A magnetic bead processing method and system based on chemiluminescent immunoassay

Abstract

The present invention discloses a magnetic bead processing method and system based on chemiluminescent immunoassay, which relates to the field of medical device cleaning and separation technology, including obtaining magnetic beads for chemiluminescent immunoassay and pre-treating them to obtain pre-treated magnetic beads; arranging magnets in a multi-track array to construct a multi-track magnet array and a magnetic field superposition effect; based on the multi-track magnet array and the magnetic field superposition effect, the pre-treated magnetic beads are cleaned and separated to achieve magnetic bead processing based on chemiluminescent immunoassay. The present invention optimizes the adsorption effect of magnetic beads on the target by adopting a multi-track magnet array and a magnetic field superposition effect to adjust the magnet arrangement angle and magnetic field strength; by adjusting the magnetic field strength and processing time in stages, the magnetic beads are cleaned and separated in three stages, the purity and recovery rate of the magnetic beads are improved, and the accuracy and reliability of magnetic bead processing are improved by dynamically adjusting the processing time and the number of cleaning times.

Description

Technical Field

[0001] The present invention relates to the technical field of cleaning and separation of medical devices, and in particular to a magnetic bead processing method and system based on chemiluminescent immunoassay. Background Art

[0002] Chemiluminescent immunoassay CLIA is a detection method that combines highly sensitive chemiluminescent measurement technology with highly specific immune response. It is widely used in the detection of antigens, haptens, antibodies, hormones, enzymes, fatty acids, vitamins and drugs. Since its birth, chemiluminescent immunoassay technology has gradually developed into a new immunoassay technology after radioimmunoassay, enzyme immunoassay, fluorescence immunoassay and time-resolved fluorescence immunoassay. Compared with traditional immunoassay technology, chemiluminescent immunoassay has significant advantages in sensitivity and specificity, can detect target molecules at low concentrations, and has shown high efficiency and accuracy in sample processing and result detection, which makes it have broad application prospects in clinical diagnosis, environmental monitoring and food safety.

[0003] However, despite the significant advantages of chemiluminescent immunoassay technology in terms of sensitivity and accuracy, existing magnetic bead cleaning and separation devices still have technical defects, which restrict their popularity and effectiveness in practical applications; magnetic bead cleaning and separation is one of the key steps in chemiluminescent immunoassay. During the cleaning and separation process of magnetic beads, it is necessary to adsorb the solid phase coated antibody (antigen)-test antigen (antibody)-acridinium ester (enzyme) labeled antibody (antigen) complex, and at the same time, clean the free impurities or free antigen (antibody) in the mixed solution, so as to achieve the purpose of cleaning and purifying the test object; in traditional magnetic bead cleaning and separation devices, mechanical or magnetic suction structures are generally used to achieve the dispersion and cleaning of the mixture; the mechanical structure is designed The design of conventional magnetic bead cleaning and separation devices is often complex, bulky, and has high requirements for manufacturing process and high cost, which limits the application scope of the device to a certain extent. The magnetic device drives the movement and separation of magnetic beads by arranging multiple groups of magnets, but this design has the problem of high precision requirement for magnet arrangement. If the magnet position is offset or the design is unreasonable, it is easy to cause the loss of magnetic beads, thereby affecting the accuracy of the final test results. In addition, conventional magnetic bead cleaning and separation devices usually require multiple cycles of cleaning to ensure the removal of impurities, which not only increases the size and cost of the device, but also makes the entire cleaning process cumbersome and inefficient. Therefore, the existing magnetic bead cleaning and separation technology is in urgent need of technical innovation and optimization to improve its operability and stability in practical applications. Summary of the invention

[0004] In view of the above-mentioned problems, the present invention is proposed.

[0005] Therefore, the problem to be solved by the present invention is how to provide a method for increasing the magnetic bead adsorption effect and reducing the magnetic bead loss rate by arranging magnets in a multi-track array and combining it with the magnetic field superposition effect, thereby simplifying the structure of the magnetic separation device, reducing the volume and optimizing the cost.

[0006] In order to solve the above technical problems, the present invention provides the following technical solutions:

[0007] In the first aspect, an embodiment of the present invention provides a method for processing magnetic beads based on chemiluminescent immunoassay, which includes obtaining magnetic beads for chemiluminescent immunoassay and pretreating them to obtain pretreated magnetic beads; arranging magnets in a multi-track array to construct a multi-track magnet array and a magnetic field superposition effect; based on the multi-track magnet array and the magnetic field superposition effect, the pretreated magnetic beads are cleaned and separated to achieve magnetic bead processing based on chemiluminescent immunoassay.

[0008] As a preferred embodiment of the magnetic bead processing method based on chemiluminescent immunoassay described in the present invention, the obtaining of magnetic beads for chemiluminescent immunoassay and pretreatment thereof include: selecting magnetic beads with uniform surface according to the detection requirements of chemiluminescent immunoassay; screening the particle size of the magnetic beads to obtain screened magnetic beads; and performing surface activation treatment on the screened magnetic beads to obtain pretreated magnetic beads.

[0009] As a preferred embodiment of the magnetic bead processing method based on chemiluminescent immunoassay described in the present invention, the construction of a multi-track magnet array and a magnetic field superposition effect refers to adjusting the arrangement of the magnets by adopting a multi-track array arrangement, simulating the magnetic field superposition effect, and adjusting the magnet arrangement angle.

[0010] As a preferred solution of the magnetic bead processing method based on chemiluminescent immunoassay of the present invention, the construction of a multi-track magnet array and a magnetic field superposition effect includes the following steps: calculation based on the magnetic moment of the magnet and the distance between the magnet and the target point, and combining the superposition of the magnetic fields of multiple magnets in space, to obtain a first total magnetic field strength, the specific formula is as follows: ,in, is the first total magnetic field strength; is the number of magnets in the multi-track magnet array; is the magnetic moment of the i-th magnet; is the position of the magnetic field action point; is the position vector of the i-th magnet; since the magnetic field will attenuate over time, the attenuation coefficient is introduced The first total magnetic field strength is optimized to obtain the second total magnetic field strength. The specific formula is as follows: ,in, is the second total magnetic field strength; is the attenuation coefficient of the i-th magnet; in order to control the direction of each magnet, the rotation matrix is ​​introduced The second total magnetic field strength is optimized to obtain the total magnetic field strength, and the specific formula is as follows: , in, is the total magnetic field strength; is the rotation matrix; is the arrangement angle of the i-th magnet.

[0011] As a preferred embodiment of the magnetic bead processing method based on chemiluminescent immunoassay described in the present invention, the cleaning and separation treatment of the pre-treated magnetic beads includes a preliminary treatment stage, a cleaning stage and a separation stage, wherein the multi-track magnet array and the magnetic field superposition effect are adjusted to enable the magnetic beads to adsorb the analyte in the mixed solution and clean the impurities.

[0012] As a preferred embodiment of the magnetic bead processing method based on chemiluminescent immunoassay of the present invention, the cleaning and separation process comprises the following steps: in the preliminary processing stage, using a rotation matrix and attenuation coefficient The magnet angle and magnetic field strength are controlled. When the total magnetic field strength When the magnetic beads are between the first threshold and the second threshold, the magnetic beads are treated for a duration of T1 seconds, so that the magnetic beads can slightly adsorb the analyte and preliminarily separate the impurities from the mixed solution; in the cleaning stage, the total magnetic field strength is increased by The magnetic beads are enhanced to between the third threshold and the fourth threshold, and the magnetic beads are processed for a duration of T2 seconds to strengthen the adsorption between the magnetic beads and the object to be tested; after the magnetic beads are processed, the total magnetic field strength is Reduce to between the first threshold and the second threshold, so that impurities on the surface of the magnetic beads fall off; repeat the steps of the cleaning stage N times to ensure that all impurities on the surface of the magnetic beads are removed; in the separation stage, by increasing the total magnetic field strength The intensity is enhanced to between the fifth threshold and the sixth threshold, and the magnetic beads are processed for a duration of T3 seconds to obtain a target magnetic bead complex.

[0013] As a preferred embodiment of the magnetic bead processing method based on chemiluminescent immunoassay described in the present invention, the method comprises the following steps: after the preliminary processing stage, the cleaning stage and the separation stage, the number of magnetic beads in each stage is obtained, and the magnetic bead loss rates in different stages are calculated and judged respectively; if the magnetic bead loss rate in the preliminary processing stage is greater than the expected threshold value Q1, the duration T1 of the magnetic bead processing is extended to improve the slight adsorption effect of the magnetic beads on the analyte; if the magnetic bead loss rate in the cleaning stage is greater than the expected threshold value Q2, the number of cleaning times N is reduced or increased according to the magnetic bead loss rate to avoid the loss of magnetic beads or the inability to completely remove impurities due to too many or too few cleaning times; if the magnetic bead loss rate in the separation stage is greater than the expected threshold value Q3, the duration T3 of the magnetic bead processing is extended to enhance the adsorption effect between the magnetic beads and the analyte.

[0014] On the second aspect, in order to further solve the safety problems existing in the cleaning and separation of medical devices, the present invention provides a magnetic bead processing system based on chemiluminescent immunoassay, which includes: a magnetic bead acquisition module, used to acquire magnetic beads and pre-treat them according to the needs of chemiluminescent immunoassay to obtain pre-treated magnetic beads; a magnet arrangement module, used to arrange magnets in a multi-track array, construct a multi-track magnet array, and simulate the magnetic field superposition effect; a magnetic bead processing module, used to clean and separate the pre-treated magnetic beads based on the multi-track magnet array and the magnetic field superposition effect, to obtain a pure target magnetic bead complex, and realize magnetic bead processing based on chemiluminescent immunoassay.

[0015] In a third aspect, an embodiment of the present invention provides a computer device, comprising a memory and a processor, wherein the memory stores a computer program, wherein: when the computer program is executed by the processor, any step of the magnetic bead processing method based on chemiluminescent immunoassay as described in the first aspect of the present invention is implemented.

[0016] In a fourth aspect, an embodiment of the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein: when the computer program is executed by a processor, any step of the magnetic bead processing method based on chemiluminescent immunoassay as described in the first aspect of the present invention is implemented.

[0017] The beneficial effects of the present invention are as follows: the present invention realizes efficient combination of magnetic beads and target substances by selecting magnetic beads with uniform surface and appropriate particle size and performing surface activation treatment, thereby improving the accuracy and sensitivity of analysis; adopts a multi-track magnet array and magnetic field superposition effect, optimizes the adsorption effect of magnetic beads on target objects by adjusting the magnet arrangement angle and magnetic field strength, can accurately control the direction and strength of the magnetic field, and avoids the problem of magnetic bead loss or insufficient treatment in traditional methods; by adjusting the magnetic field strength and treatment time in stages, the cleaning and separation of magnetic beads are carried out in three stages, the preliminary treatment stage ensures the preliminary removal of impurities, the cleaning stage ensures the thorough removal of impurities by repeated cleaning, the separation stage strengthens the combination of magnetic beads and target objects, improves the purity and recovery rate of magnetic beads, and by dynamically adjusting the treatment time and the number of cleaning times, reduces the loss of magnetic beads or incomplete cleaning, and improves the accuracy and reliability of magnetic bead treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work. Among them:

[0019] Figure 1 The overall flow chart of the magnetic bead processing method based on chemiluminescent immunoassay in Example 1;

[0020] Figure 2 A flowchart of the construction of a multi-track magnet array and magnetic field superposition effect in Example 1;

[0021] Figure 3 This is a flow chart of the cleaning and separation process in Example 1. DETAILED DESCRIPTION

[0022] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the accompanying drawings.

[0023] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0024] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments. Example 1

[0025] Reference Figure 1~Figure 3 , which is the first embodiment of the present invention, provides a magnetic bead processing method based on chemiluminescent immunoassay.

[0026] The existing magnetic bead cleaning and separation methods mainly have the following problems: in traditional magnetic bead cleaning and separation devices, mechanical or magnetic structures are generally used to achieve dispersion and cleaning of the mixture; the design of mechanical structures is often complex, bulky, has high manufacturing process requirements, and is costly, resulting in certain limitations on the application scope of the device; and the magnetic attraction device drives the movement and separation of magnetic beads by arranging multiple groups of magnets, but this design has the problem of high precision requirements for magnet arrangement. If the magnet position is offset or the design is unreasonable, it is easy to cause the magnetic beads to be lost, thereby affecting the accuracy of the final test results; in addition, traditional magnetic bead cleaning and separation devices usually require multiple cycles of cleaning to ensure the removal of impurities, which not only increases the size and cost of the device, but also makes the entire cleaning process cumbersome and inefficient.

[0027] The present application provides a method that can effectively solve the above-mentioned problems. Next, multiple embodiments will be combined to explain in detail how to implement the magnetic bead processing method based on chemiluminescent immunoassay.

[0028] Figure 1 The overall flow chart of the magnetic bead processing method based on chemiluminescent immunoassay is shown, including:

[0029] S1: Obtain magnetic beads for chemiluminescent immunoassay and pretreat them to obtain pretreated magnetic beads.

[0030] Preferably, obtaining magnetic beads for chemiluminescent immunoassay and pre-treating them includes: selecting magnetic beads with uniform surface according to the detection requirements of chemiluminescent immunoassay.

[0031] The particle size of the magnetic beads is screened to obtain screened magnetic beads, thereby improving the magnetic field response speed.

[0032] The screened magnetic beads are subjected to surface activation treatment to obtain pre-treated magnetic beads, thereby improving the affinity and chemical reaction ability of the magnetic beads.

[0033] Preferably, the present invention can significantly improve the adsorption efficiency of magnetic beads and the recognition ability of target substances by accurately screening the particle size of magnetic beads and surface activation treatment, reduce unnecessary interference, and improve the affinity of magnetic beads, so that they can quickly and efficiently capture target objects in complex biochemical environments.

[0034] S2: Arrange the magnets in a multi-track array to construct a multi-track magnet array and magnetic field superposition effect.

[0035] Preferably, Figure 2 The figure shows a flow chart for constructing a multi-track magnet array and a magnetic field superposition effect. Constructing a multi-track magnet array and a magnetic field superposition effect means adjusting the arrangement of the magnets by adopting a multi-track array arrangement, simulating the magnetic field superposition effect, and adjusting the magnet arrangement angle to maximize the magnetic field superposition effect, thereby enhancing the adsorption efficiency of the magnetic beads and achieving high efficiency in cleaning and separation.

[0036] Specifically, constructing a multi-track magnet array and a magnetic field superposition effect includes the following steps: performing calculations based on the magnetic moment of the magnet and the distance between the magnet and the target point, and combining the superposition of the magnetic fields of multiple magnets in space to obtain a first total magnetic field strength, the specific formula is as follows: ,in, is the first total magnetic field strength, that is, all magnets at point The vector sum of the magnetic field strength at ; is the number of magnets in the multi-track magnet array; is the magnetic moment of the i-th magnet, which determines the magnetic field strength; is the position of the magnetic field action point, usually the position of the magnetic bead; is the position vector of the i-th magnet, indicating the position of the magnet in space.

[0037] Since the magnetic field may attenuate over time, especially in long-term use, the attenuation coefficient is introduced The first total magnetic field strength is optimized, indicating that the change of the magnetic field strength of each magnet over time follows the exponential decay law, and the second total magnetic field strength is obtained. The specific formula is as follows: ,in, is the second total magnetic field intensity, which represents the change of the total intensity of the magnetic field at time t; is the attenuation coefficient of the i-th magnet.

[0038] The directionality of each magnet has an important influence on the distribution of the magnetic field. Especially in multi-track magnet arrays, the angular arrangement of the magnets will affect the superposition effect of the magnetic field. In order to control the direction of each magnet, a rotation matrix is ​​introduced. The second total magnetic field strength is optimized to obtain the total magnetic field strength, and the specific formula is as follows: , ,in, is the total magnetic field strength; The rotation matrix is ​​used to adjust the direction of each magnet on different tracks, thereby affecting its adsorption force on the magnetic beads. is the arrangement angle of the i-th magnet.

[0039] Preferably, compared with the traditional magnet arrangement which usually adopts a simple linear or two-dimensional array, it is difficult to maximize the adsorption effect of the magnetic field. By optimizing the arrangement angle of the magnet and utilizing the magnetic field superposition effect, the present invention significantly improves the uniformity of the magnetic field strength and the adsorption efficiency, especially under the multi-track array arrangement, which can maximize the magnetic field effect of the magnet, thereby improving the adsorption capacity of the magnetic beads in the mixed liquid and improving the efficiency of cleaning and separation; by introducing the rotation matrix and attenuation coefficient to optimize the magnetic field strength and distribution, the magnetic field can be adaptively adjusted under different time and environmental conditions to maintain the best working state.

[0040] S3: Based on the multi-track magnet array and magnetic field superposition effect, the pre-treated magnetic beads are cleaned and separated to achieve magnetic bead processing based on chemiluminescent immunoassay.

[0041] Preferably, Figure 3 The figure shows a flow chart of cleaning and separation processing. The cleaning and separation processing of the pre-treated magnetic beads includes a preliminary processing stage, a cleaning stage and a separation stage. The multi-track magnet array and the magnetic field superposition effect are adjusted so that the magnetic beads adsorb the analyte in the mixed solution and clean the impurities, thereby achieving the purpose of cleaning and purifying the analyte.

[0042] It should be noted that in chemiluminescent immunoassay, the cleaning and separation process of magnetic beads requires adsorption of the solid phase coated antibody (antigen)-test antigen (antibody)-acridinium ester (enzyme) labeled antibody (antigen) complex in the mixed solution, and at the same time, cleaning the free impurities or free antigen (antibody) in the mixed solution.

[0043] Specifically, the cleaning and separation process includes the following steps: In the preliminary processing stage, the rotation matrix is ​​used and attenuation coefficient The magnet angle and magnetic field strength are controlled. When the total magnetic field strength When the value is between the first threshold and the second threshold, the magnetic beads are processed for a duration of T1 seconds, so that the magnetic beads can slightly adsorb the analyte and the large particle impurities can be initially separated from the mixed solution.

[0044] During the cleaning phase, the total magnetic field strength is increased by The value is enhanced to between the third threshold and the fourth threshold, and the magnetic beads are processed for a duration of T2 seconds to further enhance the adsorption between the magnetic beads and the object to be tested.

[0045] After the magnetic beads are treated, the total magnetic field strength The pressure is reduced to between the first threshold and the second threshold, so that tiny impurities on the surface of the magnetic beads fall off.

[0046] Repeat the washing steps N times to ensure that all tiny impurities on the surface of the magnetic beads are removed.

[0047] During the separation phase, the total magnetic field strength is increased by The concentration is enhanced to between the fifth and sixth thresholds, and the magnetic beads are processed for a duration of T3 seconds, so that the analyte can be firmly adsorbed on the surface of the magnetic beads, reducing any form of movement or shedding, and obtaining a pure target magnetic bead complex.

[0048] It should be noted that the first threshold to the sixth threshold are arranged in order from small to large. The present invention preliminarily determines the initial data from the first threshold to the sixth threshold based on the surface characteristics of the magnetic beads, the particle size distribution and the magnetic field strength of the magnet, and obtains the variation curve of the magnetic bead loss rate under different magnetic field strengths and processing times by analyzing the experimental data, and then determines according to the needs to ensure that the magnetic beads adsorb the analyte as much as possible and remove excess impurities under the condition of meeting the magnetic bead loss rate, thereby obtaining a more accurate target magnetic bead complex, which provides a basis for subsequent chemiluminescent immunoassay, and adjusts the initial data from the first threshold to the sixth threshold in multiple repeated experiments, and finally obtains the best first to sixth thresholds.

[0049] Furthermore, after the preliminary treatment stage, the cleaning stage and the separation stage, the number of magnetic beads in each stage is obtained, and the magnetic bead loss rate in different stages is calculated and judged. If the magnetic bead loss rate in the preliminary treatment stage is greater than the expected threshold value Q1, the duration T1 of the magnetic bead treatment is extended to improve the slight adsorption effect of the magnetic beads on the analyte.

[0050] If the magnetic bead loss rate during the cleaning phase is greater than the expected threshold value Q2, the number of cleaning times N is reduced or increased according to the magnetic bead loss rate to avoid excessive cleaning leading to magnetic bead loss and insufficient cleaning leading to inability to completely remove impurities.

[0051] If the magnetic bead loss rate in the separation stage is greater than the expected threshold value Q3, the duration of the magnetic bead treatment is extended by T3 to allow the magnetic beads to have enough time to complete the firm adsorption, enhance the adsorption effect between the magnetic beads and the analyte, and ensure that they will not fall off in subsequent operations.

[0052] It should be noted that, for the expected threshold values ​​Q1 to Q3 of the magnetic bead loss rate and the duration and number of cleaning times of the magnetic bead treatment at different stages, the present invention sets the initial data according to different experimental conditions and types of magnetic beads, and adjusts the magnetic bead loss rate and the adsorption of the magnetic beads to the analyte and impurities during the experiment in real time to avoid excessive removal of the magnetic beads during the cleaning process due to too high a magnetic bead loss rate, affecting the subsequent separation effect, or the inability to completely remove impurities due to too low a magnetic bead loss rate, affecting the final purity, and then adjusting and optimizing the relevant data in multiple experiments to obtain the final expected threshold values ​​Q1 to Q3 and the duration and number of cleaning times of the magnetic bead treatment at different stages.

[0053] Preferably, compared with the traditional magnetic bead cleaning and separation which mostly depends on fixed processing time and intensity, and easily leads to the problem of magnetic bead loss or incomplete cleaning, the present invention can realize a highly adaptive cleaning and separation process by precisely controlling the magnetic field intensity at different stages and adjusting the processing time and the number of cleaning times according to the magnetic bead loss rate; in the preliminary processing stage, the magnetic field intensity is controlled within a suitable range to avoid excessive adsorption of magnetic beads due to an overly strong magnetic field; in the cleaning stage, the magnetic field is appropriately strengthened to ensure that the adsorption of the object to be tested is more stable, while avoiding the loss of magnetic beads due to excessive cleaning; in the separation stage, the processing time is extended to ensure that the magnetic beads can firmly adsorb the target object. Through this series of dynamic adjustments, the recovery rate and processing effect of the magnetic beads are greatly improved.

[0054] In summary, the present invention realizes efficient combination of magnetic beads and target substances by selecting magnetic beads with uniform surface and appropriate particle size and performing surface activation treatment, thereby improving the accuracy and sensitivity of analysis; adopts a multi-track magnet array and magnetic field superposition effect, optimizes the adsorption effect of magnetic beads on the target by adjusting the magnet arrangement angle and magnetic field strength, can accurately control the direction and strength of the magnetic field, and avoids the problem of magnetic bead loss or insufficient treatment in traditional methods; by adjusting the magnetic field strength and treatment time in stages, the cleaning and separation of magnetic beads are carried out in three stages, the preliminary treatment stage ensures the preliminary removal of impurities, the cleaning stage ensures the thorough removal of impurities by repeated cleaning, the separation stage strengthens the combination of magnetic beads and target substances, improves the purity and recovery rate of magnetic beads, and by dynamically adjusting the treatment time and the number of cleaning times, reduces the loss of magnetic beads or incomplete cleaning, and improves the accuracy and reliability of magnetic bead treatment. Example 2

[0055] As one embodiment of the present invention, a magnetic bead processing system based on chemiluminescent immunoassay is provided, comprising: a magnetic bead acquisition module, used to acquire magnetic beads according to the requirements of chemiluminescent immunoassay and perform pretreatment to obtain pretreated magnetic beads; a magnet arrangement module, used to arrange magnets in a multi-track array, construct a multi-track magnet array, and simulate the magnetic field superposition effect; a magnetic bead processing module, used to clean and separate the pretreated magnetic beads based on the multi-track magnet array and the magnetic field superposition effect to obtain a pure target magnetic bead complex, thereby realizing magnetic bead processing based on chemiluminescent immunoassay. Example 3

[0056] It is an embodiment of the present invention, which is different from the previous embodiment in that:

[0057] If the functions are implemented in the form of software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art, or the part of the technical solution, can be embodied in the form of a software product. The computer software product is stored in a storage medium, including several instructions to enable a computer device (which can be a personal computer, server, or network device, etc.) to perform all or part of the steps of the methods described in various embodiments of the present invention. The aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk, etc., which can store program codes.

[0058] The logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as an ordered list of executable instructions for implementing logical functions, and can be embodied in any computer-readable medium for use by an instruction execution system, device or apparatus (such as a computer-based system, a system including a processor, or other system that can fetch instructions from an instruction execution system, device or apparatus and execute instructions), or in conjunction with such instruction execution systems, devices or apparatuses. For the purposes of this specification, "computer-readable medium" can be any device that can contain, store, communicate, propagate or transmit a program for use by an instruction execution system, device or apparatus, or in conjunction with such instruction execution systems, devices or apparatuses.

[0059] More specific examples of computer-readable media (a non-exhaustive list) include the following: an electrical connection with one or more wires (electronic device), a portable computer disk case (magnetic device), a random access memory (RAM), a read-only memory (ROM), an erasable and programmable read-only memory (EPROM or flash memory), an optical fiber device, and a portable compact disk read-only memory (CDROM). In addition, the computer-readable medium may even be a paper or other suitable medium on which the program is printed, since the program may be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, deciphering or, if necessary, processing in another suitable manner, and then stored in a computer memory.

[0060] It should be understood that the various parts of the present invention can be implemented by hardware, software, firmware or a combination thereof. In the above-mentioned embodiments, multiple steps or methods can be implemented by software or firmware stored in a memory and executed by a suitable instruction execution system. For example, if implemented by hardware, as in another embodiment, it can be implemented by any one of the following technologies known in the art or their combination: a discrete logic circuit having a logic gate circuit for implementing a logic function for a data signal, a dedicated integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc. Example 4

[0061] As an embodiment of the present invention, a magnetic bead processing method based on chemiluminescent immunoassay is provided. In order to verify the beneficial effects of the present invention, scientific demonstration is carried out through simulation experiments.

[0062] In this example, magnetic beads with uniform surface diameter of 200-300 nanometers are selected, and an advanced multi-track magnet array system is used for magnetic bead treatment. In the magnetic bead pretreatment stage, the magnetic beads are firstly screened for precise particle size, and the surface of the magnetic beads is activated with a silane coupling agent to enhance the surface affinity and chemical reactivity of the magnetic beads, including: using 3-aminopropyltriethoxysilane to modify the surface of the magnetic beads, forming amino functional groups on the surface of the magnetic beads through condensation reaction, and enhancing the binding ability of the magnetic beads to biological molecules.

[0063] Secondly, the construction of the multi-track magnet array adopts a precise spatial layout design. It is composed of 6 magnets with different magnetic moments. The spatial arrangement angle is optimized with computer assistance to achieve the maximum superposition effect of the magnetic field. The position and angle of each magnet are accurately calculated to ensure the uniformity and optimality of the magnetic field intensity distribution. The time attenuation coefficient and rotation matrix are introduced to dynamically adjust the magnetic field intensity and magnet direction to improve the accuracy of magnetic bead processing. Among them, this example compares the multi-track magnet array constructed by the present invention with the existing single-track magnet and the traditional uniform arrangement. The specific data are shown in Table 1.

[0064] Table 1 Comparison data between multi-track magnet array and existing magnet arrangement scheme

[0065]

[0066] It can be seen from Table 1 that, compared with single-track magnets and traditional uniform arrangements, the multi-track magnet array solution of the present invention significantly improves the magnetic field uniformity and magnetic field stability coefficient, the processing repeatability is increased from 85.3% to 98.4%, and the comprehensive performance index reaches 4.9, which intuitively demonstrates the superiority of the multi-track magnet array.

[0067] In addition, by dividing the magnetic bead cleaning and separation process into three carefully designed stages, in the preliminary treatment stage, the total magnetic field strength is controlled within the range of 0.5-1.0T for 30 seconds to achieve slight adsorption of the analyte and preliminary separation of large particle impurities; in the cleaning stage, the magnetic field strength is increased to 1.5-2.0T for 45 seconds to further enhance the adsorption effect of the magnetic beads and the target substance, and the cleaning process is repeated 3 times to ensure that the impurities on the surface of the magnetic beads are fully removed; in the separation stage, the magnetic field strength is adjusted to 2.5-3.0T for 60 seconds to firmly adsorb the analyte on the surface of the magnetic beads; real-time monitoring technology is used in each stage to record the change in the number of magnetic beads, calculate the magnetic bead loss rate in each stage, dynamically adjust the processing parameters according to the preset threshold, and optimize the overall efficiency and accuracy of the magnetic bead processing, wherein Tables 2 and 3 show the relevant data of the present invention in the magnetic bead cleaning and separation process and the comparative data of the present invention with the prior art.

[0068] Table 2 The relevant data of the present invention in the magnetic bead cleaning and separation process

[0069]

[0070] Table 3 Comparison of magnetic bead processing performance

[0071]

[0072] It can be seen from the above two tables that compared with the traditional treatment method, the multi-track magnet array method of the present invention has obvious improvements in the indicators of magnetic bead loss rate, adsorption efficiency and impurity removal rate, indicating that through precise magnetic field intensity control, dynamic magnet angle adjustment and introduction of attenuation coefficient, precise regulation of the chemiluminescent immunoassay magnetic bead treatment process is achieved, which not only improves the efficiency and accuracy of magnetic bead treatment, but also significantly reduces the magnetic bead loss rate, enhances the biomolecule adsorption capacity, and provides a more reliable technical solution for chemiluminescent immunoassay.

[0073] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A magnetic bead processing method based on chemiluminescent immunoassay, characterized in that: include: Obtaining magnetic beads for chemiluminescent immunoassay and pre-treating them to obtain pre-treated magnetic beads; Arrange the magnets in a multi-track array to construct a multi-track magnet array and magnetic field superposition effect; Based on the multi-track magnet array and the magnetic field superposition effect, the pre-treated magnetic beads are cleaned and separated to achieve magnetic bead processing based on chemiluminescent immunoassay; The construction of the multi-track magnet array and the magnetic field superposition effect comprises the following steps: The calculation is performed based on the magnetic moment of the magnet and the distance between the magnet and the target point, and combined with the superposition of the magnetic fields of multiple magnets in space to obtain the first total magnetic field strength. The specific formula is as follows: in, is the first total magnetic field strength; is the number of magnets in the multi-track magnet array; is the magnetic moment of the i-th magnet; is the position of the magnetic field action point; is the position vector of the i-th magnet; Since the magnetic field will attenuate over time, the attenuation coefficient is introduced The first total magnetic field strength is optimized to obtain the second total magnetic field strength. The specific formula is as follows: in, is the second total magnetic field strength; is the attenuation coefficient of the i-th magnet; In order to control the direction of each magnet, a rotation matrix is ​​introduced The second total magnetic field strength is optimized to obtain the total magnetic field strength, and the specific formula is as follows: in, is the total magnetic field strength; is the rotation matrix; is the arrangement angle of the i-th magnet; The cleaning and separation treatment of the pretreated magnetic beads includes a preliminary treatment stage, a cleaning stage and a separation stage, wherein the multi-track magnet array and the magnetic field superposition effect are adjusted so that the magnetic beads adsorb the analyte in the mixed solution and clean the impurities; The cleaning and separation process comprises the following steps: In the preliminary processing stage, the rotation matrix is ​​used and attenuation coefficient The magnet angle and magnetic field strength are controlled. When the total magnetic field strength When the value is between the first threshold and the second threshold, the magnetic beads are treated for a duration of T1 seconds, so that the magnetic beads can slightly adsorb the analyte and the impurities can be initially separated from the mixed solution; During the cleaning phase, the total magnetic field strength is increased by Enhance to between the third threshold and the fourth threshold, and process the magnetic beads for a duration of T2 seconds to enhance the adsorption between the magnetic beads and the analyte; After the magnetic beads are treated, the total magnetic field strength Reduce to between the first threshold and the second threshold, so that impurities on the surface of the magnetic beads fall off; Repeat the steps of the washing stage N times to ensure that all impurities on the surface of the magnetic beads are removed; During the separation phase, the total magnetic field strength is increased by Enhance to between the fifth threshold and the sixth threshold, and process the magnetic beads for a duration of T3 seconds to obtain a target magnetic bead complex; After the preliminary treatment stage, the cleaning stage and the separation stage, the number of magnetic beads in each stage is obtained, and the magnetic bead loss rate in different stages is calculated and judged. If the magnetic bead loss rate in the preliminary treatment stage is greater than the expected threshold value Q1, the duration T1 of the magnetic bead treatment is extended to improve the slight adsorption effect of the magnetic beads on the analyte; If the magnetic bead loss rate in the cleaning stage is greater than the expected threshold value Q2, the number of cleaning times N is reduced or increased according to the magnetic bead loss rate to avoid excessive or insufficient cleaning times leading to magnetic bead loss or inability to completely remove impurities; If the magnetic bead loss rate in the separation stage is greater than the expected threshold value Q3, the duration T3 of the treatment of the magnetic beads is extended to enhance the adsorption effect between the magnetic beads and the analyte.

2. The magnetic bead processing method based on chemiluminescent immunoassay according to claim 1, characterized in that: The obtaining of magnetic beads for chemiluminescent immunoassay and pretreatment thereof comprises: According to the detection requirements of chemiluminescent immunoassay, select magnetic beads with uniform surface; Screening the particle size of the magnetic beads to obtain screened magnetic beads; The screened magnetic beads are subjected to surface activation treatment to obtain pre-treated magnetic beads.

3. The magnetic bead processing method based on chemiluminescent immunoassay according to claim 2, characterized in that: The construction of a multi-track magnet array and a magnetic field superposition effect refers to adjusting the arrangement of the magnets by adopting a multi-track array arrangement, simulating the magnetic field superposition effect, and adjusting the magnet arrangement angle.

4. A magnetic bead processing system based on chemiluminescent immunoassay, based on the magnetic bead processing method based on chemiluminescent immunoassay according to any one of claims 1 to 3, characterized in that: include, A magnetic bead acquisition module is used to acquire magnetic beads and pre-treat them according to the requirements of chemiluminescent immunoassay to obtain pre-treated magnetic beads; The magnet arrangement module is used to arrange magnets in a multi-track array, construct a multi-track magnet array, and simulate the magnetic field superposition effect; The magnetic bead processing module is used to clean and separate the pre-treated magnetic beads based on the multi-track magnet array and magnetic field superposition effect to obtain pure target magnetic bead complexes and realize magnetic bead processing based on chemiluminescent immunoassay.

5. A computer device comprising a memory and a processor, wherein the memory stores a computer program, wherein: When the processor executes the computer program, the steps of the magnetic bead processing method based on chemiluminescent immunoassay according to any one of claims 1 to 3 are implemented.

6. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the steps of the magnetic bead processing method based on chemiluminescent immunoassay according to any one of claims 1 to 3 are implemented.

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