directed to each detection area by a beam splitter to illuminate each object to be measured. If the position where the pre-judgment device performs optical detection on the object is not in this area, the beam can also be directed to the optical detection position (for example, dedicated position, incubation area, etc.) through the beam splitter.

In another embodiment of the present application, the coagulation analyzer may not include a pre-judgment device, and the pre-judgment result of the sample to be tested may come from other modules connected online, that is, to obtain information reflecting the condition of interfering substances in the blood sample to be tested. The information of interfering substances can come from other on-line instruments, and there is no need to install a pre-judgment device on the coagulation analyzer. Or directly make the magnetic bead method detection device and the optical method detection device share the same detection area; the analyte transport mechanism transports the reaction container containing the analyte to the common detection area under the control of the processor; the processor controls the optical The method detection device performs coagulation detection on the test object. When the optical method detection device detects inaccuracy or fails to output an electrical signal reflecting coagulation, the magnetic bead method detection device performs coagulation detection on the test object.

The blood coagulation analyzer in the above embodiments of the present application is mainly used for performing blood coagulation analysis on the test object. The difference from the prior art is that the blood coagulation analyzer in the present application can use an optical method detection device to measure the object based on the optical method. For the coagulation detection of the substance, the magnetic bead method detection device can be used for the coagulation detection of the analyte based on the magnetic bead method. And because the optical method can output the optical information curve in the test process, so that the result and the state of the instrument can be given more valuable judgment than the magnetic bead method, so the optical method is preferred in practical applications. However, when there are a large number of interfering substances that absorb specific wavelengths in the tested sample, the magnetic bead method is used to detect the coagulation item, which can avoid the influence of the interfering substances on the coagulation detection results based on the optical method.

Please refer to Fig. 8, the blood sample analysis method of pre-judging the test object and then performing coagulation analysis includes the following steps:

Step 801: Start the blood sample analysis program of the coagulation analyzer.

Step 802: Obtain the test item for the blood sample to be tested, and determine whether the test item is a coagulation method item. If the test item is a coagulation method item, perform step 803. If the test item is not a coagulation method item, perform step 807. Select another method. The test object is tested and the test result is output.

Step 803: Perform optical detection on the test object contained in the reaction container to obtain an optical detection result, and obtain interference information reflecting the situation of the interference in the test object according to the optical detection result. According to the coagulation test item of the blood sample to be tested, the specific wavelength used in the subsequent coagulation item test using the optical method can be known. In a preferred embodiment, the specific wavelength is used one by one to the test objects contained in the reaction vessel Light irradiation, and collect the transmitted light and/or scattered light of the test object after light irradiation. Among them, the test object contains at least the plasma of the blood sample to be tested, and the test object in this step may be plasma or a mixture of plasma and reagent.

According to the waterfall effect theory of blood coagulation, after the test sample is mixed with the diluent and/or mixed reagent, and within a period of time just after the trigger reagent is added, it is mainly a cascade reaction of coagulation factors, but no fibrin-bound fibers are formed For protein multimers, the absorbance caused by the cascade reaction changes little at this time. Therefore, if this period of time is analyzed, the absorbance data of the sample can be obtained substantially accurately, so that the condition of the interfering substance can be judged.

For example, for a coagulation test item with a significant luminous flux baseline period within a short period of time after the test sample is added with the trigger reagent, such as some coagulation-based testing items, a more obvious luminous flux baseline period will be formed. During the baseline period of luminous flux, the analyte undergoes a cascade of coagulation factors, so its luminous flux changes little and the luminous flux curve is flat. In this baseline period of luminous flux, the detected absorbance data is only the superposition of the absorbance data of the sample and the reagent absorbance data. Since the reagent absorbance data is known, the absorbance data of the sample to be tested can be obtained, so that the interference can be determined.

For another example, for a period of time after the test sample is added with diluent and mixed reagents (before the trigger reagent is added), the luminous flux of the test sample is basically unchanged. The absorbance data of the test sample before the trigger reagent is added is only the test sample and Superimposition of absorbance data of diluent and mixed reagent. Since the absorbance data of the diluent and mixed reagents are known, the absorbance data of the tested sample can be obtained, so that the condition of the interfering substances can be judged.

Generally, the diluent and mixed reagent are added first, followed by the trigger reagent. In some coagulation tests, it may not be necessary to add diluent and mixed reagents.

Please refer to FIG. 9, the process of optical detection of the measured object in this embodiment includes the following steps 901-903:

Step 901: Irradiate the test object with light of at least one wavelength. Within a set time period after adding the reagent to the sample to obtain the sample, the sample is irradiated with light of a specific wavelength to obtain optical information of scattered light and/or transmitted light after the beam irradiates the sample. Among them, the setting time is set according to the type of reagent added to the sample to be tested and the time of adding the reagent. Here, the light beam comes from the optical method detection device. In another embodiment, it may also be a light source unique to the prediction device.

Step 902: Detect the optical information of the test object after being subjected to light. The optical information includes the absorbance information of the test object. The absorbance information is mainly the superposition of the absorbance data of the test sample and the absorbance data of the reagent. If the absorbance data of the reagent itself is subtracted from the absorbance information of the test sample, the measured value can be obtained. The absorbance data of the sample. Generally, the pre-judgment device detects the luminous flux data, where the luminous flux data includes the luminous flux data of the transmitted light and/or scattered light, and then the absorbance information is determined according to the luminous flux data and the initial luminous flux of the light source, and the absorbance information can be obtained according to the luminous flux data . Therefore, the optical information may also include luminous flux data of scattered light and/or transmitted light after the light beam illuminates the object.

Because interfering substances such as chyle, hemoglobin, and bilirubin have their own absorption spectra, they can be irradiated with multiple beams of different wavelengths. After irradiated with beams of each wavelength, they can be judged according to the absorbance value of the measured substance. The situation of the corresponding interference, for example, whether it contains interference. For example, light beams of various wavelengths can be used to irradiate the object to be measured, and the light beams of each wavelength correspond to three kinds of interfering substances, such as chyle, hemoglobin, and bilirubin, so that the corresponding interfering substances can be judged according to the absorbance values of the light beams of each wavelength. Therefore, in one of the embodiments, more than one wavelength beam is used to illuminate the object.

Step 903: Obtain the optical detection result of the test object according to the optical information. According to the optical information, the absorbance value of the test object for each specific wavelength of light is calculated. When the absorbance value is greater than the preset threshold, it is judged that the interference in the test object will affect the coagulation detection item based on the optical method. Wherein, the preset threshold value is obtained based on the predicted absorbance information of the reagent, the predicted absorbance information of the measured sample without interference, and the predicted ratio information of the tested sample and the reagent. The absorbance information of the reagent and the ratio information of the sample to be tested and the reagent can be obtained from the setting information or detection parameters of the instrument, so it is foreseeable. The ratio information may be volume ratio information or weight ratio information.

In some embodiments, the optical detection further includes: collecting image data (such as a photo) of the measured object, obtaining color information based on the image data, and obtaining interference information reflecting the condition of the interference in the measured object according to the color information to obtain Optical inspection results.

In some embodiments, after obtaining the interference information, the prompt information and/or the alarm information may also be issued according to the interference in the tested sample. For example, the prompt information and/or the alarm information may include: Prompt information and/or warning information of the interference in the system, or prompt information that determines to use the optical method or the magnetic bead method.

After step 803, step 804 may be performed.

Step 804: According to the interference information, determine whether it will affect the detection result of the coagulation detection item based on the optical method, and determine the coagulation detection method used for the blood sample to be tested. When the interference in the sample does not affect the detection method based on the optical method Step 806 is executed when the detection result of the coagulation detection item has an influence, and step 805 is executed when the interference in the test object has an influence on the detection result of the coagulation detection item based on the optical method.

Step 805: The processor controls the magnetic bead method detection device to perform coagulation detection on the test object based on the magnetic bead method, output an electrical signal reflecting the coagulation status, and process the electrical signal to obtain the measurement parameters of the blood sample to be measured.

Step 806: The processor controls the optical method detection device to perform coagulation detection on the test object based on the optical method, output an electrical signal reflecting the coagulation status, and process the electrical signal to obtain the measurement parameters of the blood sample to be measured.

In another embodiment, when it is determined that the detection item is a coagulation item, the method of step 803 may not be used for optical detection of the test object, but the optical method detection device may be used for direct detection of the blood coagulation of the test object. When the detection device detects inaccuracy or fails to output an electrical signal reflecting the coagulation situation, the magnetic bead method detection device is then used to detect the coagulation of the test object.

The present application also provides a coagulation analyzer according to an embodiment, which is used to measure and analyze the number of specific substances related to blood coagulation/fibrinolysis function and the degree of activity thereof, and the specimen is plasma. The coagulation analyzer of the present embodiment measures the specimen by the clotting time method, the chromogenic substrate method, and the immunoturbidimetric method. The coagulation time method used in this embodiment is a measurement method that uses the coagulation process of a specimen as a change in transmitted light detection or a motion change of a magnetic bead in a specimen driven by a magnetic force. The measurement items of the clotting time method include PT (prothrombin time), APTT (activated partial thrombin time), TT (thrombin time), and FIB (fibrinogen amount). The measurement items of the chromogenic substrate method include AT-Ⅲ (antithrombin III), etc., and the measurement items of the immunoturbidimetric method include D-Dimer (D-dimer) and FDP.

This document refers to various exemplary embodiments. However, those skilled in the art will recognize that changes and modifications can be made to the exemplary embodiments without departing from the scope of this document. For example, various operation steps and components for performing operation steps may be implemented in different ways according to a specific application or considering any number of cost functions associated with the operation of the system (for example, one or more steps may be deleted, Modify or incorporate into other steps).

In addition, as understood by those skilled in the art, the principles herein may be reflected in a computer program product on a computer-readable storage medium that is pre-installed with computer-readable program code. Any tangible, non-transitory computer-readable storage medium can be used, including magnetic storage devices (hard disks, floppy disks, etc.), optical storage devices (CD-ROM, DVD, Blu Ray disks, etc.), flash memory, and/or the like . These computer program instructions can be loaded onto a general purpose computer, special purpose computer, or other programmable data processing equipment to form a machine, so that these instructions executed on a computer or other programmable data processing device can generate a device that implements a specified function. These computer program instructions can also be stored in a computer-readable memory, which can instruct the computer or other programmable data processing device to operate in a specific manner, so that the instructions stored in the computer-readable memory can form a piece Manufactured products, including implementation devices that implement specified functions. Computer program instructions can also be loaded onto a computer or other programmable data processing device, so that a series of operating steps are performed on the computer or other programmable device to produce a computer-implemented process that allows the computer or other programmable device to execute Instructions can provide steps for implementing specified functions.

Although the principles herein have been shown in various embodiments, many modifications of structures, arrangements, ratios, elements, materials, and components that are particularly suitable for specific environments and operating requirements can be made without departing from the principles and scope of this disclosure use. The above modifications and other changes or amendments will be included within the scope of this document.

The foregoing specific description has been described with reference to various embodiments. However, those skilled in the art will recognize that various modifications and changes can be made without departing from the scope of the present disclosure. Therefore, consideration of this disclosure will be in an illustrative rather than a restrictive sense, and all such modifications will be included within its scope. Also, there have been the advantages, various advantages, and solutions to the problems of the various embodiments described above. However, benefits, advantages, solutions to problems, and any elements that can produce these, or solutions that make them more explicit, should not be interpreted as critical, necessary, or necessary. The term "comprising" and any other variants used in this article are non-exclusive, so that a process, method, article, or device that includes a list of elements includes not only these elements, but also those that are not explicitly listed or do not belong to the process , Methods, systems, articles or other elements of equipment. Furthermore, the term "coupled" and any other variations thereof used herein refer to physical connection, electrical connection, magnetic connection, optical connection, communication connection, functional connection, and/or any other connection.

Those skilled in the art will recognize that many changes can be made to the details of the above-described embodiments without departing from the basic principles of the invention. Therefore, the scope of the present invention should be determined according to the following claims.

Claims

A blood sample analysis method, characterized in that the method includes:

Performing optical detection on the test object contained in the reaction vessel to obtain an optical test result, where the test object contains at least plasma of the blood sample;

Obtain interference information reflecting the condition of the interference in the object according to the optical detection result, where the interference refers to a substance that has an influence on the detection result of the coagulation detection item based on the optical method;

Determine the coagulation detection method for the blood sample to be tested according to the interference information;

When the interference in the test object does not affect the detection result of the coagulation detection item based on the optical method, the processor controls the optical method detection device to perform coagulation detection on the test object based on the optical method;

When the interference in the test object will affect the detection result of the coagulation detection item based on the optical method, the processor controls the magnetic bead method detection device to perform the coagulation detection on the test object based on the magnetic bead method.
The method according to claim 1, wherein the interfering substance refers to a substance that absorbs light of a specific wavelength, and the specific wavelength refers to light used for coagulation detection of a mixed sample of plasma and reagents by an optical method At least one of the wavelengths.
The method of claim 2, wherein the optical detection comprises:

Use at least one wavelength of light to illuminate the measured object;

Detecting the optical information of the test object after being subjected to light;

Obtain the optical detection result of the test object according to the optical information.
The method according to claim 3, wherein the optical information is transmission and/or scattered light intensity after the light beam passes through the object to be measured.
The method according to claim 3 or 4, further comprising calculating the absorbance value of the test object for each specific wavelength of light based on the optical information.
The method according to claim 5, wherein when the absorbance value is greater than a preset threshold, it is determined that the interference in the test object will affect the coagulation detection item based on the optical method.
The method according to claim 3, wherein the object to be measured is irradiated with light of at least one specific wavelength.
The method according to claim 1, wherein the optical detection comprises: collecting image data of the object to obtain an optical detection result.
8. The method according to claim 8, wherein color information is obtained based on the image data, and interference information reflecting the condition of the interference in the object is obtained based on the color information.
The method according to any one of claims 1-9, wherein the analyte in the optical detection of the analyte contained in the reaction vessel is plasma or a mixture of plasma and reagents, and the reagents include At least one of diluent, mixed reagent, and trigger reagent.
The method according to any one of claims 1 to 9, characterized in that the optical detection is performed on the test object in a dedicated position, an incubation area, an optical detection area, or a magnetic bead detection area provided for optical detection.
The method according to any one of claims 1-9, wherein magnetic beads are placed inside the reaction vessel, and the reaction vessel has a bottom for the magnetic beads to move under driving force.
A blood sample analysis method based on a blood coagulation analyzer, which includes:

Obtain interference information that reflects the condition of interferences in the blood sample being tested. The interferences refer to substances that have an effect on the detection of blood coagulation based on optical methods;

According to the interference information, it is determined whether the blood sample to be tested is subjected to coagulation detection based on the optical method or the magnetic bead method.
The method according to claim 13, wherein determining whether to perform coagulation detection on the blood sample to be tested based on the optical interference method or the magnetic bead method based on the interference information includes:

When the interfering substance in the test object will not affect the coagulation detection based on the optical method, apply the optical method detection device to perform the coagulation detection on the test object;

When the interference in the test object will affect the coagulation detection based on the optical method, the magnetic bead method detection device is used to perform the coagulation detection on the test object.
The method according to claim 13, wherein the interfering substance refers to a substance that absorbs light of a specific wavelength, and the specific wavelength refers to light used for coagulation detection of a mixed sample of plasma and reagents by an optical method At least one of the wavelengths.
The method according to any one of claims 1 to 15, wherein the optical method detection area for performing coagulation detection based on the optical method and the magnetic bead method detection area for performing coagulation detection based on the magnetic bead method are the same detection area.
The method according to any one of claims 1 to 15, further comprising: outputting prompt information for determining whether to use an optical method or a magnetic bead method.
A blood coagulation analyzer, characterized in that it includes a pre-judgment device, an optical method detection device, a magnetic bead method detection device, an object transport mechanism and a processor;

The pre-judgment device is used for performing optical detection on the test object before performing the blood coagulation test under the control of the processor to obtain an optical detection result, where the test object includes at least plasma of the blood sample;

The optical method detection device is used for performing coagulation detection on the measured object based on the optical method under the control of the processor, and outputs an electrical signal reflecting the coagulation situation;

The magnetic bead method detection device is used to perform coagulation detection on the measured object based on the magnetic bead method under the control of the processor, and output an electrical signal reflecting the coagulation situation;

The test object transfer mechanism is used to transfer the reaction container containing the test object to a preset position under the control of the processor;

The processor is used to determine whether the optical method detection device performs coagulation detection on the analyte or the magnetic bead method detection device performs coagulation detection on the analyte according to the optical detection result, and receives an electrical signal reflecting the coagulation condition, which is obtained after processing Measurement parameters of the blood sample being tested.
The coagulation analyzer according to claim 18, characterized in that the processor is used to obtain the interference information reflecting the condition of the interference in the test object according to the optical detection result, and the interference refers to the coagulation based on the optical method Substances that have an influence on the test result of the test item; when the interference in the test object does not affect the test result of the coagulation test item based on the optical method, the processor controls the optical method detection device to perform coagulation test on the test object; When the interference in the test object will affect the detection result of the coagulation test item based on the optical method, the processor controls the magnetic bead method detection device to perform the coagulation test on the test object.
The coagulation analyzer according to claim 19, wherein the interfering substance refers to a substance that absorbs light of a specific wavelength, and the specific wavelength refers to an optical method used to perform coagulation detection on a mixed sample of plasma and reagent At least one of the wavelengths of light.
The coagulation analyzer according to claim 20, wherein the pre-judgment device includes a photoelectric detection device, and the photoelectric detection device includes a light emitting end and a light receiving end, and the light emitting end is used to adopt at least one specific Wavelength light or light with a wavelength close to a specific wavelength irradiates the test object, and the light receiving end is used to detect the optical information of the test object after being subjected to light to obtain optical detection of the test object for each specific wavelength of light result.
The coagulation analyzer according to claim 21, wherein the optical information is transmitted and/or scattered light intensity after the light beam passes through the object to be measured.
The coagulation analyzer according to claim 21 or 22, wherein the processor calculates the absorbance value of the test object for each specific wavelength of light based on the optical information, and absorbance of at least one specific wavelength of light When the value is greater than the preset threshold, it is judged that the interference in the test object will affect the detection result of the coagulation detection item based on the optical method.
The coagulation analyzer according to claim 18, wherein the pre-judgment device includes an image acquisition device, and the image acquisition device is used to collect image data of the object to be measured to obtain an optical detection result; The image data identifies the color of the test object, compares the color of the test object with the preset color, and when the color of the test object is the same as or close to the preset color, it is determined that the interfering object in the test object will be based on the optical The test result of the coagulation test item of the method has an influence.
The coagulation analyzer according to claim 18, wherein the pre-judgment device performs plasma detection on the test object, and the test object is plasma or a mixture of plasma and reagents, and the reagents include diluent, At least one of a mixed reagent and a trigger reagent.
The coagulation analyzer according to claim 18, wherein the position where the pre-judgment device performs optical detection on the object is a dedicated position, an incubation area, an optical detection area, or a magnetic bead detection area.
A blood coagulation analyzer, which is characterized by including an optical method detection device, a magnetic bead method detection device, an object transport mechanism and a processor;

The optical method detection device is used for performing coagulation detection on the measured object based on the optical method under the control of the processor, and outputs an electrical signal reflecting the coagulation situation;

The magnetic bead method detection device is used to perform coagulation detection on the measured object based on the magnetic bead method under the control of the processor, and output an electrical signal reflecting the coagulation situation;

The test object transfer mechanism is used to transfer the reaction container containing the test object to a preset position under the control of the processor;

The processor is used to obtain the interference information reflecting the condition of the interference in the blood sample to be tested, and determine whether the optical method detection device performs coagulation detection on the test object or the magnetic bead method detection device on the test object according to the interference information Coagulation detection, and receiving electrical signals reflecting the coagulation situation, after processing, the measurement parameters of the blood sample to be measured are obtained, and the interfering substance refers to a substance that has an influence on the coagulation detection based on the optical method.
The coagulation analyzer according to claim 18 or 27, wherein the optical method detection area for performing coagulation detection based on the optical method and the magnetic bead method detection area for performing coagulation detection based on the magnetic bead method are the same detection area.
A blood coagulation analyzer, which is characterized by including an optical method detection device, a magnetic bead method detection device, an object transport mechanism and a processor;

The optical method detection device is used for performing coagulation detection on the measured object based on the optical method under the control of the processor, and outputs an electrical signal reflecting the coagulation situation;

The magnetic bead method detection device is used to perform coagulation detection on the measured object based on the magnetic bead method under the control of the processor, and output an electrical signal reflecting the coagulation situation; the detection area and the optical method detection device of the magnetic bead method detection device The detection area is the same detection area;

The test object transfer mechanism is used to transfer the reaction container containing the test object to the common detection area under the control of the processor;

The processor is used to control the coagulation detection of the test object by the optical method detection device. When the optical method detection device detects inaccuracy or fails to output an electrical signal reflecting the coagulation condition, the magnetic bead method detection device performs the test on the test object Perform a blood clotting test.
A computer-readable storage medium, characterized by comprising a program, which can be executed by a processor to implement the method according to any one of claims 1-17.