A method for ensuring stability of a resin chromatography column

Abstract

The application provides a method for ensuring stability of a resin chromatographic column, and relates to the technical field of chromatographic column analysis, and comprises the following steps: based on the stationary phase parameters of the resin chromatographic column, corresponding mobile phase parameters are matched; based on the stationary phase parameters and the mobile phase parameters, the resolution of the resin chromatographic column is determined; based on the resolution, buffer solvents are matched for the resin chromatographic column, and the adsorption flow rate of sample reagents at different time points in the resin chromatographic column after passing through the buffer solvents is monitored; based on the solution concentration of the sample reagents, the adsorption flow rate and the saturated adsorption capacity of the resin chromatographic column, it is judged whether the resin chromatographic column is contaminated; if the resin chromatographic column is contaminated, chromatographic column repair is performed. The method improves the separation accuracy of the chromatographic column during use, improves the stability of the resin chromatographic column, and better improves the use efficiency of the resin chromatographic column.

Description

Technical Field

[0001] This invention relates to the field of chromatographic column analysis technology, and in particular to a method for ensuring the stability of resin chromatographic columns. Background Technology

[0002] Chromatography is a separation and analysis technique, with separation being its core function. Therefore, the chromatographic column, responsible for separation, is the heart of the chromatographic system. The requirements for chromatographic columns include good stability, high column efficiency, good selectivity, and fast analysis speed. Proper use and maintenance of chromatographic columns are crucial; slight negligence can reduce stability, shorten lifespan, or even damage them. The stability of resin chromatographic columns primarily depends on the type of column packing, but by using correct methods before and during use, the stability of resin chromatographic columns can be maintained.

[0003] Therefore, the present invention provides a method for ensuring the stability of a resin chromatography column. Summary of the Invention

[0004] This invention provides a method for ensuring the stability of a resin chromatography column. The method involves analyzing the stationary phase parameters of the resin chromatography column to obtain corresponding mobile phase parameters, determining the resolution of the resin chromatography column, matching a buffer solvent to the resin chromatography column according to the resolution, and monitoring the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent. Based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin chromatography column, the method determines whether the resin chromatography column is contaminated. If the resin chromatography column is contaminated, column repair is performed. This improves the separation accuracy of the column during use, enhances the stability of the resin chromatography column, and ultimately improves the efficiency of the resin chromatography column.

[0005] This invention provides a method for ensuring the stability of a resin chromatography column, comprising:

[0006] Step 1: Based on the stationary phase parameters of the resin chromatography column, obtain the corresponding mobile phase parameters;

[0007] Step 2: Determine the resolution of the resin column based on the stationary phase parameters and the mobile phase parameters;

[0008] Step 3: Based on the resolution, a buffer solvent is matched to the resin column, and the adsorption flow rate of the sample reagent in the resin column at different times after passing through the buffer solvent is monitored.

[0009] Step 4: Based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin column, determine whether the resin column is contaminated;

[0010] Step 5: If the resin column is contaminated, perform column repair.

[0011] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, which matches the corresponding mobile phase parameters based on the stationary phase parameters of the resin chromatography column, including:

[0012] Based on the stationary phase parameters of the resin chromatography column, the corresponding range of the first mobile phase is obtained;

[0013] Based on the parameters of the sample to be tested, the corresponding range of the second mobile phase is obtained;

[0014] Based on the first mobile phase range and the second mobile phase range, a third overlapping mobile phase range is obtained;

[0015] Based on the third mobile phase range and the mobile phase database, the corresponding mobile phase parameters are matched.

[0016] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, which determines the resolution of the resin chromatography column based on stationary phase parameters and mobile phase parameters, including:

[0017] A preset number of test samples are randomly selected, and a chromatographic diagram of each selected test sample is obtained based on the stationary phase parameters and the mobile phase parameters.

[0018] Based on the retention time and peak width in the chromatographic diagram, the corresponding detection column efficiency is obtained;

[0019] The number of columns with a detection efficiency greater than a preset column efficiency is obtained and used as the first quantity;

[0020] If the first quantity is greater than the preset effective quantity, the corresponding chromatographic diagram is retained;

[0021] Based on the retained chromatographic schematic, the corresponding first resolution is obtained;

[0022] The average of all first-degree separations is taken as the separation degree.

[0023] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, comprising, based on the resolution, matching a buffer solvent to the resin chromatography column, and monitoring the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent, including:

[0024] Based on the stationary phase parameters and the mobile phase parameters, the effectiveness and ineffectiveness of the chromatographic column are obtained;

[0025] If the resolution is greater than the invalidity and less than the effectiveity, then obtain the corresponding complete chromatographic schematic diagram;

[0026] Based on the separation values ​​corresponding to the maximum peak value in each chromatogram and the overall separation values, the corresponding first ratio value is obtained;

[0027] Based on the chromatographic column and the sample to be tested, the corresponding target result quality and the corresponding first content are obtained;

[0028] Based on each first content and the corresponding mass of the sample to be tested, a second ratio value is obtained;

[0029] Extract the chromatographic column result quality corresponding to the second proportion value that is less than the first proportion value in the same test sample;

[0030] The mass of impurities remaining in the column is obtained based on the initial mass of the column, the mass of the column result, and the mass of the target result in the same sample.

[0031] Input the impurity mass and the corresponding impurity type of the sample to be tested into the impurity analysis model to estimate the first mass corresponding to each impurity type in the chromatographic column.

[0032] The first average mass is obtained based on all the first masses of the same impurity type;

[0033] Based on the first average mass corresponding to all types of impurities, a corresponding impurity removal buffer solvent is matched.

[0034] All sample reagents were buffered and then fed into the resin chromatography column to obtain the corresponding target result quality of the resin chromatography column.

[0035] Calculate the difference between the quality of the target result and the preset result quality for the same target result, and obtain the first difference value;

[0036] If the first difference is within a preset reasonable difference, the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent is obtained.

[0037] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, which determines whether the resin chromatography column is contaminated based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin chromatography column, including:

[0038] Based on the adsorption flow rate of each sample reagent in the resin chromatography column at different times during different time periods after being buffered by the solvent, a flow rate change curve was constructed.

[0039] Based on the solution concentration and flow rate change curves of the same sample reagent, the predicted adsorption mass change curve is obtained.

[0040] Based on the values ​​corresponding to each point in the adsorption mass change curve, the overall adsorption value is obtained;

[0041] If the total adsorption value is less than the saturated adsorption capacity of the resin column, then calculate the point average value corresponding to all points in the flow rate change curve.

[0042] Based on the solution concentration of the sample reagent, match the corresponding average flow rate in the resin column concentration-flow rate comparison table;

[0043] Calculate the second difference between the point average value of the reagent for the same sample and the corresponding average flow rate;

[0044] If the second difference is greater than the preset difference, the resin chromatographic column is determined to be contaminated.

[0045] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, wherein if the resin chromatography column is contaminated, the column repair process includes:

[0046] Image acquisition of discrete sampling points on a contaminated resin chromatography column after sample reagent injection, as well as laser irradiation acquisition;

[0047] Determine the sampling scale between each discrete sampling point and the initial discrete sampling points, and obtain the image segmentation accuracy from the scale-segmentation mapping table;

[0048] Based on the image segmentation accuracy, the corresponding image is segmented, and a pixel array is constructed for each pixel based on different discrete sampling points. At the same time, a laser reflection array for each pixel based on different discrete sampling points is obtained.

[0049] Perform a first consistency analysis on each pixel array and a second consistency analysis on each laser reflection array;

[0050] Based on the first consistency analysis result, the first stability of the corresponding pixel is determined, and based on the second consistency analysis result, the second stability of the corresponding pixel is determined, and the analysis array of the corresponding pixel is constructed.

[0051] Lock a first position where the first stability is less than a first preset value, and lock a second position where the second stability is less than a second preset value;

[0052] Simultaneously, based on the analysis array, the third position where the stability difference is greater than the preset difference is selected;

[0053] Based on the first, second, and third positions, a position vector is constructed and input into the position analysis model to determine the distribution edge, diffusion direction, and diffusion color. A diffusion function is then constructed, and the type of contamination in the contaminated resin chromatography is determined based on the diffusion function.

[0054] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, which, based on the real-time image set, determines the type of contamination on the contaminated resin chromatography column, including:

[0055] If the type of contamination is surface contamination, the real-time image set is input into the resin chromatography column image analysis model to obtain the surface contamination area;

[0056] If the surface contamination area is smaller than the preset contamination area, an artificial recovery signal is issued to restore the resin chromatography column.

[0057] Preferably, the present invention provides a method for ensuring the stability of a resin chromatography column, which, based on the real-time image set, determines the type of contamination on the contaminated resin chromatography column, including:

[0058] If the type of contamination is non-surface contamination, obtain the corresponding sample parameters of the sample reagents;

[0059] Based on sample parameters and a database of rinsing solvents, a corresponding rinsing solvent is matched to restore the resin column.

[0060] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures particularly pointed out in the written description, claims, and drawings.

[0061] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0062] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0063] Figure 1 This is a flowchart of a method for ensuring the stability of a resin chromatography column in an embodiment of the present invention. Detailed Implementation

[0064] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0065] Example 1:

[0066] This invention provides a method for ensuring the stability of a resin chromatography column, such as... Figure 1 As shown, it includes:

[0067] Step 1: Based on the stationary phase parameters of the resin chromatography column, obtain the corresponding mobile phase parameters;

[0068] Step 2: Determine the resolution of the resin column based on the stationary phase parameters and the mobile phase parameters;

[0069] Step 3: Based on the resolution, a buffer solvent is matched to the resin column, and the adsorption flow rate of the sample reagent in the resin column at different times after passing through the buffer solvent is monitored.

[0070] Step 4: Based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin column, determine whether the resin column is contaminated;

[0071] Step 5: If the resin column is contaminated, perform column repair.

[0072] In this embodiment, the stationary phase parameters refer to the static solid or liquid components packed in the resin chromatography column and the corresponding content of each component.

[0073] In this embodiment, the mobile phase parameters refer to the composition of the liquid flowing through the chromatographic column and the corresponding content of each component.

[0074] In this embodiment, resolution refers to the ability of the resin chromatography column to separate the target components.

[0075] In this embodiment, the buffer solvent refers to the solvent used to screen out impurities in the solution to be tested when excessive impurities in the solution to be separated affect the stability of the resin chromatography column.

[0076] In this embodiment, the sample reagent refers to the sample of the reagent to be separated, which is used to detect the stability of the resin chromatography column.

[0077] In this embodiment, the adsorption flow rate refers to the speed at which the liquid separated by adsorption flows when the sample solvent passes through the resin chromatography column.

[0078] In this embodiment, saturated adsorption capacity refers to the maximum liquid capacity that the resin chromatography column can adsorb.

[0079] In this embodiment, column repair refers to the repair method for a contaminated resin column obtained by analyzing the cause of the contamination, when the resin column is contaminated and its adsorption capacity is affected. The method includes: rinsing with solution to remove impurities.

[0080] The working principle and beneficial effects of the above technical solution are as follows: By analyzing the stationary phase parameters of the resin chromatography column, the corresponding mobile phase parameters are matched to determine the resolution of the resin chromatography column. According to the resolution, a buffer solvent is matched to the resin chromatography column, and the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent is monitored. According to the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin chromatography column, it is determined whether the resin chromatography column is contaminated. If the resin chromatography column is contaminated, the column is repaired to improve the separation accuracy of the column during use, improve the stability of the resin chromatography column, and better improve the utilization efficiency of the resin chromatography column.

[0081] Example 2:

[0082] According to the method provided in Embodiment 1 of the invention, based on the stationary phase parameters of the resin chromatography column, corresponding mobile phase parameters are matched and obtained, including:

[0083] Based on the stationary phase parameters of the resin chromatography column, the corresponding range of the first mobile phase is obtained;

[0084] Based on the parameters of the sample to be tested, the corresponding range of the second mobile phase is obtained;

[0085] Based on the first mobile phase range and the second mobile phase range, a third overlapping mobile phase range is obtained;

[0086] Based on the third mobile phase range and the mobile phase database, the corresponding mobile phase parameters are matched.

[0087] In this embodiment, the first mobile phase range refers to the composition and corresponding content of the mobile phase solution that will not contaminate or affect the adsorption capacity of the stationary phase of the resin chromatography column, obtained by analyzing the stationary phase parameters of the resin chromatography column.

[0088] In this embodiment, the parameters of the sample to be tested refer to the composition and corresponding content of the sample reagent.

[0089] In this embodiment, the second mobile phase range refers to the composition solution of the mobile phase that will not contaminate or affect the sample reagents, as well as the corresponding content.

[0090] In this embodiment, the third mobile phase range refers to the same components and corresponding contents in the first mobile phase range and the second mobile phase range.

[0091] In this embodiment, the mobile phase database refers to a database containing the components of the mobile phase and their corresponding contents.

[0092] The working principle and beneficial effects of the above technical solution are as follows: by analyzing the stationary phase parameters and the parameters of the sample to be tested, a mobile phase that will not affect or contaminate the stationary phase and sample reagents is matched, thereby improving the stability of the resin chromatography column.

[0093] Example 3:

[0094] According to the method provided in Embodiment 1 of the invention, the resolution of the resin chromatographic column is determined based on the stationary phase parameters and the mobile phase parameters, including:

[0095] A preset number of test samples are randomly selected, and a chromatographic diagram of each selected test sample is obtained based on the stationary phase parameters and the mobile phase parameters.

[0096] Based on the retention time and peak width in the chromatographic diagram, the corresponding detection column efficiency is obtained;

[0097] The number of columns with a detection efficiency greater than a preset column efficiency is obtained and used as the first quantity;

[0098] If the first quantity is greater than the preset effective quantity, the corresponding chromatographic diagram is retained;

[0099] Based on the retained chromatographic schematic, the corresponding first resolution is obtained;

[0100] The average of all first-degree separations is taken as the separation degree.

[0101] In this embodiment, the preset sample quantity refers to the number of samples randomly selected in advance to detect the resolution of the resin chromatography column.

[0102] In this embodiment, the sample to be tested refers to the sample randomly selected from all sample reagents for detecting the resolution of the resin chromatography column.

[0103] In this embodiment, the chromatographic schematic refers to an image showing the distribution of the detection signal of the separated components over time. The sample flows through the chromatographic column and detector, resulting in a signal-time curve.

[0104] In this embodiment, retention time refers to the time range of continuous peaks in the chromatographic signal in the chromatographic schematic.

[0105] In this embodiment, the peak bottom width refers to the width of the chromatographic signal at the lowest value of the chromatographic fluctuation peak in the chromatographic schematic diagram.

[0106] In this embodiment, the column efficiency refers to the performance of the chromatographic column, which is calculated from the retention time and peak width in the chromatographic diagram.

[0107] N = 16 (t / w) 2

[0108] Where N represents the detection column efficiency of the chromatogram; t represents the retention time of the chromatogram; and w represents the peak width of the chromatogram.

[0109] In this embodiment, preset column efficiency refers to the performance of a pre-set effective chromatographic column.

[0110] In this embodiment, the first quantity refers to the number of times that the detection column efficiency of all tested samples is greater than the preset column efficiency.

[0111] In this embodiment, the preset effective quantity refers to the number of effective detection column effects that are set in advance.

[0112] In this embodiment, the first resolution refers to the ability of the retained chromatographic schematic to separate the target components.

[0113] The working principle and beneficial effects of the above technical solution are as follows: by analyzing the chromatographic diagram of a randomly selected sample to be tested, the corresponding numerical resolution of the chromatographic column is obtained, thereby improving the separation accuracy of the chromatographic column during use.

[0114] Example 4:

[0115] According to the method provided in Embodiment 1 of the invention, based on the resolution, a buffer solvent is matched to the resin chromatography column, and the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent is monitored, including:

[0116] Based on the stationary phase parameters and the mobile phase parameters, the effectiveness and ineffectiveness of the chromatographic column are obtained;

[0117] If the resolution is greater than the invalidity and less than the effectiveity, then obtain the corresponding complete chromatographic schematic diagram;

[0118] Based on the separation values ​​corresponding to the maximum peak value in each chromatogram and the overall separation values, the corresponding first ratio value is obtained;

[0119] Based on the chromatographic column and the sample to be tested, the corresponding target result quality and the corresponding first content are obtained;

[0120] Based on each first content and the corresponding mass of the sample to be tested, a second ratio value is obtained;

[0121] Extract the chromatographic column result quality corresponding to the second proportion value that is less than the first proportion value in the same test sample;

[0122] The mass of impurities remaining in the column is obtained based on the initial mass of the column, the mass of the column result, and the mass of the target result in the same sample.

[0123] Input the impurity mass and the corresponding impurity type of the sample to be tested into the impurity analysis model to estimate the first mass corresponding to each impurity type in the chromatographic column.

[0124] The first average mass is obtained based on all the first masses of the same impurity type;

[0125] Based on the first average mass corresponding to all types of impurities, a corresponding impurity removal buffer solvent is matched.

[0126] All sample reagents were buffered and then fed into the resin chromatography column to obtain the corresponding target result quality of the resin chromatography column.

[0127] Calculate the difference between the quality of the target result and the preset result quality for the same target result, and obtain the first difference value;

[0128] If the first difference is within a preset reasonable difference, the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent is obtained.

[0129] In this embodiment, effectiveness refers to the value of the effective resolution of the resin chromatography column obtained by analyzing the stationary phase parameters and mobile phase parameters.

[0130] In this embodiment, invalidity refers to the resolution value of the resin chromatography column that is invalid and unusable, obtained by analyzing the stationary phase parameters and mobile phase parameters.

[0131] In this embodiment, the maximum peak value refers to the value corresponding to the maximum peak in a chromatogram where the resolution is greater than the invalidity but less than the validity.

[0132] In this embodiment, the separation value refers to the resolution value corresponding to the maximum peak in the chromatogram.

[0133] In this embodiment, the overall separation value refers to the average resolution corresponding to each point in the chromatogram.

[0134] In this embodiment, the first ratio value refers to the value of the separation value corresponding to the maximum peak value compared to the overall separation value.

[0135] In this embodiment, the target result quality refers to the type and corresponding quality of the target liquid obtained by passing the sample through the resin chromatography column.

[0136] In this embodiment, the first content refers to the content of each target result quality in the sum of all target result qualities.

[0137] In this embodiment, the second ratio value refers to the value of each first content relative to the mass of the corresponding test sample.

[0138] In this embodiment, the quality of the chromatographic column result refers to the quality of the chromatographic column at the end of the detection corresponding to the second proportion value which is less than the first proportion value in the same sample to be tested.

[0139] In this embodiment, the initial mass of the chromatographic column refers to the mass of the chromatographic column before detection.

[0140] In this embodiment, the impurity mass refers to the mass of impurities remaining in the numerical chromatography column, obtained by comprehensively analyzing the difference between the column result mass and the initial mass of the column, and the difference between the mass of the sample to be tested and the mass of all target results.

[0141] In this embodiment, the impurity type refers to the types of impurities that may be present in the sample to be tested.

[0142] In this embodiment, the impurity analysis model refers to a model trained from the mixed impurities and the mass of each corresponding impurity, which can analyze the mass of each impurity in the mixed impurities.

[0143] In this embodiment, the first mass refers to the mass of the impurity and the corresponding impurity type of the sample to be tested, which are input into the impurity analysis model and output as the corresponding mass of each impurity.

[0144] In this embodiment, the first average mass refers to the average of all first masses of the same impurity type.

[0145] In this embodiment, the preset result quality refers to the quality corresponding to each target result obtained by the sample through the numerical chromatography column when the numerical chromatography column is functioning normally.

[0146] In this embodiment, the first difference refers to the difference between the quality of the target result and the preset result quality for the same target result.

[0147] In this embodiment, the preset reasonable difference refers to the difference between the target result quality and the preset result quality, which represents the same target result that is effective for the resin chromatography column.

[0148] The working principle and beneficial effects of the above technical solution are as follows: By analyzing the effectiveness and ineffectiveness of the chromatographic column, analyzing the chromatographic diagrams of resolutions greater than the ineffectiveness and less than the effectiveness, the first ratio of the separation value corresponding to the maximum peak value and the overall separation value is obtained. Furthermore, by analyzing the sample solvent, the target result mass and the corresponding first content are obtained. The second ratio of each first content to the corresponding mass of the sample to be tested is calculated. The chromatographic column result mass corresponding to the second ratio value less than the first ratio value in the same sample to be tested is extracted and analyzed to obtain the type of each impurity remaining in the chromatographic column and its corresponding mass. The corresponding buffer solvent is matched according to the content of each impurity, thereby improving the separation accuracy of the chromatographic column during use, improving the stability of the resin chromatographic column, and better improving the utilization efficiency of the resin chromatographic column.

[0149] Example 5:

[0150] According to the method provided in Embodiment 1 of the invention, determining whether the resin chromatography column is contaminated based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin chromatography column includes:

[0151] Based on the adsorption flow rate of each sample reagent in the resin chromatography column at different times during different time periods after being buffered by the solvent, a flow rate change curve was constructed.

[0152] Based on the solution concentration and flow rate change curves of the same sample reagent, the predicted adsorption mass change curve is obtained.

[0153] Based on the values ​​corresponding to each point in the adsorption mass change curve, the overall adsorption value is obtained;

[0154] If the total adsorption value is less than the saturated adsorption capacity of the resin column, then calculate the point average value corresponding to all points in the flow rate change curve.

[0155] Based on the solution concentration of the sample reagent, match the corresponding average flow rate in the resin column concentration-flow rate comparison table;

[0156] Calculate the second difference between the point average value of the reagent for the same sample and the corresponding average flow rate;

[0157] If the second difference is greater than the preset difference, the resin chromatographic column is determined to be contaminated.

[0158] In this embodiment, the flow rate change curve refers to the curve showing how the adsorption flow rate changes over time.

[0159] In this embodiment, the adsorption mass change curve refers to the curve obtained by analyzing the solution concentration and flow rate change curves of the same sample reagent, which shows how the adsorption mass changes over time.

[0160] In this embodiment, the total adsorption value refers to the sum of the adsorption mass at all times in the adsorption mass change curve.

[0161] In this embodiment, the point average value refers to the total adsorption value that is less than the saturated adsorption capacity of the resin column and the average value over the corresponding time period.

[0162] In this embodiment, the resin column concentration-flow rate comparison table refers to a comparison table of the concentration of the solution flowing through the resin column and the corresponding flow rate change curves.

[0163] In this embodiment, the average flow rate refers to the average adsorption flow rate in the matched flow rate change curve.

[0164] In this embodiment, the second difference refers to the difference between the point average value of the same sample reagent and the corresponding average flow rate.

[0165] In this embodiment, the preset difference refers to the average point value of the same sample reagent and the corresponding average flow rate under normal conditions.

[0166] The working principle and beneficial effects of the above technical solution are as follows: by determining whether the resin chromatography column is contaminated according to the solution concentration of the sample reagent, the adsorption flow rate and the saturated adsorption capacity of the resin chromatography column, the numerical chromatography column that can be repaired is repaired, thereby improving the stability of the resin chromatography column and improving the utilization efficiency of the resin chromatography column.

[0167] Example 6:

[0168] According to the method provided in Embodiment 1 of the invention, if the resin chromatographic column is contaminated, the process of column repair includes:

[0169] Image acquisition of discrete sampling points on a contaminated resin chromatography column after sample reagent injection, as well as laser irradiation acquisition;

[0170] Determine the sampling scale between each discrete sampling point and the initial discrete sampling points, and obtain the image segmentation accuracy from the scale-segmentation mapping table;

[0171] Based on the image segmentation accuracy, the corresponding image is segmented, and a pixel array is constructed for each pixel based on different discrete sampling points. At the same time, a laser reflection array for each pixel based on different discrete sampling points is obtained.

[0172] Perform a first consistency analysis on each pixel array and a second consistency analysis on each laser reflection array;

[0173] Based on the first consistency analysis result, the first stability of the corresponding pixel is determined, and based on the second consistency analysis result, the second stability of the corresponding pixel is determined, and the analysis array of the corresponding pixel is constructed.

[0174] Lock a first position where the first stability is less than a first preset value, and lock a second position where the second stability is less than a second preset value;

[0175] Simultaneously, based on the analysis array, the third position where the stability difference is greater than the preset difference is selected;

[0176] Based on the first, second, and third positions, a position vector is constructed and input into the position analysis model to determine the distribution edge, diffusion direction, and diffusion color. A diffusion function is then constructed, and the type of contamination in the contaminated resin chromatography is determined based on the diffusion function.

[0177] In this embodiment, after the sample reagent is injected, discrete sampling points are sampled. For example, the sampling time is 3 seconds. At this time, images within 10 minutes are obtained to obtain an image set. The image set includes the image of each location point at different times. The resin of the injected sample reagent is irradiated with laser at the same interval to obtain the color of the feedback light, thus obtaining a laser reflection set. The laser reflection set includes the laser reflection results of each location point at different times. Each location point can be regarded as a pixel.

[0178] In this embodiment, the scale-segmentation mapping table includes the injection type of the injected reagent, different distance times, and the segmentation accuracy matched with the distance time, thereby enabling effective segmentation of the image. The purpose of segmentation is to better identify the pixel values ​​of the pixels, which facilitates the reliability of subsequent pixel array acquisition.

[0179] In this embodiment, for example, for the pixel array of pixel point 1: [pixel value at sampling point 1, pixel value at sampling point 2, pixel value at sampling point 3, ...].

[0180] In this embodiment, for example, for the laser reflection array of pixel 1: [laser reflection value at sampling point 1, laser reflection value at sampling point 2, laser reflection value at sampling point 3, ...].

[0181] In this embodiment, the first consistency analysis and the second consistency analysis are based on the variance calculation of the pixel array, and the specific calculation method of the first stability is as follows:

[0182]

[0183] Where, x i1This represents the pixel value at the i1th discrete sampling point of the corresponding pixel array; x i1+1 σ1 represents the pixel value at the (i1+1)th discrete sampling point of the corresponding pixel array; n1 represents the total number of discrete sampling points of the corresponding pixel array; σ1 2 W1 represents the variance of the corresponding pixel array; W1 represents the first stability of the corresponding pixel array; x n1 x1 represents the pixel value of the corresponding pixel array at the n1th discrete sampling point; x1 represents the pixel value of the corresponding pixel array at the 1st discrete sampling point.

[0184] The specific calculation method for the second stability is as follows:

[0185]

[0186] y i1 =y0 i1 ×(1+Y(θ,μ1,μ2))

[0187] Among them, y i1 This represents the reflection value of the corresponding laser reflection array at the i1th discrete sampling point; y i1+1 σ² represents the reflection value of the corresponding laser reflection array at the (i1+1)th discrete sampling point; n1 represents the total number of discrete sampling points of the corresponding laser reflection array; σ² 2 W1 represents the variance of the corresponding laser reflection array; W2 represents the first stability of the corresponding laser reflection array; y n1 y1 represents the reflection value of the corresponding laser reflection array at the n1th discrete sampling point; y2 represents the reflection value of the corresponding laser reflection array at the 1st discrete sampling point; y3 represents the reflection value of the corresponding laser reflection array at the 1st discrete sampling point; y4 represents the reflection value of the corresponding laser reflection array at the n1th discrete sampling point. i1 Y(θ,μ1,μ2) represents the initial value of the corresponding laser reflection array at the i1th discrete sampling point; Y(θ,μ1,μ2) represents the influence function on the i1th discrete sampling point, with a value range of [-0.2, 0.2]; θ represents the laser illumination angle; μ1 represents the lateral dissipation coefficient of the corresponding position point, with a value range of [0, 0.03]; μ2 represents the longitudinal dissipation coefficient of the corresponding position point, with a value range of [0, 0.04];

[0188] In this embodiment, for example, the first position is: 001, 002, 005, 008, 009, the second position is: 001, 002, 005, 009, 010, and the third position is: 023.

[0189] In this embodiment, the stability difference refers to the absolute value of the difference between two stability values ​​in the analysis array. The preset difference is set in advance and has a value of 0.3.

[0190] In this embodiment, the position vector = [001(2)002(2)005(2)008(1)009(1)010(1)023(1)], where the value in () refers to the number of occurrences.

[0191] In this embodiment, the location analysis model is trained based on the occurrence frequency, occurrence position, pixel value and reflection value of different combinations of pixels as samples, and the results of expert analysis (distribution edge, diffusion direction and diffusion color) of the samples. Therefore, the distribution edge b1, diffusion direction b2 and diffusion color b3, and diffusion function K(b1,b2,b3) can be directly obtained.

[0192] In this embodiment, the diffusion function is matched with a function-type mapping table to obtain the pollution types, and the mapping table contains several different functions and pollution types that match the functions.

[0193] In this embodiment, the type of contamination refers to the type of contamination that the resin chromatography column is contaminated with, including: morphological surface contamination and non-surface contamination.

[0194] The working principle and beneficial effects of the above technical solution are as follows: by determining the type of contamination in the contaminated resin chromatography column, the remediation method is accurately matched to improve the stability of the resin chromatography column and thus improve its utilization efficiency.

[0195] Example 7:

[0196] According to the method provided in Embodiment 1 of the invention, based on the real-time image set, the type of contamination of the contaminated resin chromatography column is determined, including:

[0197] If the type of contamination is surface contamination, the real-time image set is input into the resin chromatography column image analysis model to obtain the surface contamination area;

[0198] If the surface contamination area is smaller than the preset contamination area, an artificial recovery signal is issued to restore the resin chromatography column.

[0199] In this embodiment, surface contamination refers to contamination that is morphologically visible.

[0200] In this embodiment, the resin chromatography column image analysis model refers to a model trained from resin chromatography column images that can obtain the specific situation of resin chromatography column contamination.

[0201] In this embodiment, the surface contamination area refers to the area of ​​the resin chromatography column morphology contaminated by inputting the real-time image set into the resin chromatography column image analysis model.

[0202] In this embodiment, the preset contaminated area refers to the area of ​​surface contamination that cannot be restored, which is set in advance.

[0203] In this embodiment, the artificial recovery signal refers to a signal that includes the surface contamination area.

[0204] The working principle and beneficial effects of the above technical solution are as follows: by determining the type of contamination in the contaminated resin chromatography column, the remediation method is accurately matched to improve the stability of the resin chromatography column and thus improve its utilization efficiency.

[0205] Example 8:

[0206] According to the method provided in Embodiment 1 of the invention, based on the real-time image set, the type of contamination of the contaminated resin chromatography column is determined, including:

[0207] If the type of contamination is non-surface contamination, obtain the corresponding sample parameters of the sample reagents;

[0208] Based on sample parameters and a database of rinsing solvents, a corresponding rinsing solvent is matched to restore the resin column.

[0209] In this embodiment, non-surface contamination refers to internal contamination that is not visible in terms of morphology.

[0210] In this embodiment, the sample parameters refer to the composition and content of each solid and liquid contained in the sample reagent.

[0211] In this embodiment, the rinsing solvent database refers to a database of solvents that can react with the sample reagents and flow away, or that can remove sample reagents contaminated in the resin chromatography column.

[0212] In this embodiment, the rinsing solvent refers to a solvent that can react with the sample reagent and flow away, or that can remove sample reagents contaminated in the resin chromatography column.

[0213] The working principle and beneficial effects of the above technical solution are: by accurately matching the repair method, the stability of the resin chromatography column is improved, and the efficiency of the resin chromatography column is better improved.

[0214] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for ensuring the stability of a resin chromatography column, characterized in that, include: Step 1: Based on the stationary phase parameters of the resin chromatography column, obtain the corresponding mobile phase parameters; Step 2: Randomly select a preset number of test samples, and obtain a chromatographic diagram of each selected test sample based on the stationary phase parameters and mobile phase parameters; Based on the retention time and peak width in the chromatographic diagram, the corresponding detection column efficiency is obtained; The number of columns with a detection efficiency greater than a preset column efficiency is obtained and used as the first quantity; If the first quantity is greater than the preset effective quantity, the corresponding chromatographic diagram is retained; Based on the retained chromatographic schematic, the corresponding first resolution is obtained; The average of all first-degree separations is taken as the separation degree; Step 3: Based on the resolution, a buffer solvent is matched to the resin column, and the adsorption flow rate of the sample reagent in the resin column at different times after passing through the buffer solvent is monitored. Step 4: Based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin column, determine whether the resin column is contaminated; Step 5: If the resin column is contaminated, perform column repair.

2. The method according to claim 1, characterized in that, Based on the stationary phase parameters of the resin chromatography column, the corresponding mobile phase parameters are obtained, including: Based on the stationary phase parameters of the resin chromatography column, the corresponding range of the first mobile phase is obtained; Based on the parameters of the sample to be tested, the corresponding range of the second mobile phase is obtained; Based on the first mobile phase range and the second mobile phase range, a third overlapping mobile phase range is obtained; Based on the third mobile phase range and the mobile phase database, the corresponding mobile phase parameters are matched.

3. The method according to claim 1, characterized in that, Based on the resolution, a buffer solvent is matched to the resin column, and the adsorption flow rate of the sample reagent in the resin column at different times after passing through the buffer solvent is monitored, including: Based on the stationary phase parameters and the mobile phase parameters, the effectiveness and ineffectiveness of the chromatographic column are obtained; If the resolution is greater than the invalidity and less than the effectiveity, then obtain the corresponding complete chromatographic schematic diagram; Based on the separation values ​​corresponding to the maximum peak value in each chromatogram and the overall separation values, the corresponding first ratio value is obtained; Based on the chromatographic column and the sample to be tested, the corresponding target result quality and the corresponding first content are obtained; Based on each first content and the corresponding mass of the sample to be tested, a second ratio value is obtained; Extract the chromatographic column result quality corresponding to the second proportion value that is less than the first proportion value in the same test sample; The mass of impurities remaining in the column is obtained based on the initial mass of the column, the mass of the column result, and the mass of the target result in the same sample. Input the impurity mass and the corresponding impurity type of the sample to be tested into the impurity analysis model to estimate the first mass corresponding to each impurity type in the chromatographic column. The first average mass is obtained based on all the first masses of the same impurity type; Based on the first average mass corresponding to all types of impurities, a corresponding impurity removal buffer solvent is matched. All sample reagents were buffered and then fed into the resin chromatography column to obtain the corresponding target result quality of the resin chromatography column. Calculate the difference between the quality of the target result and the preset result quality for the same target result, and obtain the first difference value; If the first difference is within a preset reasonable difference, the adsorption flow rate of the sample reagent in the resin chromatography column at different times after passing through the buffer solvent is obtained.

4. The method according to claim 1, characterized in that, Based on the solution concentration of the sample reagent, the adsorption flow rate, and the saturated adsorption capacity of the resin chromatographic column, determine whether the resin chromatographic column is contaminated, including: Based on the adsorption flow rate of each sample reagent in the resin chromatography column at different times during different time periods after being buffered by the solvent, a flow rate change curve was constructed. Based on the solution concentration and flow rate change curves of the same sample reagent, the predicted adsorption mass change curve is obtained. Based on the values ​​corresponding to each point in the adsorption mass change curve, the overall adsorption value is obtained; If the total adsorption value is less than the saturated adsorption capacity of the resin column, then calculate the point average value corresponding to all points in the flow rate change curve. Based on the solution concentration of the sample reagent, match the corresponding average flow rate in the resin column concentration-flow rate comparison table; Calculate the second difference between the point average value of the reagent for the same sample and the corresponding average flow rate; If the second difference is greater than the preset difference, the resin chromatographic column is determined to be contaminated.

5. The method according to claim 1, characterized in that, If the resin chromatographic column is contaminated, the column remediation process includes: Image acquisition of discrete sampling points on a contaminated resin chromatography column after sample reagent injection, as well as laser irradiation acquisition; Determine the sampling scale between each discrete sampling point and the initial discrete sampling points, and obtain the image segmentation accuracy from the scale-segmentation mapping table; Based on the image segmentation accuracy, the corresponding image is segmented, and a pixel array is constructed for each pixel based on different discrete sampling points. At the same time, a laser reflection array for each pixel based on different discrete sampling points is obtained. Perform a first consistency analysis on each pixel array and a second consistency analysis on each laser reflection array; Based on the first consistency analysis result, the first stability of the corresponding pixel is determined, and based on the second consistency analysis result, the second stability of the corresponding pixel is determined, and the analysis array of the corresponding pixel is constructed. Lock a first position where the first stability is less than a first preset value, and lock a second position where the second stability is less than a second preset value; Simultaneously, based on the analysis array, the third position where the stability difference is greater than the preset difference is selected; Based on the first, second, and third positions, a position vector is constructed and input into the position analysis model to determine the distribution edge, diffusion direction, and diffusion color. A diffusion function is then constructed, and the type of contamination in the contaminated resin chromatography is determined based on the diffusion function.

6. The method according to claim 5, characterized in that, The type of contamination on the contaminated resin column is determined based on the diffusion function, including: If the type of contamination is surface contamination, the real-time image set is input into the resin chromatography column image analysis model to obtain the surface contamination area; If the surface contamination area is smaller than the preset contamination area, an artificial recovery signal is issued to restore the resin chromatography column.

7. The method according to claim 5, characterized in that, The type of contamination on the contaminated resin column is determined based on the diffusion function, including: If the type of contamination is non-surface contamination, obtain the corresponding sample parameters of the sample reagents; Based on sample parameters and a database of rinsing solvents, a corresponding rinsing solvent is matched to restore the resin column.

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