A purification system and method based on a combination of molecularly imprinted microspheres and tubular membranes

Abstract

This invention discloses a purification system and method based on a combination of molecularly imprinted microspheres and tubular membranes. The system includes an adsorption reaction unit, a membrane separation and adsorption unit, and an elution and regeneration unit. The method involves the following steps: first, mixing the feed solution with molecularly imprinted microspheres for initial adsorption; then, pumping the slurry into a tubular molecularly imprinted membrane module, where the microspheres are retained, and the membrane simultaneously adsorbs residual target molecules for a second time; after washing, the target product is eluted and collected. This invention achieves nearly 100% adsorption yield through the synergistic effect of microspheres and membranes on the same target molecule, solving the problems of easy clogging of traditional chromatography columns and low capacity of single membranes. It is particularly suitable for the efficient purification of high-value components of natural products.

Description

Technical Field

[0001] This invention relates to the field of membrane separation technology, specifically to a purification system and method based on a combination of molecularly imprinted microspheres and tubular membranes. Background Technology

[0002] Molecular imprinting (MIT) is an emerging technology integrating polymer chemistry, materials science, and biochemistry. It is characterized by its predictability, specificity, and practicality. Molecularly imprinted polymers (MIPs) prepared by MIT are materials with specific selectivity for template molecules. These materials possess advantages such as chemical stability, high selectivity and affinity, and ease of preparation, leading to their widespread application in many fields, such as enzyme catalysis simulation, chiral drug separation, solid-phase extraction, and biosensors. The imprinting of template molecules generally involves three processes: first, the template and monomer form a reversible prepolymer; second, a cross-linking agent is added, and polymerization is initiated by an initiator to form a polymer; finally, the template is eluted and removed, leaving an imprint on the polymer. In particular, molecularly imprinted microspheres, with their large specific surface area and high adsorption capacity, facilitate the entry of template molecules into recognition sites, thereby accelerating binding kinetics and enabling their use in chromatographic separation and solid-phase extraction. However, when molecularly imprinted microspheres are packed into traditional fixed-bed chromatography columns, there are drawbacks such as large bed pressure drop, easy clogging by complex samples (such as crude biological extracts), and difficulty in scale-up. Molecularly imprinted membranes (MIMs) are functional separation materials developed based on molecular imprinting technology, offering advantages such as rapid mass transfer and ease of continuous operation. However, single molecularly imprinted membranes also suffer from limited adsorption capacity.

[0003] Currently, there are no reports of combining molecularly imprinted microspheres and tubular molecularly imprinted membranes into a single purification and separation process, utilizing the synergistic adsorption of the two on the same target molecule to overcome the bottleneck of the aforementioned single technology, thereby achieving high-throughput, high-yield, and high-selectivity continuous separation and purification of the target molecule. Summary of the Invention

[0004] The purpose of this invention is to provide a purification system and method based on a combination of molecularly imprinted microspheres and tubular membranes, which can achieve high-throughput, high-yield, and high-selectivity continuous separation and purification of target molecules.

[0005] To achieve the above objectives, the solution of the present invention is: A purification system based on a combination of molecularly imprinted microspheres and tubular membranes, comprising: The raw material pretreatment unit is used to remove large particulate impurities from the raw materials; The adsorption reaction unit is used for the mixed adsorption of raw materials and molecularly imprinted polymer microspheres. A membrane separation unit is used to retain molecularly imprinted polymer microspheres from the adsorption reaction unit and to perform secondary adsorption on target molecules remaining in the raw material. The elution and regeneration unit is used to elute the target molecules adsorbed by the membrane separation unit and to regenerate the molecularly imprinted polymer microspheres and the membrane separation unit. and control unit; The raw material pretreatment unit includes a storage tank and a pretreatment filter connected to the storage tank. The adsorption reaction unit includes a reaction vessel connected to the pretreatment filter, and molecularly imprinted polymer microspheres that match the target molecules are placed inside the reaction vessel. The membrane separation unit includes a tubular molecularly imprinted membrane device connected to the reaction vessel and a waste liquid tank connected to the tubular molecularly imprinted membrane device. The tubular molecularly imprinted membrane device contains a tubular molecularly imprinted membrane that matches the target molecules. The elution and regeneration unit includes an eluent storage tank, a detergent storage tank, and an eluent recovery tank, which are respectively connected to the tubular molecularly imprinted membrane device.

[0006] The storage tank is connected to the pretreatment filter through a first feed channel. A first automatic feed pump is installed on the first feed channel and is controlled by the control unit.

[0007] The pretreatment filter is connected to the reactor through a second feed channel, and a second automatic feed pump is installed on the second feed channel. The second automatic feed pump is connected to the control unit.

[0008] The reactor is connected to the tubular molecular imprinting membrane device through a third feed channel. A third automatic feed pump is installed on the third feed channel and is controlled by the control unit. A stirring device is installed inside the reactor.

[0009] The eluent storage tank is connected to the tubular molecular imprinting membrane device through a fourth feed channel. A fourth automatic feed pump is installed on the fourth feed channel and is controlled by the control unit.

[0010] The detergent storage tank is connected to the tubular molecular imprinting membrane device through a fifth feed channel. A fifth automatic feed pump is installed on the fifth feed channel and is controlled by the control unit.

[0011] The eluent recovery tank is connected to the tubular molecular imprinting membrane device through a first discharge channel. A first automatic discharge pump is installed on the first discharge channel and is controlled by the control unit.

[0012] The waste liquid tank is connected to the tubular molecular imprinting membrane device through a second discharge channel. A second automatic discharge pump is installed on the second discharge channel and is controlled by the control unit.

[0013] A purification method based on a combination of molecularly imprinted microspheres and tubular membranes includes the following steps: Step 1, Preprocessing: First, the liquid containing the target molecules in the storage tank is processed through a pretreatment filter to remove large particulate impurities from the liquid. Step 2, Adsorption: Then, the pretreated liquid containing the target molecules is transported into the reactor and mixed with molecularly imprinted polymer microspheres under stirring to carry out the first adsorption of the target molecules. Step 3, Membrane separation and synergistic adsorption: Then, the feed solution containing molecularly imprinted polymer microspheres after the first adsorption is transported to the tubular molecularly imprinted membrane device, where cross-flow filtration is performed under pressure. The tubular molecularly imprinted membrane retains the molecularly imprinted polymer microspheres and simultaneously adsorbs the target molecules remaining in the feed solution for the second time. Step 4, Washing: Then, detergent is introduced into the tubular molecularly imprinted membrane device to wash away the trapped molecularly imprinted polymer microspheres and the non-specifically adsorbed impurities on the surface of the tubular molecularly imprinted membrane. Step 5, Washing: Then, eluent is introduced into the tubular molecularly imprinted membrane device to elute the target molecules adsorbed on the molecularly imprinted polymer microspheres and tubular molecularly imprinted membrane, and collect them in the eluent recovery tank to obtain a high-purity target molecule solution. Step 6, Regeneration: Finally, the eluted molecularly imprinted polymer microspheres and tubular molecularly imprinted membranes are cleaned to regenerate their adsorption performance and are recycled for the next adsorption cycle.

[0014] In step 4, the detergent is an ionic detergent or a nonionic detergent. The ionic detergent is sodium dodecyl sulfate or hexadecyltrimethylammonium bromide, and the nonionic detergent is Tween-20, Tween-80, NP-40, ethanol, or methanol.

[0015] In step 5, the eluent is ethanol, propanol, acetone, and acetonitrile.

[0016] After adopting the above technical solution, the purification system and method based on the combination of molecularly imprinted microspheres and tubular membranes of the present invention have the following beneficial effects: 1. Synergistic effect and extremely high yield: Molecularly imprinted polymer microspheres provide the main adsorption capacity as the "main adsorbent", while tubular molecularly imprinted membranes ensure a near 100% adsorption yield as the "end trap", greatly reducing the loss of target molecules. 2. High processing capacity: The combination of batch reaction and membrane separation completely avoids the problem of blockage in fixed bed chromatography columns, making it particularly suitable for processing complex, viscous, or solid-particle-containing crude biological extracts. 3. High selectivity and high product purity: The dual molecular imprinting recognition mechanism of molecularly imprinted polymer microspheres + tubular molecularly imprinted membrane endows the system with extremely high selectivity, enabling it to specifically separate target molecules from complex matrices. 4. Easy to scale up and continuous: The system is highly modular and can be scaled up by increasing the volume of the reactor and the area of ​​the tubular molecularly imprinted membrane, which has the potential to achieve continuous production and high production efficiency. 5. Economic and environmentally friendly: The adsorbent material can be reused hundreds of times, thereby reducing production costs and waste emissions. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the structure of a purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to the present invention. Detailed Implementation

[0018] To further explain the technical solution of the present invention, the present invention will be described in detail below through specific embodiments.

[0019] Example 1 A purification system based on a combination of molecularly imprinted microspheres and tubular membranes, such as Figure 1 As shown, it includes: The raw material pretreatment unit is used to remove large particulate impurities from the raw materials; The adsorption reaction unit is used for the mixed adsorption of raw materials and molecularly imprinted polymer microspheres. The membrane separation unit is used to retain molecularly imprinted polymer microspheres from the adsorption reaction unit and to perform secondary adsorption on target molecules remaining in the raw material, wherein the target molecules are selected from one of gallocatechin gallate (EGCG), flavonoids, anoectochilin, melatonin and resveratrol. The elution and regeneration unit is used to elute the target molecules adsorbed by the membrane separation unit and to regenerate the molecularly imprinted polymer microspheres and the membrane separation unit. And the control unit.

[0020] The raw material pretreatment unit includes a storage tank and a pretreatment filter connected to the storage tank. The storage tank is connected to the pretreatment filter through a first feed channel, on which a first automatic feed pump is installed. The first automatic feed pump is connected to a control unit. The pretreatment filter is selected from one of the following: a bag filter, a filter press, a tubular microfiltration membrane filter, and a stainless steel mesh filter.

[0021] The adsorption reaction unit includes a reaction vessel connected to a pretreatment filter. The pretreatment filter is connected to the reaction vessel through a second feed channel. A second automatic feed pump is installed on the second feed channel and is connected to a control unit.

[0022] The reactor is equipped with a stirring device, and molecularly imprinted polymer microspheres that match the target molecules are placed inside the reactor. The molecularly imprinted polymer microspheres are prepared using methods known in the art, and the general steps are as follows: 1. Pre-assembly: Template molecules and functional monomers form a composite material in a solvent through non-covalent bonds (such as hydrogen bonds, ionic bonds, van der Waals forces); 2. Polymerization: In the presence of a crosslinking agent and an initiator, polymerization is initiated by heat or light, "freezing" the composite material in a rigid three-dimensional polymer network; 3. Elution: Template molecules are removed from the three-dimensional polymer network by physical or chemical methods, leaving "imprinted cavities" that are complementary to the template molecules in size, shape, and functional group arrangement.

[0023] The membrane separation unit includes a tubular molecularly imprinted membrane device connected to the reactor and a waste liquid tank connected to the tubular molecularly imprinted membrane device. The reactor is connected to the tubular molecularly imprinted membrane device through a third feed channel. A third automatic feed pump is installed on the third feed channel and is connected to the control unit.

[0024] The tubular molecularly imprinted membrane device contains a tubular molecularly imprinted membrane that matches the target molecule. The elution and regeneration unit includes an eluent storage tank, a detergent storage tank, and an eluent recovery tank, all connected to the tubular molecularly imprinted membrane device. The eluent storage tank is connected to the tubular molecularly imprinted membrane device via a fourth feed channel, on which a fourth automatic feed pump is installed and controlled by the control unit. The detergent storage tank is connected to the tubular molecularly imprinted membrane device via a fifth feed channel, on which a fifth automatic feed pump is installed and controlled by the control unit. The eluent recovery tank is connected to the tubular molecularly imprinted membrane device via a first discharge channel, on which a first automatic discharge pump is installed and controlled by the control unit.

[0025] The waste liquid tank is connected to the tubular molecular imprinting membrane equipment through the second discharge channel. The second discharge channel is equipped with a second automatic discharge pump, which is connected to the control unit.

[0026] In this embodiment, the control unit is a PLC automatic control system, and the reaction vessel, stirring device, tubular molecular imprinting membrane equipment, eluent storage tank, detergent storage tank, eluent recovery tank, waste liquid tank, and each automatic feed pump are all well-known devices in the art.

[0027] Example 2 A purification method based on a combination of molecularly imprinted microspheres and tubular membranes includes the following steps: Step 1, Preprocessing: First, open the first feed channel and pass the liquid containing the target molecules in the storage tank through the pretreatment filter to remove large particulate impurities in the liquid. Step 2, Adsorption: Then, the second feed channel is opened to transport the pretreated liquid containing the target molecules into the reactor. Under stirring, it is mixed with molecularly imprinted polymer microspheres to carry out the first adsorption of the target molecules. Step 3, Membrane separation and synergistic adsorption: Then, the third feed channel is opened, and the liquid containing molecularly imprinted polymer microspheres after the first adsorption is transported to the tubular molecularly imprinted membrane device. Under pressure, cross-flow filtration is performed. The tubular molecularly imprinted membrane retains the molecularly imprinted polymer microspheres and simultaneously adsorbs the target molecules remaining in the liquid for the second time. The remaining waste liquid is collected into the waste liquid tank through the second discharge channel. Step 4, Washing: Then open the fifth feed channel and introduce detergent into the tubular molecular imprinted membrane equipment to wash away the trapped molecular imprinted polymer microspheres and the non-specific adsorbed impurities on the surface of the tubular molecular imprinted membrane. Step 5, Washing: Then, the fourth feed channel is opened, and the eluent is introduced into the tubular molecular imprinted membrane equipment to elute the target molecules adsorbed on the molecular imprinted polymer microspheres and tubular molecular imprinted membrane. The eluent is then collected in the eluent recovery tank through the first discharge channel to obtain a high-purity target molecule solution. Step 6, Regeneration: Finally, the eluted molecularly imprinted polymer microspheres and tubular molecularly imprinted membranes were washed with NaOH and deionized water respectively to regenerate their adsorption performance and reuse them for the next adsorption cycle.

[0028] In step 4, the detergent is either an ionic detergent or a nonionic detergent. The ionic detergent is sodium dodecyl sulfate or hexadecyltrimethylammonium bromide, and the nonionic detergent is Tween-20, Tween-80, NP-40, ethanol, or methanol, selected according to the principle that the target molecule is immiscible with the detergent.

[0029] In step 5, the eluents are ethanol, propanol, acetone, and acetonitrile.

[0030] Application Example 1: Extraction of gallic catechin gallate (EGCG) from crude tea polyphenols. 1. Preparation of molecularly imprinted polymer microspheres Step 1: Preparation of the prepolymerization solution: S1. Accurately weigh 0.114 g of gallocatechin gallate, place it in a 50 mL beaker, add about 30 mL of acetonitrile, and stir magnetically until completely dissolved; S2. Add 0.235 g of 4-vinylpyridine, 1.98 g of EGDMA and 0.032 g of AIBN in sequence, and continue stirring for about 30 minutes to ensure that all components are completely dissolved and mixed evenly. S3. Then, transfer the mixed solution through a constant pressure dropping funnel to a 100 mL three-necked flask, rinse the beaker with the remaining acetonitrile, and add the rinsing solution to the three-necked flask to make the final volume 50 mL. Step 2, Deoxygenation and Polymerization Reaction: Then, the three-necked flask was installed in the oil bath, and the other two openings were fitted with a condenser and a nitrogen inlet tube, respectively. The magnetic stirrer was turned on and the speed was set to 200 rpm. High-purity nitrogen was introduced to remove oxygen from the reaction system by bubbling for 20 minutes. The temperature of the oil bath was raised to 60°C to start the polymerization reaction. Under nitrogen protection and continuous stirring, the reaction was carried out for 24 hours to generate a molecularly imprinted polymer. Step 3: Product collection and pretreatment: After the reaction is complete, turn off the heating and stirring, let it cool naturally to room temperature, then pour the reaction solution into a 100 mL beaker, wash the three-necked flask with an appropriate amount of acetonitrile, collect the white solid product by suction filtration, wash it three times with a small amount of acetonitrile, and finally transfer the filter cake to a watch glass and dry it in a vacuum drying oven at 40℃ for 12 hours to obtain the crude molecularly imprinted polymer. Step 4: Elution of template molecules: S1. Then grind the dried crude polymer into a fine powder, put the fine powder into the filter paper sleeve of the Soxhlet extractor, add 150 mL of eluent with methanol: glacial acetic acid = 9:1 (v / v) to the extraction flask, and extract continuously at 70°C for 24 hours. S2. After elution, replace the eluent with pure methanol and wash twice more to remove residual acetic acid. Dry the final product under vacuum at 40°C for 12 hours to obtain the final molecularly imprinted polymer microspheres.

[0031] 2. Preparation of tubular molecularly imprinted membrane modules Step 1: First, mix 1% gallocatechin gallate, 4% methacrylic acid, 60% ethanol, 33% acrylonitrile and 2% azobisisobutyronitrile in a reaction vessel according to the following mass percentages, react at 60℃ for 24 h, and then cool to 35℃ to obtain EGCG composite solution. Step 2: Then, using a polyethersulfone flat sheet ultrafiltration membrane as the base membrane, the membrane is fed into a coating machine to coat the prepared EGCG composite solution onto the base membrane. The membrane is then placed in an oven and dried at 100°C. Finally, after UV curing and hot air drying, the EGCG composite membrane is obtained. Step 3: Then, the EGCG composite membrane is processed into a roll-shaped membrane module, and then the membrane module is assembled into a tubular membrane module shell. After further assembly, it becomes a membrane device equipped with a booster pump, electrical control, support, and medicine tank. Finally, ethanol is used as the eluent in the membrane device. The ethanol is injected into the membrane device through the booster pump to wash the EGCG template molecules on the membrane module, thus preparing the tubular molecularly imprinted membrane module.

[0032] 3. Extraction of EGCG A purification method based on a combination of molecularly imprinted microspheres and tubular membranes includes the following steps: Step 1, Preprocessing: First, open the first feed channel and process the crude tea polyphenols (EGCG purity of 50%) in the storage tank through the pretreatment filter to remove large particulate impurities in the liquid. Step 2, Adsorption: Then, the second feed channel is opened to transport the pretreated crude tea polyphenols into the reactor. Under stirring, the mixture is mixed with molecularly imprinted polymer microspheres and stirred at 200 rpm for 60 minutes to carry out the first adsorption of the target molecules. Step 3, Membrane separation and synergistic adsorption: Then, the third feed channel is opened, and the crude tea polyphenols containing molecularly imprinted polymer microspheres after the first adsorption are transported to the tubular molecularly imprinted membrane equipment. Under pressure, cross-flow filtration is performed. The tubular molecularly imprinted membrane retains the molecularly imprinted polymer microspheres and simultaneously performs a second adsorption on the target molecules remaining in the liquid. The remaining waste liquid is collected into the waste liquid tank through the second discharge channel. Step 4, Washing: Then, open the fifth feed channel and introduce sodium dodecyl sulfate detergent into the tubular molecular imprinted membrane equipment to wash away the trapped molecular imprinted polymer microspheres and the non-specific adsorbed impurities on the surface of the tubular molecular imprinted membrane. Step 5, Washing: Then, the fourth feed channel is opened, and a 70% (v / v) ethanol aqueous solution is introduced into the tubular molecularly imprinted membrane device to elute the EGCG adsorbed on the molecularly imprinted polymer microspheres and the tubular molecularly imprinted membrane. The eluent is then collected in the eluent recovery tank through the first discharge channel to obtain a high-purity EGCG solution. Step 6, Regeneration: Finally, the eluted molecularly imprinted polymer microspheres and tubular molecularly imprinted membranes were washed sequentially with 0.1M NaOH and deionized water, respectively, to regenerate their adsorption performance and reuse them for the next adsorption cycle.

[0033] HPLC analysis showed that the purity of EGCG in the eluted EGCG solution was as high as 96.5%, and the total yield reached 99.2%.

[0034] Application Example 2 Equal amounts of molecularly imprinted polymer microspheres were packed into a chromatography column, and equal amounts of crude tea polyphenols were loaded onto the column. The column was then washed with PBS buffer and eluted with 70% ethanol. The results showed that the column bed pressure drop was significant and the column was easily blocked by a small amount of insoluble matter in the feed solution. The yield of EGCG was 95.1%.

[0035] Application Example 3 The same amount of crude tea polyphenols was filtered and adsorbed using a tubular molecularly imprinted membrane device, and then directly eluted. The results showed that due to the limited adsorption capacity of the membrane, a large amount of EGCG was not adsorbed and permeated, resulting in a yield of only 78.3%.

[0036] Therefore, the yield of the method proposed in this invention (99.2%) is significantly higher than that of single molecularly imprinted microspheres (95.1%) and single tubular molecularly imprinted membranes (78.3%), and effectively avoids the clogging problem.

[0037] The above embodiments and figures are not intended to limit the product form and style of the present invention. Any appropriate changes or modifications made by those skilled in the art should be considered as not departing from the patent scope of the present invention.

Claims

1. A purification system based on a combination of molecularly imprinted microspheres and tubular membranes, characterized in that: include: The raw material pretreatment unit is used to remove large particulate impurities from the raw materials; The adsorption reaction unit is used for the mixed adsorption of raw materials and molecularly imprinted polymer microspheres. A membrane separation unit is used to retain molecularly imprinted polymer microspheres from the adsorption reaction unit and to perform secondary adsorption on target molecules remaining in the raw material. The elution and regeneration unit is used to elute the target molecules adsorbed by the membrane separation unit and to regenerate the molecularly imprinted polymer microspheres and the membrane separation unit. and control unit; The raw material pretreatment unit includes a storage tank and a pretreatment filter connected to the storage tank. The adsorption reaction unit includes a reaction vessel connected to the pretreatment filter, and molecularly imprinted polymer microspheres that match the target molecules are placed inside the reaction vessel. The membrane separation unit includes a tubular molecularly imprinted membrane device connected to the reaction vessel and a waste liquid tank connected to the tubular molecularly imprinted membrane device. The tubular molecularly imprinted membrane device contains a tubular molecularly imprinted membrane that matches the target molecules. The elution and regeneration unit includes an eluent storage tank, a detergent storage tank, and an eluent recovery tank, which are respectively connected to the tubular molecularly imprinted membrane device.

2. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The storage tank is connected to the pretreatment filter through a first feed channel. A first automatic feed pump is installed on the first feed channel and is controlled by the control unit.

3. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The pretreatment filter is connected to the reactor through a second feed channel, and a second automatic feed pump is installed on the second feed channel. The second automatic feed pump is connected to the control unit.

4. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The reactor is connected to the tubular molecular imprinting membrane device through a third feed channel. A third automatic feed pump is installed on the third feed channel and is controlled by the control unit. A stirring device is installed inside the reactor.

5. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The eluent storage tank is connected to the tubular molecular imprinting membrane device through a fourth feed channel. A fourth automatic feed pump is installed on the fourth feed channel and is controlled by the control unit.

6. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The detergent storage tank is connected to the tubular molecular imprinting membrane device through a fifth feed channel. A fifth automatic feed pump is installed on the fifth feed channel and is controlled by the control unit.

7. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The eluent recovery tank is connected to the tubular molecular imprinting membrane device through a first discharge channel. A first automatic discharge pump is installed on the first discharge channel and is controlled by the control unit.

8. The purification system based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 1, characterized in that: The waste liquid tank is connected to the tubular molecular imprinting membrane device through a second discharge channel. A second automatic discharge pump is installed on the second discharge channel and is controlled by the control unit.

9. A purification method using a purification system based on a combination of molecularly imprinted microspheres and tubular membranes as described in claim 1, characterized in that: Includes the following steps: Step 1, Preprocessing: First, the liquid containing the target molecules in the storage tank is processed through a pretreatment filter to remove large particulate impurities from the liquid. Step 2, Adsorption: Then, the pretreated liquid containing the target molecules is transported into the reactor and mixed with molecularly imprinted polymer microspheres under stirring to carry out the first adsorption of the target molecules. Step 3, Membrane separation and synergistic adsorption: Then, the feed solution containing molecularly imprinted polymer microspheres after the first adsorption is transported to the tubular molecularly imprinted membrane device, where cross-flow filtration is performed under pressure. The tubular molecularly imprinted membrane retains the molecularly imprinted polymer microspheres and simultaneously adsorbs the target molecules remaining in the feed solution for the second time. Step 4, Washing: Then, detergent is introduced into the tubular molecularly imprinted membrane device to wash away the trapped molecularly imprinted polymer microspheres and the non-specifically adsorbed impurities on the surface of the tubular molecularly imprinted membrane. Step 5, Washing: Then, eluent is introduced into the tubular molecularly imprinted membrane device to elute the target molecules adsorbed on the molecularly imprinted polymer microspheres and tubular molecularly imprinted membrane, and collect them in the eluent recovery tank to obtain a high-purity target molecule solution. Step 6, Regeneration: Finally, the eluted molecularly imprinted polymer microspheres and tubular molecularly imprinted membranes are cleaned to regenerate their adsorption performance and are recycled for the next adsorption cycle.

10. The purification method based on a combination of molecularly imprinted microspheres and tubular membranes according to claim 9, characterized in that: In step 4, the detergent is an ionic detergent or a nonionic detergent. The ionic detergent is sodium dodecyl sulfate or hexadecyltrimethylammonium bromide, and the nonionic detergent is Tween-20, Tween-80, NP-40, ethanol, or methanol. In step 5, the eluent is ethanol, propanol, acetone, or acetonitrile.

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