Novel integral chromatographic stationary phase forming die

Abstract

The utility model discloses a novel integral chromatographic stationary phase forming die which is used for forming a radial integral chromatographic stationary phase and comprises a cylindrical tank outer shell, a cylindrical tank outer shell outer flange, a cylindrical tank outer shell cover plate, a cylindrical tank inner shell, a cylindrical tank inner shell fixing piece, a hollow bolt and the like. All the components are fixedly connected through threads or bolts, disassembly and assembly are convenient, and the mold is convenient to clean. The center of the mold is hollow, so that the precision condition of the temperature in the polymerization process of the monomer in the mold is facilitated in the polymerization process; besides, when the mold is used for preparing the integral chromatographic stationary phase, later demolding of the integral chromatographic stationary phase is facilitated, the pore-foaming agent of the demolded integral chromatographic stationary phase can be removed in an extraction mode, and solvent waste in the preparation process of the integral chromatographic stationary phase is reduced.

Description

Technical Field

[0001] The utility model belongs to the technical field of liquid chromatography columns, and in particular relates to a novel integral chromatography stationary phase forming die. Background Art

[0002] With the rapid development of biotechnology, biopharmaceutical technology has also made great progress. The separation and purification of biological products such as proteins, peptides, nucleic acids, and antibodies has become a key step in the development of biological high technology, and has been increasingly valued by researchers. Liquid chromatography technology is one of the most effective and efficient means to achieve the separation and purification of biological products and even cells and live viruses. With the rapid development of biological treatment methods, such as the substances in the current advanced cell and gene therapy (CGT) field, such as plasmid DNA, RNA, active virus particles, etc., due to their large three-dimensional spatial structure, and traditional spherical separation media, such as silica microspheres, polymer microspheres, and polysaccharide microspheres, due to their own small pore size (less than 200nm) and high polarity, it is difficult to achieve effective separation and purification. It is becoming increasingly difficult to meet the current industrial separation needs of advanced biotechnology products, and it is urgent to find a new separation medium to meet the needs of industrial separation. The new monolithic chromatographic stationary phase has a highly internally connected porous structure, and the pore size is large, which can reach 1-3μm, so that the mobile phase has low mass transfer resistance and high mass transfer rate when passing through the pore size. In particular, the new monolithic chromatographic stationary phase has a large pore structure (micrometer level) and high permeability at high flow rates, so that its mass transfer process does not rely on the molecular diffusion mechanism but the convection mass transfer mechanism, so that the substances to be separated are quickly transferred to the active groups on the surface of the pores by means of convection mass transfer, and its efficiency is much higher than that of traditional spherical chromatographic fillers. Among them, the radial monolithic chromatographic medium stationary phase is a type of thick-walled "tube" monolithic chromatographic stationary phase with a central hole in the middle. The sample enters the entire bed from the outer surface of the chromatographic medium. The effective "column bed height" of the chromatographic column is the distance from the outer surface of the monolithic column bed to the inner surface of the monolithic column bed (i.e., the "tube" wall thickness). Due to its low "column bed height", the chromatographic separation process can achieve high-speed separation at a lower pressure, and reduce the residence time of the sample in the stationary phase, reducing the possibility of degradation or inactivation of biological samples, which makes the radial monolithic chromatographic stationary phase more and more valued.

[0003] The novel radial monolithic chromatographic medium stationary phase is different from the traditional preparation method of spherical materials. Its preparation process is to pour monomers into a mold, and directly form a monolithic chromatographic medium after polymerization. In order to ensure the performance of the entire monolithic chromatographic stationary phase, its internal pore size must be evenly distributed and accurate, so it is very necessary to provide a suitable molding mold. The preparation molds reported in the literature are only suitable for small-volume monolithic chromatographic stationary phases, such as chromatographic columns, and there is no report on the molding of large-volume, large-capacity industrial applications. Summary of the invention

[0004] In order to solve the above problems, the purpose of the utility model is to provide a new type of integral chromatographic stationary phase molding mold, which is particularly suitable for the preparation of large-volume and large-capacity integral chromatographic stationary phases.

[0005] In order to achieve the above purpose, the utility model adopts the following technical solutions:

[0006] A novel integral chromatographic stationary phase molding die is used for molding radial integral chromatographic stationary phases, characterized in that the integral chromatographic stationary phase molding die comprises a cylindrical tank shell (2), a cylindrical tank shell outer flange (13), a cylindrical tank shell cover plate (12), a cylindrical tank inner shell (8), a cylindrical tank inner shell fixing member (11) and a hollow bolt (14); the cylindrical tank shell (2) is in the shape of a round tube, and both ends thereof have external threads; the cylindrical tank shell outer flange (13) has internal threads, and can be threadedly connected to the cylindrical tank shell (2); the cylindrical tank shell outer flange (13) has threaded holes evenly distributed around it; the cylindrical tank shell cover plate (12) has a non-threaded center hole at the center; The cylindrical tank shell cover plate (12) has bolt holes evenly distributed around it, and can be fixed to the cylindrical tank shell outer flange (13) by bolts to seal the cylindrical tank; a precision sealing ring is sealed between the cylindrical tank shell (2) and the cylindrical tank shell cover plate (12); the cylindrical tank inner shell fixing piece (11) is a concentric circular accessory, and both the outer circumference and the inner hole are threaded; the cylindrical tank inner shell (8) is connected to the cylindrical tank inner shell fixing piece (11) through the internal threads at both ends; a precision sealing ring is sealed between the cylindrical tank inner shell (8) and the cylindrical tank shell cover plate (12); the cylindrical tank inner shell (8) and the cylindrical tank inner shell fixing piece (11) connection body is connected to the center hole of the cylindrical tube cover plate through a hollow bolt (14).

[0007] Furthermore, the cylindrical tank shell (2), the cylindrical tank shell outer flange (13), the cylindrical tank shell cover plate (12), the cylindrical tank inner shell (8), the cylindrical tank inner shell fixing member (11) and the hollow bolt (14) are all made of 316L stainless steel;

[0008] Furthermore, a sealing ring is provided between the cylindrical tank shell (2) and the cylindrical tank shell cover plate (12);

[0009] Furthermore, a sealing ring is provided between the cylindrical tank inner shell (8) and the cylindrical tank outer shell cover plate (12);

[0010] Furthermore, the sealing ring is made of a silicone rubber sealing ring, EPDM rubber, or a polytetrafluoroethylene sealing ring.

[0011] The advantages of this new experimental model are:

[0012] The mold is made of 316L stainless steel. During the polymerization process of the monomer in this mold, the monomer heats up quickly in the heating stage, which makes it easy to quickly reach the polymerization temperature. During the polymerization process, the monomer releases heat, and the stainless steel material makes it easy to transfer the heat of monomer polymerization to the cooling medium. All parts of the mold are connected by bolts, which is convenient for disassembly and cleaning. The center of the mold is hollow, which is convenient for the precise temperature conditions of the monomer polymerization in the mold during the polymerization process. In addition, the use of this mold to prepare the overall chromatographic stationary phase is convenient for the demoulding of the overall chromatographic stationary phase in the later stage, and the overall chromatographic stationary phase after demoulding can be extracted to remove the porogen, reducing the solvent waste in the preparation process of the overall chromatographic stationary phase. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 Schematic diagram of the structure of the new integral chromatographic stationary phase molding mold designed for the utility model

[0014] Figure 2 Cross-sectional view of cylindrical tank shell

[0015] Figure 3 Top view of cylindrical tank shell

[0016] Figure 4 Top view of the outer flange of the cylindrical tank shell

[0017] Figure 5 Cross-sectional view of the outer flange of the cylindrical tank shell

[0018] Figure 6 Top view of the cylindrical tank shell cover

[0019] Figure 7 Sectional view of the cylindrical tank shell cover

[0020] Figure 8 Cross-sectional view of the inner shell of a cylindrical tank

[0021] Fig. 9 Top view of the inner shell of a cylindrical tank

[0022] Fig.10 Top view of the inner shell fixings of the cylindrical tank

[0023] Fig.11 Cross-sectional view of the fixings of the inner shell of a cylindrical tank DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0025] Example 1

[0026] The utility model is designed to assemble a novel integral chromatographic stationary phase as follows Figure 1 As shown:

[0027] Figure 2 It is a cross-sectional view of the cylindrical tank shell, and both ends of the cylindrical tank shell have external threads;

[0028] Figure 3 It is a top view of the outer flange of the cylindrical tank shell, which contains internal threads and multiple bolt connection holes evenly distributed around it;

[0029] Figure 4 This is a top view of the cylindrical tank shell cover, with multiple bolt connection holes evenly distributed around it. The specifications and quantity of these bolt connection holes are consistent with those of the outer flange of the cylindrical tank shell, and the distribution should also be the same to facilitate the bolts to pass through and connect;

[0030] Figure 5 This is a cross-sectional view of the inner shell of a cylindrical tank, which contains internal threads.

[0031] Figure 6 This is a top view of the fixing part of the inner shell of the cylindrical tank. There are external threads on the outer circumference to facilitate direct connection with the external bolts of the inner shell of the cylindrical tank; there is a standard threaded hole in the center.

[0032] Mould assembly method:

[0033] First, the external threads (1) at both ends of the cylindrical tank shell (2) are connected to the internal threads (4) of the cylindrical tank shell outer flange (13) through internal and external threads to form a combination; then, the combination is bolted through the bolt holes (5) of the cylindrical tank shell cover plate and the threaded holes (3) of the cylindrical tank shell outer flange (13), and one end of the combination is fixed to the cylindrical tank shell cover plate (12) through the bolt holes (3); a precision rubber sealing ring can be added between the cylindrical tank shell and the cylindrical tank shell cover plate to seal; a cylindrical tank inner shell fixing piece (11) is taken and passed through its The external thread (9) is connected to the internal thread (7) at one end of the cylindrical tank inner shell (8), and in the same way, the other end of the cylindrical tank inner shell is also installed with a cylindrical tank inner shell fixing piece; the cylindrical tank inner shell assembly is placed parallel to the cylindrical tank outer shell, and a hollow bolt is passed through the center hole (6) of the cylindrical tank outer shell cover plate (12) and connected to the internal thread (10) of the cylindrical tank inner shell fixing piece in the cylindrical tank inner shell assembly, and a precision rubber sealing ring can be added to the contact surface; after precision fixing, the other end of the cylindrical tank outer shell is closed in the same way.

[0034] Example 2

[0035] According to the example of the utility model, a new type of integral chromatographic stationary phase is formed:

[0036] An oil phase mixture containing 1 g of initiator benzoyl peroxide, 40 g of monomer glycidyl methacrylate, 60 g of cross-linking agent ethylene glycol dimethacrylate, 45 g of porogen cyclohexanol and 5 g of dodecanol was stirred evenly until the benzoyl peroxide was completely dissolved, and then transferred to a reaction bottle. After vacuuming and nitrogen filling were performed alternately for 3-5 times, the mixture was slowly poured into the mold assembled in Example 1 under nitrogen protection, sealed, placed in a water bath, and reacted at 80° C. for 10 h. After the reaction was completed, the outer cover of the cylindrical tank was removed, the intermediate monolithic chromatographic stationary phase was slowly demolded, and extracted and cleaned with ethanol to obtain a novel monolithic chromatographic stationary phase.

[0037] Appendix 1 Names and functions of components of integral chromatographic stationary phase molding mold

[0038]

[0039]

[0040] The above contents are merely examples and explanations of the structure of the present utility model. The technicians in this technical field may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the structure of the present utility model or exceed the scope defined in the claims, they should all fall within the protection scope of the present utility model.

Claims

1. A novel integral chromatographic stationary phase forming mold, comprising: A cylindrical tank shell (2), a cylindrical tank shell outer flange (13), a cylindrical tank shell cover plate (12), a cylindrical tank inner shell (8), a cylindrical tank inner shell fixing member (11) and a hollow bolt (14); The characteristic of the cylindrical tank shell (2) is that the cylindrical tank shell (2) is in the shape of a round tube, and has external threads at both ends; The cylindrical tank inner shell (8) is in the shape of a circular tube, and has internal threads at both ends; The outer flange (13) of the cylindrical tank shell has internal threads and can be connected to the cylindrical tank shell (2) by threads; the outer flange (13) of the cylindrical tank shell has threaded holes evenly distributed around it; the cover plate (12) of the cylindrical tank shell has bolt holes evenly distributed around it, and a center hole without threads is provided at the center; the inner shell fixing member (11) of the cylindrical tank is a concentric circular accessory, and has threads around the outer circumference and the inner hole; The cylindrical tank inner shell (8) is connected to the cylindrical tank inner shell fixing member (11) via internal threads at both ends thereof; The cylindrical tank inner shell fixing piece is connected to the central hole of the cylindrical tank outer shell cover plate through a hollow bolt.

2. A novel integral chromatographic stationary phase forming mold according to claim 1, characterized in that A sealing ring is provided between the cylindrical tank shell (2) and the cylindrical tank shell cover plate (12).

3. A novel integral chromatographic stationary phase forming mold according to claim 1, characterized in that A sealing ring is provided between the cylindrical tank inner shell (8) and the cylindrical tank outer shell cover plate (12).

4. A novel integral chromatographic stationary phase forming mold according to claim 2, characterized in that A sealing ring is provided between the cylindrical tank shell (2) and the cylindrical tank shell cover plate (12), and the sealing ring is made of a silicone rubber sealing ring, or EPDM rubber, or a polytetrafluoroethylene sealing ring.

5. The novel integral chromatographic stationary phase forming mold according to claim 3, characterized in that The sealing ring between the cylindrical tank inner shell (8) and the cylindrical tank outer shell cover plate (12) is made of a silicone rubber sealing ring, EPDM rubber, or a polytetrafluoroethylene sealing ring.

6. A novel integral chromatographic stationary phase forming mold according to claim 1, characterized in that The cylindrical tank shell (2), the cylindrical tank shell outer flange (13), the cylindrical tank shell cover plate (12), the cylindrical tank inner shell (8), the cylindrical tank inner shell fixing member (11) and the hollow bolt (14) are made of 316L stainless steel.

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