Full-automatic sample treatment method and system for high-flux magnetic column treatment

Abstract

According to the full-automatic sample treatment method and system for high-flux magnetic column treatment, distribution characteristic information of the target substance in the sample solution and motion characteristic information of the magnetic beads in the sample solution are obtained, so that the magnetic column applied to the sample solution is adjusted, the motion state of the magnetic beads in the sample solution is changed, and the sample treatment accuracy is improved. Enabling the magnetic beads to move as far as possible to pass through a target substance-rich area in the sample solution, and ensuring that target substances are efficiently attached to the surfaces of the magnetic beads; judging whether the magnetic beads need to be separated from the interior of the sample solution or not based on the target substance adsorption state information on the surfaces of the magnetic beads; when the magnetic beads need to be separated from the inside of the sample solution, the magnetic columns applied to the sample solution are adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move according to corresponding paths, the magnetic beads are separated from the sample solution, and the magnetic beads can fully adsorb target substances in the sample solution; target substances are furthest enriched, and the purification effect is improved.

Description

Technical Field

[0001] The present invention relates to the field of biochemical detection, and in particular to a fully automatic sample processing method and system for high-throughput magnetic column processing. Background Art

[0002] In the detection process of protein substances such as nucleic acids, it is necessary to enrich, separate and purify the protein substances first to obtain the corresponding protein integrated substances, so that the protein substances can be subjected to more in-depth biochemical detection. If the content of effective protein substances in the protein integrated substances is large, the detection effectiveness will not be guaranteed during the biochemical detection process, thereby reducing the credibility of the biochemical detection results. It can be seen that the enrichment operation of protein substances directly affects the accuracy of subsequent biochemical detection. The prior art usually uses a magnetic bead method to enrich protein substances, that is, magnetic beads are placed in a sample solution containing protein substances, and the magnetic beads will rotate inside the sample solution under the action of a magnetic column applied by the outside world. The protein substances inside the sample solution will contact the surface of the magnetic beads and be adsorbed on the surface of the magnetic beads, thereby enriching the protein substances on the surface of the magnetic beads. The magnetic bead method uses a magnetic column to control the regular rotation of the magnetic beads inside the sample solution. It does not take into account the uneven distribution of protein substances inside the sample solution, and cannot ensure that the magnetic beads can fully adsorb the protein substances inside the sample solution, and cannot maximize the enrichment of protein substances, thereby reducing the purification effect of the corresponding substances. Summary of the invention

[0003] The purpose of the present invention is to provide a fully automatic sample processing method and system for high-throughput magnetic column processing, obtain target substance distribution characteristic information inside the sample solution and movement characteristic information of magnetic beads inside the sample solution, thereby adjusting the magnetic column applied to the sample solution, changing the movement state of the magnetic beads inside the sample solution, fully considering the distribution unevenness of the target substance inside the sample solution, making the magnetic beads move as much as possible through the target substance-rich area inside the sample solution, and ensuring that the target substance is efficiently attached to the surface of the magnetic beads; based on the target substance adsorption state information on the surface of the magnetic beads, judging whether it is necessary to separate the magnetic beads from the sample solution, and realizing effective extraction of the target substance from the sample solution; when it is necessary to separate the magnetic beads from the sample solution, based on the position information of the magnetic beads inside the sample solution, adjusting the magnetic column applied to the sample solution, making the magnetic beads move along the corresponding path, separating the magnetic beads from the sample solution, ensuring that the magnetic beads can fully adsorb the target substance inside the sample solution, maximally enriching the target substance, and improving the purification effect.

[0004] The present invention is achieved through the following technical solutions:

[0005] A fully automatic sample processing method for high-throughput magnetic column processing, comprising:

[0006] Detecting the sample solution to obtain distribution characteristic information of the target substance in the sample solution; acquiring a motion image of the magnetic beads in the sample solution, analyzing the motion image to obtain motion characteristic information of the magnetic beads;

[0007] Based on the target substance distribution characteristic information and the motion characteristic information, the magnetic column applied to the sample solution is adjusted to change the motion state of the magnetic beads inside the sample solution; the surface of the magnetic beads is detected to obtain the target substance adsorption state information on the surface of the magnetic beads, and based on the target substance adsorption state information, it is determined whether the magnetic beads need to be separated from the sample solution;

[0008] When the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

[0009] Optionally, the sample solution is detected to obtain the target substance distribution characteristic information inside the sample solution; the motion image of the magnetic beads inside the sample solution is acquired, and the motion image is analyzed to obtain the motion characteristic information of the magnetic beads, including:

[0010] Perform fluorescence spectrum detection on the sample solution at several time points respectively to obtain several fluorescence spectrum data corresponding to the sample solution and the several time points; analyze each fluorescence spectrum data to obtain the target substance distribution data corresponding to each time point inside the sample solution; integrate and analyze all the target substance distribution data corresponding to the several time points to obtain the target substance distribution characteristic information inside the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each of the sub-areas inside the sample solution;

[0011] The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

[0012] Optionally, based on the target substance distribution characteristic information and the motion characteristic information, adjusting the magnetic column applied to the sample solution to change the motion state of the magnetic beads inside the sample solution; detecting the surface of the magnetic beads to obtain the target substance adsorption state information on the surface of the magnetic beads, and judging whether the magnetic beads need to be separated from the sample solution based on the target substance adsorption state information, including:

[0013] Based on the target substance concentrations corresponding to all sub-regions inside the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions inside the sample solution and the movement path information of the magnetic beads inside the sample solution and the movement residence time information of all sub-regions inside the sample solution contained in the motion characteristic information, the attachment rate of the target substance inside the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance inside the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted;

[0014] When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path;

[0015] The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

[0016] Optionally, when the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along a corresponding path, thereby separating the magnetic beads from the sample solution, including:

[0017] When it is necessary to separate the magnetic beads from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

[0018] Optionally, adjusting the flux of the magnetic column applied to the sample solution comprises:

[0019] Extracting basic parameters of magnetic beads, wherein the basic parameters of magnetic beads include magnetic bead volume and magnetic bead mass;

[0020] Extracting the viscosity of the sample solution in which the magnetic beads are located;

[0021] Real-time monitoring of the movement speed of magnetic beads in the sample solution;

[0022] Obtaining a compensation adjustment coefficient of the magnetic column flux according to the basic parameters of the magnetic beads combined with the viscosity of the sample solution in which the magnetic beads are located and the moving speed of the magnetic beads in the sample solution;

[0023] The compensation adjustment coefficient of the magnetic column flux is obtained by the following formula:

[0024]

[0025] Wherein, δ represents the compensation adjustment coefficient of the magnetic column flux; n represents the number of unit times experienced by the magnetic column flux adjustment, and the unit time is 1s; v i represents the moving speed of the magnetic bead corresponding to the i-th unit time; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B i represents the magnetic field intensity corresponding to the i-th unit time of the magnetic bead; B c represents the magnetic field strength corresponding to the minimum movement speed allowed during the preset movement of the magnetic beads; B represents the current magnetic field strength; V represents the volume of the magnetic beads; m represents the mass of the magnetic beads; X represents the magnetic susceptibility of the magnetic beads; ρ represents the density of the sample solution; η represents the viscosity of the sample solution; R represents the radius of the magnetic beads; x represents the base of the preset logarithmic function, and the base is obtained by the following formula:

[0026]

[0027] Wherein, x represents the base of the preset logarithmic function; v represents the moving speed of the magnetic bead at the current moment; B represents the magnetic field strength of the magnetic bead at the current moment; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B c Indicates the magnetic field strength corresponding to the minimum allowed moving speed during the preset movement of the magnetic beads; g indicates the speed change rate of the current magnetic beads;

[0028] The current magnetic column flux is adjusted using the compensation adjustment coefficient of the magnetic column flux, wherein the adjusted magnetic column flux is obtained by the following formula:

[0029]

[0030] Where P represents the adjusted magnetic column flux; δ represents the compensation adjustment coefficient of the magnetic column flux; δ c represents the preset reference value of the compensation adjustment coefficient; B represents the magnetic field strength corresponding to the magnetic bead at the current moment; B xrepresents the magnetic field strength obtained at the previous data collection moment corresponding to the current moment; v represents the moving speed of the magnetic bead corresponding to the current moment; v x It represents the moving speed obtained at the previous data collection moment corresponding to the current moment; A represents the area through which the magnetic field lines pass; θ represents the angle between the magnetic field direction and the area normal direction.

[0031] A fully automatic sample processing system for high-throughput magnetic column processing, comprising:

[0032] A sample solution substance distribution identification module is used to detect the sample solution and obtain the target substance distribution characteristic information inside the sample solution;

[0033] A magnetic bead motion detection module, used to obtain motion images of the magnetic beads inside the sample solution, analyze the motion images, and obtain motion characteristic information of the magnetic beads;

[0034] A magnetic bead motion adjustment module, used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic beads inside the sample solution;

[0035] A magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the sample solution;

[0036] The magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads inside the sample solution when it is necessary to separate the magnetic beads from the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

[0037] Optionally, the sample solution substance distribution identification module is used to detect the sample solution to obtain target substance distribution characteristic information inside the sample solution, including:

[0038] Perform fluorescence spectrum detection on the sample solution at several time points respectively to obtain several fluorescence spectrum data corresponding to the sample solution and the several time points; analyze each fluorescence spectrum data to obtain the target substance distribution data corresponding to each time point inside the sample solution; integrate and analyze all the target substance distribution data corresponding to the several time points to obtain the target substance distribution characteristic information inside the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each of the sub-areas inside the sample solution;

[0039] The magnetic bead motion detection module is used to obtain the motion image of the magnetic bead inside the sample solution, analyze the motion image, and obtain the motion characteristic information of the magnetic bead, including:

[0040] The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

[0041] Optionally, the magnetic bead motion adjustment module is used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic beads inside the sample solution, including:

[0042] Based on the target substance concentrations corresponding to all sub-regions inside the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions inside the sample solution and the movement path information of the magnetic beads inside the sample solution and the movement residence time information of all sub-regions inside the sample solution contained in the motion characteristic information, the attachment rate of the target substance inside the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance inside the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted;

[0043] When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path;

[0044] The magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the inside of the sample solution, including:

[0045] The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

[0046] Optionally, the magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads in the sample solution when the magnetic beads need to be separated from the sample solution, so that the magnetic beads move along a corresponding path, thereby separating the magnetic beads from the sample solution, including:

[0047] When it is necessary to separate the magnetic beads from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] The fully automatic sample processing method and system for high-throughput magnetic column processing provided in the present application obtain the target substance distribution characteristic information inside the sample solution and the movement characteristic information of the magnetic beads inside the sample solution, thereby adjusting the magnetic column applied to the sample solution, changing the movement state of the magnetic beads inside the sample solution, and fully considering the uneven distribution of the target substance inside the sample solution, so that the magnetic beads can move as much as possible through the target substance-rich area inside the sample solution, and ensure that the target substance is efficiently attached to the surface of the magnetic beads; based on the target substance adsorption state information on the surface of the magnetic beads, it is determined whether the magnetic beads need to be separated from the sample solution to achieve effective extraction of the target substance from the sample solution; when the magnetic beads need to be separated from the sample solution, based on the position information of the magnetic beads inside the sample solution, the magnetic column applied to the sample solution is adjusted to make the magnetic beads move along the corresponding path, and the magnetic beads are separated from the sample solution, ensuring that the magnetic beads can fully adsorb the target substance inside the sample solution, maximally enrich the target substance, and improve the purification effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the prior art descriptions. 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:

[0051] Figure 1 A schematic flow chart of a fully automatic sample processing method for high-throughput magnetic column processing provided by the present invention.

[0052] Figure 2 A schematic structural diagram of a fully automatic sample processing system for high-throughput magnetic column processing provided by the present invention. DETAILED DESCRIPTION

[0053] In order to make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific implementation methods of the present application are described in detail below in conjunction with the accompanying drawings. It is to be understood that the specific embodiments described herein are only used to explain the present application, rather than to limit the present application. It should also be noted that, for ease of description, only some structures related to the present application are shown in the accompanying drawings, rather than all structures. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0054] The terms "including" and "having" and any variations thereof in this application are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device comprising a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products or devices.

[0055] Reference to "embodiments" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0056] See also Figure 1 As shown, an embodiment of the present application provides a fully automatic sample processing method for high-throughput magnetic column processing. The fully automatic sample processing method for high-throughput magnetic column processing includes:

[0057] Detecting the sample solution to obtain distribution characteristic information of the target substance in the sample solution; acquiring a motion image of the magnetic beads in the sample solution, analyzing the motion image, and obtaining motion characteristic information of the magnetic beads;

[0058] Based on the target substance distribution characteristic information and the motion characteristic information, the magnetic column applied to the sample solution is adjusted to change the motion state of the magnetic beads inside the sample solution; the surface of the magnetic beads is detected to obtain the target substance adsorption state information on the surface of the magnetic beads, and based on the target substance adsorption state information, it is determined whether the magnetic beads need to be separated from the sample solution;

[0059] When the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

[0060] The beneficial effects of the above embodiments are as follows: the fully automatic sample processing method for high-throughput magnetic column processing obtains the target substance distribution characteristic information inside the sample solution and the movement characteristic information of the magnetic beads inside the sample solution, thereby adjusting the magnetic column applied to the sample solution, changing the movement state of the magnetic beads inside the sample solution, and fully considering the uneven distribution of the target substance inside the sample solution, so that the magnetic beads move as much as possible through the target substance-rich area inside the sample solution, ensuring that the target substance is efficiently attached to the surface of the magnetic beads; based on the target substance adsorption state information on the surface of the magnetic beads, it is determined whether the magnetic beads need to be separated from the sample solution to achieve effective extraction of the target substance from the sample solution; when the magnetic beads need to be separated from the sample solution, based on the position information of the magnetic beads inside the sample solution, the magnetic column applied to the sample solution is adjusted to make the magnetic beads move along the corresponding path, and the magnetic beads are separated from the sample solution, ensuring that the magnetic beads can fully adsorb the target substance inside the sample solution, maximally enrich the target substance, and improve the purification effect.

[0061] In another embodiment, the sample solution is detected to obtain the target substance distribution characteristic information inside the sample solution; the motion image of the magnetic beads inside the sample solution is acquired, and the motion image is analyzed to obtain the motion characteristic information of the magnetic beads, including:

[0062] Perform fluorescence spectrum detection on the sample solution at several time points respectively to obtain several fluorescence spectrum data corresponding to the sample solution and the several time points; analyze each fluorescence spectrum data to obtain the target substance distribution data corresponding to each time point in the sample solution; integrate and analyze all the target substance distribution data corresponding to the several time points to obtain the target substance distribution characteristic information in the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each sub-region in the sample solution;

[0063] The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

[0064] The beneficial effect of the above embodiment is that the sample solution mainly contains the target substance (such as nucleic acid or other protein substances, etc.) and other impurity substances. The target substance will diffuse and move inside the sample solution, so that the concentration of the target substance in different sub-regions inside the sample solution is not the same; wherein the different sub-regions inside the sample solution may be, but are not limited to, a number of sub-regions distributed in sequence along the depth direction inside the sample solution, and each sub-region corresponds to a different depth range. The concentration distribution of the target substance in different sub-regions inside the sample solution is uneven, and the concentration of the target substance in some sub-regions is low, while the concentration of the target substance in another sub-region is high. In order to make the surface of the magnetic beads adsorb the target substance as quickly and as much as possible, it is necessary to ensure that the magnetic beads can move in the sub-region with a higher concentration of the target substance. For this purpose, it is necessary to predetermine the distribution of the concentration of the target substance inside the sample solution. By performing fluorescence spectrum detection on the global range of the sample solution at several time points, several fluorescence spectrum data of the sample solution corresponding to the several time points are obtained. Generally speaking, the greater the fluorescence intensity of the characteristic wavelength corresponding to the target substance in the fluorescence spectrum data of a certain area inside the sample solution, the greater the target substance content in the corresponding area. Each fluorescence spectrum data is then analyzed to obtain the target substance distribution data corresponding to each time point inside the sample solution; all the target substance distribution data corresponding to several time points are integrated and analyzed to obtain the target substance concentration corresponding to all sub-areas inside the sample solution. In this way, the target substance concentration of all sub-areas inside the sample solution can be quantitatively determined, and the integration and analysis of all the target substance distribution data corresponding to different time points can avoid large errors caused by determining the target substance distribution concentration based on the fluorescence spectrum data obtained from a single fluorescence spectrum detection. In addition, the movement path and speed of the magnetic beads in the sample solution will affect the adsorption efficiency of the target substance on the surface of the magnetic beads. Generally speaking, if the movement path of the magnetic beads in the sample solution passes through sub-areas with higher concentrations of the target substance and the movement speed of the magnetic beads is lower (that is, the magnetic beads stay in each sub-area for a longer time), the adsorption efficiency of the target substance on the surface of the magnetic beads is also higher. For this reason, the movement process of the magnetic beads in the sample solution is dynamically photographed and imaged to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of the magnetic beads in all sub-areas of the sample solution. By detecting the movement of the magnetic beads, a reliable basis can be provided for the subsequent adjustment of the movement path of the magnetic beads in the sample solution, so that the magnetic beads can move through the target substance-rich areas in the sample solution as much as possible.

[0065] In another embodiment, based on the target substance distribution characteristic information and the motion characteristic information, the magnetic column applied to the sample solution is adjusted to change the motion state of the magnetic beads inside the sample solution; the surface of the magnetic beads is detected to obtain the target substance adsorption state information on the surface of the magnetic beads, and based on the target substance adsorption state information, it is determined whether the magnetic beads need to be separated from the sample solution, including:

[0066] Based on the target substance concentrations corresponding to all sub-regions in the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions in the sample solution and the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-regions in the sample solution contained in the motion characteristic information, the attachment rate of the target substance in the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance in the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted;

[0067] When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path;

[0068] The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

[0069] The beneficial effect of the above embodiment is that based on the target substance concentration corresponding to each of all sub-regions in the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined, such as comparing the target substance concentration corresponding to each sub-region with the preset concentration threshold, and if the target substance concentration exceeds the preset concentration threshold, the corresponding sub-region is determined to be the target substance enrichment sub-region. Based on the distribution position information of all target substance enrichment sub-regions in the sample solution and the movement path information of the magnetic beads in the sample solution contained in the motion characteristic information and the movement residence time information of the magnetic beads in all sub-regions in the sample solution, the attachment rate of the target substance in the sample solution on the surface of the magnetic beads is modeled and estimated, and the average attachment rate of the target substance on the surface of the magnetic beads (i.e., the amount of the target substance attached to the surface of the magnetic beads per unit time) is obtained. If the average attachment rate is greater than or equal to the preset attachment rate threshold, it is judged that the magnetic beads effectively adsorb the target substance in the sample solution; otherwise, it is judged that the magnetic beads do not effectively adsorb the target substance in the sample solution, so that it can accurately judge whether it is necessary to adjust the magnetic column applied to the sample solution to change the operation of the magnetic beads in the sample solution (such as movement path and / or movement speed, etc.). When it is necessary to adjust the magnetic column applied to the sample solution, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions, so as to adjust the flux and / or direction of the magnetic column applied to the sample solution, so that the magnetic beads can move inside the sample solution at a suitable speed along the optimal movement path, so that the magnetic beads pass through as many target substance enrichment sub-regions as possible and have a sufficiently long movement residence time inside the target substance enrichment sub-region. In addition, the surface of the magnetic beads is subjected to fluorescence spectrum detection to obtain the target substance adsorption density information on the surface of the magnetic beads (such as the target substance adsorption amount per unit area of ​​the surface of the magnetic beads), and the target substance adsorption density information is compared by threshold value to determine whether the surface of the magnetic beads has reached the target substance adsorption saturation state, so as to provide an accurate basis for determining whether to separate the magnetic beads from the inside of the sample solution.

[0070] In another embodiment, when the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution, including:

[0071] When the magnetic beads need to be separated from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

[0072] The beneficial effect of the above embodiment is that when it is necessary to separate the magnetic beads from the inside of the sample solution, it indicates that it is necessary to change the current movement path of the magnetic beads inside the sample solution, so that the magnetic beads no longer rotate inside the sample solution, but move away from the sample solution along different paths. In order to ensure that the magnetic beads leave the sample solution efficiently and without collision during the separation process, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; then, based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution, providing sufficient material basis for the subsequent enrichment and purification of the target substances adsorbed on the surface of the magnetic beads.

[0073] In another embodiment, adjusting the flux of the magnetic column applied to the sample solution comprises:

[0074] Extracting basic parameters of magnetic beads, wherein the basic parameters of magnetic beads include magnetic bead volume and magnetic bead mass;

[0075] Extracting the viscosity of the sample solution in which the magnetic beads are located;

[0076] Real-time monitoring of the movement speed of magnetic beads in the sample solution;

[0077] Obtaining a compensation adjustment coefficient of the magnetic column flux according to the basic parameters of the magnetic beads combined with the viscosity of the sample solution in which the magnetic beads are located and the moving speed of the magnetic beads in the sample solution;

[0078] The compensation adjustment coefficient of the magnetic column flux is obtained by the following formula:

[0079]

[0080] Wherein, δ represents the compensation adjustment coefficient of the magnetic column flux; n represents the number of unit times experienced by the magnetic column flux adjustment, and the unit time is 1s; v i represents the moving speed of the magnetic bead corresponding to the i-th unit time; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B i represents the magnetic field intensity corresponding to the i-th unit time of the magnetic bead; B c represents the magnetic field strength corresponding to the minimum movement speed allowed during the preset movement of the magnetic beads; B represents the current magnetic field strength; V represents the volume of the magnetic beads; m represents the mass of the magnetic beads; X represents the magnetic susceptibility of the magnetic beads; ρ represents the density of the sample solution; η represents the viscosity of the sample solution; R represents the radius of the magnetic beads; x represents the base of the preset logarithmic function, and the base is obtained by the following formula:

[0081]

[0082] Wherein, x represents the base of the preset logarithmic function; v represents the moving speed of the magnetic bead at the current moment; B represents the magnetic field strength of the magnetic bead at the current moment; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B c Indicates the magnetic field strength corresponding to the minimum allowed moving speed during the preset movement of the magnetic beads; g indicates the speed change rate of the current magnetic beads;

[0083] The current magnetic column flux is adjusted using the compensation adjustment coefficient of the magnetic column flux, wherein the adjusted magnetic column flux is obtained by the following formula:

[0084]

[0085] Where P represents the adjusted magnetic column flux; δ represents the compensation adjustment coefficient of the magnetic column flux; δ c represents the preset reference value of the compensation adjustment coefficient; B represents the magnetic field strength corresponding to the magnetic bead at the current moment; B x represents the magnetic field strength obtained at the previous data collection moment corresponding to the current moment; v represents the moving speed of the magnetic bead corresponding to the current moment; v x It represents the moving speed obtained at the previous data collection moment corresponding to the current moment; A represents the area through which the magnetic field lines pass; θ represents the angle between the magnetic field direction and the area normal direction.

[0086] The beneficial effects of the above embodiments are that by real-time monitoring of the moving speed of the magnetic beads in the sample solution, and combining the basic parameters of the magnetic beads (such as volume, mass) and the viscosity of the sample solution, the technical solution can dynamically adjust the magnetic column flux. This dynamic adjustment enables the system to adapt to different experimental conditions, such as magnetic bead types, solution properties, etc., thereby improving the accuracy and stability of the experiment. Using the above mathematical formulas and parameters (such as the magnetic susceptibility of the magnetic beads, the density and viscosity of the sample solution, the radius of the magnetic beads, etc.), the technology can accurately calculate the compensation adjustment coefficient of the magnetic column flux. This coefficient not only takes into account the moving speed of the magnetic beads, but also takes into account the magnetic field intensity, the physical properties of the magnetic beads and the properties of the solution, thereby achieving high-precision adjustment of the magnetic column flux. By adjusting the magnetic column flux, the technology can optimize experimental processes such as magnetic separation or magnetic enrichment and improve experimental efficiency. For example, in the magnetic separation process, an appropriate magnetic column flux can ensure that the magnetic beads are evenly distributed in the sample solution, thereby accelerating the separation speed and improving the separation efficiency. The formulas and parameters in the technical solution can be adjusted and optimized according to specific experimental requirements. For example, by changing the preset minimum movement speed (vd) and the corresponding magnetic field strength (Bc) allowed during the movement of the magnetic beads, different types of magnetic beads and experimental conditions can be adapted. Since this technology can accurately adjust the magnetic column flux, the repeatability of the experiment can be significantly improved. This is especially important in scientific research fields that require repeated experiments to obtain reliable results.

[0087] In summary, this technical solution achieves precise adjustment and optimization of magnetic column flux by real-time monitoring and adjusting the movement speed of magnetic beads in the sample solution and combining the physical properties of magnetic beads and sample solution. This not only improves the accuracy and stability of the experiment, but also optimizes the experimental efficiency and improves the repeatability of the experiment.

[0088] See also Figure 2 As shown, an embodiment of the present application provides a fully automatic sample processing system for high-throughput magnetic column processing. The fully automatic sample processing system for high-throughput magnetic column processing includes:

[0089] The sample solution substance distribution identification module is used to detect the sample solution and obtain the target substance distribution characteristic information inside the sample solution;

[0090] A magnetic bead motion detection module is used to obtain motion images of the magnetic beads in the sample solution, analyze the motion images, and obtain motion characteristic information of the magnetic beads;

[0091] A magnetic bead motion adjustment module, used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic bead inside the sample solution;

[0092] The magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the sample solution;

[0093] The magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads in the sample solution when it is necessary to separate the magnetic beads from the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

[0094] The beneficial effects of the above embodiments are as follows: the fully automatic sample processing system for high-throughput magnetic column processing obtains the target substance distribution characteristic information inside the sample solution and the movement characteristic information of the magnetic beads inside the sample solution, thereby adjusting the magnetic column applied to the sample solution, changing the movement state of the magnetic beads inside the sample solution, and fully considering the uneven distribution of the target substance inside the sample solution, so that the magnetic beads move as much as possible through the target substance-rich area inside the sample solution, ensuring that the target substance is efficiently attached to the surface of the magnetic beads; based on the target substance adsorption state information on the surface of the magnetic beads, it is determined whether the magnetic beads need to be separated from the sample solution to achieve effective extraction of the target substance from the sample solution; when the magnetic beads need to be separated from the sample solution, based on the position information of the magnetic beads inside the sample solution, the magnetic column applied to the sample solution is adjusted to make the magnetic beads move along the corresponding path, and the magnetic beads are separated from the sample solution, ensuring that the magnetic beads can fully adsorb the target substance inside the sample solution, maximally enrich the target substance, and improve the purification effect.

[0095] In another embodiment, the sample solution substance distribution identification module is used to detect the sample solution to obtain target substance distribution characteristic information inside the sample solution, including:

[0096] Perform fluorescence spectrum detection on the sample solution at several time points respectively to obtain several fluorescence spectrum data corresponding to the sample solution and the several time points; analyze each fluorescence spectrum data to obtain the target substance distribution data corresponding to each time point in the sample solution; integrate and analyze all the target substance distribution data corresponding to the several time points to obtain the target substance distribution characteristic information in the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each sub-region in the sample solution;

[0097] The magnetic bead motion detection module is used to obtain the motion image of the magnetic bead in the sample solution, analyze the motion image, and obtain the motion characteristic information of the magnetic bead, including:

[0098] The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

[0099] The beneficial effect of the above embodiment is that the sample solution mainly contains the target substance (such as nucleic acid or other protein substances, etc.) and other impurity substances. The target substance will diffuse and move inside the sample solution, so that the concentration of the target substance in different sub-regions inside the sample solution is not the same; wherein the different sub-regions inside the sample solution may be, but are not limited to, a number of sub-regions distributed in sequence along the depth direction inside the sample solution, and each sub-region corresponds to a different depth range. The concentration distribution of the target substance in different sub-regions inside the sample solution is uneven, and the concentration of the target substance in some sub-regions is low, while the concentration of the target substance in another sub-region is high. In order to make the surface of the magnetic beads adsorb the target substance as quickly and as much as possible, it is necessary to ensure that the magnetic beads can move in the sub-region with a higher concentration of the target substance. For this purpose, it is necessary to predetermine the distribution of the concentration of the target substance inside the sample solution. By performing fluorescence spectrum detection on the global range of the sample solution at several time points, several fluorescence spectrum data of the sample solution corresponding to the several time points are obtained. Generally speaking, the greater the fluorescence intensity of the characteristic wavelength corresponding to the target substance in the fluorescence spectrum data of a certain area inside the sample solution, the greater the target substance content in the corresponding area. Each fluorescence spectrum data is then analyzed to obtain the target substance distribution data corresponding to each time point inside the sample solution; all the target substance distribution data corresponding to several time points are integrated and analyzed to obtain the target substance concentration corresponding to all sub-areas inside the sample solution. In this way, the target substance concentration of all sub-areas inside the sample solution can be quantitatively determined, and the integration and analysis of all the target substance distribution data corresponding to different time points can avoid large errors caused by determining the target substance distribution concentration based on the fluorescence spectrum data obtained from a single fluorescence spectrum detection. In addition, the movement path and speed of the magnetic beads in the sample solution will affect the adsorption efficiency of the target substance on the surface of the magnetic beads. Generally speaking, if the movement path of the magnetic beads in the sample solution passes through sub-areas with higher concentrations of the target substance and the movement speed of the magnetic beads is lower (that is, the magnetic beads stay in each sub-area for a longer time), the adsorption efficiency of the target substance on the surface of the magnetic beads is also higher. For this reason, the movement process of the magnetic beads in the sample solution is dynamically photographed and imaged to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of the magnetic beads in all sub-areas of the sample solution. By detecting the movement of the magnetic beads, a reliable basis can be provided for the subsequent adjustment of the movement path of the magnetic beads in the sample solution, so that the magnetic beads can move through the target substance-rich areas in the sample solution as much as possible.

[0100] In another embodiment, the magnetic bead motion adjustment module is used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic bead inside the sample solution, including:

[0101] Based on the target substance concentrations corresponding to all sub-regions in the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions in the sample solution and the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-regions in the sample solution contained in the motion characteristic information, the attachment rate of the target substance in the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance in the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted;

[0102] When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path;

[0103] The magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the sample solution, including:

[0104] The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

[0105] The beneficial effect of the above embodiment is that based on the target substance concentration corresponding to each of all sub-regions in the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined, such as comparing the target substance concentration corresponding to each sub-region with the preset concentration threshold, and if the target substance concentration exceeds the preset concentration threshold, the corresponding sub-region is determined to be the target substance enrichment sub-region. Based on the distribution position information of all target substance enrichment sub-regions in the sample solution and the movement path information of the magnetic beads in the sample solution contained in the motion characteristic information and the movement residence time information of the magnetic beads in all sub-regions in the sample solution, the attachment rate of the target substance in the sample solution on the surface of the magnetic beads is modeled and estimated, and the average attachment rate of the target substance on the surface of the magnetic beads (i.e., the amount of the target substance attached to the surface of the magnetic beads per unit time) is obtained. If the average attachment rate is greater than or equal to the preset attachment rate threshold, it is judged that the magnetic beads effectively adsorb the target substance in the sample solution; otherwise, it is judged that the magnetic beads do not effectively adsorb the target substance in the sample solution, so that it can accurately judge whether it is necessary to adjust the magnetic column applied to the sample solution to change the operation of the magnetic beads in the sample solution (such as movement path and / or movement speed, etc.). When it is necessary to adjust the magnetic column applied to the sample solution, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions, so as to adjust the flux and / or direction of the magnetic column applied to the sample solution, so that the magnetic beads can move inside the sample solution at a suitable speed along the optimal movement path, so that the magnetic beads pass through as many target substance enrichment sub-regions as possible and have a sufficiently long movement residence time inside the target substance enrichment sub-region. In addition, the surface of the magnetic beads is subjected to fluorescence spectrum detection to obtain the target substance adsorption density information on the surface of the magnetic beads (such as the target substance adsorption amount per unit area of ​​the surface of the magnetic beads), and the target substance adsorption density information is compared by threshold value to determine whether the surface of the magnetic beads has reached the target substance adsorption saturation state, so as to provide an accurate basis for determining whether to separate the magnetic beads from the inside of the sample solution.

[0106] In another embodiment, the magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads in the sample solution when the magnetic beads need to be separated from the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution, including:

[0107] When the magnetic beads need to be separated from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

[0108] The beneficial effect of the above embodiment is that when it is necessary to separate the magnetic beads from the inside of the sample solution, it indicates that it is necessary to change the current movement path of the magnetic beads inside the sample solution, so that the magnetic beads no longer rotate inside the sample solution, but move away from the sample solution along different paths. In order to ensure that the magnetic beads leave the sample solution efficiently and without collision during the separation process, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; then, based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution, providing sufficient material basis for the subsequent enrichment and purification of the target substances adsorbed on the surface of the magnetic beads.

[0109] In general, the fully automatic sample processing method and system for high-throughput magnetic column processing obtains the target substance distribution characteristic information inside the sample solution and the movement characteristic information of the magnetic beads inside the sample solution, thereby adjusting the magnetic column applied to the sample solution, changing the movement state of the magnetic beads inside the sample solution, and fully considering the uneven distribution of the target substance inside the sample solution, so that the magnetic beads move as much as possible through the target substance-rich area inside the sample solution, ensuring that the target substance is efficiently attached to the surface of the magnetic beads; based on the target substance adsorption state information on the surface of the magnetic beads, it is determined whether the magnetic beads need to be separated from the sample solution to achieve effective extraction of the target substance from the sample solution; when the magnetic beads need to be separated from the sample solution, based on the position information of the magnetic beads inside the sample solution, the magnetic column applied to the sample solution is adjusted to make the magnetic beads move along the corresponding path, and the magnetic beads are separated from the sample solution, ensuring that the magnetic beads can fully adsorb the target substance inside the sample solution, maximally enrich the target substance, and improve the purification effect.

[0110] The above is only a specific implementation of the present invention, and any other improvements made based on the concept of the present invention are considered to be within the protection scope of the present invention.

Claims

1. A fully automatic sample processing method for high-throughput magnetic column processing, characterized in that: include: Detecting the sample solution to obtain distribution characteristic information of the target substance in the sample solution; Acquiring a motion image of the magnetic beads inside the sample solution, and analyzing the motion image to obtain motion characteristic information of the magnetic beads; Based on the target substance distribution characteristic information and the motion characteristic information, the magnetic column applied to the sample solution is adjusted to change the motion state of the magnetic beads inside the sample solution; the surface of the magnetic beads is detected to obtain the target substance adsorption state information on the surface of the magnetic beads, and based on the target substance adsorption state information, it is determined whether the magnetic beads need to be separated from the sample solution; When the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

2. The fully automatic sample processing method for high-throughput magnetic column processing according to claim 1, characterized in that: Detecting the sample solution to obtain distribution characteristic information of the target substance in the sample solution; Acquiring a motion image of the magnetic beads in the sample solution, and analyzing the motion image to obtain motion characteristic information of the magnetic beads, including: Perform fluorescence spectrum detection on the sample solution at several time points respectively to obtain several fluorescence spectrum data corresponding to the sample solution and the several time points; analyze each fluorescence spectrum data to obtain the target substance distribution data corresponding to each time point inside the sample solution; integrate and analyze all the target substance distribution data corresponding to the several time points to obtain the target substance distribution characteristic information inside the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each of the sub-areas inside the sample solution; The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

3. The fully automatic sample processing method for high-throughput magnetic column processing according to claim 1, characterized in that: Based on the target substance distribution characteristic information and the motion characteristic information, the magnetic column applied to the sample solution is adjusted to change the motion state of the magnetic beads inside the sample solution; the surface of the magnetic beads is detected to obtain the target substance adsorption state information on the surface of the magnetic beads, and based on the target substance adsorption state information, it is determined whether the magnetic beads need to be separated from the sample solution, including: Based on the target substance concentrations corresponding to all sub-regions inside the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions inside the sample solution and the movement path information of the magnetic beads inside the sample solution and the movement residence time information of all sub-regions inside the sample solution contained in the motion characteristic information, the attachment rate of the target substance inside the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance inside the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted; When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path; The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

4. The fully automatic sample processing method for high-throughput magnetic column processing according to claim 1, characterized in that: When the magnetic beads need to be separated from the sample solution, the magnetic column applied to the sample solution is adjusted based on the position information of the magnetic beads in the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution, including: When it is necessary to separate the magnetic beads from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

5. The fully automatic sample processing method for high-throughput magnetic column processing according to claim 4, characterized in that: Adjusting the magnetic column flux applied to the sample solution includes: Extracting basic parameters of magnetic beads, wherein the basic parameters of magnetic beads include magnetic bead volume and magnetic bead mass; Extracting the viscosity of the sample solution in which the magnetic beads are located; Real-time monitoring of the movement speed of magnetic beads in the sample solution; Obtaining a compensation adjustment coefficient of the magnetic column flux according to the basic parameters of the magnetic beads combined with the viscosity of the sample solution in which the magnetic beads are located and the moving speed of the magnetic beads in the sample solution; The compensation adjustment coefficient of the magnetic column flux is obtained by the following formula: Wherein, δ represents the compensation adjustment coefficient of the magnetic column flux; n represents the number of unit times experienced by the magnetic column flux adjustment, and the unit time is 1s; v i represents the moving speed of the magnetic bead corresponding to the i-th unit time; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B i represents the magnetic field intensity corresponding to the i-th unit time of the magnetic bead; B c represents the magnetic field strength corresponding to the minimum movement speed allowed during the preset movement of the magnetic beads; B represents the current magnetic field strength; V represents the volume of the magnetic beads; m represents the mass of the magnetic beads; X represents the magnetic susceptibility of the magnetic beads; ρ represents the density of the sample solution; η represents the viscosity of the sample solution; R represents the radius of the magnetic beads; x represents the base of the preset logarithmic function, and the base is obtained by the following formula: Wherein, x represents the base of the preset logarithmic function; v represents the moving speed of the magnetic bead at the current moment; B represents the magnetic field strength of the magnetic bead at the current moment; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B c Indicates the magnetic field strength corresponding to the minimum allowed moving speed during the preset movement of the magnetic beads; g indicates the speed change rate of the current magnetic beads; The current magnetic column flux is adjusted using the compensation adjustment coefficient of the magnetic column flux, wherein the adjusted magnetic column flux is obtained by the following formula: Where P represents the adjusted magnetic column flux; δ represents the compensation adjustment coefficient of the magnetic column flux; δ c represents the preset reference value of the compensation adjustment coefficient; B represents the magnetic field strength corresponding to the magnetic bead at the current moment; B x represents the magnetic field strength obtained at the previous data collection moment corresponding to the current moment; v represents the moving speed of the magnetic bead corresponding to the current moment; v x It represents the moving speed obtained at the previous data collection moment corresponding to the current moment; A represents the area through which the magnetic field lines pass; θ represents the angle between the magnetic field direction and the area normal direction.

6. A fully automatic sample processing system for high-throughput magnetic column processing, characterized in that: include: A sample solution substance distribution identification module is used to detect the sample solution and obtain the target substance distribution characteristic information inside the sample solution; A magnetic bead motion detection module, used to obtain motion images of the magnetic beads inside the sample solution, analyze the motion images, and obtain motion characteristic information of the magnetic beads; A magnetic bead motion adjustment module, used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic beads inside the sample solution; A magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the sample solution; The magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads inside the sample solution when it is necessary to separate the magnetic beads from the sample solution, so that the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution.

7. The fully automatic sample processing system for high-throughput magnetic column processing according to claim 6, characterized in that: The sample solution substance distribution identification module is used to detect the sample solution to obtain target substance distribution characteristic information inside the sample solution, including: The sample solution is subjected to fluorescence spectrum detection at several time points to obtain a number of fluorescence spectrum data corresponding to the sample solution and the several time points; each fluorescence spectrum data is analyzed to obtain the target substance distribution data corresponding to each time point in the sample solution; all the target substance distribution data corresponding to the several time points are integrated and analyzed to obtain the target substance distribution characteristic information in the sample solution; wherein the target substance distribution characteristic information refers to the target substance concentration corresponding to each sub-area in the sample solution; the magnetic bead motion detection module is used to obtain the motion image of the magnetic bead in the sample solution, and the motion image is analyzed to obtain the motion characteristic information of the magnetic bead, including: The movement process of the magnetic beads in the sample solution is dynamically photographed to obtain a dynamic image of the movement of the magnetic beads; the dynamic image is analyzed to obtain the movement path information of the magnetic beads in the sample solution and the movement residence time information of all sub-areas of the magnetic beads in the sample solution, which is used as the movement characteristic information of the magnetic beads.

8. The fully automatic sample processing system for high-throughput magnetic column processing according to claim 6, characterized in that: The magnetic bead motion adjustment module is used to adjust the magnetic column applied to the sample solution based on the target substance distribution characteristic information and the motion characteristic information, so as to change the motion state of the magnetic beads inside the sample solution, including: Based on the target substance concentrations corresponding to all sub-regions inside the sample solution contained in the target substance distribution characteristic information, all target substance enrichment sub-regions corresponding to the sample solution are determined; based on the distribution position information of all target substance enrichment sub-regions inside the sample solution and the movement path information of the magnetic beads inside the sample solution and the movement residence time information of all sub-regions inside the sample solution contained in the motion characteristic information, the attachment rate of the target substance inside the sample solution on the surface of the magnetic beads is estimated; based on the attachment rate, whether the magnetic beads effectively adsorb the target substance inside the sample solution; if so, there is no need to adjust the magnetic column applied to the sample solution; if not, the magnetic column applied to the sample solution needs to be adjusted; When the magnetic column applied to the sample solution needs to be adjusted, the optimal movement path of the magnetic beads inside the sample solution is determined based on the distribution position information of all target substance enrichment sub-regions; and the flux and / or direction of the magnetic column applied to the sample solution is adjusted based on the optimal movement path; The magnetic bead surface substance adsorption identification module is used to detect the surface of the magnetic bead to obtain the target substance adsorption state information on the surface of the magnetic bead, and based on the target substance adsorption state information, determine whether the magnetic bead needs to be separated from the inside of the sample solution, including: The surface of the magnetic beads is subjected to fluorescence spectroscopy detection to obtain the target substance adsorption density information on the surface of the magnetic beads; and based on the target substance adsorption density information, it is determined whether the surface of the magnetic beads has reached the target substance adsorption saturation state; if so, it is determined that the magnetic beads need to be separated from the inside of the sample solution; if not, it is determined that the magnetic beads do not need to be separated from the inside of the sample solution.

9. The fully automatic sample processing system for high-throughput magnetic column processing according to claim 6, characterized in that: The magnetic bead separation and removal control module is used to adjust the magnetic column applied to the sample solution based on the position information of the magnetic beads in the sample solution when the magnetic beads need to be separated from the sample solution, so as to make the magnetic beads move along the corresponding path, thereby separating the magnetic beads from the sample solution, including: When it is necessary to separate the magnetic beads from the sample solution, the separation movement path of the magnetic beads is determined based on the position information of the magnetic beads in the sample solution and the separation and removal target position information; based on the separation movement path, the flux and / or direction of the magnetic column applied to the sample solution is adjusted, so that the magnetic beads move at a uniform speed along the separation movement path, thereby separating the magnetic beads from the sample solution.

10. The fully automatic sample processing system for high-throughput magnetic column processing according to claim 9, characterized in that: Adjusting the magnetic column flux applied to the sample solution includes: Extracting basic parameters of magnetic beads, wherein the basic parameters of magnetic beads include magnetic bead volume and magnetic bead mass; Extracting the viscosity of the sample solution in which the magnetic beads are located; Real-time monitoring of the movement speed of magnetic beads in the sample solution; Obtaining a compensation adjustment coefficient of the magnetic column flux according to the basic parameters of the magnetic beads combined with the viscosity of the sample solution in which the magnetic beads are located and the moving speed of the magnetic beads in the sample solution; The compensation adjustment coefficient of the magnetic column flux is obtained by the following formula: Wherein, δ represents the compensation adjustment coefficient of the magnetic column flux; n represents the number of unit times experienced by the magnetic column flux adjustment, and the unit time is 1s; v i represents the moving speed of the magnetic bead corresponding to the i-th unit time; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B i represents the magnetic field intensity corresponding to the i-th unit time of the magnetic bead; B c represents the magnetic field strength corresponding to the minimum movement speed allowed during the preset movement of the magnetic beads; B represents the current magnetic field strength; V represents the volume of the magnetic beads; m represents the mass of the magnetic beads; X represents the magnetic susceptibility of the magnetic beads; ρ represents the density of the sample solution; η represents the viscosity of the sample solution; R represents the radius of the magnetic beads; x represents the base of the preset logarithmic function, and the base is obtained by the following formula: Wherein, x represents the base of the preset logarithmic function; v represents the moving speed of the magnetic bead at the current moment; B represents the magnetic field strength of the magnetic bead at the current moment; v d Indicates the minimum movement speed allowed during the preset magnetic bead movement process; B c Indicates the magnetic field strength corresponding to the minimum allowed moving speed during the preset movement of the magnetic beads; g indicates the speed change rate of the current magnetic beads; The current magnetic column flux is adjusted using the compensation adjustment coefficient of the magnetic column flux, wherein the adjusted magnetic column flux is obtained by the following formula: Where P represents the adjusted magnetic column flux; δ represents the compensation adjustment coefficient of the magnetic column flux; δ c Indicates the preset reference value of the compensation adjustment coefficient; B indicates the magnetic field strength corresponding to the magnetic bead at the current moment; B x represents the magnetic field strength obtained at the previous data collection moment corresponding to the current moment; v represents the moving speed of the magnetic bead corresponding to the current moment; v x It represents the moving speed obtained at the previous data collection moment corresponding to the current moment; A represents the area through which the magnetic field lines pass; θ represents the angle between the magnetic field direction and the area normal direction.

Images