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 a patent application filed on January 27, 2022, bearing application number CN202210098560.X and entitled "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 interiors have a structure in which, at least locally, constituent molecules or both constituent molecules and pore channels are essentially ordered, and a method for producing the same. [Background technology]

[0003] Microspheres are inorganic or organic polymeric materials or polymer composites with nanometer to micrometer diameters and essentially spherical shapes. They can be solid, hollow, or porous. Applications of microspheres are closely related to daily life, including paints, cosmetics, and precision electronics. They are also widely used in high-value-added products such as separation chromatography media. Common microspheres include silica-based inorganic microspheres, biopolymer-based microspheres, and polymer-based microspheres. Microspheres, especially agarose-based biopolymer-based microspheres, are most widely used in ion-exchange chromatography, affinity chromatography, and hydrophobic chromatography columns. They are used as consumables, fillers, and polymeric chromatography supports for the separation and purification of small molecules and biologically active substances.

[0004] Due to their widespread use and great success in biopharmaceutical separations, there is a significant amount of relevant patent literature regarding biopolymer microspheres, including agarose-based microspheres. The earliest relevant literature includes Hjerten, S. Biochim. Biophys. Acta 1964, 79:393-398; and Bengtsson et al., S. Biochim. Biophys. Acta 1964, 79:399. While the first agarose microsphere-related patent is U.S. Pat. No. 4,647,536, polysaccharide microspheres for chromatography columns have appeared in academic and patent literature for some 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 protein-accessible surface area and determines protein separation performance, such as loading capacity and resolution. Therefore, when polysaccharide gel spheres are used as a chromatography column medium, their internal pore size structure, size and distribution, sphere size and distribution, shape, and mechanical performance significantly affect separation performance and speed. However, polysaccharide gel balls produced by currently known mechanical stirring, homogeneous emulsification, and membrane emulsification methods lack control over their internal pore size structure. Furthermore, given their typical flexibility, current polysaccharide gel microspheres are relatively soft and have limited pressure resistance. As a result, corresponding chromatography columns are limited to low-speed biological protein separation applications. Furthermore, the most commonly used raw material for agarose microspheres is obtained from seaweed through a multi-step extraction process, making it a relatively high-cost raw material that is not suitable for large-scale industrial 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, making the chromatographic conditions for these active substances relatively harsh. Generally, excellent mechanical properties and chemical stability, as well as efficient separation efficiency, are required; otherwise, denaturation and degradation of the separated substances will occur.

[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, whose raw material costs are low, and which have a certain strength. Summary of the Invention

[0007] The object of the present application is to provide polymeric particles having an internal structure that is essentially ordered at least locally, thereby meeting the above requirements using a combination of material synthesis and manufacturing methods.

[0008] To achieve the above object, the present application provides porous polymer particles. The polymer particles are formed by crosslinking at least a portion of a crosslinkable polymer material containing rigid nanoparticles, wherein at least one type of rigid nanoparticle has a non-spherically symmetric shape in solution, and the rigid nanoparticles form a substantially ordered structure in at least a portion of the polymer particle. At the same time, the internal pores formed by crosslinking also at least partially inherit the same substantially ordered structure, forming at least locally a substantially ordered structure.

[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 fulfills one or more of the above market needs and may address other improvements.

[0010] The primary objective of the present application is to provide porous polymeric particles, which are at least partially comprised of cross-linkable polymeric materials containing rigid nanoparticles, said rigid nanoparticles forming at least partially an essentially ordered structure within the polymeric particles.

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

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

[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 object, the present application provides porous polymeric particles, which are at least partially composed of a crosslinkable polymeric material containing rigid nanoparticles, at least one of which has a non-spherically symmetric shape in solution, and which form, at least locally, an essentially ordered structure within the polymeric particle.

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

[0016] In a further refinement of the present application, there are regions within the polymeric particle 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] In a further refinement of the present application, the shape of the non-spherically symmetric rigid nanoparticles is rod-like, strip-like, flake-like, needle-like, or wire-like, with the characteristic direction being the long axis of the molecule.

[0018] A further refinement of the present application is that the non-spherically symmetric 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 are generally internally ordered.

[0020] As a further refinement of the present application, the characteristic directions may be essentially distributed along the radial direction of the particle, distributed along the bipolar axis direction of the particle, and 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 peptides, proteins, nucleic acids, polysaccharides, and lipids.

[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 left-handed chiral biopolymers and right-handed chiral biopolymers.

[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 diameter ratio of 2:1 to 200:1.

[0028] In 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] In 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 improvement 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 2% to 90%.

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

[0033] In a further improvement of the present application, the polymer particles may comprise a cross-linking agent, and the amount of the cross-linking agent is 10% to 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] In a further refinement of the present application, the epoxy compound may be selected from small molecule organic compounds 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] On the other hand, the present application discloses porous polymer particles formed at least partially by a crosslinkable polymer material. The polymer particles are crosslinked by at least one rigid nanoparticle and have an internal pore structure. The at least one type of rigid nanoparticle has a non-spherical symmetric shape in solution, and the pore structure has a structure that is at least locally basically ordered, and the arrangement direction of the pore structure is Rigid nanoparticles This basically matches the arrangement direction of

[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 step of adding a cross-linking agent 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] In 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] A further improvement of the present application is that the emulsifier comprises one or more of a SPAN type surfactant, a Tween type emulsifier, a sialoethylene glycol, and a polyglycerol phosphate ester.

[0047] A further refinement of the present application is that 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 separation using the 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. [Effects 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 rigid nanoparticles form a pore structure that is essentially ordered, at least locally, within the particles. Furthermore, polymer particles made using rigid nanoparticles have liquid crystal orientation and uniform radial alignment, at least locally, resulting in uniform particle surface loading, reduced deformation, and excellent mechanical properties and biocompatibility. Furthermore, the porous polymer microspheres disclosed in the present application are derived from nanofiber crystalline materials, which are the most abundant, environmentally friendly, and have the most mature extraction technology in nature, significantly reducing the cost of chromatographic consumables. [Brief explanation 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. [Figure 2]Figure 2 consists of three images: (a) shows a schematic diagram and example structural formula of a rod-shaped structure of a biopolymer, (b) shows a schematic diagram and example structural formula of a bow-shaped (banana-shaped) structure of a biopolymer, and (c) shows a schematic diagram and example structural formula of a disk-shaped structure of a biopolymer. [Figure 3] Figure 3 consists of eight images. (a), (c), (e), and (g) show the arrangement of CNC nanorods when the CNC dispersion concentration is less than 3%, 3.5%-4%, 4%, and 5%, respectively. (b), (d), (f), and (h) are cross-polarized microscope images when the CNC dispersion concentration is less than 3%, 3.5%-4%, 4%, and 5%, respectively. [Figure 4] Figure 4 shows a schematic diagram of the formation process of soluble liquid crystal droplet emulsion. [Figure 5] Figure 5 shows two binding modes of rigid nanoparticles in polymer particles. [Figure 6] Figure 6 shows a schematic diagram of the chiral arrangement of biopolymers formed inside polymer particles. [Figure 7] Figure 7 is composed of four images: (a) is a cross-sectional view of a polymer particle 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 polymer particles of some examples. [Figure 8] Figure 8 consists of four images: (a) a schematic diagram of a radial structure of polymer particles; (b) a schematic diagram of a dipolar structure of polymer particles; (c) a schematic diagram of a ring structure of polymer particles; and (d) 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 polymeric 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 completely ordered polymer particles; (b), (d), and (f) are cross-polarized microscopy images of the disordered, partially ordered, and completely 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 microscope images of polymer particles produced according to Example 1 of the present application. [Figure 13] FIG. 13 shows cross-polarized microscope images of polymer particles produced according to Example 2 of the present application. [Figure 14] FIG. 14 shows a cross-polarized microscope image 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 the pressure-flow curves of the chromatography columns manufactured according to some examples and comparative examples. DETAILED DESCRIPTION OF THE INVENTION

[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 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 need for engineers to perform creative work are included in the scope of protection of the present application.

[0054] One method for producing porous microspheres for use in chromatography columns involves dispersing polysaccharide molecules (e.g., agarose) in water and then using an appropriate emulsification technique to form tiny aqueous droplets containing the polysaccharide suspended in an oil phase. Referring to Figure 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. Because the polysaccharide molecules are randomly arranged in water, the internal pore channels of the resulting gel spheres are also randomly arranged. Furthermore, given the inherent flexibility of polysaccharide molecules, these cross-linked spheres are typically relatively flexible. In nature, many biological macromolecules exhibit rigid, non-spherically symmetric shapes when dispersed in water or alone. For example, as shown in Figure 2, these include (a) rod-shaped structures, such as tobacco mosaic virus (TMV), deoxyribonucleic acid (DNA), and nanocrystalline cellulose (CNC, shown in the right-hand diagram of Figure 2(a)), (b) arcuate (banana-shaped) structures, such as the P52C molecule (shown in the right-hand diagram of Figure 2(b)), and (c) disk-shaped structures, such as 2,3,6,7,10,11-hexa(1,4,7-trioxooctane-phenylene[9,10]anthracene7) (TP6EO2M, shown in the right-hand diagram of Figure 2(c)). Tobacco mosaic virus is a rigid, rod-shaped biological nanoparticle that has been widely studied in liquid crystal physics. According to lyotropic liquid crystal theory, when such rigid nanoparticles are dispersed in a solvent, they may align randomly in the solvent depending on the concentration and properties of the rigid nanoparticles. Alternatively, with increasing concentration of rigid nanoparticles, ordered molecular arrangements of specific lyotropic liquid crystals are formed, including nematic phases (e.g., tobacco mosaic virus nanomaterials), smectic phases, cholesteric phases, and columnar phase liquid crystals. Orderly arranged liquid crystal materials typically exhibit optical birefringence. Therefore, 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, an appropriate amount of rigid nanoparticles having aspherical symmetry are uniformly dispersed in a solvent 401, either alone or together with an appropriate 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). This 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 emulsifying them by mechanical agitation (Figure 4(c)). This results in an emulsion containing lyotropic liquid crystal droplets 405 suspended in the solvent 402. The monomers or oligomers and rigid nanoparticles having polymerizable functional groups are polymerized to form a polymer network structure, resulting in polymeric 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 polymer microspheres in which the molecules are at least locally ordered and the pore channels are further ordered.

[0058] Specifically, cellulose nanocrystals (CNCs) with the appropriate aspect ratio and size distribution are biopolymers that possess a certain rigidity and form a lyotropic liquid crystalline phase in a specific solvent (water). Based on the spirit of this invention, when the biopolymer is cellulose nanocrystals (CNCs) and their concentration reaches a critical value, the CNC molecules may self-assemble, forming an ordered array, and a liquid crystalline phase may appear. As shown in Figures 3(a) and (b), for CNC nanomaterials with a specific aspect ratio, when the CNC dispersion concentration is less than 3%, the CNCs are irregularly arranged within the dispersion, and in this state, they do not form a liquid crystalline state. The corresponding solvent does not exhibit birefringence under an optical microscope with the polarizer P and polarizer A perpendicular to each other, resulting in a uniformly dark image. As shown in Figures 3(c) and (d), when the CNC dispersion concentration is between 3.5% and 4%, wavy ordered arrays may occur due to insufficient dispersion or local concentration fluctuations. As shown in Figures 3(e) and (f), when the concentration of the CNC dispersion exceeds a critical concentration of 4%, the biopolymers form a regular arrangement in the liquid crystal phase, forming an ordered structure. As shown in Figures 3(g) and (h), the chirality of the CNC biopolymers is evident when the CNC dispersion concentration is approximately 5%, forming a cholesteric molecular arrangement with a helical structure. On the other hand, when the CNC dispersion concentration exceeds 6%, the arrangement of the biopolymers becomes more ordered. As the aspect ratio and uniformity of the CNC nanomaterials change, the critical concentration also changes accordingly. At the same time, the cellulose nanocrystal (CNC) biopolymers possess chirality, and the ordered molecular arrangements they form form liquid crystal molecular arrangements with a helical structure, such as a cholesteric phase, as shown in Figure 6.

[0059] FIG. 7 is based on a published application that includes polymer particles with a porous structure. Specifically, FIG. 7(a) shows a cross-sectional view of a portion of the interior of a polymer particle along its diameter. The biopolymers may maintain at least a partial ordered arrangement even after cross-linking, and the pores formed due to the molecular arrangement may be arranged in a locally regular pattern (see FIG. 7(b)). The biopolymer solution shown in FIG. 7(a) emulsifies in a locally ordered state to form emulsion droplets. The biopolymers 201 in the emulsion 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 further cross-linking occurs to form polymer particles, their internal structure at least partially retains its previous ordered structure. At the same time, as shown in FIG. 7(b), the pores 701 formed between the biopolymer arrays also inherit essentially the same ordered structure, resulting in the pores of the polymer particles forming an essentially ordered structure at least locally. The term "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 pore and at least a local segment of an adjacent pore have a certain regularity. Specifically, at least in a local region, at least a local segment of a pore and at least a local segment of an adjacent pore are essentially arranged in a parallel, fan-shaped, or spiral pattern. As shown in Figure 7(d), a pore diameter of 1 to 1000 nm is selected as a preferred embodiment.

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

[0061] Within the scope of overall order, these basic ordered structures may form some special structures. For example, as shown in FIG. 8(a), a radial structure (characteristic directions aligned in a regular radial direction) may be formed, with pores 801 regularly arranged toward the center. Also, as shown in FIG. 8(b), a dipole-type structure (characteristic directions aligned in an orderly manner along the dipole axis) may be formed, with pores 802 ordered along the dipole axis. Furthermore, as shown in FIG. 8(c), a ring-shaped structure (characteristic directions aligned in multiple concentric circles) may be formed, with pores 803 ordered in a concentric circle. However, this application is not limited to this, and other ordered structures are also possible. At the same time, these special structures create special optical phenomena under a polarized microscope due to the optical birefringence properties typically possessed by biopolymers. For example, as shown in FIG. 8(a), the characteristic directions of biopolymers are radially ordered within a milk droplet, and the internal structure and pores of the formed polymer particles are also radially ordered, 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 region, as shown in Figure 7(a), the interior of the polymer particle contains part B shown in Figure 7(b) and part C shown in Figure 7(c). Part B is a local region in which the characteristic directions of the biopolymer are basically ordered, while part C is a region in which the characteristic directions are arranged in a disordered manner. Ordered pores 701 and disordered pores 702 are simultaneously formed within the polymer particle. At this time, the polymer particle may not have a specific structure, but its characteristic directions are still regularly arranged over a small range, and therefore coloration can be seen under a crossed polarizing microscope.

[0063] By using the manufacturing method proposed by the present invention, at least partially ordered droplets of biopolymers can be obtained with different sizes, which can be 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 typically 1-500 micrometers in an aqueous solvent, with a more preferred range being 5-150 micrometers. If the particle size of the polymer particles is too small, the counter 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, polymer particles 410 are formed by crosslinking biomolecules 201 at least partially contained in a crosslinkable polymer material. At least one biomolecule has a non-spherically symmetric shape in solution. For example, as shown in FIG. 2(a), biomolecule 201 may have a rod-like shape characterized by the long axis direction of the molecule. Alternatively, as shown in FIG. 2(b), biomolecule 203 may have an arch-like (banana-like) shape characterized by the long axis direction of the molecule. As shown in FIG. 2(c), biomolecule 205 may have a disk-like shape with a characteristic direction 206 perpendicular to the planar direction. Other non-spherically symmetric shapes, such as plate-like, needle-like, and wire-like shapes, may also be employed, but the present application is not limited thereto.

[0065] The biomolecules, whether or not they have a non-spherically symmetric shape, are selected from at least one of 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 distributed in living organisms and generally have a rod-like or flat shape in solution. As a preferred embodiment, as shown in Figure 6, biopolymers with non-spherical symmetry may or may not have chiral properties. Furthermore, biopolymers with chiral properties include left-handed and right-handed biopolymers. The liquid crystal phase they form forms a helical molecular arrangement of cholesterol phase. As shown in the corresponding part of the scanning electron microscope image indicated by the arrow in Figure 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 diameter ratio, making it easier 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 diameter ratio is 1:5 to 1:200.

[0067] As shown in Figure 7(b), the polymeric particles may further include polysaccharide compounds 101 that do not have a non-spherically symmetric shape. These polysaccharide compounds are copolymerized with biopolymers to form the polymeric particles. These polysaccharide compounds may be selected from at least one of 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, polysaccharide compounds are fluid, gel-like dispersions. After emulsification, they form emulsion droplets. Through processes such as cooling, hardening, and aging, the polysaccharide compounds 101 form double helical structures from single chains, enter a bound state, and ultimately form stable solid particles, as shown in Figure 7(b). While these polysaccharide compounds may not self-assemble in solution, they can acquire order through various interactions, including interactions with biopolymers and comprehensive hydrogen bonding, leading to the formation of ordered arrays based on the arrangement of the biopolymers. At the same time, at certain concentrations, biopolymers may become partially ordered, forming a liquid crystal phase, allowing the polysaccharide compounds to arrange themselves using the arrangement of larger molecules as a template. These polysaccharide compounds and biopolymers can then be further copolymerized with the aid of a crosslinker to form stable particle structures, further improving the pressure resistance of the formed polymer particles without compromising their ordered structure. At the same time, during the polymer particle production process, polysaccharide compounds (e.g., agar) can be used to solidify the emulsified emulsion droplets by cooling, providing structural support for the subsequent crosslinking polymerization, simplifying the manufacturing 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 may include a method 900 for preparing polymer particles. This method may 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 the specific biopolymer, such as its length ratio, size distribution, and concentration in water, the biopolymer can be adjusted to be in an ordered or disordered state in the solvent. In a preferred embodiment, the solids content of the resulting dispersion of the mixture of biopolymer and polysaccharide compound is 2% to 90%, and the volume of the biopolymer and the polysaccharide compound relative to the total volume of the polymer particles is 1% to 10%. Furthermore, the mechanical properties of the produced polymer particles, particularly their 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 an even more preferred embodiment, the mass ratio of the biopolymer to the polysaccharide compound is 1:1 to 15:1.

[0071] Next, method 900 includes a technique for emulsifying the dispersion to form emulsion droplets 902. There are various emulsification methods, including membrane emulsification. Membrane emulsification refers to a method in which the dispersed phase passes directly through the pores of a microporous membrane into the continuous phase during the emulsification process, forming emulsion droplets at the ends of the pores and then extruding drop-by-drop. Another common emulsification process involves adding an emulsifier to a continuous phase containing a dispersed phase solution of biopolymers and polysaccharide compounds, thereby forming emulsion droplets containing the biopolymers. Examples of emulsifiers include sorbitan ester (SPAN) surfactants, such as sorbitan monopalmitate (SPAN 40), sorbitan monostearate (SPAN 60), sorbitan tristearate (SPAN 65), sorbitan monooleate (SPAN 80), and sorbitan trioleate (SPAN 85). Alternatively, Tween emulsifiers such as Tween 20, Tween 40, Tween 60, Tween 80, or Tween 85, or cetyl polyethylene glycol or polyglycerol ricinoleate (PGPR), can be used. The continuous phase is an oily substance that is immiscible with the aqueous phase but dissolves the emulsifier, such as normal alkanes (e.g., n-hexane, n-hexadecane, etc.), liquid paraffin, or animal or vegetable oils (e.g., soybean oil). The emulsifier helps form a uniform emulsion droplet dispersion and simultaneously promotes the ordered arrangement of biopolymers within the droplets. By controlling the temperature and drying time, different orientations of the droplets can be produced, which in turn leads to the production of particles with corresponding orientations. Figures 10(a) and (b) show that the nanorods inside the particles are mostly randomly arranged, with some regions being ordered. Under a polarized light microscope, a few bright areas are observed, resulting in a non-uniform dark appearance across the entire image. In Figures 10(c) and (d), some regions of the nanorods inside the particle are randomly arranged, while others are ordered, and birefringence begins to appear slightly under polarized light microscopy. In Figures 10(e) and (f), the nanorods inside the particle are arranged in multiple concentric circles, but other ordering methods are also acceptable. Typical radial optical anisotropy (Maltese cross) is observed under polarized light microscopy.In 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. As a dispersion method, a general emulsification dispersion method such as a stirring method, an ultrasonic method, or a shaking method can be used.

[0072] Finally, the method 900 also includes a step of cross-linking the milk droplets 903. In particular, a cross-linking agent is added 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 an epoxy compound, a diacyl chloride, or a halogen compound. 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] Because there are many hydroxyl groups on the surface of biopolymers, further cross-linking polymerization can be carried out with the aid of a cross-linking agent to form stable polymer particles. At the same time, the cross-linking process strengthens the pore structure formed during the emulsification process. Because the biopolymers are ordered before cross-linking, the final pore structure tends to have a similar ordered arrangement, resulting in the formation of an ordered internal structure and pore structure. In a preferred embodiment, cross-linking is carried out under alkaline conditions, which is expected to make the cross-linking agent more effective.

[0076] The aforementioned polymer particles have a porous structure and can be used as a stationary phase in biochemical separations, particularly chromatography. Chromatography typically employs column-based separation techniques, specifically packing polymer particles into a chromatography column. A mobile phase containing different components is then passed through the column. Separation of substances is achieved by utilizing characteristics such as differences in the size of the molecules to be separated and purified, as well as differences in the interactions between the molecules and the stationary phase. Because polymer particles are made from biological macromolecules, they have a strong affinity with living organisms and are particularly suitable for the separation of various biological compounds. Furthermore, the ordered internal structure and pore structure of polymer particles ensure that the molecules to be separated have a regular path to enter the stationary phase, thereby significantly improving separation efficiency.

[0077] Furthermore, 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, after the formation of the dispersed phase solution, a crosslinking agent is directly added to carry out in situ polymerization without performing an emulsification operation, and the resulting 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 ratios described are mass ratios.

[0079] Example 1 0.6 g of cellulose nanocrystals and 0.06 g of agarose were dispersed in 14.34 g of water and stirred at 90 °C to form a suspension. The suspension was added to 150 g of liquid paraffin containing 10% SPAN 80 (mass percentage) and emulsified by stirring at 80 °C for 2 minutes. The mixture was then cooled to a lower temperature and form a dispersion containing solidified emulsion droplets. The suspension was then emulsified in 150 g of liquid paraffin (containing 10% SPAN 80) by stirring at 80 °C for 2 minutes. The mixture was then cooled to form a dispersion containing emulsified emulsion droplets. Figure 11(a) shows that the cellulose nanocrystals and agarose molecules are arranged in multiple concentric circles within the emulsion droplets, and Figure 11(b) shows that these emulsion droplets form a Maltese cross shape under a polarized microscope. After washing to remove the emulsifier and liquid paraffin, the resulting gel was weighed and 500 μL of an aqueous solution (10 mL) of cuminic acid glycerol ether (a crosslinker) was added and stirred for 12 hours. 500 μL of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride was added to the reaction solution and stirred for 8 hours. 500 μL of epoxychloropropane was mixed with 500 μL of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride, 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 12. Under a polarizing microscope, these polymer particles exhibited radial optical anisotropy (Maltese cross pattern), indicating a radial internal structure and pore structure.

[0080] Example 2 0.4 g of cellulose nanocrystals and 0.2 g of agarose were dispersed in 9.4 g of water and stirred at 90 °C to form a suspension. The suspension was added to 100 g of liquid paraffin containing SPAN80 (mass percentage concentration: 10%) and emulsified by stirring at 80 °C for 2 minutes. The mixture was then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing, the emulsifier and liquid paraffin were removed. The resulting gel was weighed and added with 500 μl of the crosslinking agent 1,4-butanediol diglyceride. Diethyl etherAn aqueous solution (10 ml) containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride was added to the reaction solution and stirred for 12 hours. 500 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride was added to the reaction solution and stirred for 8 hours. 500 μl of epoxychloropropane was mixed with 500 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride, 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 microscopes, these polymer particles exhibit radial optical anisotropy (Maltese cross pattern), indicating a radial internal structure and pore structure.

[0081] Example 3 0.6 g of cellulose nanocrystals and 0.9 g of agarose were dispersed in 13.5 g of water and stirred at 80°C to form a suspension. The suspension was added to 150 g of liquid paraffin containing SPAN80 (mass percentage concentration: 10%) and emulsified by stirring at 80°C for 2 minutes. The mixture was then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing, the emulsifier and liquid paraffin were removed, and the resulting gel was weighed and added with 800 μl of the crosslinking agent 1,4-butanediol diglyceride. Diethyl ether Add 15 ml of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride to the reaction mixture and stir for 12 hours. Add 800 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride to the reaction mixture and stir for 8 hours. Mix 800 μl of epoxychloropropane with 800 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride, add to the reaction mixture, and stir for another 12 hours. Wash the resulting polymer particles until the solution pH is neutral. Under crossed polarizing microscopes, these polymer particles exhibit radial optical anisotropy (Maltese cross pattern), indicating a radial internal structure and pore structure.

[0082] Example 4 0.4 g of cellulose nanocrystals was dispersed in 9.6 g of water and stirred at room temperature to form a suspension. 1 g of the suspension was taken, and 10 g of soybean oil containing 2% PGPR (mass percentage concentration: 2%) was added to it, and the mixture was stirred for 3 hours to emulsify it, forming a dispersion containing emulsion droplets. 400 μl of the crosslinking agent 1,4-butanediol was added. Monoglycidyl ether The polymer particles were dispersed in 900 μl of water and slowly added to the above dispersion, followed by stirring at room temperature for 12 hours. 400 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) was then added to the above reaction solution, followed by stirring for 12 hours. 400 ml of epoxychloropropane and 400 μl of an aqueous solution containing 40 wt% sodium hydroxide and 5 wt% sodium borohydride were then added, followed by stirring for 12 hours. The resulting polymer particles were washed to a neutral solution pH. Under crossed polarizing microscopy, these polymer particles exhibited radial optical anisotropy (Maltese cross pattern), indicating a radial internal structure and pore structure.

[0083] Example 5 0.4 g of cellulose nanocrystals was dispersed in 9.6 g of water and stirred at room temperature to form a suspension. 1 g of the suspension was taken, and 10 g of soybean oil containing PGPR (mass percentage concentration: 15%) was added to it, and the mixture was stirred for 3 hours to emulsify it, forming a dispersion containing emulsion droplets. 100 μl of the crosslinking agent 1,4-butanediol was added. Monoglycidyl ether The polymer particles were dispersed in 900 μl of water and slowly added to the above dispersion, followed by stirring at room temperature for 12 hours. 100 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) was added to the above reaction solution, followed by stirring for 12 hours. 100 ml of epoxychloropropane was then added, followed by stirring for 12 hours. The resulting polymer particles were washed to a neutral solution pH. Under crossed polarizing microscopes, these polymer particles exhibited radial optical anisotropy (Maltese cross pattern), indicating a radial internal structure and pore structure.

[0084] Example 6 0.4 g of cellulose nanocrystals and 0.2 g of agarose were dispersed in 9.4 g of water and stirred at 90 °C to form a suspension. The suspension was added to 100 g of liquid paraffin containing Tween 80 (mass percentage concentration: 10%) and emulsified by stirring at 80 °C for 2 minutes. The mixture was 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 was weighed and then added to 10 mL of a dioxane solution containing 500 μL of the crosslinker 1,4-butanediol diglycidyl ether. The mixture was stirred for 2 hours. 500 μL of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) was added to the reaction solution and stirred for 8 hours. 500 μL of epoxypropane was then mixed with 500 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 to a neutral solution pH. Their optical properties are shown in Figure 14. Under crossed polarizing microscopes, these polymer particles exhibit localized 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 exhibit radial optical anisotropy (the Maltese cross), but rather to only cause localized birefringence.

[0085] Comparison 1 0.6 g of cellulose nanocrystals and 0.3 g of agarose were dispersed in 14.1 g of water and stirred at 80 °C to form a suspension. The suspension was added to 150 g of liquid paraffin containing 10% Tween 80 by mass concentration and emulsified by stirring at 80 °C for 2 minutes. The mixture was 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 was weighed and added to 15 mL of a solution of pentaerythritol glycidyl ether, a tetrafunctional crosslinker, with 800 μl of the mixture and stirred for 12 hours. 800 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) was added to the reaction solution and stirred for 8 hours. 800 μl of epoxypropane was then 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. Under crossed polarizing microscopes, these polymer particles exhibit localized brightness, indicating that their internal structure and pore distribution are partially ordered. Under polarizing microscopes, these polymer particles exhibit varying brightness in different regions, indicating that their internal structure and pore distribution are partially ordered.

[0086] Comparison 2 0.6 g of cellulose nanocrystals and 0.3 g of agarose were dispersed in 14.1 g of water and stirred at 80°C to form a suspension. The suspension was added to 150 g of liquid paraffin containing 10% SPAN80 by mass concentration and stirred at 80°C for 2 minutes to emulsify, then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing, the emulsifier and liquid paraffin were removed, and the resulting gel was weighed and treated with a bifunctional crosslinker, 1,4-butanediol diglyceride. Diethyl etherThe resulting mixture is added to 15 ml of an aqueous solution containing 0.4 g of the above compound and stirred for 12 hours. 400 μl of an aqueous solution containing 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%), and added to the reaction solution and stirred for 12 hours. The resulting polymer particles are washed with warm water and the solution pH is adjusted to a neutral level. Due to the low content of crosslinker, 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 were dispersed in 14.1 g of water and stirred at 80 °C to form a suspension. The suspension was added to 150 g of liquid paraffin containing 10% SPAN80 by mass concentration and stirred at 80 °C for 2 minutes to emulsify, then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing, the emulsifier and liquid paraffin were removed, and the resulting gel was weighed and mixed with 9.6 g of the bifunctional crosslinker 1,4-butanediol diglyceride. Diethyl ether The resulting polymer particles were then washed with warm water and adjusted to a neutral pH. Because the crosslinker content was too high, the resulting polymer particles were prone to adhesion and aggregation, forming chemical bonds between the crosslinker and water, resulting in reduced particle yield.

[0088] Comparison 4 0.6 g of cellulose nanocrystals and 0.3 g of agarose were dispersed in 14.1 g of water and stirred at 60 °C to form a suspension. The suspension was added to 150 g of liquid paraffin containing 10% SPAN 80 by mass concentration and emulsified by stirring at 60 °C for 2 minutes. The mixture was then cooled to lower the temperature and form a dispersion containing solidified emulsion droplets. After washing, the emulsifier and liquid paraffin were removed. The resulting gel was weighed and added to 15 ml of an aqueous solution containing 800 μl of the bifunctional crosslinker 1,4-butanediol diglycidyl ether. The mixture was stirred for 12 hours. 40 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%) was added to the reaction mixture and stirred for 8 hours. 800 μl of epoxypropane was mixed with 40 μl of an aqueous solution containing sodium hydroxide (40 wt%) and sodium borohydride (5 wt%), and the mixture was added to the reaction solution and stirred for 12 hours. The resulting polymer particles were washed with warm water and the solution pH was adjusted to a neutral pH. At 60°C, the cellulose nanocrystals and agarose were incompletely mixed, a liquid crystal phase was not formed, and the crosslinker did not penetrate well into the particle pores. Therefore, the crosslinking reaction occurred only on the particle surface, resulting in low crosslinking efficiency.

[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 and 150 micrometers. They were then homogenized and packed into a glass chromatography column. Using a protein chromatograph, pressure values ​​were obtained at different flow rates. A pressure-flow rate curve was plotted and shown in Figure 16. This was done to investigate the critical pressure of this packing material. The first half of the curve shows that as the flow rate increases, the pressure inside the chromatography column gradually increases, demonstrating a linear relationship between flow rate and pressure. However, once a break is reached, the pressure inside the chromatography column no longer increases linearly with the flow rate and instead shows a sudden increase. This indicates that the shape of the polymer particles inside the chromatography column has been destroyed or the filter at the end of the column is clogged.

[0090] This description is based on the implementation methods, but each implementation method does not include a single independent technical solution. This description is provided for clarity only. 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 are understandable to those skilled in the art.

[0091] The above series of detailed descriptions are merely specific descriptions of the possible embodiments of the present invention, and are not provided to limit the protection scope of the present invention. Any equivalent embodiments or modifications that do not deviate 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 particles 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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