WO2023142842A1

WO2023142842A1 - Pes hollow fiber membrane for purification of biomacromolecule, and preparation method therefor and use thereof

Info

Publication number: WO2023142842A1
Application number: PCT/CN2022/142584
Authority: WO
Inventors: 贾建东; 黄盛�; 杨凯
Original assignee: 杭州科百特过滤器材有限公司
Priority date: 2022-01-29
Filing date: 2022-12-28
Publication date: 2023-08-03
Also published as: CN114452844A; CN114452844B

Abstract

Provided in the present invention are a PES hollow fiber membrane for the purification of a biomacromolecule, and a preparation method therefor and the use thereof. The PES hollow fiber membrane comprises a main body, wherein there are a plurality of slit-shaped first holes in an inner surface of the main body, the average value of the aperture width of the first holes is 60nm - 450nm, the hole area rate of the first holes in the inner surface is 5% - 30%, and the direction of the aperture width of the first holes is consistent with a circumferential direction of the hollow fiber membrane, so that the membrane has high interception efficiency, various biomacromolecules are purified in a tangential flow filtration mode, and the interception molecular weight of the membrane is 100K - 750K. In a thickness direction of the membrane from an inner surface to an outer surface, the average aperture of the main body is increased first and then decreased. The main body comprises a separation layer and a support layer, the support layer comprises a first macroporous region, and the average aperture of the first macroporous region is at least four times the average value of the aperture width of the first holes. The presence of the first macroporous region enables the membrane to have a high flux, and can also provide a buffer effect, the membrane permeability resistance can be reduced, and the energy conversion rate of a membrane assembly is higher.

Description

一种用于生物大分子纯化的PES中空纤维膜及其制备方法与应用A kind of PES hollow fiber membrane for biological macromolecule purification and its preparation method and application

技术领域technical field

本发明涉及膜材料技术领域，更具体的说是涉及一种用于生物大分子纯化的PES中空纤维膜及其制备方法与应用。The invention relates to the technical field of membrane materials, and more specifically relates to a PES hollow fiber membrane used for purification of biomacromolecules and its preparation method and application.

背景技术Background technique

近年来，生物类医药品(特别是免疫球蛋白等抗体)由于其治疗效果高且副作用少而被广泛利用。而抗体或病毒等生物大分子主要是由动物细胞等生物产生，因此为了作为医药品使用，需要对含有抗体、病毒等生物大分子的流体进行分离纯化；目前最常用的分离纯化生物大分子的方式就是通过膜分离，这是因为膜分离技术分离效率高，能耗低，能够在常温下进行，且有效成分即各种生物大分子的回收率高。In recent years, biopharmaceuticals (especially antibodies such as immunoglobulins) have been widely used because of their high therapeutic effects and few side effects. Biomacromolecules such as antibodies or viruses are mainly produced by organisms such as animal cells. Therefore, in order to be used as pharmaceuticals, it is necessary to separate and purify fluids containing biomacromolecules such as antibodies and viruses; currently the most commonly used method for separating and purifying biomacromolecules The method is through membrane separation. This is because membrane separation technology has high separation efficiency, low energy consumption, can be carried out at room temperature, and the recovery rate of active ingredients, namely various biological macromolecules, is high.

膜分离技术的核心就是分离膜，分离膜主要包括聚合物滤膜，它是一类以有机高分子聚合物为原材料，根据一定工艺制成的分离膜；根据高分子聚合物种类的不同，聚合物滤膜可以细分为纤维素类聚合物滤膜，聚酰胺类聚合物滤膜，砜类聚合物滤膜，聚四氟乙烯类聚合物滤膜等；而根据膜的孔径大小可以分为微滤膜、超滤膜、纳滤膜及反渗透膜。此外，也可以根据膜几何形态分为板式膜(平板膜)和中空纤维膜等；其中板式膜的结构简单，不易断裂，但设备效率低，并且在过滤过程中容易对生物大分子造成损伤；因此常用中空纤维膜分离纯化各种生物大分子，不仅效率高，并且不容易对各种生物大分子造成损伤。The core of membrane separation technology is the separation membrane. The separation membrane mainly includes polymer filter membrane, which is a kind of separation membrane made of organic high molecular polymer according to a certain process; according to the different types of high molecular polymer, the polymerization The material filter membrane can be subdivided into cellulose polymer filter membrane, polyamide polymer filter membrane, sulfone polymer filter membrane, polytetrafluoroethylene polymer filter membrane, etc.; and according to the pore size of the membrane, it can be divided into Microfiltration membrane, ultrafiltration membrane, nanofiltration membrane and reverse osmosis membrane. In addition, it can also be divided into plate membrane (flat membrane) and hollow fiber membrane according to the geometry of the membrane; the structure of the plate membrane is simple and not easy to break, but the equipment efficiency is low, and it is easy to cause damage to biological macromolecules during the filtration process; Therefore, hollow fiber membranes are often used to separate and purify various biomacromolecules, which not only has high efficiency, but also does not easily cause damage to various biomacromolecules.

在现有的市场中，已经出现了各种各样的中空纤维膜；例如专利权人东丽株式会社申请的专利公开号为CN112074340A的中国专利-多孔质中空纤维，它是以聚砜系高分子为主成分的多孔质中空纤维膜，所述多孔质中空纤维膜具有内表面侧致密、外表面侧疏松的非对称结构，内表面的孔的短径的平均值为20nm以上且40nm以下，内表面的开孔率为10％以上且30％以下，并且外表面或内表面中的至少一侧的表面担载有含有单羧酸乙烯基酯单元的高分子；多孔质中空纤维对病毒等分离对象物质的除去性能优异且能够用作在低压力下处理也具有高透过性。In the existing market, various hollow fiber membranes have appeared; for example, the patent publication number CN112074340A applied by the patentee Toray Co., Ltd. is the Chinese patent-porous hollow fiber, which is made of polysulfone series high A porous hollow fiber membrane having a molecular main component, the porous hollow fiber membrane has an asymmetric structure with a dense inner surface and a loose outer surface, and the average value of the short diameter of the pores on the inner surface is not less than 20 nm and not more than 40 nm, The porosity of the inner surface is not less than 10% and not more than 30%, and at least one of the outer surface or the inner surface is loaded with a polymer containing a vinyl monocarboxylate unit; the porous hollow fiber is resistant to viruses, etc. It has excellent removal performance of the separation object substance and can be used for treatment under low pressure and has high permeability.

例如专利权人旭化成株式会社申请的公告号为CN109310956B的中国专利-多孔膜及多孔膜的制造方法，它是以聚砜类或偏氟乙烯类高分子为主成分的中空纤维膜，其膜厚为150μm以上，该多孔膜的一个表面的孔径的平均值小于另一个表面的孔径的平均值，该一个表面的孔径的平均值为60nm以下，该孔径的变化系数为10％以上且250％以下，其具有三维网状结构，以纯水透水率F与膜厚D的比表示的透水系数P为5200L/m/hr/mm以上；该中空纤维膜对于病毒、细菌等物质具有高阻止性能、且透水性能优异、可进行长期而稳定的过滤运转。For example, the patentee Asahi Kasei Co., Ltd. applied for a Chinese patent with the notification number CN109310956B - porous membrane and porous membrane manufacturing method. It is a hollow fiber membrane mainly composed of polysulfone or vinylidene fluoride polymers. 150 μm or more, the average value of the pore diameter of one surface of the porous membrane is smaller than the average value of the pore diameter of the other surface, the average value of the pore diameter of the one surface is 60 nm or less, and the variation coefficient of the pore diameter is 10% or more and 250% or less , which has a three-dimensional network structure, and the water permeability coefficient P expressed by the ratio of pure water permeability F to membrane thickness D is above 5200L/m/hr/mm; the hollow fiber membrane has high resistance to viruses, bacteria and other substances, Moreover, it has excellent water permeability and can perform long-term and stable filtration operation.

此外，专利权人东丽株式会社申请的专利公告号为JP6690688B2的日本专利-多孔质膜，它是以聚砜类高分子为主成分的多孔中空纤维膜，所述多孔质中空纤维膜，该多孔质膜其中一个表面的孔的短径的平均值小于另一个表面的孔的短径的平均值；在孔的短径的平均值较小的一侧的表面，孔的短径的平均值为10nm以上且50nm以下；所述表面的孔的短径的平均值小的一侧的表面的孔的长径的平均值为其侧的表面的孔的短径的平均值的2.5倍以上，所述表面的孔的短径的平均值小的一侧的表面的孔的短径的标准偏差为30nm以下；该多孔膜在高压下也能使用(耐压强度高)，并且其具有去除病毒的性能和水的渗透性。In addition, the Japanese Patent No. JP6690688B2 applied by the patentee Toray Co., Ltd. - Porous Membrane is a porous hollow fiber membrane mainly composed of polysulfone polymers. The porous hollow fiber membrane, the The average value of the short diameter of the pores on one surface of the porous membrane is smaller than the average value of the short diameter of the pores on the other surface; on the surface where the average value of the short diameter of the pores is smaller, the average value of the short diameter of the pores It is more than 10nm and less than 50nm; the average value of the major diameter of the pores on the surface on the side where the average value of the minor diameter of the pores on the surface is small is more than 2.5 times the average value of the minor diameter of the pores on the surface on the side, The standard deviation of the minor diameter of the pores on the surface on the side where the average value of the minor diameter of the pores on the surface is small is below 30nm; the porous membrane can also be used under high pressure (high compressive strength), and it has the ability to remove viruses performance and water permeability.

上述三种中空纤维膜都是用于去除病毒等细小杂质，在去除病毒时，都是通过死端过滤的方式进行，从膜孔径较大的一侧表面流动到孔径较小的一侧表面，大颗粒物质被截留在预过滤层(大孔区)，而病毒被截留在分离层(小孔区)，这样的过滤方式虽然能够具有高截留效率，但由于病毒都被截留在膜内，而膜内部的容量是有限的，因此使用寿命较短，并且被截留的病毒是杂质，是不需要的；而在生物纯化过程中，许多病毒载体恰巧是我们所需要的，因此需要选择一款合适的中空纤维膜用于生物大分子(生物大分子主要是指生物体细胞内存在的蛋白质、核酸、多糖等大分子；生物大分子的分子量从几万到几百万)的纯化，并且还希望该中空纤维膜具有高通量和高截留效率，更重要的是，中空纤维膜内部的流体形成的层流流动状态，具有极其柔和的剪切力，有利于避免生物大分子在剪切力的影响下发生变性失活。The above three hollow fiber membranes are used to remove small impurities such as viruses. When removing viruses, they are all carried out by dead-end filtration, flowing from the surface of the membrane with a larger pore size to the surface of the side with a smaller pore size. Large particles are trapped in the pre-filter layer (large pore area), while viruses are trapped in the separation layer (small pore area). Although such a filtration method can have high retention efficiency, since the viruses are all trapped in the membrane, the The capacity inside the membrane is limited, so the service life is short, and the trapped virus is an impurity, which is unnecessary; and in the biological purification process, many viral vectors happen to be what we need, so we need to choose a suitable one. The hollow fiber membrane is used for the purification of biomacromolecules (biomacromolecules mainly refer to macromolecules such as proteins, nucleic acids, and polysaccharides existing in living cells; the molecular weight of biomacromolecules ranges from tens of thousands to several million), and it is also hoped that The hollow fiber membrane has high flux and high retention efficiency. More importantly, the laminar flow state formed by the fluid inside the hollow fiber membrane has extremely gentle shearing force, which is beneficial to avoid biological macromolecules under shearing force. Under the influence of denaturation and inactivation.

发明内容Contents of the invention

针对现有技术存在的不足，本发明的目的在于提供一种用于生物大分子纯化的PES中空纤维膜及其制备方法与应用，该PES中空纤维膜以切向流过滤的方式纯化生物大分子；该PES中空纤维膜的截流分子量为100K-750K，且该膜具有高通量和高截留效率，同时能够得到较高的蛋白质收率，满足了实际应用的需求。In view of the deficiencies in the prior art, the object of the present invention is to provide a PES hollow fiber membrane for purification of biomacromolecules and its preparation method and application. The PES hollow fiber membrane purifies biomacromolecules by means of tangential flow filtration The cut-off molecular weight of the PES hollow fiber membrane is 100K-750K, and the membrane has high flux and high retention efficiency, and at the same time can obtain a higher protein yield, which meets the needs of practical applications.

为实现上述目的，本发明提供了如下技术方案：一种用于生物大分子纯化的PES中空纤维膜，包括主体，所述主体的一侧为内表面，另一侧为外表面，所述主体内具有非定向曲折通路，所述内表面上具有若干个狭缝形的第一孔洞，所述第一孔洞的孔径宽度平均值为60nm-450nm，所述第一孔洞在内表面上的孔洞面积率为5-30％，其中所述第一孔洞的孔径宽度方向与中空纤维膜的周向一致；在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小；In order to achieve the above object, the present invention provides the following technical solutions: a PES hollow fiber membrane for biomacromolecule purification, comprising a main body, one side of the main body is an inner surface, the other side is an outer surface, and the main body There is a non-directional tortuous passage inside, and there are several slit-shaped first holes on the inner surface. The average aperture width of the first holes is 60nm-450nm, and the hole area on the inner surface of the first holes is The rate is 5-30%, wherein the pore width direction of the first hole is consistent with the circumferential direction of the hollow fiber membrane; in the membrane thickness direction from the inner surface to the outer surface, the average pore diameter of the main body first increases and then decreases Small;

所述主体包括分离层和支撑层，所述分离层的一侧为内表面，所述支撑层的一侧为外表面；所述支撑层包括第一大孔区，所述第一大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的4倍以上；所述第一大孔区到内表面的最近距离小于所述第一大孔区到外表面的最近距离。The main body includes a separation layer and a support layer, one side of the separation layer is an inner surface, and one side of the support layer is an outer surface; the support layer includes a first macroporous region, and the first macroporous region The average pore diameter of the first hole is at least 4 times the average pore width of the first hole; the shortest distance from the first large pore area to the inner surface is smaller than the shortest distance from the first large pore area to the outer surface.

在本发明所提供的PES中空纤维膜的膜主体结构中，可以清楚看到膜的内外表面上的孔洞孔径大小是不同的，存在一定的差距；即相较于外表面，内表面上的第一孔洞孔径较小，且第一孔洞数量较少(即内表面相对较致密)；此外通过观察发现，第一孔洞的形状并不是常见的圆形或者椭圆形，其为狭缝形(狭缝状)，即在与中空纤维膜膜长度方向一致的方向上，第一孔洞的孔径较大，因此该值被认为是第一孔洞的孔径长度值，而在与中空纤维膜膜周向方向一致的方向上，第一孔洞的孔径较小，因此该值被认为是第一孔洞的孔径宽度值，其中孔径宽度值的大小影响了膜整体的截留效率，而孔径长度值则影响了膜整体的通量，因此这样的内表面的第一孔洞形状更有利于膜具有高截留效率和高通量；经过测量发现了第一孔洞的孔径宽度平均值为60nm-450nm(第一孔洞的孔径宽度方向与中空纤维膜的周向一致)，所述第一孔洞在内表面上的孔洞面积率为5-30％，这样的孔径大小，适合截流分子量为100K-750K的生物大分子物质，同时内表面相对致密，保证具有较高的截留效率；同时该中空纤维膜通过以切向流的形式纯化各种生物大分子(相应的流体在中空纤维膜的内腔中流动)，其剪切力较小，避免了生物大分子变性失活；In the membrane main structure of the PES hollow fiber membrane provided by the present invention, it can be clearly seen that the hole diameters on the inner and outer surfaces of the membrane are different, and there is a certain gap; that is, compared with the outer surface, the first hole on the inner surface The diameter of the first hole is small, and the number of first holes is relatively small (that is, the inner surface is relatively dense); in addition, it is found through observation that the shape of the first hole is not a common circle or ellipse, but a slit shape (slit shape), that is, in the direction consistent with the length direction of the hollow fiber membrane, the pore diameter of the first hole is relatively large, so this value is considered to be the pore length value of the first hole, and in the direction consistent with the circumferential direction of the hollow fiber membrane In the direction of , the pore diameter of the first hole is smaller, so this value is considered as the pore width value of the first pore, where the pore width value affects the overall retention efficiency of the membrane, while the pore length value affects the overall membrane retention efficiency. flux, so the first hole shape of such an inner surface is more conducive to the high retention efficiency and high flux of the membrane; through measurement, it is found that the average value of the aperture width of the first hole is 60nm-450nm (the aperture width direction of the first hole Consistent with the circumference of the hollow fiber membrane), the pore area ratio of the first hole on the inner surface is 5-30%, such a pore size is suitable for biological macromolecular substances with a cut-off molecular weight of 100K-750K, Relatively compact, ensuring high retention efficiency; at the same time, the hollow fiber membrane purifies various biological macromolecules in the form of tangential flow (the corresponding fluid flows in the inner cavity of the hollow fiber membrane), and its shear force is small , to avoid denaturation and inactivation of biological macromolecules;

进一步观察膜主体结构发现，在靠近内表面的一侧区域，其孔径相对较小，该区域在本发明中被称为分离层(膜丝的截留分子量为100kD-750kD)，分离层的存在保证了中空纤维膜具有高截留效率；而其余区域的孔径相对较大，在本发明中被称为支撑层；其中支撑层主要起的是对分离层的支撑作用，特别是由于本发明的物料是在中空纤维膜的内腔中流动，支撑层的存在，保证了膜整体具有较高的耐压强度，也保证分离层能够一直起到分离作用；纯化各种生物大分子；Further observation of the main body structure of the membrane finds that the area near the inner surface has a relatively small aperture, which is referred to as the separation layer in the present invention (the molecular weight cut-off of the membrane silk is 100kD-750kD), and the existence of the separation layer ensures that The hollow fiber membrane has a high interception efficiency; and the pore size of the remaining areas is relatively large, which is called a support layer in the present invention; where the support layer mainly plays a role in supporting the separation layer, especially because the material of the present invention is Flowing in the inner cavity of the hollow fiber membrane, the existence of the support layer ensures that the membrane has a high compressive strength as a whole, and also ensures that the separation layer can always play a role in separation; purify various biological macromolecules;

此外，在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小，这样的变化的膜孔结构，使得在膜主体结构中出现了一个第一大孔区，第一大孔区位于支撑层内；且第一大孔区到内表面的最近距离(第一大孔区到内表面的最近距离是指第一大孔区最靠近内表面的一侧到内表面的距离)小于所述第一大孔区到外表面的最近距离(第一大孔区到外表面的最近距离是指第一大孔区最靠近外表面的一侧到外表面的距离)，即第一大孔区更加靠近内表面；第一大孔区内孔洞孔径较大，孔隙率也较高；经过测量发现，第一大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的4倍以上；第一大孔区的存在，一方面大大增加了膜整体的通量，传质阻力大大变小，更有利于进行各种生物大分子的纯化；另一方面，第一大孔区也能提供一定的缓冲作用，使得外表面的变形量较低，而中空纤维膜的外表面部分是与胶水相粘结在一起，从而形成完整的组件，如果外表面的变形程度过大，那么外表面与胶水之间的牢固性就容易变弱，继而影响组件的完整性，使用寿命也大大降低，因此第一大孔区的存在还能保住整个过滤组件有较长的使用寿命，经济效益高。In addition, in the film thickness direction from the inner surface to the outer surface, the average pore diameter of the main body first increases and then decreases, such a changed membrane pore structure makes a first large pore area appear in the main membrane structure , the first macroporous area is located in the support layer; and the shortest distance from the first macroporous area to the inner surface (the shortest distance from the first macroporous area to the inner surface refers to the side of the first macroporous area closest to the inner surface to the The distance from the inner surface) is less than the shortest distance from the first macroporous area to the outer surface (the shortest distance from the first macroporous area to the outer surface refers to the distance from the side of the first macroporous area closest to the outer surface to the outer surface ), that is, the first large pore area is closer to the inner surface; the hole diameter in the first large pore area is larger, and the porosity is also higher; after measurement, it is found that the average pore diameter of the first large pore area is at least the aperture width of the first hole The average value is more than 4 times; the existence of the first macroporous region, on the one hand, greatly increases the overall flux of the membrane, and the mass transfer resistance is greatly reduced, which is more conducive to the purification of various biological macromolecules; on the other hand, the second The large pore area can also provide a certain cushioning effect, so that the deformation of the outer surface is low, and the outer surface of the hollow fiber membrane is bonded with glue to form a complete module. If the degree of deformation of the outer surface If it is too large, the firmness between the outer surface and the glue will easily weaken, which will affect the integrity of the component and greatly reduce the service life. Therefore, the existence of the first large pore area can also keep the entire filter component for a longer period of use. Long life, high economic benefit.

膜表面平均孔径的测量方式可以通过使用扫描电子显微镜对膜结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量，并进行相应计算；在膜的制备过程中，在垂直于膜厚度方向上(如果膜是平板膜形态，则该方向是平面方向；如果膜是中空纤维膜形态，则该方向是垂直于半径方向)，其各项特征如孔径分布是大致均匀的，基本保持一致；所以可以通过在相应平面上部分区域的平均孔径大小，来反映该平面上整体的平均孔径大小。在实际进行测量时，可以先用电子显微镜对膜表面进行表征，获得相应的SEM图，而由于膜表面孔洞大致是均匀的，因此可以选取一定的面积，例如1μm ²(1μm乘以1μm)或者25μm ²(5μm乘以5μm)，具体面积大小视实际情况而定，再用相应计算机软件或者手工测出该面积上所有孔洞的孔径，然后进行计算，获得该表面的平均孔径；内表面的孔洞面积率即为该表面上所有孔洞面积之和与该表面的面积之比；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考； The average pore size of the membrane surface can be measured by using a scanning electron microscope to characterize the membrane structure, then use computer software (such as Matlab, NIS-Elements, etc.) or manually measure, and perform corresponding calculations; in the membrane preparation process Among them, in the direction perpendicular to the thickness of the membrane (if the membrane is in the form of a flat membrane, the direction is the plane direction; if the membrane is in the form of a hollow fiber membrane, then the direction is perpendicular to the radial direction), its various characteristics such as the pore size distribution are Roughly uniform and basically consistent; therefore, the average pore size of the entire area on the corresponding plane can be reflected by the average pore size of some regions on the corresponding plane. In the actual measurement, the surface of the membrane can be characterized with an electron microscope to obtain the corresponding SEM image. Since the pores on the surface of the membrane are roughly uniform, a certain area can be selected, such as ^1μm2 (1μm times 1μm) or 25μm ² (5μm multiplied by 5μm), the specific area depends on the actual situation, and then use the corresponding computer software or manually measure the pore diameter of all holes on the area, and then calculate to obtain the average pore diameter of the surface; the holes on the inner surface The area ratio is the ratio of the sum of the areas of all holes on the surface to the area of the surface; of course, those skilled in the art can also obtain the above parameters through other measurement methods, and the above measurement methods are for reference only;

本发明中第一大孔区的平均孔径，孔隙率，厚度等参数可以通过使用扫描电子显微镜对膜截面结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量后计算测得；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考；In the present invention, parameters such as the average pore diameter of the first macroporous region, porosity, and thickness can be characterized by using a scanning electron microscope to characterize the cross-sectional structure of the membrane, and then using computer software (such as Matlab, NIS-Elements, etc.) or manually Calculate and measure after measurement; Of course, those skilled in the art can also obtain the above-mentioned parameters by other measurement means, and the above-mentioned measurement means are for reference only;

此外分离层背离内表面的一侧和支撑层背离外表面的一侧是以连续的纤维过渡，可以理解的是，“连续”是指基本上所有的纤维呈整体地相互连接，如一体形成，而无需使用另外的粘合剂等使其相互连接，除非通过外力撕裂，否则网络状的纤维之间不能够相互分离；与此同时，所述连续的网络状纤维与内表面和外表面之间也是相互连接的；本发明中PES中空纤维膜各处的材质是均一的，即整个膜均是由PES材料制得，在材质上不存在变化；In addition, the side of the separation layer facing away from the inner surface and the side of the support layer facing away from the outer surface are transitioned by continuous fibers. It can be understood that "continuous" means that basically all the fibers are integrally connected to each other, such as integrally formed, There is no need to use additional adhesives or the like to connect them to each other, and the network-like fibers cannot be separated from each other unless they are torn by external force; meanwhile, the continuous network-like fibers and the inner surface and the outer surface The space is also connected to each other; the material of the PES hollow fiber membrane is uniform everywhere in the present invention, that is, the whole membrane is made of PES material, and there is no change in the material;

在本发明中，PES中空纤维膜是一种不对称膜，不对称膜应理解为这样的膜，其中分离层和支撑层均是由同种的材料组成，两层结合成为一个整体结构，并在膜制备过程中是直接形成的；在从分离层到支撑层的过渡中，只在膜结构方面有一变化；与此相反的是例如复合膜，复合膜有多层结构，它是用一分开的过程步骤将作为分离层的致密层涂加在一多孔材料上，经常是微孔的支撑层或支撑膜上，复合膜中构成支撑层和分离层的材料也往往是不同的。In the present invention, the PES hollow fiber membrane is an asymmetric membrane, and the asymmetric membrane should be understood as a membrane in which the separation layer and the support layer are made of the same material, and the two layers are combined into an integral structure, and It is formed directly during the membrane preparation process; in the transition from the separation layer to the support layer, there is only a change in the membrane structure; in contrast to this, such as a composite membrane, which has a multi-layer structure, it is separated by a The process step is to apply a dense layer as a separation layer on a porous material, often a microporous support layer or a support membrane, and the materials constituting the support layer and separation layer in the composite membrane are often different.

作为本发明的进一步改进，所述内表面上还包括有若干个短纤维，所述短纤维的两端均与第一孔洞内壁相连接，相邻第一孔洞之间通过短纤维相隔开,所述短纤维的平均直径为10-40nm。As a further improvement of the present invention, the inner surface also includes several short fibers, both ends of the short fibers are connected to the inner wall of the first hole, and the adjacent first holes are separated by short fibers, The average diameter of the short fibers is 10-40 nm.

在对相应的物料进行过滤纯化时，为了保证有足够的膜整体具有合适的通量，都会对膜内表面进行加压；当施加于膜内表面的压力逐渐上升时，内表面的孔洞就容易被扩张，特别容易使膜孔洞的宽度变大，这样就无法保证膜具有高效的截留作用，而由于本发明中存在着第一大孔区，第一大孔区的存在虽然大大提高了膜通量，降低了传质阻力；但又由于第一大孔区内部孔隙率高，相较于没有第一大孔区的相对致密的中空纤维膜，本发明的内表面更容易被扩张，膜孔洞的宽度相对更容易被扩张继而降低截留效率；但令人惊喜的是，在中空纤维膜的内表面上，存在着若干个短纤维，这些短纤维的两端均与第一孔洞内壁相连接，即短纤维的长度基本与第一孔洞的孔径宽度相同，短纤维的长度方向与中空纤维膜的周向一致；短纤维的存在，起到了对第一孔洞的支撑作用，抑制了内表面第一孔洞的孔径宽度的扩张，继而保证了膜具有高通量的同时还具有高截留效率；经过测量短纤维的平均直径(粗细)为10-40nm(短纤维的直径方向基本与中空纤维膜的膜丝长度方向一致)，短纤维过细(直径过小)，则无法起到对第一孔洞的支撑稳定作用，短纤维过粗(直径过大)，则会降低膜整体的通量以及提高传质阻力。When filtering and purifying the corresponding materials, in order to ensure that there is enough membrane as a whole to have a suitable flux, the inner surface of the membrane will be pressurized; when the pressure applied to the inner surface of the membrane gradually rises, the pores on the inner surface will be easy. It is particularly easy to make the width of the membrane hole larger, so that the membrane cannot be guaranteed to have a high-efficiency interception effect, and because there is the first macroporous region in the present invention, although the existence of the first macroporous region has greatly improved the membrane flow rate. However, due to the high internal porosity of the first macroporous region, compared with the relatively dense hollow fiber membrane without the first macroporous region, the inner surface of the present invention is easier to expand, and the membrane pores The width is relatively easier to expand and then reduce the retention efficiency; but surprisingly, on the inner surface of the hollow fiber membrane, there are several short fibers, and the two ends of these short fibers are connected with the inner wall of the first hole, That is, the length of the short fibers is basically the same as the aperture width of the first hole, and the length direction of the short fibers is consistent with the circumferential direction of the hollow fiber membrane; the existence of the short fibers plays a role in supporting the first holes, and inhibits the first hole on the inner surface. The expansion of the pore width of the hole, in turn, ensures that the membrane has high flux and high retention efficiency; after measuring the average diameter (thickness) of the short fiber is 10-40nm (the diameter direction of the short fiber is basically the same as that of the hollow fiber membrane. If the short fiber is too thin (too small in diameter), it will not be able to support and stabilize the first hole; if the short fiber is too thick (too large in diameter), the overall flux of the membrane will be reduced and the mass transfer will be improved. resistance.

短纤维平均直径的测量方式可以通过使用扫描电子显微镜对膜结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量，并进行相应计算；例如先用电子显微镜对膜表面进行表征，获得相应的SEM图，具体面积大小视实际情况而定，再用相应计算机软件或者手工测出该面积上所有短纤维的直径，然后进行计算，获得该内表面上的短纤维平均直径；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考；The average diameter of the short fibers can be measured by using a scanning electron microscope to characterize the morphology of the membrane structure, and then use computer software (such as Matlab, NIS-Elements, etc.) or manually measure and calculate accordingly; for example, use an electron microscope Characterize the surface of the membrane and obtain the corresponding SEM image. The specific area depends on the actual situation. Then use the corresponding computer software or manually measure the diameters of all the short fibers on the area, and then calculate to obtain the short fibers on the inner surface. Fiber average diameter; Certainly those skilled in the art can also obtain above-mentioned parameter by other measuring means, and above-mentioned measuring means is for reference only;

作为本发明的进一步改进，所述分离层的厚度为0.5-15μm，所述分离层厚度占膜厚度的0.5-12.5％；所述分离层的孔隙率为10-45％；所述内表面的第一水接触角为45°-70°。As a further improvement of the present invention, the thickness of the separation layer is 0.5-15 μm, and the thickness of the separation layer accounts for 0.5-12.5% of the membrane thickness; the porosity of the separation layer is 10-45%; The first water contact angle is 45°-70°.

相较于支撑层，分离层内部的孔洞孔径较小，且孔隙率相对较低，相对致密，使得内表面的第一孔洞在受压时不容易被扩张，孔径宽度变化较小，具有高截留效率；同时由于以切向流的形式用于生物纯化，所以分离层的厚度要相对较小，经过测量发现，本发明PES中空纤维膜分离层的厚度为0.5-15μm，且分离层厚度占膜厚度的0.5-12.5％，这在保证高效截留的同时，使得膜具有较大的通量，在单位时间能够纯化更多的物料，经济效益高；由于需要被纯化的物料是在膜的内腔中反复流动，因此内表面的亲水性高低会对蛋白质收率造成极大的影响，膜内表面的亲水性越好，则蛋白收率越高；经过接触角测试发现，本发明中内表面的第一水接触角为45°-70°(接触角越小，越亲水)，从而说明了内表面非常亲水，膜整体具有较高的亲水性，对各种蛋白质是低吸附，因此能够具有高蛋白质收率，进一步提高经济效益。Compared with the support layer, the pores inside the separation layer have a smaller pore size, relatively lower porosity, and are relatively dense, so that the first pores on the inner surface are not easily expanded under pressure, and the pore width changes less, with high retention Efficiency; at the same time, because it is used for biological purification in the form of tangential flow, the thickness of the separation layer is relatively small. After measurement, it is found that the thickness of the separation layer of the PES hollow fiber membrane of the present invention is 0.5-15 μm, and the thickness of the separation layer accounts for 0.5-12.5% of the thickness, while ensuring high-efficiency retention, the membrane has a larger flux, and can purify more materials per unit time, with high economic benefits; since the materials to be purified are in the inner cavity of the membrane Therefore, the hydrophilicity of the inner surface will have a great impact on the protein yield. The better the hydrophilicity of the inner surface of the membrane, the higher the protein yield; through the contact angle test, it is found that the inner surface of the present invention The first water contact angle on the surface is 45°-70° (the smaller the contact angle, the more hydrophilic), which shows that the inner surface is very hydrophilic, the overall membrane has high hydrophilicity, and has low adsorption to various proteins , so it can have high protein yield and further improve economic benefits.

本发明中分离层的孔隙率，厚度等参数可以通过先将PES中空纤维膜撕开，分成分离层和支撑层，再对分离层进行相应参数测试；或者通过使用扫描电子显微镜对膜截面结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量后计算测得；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考。The parameters such as the porosity and thickness of the separation layer in the present invention can be divided into a separation layer and a support layer by first tearing the PES hollow fiber membrane, and then the separation layer is tested for corresponding parameters; or by using a scanning electron microscope to analyze the membrane cross-sectional structure. After the morphology is characterized, computer software (such as Matlab, NIS-Elements, etc.) or manual measurement can be used to calculate and measure; of course, those skilled in the art can also obtain the above parameters through other measurement methods, and the above measurement methods are for reference only.

作为本发明的进一步改进，所述第一大孔区的平均孔径为1.5-4.5μm；所述第一大孔区到内表面的最近距离为15-50μm；所述第一大孔区的厚度为5-18μm。As a further improvement of the present invention, the average pore diameter of the first macroporous region is 1.5-4.5 μm; the shortest distance from the first macroporous region to the inner surface is 15-50 μm; the thickness of the first macroporous region 5-18μm.

作为本发明的进一步改进，所述第一大孔区内具有形成多孔结构的第一纤维，所述第一纤维的平均直径为80-200nm；所述第一大孔区的孔隙率为55-90％；所述第一大孔区到内表面的最近距离占膜厚度的10-40％；所述第一大孔区的厚度占膜厚度的3.5-16.5％。As a further improvement of the present invention, there are first fibers forming a porous structure in the first macroporous region, the average diameter of the first fibers is 80-200 nm; the porosity of the first macroporous region is 55- 90%; the shortest distance from the first macroporous region to the inner surface accounts for 10-40% of the film thickness; the thickness of the first macroporous region accounts for 3.5-16.5% of the film thickness.

第一大孔区的存在，有助于膜整体的通量，降低膜整体的透膜阻力；但也有可能对膜整体的机械强度(耐压强度)以及膜的截留效率造成一定的影响；而本发明中具有合适的第一大孔区，第一大孔区的平均孔径为1.5-4.5μm，其孔径远远大于内表面的第一孔洞的孔径宽度，且第一大孔区的孔隙率为55-90％，保证了膜整体具有较大的通量，以及较低的透膜阻力；除此以外，第一大孔区的厚度也会大大影响膜整体的通量，如果厚度过小，则膜整体的通量依然较小，但如果膜的厚度过大，且第一大孔区的厚度占膜厚度的比例过高，那么膜整体的耐压强度就会降低，膜的截留效率也会降低；本发明中第一大孔区的厚度为5-18μm，且第一大孔区的厚度占膜厚度的3.5-16.5％，这样的厚度大小及占比，保证了膜整体的耐压强度和截留效率基本不会变化，而膜的通量能够显著提高，透膜阻力能够大大降低，能量转化率变高，经济效益更高；此外，为了进一步保证截留效率(避免因为第一大孔区的存在而导致内表面上第一孔洞的孔径宽度在受压容易扩大)，因此第一大孔区需要与内表面存在的一定距离，距离不能过近，但也不能过远(过远的话第一大孔区就无法起到很好的缓冲作用，传质阻力小)；而所述第一大孔区到内表面的最近距离为15-50μm；且第一大孔区到内表面的最近距离占膜厚度的10-40％，一方面第一大孔区比较靠近内表面，同时与内表面也存在着一定距离；这样第一大孔区就更不容易影响膜整体的截留效率，同时还能起到很好的缓冲作用，传质阻力变小，膜外表面的变形量更小，同时膜的使用寿命更长。此外，第一大孔区内具有形成多孔结构的第一纤维，其平均直径为80-200nm，从而说明了第一纤维具有合适的粗细，从而形成了相应孔径相应孔隙率的第一大孔区。The existence of the first macroporous region contributes to the overall flux of the membrane and reduces the membrane resistance of the overall membrane; but it may also have a certain impact on the overall mechanical strength (compressive strength) of the membrane and the retention efficiency of the membrane; and In the present invention, there is a suitable first macroporous region, the average pore diameter of the first macroporous region is 1.5-4.5 μm, and its pore diameter is far greater than the pore width of the first hole on the inner surface, and the porosity of the first macroporous region It is 55-90%, which ensures that the overall membrane has a large flux and low membrane resistance; in addition, the thickness of the first macropore area will also greatly affect the overall flux of the membrane. If the thickness is too small , the overall flux of the membrane is still small, but if the thickness of the membrane is too large, and the ratio of the thickness of the first macropore area to the membrane thickness is too high, the overall compressive strength of the membrane will decrease, and the retention efficiency of the membrane will decrease. It will also be reduced; the thickness of the first macroporous region is 5-18 μm in the present invention, and the thickness of the first macroporous region accounts for 3.5-16.5% of the film thickness. Such thickness and proportion ensure the overall resistance of the film. The compressive strength and interception efficiency will basically not change, while the flux of the membrane can be significantly improved, the membrane resistance can be greatly reduced, the energy conversion rate will be higher, and the economic benefit will be higher; in addition, in order to further ensure the interception efficiency (to avoid the The existence of the pore area causes the aperture width of the first hole on the inner surface to expand easily under pressure), so the first large pore area needs to have a certain distance from the inner surface, and the distance cannot be too close, but it cannot be too far (too far If the first large pore area can not play a good buffering effect, the mass transfer resistance is small); and the shortest distance from the first large pore area to the inner surface is 15-50 μm; and the first large pore area to the inner surface The shortest distance of the membrane accounts for 10-40% of the membrane thickness. On the one hand, the first large pore area is relatively close to the inner surface, and there is also a certain distance from the inner surface; in this way, the first large pore area is less likely to affect the overall interception efficiency of the membrane. , At the same time, it can also play a good buffering role, the mass transfer resistance becomes smaller, the deformation of the outer surface of the membrane is smaller, and the service life of the membrane is longer. In addition, there are first fibers forming a porous structure in the first macroporous region, and its average diameter is 80-200nm, thereby illustrating that the first fibers have a suitable thickness, thereby forming the first macroporous region with corresponding pore diameter and corresponding porosity .

本发明中第一大孔区的平均孔径、第一大孔区的厚度和第一纤维的平均直径等参数可以通过使用扫描电子显微镜对膜截面结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量后计算测得；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考。In the present invention, parameters such as the average pore diameter of the first macropore region, the thickness of the first macropore region, and the average diameter of the first fiber can be characterized by using a scanning electron microscope for the morphology of the film cross-sectional structure, and then using computer software (such as Matlab, NIS-Elements, etc.) or manual measurement and calculation; of course, those skilled in the art can also obtain the above parameters by other measurement means, and the above measurement means are for reference only.

作为本发明的进一步改进，所述支撑层还包括有孔洞平均孔径不超过1μm的小孔区；所述小孔区内具有形成多孔结构的多孔纤维；所述多孔纤维的平均直径为70-180nm；所述小孔区的孔隙率为35-72％。As a further improvement of the present invention, the support layer also includes a small hole area with an average pore diameter of no more than 1 μm; the small hole area has porous fibers forming a porous structure; the average diameter of the porous fibers is 70-180 nm ; The porosity of the small hole area is 35-72%.

作为本发明的进一步改进，所述多孔纤维的平均直径与第一纤维的平均直径与之比不低于0.8；所述第一大孔区的孔隙率至少比小孔区的孔隙率大10％以上。As a further improvement of the present invention, the ratio of the average diameter of the porous fibers to the average diameter of the first fibers is not less than 0.8; the porosity of the first macropore region is at least 10% greater than the porosity of the small pore region above.

在从内表面至外表面的膜厚度方向上，主体的平均孔径先增大再减小，因此在支撑层内存在着第一大孔区；而除了第一大孔区，由于孔径逐渐减小，支撑层还存在孔径相对较小的区域，本发明中在支撑层内孔洞平均孔径不超过1μm的区域被称为小孔区；在膜的主体结构中大部分区域是支撑层，而支撑层中的大部分区域是小孔区，因此小孔区的相关特征对膜整体的性能影响很大；本发明中小孔区的孔隙率为35-72％，形成小孔区内多孔结构的多孔纤维的平均直径为70-180nm，在这两者的协同作用下，进一步保证了膜整体具有较高的通量以及优异的耐压强度(机械强度)，应用范围广；In the film thickness direction from the inner surface to the outer surface, the average pore diameter of the main body first increases and then decreases, so there is a first macroporous region in the support layer; , the support layer also has a region with a relatively small pore diameter. In the present invention, the region where the average pore diameter of the holes in the support layer is no more than 1 μm is called the small hole region; in the main structure of the membrane, most of the regions are the support layer, and the support layer Most of the regions in the film are small pore regions, so the relevant characteristics of the small pore regions have a great influence on the performance of the membrane as a whole; the porosity of the small pore regions in the present invention is 35-72%, forming a porous structure of the porous structure in the small pore regions. The average diameter of the fiber is 70-180nm. Under the synergistic effect of the two, it further ensures that the overall membrane has a high flux and excellent compressive strength (mechanical strength), and has a wide range of applications;

此外，由于第一大孔区和小孔区均位于支撑层内，因此对第一大孔区和小孔区的相关特征进行对比发现，第一大孔区与小孔区的主要区别在与孔洞孔径的不同，以及孔隙率的不同(第一大孔区的孔隙率至少比小孔区的孔隙率大10％以上)，而两个区域的纤维粗纤是基本相同的(多孔纤维的平均直径与第一纤维的平均直径与之比不低于0.8)，这也进一步证明了该中空纤维膜是一体成型，在沿膜的厚度方向上，主要变化的是膜孔大小和相应孔隙率，进一步保证了该PES中空纤维膜具有较高的耐压强度，工业实用性强。In addition, since the first large pore area and the small pore area are both located in the support layer, a comparison of the relevant features of the first large pore area and the small pore area shows that the main difference between the first large pore area and the small pore area lies in the The difference in pore diameter and porosity (the porosity of the first large pore area is at least 10% larger than that of the small pore area), while the fiber coarse fibers in the two areas are basically the same (the average of the porous fiber The ratio of diameter to the average diameter of the first fiber is not less than 0.8), which further proves that the hollow fiber membrane is integrally formed. Along the thickness direction of the membrane, the main change is the membrane pore size and corresponding porosity. It is further ensured that the PES hollow fiber membrane has high compressive strength and strong industrial applicability.

作为本发明的进一步改进，所述外表面上具有若干个第二孔洞，所述第二孔洞的平均孔径为150nm-2500nm，所述第二孔洞在外表面上的孔洞面积率为12-65％；所述第二孔洞的平均孔径大于第一孔洞的孔径宽度平均值。As a further improvement of the present invention, there are several second holes on the outer surface, the average pore diameter of the second holes is 150nm-2500nm, and the hole area ratio of the second holes on the outer surface is 12-65%; The average pore diameter of the second holes is larger than the average pore width of the first holes.

在中空纤维膜的外表面上也存在着一定数量，一定孔径的第二孔洞，经过测量发现外表面上第二孔洞的平均孔径为150nm-2500nm(第二孔洞的平均孔径大于第一孔洞的孔径宽度平均值)，且第二孔洞在外表面上的孔洞面积率为12-65％；这样孔径大小的第二孔洞以及一定数量的第二孔洞共同作用下，进一步保证了PES中空纤维膜整体具有较高的通量和较大的耐压强度(机械强度)，应用范围广。Also there is a certain amount on the outer surface of the hollow fiber membrane, the second hole of a certain pore diameter, through measuring, find that the average pore diameter of the second hole on the outer surface is 150nm-2500nm (the average pore diameter of the second hole is greater than the pore diameter of the first hole Width average value), and the hole area ratio of the second hole on the outer surface is 12-65%; under the joint action of the second hole with such a pore size and a certain number of second holes, it further ensures that the PES hollow fiber membrane has a relatively high overall performance. High flux and greater compressive strength (mechanical strength), wide range of applications.

膜外表面平均孔径的测量方式可以通过使用扫描电子显微镜对膜结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量，并进行相应计算；外表面的第二孔洞面积率即为该表面上所有第二孔洞面积之和与该表面的面积之比；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考.The average pore size of the outer surface of the membrane can be measured by using a scanning electron microscope to characterize the morphology of the membrane structure, and then using computer software (such as Matlab, NIS-Elements, etc.) or manual measurement, and corresponding calculations; The area ratio of the second holes is the ratio of the sum of the areas of all the second holes on the surface to the area of the surface; of course, those skilled in the art can also obtain the above parameters through other measurement methods, and the above measurement methods are for reference only.

作为本发明的进一步改进，所述第一孔洞的孔径长度平均值为120-800nm，所述第一孔洞的孔径长度平均值为第一孔洞的孔径宽度平均值的1.3-6；其中所述第一孔洞的孔径长度方向与中空纤维膜的长度方向一致。As a further improvement of the present invention, the average pore length of the first hole is 120-800nm, and the average pore length of the first hole is 1.3-6 of the average pore width of the first hole; wherein the first The length direction of the aperture of a hole is consistent with the length direction of the hollow fiber membrane.

由于内表面上的第一孔洞为狭缝形，其孔径宽度的大小对相应粒径物质的截留效率起到了重要影响；而第一孔洞的孔径长度大小则会影响膜整体的通量，如果第一孔洞的孔径长度过小，则会较低膜整体的通量；而如果第一孔洞的孔径长度过大(此时孔径长度与孔径宽度之比也会过大)，那么在受到较大压力时，第一孔洞(特别是第一孔洞的孔径宽度)就容易扩大，这样截留效率就会降低，无法满足实际应用的需求；本发明中第一孔洞的孔径长度平均值为120-800nm，且第一孔洞的孔径长度平均值为第一孔洞的孔径宽度平均值的1.3-6；即第一孔洞具有合适的孔径长度，且具有合适的孔径长度与孔径宽度之比，在保证膜具有高截留效率的同时，进一步提高膜整体的通量。Since the first hole on the inner surface is in the shape of a slit, the size of its pore width plays an important role in the interception efficiency of the corresponding particle size; while the length of the first hole will affect the overall flux of the membrane. If the aperture length of the first hole is too small, the overall flux of the membrane will be lower; and if the aperture length of the first hole is too large (at this time, the ratio of the aperture length to the aperture width will also be too large), then under greater pressure , the first hole (especially the aperture width of the first hole) is just easy to expand, so the interception efficiency will be reduced, which cannot meet the needs of practical applications; the average value of the aperture length of the first hole in the present invention is 120-800nm, and The average value of the aperture length of the first hole is 1.3-6 of the average value of the aperture width of the first hole; that is, the first hole has a suitable aperture length, and has a suitable ratio of the aperture length to the aperture width, ensuring that the membrane has a high cut-off While improving the efficiency, the overall flux of the membrane is further improved.

作为本发明的进一步改进，在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小，减小后再进一步增大；所述支撑层还包括有第二大孔区，所述第二大孔区一侧为外表面；所述第二大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的1.5倍以上；所述第二大孔区的厚度为4-15μm。As a further improvement of the present invention, in the film thickness direction from the inner surface to the outer surface, the average pore diameter of the main body first increases and then decreases, and then further increases after decreasing; the supporting layer also includes a second Large pore area, one side of the second large pore area is the outer surface; the average pore diameter of the second large pore area is at least 1.5 times the average value of the aperture width of the first hole; the second large pore area The thickness is 4-15 μm.

在经济快速发展的今天，人们越来越讲究效率；因此人们越来越需要在保证截留效率的同时，膜整体具有更高的通量，这样单位时间的经济效益就会更高；而一次偶然的意外，在制备过程中一个因素的改变,使得膜整体的通量有了进一步的提高，通过观察这些膜的主体结构中，可以清楚看到在膜的主体结构中，除了第一大孔区，还出现了第二大孔区(该区域的孔洞孔径也较大，经过测量发现第二大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的1.5倍以上)，第二大孔区的一侧即为中空纤维膜的外表面，即此时在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小，减小后再进一步增大；而正是由于内部孔径较大的第二大孔区的存在，使得膜整体的通量进一步增大；并且第二大孔区的厚度为4-15μm，在该厚度下，既不会对膜整体的耐压强度和截留效率造成影响，而膜整体的通量有了进一步显著的提高，传质阻力更低，透膜阻力更小，能量有效转化率更高，更节能。Today, with the rapid economic development, people pay more and more attention to efficiency; therefore, people increasingly need to ensure the interception efficiency and at the same time, the overall membrane has a higher flux, so that the economic benefit per unit time will be higher; and an accidental Unexpectedly, a factor change in the preparation process has further improved the overall flux of the membrane. By observing the main structure of these membranes, it can be clearly seen that in the main structure of the membrane, except for the first macroporous area , the second largest pore area also appeared (the pore diameter in this area is also larger, and it is found that the average pore diameter of the second largest pore area is at least 1.5 times the average pore width of the first hole after measurement), the second largest pore One side of the hollow fiber membrane is the outer surface of the hollow fiber membrane, that is, at this time, in the membrane thickness direction from the inner surface to the outer surface, the average pore size of the main body first increases and then decreases, and then further increases after decreasing; It is precisely because of the existence of the second macroporous region with a larger internal pore size that the overall flux of the membrane is further increased; and the thickness of the second macroporous region is 4-15 μm. The overall compressive strength and interception efficiency are affected, while the overall flux of the membrane has been further significantly improved, the mass transfer resistance is lower, the membrane penetration resistance is smaller, the effective conversion rate of energy is higher, and it is more energy-saving.

作为本发明的进一步改进，所述第二大孔区的平均孔径为200-2000nm；且所述第二大孔区的平均孔径小于第一大孔区的平均孔径；所述第二大孔区内具有形成多孔结构的第二纤维，所述第二纤维平均直径为50-500nm；所述第二大孔区的孔隙率为50-85％；所述第二大孔区的厚度占膜厚度的3-13％。As a further improvement of the present invention, the average pore diameter of the second macroporous region is 200-2000nm; and the average pore diameter of the second macroporous region is smaller than the average pore diameter of the first macroporous region; the second macroporous region There are second fibers forming a porous structure inside, the average diameter of the second fibers is 50-500nm; the porosity of the second macroporous region is 50-85%; the thickness of the second macroporous region accounts for the thickness of the film 3-13%.

第二大孔区内具有若干用于形成多孔结构的第二纤维，其平均直径为50-500nm，这样粗细的第二纤维形成了相应孔径和相应孔隙率的第二大孔区，继而保证膜整体的耐压强度和通量；There are several second fibers used to form porous structure in the second macroporous region, the average diameter of which is 50-500nm, such thick and thin second fibers form the second macroporous region of corresponding pore diameter and corresponding porosity, and then guarantee the membrane Overall compressive strength and flux;

第二大孔区的存在，有助于膜整体的通量，降低膜整体的透膜阻力；但也有可能对膜整体的机械强度(耐压强度)造成一定的影响(第二大孔区距离内表较远，因此第二大孔去的存在对膜的截留效率影响较小)；而本发明中具有合适的第二大孔区，第二大孔区的平均孔径为200-2000nm，且第二大孔区的平均孔径小于第一大孔区的平均孔径，第二大孔区的孔隙率为50-85％，即第二大孔区具有合适的平均孔径和孔隙率，使得膜整体依然具有较高的耐压强度，而膜的通量显著提高；此外如果第二大孔区的厚度占膜厚度的比例过高，那么膜整体的耐压强度就会降低；本发明中第二大孔区的厚度占膜厚度的3-13％，所占比例较小，进一步保证了膜整体的耐压强度基本不会变化，而膜的通量能够显著提高，透膜阻力能够大大降低，能量转化率变高，经济效益更高。The existence of the second large pore area is helpful to the overall flux of the membrane and reduces the overall membrane resistance of the membrane; but it may also have a certain impact on the overall mechanical strength (compressive strength) of the membrane (the distance between the second large pore area The inner surface is far away, so the presence of the second macropore has less impact on the interception efficiency of the membrane); and there is a suitable second macropore region in the present invention, and the average pore diameter of the second macropore region is 200-2000nm, and The average pore diameter of the second macroporous region is less than the average pore diameter of the first macroporous region, and the porosity of the second macroporous region is 50-85%, that is, the second macroporous region has suitable average pore diameter and porosity, so that the membrane as a whole Still have higher compressive strength, and the flux of membrane significantly improves; In addition, if the thickness of the second macropore area accounts for the ratio of membrane thickness too high, so the compressive strength of membrane integral body will reduce; In the present invention, the second The thickness of the macropore area accounts for 3-13% of the membrane thickness, which is a relatively small proportion, which further ensures that the overall compressive strength of the membrane will basically not change, while the flux of the membrane can be significantly improved, and the membrane penetration resistance can be greatly reduced. The energy conversion rate becomes higher and the economic benefit is higher.

本发明中第二大孔区的平均孔径、第二大孔区的厚度和第二纤维的平均直径等参数可以通过使用扫描电子显微镜对膜截面结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量后计算测得；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考。In the present invention, parameters such as the average pore diameter of the second macropore region, the thickness of the second macropore region and the average diameter of the second fiber can be characterized by the morphology of the membrane cross-sectional structure by using a scanning electron microscope, and then computer software (such as Matlab, NIS-Elements, etc.) or manual measurement and calculation; of course, those skilled in the art can also obtain the above parameters by other measurement means, and the above measurement means are for reference only.

作为本发明的进一步改进，所述PES中空纤维膜的内腔直径为0.3mm-1.5mm，膜厚为110-150μm，膜整体孔隙率为40-70％。As a further improvement of the present invention, the inner cavity diameter of the PES hollow fiber membrane is 0.3 mm-1.5 mm, the membrane thickness is 110-150 μm, and the overall porosity of the membrane is 40-70%.

所述PES中空纤维膜以切向流的形式用于生物大分子的纯化，各种物料是在中空纤维膜的内腔中流动，因此内径直径的大小也会影响单位时间物料纯化的多少；内腔越大，单位时间能纯化的物料越多；但如果内腔过大，则膜整体的耐压强度就会过低；本发明中PES中空纤维膜的内腔直径为0.3mm-1.5mm，既保证了膜整体具有较高的耐压强度，又能使较多的物料在单位时间内被纯化，经济效益高；The PES hollow fiber membrane is used for the purification of biological macromolecules in the form of tangential flow. Various materials flow in the inner cavity of the hollow fiber membrane, so the size of the inner diameter will also affect the amount of material purification per unit time; The larger the cavity, the more material that can be purified per unit time; but if the cavity is too large, the overall compressive strength of the membrane will be too low; the cavity diameter of the PES hollow fiber membrane in the present invention is 0.3mm-1.5mm, It not only ensures the high compressive strength of the membrane as a whole, but also enables more materials to be purified per unit time, with high economic benefits;

膜的厚度可以通过使用扫描电子显微镜对膜结构进行形貌表征后，再利用计算机软件(如Matlab、NIS-Elements等)或手工进行测量后计算测得；当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考；当膜的厚度过小时，其膜的机械强度就会较低；当膜的厚度过大时，其过滤时间就会过长，时间成本过大；本发明PES滤膜的厚度为110-150μm，保证了PES滤膜不仅具有较高的机械强度，而且能够进行有效的过滤且过滤效率较高，过滤时间较短，时间成本较低；The thickness of the film can be calculated and measured by computer software (such as Matlab, NIS-Elements, etc.) or manually measured after using a scanning electron microscope to characterize the film structure; of course, those skilled in the art can also use other measurements The above-mentioned parameters are obtained by means, and the above-mentioned measurement means are for reference only; when the thickness of the membrane is too small, the mechanical strength of the membrane will be low; when the thickness of the membrane is too large, the filtration time will be too long, and the time cost will be too large; The thickness of the PES filter membrane of the present invention is 110-150 μm, which ensures that the PES filter membrane not only has high mechanical strength, but also can perform effective filtration with high filtration efficiency, short filtration time and low time cost;

当膜的孔隙率过高时，会导致膜的拉伸强度过低，其机械性能较差，工业实用价值较低，无法满足市场需求；而当膜的孔隙率过低时，一方面会影响膜的流速，导致膜的过滤速度较慢，过滤时间较长，时间成本较大；本发明中多孔膜的孔隙率为40-70％，使得该膜不仅具有不错的拉伸强度，而且具有较快的过滤速度，通量大，使用寿命长，经济成本较低。When the porosity of the membrane is too high, the tensile strength of the membrane will be too low, its mechanical properties are poor, the industrial practical value is low, and it cannot meet the market demand; and when the porosity of the membrane is too low, on the one hand, it will affect The flow rate of the membrane causes the filtration speed of the membrane to be slower, the filtration time is longer, and the time cost is larger; the porosity of the porous membrane in the present invention is 40-70%, so that the membrane not only has good tensile strength, but also has relatively high Fast filtration speed, large flux, long service life and low economic cost.

作为本发明的进一步改进，所述PES中空纤维膜的水通量为400-3000L*h ^-1*m ^-2@10psi；所述PES中空纤维膜的耐压强度不低于30psi；所述PES中空纤维膜对于分子量为100kD-750kD的物质的截留效率大于90％；所述PES中空纤维膜的蛋白质收率不低于90％。 As a further improvement of the present invention, the water flux of the PES hollow fiber membrane is 400-3000L*h ^-1 *m ^-2 @10psi; the compressive strength of the PES hollow fiber membrane is not less than 30psi; the PES The retention efficiency of the hollow fiber membrane for substances with a molecular weight of 100kD-750kD is greater than 90%; the protein yield of the PES hollow fiber membrane is not lower than 90%.

渗透通量也称渗透速率，简称通量，指滤膜在分离过程中一定工作压力下单位时间内通过单位膜面积上的物质透过量；通量的大小，就反映着过滤速度的快慢；通量越大，说明膜的过滤速度越快；本发明中PES滤膜的水通量为400-3000L*h ^-1*m ^-2@10psi，其通量较大，说明中空纤维膜的过滤速度较快，在保证截留效率的同时，流体能够快速通过中空纤维膜，时间成本较低，经济效益较高。 Permeation flux is also called permeation rate, referred to as flux, which refers to the amount of material permeated through the unit membrane area per unit time under a certain working pressure in the separation process of the filter membrane; the size of the flux reflects the speed of filtration; The larger the amount, the faster the filtration rate of the membrane; the water flux of the PES filter membrane in the present invention is 400-3000L*h ^-1 *m ^-2 @10psi, and its flux is larger, indicating that the filtration rate of the hollow fiber membrane Faster, while ensuring the interception efficiency, the fluid can quickly pass through the hollow fiber membrane, the time cost is low, and the economic benefit is high.

在对相应的物料进行过滤纯化时，为了保证有足够的膜整体具有合适的通量，都会对膜内表面进行加压；一般情况加压的压力越大，膜整体的通量就能越大，单位时间经济效益就越高；并且本发明中所需要纯化的物料也是在膜内腔中流动，这就需要膜整体具有较高的耐压强度，经过测量PES中空纤维膜的耐压强度不低于30psi，这一方面保证了膜整体具有较高的通量，同时说明其机械性能较好，工业实用价值较高，完全能够满足市场需求；耐压强度可以通过万能拉力试验机测得，当然本领域技术人员也可以通过其他测量手段获得上述参数，上述测量手段仅供参考。When filtering and purifying the corresponding materials, in order to ensure that there is enough membrane to have a suitable flux, the inner surface of the membrane will be pressurized; generally, the greater the pressurized pressure, the greater the overall flux of the membrane. , the higher the economic benefit per unit time; and the material that needs to be purified in the present invention also flows in the membrane cavity, which requires the membrane as a whole to have a higher compressive strength. After measuring the compressive strength of the PES hollow fiber membrane is not Lower than 30psi, on the one hand, it ensures that the membrane has a higher flux as a whole, and at the same time, it shows that its mechanical properties are better, and its industrial practical value is higher, which can fully meet the market demand; the compressive strength can be measured by a universal tensile testing machine, Of course, those skilled in the art can also obtain the above parameters through other measurement means, and the above measurement means are for reference only.

本发明中PES中空纤维膜对于分子量为100kD-750kD的物质的截留效率大于90％，截留效率高，说明了该PES中空纤维膜特别适合应用于生物纯化，满足实际应用的需求；In the present invention, the interception efficiency of the PES hollow fiber membrane for substances with a molecular weight of 100kD-750kD is greater than 90%, and the interception efficiency is high, which shows that the PES hollow fiber membrane is particularly suitable for biological purification and meets the needs of practical applications;

PES中空纤维膜的蛋白质收率不低于90％，说明了物料中的有效物质蛋白质不容易吸附在膜上，一方面不会将膜孔堵住，保证滤膜依然具有较高的使用寿命，另一方面保证流体中的有效物质各种蛋白质的含量变化很小，蛋白质基本不会损失，经济效益有保证。The protein yield of the PES hollow fiber membrane is not less than 90%, which shows that the effective substance protein in the material is not easy to adsorb on the membrane. On the one hand, it will not block the membrane pores, ensuring that the filter membrane still has a high service life. On the other hand, it is guaranteed that the content of various proteins in the effective substances in the fluid changes very little, the protein will not be lost basically, and the economic benefit is guaranteed.

另一方面，本发明还提供了一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：On the other hand, the present invention also provides a method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：所述铸膜液包括下列重量份物质组成：聚醚砜15-25份，亲水添加剂10-30份；有机溶剂55-90份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为30-70％；所述非溶剂为水；所述亲水添加剂为聚乙二醇、聚乙烯吡咯烷酮、聚乙烯亚胺和聚乙烯醇中的至少一种；所述有机溶剂为二甲亚砜、二甲基甲酰胺、N-乙基吡咯烷酮、二甲基乙酰胺和N-甲基吡咯烷酮中的至少一种；Step 1: Prepare casting solution and core solution: the casting solution includes the following components by weight: 15-25 parts of polyethersulfone, 10-30 parts of hydrophilic additive; 55-90 parts of organic solvent; the core solution Including organic solvents and non-solvents; the content of non-solvents in the core liquid is 30-70%; the non-solvents are water; the hydrophilic additives are polyethylene glycol, polyvinylpyrrolidone, polyethyleneimine and poly At least one of vinyl alcohol; the organic solvent is at least one of dimethylsulfoxide, dimethylformamide, N-ethylpyrrolidone, dimethylacetamide and N-methylpyrrolidone;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为50-70℃，芯液温度为20-30℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution and the core solution are extruded from the double spinning nozzle, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 50- 70°C, the temperature of the core liquid is 20-30°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；Step 3: pre-separation: pre-separation of the molded product through the air section;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；Step 4: Re-phase separation: Put the pre-phase-separated molded product into the coagulation bath and then separate the phases to form a raw film;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane.

作为本发明的进一步改进，步骤三中预分相是指将成型品放置在湿度为70-100％的空气段中进行预分相，空气段长度为5-300mm，预分相时间为0.2-1s。As a further improvement of the present invention, pre-separation in step 3 refers to placing the molded product in an air section with a humidity of 70-100% for pre-separation, the length of the air section is 5-300mm, and the pre-separation time is 0.2- 1s.

作为本发明的进一步改进，步骤三中预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为10-400mm，预分相时间为0.5-2s。As a further improvement of the present invention, pre-phase separation in step 3 refers to placing the molded product in an air section filled with organic solvent vapor for pre-phase separation. The length of the air section is 10-400mm, and the pre-phase separation time is 0.5-2s.

作为本发明的进一步改进，步骤四再分相是指将预分相后的成型品放入温度为40-70℃的凝固浴中再分相，再分相时间为20-60s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为60-100％。As a further improvement of the present invention, the phase separation in step 4 refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 40-70°C for phase separation, and the phase separation time is 20-60s; the solidification The bath is a mixture of water and an organic solvent, and the water content in the coagulation bath is 60-100%.

作为本发明的进一步改进，拉伸处理是指对生膜进行1-5倍的拉伸，拉伸速率为3-12m/min。As a further improvement of the present invention, the stretching treatment refers to stretching the raw film by 1-5 times, and the stretching rate is 3-12m/min.

在制备本发明的PES中空纤维膜时，先配置铸膜液，铸膜液包括成膜物质聚醚砜(PES)，有机溶剂(用于溶剂聚醚砜材料)和亲水添加剂；其中亲水添加剂为聚乙二醇、聚乙烯吡咯烷酮、聚乙烯亚胺和聚乙烯醇中的至少一种，亲水添加剂的加入能够有空控制体系的粘度，抑制膜丝在分相过程中形成大孔，还能有效提高膜通量的稳定性；此外能够大大改善成膜的亲水性，使得膜丝具有较高的亲水性，具有低蛋白吸附；通过调节聚醚砜、有机溶剂和亲水添加剂的比例，使得铸膜液具有合适的粘度，铸膜液粘度会对最终形成的滤膜的结构以及性能产生较大的影响，例如影响滤膜的孔径，厚度，流速等；从而保证了最终制得的PES中空纤维膜具有合适的厚度以及理想的膜孔结构和孔径大小，继而应用于纯化生物大分子；此外本发明中空纤维膜挤出时采用的内芯为液体形式，因此需要选择合适的芯液，芯液中包括有机溶剂和非溶剂，其中有机溶剂即为铸膜液中的有机溶剂，而非溶剂为水；选择合适的芯液一方面能够保证中空纤维膜腔内压强与外界压强保持平衡，从而稳定中空纤维膜的腔，使得中空纤维膜的壁厚基本相同，另一方面芯液还会影响内表面的孔径大小，在和凝固浴等条件的共同作用下，通过控制膜分相过程中的变化，从而制造出理想截留分子量，理想孔径分布的PES中空纤维膜，该中空纤维膜特别适合应用于生物大分子纯化；When preparing the PES hollow fiber membrane of the present invention, the casting solution is first configured, and the casting solution includes a film-forming substance polyethersulfone (PES), an organic solvent (for solvent polyethersulfone material) and a hydrophilic additive; wherein the hydrophilic The additive is at least one of polyethylene glycol, polyvinylpyrrolidone, polyethyleneimine and polyvinyl alcohol, and the addition of the hydrophilic additive can effectively control the viscosity of the system and inhibit the formation of macropores during the phase separation process of the membrane filament. It can also effectively improve the stability of the membrane flux; in addition, it can greatly improve the hydrophilicity of the membrane, making the membrane silk have high hydrophilicity and low protein adsorption; by adjusting polyethersulfone, organic solvents and hydrophilic additives The proportion of the casting solution makes the casting solution have a suitable viscosity, and the viscosity of the casting solution will have a great impact on the structure and performance of the final filter membrane, such as affecting the pore size, thickness, flow rate, etc. of the filter membrane; thus ensuring the final production The obtained PES hollow fiber membrane has suitable thickness and ideal membrane pore structure and pore size, and is then applied to the purification of biomacromolecules; Core liquid, the core liquid includes organic solvent and non-solvent, among which the organic solvent is the organic solvent in the casting liquid, and the non-solvent is water; choosing a suitable core liquid can ensure the pressure inside the hollow fiber membrane cavity and the external pressure on the one hand Maintain balance, thereby stabilizing the cavity of the hollow fiber membrane, so that the wall thickness of the hollow fiber membrane is basically the same. On the other hand, the core fluid will also affect the pore size of the inner surface. Changes in the phase process, so as to produce a PES hollow fiber membrane with an ideal molecular weight cut-off and an ideal pore size distribution, which is especially suitable for the purification of biological macromolecules;

第二步是将纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；该成型品，即中空纤维膜；所挤出的中空纤维膜具有面向腔的表面，即内表面，和与腔相反的表面，即外表面；The second step is spinning: the casting solution and the core solution are extruded from the double spinning nozzle, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the molded product, that is, the hollow fiber membrane The extruded hollow fiber membrane has a surface facing the cavity, i.e. an inner surface, and a surface opposite to the cavity, i.e. an outer surface;

步骤三：预分相：将所述成型品经过空气段下进行预分相；在进行预分相时，由于内表面与芯液直接接触，相分离发生较快，容易形成小孔；并且由于芯液中含有了一定量的非溶剂水，这些非溶剂水能够与铸膜液中的溶剂进行置换，从而进行保证内表面形成合适大小的孔径，并且内表面相对致密(孔洞面积率较低)；此外，通过温度的控制，铸膜液的温度为50-70℃，芯液温度为20-30℃；喷嘴温度和铸膜液温度相同，即喷出的膜丝温度和内部的芯液温度有一定的差别，之所以这样设置，是因为膜的分相速度除了与溶剂与非溶剂之间的交换速度有关外，还与温度以及温差有关，温差变化越大，越能加快膜的分相速度；通过上述各因素的共同作用，从而有利于膜丝内表面形成相对致密的孔径较小的分离皮层，分离皮层的存在就使得中空纤维膜能够以切向流的形式用于生物大分子的纯化；在分离皮层形成后，分离皮层会阻碍了非溶剂水的扩散，使得成型品中有机溶剂与芯液中非溶剂水的交换速度，需要更多的非溶剂才能发生相分离(相较于凝固浴，芯液中的非溶剂水含量也不高)，相分离速度减缓，就容易形成大孔结构(即本发明成膜的第一大孔区)，并且形成的大孔结构会更靠近内表面(较远离外表面)；Step 3: Pre-separation: Pre-separate the molded product through the air section; during the pre-separation, due to the direct contact between the inner surface and the core liquid, the phase separation occurs quickly and small holes are easily formed; and because The core liquid contains a certain amount of non-solvent water, which can be replaced with the solvent in the casting liquid, so as to ensure that the inner surface forms a suitable pore size, and the inner surface is relatively dense (lower hole area ratio) ;In addition, through temperature control, the temperature of the casting liquid is 50-70°C, and the temperature of the core liquid is 20-30°C; the temperature of the nozzle and the temperature of the casting liquid are the same, that is, the temperature of the ejected film filament and the temperature of the internal core liquid There is a certain difference. The reason for this setting is that the phase separation speed of the membrane is not only related to the exchange speed between the solvent and the non-solvent, but also related to the temperature and the temperature difference. The greater the change in the temperature difference, the faster the phase separation of the membrane. Speed; through the joint action of the above factors, it is beneficial to form a relatively dense separation skin with a small pore size on the inner surface of the membrane filament. The existence of the separation skin makes the hollow fiber membrane available in the form of tangential flow for biological macromolecules. Purification; after the separation cortex is formed, the separation cortex will hinder the diffusion of non-solvent water, so that the exchange rate between the organic solvent in the molded product and the non-solvent water in the core liquid requires more non-solvent to phase separate (compared to coagulation bath, the non-solvent water content in the core liquid is not high), the phase separation speed slows down, and it is easy to form a macroporous structure (that is, the first macroporous region of the present invention), and the formed macroporous structure will be closer to the inner surface (further away from the outer surface);

与此同时，在进行预分相的过程中，通过将成型品放置在湿度为70-100％的空气段中进行预分相，空气段长度为5-300mm，预分相时间为0.2-1s；通过一定湿度的空气段(空气中含有一定的水汽)、空气段的长度、预分相时间以及铸膜液等因素的共同作用下，保证了外表面也出现了合适孔径大小，合适孔径数量的孔洞，外表面的孔洞孔径一般都比内表面的孔洞孔径大，保证了中空纤维膜具有较高的水通量；有时候需要进一步提高膜丝的水通量，那么通过将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为10-400mm，预分相时间为0.5-2s，该有机溶剂与铸膜液中的有机溶剂相同，相较于在一定湿度的空气段，成型品在充满有机溶剂蒸气的空气段中的分相速度会更慢，分相速度越慢，形成的孔洞孔径就会越大，从而形成了本发明中空纤维膜的第二大孔区；At the same time, in the process of pre-phase separation, pre-phase separation is carried out by placing the molded product in an air section with a humidity of 70-100%, the length of the air section is 5-300mm, and the pre-phase separation time is 0.2-1s ;Under the joint action of factors such as the air section with a certain humidity (the air contains a certain amount of water vapor), the length of the air section, the pre-phase separation time, and the casting solution, it is ensured that the outer surface also has a suitable pore size and a suitable pore size. The holes on the outer surface are generally larger than the holes on the inner surface, which ensures that the hollow fiber membrane has a higher water flux; Pre-phase separation is carried out in the air section of the organic solvent vapor. The length of the air section is 10-400mm, and the pre-phase separation time is 0.5-2s. The organic solvent is the same as the organic solvent in the casting solution. Compared with the air at a certain humidity Section, the phase separation speed of the molded product in the air section full of organic solvent vapor will be slower, the slower the phase separation speed, the larger the hole diameter will be, thus forming the second macropore area of the hollow fiber membrane of the present invention ;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，成型品放入温度为40-70℃的凝固浴中再分相，再分相时间为20-60s；凝固浴为水和有机溶剂的混合物(该有机溶剂与铸膜液中的有机溶剂相同)，凝固浴中水含量为60-100％(即假设凝固浴有100ml，那么其中水体积为60-100ml，剩余液体为有机溶剂)；通过合适的凝固浴种类和温度、相应的分相固化时间，并且与铸膜液体系共同作用下，从而有利于获得理想膜孔径大小的中空纤维膜；Step 4: Re-phase separation: Put the pre-phase-separated molded product into the coagulation bath and then phase-separate. The molded product is placed in a coagulation bath with a temperature of 40-70°C and then phase-separate. The time of the phase-separation is 20-60s The coagulation bath is the mixture of water and organic solvent (this organic solvent is identical with the organic solvent in the film-casting liquid), and in the coagulation bath, water content is 60-100% (assuming that coagulation bath has 100ml, so wherein water volume is 60-100% 100ml, the remaining liquid is an organic solvent); through the appropriate type and temperature of the coagulation bath, the corresponding phase separation solidification time, and the joint action of the casting liquid system, it is beneficial to obtain a hollow fiber membrane with an ideal membrane pore size;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜；拉伸处理是指对生膜进行1-5倍的拉伸，拉伸速率为3-12m/min；拉伸的方式，可以通过前后辊的速度差形成相应的拉伸；通过对生膜进行拉伸后，其机械强度会提高，成为强韧的膜丝，从而保证成膜具有较高的耐压强度应用范围更广；同时对生膜仅仅是低倍数的拉伸，是防止对膜丝的孔径大小大小影响，保证最后的成膜依然具有合适的孔径大小，具有高截留效率；同时由于经过拉伸，成膜内表面的第一孔洞就变成了狭缝形；在拉伸的同时可以用水清洗(也可以在拉伸之后再用水清洗)，进一步除去膜丝中含有的有机溶剂，最后烘干(可以自然烘干也可以选择其他方式烘干)，最终制得所需要的成膜。Step 5: Stretch the raw film, wash it in water, and finally dry it to obtain a PES hollow fiber membrane; the stretching treatment refers to stretching the raw film by 1-5 times, and the stretching rate is 3-5 times. 12m/min; the way of stretching can be stretched according to the speed difference between the front and rear rollers; after stretching the raw film, its mechanical strength will increase and become a strong film filament, thus ensuring that the film has a relatively high High compressive strength has a wider range of applications; at the same time, the raw film is only stretched at a low multiple to prevent the impact on the pore size of the membrane filament, ensuring that the final film still has a suitable pore size and high retention efficiency; At the same time, due to stretching, the first hole on the inner surface of the film becomes a slit; it can be washed with water while stretching (it can also be washed with water after stretching) to further remove the organic matter contained in the film filament. The solvent is finally dried (it can be dried naturally or other methods can be selected), and finally the required film is obtained.

一种用于纯化生物大分子的PES中空纤维膜的应用，所述PES中空纤维膜以切向流的形式用于：(a)疫苗或病毒载体的纯化、浓缩和透析；(b)蛋白质的浓缩和透析；(c)发酵液中细胞和细菌的澄清过滤；(d)细胞和菌体的回收和透析。An application of a PES hollow fiber membrane for purifying biomacromolecules, the PES hollow fiber membrane is used in the form of tangential flow for: (a) purification, concentration and dialysis of vaccines or viral vectors; (b) purification of proteins Concentration and dialysis; (c) clarification and filtration of cells and bacteria in the fermentation broth; (d) recovery and dialysis of cells and bacteria.

不同粘度，不同种类的物料选择合适内径大小，合适膜孔大小和合适厚度的中空纤维膜，从而保证高截留效率和高通量，并且具有较长的使用寿命。Different viscosities, different types of materials, choose hollow fiber membranes with appropriate inner diameter, appropriate membrane pore size and appropriate thickness, so as to ensure high retention efficiency and high flux, and have a long service life.

本发明的有益效果：本发明提供了一种PES中空纤维膜，包括主体，主体的一侧为内表面，另一侧为外表面；内表面上具有若干个狭缝形的第一孔洞，所述第一孔洞的孔径宽度平均值为60nm-450nm，第一孔洞在内表面上的孔洞面积率为5-30％，其中所述第一孔洞的孔径宽度方向与中空纤维膜的周向一致；从而使得该PES中空纤维膜具有高截留效率，以切向流过滤的方式纯化各种生物大分子，其截流分子量为100K-750K；在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小；主体包括分离层和支撑层，支撑层包括第一大孔区，第一大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的4倍以上，第一大孔区的存在使得膜具有高通量，同时能够提供缓冲作用，降低透膜阻力，膜组件的能量转化率更高，经济效益更高；本发明提供的制备方法，可以方便、快速、有效地制备获得上述PES中空纤维膜。Beneficial effects of the present invention: the present invention provides a PES hollow fiber membrane, including a main body, one side of the main body is an inner surface, and the other side is an outer surface; the inner surface has several slit-shaped first holes, so The average pore width of the first hole is 60nm-450nm, the area ratio of the first hole on the inner surface is 5-30%, wherein the pore width direction of the first hole is consistent with the circumferential direction of the hollow fiber membrane; Therefore, the PES hollow fiber membrane has a high retention efficiency, and various biomacromolecules are purified by tangential flow filtration, and its cut-off molecular weight is 100K-750K; in the direction of membrane thickness from the inner surface to the outer surface, the main body The average pore diameter first increases and then decreases; the main body includes a separation layer and a support layer, and the support layer includes a first large pore area, and the average pore diameter of the first large pore area is at least 4 times the average value of the pore width of the first hole, The existence of the first macroporous area makes the membrane have high flux, and at the same time can provide a buffering effect, reduce the resistance of the membrane, the energy conversion rate of the membrane module is higher, and the economic benefit is higher; the preparation method provided by the invention can be convenient and fast , and effectively prepare and obtain the above-mentioned PES hollow fiber membrane.

附图说明Description of drawings

图1为实施例1制备获得的PES中空纤维膜整体的扫描电镜(SEM)图，其中放大倍率为60×；Fig. 1 is the scanning electron microscope (SEM) figure of the whole PES hollow fiber membrane that the embodiment 1 prepares, and wherein magnification is 60 *;

图2为实施例1制备获得的PES中空纤维膜截面中靠近内表面一侧的扫描电镜(SEM)图，其中放大倍率为1000×；Fig. 2 is the scanning electron microscope (SEM) picture of the side close to the inner surface in the cross-section of the PES hollow fiber membrane prepared in Example 1, wherein the magnification is 1000 ×;

图3为实施例1制备获得的PES中空纤维膜截面中靠近内表面一侧进一步放大的扫描电镜(SEM)图，其中放大倍率为2000×；Fig. 3 is the further enlarged scanning electron microscope (SEM) picture of the side close to the inner surface in the cross-section of the PES hollow fiber membrane prepared in Example 1, wherein the magnification is 2000 ×;

图4为实施例1制备获得的PES中空纤维膜截面中靠近内表面一侧更进一步放大的扫描电镜(SEM)图，其中放大倍率为10000×；Fig. 4 is the further enlarged scanning electron microscope (SEM) picture of the side close to the inner surface in the cross-section of the PES hollow fiber membrane prepared in Example 1, wherein the magnification is 10000 ×;

图5为实施例1制备获得的PES中空纤维膜内表面的扫描电镜(SEM)图，其中放大倍率为10000×；5 is a scanning electron microscope (SEM) image of the inner surface of the PES hollow fiber membrane prepared in Example 1, wherein the magnification is 10000×;

图6为实施例1制备获得的PES中空纤维膜外表面的扫描电镜(SEM)图，其中放大倍率为2000×；6 is a scanning electron microscope (SEM) image of the outer surface of the PES hollow fiber membrane prepared in Example 1, wherein the magnification is 2000×;

图7为实施例2制备获得的PES中空纤维膜内表面的扫描电镜(SEM)图，其中放大倍率为10K×；Figure 7 is a scanning electron microscope (SEM) image of the inner surface of the PES hollow fiber membrane prepared in Example 2, wherein the magnification is 10K×;

图8为实施例2制备获得的PES中空纤维膜内表面进一步放大的扫描电镜(SEM)图，其中放大倍率为20K×；Figure 8 is a further enlarged scanning electron microscope (SEM) image of the inner surface of the PES hollow fiber membrane prepared in Example 2, wherein the magnification is 20K×;

图9为实施例2制备获得的PES中空纤维膜外表面的扫描电镜(SEM)图，其中放大倍率为2000×；9 is a scanning electron microscope (SEM) image of the outer surface of the PES hollow fiber membrane prepared in Example 2, wherein the magnification is 2000×;

图10为实施例3制备获得的PES中空纤维膜截面的扫描电镜(SEM)图，其中放大倍率为500×；Figure 10 is a scanning electron microscope (SEM) image of the cross-section of the PES hollow fiber membrane prepared in Example 3, wherein the magnification is 500×;

图11为实施例3制备获得的PES中空纤维膜截面中靠近内表面一侧的扫描电镜(SEM)图，其中放大倍率为5000×；Figure 11 is a scanning electron microscope (SEM) image of the side near the inner surface in the section of the PES hollow fiber membrane prepared in Example 3, wherein the magnification is 5000×;

图12为实施例3制备获得的PES中空纤维膜截面中靠近外表面一侧的扫描电镜(SEM)图，其中放大倍率为5000×；Figure 12 is a scanning electron microscope (SEM) image of the side near the outer surface of the PES hollow fiber membrane section prepared in Example 3, wherein the magnification is 5000×;

图13为实施例4制备获得的PES中空纤维膜截面中第一大孔区处的扫描电镜(SEM)图，其中放大倍率为2K×；Figure 13 is a scanning electron microscope (SEM) image of the first macropore area in the section of the PES hollow fiber membrane prepared in Example 4, wherein the magnification is 2K×;

图14为实施例4制备获得的PES中空纤维膜截面中第一大孔区处进一步放大的扫描电镜(SEM)图，其中放大倍率为10K×；Figure 14 is a scanning electron microscope (SEM) image further enlarged at the first macropore area in the section of the PES hollow fiber membrane prepared in Example 4, wherein the magnification is 10K×;

图15为实施例7制备获得的PES中空纤维膜截面的扫描电镜(SEM)图，其中放大倍率为500×；Figure 15 is a scanning electron microscope (SEM) image of the cross-section of the PES hollow fiber membrane prepared in Example 7, wherein the magnification is 500×;

图16为实施例7制备获得的PES中空纤维膜截面中靠近内表面一侧的扫描电镜(SEM)图，其中放大倍率为1000×；Figure 16 is a scanning electron microscope (SEM) image of the side near the inner surface in the section of the PES hollow fiber membrane prepared in Example 7, wherein the magnification is 1000×;

图17为实施例7制备获得的PES中空纤维膜截面中靠近外表面一侧的扫描电镜(SEM)图，其中放大倍率为1000×；Figure 17 is a scanning electron microscope (SEM) image of the side near the outer surface of the PES hollow fiber membrane section prepared in Example 7, wherein the magnification is 1000×;

图18为实施例7制备获得的PES中空纤维膜截面中靠近外表面一侧进一步放大的扫描电镜(SEM)图，其中放大倍率为2000×；Figure 18 is a further enlarged scanning electron microscope (SEM) image of the side near the outer surface of the cross-section of the PES hollow fiber membrane prepared in Example 7, wherein the magnification is 2000×;

图19为实施例7制备获得的PES中空纤维膜截面中靠近外表面一侧更加一步放大的扫描电镜(SEM)图，其中放大倍率为5000×；Figure 19 is a further enlarged scanning electron microscope (SEM) image of the side near the outer surface in the section of the PES hollow fiber membrane prepared in Example 7, wherein the magnification is 5000×;

图20为本发明PES中空纤维膜通量测试装置的示意图；Figure 20 is a schematic diagram of the PES hollow fiber membrane flux testing device of the present invention;

图21为本发明PES中空纤维膜截留效率测试时测试装置的示意图。Fig. 21 is a schematic diagram of the test device for the test of the retention efficiency of the PES hollow fiber membrane of the present invention.

具体实施方式Detailed ways

为了更清楚的阐释本申请的整体构思，下面以实施例的方式进行详细说明。如未特殊说明，在下述实施例中，制备滤膜所用的原料及设备均可通过商业途径购得。其中，采用日立公司提供的型号为S-5500的扫描电镜对滤膜的结构形貌进行表征。In order to illustrate the overall concept of the present application more clearly, the following will be described in detail in the form of examples. Unless otherwise specified, in the following examples, the raw materials and equipment used to prepare the filter membranes can be purchased from commercial sources. Among them, the S-5500 scanning electron microscope provided by Hitachi was used to characterize the structure and morphology of the filter membrane.

实施例1一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 1 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：铸膜液包括下列重量份物质组成：聚醚砜17份，亲水添加剂聚乙二醇13份；有机溶剂64份；芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为30-70％；所述非溶剂为水；有机溶剂均为二甲基甲酰胺；Step 1: Prepare casting solution and core solution: casting solution includes the following components by weight: 17 parts of polyethersulfone, 13 parts of hydrophilic additive polyethylene glycol; 64 parts of organic solvent; core solution includes organic solvent and non-solvent ; The content of the non-solvent in the core liquid is 30-70%; the non-solvent is water; the organic solvent is dimethylformamide;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；铸膜液的温度为55℃，芯液温度为20℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: The casting liquid is extruded from the double spinning nozzle together with the core liquid, and the casting liquid forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting liquid is 55°C, and the core The temperature of the liquid is 20°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相：将成型品放置在湿度为95％的空气段中进行预分相，空气段长度为30mm，预分相时间为0.3s；Step 3: Pre-separation: Pre-separate the molded product through the air section: place the molded product in an air section with a humidity of 95% for pre-separation, the length of the air section is 30mm, and the pre-separation time is 0.3s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为40℃的凝固浴中再分相，再分相时间为25s；凝固浴为水和有机溶剂的混合物，凝固浴中水含量为95％。Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then separate the phase to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 40°C Re-phase separation in the middle, and the phase separation time is 25s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 95%.

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜；其中拉伸处理是指对生膜进行2倍的拉伸，拉伸速率为5m/min。Step 5: Stretch the raw film, wash it in water, and finally dry it to obtain a PES hollow fiber membrane; the stretching treatment refers to stretching the raw film by 2 times, and the stretching rate is 5m/min .

实施例2一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 2 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：所述铸膜液包括下列重量份物质组成：聚醚砜20份，亲水添加剂聚乙烯吡咯烷酮13份；有机溶剂72份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为55％；所述非溶剂为水；所述有机溶剂均为N-乙基吡咯烷酮；Step 1: Prepare casting solution and core solution: the casting solution includes the following components by weight: 20 parts of polyethersulfone, 13 parts of hydrophilic additive polyvinylpyrrolidone; 72 parts of organic solvent; the core solution includes organic solvent and non-solvent; the content of non-solvent in the core liquid is 55%; the non-solvent is water; the organic solvent is N-ethylpyrrolidone;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；其中铸膜液的温度为59℃，芯液温度为23℃；喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting liquid is extruded from the double spinning nozzle together with the core liquid, and the casting liquid forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting liquid is 59°C, The core liquid temperature is 23°C; the nozzle temperature is the same as the casting liquid temperature;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在湿度为90％的空气段中进行预分相，空气段长度为80mm，预分相时间为0.5s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section with a humidity of 90% for pre-separation, and the length of the air section is 80mm. The pre-phase splitting time is 0.5s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为50℃的凝固浴中再分相，再分相时间为35s；凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为85％；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 50°C Phase separation again, the phase separation time is 35s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 85%;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜；拉伸处理是指对生膜进行3倍的拉伸，拉伸速率为7m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane; the stretching treatment refers to stretching the raw membrane 3 times, and the stretching rate is 7m/min.

实施例3一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 3 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：Step 1: Prepare casting solution and core solution:

所述铸膜液包括下列重量份物质组成：聚醚砜22份，亲水添加剂聚乙烯亚胺21份；有机溶剂80份；The casting solution comprises the following components by weight: 22 parts of polyethersulfone, 21 parts of hydrophilic additive polyethyleneimine; 80 parts of organic solvent;

所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为45％；非溶剂为水；有机溶剂均为二甲基乙酰胺；The core liquid includes an organic solvent and a non-solvent; the content of the non-solvent in the core liquid is 45%; the non-solvent is water; the organic solvent is dimethylacetamide;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；铸膜液的温度为63℃，芯液温度为26℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: The casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 63°C, and the core The temperature of the liquid is 26°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在湿度为85％的空气段中进行预分相，空气段长度为150mm，预分相时间为0.7s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section with a humidity of 85% for pre-separation, and the length of the air section is 150mm. The pre-phase splitting time is 0.7s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为60℃的凝固浴中再分相，再分相时间为45s；凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为75％；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 60°C Phase separation again, the phase separation time is 45s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 75%;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜；拉伸处理是指对生膜进行4倍的拉伸，拉伸速率为9m/min。Step 5: Stretch the raw film, wash it in water, and finally dry it to obtain a PES hollow fiber membrane; the stretching treatment refers to stretching the raw film 4 times, and the stretching rate is 9m/min.

实施例4一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 4 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：所述铸膜液包括下列重量份物质组成：聚醚砜25份，亲水添加剂聚乙烯醇26份；有机溶剂88份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为35％；所述非溶剂为水；所述有机溶剂为N-甲基吡咯烷酮；Step 1: Prepare casting solution and core solution: the casting solution includes the following components by weight: 25 parts of polyethersulfone, 26 parts of hydrophilic additive polyvinyl alcohol; 88 parts of organic solvent; the core solution includes organic solvent and non-solvent; the content of non-solvent in the core liquid is 35%; the non-solvent is water; the organic solvent is N-methylpyrrolidone;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为67℃，芯液温度为29℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 67°C , the temperature of the core liquid is 29°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在湿度为80％的空气段中进行预分相，空气段长度为200mm，预分相时间为0.9s。Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section with a humidity of 80% for pre-separation, and the length of the air section is 200mm. The pre-phase splitting time is 0.9s.

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为70℃的凝固浴中再分相，再分相时间为55s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为65％；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 70°C Phase separation again, the phase separation time is 55s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 65%;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。拉伸处理是指对生膜进行5倍的拉伸，拉伸速率为11m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane. Stretching treatment refers to stretching the raw film 5 times at a stretching rate of 11 m/min.

实施例5一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 5 A kind of preparation method of the PES hollow fiber membrane that is used to purify biomacromolecule, comprises the following steps:

步骤一：制备铸膜液和芯液：铸膜液包括下列重量份物质组成：聚醚砜15份，亲水添加剂11份；有机溶剂60份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为60％；所述非溶剂为水；所述亲水添加剂为聚乙烯醇；所述有机溶剂均为二甲亚砜；Step 1: Prepare casting solution and core solution: casting solution includes the following components by weight: 15 parts of polyethersulfone, 11 parts of hydrophilic additive; 60 parts of organic solvent; the core solution includes organic solvent and non-solvent; The content of non-solvent in the core liquid is 60%; the non-solvent is water; the hydrophilic additive is polyvinyl alcohol; the organic solvent is dimethyl sulfoxide;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为57℃，芯液温度为21℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 57°C , the temperature of the core liquid is 21°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为70mm，预分相时间为0.5s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section full of organic solvent vapor for pre-separation, and the length of the air section is 70mm. The pre-phase splitting time is 0.5s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为45℃的凝固浴中再分相，再分相时间为20s；所述凝固浴为纯水；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 45°C Phase separation again, the phase separation time is 20s; the coagulation bath is pure water;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。拉伸处理是指对生膜进行1倍的拉伸，拉伸速率为3m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane. Stretching treatment refers to stretching the raw film by 1 time, and the stretching rate is 3m/min.

实施例6一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 6 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：所述铸膜液包括下列重量份物质组成：聚醚砜18份，亲水添加剂15份；有机溶剂68份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为50％；所述非溶剂为水；所述亲水添加剂为聚乙烯亚胺；所述有机溶剂均为二甲基乙酰胺；Step 1: Prepare casting solution and core solution: the casting solution includes the following components by weight: 18 parts of polyethersulfone, 15 parts of hydrophilic additives; 68 parts of organic solvent; the core solution includes organic solvent and non-solvent The content of the non-solvent in the core liquid is 50%; the non-solvent is water; the hydrophilic additive is polyethyleneimine; the organic solvent is dimethylacetamide;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为60℃，芯液温度为24℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 60°C , the temperature of the core liquid is 24°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为150mm，预分相时间为1s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section full of organic solvent vapor for pre-separation, and the length of the air section is 150mm. The pre-phase splitting time is 1s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为55℃的凝固浴中再分相，再分相时间为30s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为90％；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 55°C Phase separation again, the phase separation time is 30s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 90%;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。拉伸处理是指对生膜进行2倍的拉伸，拉伸速率为5m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane. Stretching treatment refers to stretching the raw film by 2 times, and the stretching rate is 5m/min.

实施例7一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 7 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：所述铸膜液包括下列重量份物质组成：聚醚砜21份，亲水添加剂19份；有机溶剂76份；所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为40％；所述非溶剂为水；所述亲水添加剂为聚乙烯吡咯烷酮；所述有机溶剂均为N-乙基吡咯烷酮；Step 1: Prepare casting solution and core solution: the casting solution includes the following components by weight: 21 parts of polyethersulfone, 19 parts of hydrophilic additives; 76 parts of organic solvent; the core solution includes organic solvent and non-solvent The content of the non-solvent in the core liquid is 40%; the non-solvent is water; the hydrophilic additive is polyvinylpyrrolidone; the organic solvents are all N-ethylpyrrolidone;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为65℃，芯液温度为27℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 65°C , the temperature of the core liquid is 27°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为250mm，预分相时间为1.5s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section full of organic solvent vapor for pre-separation, and the length of the air section is 250mm. The pre-phase splitting time is 1.5s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为65℃的凝固浴中再分相，再分相时间为40s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为80％。Step 4: Re-phase separation: Put the pre-phase-separated molded product into the coagulation bath and then separate the phase to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into the coagulation bath with a temperature of 65°C Re-separation of phases, the re-separation time is 40s; the coagulation bath is a mixture of water and an organic solvent, and the water content in the coagulation bath is 80%.

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。拉伸处理是指对生膜进行3倍的拉伸，拉伸速率为7m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane. Stretching treatment refers to stretching the raw film 3 times, and the stretching rate is 7m/min.

实施例8一种用于纯化生物大分子的PES中空纤维膜的制备方法，包括以下步骤：Embodiment 8 A method for preparing a PES hollow fiber membrane for purifying biological macromolecules, comprising the following steps:

步骤一：制备铸膜液和芯液：铸膜液包括下列重量份物质组成：聚醚砜23份，亲水添加剂24份；有机溶剂84份；芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为30％；所述非溶剂为水；亲水添加剂为聚乙二醇；所述有机溶剂均为二甲基甲酰胺；Step 1: Prepare casting solution and core solution: casting solution includes the following components by weight: 23 parts of polyethersulfone, 24 parts of hydrophilic additives; 84 parts of organic solvent; core solution includes organic solvent and non-solvent; the core The content of the non-solvent in the liquid is 30%; the non-solvent is water; the hydrophilic additive is polyethylene glycol; the organic solvent is dimethylformamide;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为70℃，芯液温度为30℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution is extruded from the double spinning nozzle together with the core solution, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 70°C , the temperature of the core liquid is 30°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为360mm，预分相时间为2s；Step 3: Pre-separation: Pre-separate the molded product through the air section; pre-separation refers to placing the molded product in an air section full of organic solvent vapor for pre-separation, and the length of the air section is 360mm. The pre-phase splitting time is 2s;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；再分相是指将预分相后的成型品放入温度为70℃的凝固浴中再分相，再分相时间为50s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为70％；Step 4: Re-phase separation: put the pre-phase-separated molded product into the coagulation bath and then phase-separate to form a raw film; re-phase separation refers to putting the pre-phase-separated molded product into a coagulation bath with a temperature of 70°C Phase separation again, the phase separation time is 50s; the coagulation bath is a mixture of water and organic solvent, and the water content in the coagulation bath is 70%;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。拉伸处理是指对生膜进行4倍的拉伸，拉伸速率为9m/min。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane. Stretching treatment refers to stretching the raw film 4 times, and the stretching rate is 9m/min.

一：结构表征1: Structural characterization

用扫描电镜对各实施例所获得的PES中空纤维膜的膜结构进行形貌表征，然后获得所需数据；具体结果如下表：The membrane structure of the PES hollow fiber membrane obtained in each embodiment was characterized by scanning electron microscopy, and then the required data was obtained; the specific results are as follows:

表1：Table 1:

表2Table 2

表3table 3

表4Table 4

表5table 5

表6Table 6

由表1-6可知，本发明实施例1-8制得的PES中空纤维膜均是一体成膜，没有经过复合工艺，工艺制备简单，适合大规模推广应用；且实施例1-8制得的PES中空纤维膜均具有理想的膜结构，内表面上第一孔洞具有合适的孔径宽度，适宜截留不同分子量的物质，从而进行各种生物大分子的纯化；在靠近内表面的一侧均具有第一大孔区，第一大孔区的存在，大大提高了膜整体的通量，降低了传质阻力，提高了膜组件的完整性，使用寿命变长；并且根据表2表3可知(例如以实施例1-4进行对比)，当内表面上第一孔洞的孔径宽度平均值越小时，第一大孔区的厚度就要越小，且第一大孔区距离内表面的最近距离也要变大，这样就能很好防止第一大孔区对膜整体截留效率造成不良的影响，膜整体依然具有高截留效率，特别适合以切向流的形式纯化各种生物大分子。It can be seen from Table 1-6 that the PES hollow fiber membranes prepared in Examples 1-8 of the present invention are all integrally formed into membranes, without a composite process, the process preparation is simple, and suitable for large-scale popularization and application; and Examples 1-8 obtained All PES hollow fiber membranes have an ideal membrane structure, and the first hole on the inner surface has a suitable pore width, which is suitable for intercepting substances with different molecular weights, so as to purify various biological macromolecules; on the side close to the inner surface, there are The first macroporous region, the existence of the first macroporous region, greatly improves the overall flux of the membrane, reduces the mass transfer resistance, improves the integrity of the membrane module, and prolongs the service life; and according to Table 2 and Table 3, it can be seen that ( For example, compare with Embodiment 1-4), when the average value of the aperture width of the first hole on the inner surface is smaller, the thickness of the first macropore area will be smaller, and the shortest distance between the first macropore area and the inner surface It should also be larger, so that it can well prevent the first large pore area from adversely affecting the overall retention efficiency of the membrane. The overall membrane still has a high retention efficiency, and is especially suitable for purifying various biological macromolecules in the form of tangential flow.

性能特征performance characteristics

膜通量计算如下式：膜通量(J)的计算公式为：J＝V/(T×A)式中:The calculation formula of membrane flux is as follows: the calculation formula of membrane flux (J) is: J=V/(T×A) where:

J--膜通量单位：L*h ^-1*m ^-2 J--membrane flux unit: L*h ^-1 *m ^-2

V--取样体积(L)；T--取样时间(h)；A--膜有效面积(m2)V--sampling volume (L); T--sampling time (h); A--membrane effective area (m2)

本发明中PES滤膜分离性能测定采用的操作条件为：进液为去离子水，操作压力为10psi，操作温度为25℃，溶液pH为7；通量测试装置为图20；The operating conditions used in the determination of the separation performance of the PES filter membrane in the present invention are: the inlet liquid is deionized water, the operating pressure is 10 psi, the operating temperature is 25 ° C, and the pH of the solution is 7; the flux testing device is shown in Figure 20;

过滤精度测试：对各示例所得PES滤膜进行拦截效率的测试；其中：实施例1和实施例5截留的物质的分子量为100K；实施例2和实施例6截留的物质的分子量为300K；实施例3和实施例7截留的物质的分子量为500K；实施例4和实施例8截留的物质的分子量为750K；Filtration precision test: each example gained PES filter membrane is carried out the test of interception efficiency; Wherein: the molecular weight of the substance intercepted in embodiment 1 and embodiment 5 is 100K; The molecular weight of the substance intercepted in embodiment 2 and embodiment 6 is 300K; implement The molecular weight of the substance intercepted by example 3 and embodiment 7 is 500K; the molecular weight of the substance intercepted by embodiment 4 and embodiment 8 is 750K;

实验设备：天津罗根颗粒计数器KB-3；实验准备：按图21组装实验装置，确保装置清洁，使用超纯水对装置进行冲洗；取直径47mm的滤膜，装于蝶形过滤器中，确保组装好的过滤器气密性良好。Experimental equipment: Tianjin Logan Particle Counter KB-3; Experimental preparation: Assemble the experimental device according to Figure 21, ensure that the device is clean, and rinse the device with ultrapure water; take a filter membrane with a diameter of 47mm and install it in a butterfly filter. Make sure that the assembled filter is airtight.

实验步骤：将挑战液倒入到储罐中，注意蝶形过滤器的排气，加压至10kPa，使用洁净的瓶子接取蝶形下游滤液。Experimental steps: pour the challenge liquid into the storage tank, pay attention to the exhaust of the butterfly filter, pressurize to 10kPa, and use a clean bottle to receive the downstream filtrate of the butterfly.

用颗粒计数器测试滤液和原液中的颗粒数。Test the filtrate and stock solution for particle counts with a particle counter.

拦截效率：

Interception efficiency:

式中：η───拦截效率，％；n ₀───原液中的颗粒数，5组计数的平均值，个； In the formula: η───interception efficiency, %; n ₀ ───the number of particles in the stock solution, the average of 5 groups of counts, pcs;

n ₁───滤液中的颗粒数，5组计数的平均值，个。 n ₁ ───The number of particles in the filtrate, the average of 5 groups of counts, pcs.

the	通量/Lh ^-1m ^-2@10psi Flux/Lh ^-1 m ^-2 @10psi	截留效率Retention efficiency
实施例1Example 1	800800	大于90％greater than 90%
实施例2Example 2	12001200	大于90％greater than 90%
实施例3Example 3	17001700	大于90％greater than 90%
实施例4Example 4	23002300	大于90％greater than 90%
实施例5Example 5	900900	大于90％greater than 90%
实施例6Example 6	14001400	大于90％greater than 90%
实施例7Example 7	20002000	大于90％greater than 90%
实施例8Example 8	26002600	大于90％greater than 90%

本发明实施例1-8制得的PES中空纤维膜以切向流过滤的方式纯化各种生物大分子；其截流分子量为100K-750K，且该膜具有高通量和高截留效率。The PES hollow fiber membranes prepared in Examples 1-8 of the present invention purify various biomacromolecules by means of tangential flow filtration; their cut-off molecular weights are 100K-750K, and the membranes have high flux and high retention efficiency.

此外经过耐压强度测试，本发明实施例1-8制得的PES中空纤维膜的耐压强度均不低于30psi，工艺实用性强度；此外经过蛋白质收率测试(可以根据中国CN201010154974.7-超多孔膜及其制备方法中所使用的蛋白质收率测试方法进行测试，也可以用其他方法进行测试)，PES中空纤维膜的蛋白质收率均大于90％，同时能够得到较高的蛋白质收率，经济效益高。In addition, through the compressive strength test, the compressive strength of the PES hollow fiber membranes obtained in Examples 1-8 of the present invention is not less than 30psi, and the process is practical; The protein yield test method used in the ultraporous membrane and its preparation method is tested, and other methods can also be used to test), the protein yield of the PES hollow fiber membrane is greater than 90%, and a higher protein yield can be obtained at the same time , high economic benefit.

以上所述仅是本发明的优选实施方式，本发明的保护范围并不仅局限于上述实施例，凡属于本发明思路下的技术方案均属于本发明的保护范围。应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理前提下的若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above descriptions are only preferred implementations of the present invention, and the scope of protection of the present invention is not limited to the above examples, and all technical solutions that fall under the idea of the present invention belong to the scope of protection of the present invention. It should be pointed out that for those skilled in the art, some improvements and modifications without departing from the principles of the present invention should also be regarded as the protection scope of the present invention.

Claims

一种用于生物大分子纯化的PES中空纤维膜，包括主体，所述主体的一侧为内表面，另一侧为外表面，所述主体内具有非定向曲折通路，其特征在于：A PES hollow fiber membrane used for purification of biological macromolecules, comprising a main body, one side of the main body is an inner surface, and the other side is an outer surface, and the main body has a non-directional tortuous passage, and is characterized in that:

所述内表面上具有若干个狭缝形的第一孔洞，所述第一孔洞的孔径宽度平均值为60nm-450nm，所述第一孔洞在内表面上的孔洞面积率为5-30％，其中所述第一孔洞的孔径宽度方向与中空纤维膜的周向一致；There are several slit-shaped first holes on the inner surface, the average width of the first holes is 60nm-450nm, and the area ratio of the first holes on the inner surface is 5-30%, Wherein the aperture width direction of the first hole is consistent with the circumferential direction of the hollow fiber membrane;

在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小；In the film thickness direction from the inner surface to the outer surface, the average pore size of the main body first increases and then decreases;

所述主体包括分离层和支撑层，所述分离层的一侧为内表面，所述支撑层的一侧为外表面；The main body includes a separation layer and a support layer, one side of the separation layer is an inner surface, and one side of the support layer is an outer surface;

所述支撑层包括第一大孔区，所述第一大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的4倍以上；The support layer includes a first macroporous region, the average pore diameter of the first macroporous region is at least 4 times the average pore width of the first holes;

所述第一大孔区到内表面的最近距离小于所述第一大孔区到外表面的最近距离。The closest distance from the first macroporous region to the inner surface is smaller than the closest distance from the first macroporous region to the outer surface.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述内表面上还包括有若干个短纤维，所述短纤维的两端均与第一孔洞内壁相连接，相邻第一孔洞之间通过短纤维相隔开,所述短纤维的平均直径为10-40nm。A kind of PES hollow fiber membrane used for biomacromolecule purification according to claim 1, characterized in that: the inner surface also includes several short fibers, and the two ends of the short fibers are connected to the first hole The inner walls are connected, and the adjacent first holes are separated by short fibers, and the average diameter of the short fibers is 10-40nm.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述分离层的厚度为0.5-15μm，所述分离层厚度占膜厚度的0.5-12.5％；所述分离层的孔隙率为10-45％；所述内表面的第一水接触角为45°-70°。A PES hollow fiber membrane for purification of biological macromolecules according to claim 1, characterized in that: the thickness of the separation layer is 0.5-15 μm, and the thickness of the separation layer accounts for 0.5-12.5% of the membrane thickness; The porosity of the separation layer is 10-45%; the first water contact angle of the inner surface is 45°-70°.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述第一大孔区的平均孔径为1.5-4.5μm；A PES hollow fiber membrane for purification of biological macromolecules according to claim 1, characterized in that: the average pore diameter of the first macroporous region is 1.5-4.5 μm;

所述第一大孔区到内表面的最近距离为15-50μm；The shortest distance from the first macroporous area to the inner surface is 15-50 μm;

所述第一大孔区的厚度为5-18μm。The thickness of the first macroporous region is 5-18 μm.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述第一大孔区内具有形成多孔结构的第一纤维，所述第一纤维的平均直径为80-200nm；A kind of PES hollow fiber membrane that is used for biomacromolecule purification according to claim 1, is characterized in that: the first fiber that forms porous structure is arranged in described first macroporous region, the average diameter of described first fiber 80-200nm;

所述第一大孔区的孔隙率为55-90％；The porosity of the first macroporous region is 55-90%;

所述第一大孔区到内表面的最近距离占膜厚度的10-40％；The shortest distance from the first macroporous area to the inner surface accounts for 10-40% of the film thickness;

所述第一大孔区的厚度占膜厚度的3.5-16.5％。The thickness of the first macroporous region accounts for 3.5-16.5% of the film thickness.
根据权利要求5所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述支撑层还包括有孔洞平均孔径不超过1μm的小孔区；所述小孔区内具有形成多孔结构的多孔纤维；所述多孔纤维的平均直径为70-180nm；A kind of PES hollow fiber membrane for biomacromolecule purification according to claim 5, characterized in that: the support layer also includes a small hole area with an average pore diameter of no more than 1 μm; the small hole area has Porous fibers forming a porous structure; the average diameter of the porous fibers is 70-180nm;

所述小孔区的孔隙率为35-72％。The porosity of the small hole area is 35-72%.
根据权利要求6所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述多孔纤维的平均直径与第一纤维的平均直径与之比不低于0.8；A PES hollow fiber membrane for purification of biological macromolecules according to claim 6, wherein the ratio of the average diameter of the porous fibers to the average diameter of the first fibers is not less than 0.8;

所述第一大孔区的孔隙率至少比小孔区的孔隙率大10％以上。The porosity of the first large pore area is at least 10% greater than the porosity of the small pore area.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述外表面上具有若干个第二孔洞，所述第二孔洞的平均孔径为150nm-2500nm，所述第二孔洞在外表面上的孔洞面积率为12-65％；所述第二孔洞的平均孔径大于第一孔洞的孔径宽度平均值。A kind of PES hollow fiber membrane for biomacromolecule purification according to claim 1, characterized in that: there are several second holes on the outer surface, the average pore diameter of the second holes is 150nm-2500nm, The hole area ratio of the second hole on the outer surface is 12-65%; the average hole diameter of the second hole is larger than the average hole width of the first hole.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述第一孔洞的孔径长度平均值为120-800nm，所述第一孔洞的孔径长度平均值为第一孔洞的孔径宽度平均值的1.3-6；其中所述第一孔洞的孔径长度方向与中空纤维膜的长度方向一致。A kind of PES hollow fiber membrane for biomacromolecule purification according to claim 1, characterized in that: the average value of the aperture length of the first hole is 120-800nm, and the average value of the aperture length of the first hole is It is 1.3-6 of the average value of the aperture width of the first hole; wherein the aperture length direction of the first hole is consistent with the length direction of the hollow fiber membrane.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：在从内表面至外表面的膜厚度方向上，所述主体的平均孔径先增大再减小，减小后再进一步增大；A PES hollow fiber membrane for purification of biological macromolecules according to claim 1, characterized in that: in the membrane thickness direction from the inner surface to the outer surface, the average pore size of the main body first increases and then decreases , decrease and then further increase;

所述支撑层还包括有第二大孔区，所述第二大孔区一侧为外表面；所述第二大孔区的平均孔径至少为第一孔洞的孔径宽度平均值的1.5倍以上；The support layer also includes a second macroporous area, one side of the second macroporous area is the outer surface; the average pore diameter of the second macroporous area is at least 1.5 times the average value of the pore width of the first hole ;

所述第二大孔区的厚度为4-15μm。The thickness of the second macroporous region is 4-15 μm.
根据权利要求10所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述第二大孔区的平均孔径为200-2000nm；且所述第二大孔区的平均孔径小于第一大孔区的平均孔径；A kind of PES hollow fiber membrane for biomacromolecule purification according to claim 10, characterized in that: the average pore diameter of the second macroporous region is 200-2000nm; and the average pore diameter of the second macroporous region The pore size is smaller than the average pore size of the first large pore area;

所述第二大孔区内具有形成多孔结构的第二纤维，所述第二纤维平均直径为50-500nm；所述第二大孔区的孔隙率为50-85％；There are second fibers forming a porous structure in the second macroporous region, and the average diameter of the second fibers is 50-500 nm; the porosity of the second macroporous region is 50-85%;

所述第二大孔区的厚度占膜厚度的3-13％。The thickness of the second macroporous region accounts for 3-13% of the film thickness.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：所述PES中空纤维膜的内腔直径为0.3mm-1.5mm，膜厚度为100-200μm，膜整体孔隙率为40-70％。A PES hollow fiber membrane for purification of biological macromolecules according to claim 1, characterized in that: the inner diameter of the PES hollow fiber membrane is 0.3mm-1.5mm, the membrane thickness is 100-200μm, the membrane The overall porosity is 40-70%.
根据权利要求1所述的一种用于生物大分子纯化的PES中空纤维膜，其特征在于：A kind of PES hollow fiber membrane that is used for biomacromolecule purification according to claim 1, is characterized in that:

所述PES中空纤维膜的水通量为400-3000L*h ^-1*m ^-2@10psi； The water flux of the PES hollow fiber membrane is 400-3000L*h ^-1 *m ^-2 @10psi;

所述PES中空纤维膜的耐压强度不低于30psi；The compressive strength of the PES hollow fiber membrane is not less than 30psi;

所述PES中空纤维膜对于分子量为100kD-750kD的物质的截留效率大于90％；The interception efficiency of the PES hollow fiber membrane for substances with a molecular weight of 100kD-750kD is greater than 90%;

所述PES中空纤维膜的蛋白质收率不低于90％。The protein yield of the PES hollow fiber membrane is not lower than 90%.
如权利要求1-13任意一项所述的一种用于生物大分子纯化的PES中空纤维膜的制备方法，其特征在于：包括以下步骤：A kind of preparation method for the PES hollow fiber membrane that is used for biomacromolecule purification as described in any one of claim 1-13, it is characterized in that: comprise the following steps:

步骤一：制备铸膜液和芯液：Step 1: Prepare casting solution and core solution:

所述铸膜液包括下列重量份物质组成：聚醚砜15-25份，亲水添加剂10-30份；有机溶剂55-90份；The casting solution includes the following components by weight: 15-25 parts of polyethersulfone, 10-30 parts of hydrophilic additives; 55-90 parts of organic solvent;

所述芯液包括有机溶剂和非溶剂；所述芯液中非溶剂的含量为30-70％；所述非溶剂为水；The core liquid includes an organic solvent and a non-solvent; the content of the non-solvent in the core liquid is 30-70%; the non-solvent is water;

所述亲水添加剂为聚乙二醇、聚乙烯吡咯烷酮、聚乙烯亚胺和聚乙烯醇中的至少一种；The hydrophilic additive is at least one of polyethylene glycol, polyvinylpyrrolidone, polyethyleneimine and polyvinyl alcohol;

所述有机溶剂为二甲亚砜、二甲基甲酰胺、N-乙基吡咯烷酮、二甲基乙酰胺和N-甲基吡咯烷酮中的至少一种；The organic solvent is at least one of dimethylsulfoxide, dimethylformamide, N-ethylpyrrolidone, dimethylacetamide and N-methylpyrrolidone;

步骤二：纺丝：该铸膜液与芯液一同从双重纺丝喷嘴中挤出，铸膜液在喷嘴中形成具有内表面和外表面的成型品；所述铸膜液的温度为50-70℃，芯液温度为20-30℃；所述喷嘴温度和铸膜液温度相同；Step 2: Spinning: the casting solution and the core solution are extruded from the double spinning nozzle, and the casting solution forms a molded product with an inner surface and an outer surface in the nozzle; the temperature of the casting solution is 50- 70°C, the temperature of the core liquid is 20-30°C; the temperature of the nozzle is the same as that of the casting liquid;

步骤三：预分相：将所述成型品经过空气段下进行预分相；Step 3: pre-separation: pre-separation of the molded product through the air section;

步骤四：再分相：将预分相后的成型品放入凝固浴中再分相，形成生膜；Step 4: Re-phase separation: Put the pre-phase-separated molded product into the coagulation bath and then separate the phases to form a raw film;

步骤五：将生膜进行拉伸处理，并在水中清洗，最后烘干，制得PES中空纤维膜。Step 5: Stretch the raw membrane, wash it in water, and finally dry it to obtain a PES hollow fiber membrane.
根据权利要求14所述的一种用于生物大分子纯化的PES中空纤维膜的制备方法，其特征在于：步骤三中预分相是指将成型品放置在湿度为70-100％的空气段中进行预分相，空气段长度为5-300mm，预分相时间为0.2-1s。A method for preparing a PES hollow fiber membrane used for purification of biological macromolecules according to claim 14, characterized in that: pre-phase separation in step 3 refers to placing the molded product in an air section with a humidity of 70-100% The pre-phase separation is carried out in the medium, the length of the air section is 5-300mm, and the pre-phase separation time is 0.2-1s.
根据权利要求14所述的一种用于生物大分子纯化的PES中空纤维膜的制备方法，其特征在于：步骤三中预分相是指将成型品放置在充满有机溶剂蒸气的空气段中进行预分相，空气段长度为10-400mm，预分相时间为0.5-2s。A method for preparing a PES hollow fiber membrane for purification of biological macromolecules according to claim 14, characterized in that: pre-phase separation in step 3 refers to placing the molded product in an air section filled with organic solvent vapor Pre-phase separation, the length of the air section is 10-400mm, and the pre-phase separation time is 0.5-2s.
根据权利要求14所述的一种用于生物大分子纯化的PES中空纤维膜的制备方法，其特征在于：步骤四再分相是指将预分相后的成型品放入温度为40-70℃的凝固浴中再分相，再分相时间为20-60s；所述凝固浴为水和有机溶剂的混合物，所述凝固浴中水含量为60-100％。A method for preparing a PES hollow fiber membrane used for purification of biological macromolecules according to claim 14, characterized in that: Step 4 and then phase separation refers to putting the molded product after pre-phase separation at a temperature of 40-70 phase separation in a coagulation bath at ℃, and the phase separation time is 20-60s; the coagulation bath is a mixture of water and an organic solvent, and the water content in the coagulation bath is 60-100%.
根据权利要求14所述的一种用于生物大分子纯化的PES中空纤维膜的制备方法，其特征在于：拉伸处理是指对生膜进行1-5倍的拉伸，拉伸速率为3-12m/min。A method for preparing a PES hollow fiber membrane used for purification of biological macromolecules according to claim 14, characterized in that: stretching treatment refers to stretching the raw membrane by 1-5 times, and the stretching rate is 3 -12m/min.
如权利要求1-13任意一项所述的一种用于生物大分子纯化的PES中空纤维膜的应用，其特征在于：所述PES中空纤维膜以切向流的形式用于：The application of a PES hollow fiber membrane for biomacromolecule purification according to any one of claims 1-13, characterized in that: the PES hollow fiber membrane is used in the form of tangential flow for:

(a)疫苗或病毒载体的纯化、浓缩和透析；(a) purification, concentration and dialysis of vaccine or viral vectors;

(b)蛋白质的浓缩和透析；(b) concentration and dialysis of proteins;

(c)发酵液中细胞和细菌的澄清过滤；(c) clarification and filtration of cells and bacteria in the fermentation broth;

(d)细胞和菌体的回收和透析。(d) Recovery and dialysis of cells and bacteria.