Polymer particles, their manufacturing method and applications

Abstract

The present application relates to polymer particles and their manufacturing method and application. The polymer particles include rigid nanoparticles, which are at least partially crosslinked by a crosslinkable polymer material, and at least one type of rigid nanoparticle has a non-spherical symmetric shape in solution and forms an essentially ordered array structure at least locally within the polymer particles. The polymer particles disclosed in the present application exhibit excellent mechanical performance and excellent biocompatibility when used as a stationary phase for chromatographic separation, and at the same time efficiently improve the separation effect.

Description

[Technical field]

[0001] This application claims priority to an invention patent application filed on January 27, 2022, with application number CN202210098560.X and titled "Polymer particles and their manufacturing method and application", the entire contents of which are incorporated herein by reference.

[0002] The present application relates to polymer particles having a porous structure, and more particularly to polymer particles whose interior has a structure in which, at least locally, constituent molecules or both constituent molecules and pores are essentially ordered, and a method for producing the same. [Background technology]

[0003] Microspheres refer to inorganic or organic polymeric materials or polymeric composites with nanometer to micrometer diameters and basically spherical in shape, and their morphology can be varied, such as solid, hollow, porous, etc. The applications of microsphere materials are closely related to our lives, and involve fields such as paints, cosmetics, and precision electronic products. They are also widely used in high-value-added products such as separation chromatography media. Common microspheres include silica inorganic microspheres, biopolymer matrix microspheres, and polymer matrix microspheres. Microspheres, especially agarose biopolymer matrix microspheres, are most widely used in ion exchange chromatography, affinity chromatography, and hydrophobic chromatography columns, and are used in the separation and purification of small molecules, biologically active substances, etc., as consumables, packing materials, and polymer chromatography carriers.

[0004] Due to their widespread use and great success in biopharmaceutical separations, there is a large amount of relevant patent literature on biopolymer microspheres, including agarose-based microspheres. The first relevant literature includes Hjerten, S. Biochim. Biophys. Acta 1964, 79:393-398; and Bengtsson et al., S. Biochim. Biophys. Acta 1964. 79:399. The first agarose microsphere-related patent includes US Pat. No. 4,647,536, but polysaccharide microspheres for chromatography columns have been found in academic and patent literature for a long time. Research has shown that in techniques such as affinity chromatography and ion exchange chromatography, the pore structure of the medium is closely related to the surface area accessible to proteins, which determines the protein separation effect, such as loading capacity and resolution. Therefore, when polysaccharide gel spheres are used as a medium in chromatography columns, their internal pore size structure, size and distribution, sphere size and distribution, shape, and mechanical performance have a great impact on the separation effect and separation speed. However, the polysaccharide gel balls produced by currently known mechanical stirring, homogeneous emulsification, and membrane emulsification methods cannot control the internal pore size structure. In addition, considering the normal flexibility, the current polysaccharide gel microspheres are relatively soft and the pressure they can withstand is limited. As a result, the corresponding chromatography columns are limited to low-speed biological protein separation applications. In addition, the most commonly used raw material for agarose microspheres is obtained from seaweed through a multi-step extraction process, which is a relatively high-cost raw material that is not suitable for large-scale industrialized production.

[0005] On the other hand, some biologically active substances to be separated have poor resistance to changes in temperature, shear force, and solution environment, and are prone to losing activity due to structural changes, so the chromatographic conditions for the active substances are relatively severe. Usually, excellent mechanical properties and chemical stability, as well as more efficient separation efficiency, are required. Otherwise, it will lead to denaturation and deterioration of the separated substances.

[0006] Therefore, in order to improve the separation purity and efficiency in chromatographic separation and reduce the separation cost of biological proteins, it is necessary to provide porous polymer particles whose internal structure and pore distribution can be controlled, which have low raw material costs and consistent strength. Summary of the Invention

[0007] The aim of the present application is to provide polymeric particles having an internal essentially ordered structure, at least locally, which meets the above requirements using a combination of materials synthesis and manufacturing methods.

[0008] In order to achieve the above object, the present application provides a porous polymer particle, which is formed by crosslinking at least a part of a crosslinkable polymer material containing rigid nanoparticles, at least one rigid nanoparticle has a non-spherical symmetric shape in solution, and the rigid nanoparticles form a basically ordered structure in at least a part of the polymer particle. At the same time, the internal pores formed by crosslinking also basically inherit the same ordered structure at least partially, forming a basically ordered structure at least locally.

[0009] The following examples are provided to illustrate embodiments of the present invention and its objectives in combination with systems, tools, and methods. These examples are suggestive and illustrative, not limiting. In different embodiments, the present invention satisfies one or more of the above market needs and may address other improvements.

[0010] The main objective of the present application is to provide porous polymeric particles, which are at least partially composed of crosslinkable polymeric materials containing rigid nanoparticles, said rigid nanoparticles forming at least partially essentially ordered structures within the polymeric particles.

[0011] It is yet another object of the present application to provide porous polymeric particles having a pore structure bridged by rigid nanoparticles and at least partially having a substantially ordered structure.

[0012] Yet another object of the present application is to provide porous polymeric particles that contain polysaccharide compounds to provide pressure resistance and structural support, in addition to rigid nanoparticles to provide ordered arrangement.

[0013] Furthermore, another object of the present application is to provide a method for producing polymer particles to obtain the basic structure of the polymer particles provided in the present application.

[0014] Based on the above objective, the present application provides a porous polymeric particle, which is at least partially composed of a crosslinkable polymeric material containing rigid nanoparticles, at least one of said rigid nanoparticles having a non-spherically symmetric shape in solution, and which form, at least locally, an essentially ordered structure in the polymeric particle.

[0015] A further refinement of the present application is that said rigid nanoparticles are biopolymers.

[0016] As a further refinement of the present application, the polymeric particle has regions within it that are essentially ordered with at least one rigid nanoparticle, and the molecular arrangement between these regions may be unrelated, related, or partially related.

[0017] As a further refinement of the present application, the shape of the non-spherically symmetric rigid nanoparticles may be rod-like, strip-like, flake-like, needle-like, or wire-like, with the characteristic direction being along the long axis of the molecule.

[0018] As a further refinement of the present application, the non-spherically symmetrically shaped rigid nanoparticles are disc-shaped with a characteristic direction perpendicular to the planar direction.

[0019] A further improvement of the present application is that the polymer particles have a globally ordered interior.

[0020] As a further refinement of the present application, the characteristic directions may be essentially distributed along the radial direction of the particle, along the bipolar axis direction of the particle, and / or distributed in multiple concentric circles therein.

[0021] As a further refinement of the present application, in the essentially ordered local regions, the characteristic directions may be essentially parallel, fan-shaped, or spiral.

[0022] In a further refinement of the present application, the biopolymer is selected from a peptide, a protein, a nucleic acid, a polysaccharide, and a lipid.

[0023] As a further refinement of the present application, biopolymers with non-spherically symmetric shapes may or may not possess chirality.

[0024] In a further refinement of the present application, the chiral biopolymers include biopolymers with left-handed chirality and biopolymers with right-handed chirality.

[0025] As a further improvement of the present application, the biopolymer having a non-spherical symmetric shape includes cellulose nanocrystals or cellulose nanofibers, which are abundant in nature and low in cost.

[0026] In a further refinement of the present application, the cellulose nanocrystals have a length of 20-1000 nm and a width of 2-100 nm.

[0027] In a further refinement of the present application, the cellulose nanocrystals in solution have a long axis ratio of 2:1 to 200:1.

[0028] As a further refinement of the present application, the polymeric particles may include polysaccharide compounds that do not have a well-defined non-spherically symmetric shape, which are copolymerized with the rigid nanoparticles to form the polymeric particles.

[0029] As a further refinement of the present application, the polysaccharide compound is at least one selected from agar, agarose, dextran, starch, chitin, and alginic acid.

[0030] In a further refinement of the present application, the mass ratio of the rigid nanoparticles to the polysaccharide compound is 1:10 to 50:1.

[0031] In a further improvement of the present application, after dissolving the rigid nanoparticles and the polysaccharide compound in water, the solid content of the dispersion is between 2% and 90%.

[0032] As a further improvement of the present application, the volume ratio of the rigid nanoparticles and the polysaccharide compound is 1% to 10% of the total polymer particles.

[0033] As a further improvement of the present application, the polymer particles may include a cross-linking agent, and the amount of the cross-linking agent is 10%-100% of the total mass of the biopolymer and the polysaccharide compound.

[0034] As a further improvement of the present application, the crosslinking agent may be selected from any one of an epoxy compound, a diacyl chloride compound, and a halogen compound.

[0035] As a further refinement of the present application, the epoxy compound may be selected from small molecule organics of the glycerol ether type.

[0036] In a further refinement of the present application, the polymeric particles have a particle size range of 1 to 500 micrometers.

[0037] Meanwhile, the present application discloses porous polymer particles formed at least partially by a crosslinkable polymer material, the polymer particles being crosslinked by at least one rigid nanoparticle and having an internal pore structure, the at least one rigid nanoparticle having a non-spherical symmetric shape in solution, the pore structure having a structure that is essentially ordered at least locally, and the arrangement direction of the pore structure essentially coincides with the arrangement direction of the biopolymer.

[0038] A further refinement of the present application is that the rigid nanoparticles are biopolymers.

[0039] In a further refinement of the present application, the pore size is between 1 and 1000 nm.

[0040] As a further refinement of the present application, in at least some localized regions, the orientation and positional arrangement of both at least localized segments of the pores and at least localized segments of adjacent pores has a certain regularity.

[0041] As a further refinement of the present application, in at least some local regions, the pores of at least the local segment are essentially aligned in a parallel, fan-shaped or spiral manner.

[0042] Meanwhile, the present application discloses a method for producing the above polymer particles, which includes the following steps: (1) Dispersing rigid nanoparticles in water to form a dispersed phase solution. (2) Dispersing the dispersed phase solution in a continuous phase containing an emulsifier to form emulsion droplets containing rigid nanoparticles. (3) A cross-linking agent is added to cross-link the biopolymers in the milk droplets to form polymer particles.

[0043] A further refinement of the present application is that the rigid nanoparticles are biopolymers.

[0044] As a further refinement of the present application, step (1) also includes adding a polysaccharide compound.

[0045] A further improvement of the present application is that the mass concentration of the emulsifier in the continuous phase is between 2% and 20%.

[0046] As a further refinement of the present application, the emulsifier comprises one or more of a SPAN type surfactant, a Tween type emulsifier, a sialoyl ethylene glycol, and a polyglycerol phosphate ester.

[0047] As a further refinement of the present application, the continuous phase is selected from one or more of hexane, hexadecane, liquid paraffin, and soybean oil.

[0048] A further refinement of the present application is that step (3) is carried out under alkaline conditions.

[0049] The present application also discloses the application of chromatographic separations using the above-mentioned porous polymer particles as a stationary phase.

[0050] Furthermore, the present application discloses another application scenario for the above polymer particles: after forming the dispersed phase solution in step (1), a crosslinker can be added directly without emulsification, and the resulting product can be used as the overall column stationary phase. Effect of the Invention

[0051] The polymer particles disclosed in the present application can improve separation efficiency when used as a stationary phase for chromatographic separation because the rigid nanoparticles form a basically ordered pore structure at least locally inside the polymer particles. In addition, the polymer particles made using the rigid nanoparticles have liquid crystal orientation and uniform radial alignment at least locally, so that the particle surface load is uniform, deformation is small, and the particles have excellent mechanical properties and biocompatibility. In addition, the porous polymer microspheres disclosed in the present application are obtained from nanofiber crystal materials, which are the most abundant and environmentally friendly in nature and have the most mature extraction technology, and can greatly reduce the cost of chromatographic consumables. [Brief description of the drawings]

[0052] [Figure 1] FIG. 1 shows a schematic diagram of the structure of a polysaccharide microsphere in the prior art and an enlarged schematic diagram of part A in FIG. [Diagram 2]Figure 2 consists of three images: (a) shows a schematic diagram and an example of a structural formula for a rod-shaped biopolymer structure, (b) shows a schematic diagram and an example of a structural formula for a bow-shaped (banana-shaped) biopolymer structure, and (c) shows a schematic diagram and an example of a structural formula for a disk-shaped biopolymer structure. [Diagram 3] Figure 3 consists of eight images, (a), (c), (e), and (g) show the schematic arrangement of CNC nanorods when the CNC dispersion concentration is less than 3%, 3.5%-4%, 4%, and 5%, respectively, and (b), (d), (f), and (h) are cross-polarized microscopy images when the CNC dispersion concentration is less than 3%, 3.5%-4%, 4%, and 5%, respectively. [Figure 4] FIG. 4 shows a schematic diagram of the formation process of a soluble liquid crystal droplet emulsion. [Diagram 5] FIG. 5 shows two binding modes of rigid nanoparticles in polymer particles. [Figure 6] FIG. 6 shows a schematic diagram of chiral arrangement of biopolymers formed inside a polymer particle. [Figure 7] Figure 7 is composed of four images, (a) is a cross-sectional view of the polymer particles disclosed in the present application, (b) is an enlarged view of part B in Figure 7(a), (c) is an enlarged view of part C in Figure 7(a), and (d) is a scanning electron microscope image of the polymer particles of some examples. [Figure 8] Figure 8 is composed of four images: (a) is a schematic diagram of a radial structure of polymer particles, (b) is a schematic diagram of a dipolar structure of polymer particles, (c) is a schematic diagram of a ring structure of polymer particles, and (d) is an orthogonal polarizing microscope image of a radial structure of polymer particles. [Figure 9] FIG. 9 shows a flow chart of a method for producing polymer particles according to an embodiment. [Figure 10] Figure 10 consists of six images: (a), (c), and (e) are schematic diagrams of the internal structure of essentially disordered, partially ordered, and fully ordered polymer particles, and (b), (d), and (f) are cross-polarized microscopy images of the disordered, partially ordered, and fully ordered polymer particles. [Figure 11] FIG. 11 shows a schematic diagram (a) and an orthogonal polarizing microscope image (b) of the internal structure of a milk droplet produced according to Example 1 of the present application. [Figure 12] FIG. 12 shows cross-polarized microscopy images of polymer particles produced according to Example 1 of the present application. [Figure 13] FIG. 13 shows cross-polarized microscopy images of polymer particles produced according to Example 2 of the present application. [Figure 14] FIG. 14 shows cross-polarized microscopy images of polymer particles produced according to Example 6 of the present application. [Figure 15] FIG. 15 shows a cross-polarized microscope image of polymer particles produced according to Comparative Example 4 of the present application. [Figure 16] FIG. 16 shows pressure-flow curves of chromatography columns manufactured according to some examples and comparative examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0053] In order to make the objectives, technical solutions and advantages of the present application clearer, the following will clearly and completely describe the technical solutions of the present application based on specific embodiments and the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, not all embodiments, and are not used to limit the scope of the present invention. All other embodiments obtained based on the embodiments of the present application without the engineers performing creative labor are included in the scope of protection of the present application.

[0054] One method for producing porous microspheres for use in chromatography columns is to disperse polysaccharide molecules (e.g., agarose) in water and form tiny aqueous droplets containing the polysaccharide suspended in an oil phase by a suitable emulsification technique. Referring to FIG. 1, when the emulsion is cooled, the single chains of the polysaccharide compound 101 form a double helical structure, forming pore channels 102 between the molecular bundles, and finally forming microspheres 100 through the action of a cross-linking agent 103. Since the polysaccharide molecules are randomly arranged in water, the arrangement of the internal pore channels of the gel spheres formed thereby is also random. Also, considering the inherent flexibility of the polysaccharide molecules, these cross-linked spheres are usually relatively flexible. In nature, many biopolymers exhibit rigid, non-spherically symmetric shapes when alone or dispersed in water. For example, as shown in Figure 2, these include (a) rod-like shapes, i.e., tobacco mosaic virus (TMV), deoxyribonucleic acid (DNA), nanocrystalline cellulose (CNC, schematic and structural formula as shown in Figure 2(a) right), (b) bow-like (banana-like) shapes, i.e., P52C molecule (schematic and structural formula as shown in Figure 2(b) right), and (c) plate-like shapes, i.e., 2,3,6,7,10,11-hexa(1,4,7-trioxooctane-phenylene[9,10]anthracene7) (TP6EO2M, schematic and structural formula as shown in Figure 2(c) right). Tobacco mosaic virus is a rigid rod-like biological nanoparticle that has been widely studied in liquid crystal physics. According to the lyotropic liquid crystal theory, when such rigid nanoparticles are dispersed in a solvent, the rigid nanoparticles may be arranged randomly in the solvent depending on the concentration and properties of the rigid nanoparticles. Alternatively, with an increase in the concentration of rigid nanoparticles, an ordered molecular arrangement of certain lyotropic liquid crystals is formed, including nematic phase (such as tobacco mosaic virus nanomaterials), smectic phase, cholesteric phase, columnar phase liquid crystals, etc. Orderly arranged liquid crystal materials usually exhibit birefringence properties of light, so that microdroplets or solvents containing non-spherically symmetric biopolymers can be clearly observed under a polarizing microscope, showing the typical structure of liquid crystals (see Figure 3).

[0055] Specifically, based on the spirit of the present invention, by utilizing rigid nanoparticles that do not have spherical symmetry, it is possible to produce porous polymer microspheres with orderly molecular arrangement, controllable pore channels, and excellent mechanical properties.

[0056] As shown in Figure 4, in accordance with the spirit of the present invention, a suitable amount of rigid nanoparticles with aspherical symmetry are uniformly dispersed in a solvent 401, either alone or together with a suitable amount of amorphous monomers or oligomers 101, to form a partially or fully ordered lyotropic liquid crystal solution 400, as shown in Figure 4(a). The lyotropic liquid crystal solution 400 is formed by a suitable emulsification method, such as film emulsification (as shown in Figure 4(b)) or by adding a solvent 402 and an emulsifier 403 that are incompatible with the lyotropic liquid crystal solution, and emulsified by mechanical stirring (Figure 4(c)), to form an emulsion containing lyotropic liquid crystal droplets 405 suspended in the solvent 402. The monomers or oligomers and rigid nanoparticles with polymerizable functional groups are polymerized to form a polymer network structure, forming polymer microspheres, i.e., polymer particles 410, containing rigid nanoparticles and at least locally ordered, as shown in Figures 4(d), (e), (f), and (g). Rigid nanoparticles may be physically embedded in the surrounding polymer and anchored to the microsphere (see Figure 5(b)), or they may directly participate in the cross-linking reaction and become chemically bound as part of the polymer (see Figure 5(a)).

[0057] In accordance with the spirit of the present invention, when the rigid nanoparticles are biopolymers, it is possible to produce porous biopolymer microspheres having at least locally ordered molecules and further ordered pore channels.

[0058] Specifically, cellulose nanocrystals (CNCs) with a suitable aspect ratio and size distribution are biopolymers that have a certain rigidity in a specific solvent (water) and form a lyotropic liquid crystal phase. Based on the spirit of this invention, when the biopolymer is cellulose nanocrystals (CNCs) and its concentration reaches a critical value, the CNC molecules may self-organize, form an ordered array, and a liquid crystal phase may appear. As shown in Figures 3(a) and (b), for a CNC nanomaterial with a specific aspect ratio, when the concentration of the CNC dispersion is less than 3%, the CNCs are irregularly arranged in the dispersion, and in this state, they do not become liquid crystal. The corresponding solvent does not show birefringence characteristics even under an optical microscope where the directions of the polarizer P and the polarizer A are perpendicular to each other, and the image is in a uniform dark state. As shown in Figures 3(c) and (d), when the concentration of the CNC dispersion is between 3.5% and 4%, a wavy ordered array may occur due to insufficient dispersion or local concentration fluctuations. As shown in Figure 3(e) and (f), when the concentration of the CNC dispersion exceeds the critical concentration of 4%, the biopolymer forms an ordered arrangement in the liquid crystal phase, and an ordered arrangement structure is formed. As shown in Figure 3(g) and (h), the CNC biopolymer has chirality, so when the concentration of the CNC dispersion is about 5%, the chirality of the biopolymer is clearly manifested, and a cholesteric phase molecular arrangement with a helical structure is formed. Meanwhile, when the concentration of the CNC dispersion exceeds 6%, the arrangement of the biopolymer becomes more ordered. When the aspect ratio and uniformity of the CNC nanomaterial change, the critical concentration also changes accordingly. At the same time, the cellulose nanocrystal (CNC) biopolymer has chirality, and the ordered arrangement structure of the molecules formed forms a liquid crystal molecular arrangement with a helical structure such as a cholesteric phase, as shown in Figure 6.

[0059] FIG. 7 is based on a kind of public application having a polymer particle having a porous structure. Specifically, FIG. 7(a) shows a cross-sectional view of a part of the inside of a polymer particle along the diameter direction, in which the biopolymers may at least partially maintain an ordered arrangement even after the cross-linking reaction, and the pores formed under the influence of the molecular arrangement may be arranged regularly locally (see FIG. 7(b)). The biopolymer solution shown in FIG. 7(a) is emulsified in a locally ordered state to form milk droplets. The biopolymers 201 in the milk droplets also tend to move toward the partially ordered arrangement shown in FIG. 7(a). When the emulsion is cooled, the biopolymers 201 retain their arrangement, and when the polymer particles are formed by further cross-linking reaction, their internal structure at least partially retains the previous ordered arrangement structure, and at the same time, as shown in FIG. 7(b), the pores 701 generated between the arrangements of the biopolymers also inherit the basically same ordered arrangement structure, and the pores of the polymer particles are formed at least locally into a basically ordered arrangement structure. "Essentially ordered" refers to the fact that, at least in a local region, the orientation and positional arrangement of at least a local segment of a hole and at least a local segment of an adjacent hole have a certain regularity. Specifically, at least in a local region, at least a local segment of a hole and at least a local segment of an adjacent hole are essentially arranged in a parallel, fan-shaped, or spiral shape. As shown in FIG. 7(d), the diameter of the hole is selected to be 1 to 1000 nm as a preferential embodiment.

[0060] In accordance with the spirit of the present invention, the essentially ordered array structure in which the biopolymers are formed within the milk droplet may include one or more regions. Furthermore, the molecular arrays of the multiple regions may be unrelated, related, or partially related. Furthermore, the essentially ordered array structure may be globally ordered or partially ordered. When globally ordered, in the essentially ordered local regions, the characteristic directions of the biopolymers may be essentially distributed along the radial direction of the particle, essentially distributed along the bipolar axis direction of the particle, or distributed in multiple concentric circles within the particle. When partially ordered, in the essentially ordered local regions, the characteristic directions of the biopolymers may be essentially arranged in parallel, fan-shaped, or spiral shapes.

[0061] Within the range of the overall order, these basic ordered structures may form some special structures. For example, as shown in FIG. 8(a), a radial structure (characteristic directions are regularly aligned in the radial direction) may be formed inside, and holes 801 regularly aligned toward the center may be formed. Also, as shown in FIG. 8(b), a dipole-type structure (characteristic directions are ordered along the dipole axis direction) may be formed inside, and holes 802 ordered along the dipole axis direction may be formed inside. Furthermore, as shown in FIG. 8(c), a ring-shaped structure (characteristic directions form a plurality of concentric circular arrangements) may be formed inside, and holes 803 ordered in concentric circles may be formed inside. However, the present application is not limited to this, and other ordered structures are also possible. At the same time, these special structures form special optical phenomena under a polarizing microscope due to the optical birefringence properties that biopolymers usually have. For example, as shown in FIG. 8(a), the characteristic directions of biopolymers are ordered in the radial direction within a milk drop, and the internal structure and holes of the formed polymer particles are also ordered in the radial direction, resulting in a radial structure. This structure can exhibit a Maltese cross optical anisotropy under cross-polarized light microscopy (see Figure 8(d)).

[0062] In the partially ordered range, as shown in FIG. 7(a), the interior of the polymer particle contains part B shown in FIG. 7(b) and part C shown in FIG. 7(c). Part B is a local region in which the characteristic directions of the biopolymers are basically ordered, and part C is a region in which the characteristic directions are arranged in a disordered manner. In the interior of the polymer particle, ordered holes 701 and disordered holes 702 are formed at the same time. At this time, the polymer particle may not have a specific structure, but its characteristic directions are still regularly arranged in a small range, so that coloring can be seen under a crossed polarizing microscope.

[0063] By using the preparation method proposed by the present invention, at least partially ordered droplets of biopolymers can be obtained with different sizes, which are cross-linked to form polymer particles with at least locally ordered molecular and pore channels. In a preferred embodiment, the average particle size of the polymer particles is usually 1-500 micrometers in an aqueous medium, more preferably 5-150 micrometers. If the particle size of the polymer particles is too small, the back pressure will be high, and if the particle size is too large, the separation effect will be reduced.

[0064] In accordance with the spirit of the present invention, the polymer particle 410 is formed by crosslinking biomolecules 201 at least partially contained in a crosslinkable polymeric material. At least one biomolecule has a non-spherically symmetric shape in solution. For example, as shown in FIG. 2(a), the biomolecule 201 may have a rod-like shape characterized by the direction of the long axis of the molecule. Alternatively, as shown in FIG. 2(b), the biomolecule 203 may have an arch-like (banana-like) shape characterized by the direction of the long axis of the molecule. As shown in FIG. 2(c), the biomolecule 205 may have a disk-like shape with a characteristic direction 206 perpendicular to the planar direction. Alternatively, other non-spherically symmetric shapes such as plate-like, needle-like, wire-like, etc. may be adopted, but the present application is not limited thereto.

[0065] The biomolecules with or without non-spherical symmetry are at least one selected from polypeptides (e.g. insulin, growth hormone), proteins (e.g. chlorophyll, collagen, etc.), nucleic acids (e.g. DNA), polysaccharides (e.g. cellulose, chitin, etc.), and lipids (e.g. glycerol fatty acid esters, phospholipids, glycolipids, steroids, etc.). These biomolecules are widely present in living organisms and generally have a rod-like or flat shape in solution. As a preferential embodiment, as shown in FIG. 6, the biopolymers with non-spherical symmetry may or may not have chiral properties. Furthermore, the biopolymers with chiral properties include left-handed biopolymers and right-handed biopolymers. The liquid crystal phase they form forms a liquid crystal molecular arrangement with a helical structure of the cholesterol phase. As shown in the corresponding part of the scanning electron microscope image indicated by the arrow in FIG. 6, the broken part of the polymer particle shows a helical band-like internal structure. A specific embodiment of this application is cellulose nanocrystals (CNC), whose structural formula is as follows: [ka]

[0066] The rod-like structure formed by the biopolymer has a large long axis ratio and is likely to form a liquid crystal phase. In a further preferred embodiment, the length of the cellulose nanocrystal is 20 to 1000 nm, the width is 2 to 100 nm, and the long axis ratio is 1:5 to 1:200.

[0067] As shown in FIG. 7(b), the polymer particles may further include polysaccharide compounds 101 that do not have a non-spherical symmetric shape. These polysaccharide compounds are copolymerized with the biopolymers to form the polymer particles. These polysaccharide compounds may be at least one selected from agar, agarose, starch, chitin, alginic acid, and fucose. In a specific embodiment of the present application, the polysaccharide compound is agar, and its structural formula is as follows: [ka]

[0068] Before emulsification, the polysaccharide compound is a fluid gel-like dispersion, which is emulsified into milk droplets. After undergoing processes such as cooling, hardening, and aging, the polysaccharide compound 101 will form a double helix structure from a single chain, enter a bound state, and finally become a stable solid particle, as shown in Figure 7(b). Although these polysaccharide compounds may not self-order in solution, they will have order according to the arrangement of the biopolymer through various interactions, including interactions with biopolymers and comprehensive hydrogen bonds, and will eventually form an ordered arrangement. At the same time, at a certain concentration, the biopolymer may become partially ordered and form a liquid crystal phase, and the polysaccharide compound will use the arrangement of the large molecule as a template to arrange itself. These polysaccharide compounds and biopolymers can be further copolymerized with the assistance of a cross-linking agent to form a stable particle structure, which can further improve the pressure resistance of the polymer particles without compromising the ordered structure of the formed polymer particles. At the same time, in the process of producing polymer particles, the polysaccharide compound (e.g., agar) can cool and solidify the emulsified milk droplets, providing structural support for the subsequent cross-linking polymerization, thereby simplifying the production process.

[0069] According to the spirit of the present invention, the present application also provides a method for preparing polymer particles, the specific process of which is described below.

[0070] As shown in FIG. 9, an embodiment of the present invention can include a method 900 for preparing polymer particles. The method can include dispersing a biopolymer and a polysaccharide compound to form a dispersion 901. Specifically, the biopolymer and the polysaccharide compound are dispersed in water to form a dispersed phase solution. By controlling the properties of a specific biopolymer, such as its major axis ratio and size distribution, and its concentration in water, the biopolymer can be adjusted to be in an ordered or disordered state in the solvent. In a preferred embodiment, the solid content of the resulting dispersion of the mixture of the biopolymer and the polysaccharide compound is 2% to 90%, and the volume of the biopolymer and the polysaccharide compound and the ratio of the total volume of the polymer particles to the total volume of the polymer particles are 1% to 10%. Furthermore, the mechanical properties of the produced polymer particles, especially its pressure resistance, can be adjusted by adjusting the mass ratio of the polysaccharide compound to the biopolymer. In a preferred embodiment, the mass ratio of the biopolymer to the polysaccharide compound is 1:10 to 50:1. In a further preferred embodiment, the mass ratio of the biopolymer to the polysaccharide compound is 1:1 to 15:1.

[0071] Next, the method 900 includes a technique for emulsifying the dispersion to form emulsion droplets 902. There are various methods of emulsification, including membrane emulsification. Membrane emulsification refers to a method in which the dispersed phase enters the continuous phase directly through the pores of a microporous membrane during the emulsification process, and emulsion droplets are formed at the ends of the pores and extruded drop by drop. Another common emulsification process is a method in which an emulsifier is included in the continuous phase containing the dispersed phase solution in which the biopolymer and the polysaccharide compound are dispersed together, and emulsion droplets containing the biopolymer are formed. The emulsifier can be a sorbitan ester (SPAN) surfactant, such as sorbitan monopalmitate (SPAN40), sorbitan monostearate (SPAN60), sorbitan tristearate (SPAN65), sorbitan monooleate (SPAN80), or sorbitan trioleate (SPAN85). Also, Tween emulsifiers such as Tween 20, Tween 40, Tween 60, Tween 80, or Tween 85, or cetyl polyethylene glycol, polyglycerol ricinoleate (PGPR), etc. can be used. The continuous phase is an oily substance that is incompatible with the water phase but dissolves the emulsifier, including linear alkanes (e.g., normal hexane, normal hexadecane, etc.), liquid paraffin, and animal or vegetable oils (e.g., soybean oil, etc.). The emulsifier helps to form a uniform emulsion dispersion and at the same time helps the biopolymers to be ordered in the emulsion droplets, and by controlling the temperature and drying time, it is possible to produce emulsion droplets with different orientation effects, and thereby produce particles with corresponding orientation effects. In Figures 10(a) and (b), most of the nanorods inside the particles are arranged in a disordered manner, and some areas are ordered, and a few areas are bright under a polarized microscope, resulting in a non-uniform dark state throughout the image. In Figure 10(c) and (d), some areas of the nanorods inside the particle are randomly arranged, and some areas are ordered, and birefringence characteristics begin to appear slightly under polarized light microscope. In Figure 10(e) and (f), the nanorods inside the particle are arranged in multiple concentric circles, and other ordered arrangements are also acceptable. Typical radial optical anisotropy (Maltese cross) is seen under polarized light microscope.As a preferred embodiment, the mass concentration of the emulsifier in the continuous phase is preferably 2% to 20%. The ratio of the dispersed phase to the continuous phase is preferably 1:1 to 1:15. The dispersion method may be a general emulsification dispersion method such as a stirring method, an ultrasonic method, or a shaking method.

[0072] Finally, the method 900 also includes a step of cross-linking the milk droplets 903, and the specific process is to add a cross-linking agent to the milk droplets formed in step 902 to cross-link the biopolymers in the milk droplets to form polymer particles. The cross-linking agent can be selected from epoxy compounds, diacyl chlorides, or halogen compounds. In a specific embodiment of the present application, the epoxy compound is a glyceryl ether small molecule organic compound.

[0073] When the crosslinking agent is an epoxy compound, the crosslinking process is as follows: [ka]

[0074] When the crosslinking agent is a halogen compound, the crosslinking process is as follows. [ka]

[0075] Since there are many hydroxyl groups on the surface of the biopolymer, the crosslinking agent is assisted to further crosslink polymerization to form stable polymer particles. At the same time, the crosslinking strengthens the pore structure formed during the emulsification process. Since the biopolymer is ordered before crosslinking, the final pore structure tends to have a similar ordered arrangement, resulting in an ordered internal structure and pore structure. In a preferred embodiment, the crosslinking is carried out under alkaline conditions, which is expected to make the crosslinking agent work more effectively.

[0076] The above-mentioned polymer particles have a porous structure and can be applied as a stationary phase in biochemical separation, especially chromatographic separation. Chromatographic separation methods usually adopt column operation, specifically, polymer particles are packed into a chromatography column, and a mobile phase containing different components is passed through the chromatography column to achieve separation of substances by characteristics such as the difference in the interaction between the molecules to be separated and the stationary phase based on the difference in size of the molecules to be separated and purified. Since the polymer particles are made from biological polymers, they have a very high affinity with living organisms and are particularly suitable for the separation of various biological compounds. In addition, since the polymer particles have an ordered internal structure and pore structure, the route through which the molecules to be separated enter the stationary phase is regular, which greatly improves the separation efficiency.

[0077] In addition, in order to further achieve the object of the present application, the present application also provides another application example of the above-mentioned polymer particles, specifically, a method is disclosed in which after the dispersed phase solution is formed, a crosslinking agent is directly added to carry out in situ polymerization without carrying out an emulsification operation, and the obtained product is used as a monolithic column stationary phase.

[0078] Next, the structure, optical properties, and manufacturing method of the polymer particles will be described in detail based on specific examples. Unless otherwise specified in the present invention, all the ratios described are mass ratios.

[0079] Example 1 0.6 g of cellulose nanocrystals and 0.06 g of agarose are dispersed in 14.34 g of water and stirred at 90 °C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing SPAN80 (mass percentage concentration: 10%) and emulsified by stirring at 80 °C for 2 minutes, then cooled to reduce the temperature to form a dispersion containing solidified milk droplets. The above suspension is emulsified in 150 g of liquid paraffin (mass percentage concentration: 10% SPAN80) by stirring at 80 °C for 2 minutes, then cooled to form a dispersion containing emulsified droplets. Figure 11 (a) shows that the cellulose nanocrystals and agarose molecules are arranged in multiple concentric circles within the milk droplets, and Figure 11 (b) shows that these milk droplets show a Maltese cross under a polarizing microscope. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and 500 μl of an aqueous solution (10 ml) of cumyl glycerin ether, a crosslinking agent, is added and reacted with stirring for 12 hours. 500 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride is added to the above reaction solution and reacted with stirring for 8 hours. 500 μl of epoxy chloropropane and 500 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride are mixed and added to the reaction solution and reacted with stirring for another 12 hours. The resulting polymer particles are washed to a neutral solution pH, and their optical properties are shown in Figure 12. Under a polarizing microscope, these polymer particles show radial optical anisotropy (Maltese cross), indicating that they have a radial internal structure and pore structure.

[0080] Example 2 0.4g of cellulose nanocrystals and 0.2g of agarose are dispersed in 9.4g of water and stirred at 90°C to form a suspension. The above suspension is added to 100g of liquid paraffin containing SPAN80 (mass percentage concentration: 10%) and emulsified by stirring at 80°C for 2 minutes, then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and 500μl of an aqueous solution (10ml) of 1,4-butanediol diglycidol, a crosslinking agent, is added and reacted with stirring for 12 hours. 500μl of an aqueous solution containing 40wt% sodium hydroxide and 5wt% sodium borohydride is added to the above reaction solution and reacted with stirring for 8 hours. 500μl of epoxycyclopropane was mixed with 500μl of an aqueous solution containing 40wt% sodium hydroxide and 5wt% sodium borohydride, and the mixture was added to the reaction solution and stirred for another 12 hours. The resulting polymer particles were washed to a neutral solution pH, and their optical properties are shown in Figure 13. Under crossed polarizing microscope, these polymer particles exhibited radial optical anisotropy (Maltese cross), indicating that they have radial internal structure and pore structure.

[0081] Example 3 0.6 g of cellulose nanocrystals and 0.9 g of agarose are dispersed in 13.5 g of water and stirred at 80 ° C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing SPAN80 (mass percentage concentration: 10%) and emulsified by stirring at 80 ° C for 2 minutes, then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and 800 μl of an aqueous solution (15 ml) of 1,4-butanediol diglycidol, a crosslinking agent, is added and reacted with stirring for 12 hours. 800 μl of an aqueous solution containing 40 wt % sodium hydroxide and 5 wt % sodium borohydride is added to the above reaction solution and reacted with stirring for 8 hours. 800μl of epoxycyclopropane was mixed with 800μl of an aqueous solution containing 40wt% sodium hydroxide and 5wt% sodium borohydride, added to the reaction solution, and stirred for another 12 hours. The resulting polymer particles were washed to a neutral solution pH. Under crossed polarizing microscope, these polymer particles showed radial optical anisotropy (Maltese cross), indicating that they have a radial internal structure and pore structure.

[0082] Example 4 0.4g of cellulose nanocrystals is dispersed in 9.6g of water and stirred at room temperature to form a suspension. 1g of the suspension is taken, and 10g of soybean oil containing 2% PGPR (mass percentage concentration: 2%) is added thereto, and emulsified by stirring for 3 hours to form a dispersion containing milky droplets. 400μl of 1,4-butanediol diglycidol, a crosslinking agent, is dispersed in 900μl of water, slowly added to the above dispersion, and stirred and reacted at room temperature for 12 hours. 400μl of an aqueous solution containing sodium hydroxide (40wt%) and sodium borohydride (5wt%) is added to the above reaction solution, and stirred and reacted for 12 hours. Furthermore, 400ml of epoxy chloropropane and 400μl of an aqueous solution containing 40wt% sodium hydroxide and 5wt% sodium borohydride are added, and stirred and reacted for 12 hours. The obtained polymer particles are washed to a neutral solution pH. Under crossed polarizing microscopy, these polymer particles exhibit radial optical anisotropy (Maltese cross), indicating that they have radial internal structure and pore structure.

[0083] Example 5 0.4g of cellulose nanocrystals is dispersed in 9.6g of water and stirred at room temperature to form a suspension. 1g of the suspension is taken, 10g of soybean oil containing PGPR (mass percentage concentration: 15%) is added thereto, and emulsified by stirring for 3 hours to form a dispersion containing milky droplets. 100μl of 1,4-butanediol diglycidol, a crosslinking agent, is dispersed in 900μl of water and slowly added to the above dispersion and stirred at room temperature for 12 hours. 100μl of an aqueous solution containing sodium hydroxide (40wt%) and sodium borohydride (5wt%) is added to the above reaction solution and stirred for 12 hours. 100ml of epoxy chloropropane is further added and stirred for 12 hours. The obtained polymer particles are washed to a neutral solution pH. Under cross-polarized light microscope, these polymer particles show radial optical anisotropy (Maltese cross), indicating that they have a radial internal structure and pore structure.

[0084] Example 6 0.4g of cellulose nanocrystals and 0.2g of agarose are dispersed in 9.4g of water and stirred at 90°C to form a suspension. The above suspension is added to 100g of liquid paraffin containing Tween 80 (mass percentage concentration: 10%), emulsified by stirring at 80°C for 2 minutes, and then cooled to lower the temperature to form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and then 10ml of a dioxane solution containing 500μl of crosslinker 1,4-butanediol diglycidyl ether is added and reacted with stirring for 2 hours. 500μl of an aqueous solution containing sodium hydroxide (40wt%) and sodium borohydride (5wt%) is added to the above reaction solution and reacted with stirring for 8 hours. Furthermore, 500μl of epoxypropane and 500μl of an aqueous solution containing sodium hydroxide (40wt%) and sodium borohydride (5wt%) are mixed, added to the reaction solution, and reacted with stirring for 12 hours. The obtained polymer particles are washed until the solution pH becomes neutral. Its optical properties are shown in Figure 14. Under crossed polarizing microscope, these polymer particles show local brightness, indicating that their internal structure and pore structure are partially ordered. This may be because when Tween 80 is used as an emulsifier, the structural change ability of cellulose nanocrystals is relatively weak, and it is not enough for the emulsion droplets to show radial optical anisotropy (Maltese black cross), but only to cause the phenomenon of localized birefringence.

[0085] Comparison 1 0.6 g of cellulose nanocrystals and 0.3 g of agarose are dispersed in 14.1 g of water and stirred at 80 ° C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing Tween 80 with a mass percentage concentration of 10%, emulsified by stirring at 80 ° C for 2 minutes, and then cooled to reduce the temperature to form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and 800 μl is added to a 15 ml solution of pentaerythritol glycidyl ether, a 4-functional crosslinker, and reacted with stirring for 12 hours. 800 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) is added to the above reaction solution and reacted with stirring for 8 hours. Furthermore, 800 μl of epoxypropane and 400 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) are mixed, added to the reaction solution, and reacted with stirring for 12 hours. The resulting polymer particles are washed with warm water and adjusted to a neutral solution pH. Under crossed polarizing microscopes, these polymer particles show localized brightness, indicating that their internal structure and pore distribution are partially ordered. Under polarizing microscopes, these polymer particles show different brightness in different regions, indicating that their internal structure and pore structure are partially ordered.

[0086] Comparison 2 0.6 g of cellulose nanocrystals and 0.3 g of agarose are dispersed in 14.1 g of water and stirred at 80 ° C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing 10% SPAN80 by mass percentage concentration, emulsified by stirring at 80 ° C for 2 minutes, and then cooled to reduce the temperature to form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed and added to 15 ml of an aqueous solution containing 0.4 g of the bifunctional crosslinker 1,4-butanediol diglycidol and stirred for 12 hours. An aqueous solution containing 400 μl of sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) is added to the above reaction solution and stirred for 8 hours. 0.4 g of epoxypropane is mixed with 400 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%), added to the reaction solution, and stirred for 12 hours. The resulting polymer particles are washed with warm water and adjusted to a neutral solution pH. Due to the low content of crosslinking agent, the resulting particles have a low degree of crosslinking and relatively low pressure resistance.

[0087] Comparison 3 0.6 g of cellulose nanocrystals and 0.3 g of agarose are dispersed in 14.1 g of water and stirred at 80 ° C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing 10% SPAN80 by mass percentage concentration, emulsified by stirring at 80 ° C for 2 minutes, and then cooled to reduce the temperature to form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed and added to 15 ml of an aqueous solution containing 9.6 g of the bifunctional crosslinker 1,4-butanediol diglycidol and stirred for 12 hours. An aqueous solution containing 400 μl of sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) is added to the above reaction solution and stirred for 8 hours. 9.6 g of epoxypropane is mixed with 400 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%), added to the reaction solution, and stirred for 12 hours. The resulting polymer particles are washed with warm water and adjusted to a neutral solution pH. Due to the excessive content of crosslinker, the produced polymer particles are prone to adhesion and aggregation, and chemical bonds are formed between the crosslinker and water, resulting in a low particle yield.

[0088] Comparison 4 0.6 g of cellulose nanocrystals and 0.3 g of agarose are dispersed in 14.1 g of water and stirred at 60 ° C to form a suspension. The above suspension is added to 150 g of liquid paraffin containing 10% SPAN80 by mass percentage concentration, emulsified by stirring at 60 ° C for 2 minutes, and then cooled to reduce the temperature to form a dispersion containing solidified emulsion droplets. After washing to remove the emulsifier and liquid paraffin, the resulting gel is weighed, and 15 ml of an aqueous solution containing 800 μl of the crosslinker bifunctional crosslinker 1,4-butanediol diglycidyl ether is added and reacted with stirring for 12 hours. 40 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) is added to the above reaction solution and reacted with stirring for 8 hours. Mix 800μl of epoxypropane with 40μl of an aqueous solution containing sodium hydroxide (40wt%) and sodium borohydride (5wt%), add to the reaction solution, and react with stirring for 12 hours. The resulting polymer particles are washed with warm water and adjusted to a neutral solution pH. Under the condition of 60℃, the mixture of cellulose nanocrystals and agarose is incomplete, the liquid crystal phase is not formed, and the crosslinking agent does not penetrate well into the pores of the particles, so the crosslinking reaction occurs only on the surface of the particles, and therefore the crosslinking effect is low.

[0089] The particles obtained in Examples 1 to 3 and Control Examples 1, 2, and 4 were all sieved to retain polymer particles with particle sizes between 40 micrometers and 150 micrometers, and then processed by homogenization to fill a glass chromatography column. Using a protein chromatograph device, the corresponding pressure values ​​were obtained by changing different flow rates, and a pressure-flow rate curve was drawn and shown in Figure 16. This is to investigate the critical pressure value of this packing material. From the first half of the curve, it can be seen that as the flow rate increases, the pressure in the chromatography column gradually increases, and the flow rate and pressure are in a linear relationship. However, when the break point is reached, the pressure in the chromatography column no longer increases linearly with the flow rate, and shows a sharp increase. This means that the shape of the polymer particles in the chromatography column is broken or the filter at the end of the column is clogged.

[0090] In this description, the description is based on the implementation methods, but each implementation method does not include a single independent technical solution. Such a description method is merely for clarity. Those skilled in the art can consider this description as a whole and appropriately combine the technical solutions of each implementation method to form additional implementation methods that can be understood by those skilled in the art.

[0091] The above detailed description is merely a specific description of the possible embodiments of the present invention, and is not provided to limit the protection scope of the present invention. Any equivalent embodiment or modification that does not depart from the technical spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. Porous polymeric particles formed by crosslinking an at least partially crosslinkable polymeric material comprising rigid nanoparticles, at least one of said rigid nanoparticles having a non-spherically symmetric shape in solution, said rigid nanoparticles forming at least a partially essentially ordered structure within the polymeric particle; the rigid nanoparticles are biopolymers, the biopolymers being cellulose nanocrystals; The porous polymer particles further contain a crosslinking agent.

2. 2. The polymer particle of claim 1, wherein the polymer particle has one or more regions therein that contain at least partially essentially ordered rigid nanoparticles, and the molecular arrangement between the multiple regions is unrelated, related, or partially related.

3. A polymer particle as described in claim 1, characterized in that the cellulose nanocrystals have a non-spherical symmetric shape in solution, and the non-spherical symmetric shape is rod-shaped, strip-shaped, plate-shaped, needle-shaped, or linear, with the characteristic direction being the long axis direction of the molecule.

4. Polymer particles as described in claim 1, characterized in that the cellulose nanocrystals have a non-spherical symmetric shape in solution, and the non-spherical symmetric shape is disk-shaped with a characteristic direction perpendicular to the planar direction.

5. 5. The polymer particle according to claim 4, wherein the entire interior of the polymer particle is orderly arranged.

6. The polymer particle according to claim 5, characterized in that the characteristic direction is distributed essentially along the radial direction of the particle, along the bipolar axis direction of the particle, or in multiple concentric circles within the particle.

7. 5. The polymer particle according to claim 4, wherein in the essentially ordered local regions, the characteristic directions are essentially parallel, fan-shaped, or spirally aligned.

8. A polymer particle as described in claim 1, characterized in that the cellulose nanocrystals have chirality.

9. 9. The polymer particle according to claim 8, wherein the chiral biopolymers include a biopolymer having left-handed chirality and a biopolymer having right-handed chirality.

10. The polymer particle according to claim 1, wherein the cellulose nanocrystals have a length of 20 to 1000 nm and a width of 2 to 100 nm.

11. 2. The polymer particle according to claim 1, wherein the cellulose nanocrystals have a major axis ratio of 2:1 to 200:

1.

12. The polymer particle of claim 1, wherein the polymer particle comprises a polysaccharide compound that is not spherically symmetric in solution, and the polysaccharide compound copolymerizes with the rigid nanoparticles to form the polymer particle.

13. 13. The polymer particle according to claim 12, wherein the polysaccharide compound is at least one selected from the group consisting of agar, agarose, starch, chitin, and alginic acid.

14. Polymer particles as described in claim 1, characterized in that the crosslinking agent is one or more selected from epoxy compounds, diacyl chloride compounds, and halogen compounds.

15. 13. The polymer particle according to claim 12, wherein the mass ratio of the rigid nanoparticles to the polysaccharide compound is 1:10 to 50:

1.

16. 16. The polymer particles according to any one of claims 12, 13 and 15, characterized in that after dissolving the rigid nanoparticles and the polysaccharide compound in water, the resulting dispersion has a solid content of 2 to 90%.

17. 16. The polymer particle according to claim 12, wherein the volume ratio of the rigid nanoparticles to the polysaccharide compound is 1 to 10% of the total polymer particle.

18. A polymer particle described in any one of claims 12, 13 and 15, characterized in that the amount of the crosslinking agent is 10% to 100% of the total mass of the biopolymer and polysaccharide compound.

19. Polymer particles as described in claim 18, characterized in that the crosslinking agent is one or more selected from cumic acid glycerin ether, 1,4-butanediol diglycidyl ether, and 1,4-butanediol monoglycidyl ether.

20. The polymer particles according to claim 14, wherein the epoxy compound is a glycerin ether-type small molecule organic compound.

21. 2. The polymer particles according to claim 1, wherein the particle size of the polymer particles is in the range of 1 to 500 μm.

22. A polymer particle as described in claim 1, wherein a pore structure exists inside the polymer particle, at least a portion of the pores constituting the pore structure have a structure that is basically ordered at least locally, and the arrangement direction of the pores basically coincides with the arrangement direction of the rigid nanoparticles.

23. 23. The polymer particle according to claim 22, wherein the pore diameter is 1 to 1000 nm.

24. 23. The polymer particle according to claim 22, characterized in that, at least in a local region, the orientation and positional arrangement of both at least a local segment of a pore and at least a local segment of an adjacent pore has a certain regularity.

25. 25. The polymeric particle of claim 24, wherein, at least in a localized region, the pores of at least a localized segment are essentially aligned in a parallel, fan-shaped, or spiral manner.

26. (1) dispersing at least partially crosslinkable rigid nanoparticles in water to form a dispersed phase solution, wherein the rigid nanoparticles are biopolymers, and the biopolymers are cellulose nanocrystals having a non-spherically symmetric shape in solution; (2) dispersing the dispersed phase solution in a continuous phase containing an emulsifier to form emulsion droplets containing rigid nanoparticles; (3) A method for producing polymer particles, comprising the step of adding a crosslinking agent to crosslink the biopolymers in the milk droplets to form polymer particles.

27. 27. The method of claim 26, wherein step (1) comprises adding a polysaccharide compound.

28. The method of claim 27, wherein the polysaccharide compound is at least one selected from agar, agarose, starch, chitin, and alginic acid.

29. 27. The method of claim 26, wherein the emulsifier has a mass concentration in the continuous phase of 2% to 20%.

30. the emulsifier is one or more of a SPAN surfactant, a Tween emulsifier, cetyl polyethylene glycol, and polyglyceryl ricinoleate; The method according to claim 26, wherein the crosslinking agent is one or more selected from the group consisting of epoxy compounds, diacyl chloride compounds, and halogen compounds.

31. 27. The method of claim 26, wherein the continuous phase is one or more selected from heptane, hexadecane, liquid paraffin, or soybean oil.

32. 27. The method of claim 26, wherein step (3) is carried out under alkaline conditions.

33. 26. The polymer particles according to any one of claims 1 to 15 and 21 to 25, wherein the polymer particles are used as a stationary phase in chromatography.

34. 27. The method according to claim 26, wherein in step (1), after forming the dispersed phase solution, a crosslinker is directly added to the dispersed phase solution to carry out in situ polymerization without emulsification, and the resulting product is used as the entire column stationary phase.

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