Full-automatic whole blood sample pretreatment device for separating plasma through immunomagnetic beads

Abstract

The utility model discloses a full-automatic whole blood sample pretreatment device for separating plasma through immunomagnetic beads. The full-automatic whole blood sample pretreatment device comprises a plasma separation mechanism for extracting a plasma sample from a whole blood sample, a conveying mechanism for conveying a blood collection tube and a sample cup, and a feeding mechanism for providing the sample cup, the plasma separation mechanism comprises a sample loading and shaking module for uniformly mixing a whole blood sample in the blood collection tube, a puncture sampling module for collecting the whole blood sample or the plasma sample, and a magnetic separation module for separating the plasma sample; the magnetic separation module comprises an oscillation assembly, a magnetic attraction assembly and a reaction cup, and freeze-dried immunomagnetic beads and an antibody reagent are pre-stored in the reaction cup. The device provided by the utility model can be used for comprehensively and automatically pretreating a whole blood sample and improving the quality and the efficiency of plasma separation.

Description

Technical Field

[0001] The utility model belongs to the technical field of medical detection, and in particular relates to a fully automatic whole blood sample pre-processing device for separating plasma with immunomagnetic beads. Background Art

[0002] When IVD (In Vitro Diagnostics) uses blood samples to obtain clinical diagnostic information, it is usually pre-treated to separate plasma / serum from whole blood samples before testing. If whole blood samples are used directly for testing, the blood cells in them will interfere with the analysis process and affect the accuracy of the test results. At present, the more mature whole blood separation method is to use special centrifugal equipment to separate plasma / serum, with a relative centrifugal force RCF of 1000-1200g and a centrifugation time of 5-10 minutes. The problem is that the centrifugal equipment is large and difficult to integrate with small and medium-sized testing equipment and realize automation; the centrifugation time is long, which is difficult to meet the growing clinical demand for rapid testing. The filtration separation method uses filter membranes, microcolumns, microspheres, etc. to capture or intercept blood cells and separate plasma / serum. The problems are slow filtration speed; the filter membrane adsorbs markers, resulting in reduced detection sensitivity; when the filter membrane is overloaded and blocked, it is difficult to filter out plasma, resulting in a low plasma recovery rate, which cannot meet the blood volume requirements for multi-item testing.

[0003] The immunomagnetic bead separation method uses magnetic beads labeled with antibodies to bind to blood cell antigens in whole blood samples to separate plasma / serum. It has the advantages of good separation quality, high efficiency, simple operation, and easy automation. It is particularly suitable for POCT (Point-of-Care Testing) applications.

[0004] Patent document CN103575882A discloses a whole blood labeled immunoassay method and instant detection system, which includes the steps of magnetic bead capture, blood elution, detection antibody labeling, detection antibody elution, detection, etc., and the magnetic bead-labeled capture antibody is combined with the antigen to be tested in the whole blood sample. This method uses the capture antibody to combine with the antigen to be tested in the whole blood sample. The red blood cells in the whole blood sample will interfere with the antibody capturing the antigen to be tested, and the hemolysis of red blood cells causes a large amount of hemoglobin, enzymes, ions and other cell contents in the cells to be released, which interferes with the immunoassay process and affects the accuracy of the test results. In addition, the test results need to obtain the hematocrit of the whole blood sample for conversion.

[0005] Patent document CN117625529A discloses an immunomagnetic bead freeze-dried microsphere for separating red blood cells, and its preparation method, application and blood processing device, the device includes a blood collection test tube and an immunomagnetic bead freeze-dried microsphere built into the test tube, the blood collection test tube is fixed by a bracket, a magnet is installed in the bracket, and the magnet is located directly below the test tube. In order to obtain a faster separation speed, the device uses a larger amount of magnetic beads. The amount of magnetic beads used to process 100uL of whole blood sample is as high as 30mg, and as the amount of whole blood sample increases, the immunomagnetic bead freeze-dried microsphere is increased proportionally, resulting in a longer separation time. When the blood volume required for multi-item testing is large, the use cost and separation efficiency of the device cannot be met. In addition, the device is manually operated, which is difficult to meet the requirements of online inspection automation integration. Utility Model Content

[0006] The utility model aims to provide a fully automatic whole blood sample pre-processing device for separating plasma by immunomagnetic beads, which can fully automate the whole blood sample pre-processing and improve the quality and efficiency of plasma separation.

[0007] In order to achieve the purpose of the utility model, the following technical scheme is provided: a fully automatic whole blood sample pretreatment device for separating plasma by immunomagnetic beads, comprising a plasma separation mechanism for extracting a plasma sample from a whole blood sample, a transmission mechanism for transmitting a blood collection tube and a sample cup, and a loading mechanism for providing a sample cup, wherein the blood collection tube is used to store the whole blood sample, and the sample cup is used to store the acquired plasma sample; the plasma separation mechanism comprises a sample loading and shaking module for mixing the whole blood sample in the blood collection tube, a puncture sampling module for collecting whole blood samples or plasma samples, and a magnetic separation module for separating the plasma sample; the magnetic separation module comprises an oscillating component, a magnetic absorption component and a reaction cup, wherein freeze-dried immunomagnetic beads and antibody reagents are pre-stored in the reaction cup, the oscillating component is used to oscillate and mix the whole blood sample loaded in the reaction cup with the pre-stored freeze-dried immunomagnetic beads and antibody reagents, the magnetic absorption component is used to adsorb the immunomagnetic beads after the reaction is completed to the inner wall of the reaction cup, and the magnetic absorption component arranges the magnets in a Halbach ring array.

[0008] Specifically, the magnetic separation module also includes a first clamping claw for transferring the reaction cup after oscillation and mixing from the oscillating component to the magnetic attraction component.

[0009] Specifically, the sample loading and shaking module includes a detection component for identifying and detecting the blood collection tube, a third clamping jaw for clamping the blood collection tube for shaking, and a swinging motor for providing driving force for the third clamping jaw.

[0010] Specifically, the detection component includes a photoelectric sensor for determining whether the blood collection tube has a cap, a barcode scanner for obtaining coded information on the blood collection tube, a rotating motor for rotating the blood collection tube, and a lifting motor for pressing down and fixing the blood collection tube.

[0011] Specifically, the transmission mechanism includes a first sample rack for loading blood collection tubes, a second sample rack for loading sample cups, a first sample conveyor belt for conveying the first sample rack into / out of the pre-processing device, a second sample conveyor belt for conveying the second sample rack into the pre-processing device, a third sample conveyor belt for driving the first sample rack to move in the sample loading and shaking module, a first lever assembly for transferring the first sample rack to the third sample conveyor belt, a second lever assembly for transferring the first sample rack from the third sample conveyor belt to the first sample conveyor belt, and a circulation module for circulating and storing the second sample rack.

[0012] Specifically, the flow module includes a first lifting platform for driving the second sample rack in / out of the pre-treatment device, a third lever assembly for moving the second sample rack, a liquid extraction needle assembly for extracting plasma waste liquid, a buffer area for temporarily storing the second sample rack, and a second lifting platform for lifting the second sample rack to the sample cup loading position.

[0013] Specifically, the feeding mechanism includes a hopper for storing sample cups, a push rod for pushing out a single sample cup, a channel for adjusting the posture of the pushed out sample cup, and a second clamp for clamping the sample cup discharged from the channel.

[0014] Specifically, a photoelectric sensor for detecting the presence of a sample cup is provided in the channel. When no sample cup is detected, the push rod is controlled to push a single sample cup into the channel.

[0015] Compared with the prior art, the utility model has the following beneficial effects:

[0016] The immunomagnetic bead method is used to separate plasma, which has a short plasma separation time and high recovery efficiency. The immunomagnetic beads and antibody reagents are pre-stored in a reaction cup after vacuum freeze-drying. On the one hand, the storage time of the reagents is extended, and on the other hand, the good dispersion of the magnetic beads is conducive to the reaction of the antibody reagent and the whole blood sample.

[0017] The magnets are arranged in a Halbach circular array. The magnetic field inside the array is significantly enhanced and evenly distributed, which can effectively shorten the time it takes for the magnetic beads to adsorb to the inner wall of the reaction cup after the reaction and improve the efficiency of plasma separation.

[0018] Supports loading of original blood collection tubes, and the plasma separation mechanism can automatically identify blood collection tubes, shake blood collection tubes, automatically puncture and sample / add samples, oscillate and mix whole blood samples, separate plasma by magnetic beads, and collect and recover plasma samples, automating the entire process;

[0019] The sample rack loaded with original blood collection tubes is automatically transferred to the whole blood sample pre-processing device through a sample conveyor belt, and the sample rack loaded with plasma sample cups is automatically transferred through a special transfer module and stored in the whole blood sample pre-processing device. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 A schematic diagram of the structure of a fully automatic whole blood sample pre-treatment device provided in this embodiment;

[0021] Figure 2 A top view of a fully automatic whole blood sample pretreatment device provided in this embodiment

[0022] Figure 3 A schematic diagram of the structure of the sample loading and shaking module provided in this embodiment;

[0023] Figure 4 A top view of the sample loading and shaking module provided in this embodiment;

[0024] Figure 5 A schematic diagram of the structure of the puncture sampling module provided in this embodiment;

[0025] Figure 6 A schematic diagram of the structure of the magnetic separation module provided in this embodiment;

[0026] Figure 7 A schematic diagram of a magnet provided in the magnetic attraction assembly provided in this embodiment;

[0027] Figure 8 A schematic diagram of the structure of the flow module provided in this embodiment;

[0028] Fig. 9 A schematic diagram of the structure of the feeding mechanism provided in this embodiment;

[0029] In the figure, 1, plasma separation mechanism; 2, transmission mechanism; 3, feeding mechanism; 3-1, hopper; 3-2, push rod; 3-3, channel; 3-4, photoelectric sensor; 3-5, second clamp; 4, sample loading and shaking module; 4-1, detection component; 4-2, third clamp; 4-3, swing motor; 4-4, photoelectric sensor; 4-5, barcode scanner; 4-6, rotating motor; 4-7, lifting motor; 4-8, first sample rack; 5, puncture sampling module; 5-1, sample adding needle; 5-2, needle cleaning component; 5 -3, driving module; 6, magnetic separation module; 6-1, oscillation component; 6-2, magnetic attraction component; 6-3, reaction cup; 6-4, first clamp; 7, first sample conveyor belt; 7-1, first lever assembly; 7-2, second lever assembly; 8, second sample conveyor belt; 9, third sample conveyor belt; 10, flow module; 10-1, second sample rack; 10-2, first lifting platform; 10-3, third lever assembly; 10-4, liquid extraction needle assembly; 10-5, buffer area; 10-6, second lifting platform. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solution and advantages of the utility model more clear, the utility model is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the utility model and are not used to limit the utility model.

[0031] like Figure 1 and Figure 2 As shown, a fully automatic whole blood sample pre-processing device provided in this embodiment includes a plasma separation mechanism 1 for extracting a plasma sample from a whole blood sample, a transmission mechanism 2 for transmitting a blood collection tube and a sample cup, and a loading mechanism 3 for providing a sample cup, wherein the blood collection tube is used to provide a whole blood sample, and the sample cup is used to store the obtained plasma sample. In this embodiment, a ten-hole sample rack is used to load the blood collection tube, and a five-hole sample rack is used to load the sample cup.

[0032] Furthermore, the plasma separation mechanism 1 includes a sample loading and shaking module 4 for mixing the whole blood sample in the blood collection tube, a puncture sampling module 5 for collecting the whole blood sample and the plasma sample, and a magnetic separation module 6 for separating the plasma sample.

[0033] like Figure 3 and Figure 4 As shown, the sample loading and shaking module 4 provided in this example includes a detection component 4-1 for identifying the blood collection tube, a third clamping jaw 4-2 for clamping the blood collection tube, and a swing motor 4-3 for swinging the blood collection tube, wherein the detection component 4-1 includes a photoelectric sensor 4-4 for judging whether the blood collection tube has a cap, a scanner 4-5 for obtaining the coding information of the blood collection tube, a rotating motor 4-6 for rotating the blood collection tube, and a lifting motor 4-7 for pressing down the blood collection tube.

[0034] The working process is as follows:

[0035] (1) Identifying the blood collection tube: The lifting motor 4-7 drives the rotating motor 4-6 to press down and rotate the blood collection tube, and the photoelectric sensor 4-4 determines whether the blood collection tube has a cap, and the code information of the blood collection tube is obtained through the barcode scanner 4-5.

[0036] (2) Shaking the blood collection tubes: Move the first sample rack 4-8 ​​loaded with the blood collection tubes along the y direction. When the blood collection tubes are aligned with the opening of the third clamp 4-2, the third clamp 4-2 clamps the blood collection tubes out, and the swing motor 4-3 drives the blood collection tubes to be shaken. After shaking, the third clamp 4-2 puts the blood collection tubes back into the first sample rack 4-8. The first sample rack 4-8 ​​continues to move along the y direction. When the blood collection tubes are aligned with the puncture sampling position, the lifting motor 4-7 drives the pressure block to press down the blood collection tubes, and completes the collection of the whole blood sample through the puncture sampling module 5.

[0037] like Figure 5As shown, the puncture sampling module 5 provided in this embodiment includes a sample loading needle 5-1, a needle cleaning component 5-2, and a driving module 5-3 for moving the sample loading needle 5-1. After the sample loading needle 5-1 is driven by the driving module 5-3 to complete the collection of a whole blood sample or a plasma sample, it is inserted into the needle cleaning component 5-2 to clean the inner and outer walls of the needle.

[0038] like Figure 6 As shown, the magnetic separation module 6 provided in this embodiment includes an oscillating component 6-1, a magnetic attraction component 6-2, and a reaction cup 6-3.

[0039] The reaction cup 6-3 is pre-stored with freeze-dried immune magnetic beads and antibody reagents. When working, the whole blood sample is loaded into the reaction cup 6-3 through the puncture sampling module 5, and the reaction cup 6-3 is driven by the oscillation component 6-1 to oscillate and mix. After the red blood cells in the whole blood sample react fully with the magnetic beads and reagents pre-stored in the reaction cup 6-3, the first clamp 6-4 transfers the reaction cup 6-3 from the oscillation component 6-1 to the magnetic absorption component 6-2, and the magnetic beads after the reaction are adsorbed to the inner wall of the reaction cup 6-3 by the magnet set in the magnetic absorption component 6-2, and the separated plasma sample is collected into the sample cup through the puncture sampling module 5.

[0040] More specifically, the oscillation components 6-1 and magnetic absorption components 6-2 provided in this embodiment can be provided in n numbers, so that the operation procedure can sequentially and simultaneously perform the oscillation mixing and magnetic bead absorption processes of n reaction cups 6-3 to improve the magnetic separation efficiency.

[0041] like Figure 7 As shown, the magnets provided in the magnetic attraction component 6-2 of this example are arranged in a Halbach circular array. Through the arrangement of permanent magnets in different magnetization directions, the magnetic field inside the array is significantly enhanced, while the magnetic field outside is significantly weakened, thereby using the least amount of magnets to generate the strongest magnetic field in the working area. The advantages of this array arrangement are high utilization of permanent magnets, strong magnetic properties, uniform magnetic field distribution, high power density, and less space occupation, thereby effectively shortening the magnetic bead adsorption time and improving the plasma separation efficiency.

[0042] More specifically, the magnets mentioned in this embodiment are preferably neodymium iron boron, the magnet brand is preferably N52, and 8 magnets are arranged in a ring-shaped Halbach array.

[0043] The transmission mechanism 2 includes a first sample conveyor belt 7 for conveying the first sample rack 4-8 ​​loaded with blood collection tubes into / out of the pretreatment device, the first sample conveyor belt 7 is also used to convey the second sample rack 10-1 loaded with sample cups out of the pretreatment device, a second sample conveyor belt 8 for conveying the second sample rack 10-1 loaded with sample cups into the pretreatment device, a third sample conveyor belt 9 for driving the first sample rack 4-8 ​​to move in the sample loading and shaking module 4, and a circulation module 10 for circulating and storing the second sample rack 10-1.

[0044] like Figure 8 As shown, the flow module 10 provided in this example includes a second sample rack 10-1 for loading sample cups, a first lifting platform 10-2 for driving the second sample rack 10-1 in / out of the pre-treatment device, a third lever assembly 10-3 for moving the second sample rack 10-1, a liquid extraction needle assembly 10-4 for extracting plasma waste liquid, a buffer area 10-5 for temporarily storing the second sample rack 10-1, and a second lifting platform 10-6 for lifting the second sample rack 10-1 to the sample cup loading position.

[0045] The working process is as follows:

[0046] (1) Circulation of blood collection tube sample racks: The first sample conveyor belt 7 conveys the first sample rack 4-8 ​​loaded with the blood collection tubes to be processed to the pre-processing device, and transfers it to the third sample conveyor belt 9 via the first lever assembly 7-1. The third sample conveyor belt 9 drives the first sample rack 4-8 ​​into the sample loading and shaking module 4, and the sample loading and shaking module 4 completes the blood collection tube identification and shaking operation, and the puncture sampling module 5 completes the whole blood sample collection operation. After completion, the first sample rack 4-8 ​​loaded with the processed blood collection tubes is transferred to the first sample conveyor belt 7 via the second lever assembly 7-2, and the first sample conveyor belt 7 then conveys the first sample rack 4-8 ​​out of the pre-processing device.

[0047] (2) Circulation of sample cups and sample racks: The second sample conveyor belt 8 conveys the second sample rack 10-1 loaded with used sample cups to the pre-processing device, and is driven by the first lifting platform 10-2 to enter the circulation module 10, and is transferred to the waste liquid extraction location via the third lever assembly 10-3. The liquid extraction needle assembly 10-4 removes the residual plasma waste liquid in the sample cups. The third lever assembly 10-3 continues to move the second sample rack 10-1 to the second lifting platform 10-6, and the second lifting platform 10-6 lifts the second sample rack 10-1 to the sample cup loading location, and then the second clamp 3-5 discards the used sample cups into the waste bin, and clamps the unused sample cups and loads them into the second sample rack 10-1. The second sample rack 10-1 loaded with unused sample cups is then transferred to the first sample conveyor belt 7 via the second lifting platform 10-6, the third lever assembly 10-3, and the first lifting platform 10-2, and the first sample conveyor belt 7 then conveys the second sample rack 10-1 out of the pre-processing device. In the above steps, if there is a sample rack on the second lifting platform 10-6 that is undergoing sample cup replacement, the third lever assembly 10-3 continues to move the second sample rack 10-1 after the waste liquid is extracted to the buffer area 10-5, and waits for the second lifting platform 10-6 to be idle before moving the temporarily stored second sample rack 10-1 to the second lifting platform 10-6 for the next step of processing. In this example, the buffer area 10-5 is provided with 4 second sample rack 10-1 cache positions, and the circulation module 10 can accommodate 5 second sample racks 10-1 for circulation at the same time.

[0048] like Fig. 9 As shown, the loading mechanism 3 includes a hopper 3-1 for storing sample cups, a push rod 3-2 for pushing out a single sample cup, a channel 3-3 for adjusting the posture of the sample cup, a photoelectric sensor 3-4 for detecting the presence of a sample cup, and a second clamp 3-5 for clamping the sample cup. When the photoelectric sensor 3-4 detects that there is no sample cup in the channel 3-3, the single sample cup in the hopper 3-1 is pushed out by the push rod 3-2, and enters the channel 3-3 to automatically adjust the posture to a vertical state, and then the second clamp 3-5 transfers the sample cup to a designated position, waiting for the puncture sampling module 5 to add the collected plasma sample to the sample cup.

[0049] In addition, the terms "upper", "lower", "inner", "outer", "front", "rear" are used for descriptive purposes only and should not be understood as indicating or implying relative importance. Unless otherwise specifically stated, the relative steps, numerical expressions and values ​​of the components and steps described in these embodiments do not limit the scope of the present invention.

[0050] Of course, the above description is only a specific embodiment of the present invention and is not intended to limit the scope of implementation of the present invention. Any equivalent changes or modifications made according to the structure, characteristics and principles described in the patent application scope of the present invention should be included in the patent application scope of the present invention.

[0051] Finally, it should be noted that the above-described embodiments are only specific implementation methods of the utility model, which are used to illustrate the technical solution of the utility model, rather than to limit it. The protection scope of the utility model is not limited thereto. Although the utility model is described in detail with reference to the above-mentioned embodiments, ordinary technicians in the field should understand that any technician familiar with the technical field can still modify the technical solution recorded in the above-mentioned embodiments within the technical scope disclosed by the utility model, or can easily think of changes, or make equivalent replacements for some of the technical features therein; and these modifications, changes or replacements do not make the essence of the corresponding technical solution deviate from the spirit and scope of the technical solution of the embodiment of the utility model, and should be included in the protection scope of the utility model. Therefore, the protection scope of the utility model should be based on the protection scope of the claims.

Claims

1. A fully automatic whole blood sample pretreatment device for separating plasma using immunomagnetic beads, characterized in that: It includes a plasma separation mechanism for extracting a plasma sample from a whole blood sample, a transmission mechanism for transmitting a blood collection tube and a sample cup, and a loading mechanism for providing a sample cup, wherein the blood collection tube is used to store the whole blood sample, and the sample cup is used to store the obtained plasma sample; The plasma separation mechanism includes a sample loading and shaking module for mixing the whole blood sample in the blood collection tube, a puncture sampling module for collecting the whole blood sample or the plasma sample, and a magnetic separation module for separating the plasma sample; The magnetic separation module includes an oscillating component, a magnetic absorption component and a reaction cup. The reaction cup is pre-stored with freeze-dried immunomagnetic beads and antibody reagents. The oscillating component is used to oscillate and mix the whole blood sample loaded in the reaction cup with the pre-stored freeze-dried immunomagnetic beads and antibody reagents. The magnetic absorption component is used to adsorb the immunomagnetic beads after the reaction is completed to the inner wall of the reaction cup. The magnetic absorption component arranges the magnets in a Halbach ring array.

2. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 1, characterized in that: The magnetic separation module also includes a first clamping claw for transferring the reaction cup after oscillation and mixing from the oscillating component to the magnetic attraction component.

3. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 1, characterized in that: The sample loading and shaking module includes a detection component for identifying and detecting the blood collection tube, a third clamping jaw for clamping the blood collection tube for shaking, and a swinging motor that provides driving force for the third clamping jaw.

4. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 3, characterized in that: The detection component includes a photoelectric sensor for determining whether the blood collection tube has a cover, a barcode scanner for acquiring coded information on the blood collection tube, a rotating motor for rotating the blood collection tube, and a lifting motor for pressing down and fixing the blood collection tube.

5. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 1, characterized in that: The transmission mechanism includes a first sample rack for loading blood collection tubes, a second sample rack for loading sample cups, a first sample conveyor belt for conveying the first sample rack into / out of the pre-processing device, a second sample conveyor belt for conveying the second sample rack into the pre-processing device, a third sample conveyor belt for driving the first sample rack to move in the sample loading and shaking module, a first lever assembly for transferring the first sample rack to the third sample conveyor belt, a second lever assembly for transferring the first sample rack from the third sample conveyor belt to the first sample conveyor belt, and a circulation module for circulating and storing the second sample rack.

6. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 5, characterized in that: The flow module includes a first lifting platform for driving the second sample rack in / out of the pre-processing device, a third lever assembly for moving the second sample rack, a liquid extraction needle assembly for extracting plasma waste liquid, a buffer area for temporarily storing the second sample rack, and a second lifting platform for lifting the second sample rack to the sample cup loading position.

7. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 1, characterized in that: The feeding mechanism comprises a hopper for storing sample cups, a push rod for pushing out a single sample cup, a channel for adjusting the posture of the pushed-out sample cup, and a second clamping claw for clamping the sample cup discharged from the channel.

8. The fully automatic whole blood sample pre-treatment device for separating plasma with immunomagnetic beads according to claim 7, characterized in that: A photoelectric sensor for detecting the presence of a sample cup is arranged in the channel. When no sample cup is detected, the push rod is controlled to push a single sample cup into the channel.

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