A sample analyzer and method for detecting blood clotting time based on magnetic bead method

Abstract

The application provides a sample analyzer and method for detecting blood clotting time based on a magnetic bead method. The sample analyzer comprises a detection device and a controller, the detection device comprises a driving assembly and a sensing assembly, the controller is used for detecting a first reaction solution in the reaction container by controlling the detection device; and in a time period of 0 to T0 of the detection process, the driving assembly is controlled to drive the magnetic beads to oscillate in the reaction container at the first average power, and in a time period of T0 to T1 of the detection process, the driving assembly is controlled to switch to drive the magnetic beads to oscillate in the reaction container at the second average power; the end time of the reaction is judged based on the amplitude degree of the magnetic beads of the reaction container in the time period of 0-T1, and the blood clotting time of the sample is output. The application adopts a time period detection method for the same reaction solution, so as to improve the accuracy of the detection of samples with low blood clotting function.

Description

Technical Field

[0001] This invention is applied to the field of in vitro diagnostics, specifically relating to a sample analyzer and method for detecting blood clotting time based on magnetic bead method. Background Technology

[0002] A coagulation analyzer is a clinical instrument used to analyze the coagulation and anticoagulation, fibrinolysis, and antifibrinolysis functions of a patient's blood. The coagulation method can be used to determine the coagulation or fibrinolytic properties of a blood sample. Currently, the magnetic bead method is commonly used to test the coagulation characteristics of blood samples, such as clotting time. Its basic principle is to drive the movement of magnetic beads through a magnetic field and assess the clotting time based on the movement of the beads. During the test, when the sample's coagulation function is weak, the resulting fragile fibrin network is insufficient to exert enough binding force on the magnetic beads. This causes the sample to fail to coagulate or the magnetic beads to restart oscillation during the testing phase, thus affecting the accuracy of the clotting time measurement and ultimately failing to accurately reflect the sample's coagulation function. Summary of the Invention

[0003] To address the problem of inaccurate detection results in existing technologies, the first aspect of this invention provides a sample analyzer, comprising: A detection device is used to detect the blood clotting time of a sample within a reaction vessel. The detection device includes a driving component and a sensing component. The driving component periodically applies a driving electromagnetic field to the reaction vessel, having an average power in each cycle to drive magnetic beads to oscillate within the reaction vessel. The driving component contains at least a first average power and a second average power, with the second average power being lower than the first average power. The sensing component collects data on the movement of the magnetic beads during the blood clotting reaction of the sample, and this movement reflects the reaction information of the sample. Controller, used for: The detection device is controlled to detect the first reaction solution in the reaction container; and during the detection process from 0 to T0, the driving component is controlled to drive the magnetic bead to oscillate in the reaction container with the first average power, and during the detection process from T0 to T1, the driving component is controlled to switch to drive the magnetic bead to oscillate in the reaction container with the second average power; the reaction end time is determined based on the amplitude of the magnetic bead in the reaction container during the 0-T1 time period, and the blood coagulation time of the sample is output.

[0004] A second aspect of the present invention also provides a method for detecting blood clotting time, comprising: The sample and reaction reagents are placed in a reaction container with magnetic beads and mixed to form the first reaction solution; The first reaction solution in the reaction vessel is detected. During the detection process, a driving electromagnetic field is periodically applied to the reaction vessel, and each cycle has an average power. During the detection process from 0 to T0, the magnetic beads are driven to oscillate within the reaction container with a first average power. During the detection process from T0 to T1, the magnetic beads are driven to oscillate within the reaction container with a second average power. The reaction end time is determined based on the amplitude of the magnetic beads in the reaction container from 0 to T1, and the blood coagulation time of the sample is output. The second average power is lower than the first average power. Attached Figure Description

[0005] Figure 1 This is a block diagram of the sample analyzer in one embodiment. Detailed Implementation

[0006] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. This application will now be described in detail with reference to the accompanying drawings and embodiments.

[0007] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0008] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps described in these embodiments do not limit the scope of this application. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters in the following drawings denote similar items; therefore, once an item is defined in one drawing, it need not be further discussed in subsequent drawings.

[0009] To address the problem of insufficient accuracy in existing technologies using magnetic beads to detect blood clotting time, where samples with low coagulation function may not coagulate under a magnetic field of fixed average power or may experience re-oscillation, such as... Figure 1 As shown, the first aspect of this invention provides a sample analyzer applied in the field of coagulation, capable of performing various coagulation tests and outputting corresponding test results. For example, the test items include fibrinogen (FIB), prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT), coagulation factors, clinical anticoagulants, or other custom items, etc., without specific limitations here.

[0010] The sample analyzer 1 includes an analyzer execution unit (not shown in the figure) and a controller 10 communicatively connected to the analyzer execution unit. The analyzer execution unit includes a detection device 20. The detection device 20 is used to detect the blood clotting time of the sample in the reaction vessel. The detection device 20 uses a magnetic bead method, which drives the magnetic beads to reciprocate within the reaction vessel by applying an alternating magnetic field, and collects the motion state of the magnetic beads. The controller 10 evaluates the blood clotting time based on the motion state of the magnetic beads, thereby outputting the detection results of the corresponding coagulation test item.

[0011] In this embodiment, the reaction container is used to hold the reaction solution required for the detection, such as a first reaction solution formed by the sample and reaction reagents. It is understood that, depending on the detection requirements, the reaction container can also hold other solutions required for the detection. For example, when the sample needs to be diluted, the reaction container can also hold a first reaction solution comprising the sample, diluent, and reaction reagents; this is not specifically limited here.

[0012] In some embodiments, the reaction vessel may be pre-loaded with magnetic beads.

[0013] In some embodiments, the sample analyzer also includes a bead-adding mechanism capable of adding magnetic beads into the reaction vessel.

[0014] In some embodiments, the sample includes a blood sample from a patient, specifically a blood sample stored in a sample tube containing an anticoagulant, or an artificially prepared simulated blood sample; the reaction reagent contains at least a factor capable of inducing blood coagulation, exemplarily including tissue factor, thrombin, etc. In some embodiments, the detection device 20 includes a driving component 210, which is used to periodically apply a driving electromagnetic field to the reaction vessel. It is understood that the reaction vessel is placed within the driving electromagnetic field, and the movement of the magnetic bead can be driven by the driving component 210.

[0015] In some embodiments, an average power is provided for each cycle to drive the magnetic bead to oscillate within the reaction vessel. Specifically, the driving assembly 210 includes two sets of driving coils, which are respectively distributed on both sides of the reaction vessel. These coils generate periodic driving electromagnetic fields to drive the magnetic bead to reciprocate within the reaction vessel. It is understood that the two sets of driving coils use the same average power to ensure the generation of a magnetic field of equal strength, thus avoiding the introduction of unnecessary interference factors into the detection process.

[0016] In the prior art, the driving component 210 generally applies a driving electromagnetic field with a fixed average power to the reaction vessel. Since the concentration of fibrinogen in different samples is different, the binding force of the fibrin network formed on the magnetic beads is different. Applying a driving electromagnetic field with a fixed average power is not conducive to accurate detection of different samples. In particular, when the sample has a weak coagulation function, the binding force of the fibrin network formed by the reaction on the magnetic beads is weak. Continuing to apply a driving electromagnetic field with a fixed average power will cause the driving component 210 to have an excessive driving force on the magnetic beads or an excessively long driving time, which will prolong the blood coagulation time and make the detection inaccurate.

[0017] To address the aforementioned issues, in this embodiment, the driving component 210 has a first average power and a second average power, with the second average power being lower than the first average power. This means that the driving component 210 can apply two driving electromagnetic fields with different average powers to the reaction vessel. When the sample has a weak coagulation function, the driving component 210 applies a lower second average power to the reaction vessel, which can reduce interference with the coagulation process and thus obtain more accurate detection results.

[0018] It is understandable that the average power P of the drive component 210 over one cycle T is equal to the total work done in one cycle (W) / cycle T, where the total work (W) = U 2 / R×ΔT, where ΔT is the time the drive component 210 is energized within one cycle, i.e., the average power of the drive component 210 within one cycle T, P=U. 2 / R×ΔT / T, where the resistance R and period T of the drive coil in the drive component 210 generally do not change.

[0019] In some embodiments, the average power is adjusted by regulating the voltage applied to the driving component 210. Since changing the voltage applied to the driving component 210 alters the current flowing through it, the strength of the driving electromagnetic field generated by the driving component 210 is indirectly adjusted. In other words, by adjusting the voltage applied to the driving component 210, the magnitude of the driving force on the magnetic bead can be changed. When the driving component 210 outputs a lower average power (second average power), the driving force on the magnetic bead is smaller, allowing samples with weaker coagulation function to complete the blood coagulation process normally during the reaction, thus obtaining the blood coagulation time and ensuring the accuracy of the detection.

[0020] In other embodiments, the average power is adjusted by changing the energizing time of the driving component 210, i.e., adjusting the duration of the driving electromagnetic field generated by the driving component 210, thereby changing the time the magnetic bead is driven by the driving force. In other words, while keeping the driving force constant, the kinetic energy of the magnetic bead is affected by changing the duration of its driving force. When the driving component 210 outputs a lower average power (second average power), the magnetic bead is driven for a shorter time, which better meets the detection requirements of samples with weak coagulation function and ensures detection accuracy.

[0021] In some embodiments, the detection device 20 further includes a sensing component 220, which is used to collect the movement of the magnetic beads during the blood coagulation reaction of the sample. The movement reflects the reaction information of the sample. Specifically, the sensing component 220 includes an induction coil, which generates an induced electromagnetic field to detect the movement of the magnetic beads within the reaction container, such as changes in the amplitude of the magnetic beads. Specifically, when the magnetic beads move within the induced electromagnetic field, the induction coil generates a corresponding induced current. By converting or processing the induced current, the movement of the magnetic beads can be determined. It is understood that the reaction container is simultaneously positioned within both the driving electromagnetic field and the induced electromagnetic field, and the driving component 210 and the sensing component 220 can complete both the driving and detection of the magnetic beads' movement.

[0022] In some embodiments, the controller 10 is at least used, specifically, for the controller's processor to invoke a computer program in memory to implement the following method steps: The control and detection device 20 detects the first reaction solution in the reaction vessel; and during the detection process from 0 to T0, the control and drive component 210 drives the magnetic bead to oscillate in the reaction vessel with the first average power, and during the detection process from T0 to T1, the control and drive component 210 switches to drive the magnetic bead to oscillate in the reaction vessel with the second average power.

[0023] This application employs a time-segmented detection method for the same reaction solution. By driving the magnetic beads to oscillate with different average power outputs from the drive component 210 at different time periods, a wider detection range of sample coagulation function can be achieved. Specifically, the controller controls the detection device 20 to continuously detect the first reaction solution in the reaction container during the 0-T1 time period, where T0 is one of the moments within the 0-T1 time period. During the continuous detection process, a fixed high level of first average power is used during the 0-T0 time period to establish a uniform magnetic bead movement trajectory for samples within the detection linear range, which can be subsequently detected, providing standardized mechanical initial conditions for all samples. For samples that cannot complete blood coagulation within the 0-T0 time period, the magnetic beads are driven to oscillate with a weaker second average power during the T0-T1 time period. This allows samples that could not complete blood coagulation as scheduled during the 0-T0 time period due to the disruption of the weak fibrin network formed during the reaction process caused by the high-intensity movement of the magnetic beads, to continue the reaction under the weaker magnetic bead movement state during the T0-T1 time period. During the reaction, there is no need to change the reaction solution, which improves detection efficiency while ensuring the consistency of the detection liquid environment used for different test samples as much as possible, thereby improving the accuracy of testing samples with low coagulation function.

[0024] In some embodiments, when the controller 10 switches the control drive component 210 to apply the driving electromagnetic field to the reaction vessel with the first average power to the second average power, the drive component 210 directly switches from the first average power to the second average power. That is, if the reaction is not over based on the amplitude of the magnetic bead during the 0-T0 time period, it indicates that the coagulation ability of the sample in the reaction vessel is weak. The current first average power has a strong driving force on the magnetic bead or the magnetic bead is driven for a long time, so an accurate result cannot be obtained. After reaching the T0 time, it directly switches to the lower second average power to ensure the efficiency of detection.

[0025] In other embodiments, when the controller 10 switches the driving electromagnetic field applied to the reaction vessel by the driving component 210 with a first average power to a second average power, the driving component 210 gradually reduces from the first average power to the second average power. The driving intensity of the driving electromagnetic field can decrease linearly or non-linearly. It is understood that the time for switching from the first average power to the second average power is assumed to be T. 切 Then (T0+T) 切 (T0) is less than or equal to T1, preferably (T0+T) 切 If the driving intensity is less than T1, then after the driving intensity is switched, the magnetic bead is continuously driven to move in the reaction vessel with the second average power, so that the magnetic bead can continue to complete the detection under a weaker driving force or a shorter driving time.

[0026] Preferably, the driving component 210 gradually decreases from the first average power to the second average power in a linear manner. In this way, the driving force on the magnetic bead gradually decreases or the driving time gradually decreases, which is conducive to the smooth reduction of the magnetic bead amplitude, avoids misjudging the end of the reaction due to sudden changes in the movement of the magnetic bead, and improves the repeatability of the detection, which is conducive to controlling the coefficient of variation (CV) of the experimental results.

[0027] In some embodiments, the controller is further configured to: determine the reaction end time based on the amplitude of the magnetic bead in the reaction vessel during the 0-T1 time period, and output the blood clotting time of the sample. That is, the reaction end time is determined based on the attenuation of the magnetic bead's amplitude. In some embodiments, based on the initial amplitude of the magnetic bead, a termination amplitude (e.g., 50% of the initial amplitude) is set to indicate the end of the reaction. When the sensing component 220 detects that the amplitude of the magnetic bead's amplitude has attenuated to the termination amplitude, the controller determines that the reaction has ended, thereby outputting the blood clotting time of the sample.

[0028] In some embodiments, the second average power is 50%-90% of the first average power. If the second average power is too weak, it cannot drive the magnetic beads to vibrate in the first reaction solution, which is detrimental to collecting reaction information of the blood coagulation reaction process of the sample. If the second average power is too strong, the driving force for the magnetic bead oscillation is still large, and if the fibrin network formed by the sample with coagulation function is easily destroyed by the magnetic beads, it will lead to inaccurate detection. Specifically, it can be determined based on the average power corresponding to the blood coagulation that can occur in the 0-T1 time period of the sample with weak coagulation function. For example, a sample with weak coagulation function can refer to a low fibrinogen sample, wherein the fibrinogen content in the low fibrinogen sample can be lower than 0.5 g / L, 0.4 g / L, 0.3 g / L, or 0.1 g / L.

[0029] In some embodiments, T1 is not less than 90s, 100s, 110s, 120s, 130s, 140s, 150s, 160s, 170s, or 180s.

[0030] In some embodiments, the controller is further configured to: determine the reaction end time based on the magnetic bead amplitude of the reaction vessel during the 0-T1 time period; if the reaction ends, control the drive component to stop working at the reaction end time; otherwise, control the drive component to stop working and output a reaction abnormality signal at time T1.

[0031] Specifically, if the end of the reaction is detected at any time within the 0-T1 time period, the blood clotting time of the sample is output. If the end of the reaction is not detected within the 0-T1 time period, it indicates that the current sample's clotting function is weak, and the blood clotting time cannot be obtained by changing the driving strength. In this case, an abnormal reaction signal is sent to the user, which can reduce the burden on the user in analyzing experimental results and improve detection efficiency.

[0032] In some embodiments, the controller is further configured to determine the concentration of the analyte in the sample based on the blood clotting time and calibration curve corresponding to the sample. The sample is a blood sample containing an unknown concentration of the analyte, and the calibration curve is a curve obtained after performing detection on a multi-level calibrator of known concentration in the aforementioned sample analyzer's detection device 20. Specifically, the calibration curve can be used to reflect the relationship between the blood clotting time and the concentration of the analyte in the sample.

[0033] In this embodiment, the multi-level calibrators with known concentrations can be simulated blood samples obtained by pre-preparing a stock solution using a known amount of the analyte and then diluting it at different dilution ratios, or simulated blood samples prepared separately using known amounts of the analyte at different levels. These calibrators are tested in the aforementioned sample analyzer, ensuring that the calibrators and samples are tested using the same control methods. Furthermore, the blood clotting time of the first-level calibrator is greater than T0, and the blood clotting time of the second-level calibrator is less than T0. This means that at least one low-level calibrator completes its reaction within the T0-T1 time period, and one high-level calibrator completes its reaction within the 0-T0 time period, thereby ensuring that the multi-level calibrators can cover detection environments under different time periods and driving intensities. The resulting calibration curve, generated using the same sample analyzer under the same time-segmented average power adjustment reaction conditions, can accurately reflect the analyte concentration in the sample.

[0034] In some embodiments, T0 is greater than or equal to the blood clotting time corresponding to the lowest concentration of the analyte in the sample that the detection device 20 can detect when performing detection at a first average power. Specifically, when the detection device 20 performs detection at a fixed first average power, the blood clotting time can be obtained for samples containing a first detection low value. If the concentration of the analyte in the sample is further lower than the first detection low value, the blood clotting time cannot be detected under the first average power condition due to excessive driving intensity. In this case, the first detection low value is the lowest concentration of the analyte in the sample that the detection device 20 can detect when performing detection at the first average power.

[0035] Specifically, when the detection device 20 performs detection at a fixed first average power, the blood clotting time for a sample containing 0.5 g / L fibrinogen is 55 seconds. Samples with fibrinogen levels below 0.5 g / L cannot be further detected at the first average power to obtain a blood clotting time. Therefore, 0.5 g / L is the lowest concentration of fibrinogen that the detection device 20 can detect at the first average power, and T0 should be greater than or equal to 55 seconds, for example, T0 = 60 seconds. Samples with fibrinogen levels below 0.5 g / L will be detected at the second average power within the T0-T1 time period in the detection device 20. Therefore, the end time of the blood clotting reaction for samples with fibrinogen levels below 0.5 g / L will inevitably fall within the T0-T1 time period.

[0036] In this embodiment, the lowest concentration detected by the sample analyzer in a single detection cycle is lower than the lowest concentration of the analyte in the sample that the detection device 20 can detect when performing detection at the first average power. This means that the control method provided by the present invention further broadens the detection range. Simultaneously, samples within the detection range at the first average power are unaffected, and the blood clotting time of low-concentration samples does not overlap with the clotting time of concentrations within the normal range, thereby improving detection accuracy.

[0037] In some embodiments, the sample analyzer further includes a reaction solution preparation device 40, which is used to dispense the sample and reaction reagents into the reaction container to form a first reaction solution. It is understood that, depending on the detection requirements, if other solutions required for detection need to be dispensed, for example, when the sample needs to be diluted, the reaction solution preparation device 40 can also be used to dispense diluent to form a first reaction solution with the sample and reaction reagents. This is not specifically limited here.

[0038] In some embodiments, the reaction solution preparation apparatus 40 includes a sample dispensing mechanism, a reagent dispensing mechanism, and / or a diluent dispensing mechanism, for dispensing samples, reagents, and / or diluents into the reaction vessel, respectively.

[0039] The sample dispensing mechanism includes a sample needle, a sample needle moving assembly, and a first liquid path system. The sample needle moving assembly is used to drive the sample needle to move between the aspiration position and the dispensing position, and the first liquid path system is used to realize the sample aspiration and dispensing operations.

[0040] The reagent dispensing mechanism includes a reagent needle, a reagent needle moving assembly, and a second liquid path system. The reagent needle moving assembly is used to drive the reagent needle to move between the reagent aspiration position and the reagent dispensing position, and the second liquid path system is used to realize the reagent aspiration and dispensing operations.

[0041] The diluent dispensing mechanism includes a diluent needle, a diluent needle moving assembly, and a third liquid path system. The diluent needle moving assembly is used to drive the diluent needle to move between the diluent suction position and the diluent discharge position, and the third liquid path system is used to realize the diluent suction and discharge operations.

[0042] In some implementations, the reagent dispensing mechanism and the diluent dispensing mechanism are the same dispensing mechanism.

[0043] In some embodiments, the sample analyzer also includes a reaction vessel transfer device 30, which includes grippers, a gripper tensioning drive assembly, and a gripper movement drive assembly. The gripper tensioning drive assembly is used to drive the grippers to grasp or release the reaction vessel, and the gripper movement drive assembly is used to drive the grippers to transfer the reaction vessel between different devices, for example, to transfer the reaction vessel configured in the reaction solution preparation device 40 to the detection device 20.

[0044] In some embodiments, the sample analyzer also includes a sample storage mechanism (not shown) for storing samples.

[0045] In some embodiments, the sample analyzer further includes a reagent storage mechanism (not shown) for storing reaction reagents and / or diluents.

[0046] In some embodiments, the controller is also used to control the reaction solution preparation device 40 to add the sample and reaction reagent to the reaction container according to a first preset ratio; control the reaction container transfer device 30 to transfer the reaction container after the first reaction solution has been prepared to the detection device 20 for detection, and output the blood coagulation time.

[0047] In some embodiments, the controller is further configured to execute a retest process if the reaction has not ended at time T1. Specifically, this includes controlling the reaction solution preparation device 40 to add the sample and reaction reagents to another reaction container according to a second preset ratio, and controlling the reaction container transfer device 30 to transfer the reaction container with the second reaction solution prepared to the detection device 20 for detection. The sample content in the second reaction solution is greater than the sample content in the first reaction solution. By increasing the sample content, the ability of the sample to form a fibrin network in a magnetic field is enhanced, enabling the detection device 20 to detect samples with lower fibrinogen content and obtain blood clotting time, further expanding the detectable range of the detection device 20.

[0048] In some specific embodiments, the proportion of the sample in the total volume of the second reaction solution can be increased by increasing the amount of sample or decreasing the amount of reaction reagent, thereby increasing the proportion of the analyte in the total volume of the second reaction solution.

[0049] In some specific embodiments, the first reaction solution and / or the second reaction solution further include a diluent, and the controller is also used to control the reaction solution preparation device to add the diluent to the reaction vessel or reaction container to form the first reaction solution or the second reaction solution.

[0050] In some more specific embodiments, the proportion of the sample in the total volume of the second reaction solution can be increased by increasing the amount of sample or decreasing the amount of diluent, thereby increasing the proportion of the analyte in the total volume of the second reaction solution. Thus, the amount of reaction reagent containing coagulation activating factor remains unchanged, which is more conducive to ensuring the accuracy of the detection.

[0051] In some embodiments, the total volume of the second reaction solution is equal to the total volume of the first reaction solution.

[0052] In some embodiments, the controller is further configured to determine the concentration of the analyte based on the sample output blood clotting time, calibration curve, and concentration parameters. The calibration curve is a curve obtained after performing detection in the aforementioned detection device 20 using multi-level calibrators of known concentrations. Specifically, the calibration curve can be used to reflect the relationship between the blood clotting time of the sample and the concentration of the analyte in the sample.

[0053] In this embodiment, the multi-level calibrators with known concentrations can be simulated blood samples obtained by pre-preparing a stock solution using a known amount of the analyte and then diluting it at different dilution ratios, or simulated blood samples prepared separately using known amounts of the analyte at different levels. These calibrators are tested in the aforementioned sample analyzer, ensuring that the calibrators and samples are tested using the same control methods. Furthermore, the blood clotting time of the first-level calibrator is greater than T0, and the blood clotting time of the second-level calibrator is less than T0. This means that at least one low-level calibrator completes its reaction within the T0-T1 time period, and one high-level calibrator completes its reaction within the 0-T0 time period, thereby ensuring that the multi-level calibrators can cover detection environments with different time periods and different average power drives. Therefore, the calibration curve is generated based on the same sample analyzer under the same time-segmented average power adjustment reaction conditions, and can be used to accurately reflect the analyte concentration in the sample.

[0054] The concentration parameter is obtained by dividing the proportion of the sample in the total volume of the second reaction solution by the proportion of the sample in the total volume of the first reaction solution.

[0055] A second aspect of the present invention also provides a method for detecting blood clotting time, applied to a sample analyzer, comprising: The sample and reaction reagents are mixed in a reaction vessel containing magnetic beads to form the first reaction solution; The first reaction solution in the reaction vessel is detected. During the detection process, a driving electromagnetic field is periodically applied to the reaction vessel, and each cycle has an average power. During the time period from 0 to T0, the magnetic beads are driven to oscillate in the reaction vessel with the first average power, and during the time period from T0 to T1, the magnetic beads are driven to oscillate in the reaction vessel with the second average power. The reaction end time is determined based on the amplitude of the magnetic beads in the reaction vessel from 0 to T1, and the blood coagulation time of the sample is output, wherein the second average power is lower than the first average power.

[0056] When the sample has a weak coagulation function, the magnetic beads are driven to oscillate in the reaction vessel with a second average power lower than the first average power. This reduces the interference of the magnetic beads on the coagulation process, allowing such samples to complete blood coagulation, and thus the blood coagulation time corresponding to the sample can be detected.

[0057] This approach employs a time-segmented detection method for the same reaction solution. By driving the magnetic beads to oscillate at different average powers during different time periods, the blood clotting time of the samples is detected. This allows for the detection of samples with a wider detection range without changing the reagent kit composition. Specifically, the first reaction solution in the reaction vessel is continuously and uninterruptedly detected during the 0-T1 time period, where T0 is one of the moments within the 0-T1 time period. During the continuous detection, a fixed high level of the first average power is used during the 0-T0 time period to establish a uniform magnetic bead motion trajectory for samples within the detection linear range, providing standardized initial mechanical conditions for all samples. For low-concentration samples that cannot complete blood clotting within the first time period, the magnetic bead oscillation is switched to a weaker second average power during the T0-T1 time period. This allows samples that could not complete blood clotting due to the disruption of the weak fibrin network formed during the reaction process caused by the high-intensity magnetic bead motion during the 0-T0 time period to continue the reaction under the low-intensity magnetic bead motion environment during the T0-T1 time period. During the reaction process, there is no need to change the reaction solution, which improves detection efficiency while ensuring the consistency of the detection liquid environment used for different test samples as much as possible, thereby improving the accuracy of detection of low-concentration samples.

[0058] In some embodiments, during the time period from 0 to T0, the magnetic beads are driven to oscillate within the reaction vessel at a first average power. At time T0 within the time period from T0 to T1, the first average power is directly switched to a second average power to drive the magnetic beads to oscillate within the reaction vessel. That is, if the reaction is not complete based on the amplitude of the magnetic beads during the 0-T0 time period, it indicates that the fibrin network formed in the reaction vessel is weak and blood coagulation cannot be completed, resulting in inaccurate results. Switching directly to a lower second average power after time T0 ensures detection efficiency.

[0059] In another embodiment, during the time period from 0 to T0, the magnetic beads are driven to oscillate within the reaction vessel at a first average power, and during the time period from T0 to T1, the first average power is gradually reduced to drive the magnetic beads to oscillate within the reaction vessel at a second average power. Specifically, the reduction can be linear or non-linear.

[0060] It is understandable that we assume the time for switching from the first average power to the second average power is T. 切 Then (T0+T) 切 (T0) is less than or equal to T1, preferably (T0+T) 切 If the driving intensity is less than T1, then after the switching of driving intensity is completed, the magnetic bead is continuously driven to move in the reaction vessel with the second average power to ensure that the magnetic bead can continue to complete the detection under a lower driving force.

[0061] Preferably, the first average power gradually decreases to the second average power in a linear manner. In this way, the driving force on the magnetic bead gradually decreases, which is conducive to the smooth reduction of the magnetic bead amplitude. This avoids misjudging the end of the reaction due to sudden changes in the movement of the magnetic bead, and has good repeatability, which is helpful in controlling the coefficient of variation (CV) of the experimental results.

[0062] In some embodiments, the method further includes: determining the reaction end time based on the amplitude of the magnetic bead in the reaction container during the 0-T1 time period, and outputting the blood clotting time of the sample. That is, the reaction end time is determined based on the attenuation of the magnetic bead's amplitude. In some embodiments, based on the initial amplitude of the magnetic bead, a termination amplitude (e.g., 50% of the initial amplitude) is set to indicate the end of the reaction. When the sensing component 220 detects that the amplitude of the magnetic bead's amplitude has attenuated to the termination amplitude, the controller determines that the reaction has ended, thereby outputting the blood clotting time of the sample.

[0063] In some embodiments, the second average power is 50%-90% of the first average power. If the second average power is too weak, it cannot drive the magnetic beads to vibrate in the first reaction solution, which is detrimental to collecting reaction information of the blood coagulation reaction process of the sample. If the second average power is too strong, the driving force of the magnetic bead oscillation is still large, and the fibrin network formed by samples with weak coagulation function is easily destroyed by the magnetic beads, resulting in inaccurate detection. Specifically, it can be determined based on the average power corresponding to the coagulation of samples with weak coagulation function before time T1. For example, a sample with weak coagulation function can refer to a low fibrinogen sample, wherein the fibrinogen content in the low fibrinogen sample can be lower than 0.5 g / L, 0.4 g / L, 0.3 g / L, or 0.1 g / L.

[0064] In some implementations, T1 is not less than 90s, 100s, 110s, 120s, 130s, 140s, 150s, 160s, 170s, or 180s.

[0065] In some embodiments, the method further includes: determining the reaction progress based on the amplitude of the magnetic bead in the reaction vessel during the time period 0-T1; if the reaction ends, controlling the drive component to stop working at the time of reaction end; otherwise, controlling the drive component to stop working and outputting a reaction abnormality signal at time T1.

[0066] Specifically, if the end of the reaction is detected at any time within the 0-T1 time period, the blood clotting time of the sample is output. If the end of the reaction is not detected within the 0-T1 time period, it indicates that the current sample has poor clotting function and the blood clotting time cannot be obtained by changing the driving strength. In this case, an abnormal reaction signal is sent to the user, which can reduce the burden on the user in analyzing experimental results and improve detection efficiency.

[0067] In some embodiments, the method further includes determining the concentration of the analyte in the sample based on the blood clotting time and calibration curve corresponding to the sample. The sample is a blood sample containing an unknown concentration of the analyte, and the calibration curve is a curve obtained after performing detection on a multi-level calibrator of known concentration in the detection device 20 of the aforementioned sample analyzer. That is, curves obtained after performing detection on different levels of calibrators and samples using the same detection method.

[0068] In this embodiment, the multi-level calibrators with known concentrations can be simulated blood samples obtained by pre-preparing a stock solution using a known amount of the analyte and then diluting it at different dilution ratios, or simulated blood samples prepared separately using known amounts of the analyte at different levels. These calibrators are tested in the preceding sample analyzer, ensuring that they are tested using the same control methods as the samples. Furthermore, the first-level calibrator has a blood clotting time greater than T0, while the second-level calibrator has a blood clotting time less than T0. This means that at least one low-level calibrator completes its reaction within the T0-T1 time period, and one high-level calibrator completes its reaction within the 0-T0 time period, thus ensuring that the multi-level calibrators can cover detection environments under different time periods and driving intensities. The resulting calibration curve, generated using the same sample analyzer under the same time-segmented average power adjustment reaction conditions, can accurately reflect the concentration of the analyte in the sample.

[0069] In some implementations, T0 is greater than or equal to the blood clotting time corresponding to the lowest concentration of the analyte in the sample that can be detected when the detection is performed at the first average power. Specifically, when the detection is performed at a fixed first average power, the blood clotting time can be obtained for samples containing a first detection low value. If the concentration of the analyte in the sample is further lower than the first detection low value, the blood clotting time cannot be detected under the first average power condition due to excessive driving intensity. In this case, the first detection low value is the lowest concentration of the analyte in the sample that can be detected when the detection is performed at the first average power, as mentioned above.

[0070] Specifically, when performing detection at a fixed first average power, the blood clotting time for a sample containing 0.5 g / L fibrinogen is 55 seconds. Samples with fibrinogen concentrations below 0.5 g / L cannot be further detected at the first average power to obtain their clotting time. Therefore, 0.5 g / L is the lowest concentration of fibrinogen detectable at the first average power, and T0 should be greater than or equal to 55 seconds, for example, T0 = 60 seconds. Samples with concentrations below 0.5 g / L will then be detected at the second average power within the T0-T1 time period. Therefore, the end time of the blood clotting reaction for samples with concentrations below 0.5 g / L will inevitably fall within the T0-T1 time period.

[0071] Based on the above method, the lowest concentration detected by the sample analyzer in a single detection cycle is lower than the lowest concentration of the analyte in the sample that can be detected when the first average power is used. In other words, the control method provided by this invention further broadens the detection range. At the same time, samples within the detection range under the first average power are not affected, and the blood clotting time of low-concentration samples will not overlap with the clotting time of concentrations within the normal range, thereby improving the accuracy of detection.

[0072] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0073] The above embodiments merely illustrate several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of this patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A sample analyzer, characterized in that, include: A detection device used to detect the blood clotting time of samples inside a reaction vessel; The detection device includes a driving component and a sensing component. The driving component is used to periodically apply a driving electromagnetic field to the reaction vessel, and has an average power in each cycle to drive the magnetic beads to oscillate within the reaction vessel. The driving component contains at least a first average power and a second average power, and the second average power is lower than the first average power. The sensing component is used to collect the movement of the magnetic beads during the blood coagulation reaction of the sample, and the movement is used to reflect the reaction information of the sample. Controller, used for: The detection device is controlled to detect the first reaction solution in the reaction container; and during the detection process from 0 to T0, the driving component is controlled to drive the magnetic bead to oscillate in the reaction container with the first average power, and during the detection process from T0 to T1, the driving component is controlled to switch to drive the magnetic bead to oscillate in the reaction container with the second average power; the reaction end time is determined based on the amplitude of the magnetic bead in the reaction container during the 0-T1 time period, and the blood coagulation time of the sample is output.

2. The sample analyzer according to claim 1, characterized in that, The controller is further configured to: determine the reaction end time based on the amplitude of the magnetic bead in the reaction vessel during the time period 0-T1; if the reaction ends, control the drive component to stop working at the reaction end time; otherwise, control the drive component to stop working and output a reaction abnormality signal at time T1.

3. The sample analyzer according to claim 1, characterized in that, The second average power is 50% to 90% of the first average power.

4. The sample analyzer according to claim 1, characterized in that, The controller is further configured to: determine the concentration of the analyte in the sample based on the blood clotting time and calibration curve corresponding to the sample, wherein the calibration curve is a curve obtained after a multi-level calibrator of known concentration is tested in the detection device, wherein the blood clotting time of the first level calibrator is greater than T0, and the blood clotting time of the second level calibrator is less than T0.

5. The sample analyzer according to claim 4, characterized in that, The T0 is greater than or equal to the blood clotting time corresponding to the lowest concentration of the analyte in the sample that the detection device can detect when performing detection at the first average power.

6. The sample analyzer according to claim 1, characterized in that, The sample analyzer also includes: A reaction solution preparation apparatus for adding the sample, diluent, and reaction reagents to the reaction vessel; A reaction vessel transfer device for transferring the reaction vessel; The controller is also used for: The reaction solution preparation device is controlled to add the sample, the diluent and the reaction reagent to the reaction container in a first preset ratio to form the first reaction solution; The reaction vessel transfer device controls the transfer of the reaction vessel containing the first reaction solution to the detection device for detection.

7. The sample analyzer according to claim 6, characterized in that, The controller is further configured to: if the reaction is not completed within the 0-T1 time period, execute a retest process, specifically including: The reaction solution preparation device is controlled to add the sample, the diluent, and the reaction reagent to another reaction vessel according to a second preset ratio to form a second reaction solution; The reaction vessel transfer device controls the transfer of the other reaction vessel containing the second reaction solution to the detection device for detection, and outputs the blood clotting time, wherein the sample content in the second reaction solution is greater than the sample content in the first reaction solution.

8. The sample analyzer according to claim 7, characterized in that, The controller is further configured to: determine the concentration of the analyte in the sample based on the blood clotting time, calibration curve and concentration parameters output by the sample, wherein the calibration curve is a curve obtained after performing detection in the detection device based on a multi-level calibrator of known concentration, wherein the blood clotting time of the first level calibrator is greater than T0 and the blood clotting time of the second level calibrator is less than T0.

9. The sample analyzer according to claim 7, characterized in that, The total volume of the first reaction solution is equal to the total volume of the second reaction solution.

10. A method for detecting blood clotting time, said method being applied to a sample analyzer, characterized in that, The method includes: The sample and reaction reagents are placed in a reaction container with magnetic beads and mixed to form the first reaction solution; The first reaction solution in the reaction vessel is detected. During the detection process, a driving electromagnetic field is periodically applied to the reaction vessel, and each cycle has an average power. During the detection process from 0 to T0, the magnetic beads are driven to oscillate within the reaction container with a first average power. During the detection process from T0 to T1, the magnetic beads are driven to oscillate within the reaction container with a second average power. The reaction end time is determined based on the amplitude of the magnetic beads in the reaction container from 0 to T1, and the blood coagulation time of the sample is output. The second average power is lower than the first average power.

11. The method according to claim 10, characterized in that, The second average power is 50% to 90% of the first average power.

12. The method according to claim 10, characterized in that, The method further includes determining the concentration of the analyte in the sample based on the blood clotting time and calibration curve corresponding to the sample, wherein the calibration curve is a curve obtained after detection based on a multi-level calibrator of known concentration, wherein the blood clotting time of the first level calibrator is greater than T0, and the blood clotting time of the second level calibrator is less than T0.

13. The method according to claim 10, characterized in that, The method further includes: judging the reaction progress based on the amplitude of the magnetic bead in the reaction vessel at time 0-T1; if the reaction ends, stopping the oscillation of the magnetic bead at the time of reaction end; otherwise, stopping the oscillation of the magnetic bead at time T1 and outputting a reaction abnormality signal.

14. The sample analyzer according to claim 12, characterized in that, The T0 is greater than or equal to the blood clotting time corresponding to the lowest concentration of the analyte in the sample that can be detected when the first average power is used for detection.

Images