Heparinase detection method and device based on magnetic bead method, sample analyzer and storage medium

Abstract

Embodiments of the present application disclose a heparinase detection method based on a magnetic bead method, applied to a sample analyzer, the method comprising: detecting a sample containing heparinase by using the magnetic bead method, determining a first coagulation time corresponding to the sample with heparinase according to collected first magnetic bead oscillation waveform data; as a comparison, detecting a sample without containing heparinase by using the magnetic bead method, determining a second coagulation time corresponding to the sample without heparinase according to collected second magnetic bead oscillation waveform data; and determining a detection result according to the first coagulation time and the second coagulation time. The method not only greatly reduces the cost, but also greatly improves the timeliness due to the simple detection method. In addition, a heparinase detection device based on the magnetic bead method, a sample analyzer and a storage medium are also proposed.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical detection, in particular to a blood coagulation analysis method and a blood coagulation analyzer. BACKGROUND

[0002] The traditional thromboelastogram is generated by a thromboelastograph (TEG), which is an analyzer for detecting the coagulation process from the whole dynamic process of platelet aggregation, coagulation, and fibrinolysis, and is used for monitoring and analyzing the coagulation state of a blood sample. The principle is to simulate the change of the viscoelasticity of the blood clot formed in the blood coagulation process over time, and to draw a thromboelastogram using the principle of mechanics.

[0003] The traditional heparinase contrast detection is based on the thromboelastograph, which detects the same whole blood sample by using an ordinary cup and a heparinase cup at the same time. The heparinase cup contains heparinase, which can degrade heparin in the blood and is not affected by residual heparin. The ordinary cup does not contain heparinase. Both groups of samples are activated by adding kaolin to the coagulation process, and the TEG records the coagulation time (R time). The thromboelastogram curve of the ordinary cup and the thromboelastogram curve of the heparinase cup are superimposed, and the coagulation time is compared. If they are similar, it means that there is no heparin in the body or the heparin has not taken effect. If the R time of the heparinase-free group is significantly prolonged, it means that the residual heparin in the body affects the coagulation process, or there is resistance, etc.

[0004] The traditional heparinase contrast detection needs a special thromboelastograph to realize it, that is, a special thromboelastograph needs to be purchased for detection, resulting in high cost, and the thromboelastograph has slow detection speed and needs to be manually operated by a special person, which not only has low timeliness but also cannot meet the high timeliness demand in emergency situations. SUMMARY

[0005] Therefore, it is necessary to propose a heparinase detection method and device based on magnetic bead method with high timeliness and low cost, a sample analyzer and a storage medium.

[0006] A heparinase detection method based on magnetic bead method, applied to a sample analyzer, the method comprises:

[0007] The sample containing heparinase is detected by using the magnetic bead method, and the first coagulation time corresponding to the sample added with heparinase is determined according to the collected first magnetic bead oscillation waveform data;

[0008] As a comparison, the sample without containing heparinase is detected by using the magnetic bead method, and the second coagulation time corresponding to the sample without adding heparinase is determined according to the collected second magnetic bead oscillation waveform data;

[0009] The detection result is determined according to the first coagulation time and the second coagulation time.

[0010] A heparinase detection device based on magnetic bead method, applied to a sample analyzer, the method comprising:

[0011] a first detection module for detecting a sample containing heparinase by magnetic bead method, determining a first coagulation time corresponding to the sample with heparinase according to the first magnetic bead oscillation waveform data collected;

[0012] a second detection module for detecting a sample without heparinase by magnetic bead method as a comparison, determining a second coagulation time corresponding to the sample without heparinase according to the second magnetic bead oscillation waveform data collected;

[0013] a determination module for determining a detection result according to the first coagulation time and the second coagulation time.

[0014] A computer readable storage medium has a computer program stored therein, the computer program, when executed by a processor, causes the processor to perform the following steps:

[0015] detecting a sample containing heparinase by magnetic bead method, determining a first coagulation time corresponding to the sample with heparinase according to the first magnetic bead oscillation waveform data collected;

[0016] detecting a sample without heparinase by magnetic bead method as a comparison, determining a second coagulation time corresponding to the sample without heparinase according to the second magnetic bead oscillation waveform data collected;

[0017] determining a detection result according to the first coagulation time and the second coagulation time.

[0018] A sample analyzer comprising a memory and a processor, the memory has a computer program stored therein, the computer program, when executed by the processor, causes the processor to perform the following steps:

[0019] detecting a sample containing heparinase by magnetic bead method, determining a first coagulation time corresponding to the sample with heparinase according to the first magnetic bead oscillation waveform data collected;

[0020] detecting a sample without heparinase by magnetic bead method as a comparison, determining a second coagulation time corresponding to the sample without heparinase according to the second magnetic bead oscillation waveform data collected;

[0021] determining a detection result according to the first coagulation time and the second coagulation time.

[0022] The heparinase detection method, device, sample analyzer and storage medium based on the magnetic bead method have the advantages that the magnetic bead method is used to detect samples containing heparinase and samples without heparinase, first magnetic bead oscillation waveform data and second magnetic bead oscillation waveform data are collected, a first clotting time is determined according to the first magnetic bead oscillation waveform data, a second clotting time is determined according to the second magnetic bead oscillation waveform data, and finally, a detection result is determined by comparing the first clotting time and the second clotting time. In the method, a special thrombelastograph is not needed to realize, and the existing sample analyzer can be used to realize. The magnetic bead method is a common detection method in the sample analyzer, and only a calculation method for determining the clotting time according to the magnetic bead oscillation waveform data needs to be added to the sample analyzer. The method greatly reduces the cost, and greatly improves the timeliness due to the simple detection method. BRIEF DESCRIPTION OF DRAWINGS

[0023] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative effort.

[0024] Among them:

[0025] Figure 1 It is a flow chart of the thrombelastogram detection method based on the magnetic bead method in an embodiment;

[0026] Figure 2A It is a schematic diagram of the first type of elastogram in an embodiment;

[0027] Figure 2B It is a schematic diagram of the second type of elastogram in an embodiment;

[0028] Figure 3 It is a detection process schematic diagram of a sample analyzer in an embodiment;

[0029] Figure 4 It is a flow chart of the thrombelastogram generation method based on the magnetic bead method in an embodiment;

[0030] Figure 5 It is a flow chart of the method for converting and calculating to obtain the thrombelastogram in an embodiment;

[0031] Figure 6 It is a schematic diagram of the magnetic bead oscillation waveform data in an embodiment;

[0032] Figure 7 It is a flow chart of the first derivative wave peak baseline and the first derivative wave trough baseline calculated in an embodiment;

[0033] Figure 8 A diagram of the peak baseline and the trough baseline obtained in an embodiment;

[0034] Figure 9 A diagram of the initial thrombelastogram obtained in an embodiment;

[0035] Figure 10 A diagram of the thrombelastogram obtained in an embodiment after fitting;

[0036] Figure 11 A flowchart of the calculation of the first-order peak baseline and the trough baseline in an embodiment;

[0037] Figure 12 A flowchart of the heparinase detection method based on the magnetic bead method in an embodiment;

[0038] Figure 13 A diagram of the thrombelastogram in an embodiment;

[0039] Figure 14 A structural block diagram of the thrombelastogram detection device based on the magnetic bead method in an embodiment;

[0040] Figure 15 A structural block diagram of the thrombelastogram generation device based on the magnetic bead method in an embodiment;

[0041] Figure 16 A structural block diagram of the calculation module in an embodiment;

[0042] Figure 17 A structural block diagram of the heparinase detection device based on the magnetic bead method in an embodiment;

[0043] Figure 18 An internal structural diagram of the sample analyzer in an embodiment. DETAILED DESCRIPTION

[0044] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all the other embodiments obtained by those of ordinary skill in the art without any creative work fall within the scope of protection of the present application.

[0045] The magnetic bead method refers to putting a magnetic bead in a detection cup (i.e. a reaction cup), and the detection cup has a set of drive coils on both sides, which generate a constant alternating electromagnetic field, so that the specially designed demagnetizing small steel bead in the detection cup maintains an equal amplitude oscillation movement. After the coagulation activator is added, as the amount of fibrin produced increases, the viscosity of the plasma increases, and the movement amplitude of the small steel bead gradually decreases. The instrument collects the movement changes of the small steel bead to obtain the magnetic bead oscillation waveform data according to the changes in the movement of the small steel bead sensed by another set of measurement coils.

[0046] As shown in Figure 1 , a thrombelastogram detection method based on the magnetic bead method is proposed, which is applied to a sample analyzer. The method comprises:

[0047] Step 102: When it is detected that the to-be-detected item contains thrombelastogram detection, the sample is detected by the magnetic bead method to obtain magnetic bead oscillation waveform data.

[0048] Among the to-be-detected items, there can be one or more detection items. Thrombelastogram detection is one of the detection items. There are various ways to obtain the to-be-detected items, one of which is to directly receive a detection instruction containing information of the to-be-detected items. Another way is to obtain the to-be-detected items by scanning a code, that is, to store the to-be-detected item information in the form of a bar code.

[0049] When it is detected that the to-be-detected item contains thrombelastogram detection, the sample needs to be detected by the magnetic bead method to collect the magnetic bead oscillation waveform data. The to-be-detected item can contain multiple detection items at the same time. For example, the to-be-detected item contains thrombelastogram detection and four coagulation items, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The detection of the four coagulation items can be performed by the magnetic bead method or the optical method. When the four coagulation items are detected by the magnetic bead method, the thrombelastogram detection and the four coagulation items can be detected simultaneously by the magnetic bead method. In an embodiment, each magnetic bead method detection item can correspond to a thrombelastogram. For example, the TT item detected by the magnetic bead method can correspond to a TT thrombelastogram, and the APTT item detected by the magnetic bead method can correspond to an APTT thrombelastogram.

[0050] Since the detection of the four coagulation items requires a plasma sample, the thrombelastogram obtained based on the plasma sample is not a standard thrombelastogram. In order to distinguish, the thrombelastogram obtained based on the plasma sample is called "second type thrombelastogram", that is, the TT thrombelastogram and the APTT thrombelastogram actually belong to the second type thrombelastogram.

[0051] That is, the elasticogram detection is actually divided into two types, the first type elasticogram detection and the second type elasticogram detection. The first type elasticogram is a standard elasticogram detected based on a whole blood sample, and the second type elasticogram detection is a non-standard elasticogram detected based on a plasma sample.

[0052] Therefore, when the to-be-detected item contains elasticogram detection, it is further necessary to distinguish which type of elasticogram detection is contained, so as to determine the sample type required for detection, that is, whether to use a plasma sample or a whole blood sample.

[0053] In step 104, the elasticogram is drawn according to the magnetic bead oscillation waveform data, and a thrombus elasticogram is generated.

[0054] Among them, the thrombus elasticogram is drawn by converting the magnetic bead oscillation waveform data. There are many methods for converting and calculating the magnetic bead oscillation waveform data.

[0055] In one embodiment, the conversion calculation can be calculated by the following method: first, the magnetic bead oscillation waveform data is subjected to first-order derivation to obtain first-order derivation graph data, then the first-order derivation graph data is subjected to second-order derivation to obtain second-order derivation graph data, the wave peaks and wave troughs of the first-order derivation graph data are determined according to the second-order derivation graph data, then the wave peak baseline and the wave trough baseline are extracted, and the initial elasticogram is obtained by inverse transformation based on the wave peak baseline and the wave trough baseline, and then the fitting calculation is performed to draw the thrombus elasticogram.

[0056] In another embodiment, the conversion calculation can also be calculated by the following method: first, the magnetic bead oscillation waveform data is subjected to inverse transformation to obtain inverse transformed magnetic bead oscillation waveform data, then the transformed magnetic bead oscillation waveform data is subjected to first-order derivation and second-order derivation, the wave peaks and wave troughs of the first-order derivation are determined based on the second-order derivation, the wave peak baseline and the wave trough baseline are extracted, and then the fitting calculation is performed to obtain the thrombus elasticogram.

[0057] The above-mentioned elasticogram detection method based on the magnetic bead method, when the to-be-detected item contains elasticogram detection, the sample is detected by the magnetic bead method, the magnetic bead oscillation waveform data is obtained, the elasticogram is drawn according to the magnetic bead oscillation waveform data, and the thrombus elasticogram is generated. In this method, a special thrombus elasticogram instrument is not required to realize, and the existing sample analyzer can be used to realize, the magnetic bead method is a common detection method in the sample analyzer, and only the corresponding elasticogram drawing method needs to be added in the sample analyzer to draw the thrombus elasticogram. The thrombus elasticogram detection method not only greatly reduces the cost, but also greatly improves the timeliness due to the simple detection method.

[0058] In one embodiment, when the thromboelastography detection included in the to-be-detected item is the first type of thromboelastography detection, the sample is a whole blood sample, and the thromboelastography is the first type of thromboelastography; when the thromboelastography detection included in the to-be-detected item is the second type of thromboelastography detection, the sample is a plasma sample, and the thromboelastography is the second type of thromboelastography.

[0059] The first type of thromboelastography is a standard thromboelastography, and the thromboelastography includes a full-branch thromboelastography drawing. The second type of thromboelastography is a non-standard thromboelastography, and the thromboelastography only includes a half-branch thromboelastography drawing (i.e., only the first half part). As shown in FIG. 1, it is a schematic diagram of the first type of thromboelastography. As shown in FIG. 2, it is a schematic diagram of the second type of thromboelastography. Different samples are used for different types of thromboelastography, so that the to-be-detected item can be determined according to actual needs, and the to-be-detected item can be selected more flexibly and variously. Figure 2A Figure 2B The first type of thromboelastography is a standard thromboelastography, and the thromboelastography includes a full-branch thromboelastography drawing. The second type of thromboelastography is a non-standard thromboelastography, and the thromboelastography only includes a half-branch thromboelastography drawing (i.e., only the first half part). As shown in FIG. 1, it is a schematic diagram of the first type of thromboelastography. As shown in FIG. 2, it is a schematic diagram of the second type of thromboelastography. Different samples are used for different types of thromboelastography, so that the to-be-detected item can be determined according to actual needs, and the to-be-detected item can be selected more flexibly and variously.

[0060] In one embodiment, when the to-be-detected item only includes the first type of thromboelastography detection, the sample is detected by using the magnetic bead method to obtain magnetic bead oscillation waveform data, including: controlling a sample needle to suck a whole blood sample and add the whole blood sample to a magnetic bead reaction cup; transferring the magnetic bead reaction cup in which the whole blood sample is added to a reagent adding position, adding a whole blood reagent at the reagent adding position, and transferring the magnetic bead reaction cup in which the whole blood reagent is added to a magnetic bead detection position; detecting the sample by using the magnetic bead method at the magnetic bead detection position, and collecting magnetic bead oscillation waveform data.

[0061] When the to-be-detected item only includes the first type of thromboelastography detection, the whole blood sample is directly used for detection in the sample analyzer, that is, the provided sample is a whole blood sample, the sample needle is used to suck the whole blood sample, and then the magnetic bead reaction cup in which the whole blood sample is added is transferred to the reagent adding position, the whole blood reagent is added at the reagent adding position, and then the magnetic bead reaction cup is transferred to the magnetic bead detection position, so that the whole blood sample is detected by using the magnetic bead method to obtain the magnetic bead oscillation waveform data. The sample analyzer provides the above-mentioned thromboelastography detection mode, and the first type of thromboelastography can be detected by using the sample analyzer.

[0062] In one embodiment, when the to-be-detected item only includes the first type of thromboelastography detection, the sample is detected by using the magnetic bead method to obtain magnetic bead oscillation waveform data, including: controlling a sample needle to suck a whole blood sample and add the whole blood sample to a magnetic bead reaction cup; transferring the magnetic bead reaction cup in which the whole blood sample is added to a reagent adding position, adding a whole blood reagent at the reagent adding position, and transferring the magnetic bead reaction cup in which the whole blood reagent is added to a magnetic bead detection position; detecting the sample by using the magnetic bead method at the magnetic bead detection position, and collecting magnetic bead oscillation waveform data.

[0063] ​When the first type of elastic diagram detection is not included in the to-be-detected items, it indicates that other detection items need to be detected, and the samples required by the other detection items are usually plasma samples. Therefore, in order to realize that the samples used for the first type of elastic diagram detection and the other detection items can be used, the sample provided is a centrifuged whole blood sample, and the upper layer of the centrifuged whole blood sample is plasma. When the other items are detected, the upper plasma of the centrifuged whole blood sample is taken for detection, and when the first type of elastic diagram detection is performed, the centrifuged whole blood sample is mixed first, and then the mixed whole blood sample is taken for detection. When the other items and the first type of elastic diagram detection exist at the same time, since the centrifuged whole blood sample is provided, the item requiring the plasma sample is detected first, that is, the plasma sample is taken for detection first, and then the mixed whole blood sample is taken. This is beneficial to save time and reduce the physical and economic burden on doctors and patients caused by repeated blood sampling for multiple items.

[0064] In one embodiment, when the second type of elastic diagram detection is included in the to-be-detected items, the sample is detected by using the magnetic bead method to obtain magnetic bead oscillation waveform data, including: controlling a sample needle to take a plasma sample and add it to a magnetic bead reaction cup, transferring the magnetic bead reaction cup in which the plasma sample is added to a reagent adding position, adding a plasma reagent at the reagent adding position, and transferring the magnetic bead reaction cup in which the plasma reagent is added to a magnetic bead detection position; detecting the plasma sample by using the magnetic bead method at the magnetic bead detection position to obtain magnetic bead oscillation waveform data.

[0065] The second type of elastic diagram detection uses a plasma sample, and other detection items (such as four items of blood coagulation) also basically use a plasma sample. Therefore, whether the to-be-detected items include other detection items in addition to the second type of elastic diagram detection, a plasma sample is used. Similarly, the plasma sample is detected by using the magnetic bead method to obtain corresponding magnetic bead oscillation waveform data.

[0066] In one embodiment, the elastic diagram detection method based on the magnetic bead method further includes: when the to-be-detected items do not include elastic diagram detection, controlling a sample needle to take plasma and add it to a reaction cup, and transferring the reaction cup in which the sample is added to a detection position, which is a magnetic bead detection position or an optical detection position.

[0067] In addition to the detection of the project containing the elastic map detection, the sample analyzer can also detect the project without the elastic map detection, such as the general coagulation four-item detection. That is, the sample analyzer can detect the general coagulation four-item detection and the elastic map detection. The detection method used in the sample analyzer can not only use the magnetic bead method, but also use the optical method, that is, the sample analyzer has both the magnetic bead detection channel and the optical detection channel. It should be noted that before the magnetic bead method or the optical method is used for detection, the coagulation activator is added to the sample, so that the coagulation reaction can occur, which is the basis of the sample detection, and will not be described here.

[0068] In one embodiment, when the detection project contains both the elastic map detection and the optical detection project, the method further comprises: controlling the sample needle to suck the sample and add it to the optical reaction cup; transferring the optical reaction cup with the added sample to the optical detection position; and using the optical method to detect the sample at the optical detection position.

[0069] When the detection project contains not only the elastic map detection but also the optical detection project, the sample needs to be added to the optical reaction cup, and then the optical method is used to detect the sample at the optical detection position. That is, the multiple detection projects can be detected by the same method or by different methods.

[0070] In one embodiment, when the detection project contains not only the elastic map detection but also the optical detection project, the method further comprises: obtaining the detection results of the other projects except the elastic map detection; and generating a detection report according to the detection results of the other projects and the thromboelastography.

[0071] In order to comprehensively reflect the coagulation condition, the detection results of multiple detection projects are put together to generate a detection report, such as the coagulation four-item detection and the elastic map detection together as a detection report for the doctor to refer to.

[0072] As Figure 3As shown, a detection flowchart of a sample analyzer (such as a coagulation analyzer) for implementing the above-mentioned thromboelastography detection method based on magnetic beads in an embodiment is shown. First, place the coagulation detection sample (whole blood after centrifugation) in the sample position. Then scan the barcode to obtain the detection items, determine whether there are items that need to use plasma in the detection items, if not, use vibration or suction to mix the whole blood after centrifugation into whole blood, then suck the whole blood into the magnetic bead reaction cup and transfer it to the magnetic bead detection position for magnetic bead detection, collect the magnetic bead oscillation waveform data, and then obtain the first type of thromboelastogram; if so, control the sampling needle to suck the plasma, and then transfer it to the detection module (including magnetic bead detection and optical detection), and use the magnetic bead method or the optical method for detection in the detection module according to the type of the detection items (if the second type of thromboelastogram detection is included, the magnetic bead method is used to obtain the second type of thromboelastogram). Then continue to determine whether there are items that need to use whole blood detection (first type of thromboelastogram detection) in the detection items, if so, use vibration or suction to mix the whole blood after centrifugation into whole blood, then suck the whole blood into the magnetic bead reaction cup and transfer it to the magnetic bead detection position for magnetic bead detection, collect the magnetic bead oscillation waveform data, and then obtain the first type of thromboelastogram.

[0073] As shown, a thromboelastogram generation method based on magnetic beads is proposed, which comprises: Figure 4

[0074] Step 402, obtaining the magnetic bead oscillation waveform data detected based on the magnetic bead method.

[0075] Among them, the magnetic bead method refers to putting a magnetic bead (the magnetic bead can be pre-placed in the detection cup, or it can be placed in time during the detection process, and the detection cup can also be a detection cup with a sealing structure) in the detection cup (i.e. the reaction cup), and in the detection position, there is a group of driving coils and a group of receiving coils on both sides of the detection cup, which generates a constant alternating electromagnetic field, so that the specially designed demagnetizing small steel balls in the detection cup maintain an equal amplitude oscillation motion. After the addition of coagulation activator, as the production of fibrin increases, the viscosity of plasma increases, and the motion amplitude of the small steel balls gradually weakens. The instrument collects the motion change of the small steel balls according to the change of the motion of the small steel balls sensed by another group of measurement coils to obtain the magnetic bead oscillation waveform data.

[0076] Step 404, converting and calculating based on the magnetic bead oscillation waveform data to obtain the thromboelastogram.

[0077] Among them, the magnetic bead oscillation waveform data is converted to draw the thromboelastogram. There are many methods for converting and calculating the magnetic bead oscillation waveform data.

[0078] ​In one embodiment, the conversion calculation can be calculated by the following method: first, the first derivative of the magnetic bead oscillation waveform data is obtained to obtain the first derivative graph data, and then the first derivative graph data is differentiated again to obtain the second derivative graph data, and the wave peak and wave trough of the first derivative graph data are determined according to the second derivative graph data, and then the wave peak baseline and the wave trough baseline are extracted, and the initial thrombelastogram is obtained by inverse transformation based on the wave peak baseline and the wave trough baseline, and then the fitting calculation is performed to obtain the thrombelastogram.

[0079] In another embodiment, the conversion calculation can also be calculated by the following method: first, the magnetic bead oscillation waveform data is inversely transformed to obtain the inversely transformed magnetic bead oscillation waveform data, and then the first derivative and the second derivative of the transformed magnetic bead oscillation waveform data are performed, and the wave peak and wave trough of the first derivative are determined based on the second derivative, and the wave peak baseline and the wave trough baseline are extracted, and then the fitting calculation is performed to obtain the thrombelastogram.

[0080] The above-mentioned thrombelastogram generation method based on the magnetic bead method can obtain the thrombelastogram by converting the magnetic bead oscillation waveform data, and the method does not need a special thrombelastogram instrument to realize, and can be realized by using the existing sample analyzer. The magnetic bead method is a common detection method in the sample analyzer, and only the corresponding conversion calculation method needs to be added in the sample analyzer to draw the thrombelastogram. The thrombelastogram generation method not only greatly reduces the cost, but also greatly improves the timeliness due to the simple detection method.

[0081] As shown in the figure, Figure 5 In one embodiment, the conversion calculation based on the magnetic bead oscillation waveform data obtains the thrombelastogram in step 404, which includes:

[0082] Step 404A, the wave peak baseline and the wave trough baseline of the first derivative are calculated according to the magnetic bead oscillation waveform data.

[0083] The wave peak baseline of the first derivative refers to the wave peak baseline in the first derivative graph data obtained by first-order differentiation of the magnetic bead oscillation waveform data. The wave peak baseline refers to a line composed of multiple wave peaks, that is, a straight line connecting multiple wave peaks. The wave trough baseline of the first derivative refers to the wave trough baseline in the first derivative graph data obtained by first-order differentiation of the magnetic bead oscillation waveform data. The wave trough baseline is a line composed of multiple wave troughs, that is, a straight line connecting multiple wave troughs. As known from the above, the thrombelastogram is divided into a first type of thrombelastogram and a second type of thrombelastogram, which are respectively obtained by detecting the whole blood and the plasma.

[0084] The following takes the second type of thrombelastogram obtained by detecting the plasma sample as an example to illustrate the whole thrombelastogram calculation process. As shown in the figure, Figure 6The image shown is a graphical representation of the oscillation waveform data of the collected magnetic beads. Figure 7 The image shown is a graphical representation of the first-order derivative obtained by taking the first-order derivative of the magnetic bead oscillation waveform data. Figure 8 The figure shows a schematic diagram of the peak and trough baselines obtained based on the first-order derivative graphical data.

[0085] Step 404B: Obtain the initial elasticity diagram by performing an inverse transformation based on the peak and trough baselines of the first-order derivative.

[0086] Among them, such as Figure 9 As shown, the initial elasticity map is obtained by inversely transforming the peak and trough baselines of the first-order derivative relative to the zero baseline. From Figure 9 The signal can be emitted, and after inverse transformation, the original peak baseline and trough baseline become 0 baseline, and then the 0 baseline after the peak baseline and trough baseline becomes the original peak baseline and trough baseline.

[0087] Step 404C: Fit the initial elasticity map to obtain the thromboelastography map.

[0088] Among them, such as Figure 10 The image shown is the thromboelastography map obtained after fitting. Figure 9 The initial elasticity map obtained is not a smooth curve. Therefore, to obtain a smooth curve, the initial elasticity map is fitted to obtain a smoothed thromboelastography map. The initial elasticity map can be fitted using four-parameter fitting, three-parameter fitting, or five-parameter fitting.

[0089] Thromboelastography (TEG) was obtained through the conversion and calculation of the aforementioned magnetic bead oscillation waveform data, realizing the function of detecting TEG using the magnetic bead method. This not only reduces costs but also improves the timeliness of detection. Furthermore, existing sample analyzers often have multiple channels capable of simultaneous detection, further enhancing the efficiency of detecting multiple samples. In addition, using the magnetic bead method for TEG detection allows for the simultaneous testing of multiple items to generate a single report; for example, the magnetic bead method can be used to detect coagulation parameters while simultaneously performing TEG detection.

[0090] like Figure 11 As shown, in one embodiment, the peak baseline and trough baseline of the first derivative are calculated based on the oscillation waveform data of the magnetic bead, including:

[0091] Step 1102: Perform first-order differentiation on the magnetic bead oscillation waveform data to obtain first-order derivative graphical data.

[0092] Among them, reference Figure 6 The image shown is a graphical schematic diagram of the oscillation waveform data of a magnetic bead in one embodiment. (Refer to...)Figure 7 The first derivative graph data is obtained by first-order derivation of the magnetic bead oscillation waveform data.

[0093] In step 1104, the second derivative graph data is obtained by derivation of the first derivative graph data.

[0094] In order to obtain the peak and valley data in the first derivative graph data, the second derivative graph data is obtained by further derivation of the first derivative graph data.

[0095] In step 1106, the plurality of peaks and the plurality of valleys in the first derivative graph data are determined according to the second derivative graph data.

[0096] The peaks and valleys in the first derivative graph data are determined by the extreme value method based on the second derivative graph data. The maximum value in the second derivative graph data is taken as the valley, and the minimum value is taken as the peak.

[0097] In step 1108, the peak baseline of the first derivative is determined according to the plurality of peaks, and the valley baseline of the first derivative is determined according to the plurality of valleys.

[0098] After the plurality of peaks and the plurality of valleys are determined, the peak baseline is further determined according to the plurality of peaks, and the valley baseline is further determined according to the plurality of valleys.

[0099] The above process determines the peak baseline and the valley baseline of the first derivative according to the second derivative graph data, which is simple to calculate and can determine the peak baseline and the valley baseline without complex calculation, thereby improving the efficiency of thrombelastography generation.

[0100] In one embodiment, the peak baseline of the first derivative is determined according to the plurality of peaks, and the valley baseline of the first derivative is determined according to the plurality of valleys, including: determining the end point of the peak baseline of the first derivative, and extracting the peak baseline of the first derivative according to the end point of the peak baseline of the first derivative; determining the end point of the valley baseline of the first derivative, and extracting the valley baseline of the first derivative according to the end point of the valley baseline of the first derivative.

[0101] Extracting the peak baseline essentially involves determining its endpoint, since the starting point is already determined—the position of the first peak. Similarly, extracting the trough baseline also involves determining its endpoint, with the starting point being the position of the first trough. Determining the endpoints of the peak and trough baselines is crucial. Not all peak data obtained using the second-order derivative graphs mentioned above falls within the baseline range. After adding coagulation reagent, during the detection process, as the coagulation reaction occurs, the amplitude of the magnetic bead oscillation data decreases. After the coagulation time is reached, the amplitude becomes very small. Peaks and troughs after the coagulation time are not within the range for peak and trough baseline extraction. Therefore, it is necessary to find the endpoint of the peak and trough baselines, which corresponds to the coagulation time; that is, to find the coagulation time reached by the sample for baseline extraction.

[0102] In one embodiment, determining the endpoint of the first derivative peak baseline and extracting the first derivative peak baseline based on the endpoint of the first derivative peak baseline includes: calculating the mean of the first N peaks; when the value of the (N+1)th peak is less than a preset proportion of the mean of the first N peaks, the first N+1 peaks are taken as the endpoint of the first derivative peak baseline; and extracting the first derivative peak baseline based on the endpoint and starting point of the first derivative peak baseline, wherein the starting point of the first derivative peak baseline refers to the position of the first peak in the first derivative graph.

[0103] The determination of the endpoint of the peak baseline requires dynamic calculation. The average of the first two peaks is calculated sequentially, from smallest to largest N. The value of the third peak is compared with the average of the first two peaks. If the value of the third peak is not less than a preset percentage (e.g., 98%) of the average of the first two peaks, the average of the first three peaks is calculated again. Then, the value of the fourth peak is checked to see if it meets the above condition. This process continues until the value of the (N+1)th peak is found to be less than a preset percentage of the average of the first N peaks. The (N+1)th peak is then taken as the endpoint of the first-order derivative peak baseline. (Reference) Figure 8 The upper part is the extracted peak baseline.

[0104] In one embodiment, determining the endpoint of the first derivative's valley baseline and extracting the first derivative's valley baseline based on the endpoint of the first derivative's valley baseline includes: calculating the mean of the absolute values ​​of the first N valleys; when the absolute value of the (N+1)th valley is less than a preset proportion of the mean of the absolute values ​​of the first N valleys, the (N+1)th valley is taken as the endpoint of the first derivative's valley baseline; and extracting the first derivative's valley baseline based on the endpoint and starting point of the first derivative's valley baseline, wherein the starting point of the first derivative's valley baseline refers to the position of the first valley in the first derivative graph.

[0105] The determination of the end point of the trough baseline needs to be obtained by dynamic calculation. The average of the first two troughs is calculated in ascending order of N values. The value of the third trough is compared with the average of the first two troughs. When the value of the third trough is not less than the preset proportion (such as 98%) of the average of the first two troughs, the average of the first three troughs is calculated, and then it is judged whether the value of the fourth trough meets the above condition. The same is true for the subsequent steps until the value of the N+1th trough is less than the preset proportion of the average of the previous N troughs. The N+1th trough is taken as the end point of the first derivative trough baseline. Reference Figure 8 The following part is the extracted trough baseline.

[0106] In one embodiment, the end point of the first derivative peak baseline is determined, and the first derivative peak baseline is extracted according to the end point of the first derivative peak baseline, including: differentiating the plurality of peaks of the first derivative, and taking the point with the fastest rate of change as the end point of the first derivative peak baseline; differentiating the plurality of troughs of the first derivative, and taking the point with the fastest rate of change as the end point of the first derivative trough baseline.

[0107] In one embodiment, the end point of the first derivative peak baseline is determined, and the first derivative peak baseline is extracted according to the end point of the first derivative peak baseline, including: differentiating the plurality of peaks of the first derivative, and taking the point with the fastest rate of change as the end point of the first derivative peak baseline; differentiating the plurality of troughs of the first derivative, and taking the point with the fastest rate of change as the end point of the first derivative trough baseline.

[0108] In one embodiment, the first derivative of the magnetic bead oscillation waveform data is obtained to obtain the first derivative graph data, including: determining the amplitude graph of the magnetic bead swing according to the magnetic bead oscillation waveform data; and performing first derivative on the amplitude graph to obtain the first derivative graph data.

[0109] In one embodiment, the first derivative of the magnetic bead oscillation waveform data is obtained to obtain the first derivative graph data, including: determining the amplitude graph of the magnetic bead swing according to the magnetic bead oscillation waveform data; and performing first derivative on the amplitude graph to obtain the first derivative graph data.

[0110] In one embodiment, the initial elastic diagram is fitted to obtain a thrombus elastic diagram, including: using a four-parameter fitting method to fit the initial elastic diagram to obtain a thrombus elastic diagram. The four parameters in the four-parameter fitting method are obtained through experiments.

[0111] The four-parameter fitting formula is as follows: F(x) = D + (A-D) / (1+(x / C)^B), wherein A, B, C and D are four parameters, the four parameters are empirical values obtained through experiments, x represents an independent variable (point coordinates on the elastic diagram), and F(x) represents a fitting result. The thrombelastogram obtained by fitting the initial elastic diagram with the four parameters is smoother and closer to the actual situation, that is, the detection result is more accurate.

[0112] In addition, the magnetic bead method can also be used for heparinase detection. Traditional heparinase contrast detection is based on a thrombelastograph. A common cup and a heparinase cup are used to detect the same whole blood sample. The heparinase cup contains heparinase, which can degrade heparin in the blood and is not affected by residual heparin. The common cup does not contain heparinase. Both groups of samples are activated by adding kaolin to activate the coagulation process, and the TEG records the coagulation time (R time). The elastic diagram curve of the common cup and the elastic diagram curve of the heparinase cup are superimposed, and the coagulation time is compared. If they are similar, it means that there is no heparin in the body or that heparin has not taken effect. If the R time of the group without heparinase is significantly prolonged, it means that the residual heparin in the body affects the coagulation process or there is resistance. Traditional heparinase contrast detection requires a special thrombelastograph, that is, a special thrombelastograph needs to be purchased for detection, resulting in high cost and slow detection speed of the thrombelastograph, low timeliness, and inability to meet the high timeliness demand in emergency situations. Therefore, the magnetic bead method for heparinase detection can solve the above problems, not only improving the timeliness, but also greatly saving the detection cost.

[0113] As shown in Figure 12 A heparinase detection method based on a magnetic bead method is proposed, which is applied to a sample analyzer. The method comprises the following steps:

[0114] In step 1202, the sample containing heparinase is detected by the magnetic bead method, and the first coagulation time corresponding to the sample added with heparinase is determined according to the collected first magnetic bead oscillation waveform data.

[0115] In one embodiment, the sample containing heparinase is detected by the magnetic bead method, and an elastic diagram is drawn according to the first magnetic bead oscillation waveform data, and the corresponding first coagulation time is determined according to the elastic diagram.

[0116] In another embodiment, the elastic diagram can not be drawn, and the coagulation time point can be directly calculated according to the first magnetic bead oscillation waveform data to determine the corresponding first coagulation time.

[0117] The sample can be plasma or whole blood when the magnetic bead method is used for heparinase detection. Compared with the traditional method which can only use whole blood for detection, the sample selection is more flexible.

[0118] Step 1204, the sample without containing heparinase is detected by the magnetic bead method, and the second coagulation time corresponding to the sample without adding heparinase is determined according to the collected second magnetic bead oscillation waveform data.

[0119] As a comparison of heparinase detection, the sample without containing heparinase is detected by the magnetic bead method, and the second coagulation time is determined according to the second magnetic bead oscillation waveform data. In another embodiment, the elastic diagram or similar elastic diagram can also be drawn according to the second magnetic bead oscillation waveform data, and the coagulation time point can also be found by calculation according to the second magnetic bead oscillation waveform data, that is, the second coagulation time is determined.

[0120] It should be noted that the order of steps 1202 and 1204 can be interchanged, and in addition, both can be performed simultaneously.

[0121] Step 1206, determining the detection result according to the first coagulation time and the second coagulation time.

[0122] Wherein, compared with the first coagulation time and the second coagulation time, if they are similar, it means that there is no heparin in the body or the heparin has not taken effect; if the coagulation time of the group without adding heparinase is significantly prolonged, it means that the residual heparin in the body affects the coagulation process, or there is resistance, etc.

[0123] The above-mentioned heparinase detection method based on the magnetic bead method detects the sample containing heparinase and the sample without heparinase by the magnetic bead method respectively, collects the first magnetic bead oscillation waveform data and the second magnetic bead oscillation waveform data, and then determines the first coagulation time according to the first magnetic bead oscillation waveform data and the second coagulation time according to the second magnetic bead oscillation waveform data. Finally, the detection result is determined by comparing the first coagulation time and the second coagulation time. In this method, a special thromboelastogram instrument is not needed to realize, and the existing sample analyzer can be used to realize. The magnetic bead method is a common detection method in the sample analyzer, and only the calculation method of determining the coagulation time according to the magnetic bead oscillation waveform data needs to be added in the sample analyzer. This method not only greatly reduces the cost, but also greatly improves the timeliness due to the simplicity of the detection method.

[0124] In one embodiment, the sample containing heparinase is detected by the magnetic bead method, and the first coagulation time corresponding to the sample with heparinase is determined according to the collected first magnetic bead oscillation waveform data, including: image drawing is performed according to the first magnetic bead oscillation waveform data to obtain a first thromboelastogram; and the corresponding first coagulation time is determined according to the first thromboelastogram.

[0125] The magnetic bead method is used to detect the sample without containing heparinase, and the second coagulation time corresponding to the sample without adding heparinase is determined according to the collected second magnetic bead oscillation waveform data, including: image drawing is performed according to the second magnetic bead oscillation waveform data to obtain a second thromboelastogram; and the corresponding second coagulation time is determined according to the second thromboelastogram.

[0126] In order to determine the coagulation time, the thromboelastogram is drawn, that is, the image is drawn according to the magnetic bead oscillation waveform data to obtain the thromboelastogram, and then the corresponding coagulation time is determined according to the drawn thromboelastogram, as shown in FIG. 1. Figure 13 In one embodiment, the thromboelastogram is shown in FIG. 1, and the coagulation time can be determined from the thromboelastogram.

[0127] In one embodiment, the magnetic bead method is used to detect the sample containing heparinase, the first coagulation time corresponding to the sample with heparinase is determined according to the collected first magnetic bead oscillation waveform data, including: the sample needle is controlled to suck the sample and add it to the first magnetic bead reaction cup, the first magnetic bead reaction cup is transferred to the reagent adding position, and the heparinase and the coagulation activator are added to the first magnetic bead reaction cup at the reagent adding position; the sample is detected by the magnetic bead method at the magnetic bead detection position, and the first magnetic bead oscillation waveform data is collected; and the corresponding first coagulation time is determined according to the first magnetic bead oscillation waveform data.

[0128] The magnetic bead method is used to detect the sample without containing heparinase, and the second coagulation time corresponding to the sample without adding heparinase is determined according to the collected second magnetic bead oscillation waveform data, including: the sample needle is controlled to suck the sample and add it to the first magnetic bead reaction cup, the first magnetic bead reaction cup is transferred to the reagent adding position, and the heparinase and the coagulation activator are added to the first magnetic bead reaction cup at the reagent adding position; the sample is detected by the magnetic bead method at the magnetic bead detection position, and the first magnetic bead oscillation waveform data is collected; and the corresponding first coagulation time is determined according to the first magnetic bead oscillation waveform data.

[0129] In order to compare, the same sample is added to the first magnetic bead reaction cup and the second magnetic bead reaction cup, and then the heparinase and the coagulation activator are added to the first magnetic bead reaction cup, and only the coagulation activator is added to the second magnetic bead reaction cup. The coagulation activator can be kaolin. After the reagent is added, the viscosity of the plasma increases with the increase of the produced fibrin, and the movement amplitude of the small steel balls gradually weakens. The instrument senses the change of the movement of the small steel balls according to another group of measurement coils, and converts the magnetic bead movement pattern into a thromboelastogram pattern through software calculation, and compares the coagulation time of the reaction cup with the heparinase and the reaction cup without the heparinase.

[0130] In one embodiment, adding heparinase and coagulation activator to the first magnetic bead reaction vessel at the reagent addition site includes: adding heparinase to the first magnetic bead reaction vessel at the reagent addition site and mixing and incubating; adding coagulation activator to the first magnetic bead reaction vessel after mixing and incubation.

[0131] Among them, the magnetic bead method for heparinase detection can use ordinary magnetic bead reaction cups, which is more convenient and cost-effective than the traditional method that requires special heparinase cups.

[0132] When performing heparinase testing, there is a specific order in which heparinase and coagulation activator are added. Heparinase is added first, and after mixing and incubation, the coagulation activator is added. This is because the coagulation reaction begins after the coagulation activator is added, and the coagulation activator is added later to facilitate timely detection of coagulation changes.

[0133] In one embodiment, the sample analyzer includes multi-channel detection and uses a magnetic bead method to perform parallel detection of samples with added heparinase and samples without added heparinase.

[0134] The sample analyzer includes multi-channel detection. To accelerate the detection speed, samples with added heparinase and samples without added heparinase are detected in parallel.

[0135] In one embodiment, the sample is plasma or whole blood.

[0136] The sample used for heparinase detection can be either plasma or whole blood, offering flexibility in selection. When using whole blood samples, the sample can be directly aspirated using a syringe for testing; that is, the sample provided from the beginning is whole blood. If a centrifuged whole blood sample is initially provided, it needs to be mixed thoroughly before aspirating the mixed whole blood sample.

[0137] In one embodiment, when the sample is whole blood, controlling the sampling needle to aspirate the sample and add it to the first magnetic bead reaction cup includes: controlling the sampling needle to mix the centrifuged whole blood sample and aspirating the mixed whole blood sample into the first magnetic bead reaction cup; controlling the sampling needle to aspirate the sample and add it to the second magnetic bead reaction cup includes: controlling the sampling needle to mix the centrifuged whole blood sample and aspirating the mixed whole blood sample into the second magnetic bead reaction cup.

[0138] If a centrifuged whole blood sample is provided, it needs to be mixed before aspiration to obtain a whole blood sample.

[0139] like Figure 14 As shown, in one embodiment, a thromboelastography detection device based on the magnetic bead method is proposed, the device comprising:

[0140] detecting, by a detection module 1402, the sample by using a magnetic bead method when it is detected that the to-be-detected item contains the thrombelastogram detection, to obtain magnetic bead oscillation waveform data;

[0141] generating, by a generation module 1404, a thrombelastogram according to the magnetic bead oscillation waveform data.

[0142] In one embodiment, when the thrombelastogram detection contained in the to-be-detected item is a first type of thrombelastogram detection, the sample is a whole blood sample, and the thrombelastogram is a first type of thrombelastogram; when the thrombelastogram detection contained in the to-be-detected item is a second type of thrombelastogram detection, the sample is a plasma sample, and the thrombelastogram is a second type of thrombelastogram.

[0143] In one embodiment, when the to-be-detected item only contains the first type of thrombelastogram detection, the detection module 1402 is further configured to control a sample adding needle to mix the centrifuged whole blood sample, and to suck the mixed whole blood sample and add it to a magnetic bead reaction cup; to transfer the magnetic bead reaction cup to which the whole blood sample is added to a reagent adding position, to add a whole blood reagent at the reagent adding position, to transfer the magnetic bead reaction cup to which the whole blood reagent is added to a magnetic bead detection position; and to transfer the magnetic bead reaction cup to which the mixed whole blood sample is added to the magnetic bead detection position, to detect by using the magnetic bead method, and to collect the magnetic bead oscillation waveform data.

[0144] In one embodiment, when the to-be-detected item contains the first type of thrombelastogram detection, the detection module 1402 is further configured to control a sample adding needle to mix the centrifuged whole blood sample, and to suck the mixed whole blood sample and add it to a magnetic bead reaction cup; to transfer the magnetic bead reaction cup to which the whole blood sample is added to a reagent adding position, to add a whole blood reagent at the reagent adding position, to transfer the magnetic bead reaction cup to which the whole blood reagent is added to a magnetic bead detection position; and to transfer the magnetic bead reaction cup to which the mixed whole blood sample is added to the magnetic bead detection position, to detect by using the magnetic bead method, and to collect the magnetic bead oscillation waveform data.

[0145] In one embodiment, when the to-be-detected item contains the second type of thrombelastogram detection, the detection module 1402 is further configured to control a sample adding needle to suck a plasma sample and add it to a magnetic bead reaction cup, to transfer the magnetic bead reaction cup to which the plasma sample is added to a reagent adding position, to add a plasma reagent at the reagent adding position, to transfer the magnetic bead reaction cup to which the plasma reagent is added to a magnetic bead detection position; and to detect the plasma sample by using the magnetic bead method at the magnetic bead detection position, and to collect the magnetic bead oscillation waveform data.

[0146] In one embodiment, the detection module is further configured to, when the items to be detected do not include the thromboelastography detection, control the sample adding needle to suck the plasma and add it to the reaction cup, and transfer the reaction cup with the added sample to a detection position, which is a magnetic bead detection position or an optical detection position.

[0147] In one embodiment, when the items to be detected include both the thromboelastography detection and the optical detection item, the detection module is further configured to control the sample adding needle to suck the sample and add it to the optical reaction cup, transfer the optical reaction cup with the added sample to an optical detection position, and detect the sample by using the optical method at the optical detection position.

[0148] In one embodiment, when the items to be detected include only the thromboelastography detection, the device further includes a merging module configured to obtain the detection results of other items except the thromboelastography detection, and generate a detection report according to the detection results of the other items and the thromboelastography.

[0149] In one embodiment, the generation module is further configured to determine the wave peak baseline and the wave trough baseline of the first derivative according to the magnetic bead oscillation waveform data, perform inverse transformation according to the wave peak baseline and the wave trough baseline of the first derivative to obtain an initial thromboelastography, and perform fitting processing on the initial thromboelastography to obtain the thromboelastography.

[0150] In one embodiment, the generation module is further configured to perform first derivative on the amplitude graph to obtain a first derivative graph, perform derivative on the first derivative graph to obtain a second derivative graph, determine a plurality of wave peaks and a plurality of wave troughs in the first derivative graph according to the second derivative graph, determine the wave peak baseline of the first derivative according to the plurality of wave peaks, and determine the wave trough baseline of the first derivative according to the plurality of wave troughs.

[0151] In one embodiment, the generation module is further configured to determine the end point of the wave peak baseline of the first derivative, extract the wave peak baseline of the first derivative according to the end point of the wave peak baseline of the first derivative, determine the end point of the wave trough baseline of the first derivative, and extract the wave trough baseline of the first derivative according to the end point of the wave trough baseline of the first derivative.

[0152] As shown in Figure 15 a thromboelastography generation device based on the magnetic bead method is provided, which includes:

[0153] The acquisition module 1502 is configured to acquire magnetic bead oscillation waveform data detected based on the magnetic bead method.

[0154] The calculation module 1504 is configured to perform conversion calculation based on the magnetic bead oscillation waveform data to obtain the thromboelastography.

[0155] As shown in Figure 16As shown, in one embodiment, the computing module 1504 comprises:

[0156] a baseline computing module 1504A configured to calculate a first derivative peak baseline and a first derivative valley baseline according to the magnetic bead oscillation waveform data;

[0157] an inverse transform module 1504B configured to perform inverse transform on the first derivative peak baseline and the first derivative valley baseline to obtain an initial thrombelastogram;

[0158] a fitting module 1504C configured to perform fitting processing on the initial thrombelastogram to obtain the thrombelastogram.

[0159] In one embodiment, the baseline computing module is further configured to perform first derivative calculation on the magnetic bead oscillation waveform data to obtain first derivative graph data; perform second derivative calculation on the first derivative graph data to obtain second derivative graph data; determine a plurality of peaks and a plurality of valleys in the first derivative graph data according to the second derivative graph data; determine the first derivative peak baseline according to the plurality of peaks, and determine the first derivative valley baseline according to the plurality of valleys.

[0160] In one embodiment, the baseline computing module is further configured to determine an end point of the first derivative peak baseline, and extract the first derivative peak baseline according to the end point of the first derivative peak baseline; determine an end point of the first derivative valley baseline, and extract the first derivative valley baseline according to the end point of the first derivative valley baseline.

[0161] In one embodiment, the baseline computing module is further configured to calculate a mean value of the first N peaks, and when a value of the N+1 peak is less than a preset proportion of the mean value of the first N peaks, take the N+1 peak as the end point of the first derivative peak baseline, wherein N is a positive integer, and extract the first derivative peak baseline according to the end point and a start point of the first derivative peak baseline, the start point of the first derivative peak baseline referring to a first peak position in the first derivative graph.

[0162] The baseline computing module is further configured to calculate a mean value of absolute values of the first N valleys, and when an absolute value of the N+1 valley is less than a preset proportion of the mean value of the absolute values of the first N valleys, take the N+1 valley as the end point of the first derivative valley baseline, wherein N is a positive integer, and extract the first derivative valley baseline according to the end point and a start point of the first derivative valley baseline, the start point of the first derivative valley baseline referring to a first valley position in the first derivative graph.

[0163] In one embodiment, the baseline calculation module is further configured to derive the plurality of peaks of the first derivative, and take the point with the fastest rate of change as the end point of the peak baseline of the first derivative; derive the plurality of valleys of the first derivative, and take the point with the fastest rate of change as the end point of the valley baseline of the first derivative.

[0164] In one embodiment, the baseline calculation module is further configured to determine, according to the magnetic bead oscillation waveform data, an amplitude pattern of the magnetic bead swing; and derive, by first-order derivation, the amplitude pattern to obtain first-order derivation pattern data.

[0165] In one embodiment, the fitting module is further configured to perform fitting processing on the initial elasticogram by using a four-parameter fitting method to obtain the thromboelastogram, wherein the four parameters in the four-parameter fitting method are obtained through experiments.

[0166] As shown in Figure 17 In one embodiment, a heparinase detection device based on a magnetic bead method is provided, which is applied to a sample analyzer and includes:

[0167] A first detection module 1702 is configured to detect a sample containing heparinase by using a magnetic bead method, and determine a first coagulation time corresponding to the sample with heparinase added according to first magnetic bead oscillation waveform data collected.

[0168] A second detection module 1704 is configured to detect, as a comparison, a sample without heparinase by using a magnetic bead method, and determine a second coagulation time corresponding to the sample without heparinase added according to second magnetic bead oscillation waveform data collected.

[0169] A determination module 1706 is configured to determine a detection result according to the first coagulation time and the second coagulation time.

[0170] In one embodiment, the first detection module 1702 is further configured to perform image plotting according to the first magnetic bead oscillation waveform data to obtain a first thromboelastogram, and determine the corresponding first coagulation time according to the first thromboelastogram.

[0171] The second detection module 1704 is further configured to perform image plotting according to the second magnetic bead oscillation waveform data to obtain a second thromboelastogram, and determine the corresponding second coagulation time according to the second thromboelastogram.

[0172] In one embodiment, the first detection module is further configured to control the sample needle to suck the sample and add it to the first magnetic bead reaction cup, transfer the first magnetic bead reaction cup to a reagent adding position, and add heparinase and a coagulation activator to the first magnetic bead reaction cup at the reagent adding position; detect the sample by using the magnetic bead method at a magnetic bead detection position, and collect first magnetic bead oscillation waveform data; and determine a first coagulation time corresponding to the first magnetic bead oscillation waveform data.

[0173] The second detection module is further configured to control the sample needle to suck the sample and add it to the first magnetic bead reaction cup, transfer the first magnetic bead reaction cup to a reagent adding position, and add only the coagulation activator to the first magnetic bead reaction cup at the reagent adding position; detect the sample by using the magnetic bead method at a magnetic bead detection position, and collect second magnetic bead oscillation waveform data; and determine a second coagulation time corresponding to the second magnetic bead oscillation waveform data.

[0174] In one embodiment, the first detection module is further configured to add the heparinase to the first magnetic bead reaction cup at the reagent adding position, and perform mixing and incubation; and add the coagulation activator to the first magnetic bead reaction cup after the mixing and incubation.

[0175] In one embodiment, the sample analyzer comprises multi-channel detection, and the sample with heparinase and the sample without heparinase are detected in parallel by using the magnetic bead method.

[0176] In one embodiment, the sample is plasma or whole blood.

[0177] In one embodiment, when the sample is whole blood, the first detection module is further configured to control the sample needle to mix the centrifuged whole blood sample, and suck the mixed whole blood sample and add it to the first magnetic bead reaction cup; and the second detection module is further configured to control the sample needle to mix the centrifuged whole blood sample, and suck the mixed whole blood sample and add it to the second magnetic bead reaction cup.

[0178] In one embodiment, the first detection module is further configured to determine a wave peak baseline and a wave trough baseline of a first derivative according to the first magnetic bead oscillation waveform data, perform inverse transformation on the wave peak baseline and the wave trough baseline of the first derivative to obtain an initial elasticogram, and perform fitting processing on the initial elasticogram to obtain the first thrombus elasticogram.

[0179] The second detection module is further configured to determine a wave peak baseline and a wave trough baseline of a first derivative according to the second magnetic bead oscillation waveform data, perform inverse transformation on the wave peak baseline and the wave trough baseline of the first derivative to obtain an initial elasticogram, and perform fitting processing on the initial elasticogram to obtain the second thrombus elasticogram.

[0180] Figure 18An internal structure diagram of a sample analyzer in an embodiment is shown. As shown in Figure 18 The sample analyzer includes a processor, a magnetic bead method detection module and a memory connected through a system bus. The memory includes a non-volatile storage medium and an internal memory. The non-volatile storage medium of the sample analyzer stores an operating system, and can also store a computer program which, when executed by the processor, can enable the processor to implement the above-mentioned thrombelastogram detection method based on the magnetic bead method, the thrombelastogram generation method based on the magnetic bead method, or the heparinase detection method based on the magnetic bead method. The internal memory can also store a computer program which, when executed by the processor, can enable the processor to execute the above-mentioned thrombelastogram detection method based on the magnetic bead method, the thrombelastogram generation method based on the magnetic bead method, or the heparinase detection method based on the magnetic bead method. Those skilled in the art can understand that Figure 18 The structure shown in the embodiment is only a block diagram of part of the structure related to the scheme of the present application, and does not constitute a limitation on the sample analyzer to which the scheme of the present application is applied. The specific sample analyzer can include more or fewer components than those shown in the figure, or combine certain components, or have a different arrangement of components.

[0181] A computer readable storage medium stores a computer program which, when executed by a processor, enables the processor to execute the steps of the above-mentioned thrombelastogram detection method based on the magnetic bead method, the thrombelastogram generation method based on the magnetic bead method, or the heparinase detection method based on the magnetic bead method.

[0182] A sample analyzer includes a memory and a processor, the memory stores a computer program which, when executed by the processor, enables the processor to execute the steps of the above-mentioned thrombelastogram detection method based on the magnetic bead method, the thrombelastogram generation method based on the magnetic bead method, or the heparinase detection method based on the magnetic bead method.

[0183] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiment methods can be completed by instructing the relevant hardware through a computer program. The program can be stored in a non-volatile computer readable storage medium, and when the program is executed, the processes of the above-mentioned embodiment methods can be included. Any reference to memory, storage, database, or other medium used in the embodiments provided in the present application can include non-volatile and / or volatile memory. Non-volatile memory can include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM), or flash memory. Volatile memory can include random access memory (RAM) or external cache memory. As an illustration but not limitation, RAM is available in various forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDR SDRAM), enhanced SDRAM (ESDRAM), synchronous link (Synchlink) DRAM (SLDRAM), memory bus (Rambus) direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.

[0184] The technical features of the above embodiments can be combined in any way. In order to make the description simple, not all possible combinations of the technical features in the above embodiments are described, but as long as the combinations of the technical features do not exist, they should be considered as the scope of the present application.

[0185] The above embodiments only express several implementation manners of the present application, and the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent of the present application. It should be pointed out that for ordinary skilled in the art, without departing from the concept of the present application, some modifications and improvements can be made, which are all within the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A heparinase detection method based on magnetic beads, applied to a sample analyzer, characterized in that, The method includes: The magnetic bead method was used to detect samples containing heparinase, and the first coagulation time corresponding to the sample containing heparinase was determined based on the collected first magnetic bead oscillation waveform data. In contrast, the magnetic bead method was used to test samples that did not contain heparinase. The second coagulation time corresponding to the sample without heparinase was determined based on the collected second magnetic bead oscillation waveform data. The test results are determined based on the first clotting time and the second clotting time; The method of using magnetic beads to detect samples containing heparinase, and determining the first clotting time corresponding to the sample with added heparinase based on the collected first magnetic bead oscillation waveform data, includes: The first thromboelastography map is obtained by plotting the image based on the oscillation waveform data of the first magnetic bead. The corresponding first clotting time is determined based on the first thromboelastogram. The method employs a magnetic bead method to detect samples that do not contain heparinase. Based on the collected second magnetic bead oscillation waveform data, the second clotting time corresponding to the sample without added heparinase is determined, including: The second thromboelastography map is obtained by plotting the image based on the oscillation waveform data of the second magnetic bead. The corresponding second clotting time is determined based on the second thromboelastography. The steps of drawing an image based on the oscillation waveform data of the first magnetic bead to obtain a first thromboelastography map, and drawing an image based on the oscillation waveform data of the second magnetic bead to obtain a second thromboelastography map, include: The peak and trough baselines of the first-order derivative are determined based on the oscillation waveform data of the first or second magnetic bead. The initial elasticity diagram is obtained by inverse transformation of the peak baseline and trough baseline of the first-order derivative; The initial elasticity map is fitted to obtain the first thromboelastography map or the second thromboelastography map; The step of determining the peak and trough baselines of the first derivative based on the oscillation waveform data of the first or second magnetic bead includes: The first derivative of the oscillation waveform data of the first magnetic bead or the oscillation waveform data of the second magnetic bead is obtained by taking the first derivative graphical data. Differentiating the first-order derivative graph data again yields the second-order derivative graph data; Based on the second-order derivative graph data, determine multiple peaks and multiple troughs in the first-order derivative graph data; The peak baseline of the first-order derivative is determined based on the multiple peaks, and the trough baseline of the first-order derivative is determined based on the multiple troughs. The step of determining the peak baseline of the first derivative based on the plurality of peaks and the trough baseline of the first derivative based on the plurality of troughs includes: Determine the endpoint of the peak baseline of the first-order derivative, and extract the peak baseline of the first-order derivative based on the endpoint of the peak baseline of the first-order derivative; determine the endpoint of the trough baseline of the first-order derivative, and extract the trough baseline of the first-order derivative based on the endpoint of the trough baseline of the first-order derivative.

2. The method according to claim 1, characterized in that, The method of using magnetic beads to detect samples containing heparinase, and determining the first clotting time corresponding to the sample with added heparinase based on the collected first magnetic bead oscillation waveform data, includes: The sample is drawn by the control needle and added to the first magnetic bead reaction cup. The first magnetic bead reaction cup is then transferred to the reagent addition position, where heparinase and coagulation activator are added to the first magnetic bead reaction cup respectively. The sample is detected using the magnetic bead method at the magnetic bead detection position, and the first magnetic bead oscillation waveform data is collected. The corresponding first clotting time is determined based on the oscillation waveform data of the first magnetic bead. The method employs a magnetic bead method to detect samples that do not contain heparinase. Based on the collected second magnetic bead oscillation waveform data, the second clotting time corresponding to the sample without added heparinase is determined, including: The sample is drawn up by the sampling needle and added to the second magnetic bead reaction cup. The second magnetic bead reaction cup is then transferred to the reagent addition position, where only the coagulation activator is added to the second magnetic bead reaction cup. The sample is detected using the magnetic bead method at the magnetic bead detection position, and the second magnetic bead oscillation waveform data is collected. The corresponding second clotting time is determined based on the oscillation waveform data of the second magnetic bead.

3. The method according to claim 2, characterized in that, The step of adding heparinase and coagulation activator to the first magnetic bead reaction vessel at the reagent addition site includes: The heparinase is added to the first magnetic bead reaction vessel at the reagent addition site and then mixed and incubated. The coagulation activator is added to the first magnetic bead reaction vessel after mixing and incubation.

4. The method according to claim 1, characterized in that, The sample analyzer includes multi-channel detection and uses the magnetic bead method to perform parallel detection on samples with added heparinase and samples without added heparinase.

5. The method according to claim 2, characterized in that, The sample is plasma or whole blood.

6. The method according to claim 5, characterized in that, When the sample is whole blood, the control needle aspirates the sample and adds it to the first magnetic bead reaction cup, including: The sampling needle is used to mix the centrifuged whole blood sample, and the mixed whole blood sample is then added to the first magnetic bead reaction cup. The control needle aspirates the sample and adds it to the second magnetic bead reaction cup, including: The sample is mixed by controlling the injection needle, and the mixed whole blood sample is then added to the second magnetic bead reaction cup.

7. A heparinase detection device based on magnetic bead method, applied to a sample analyzer, characterized in that, The device is a module for performing the steps of the heparinase detection method based on the magnetic bead method as described in any one of claims 1-6.

8. A computer-readable storage medium having a stored computer program, which, when executed by a processor, causes the processor to perform the steps of the heparinase detection method based on the magnetic bead method as described in any one of claims 1 to 6.

9. A sample analyzer, comprising a memory and a processor, the memory having a stored computer program, which, when executed by the processor, causes the processor to perform the steps of the heparinase detection method based on the magnetic bead method as described in any one of claims 1 to 6.

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