Semi-permeable membrane, cell culture device as well as preparation method and application of semi-permeable membrane

By designing a semipermeable membrane that penetrates multiple pores of the membrane body, the existing semipermeable membrane leakage risk is solved, and the conduction and drug release are controlled through microfilament dissolution, a more efficient and flexible cell culture and drug sustained release effect is achieved.

CN119524654APending Publication Date: 2025-02-28BEIJING BOE TECH DEV CO LTD +1
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Patent Information

Application Number
CN202311120952.2
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-08-31
Publication Date
2025-02-28

AI Technical Summary

Technical Problem

The existing semipermeable membranes have a risk of liquid leakage during use, mainly because they need to cooperate with another bonding surface to form a closed channel.

Method used

A semipermeable membrane is designed, wherein the membrane body penetrates multiple pores, which can be hollow structure or filled with a first microfilament. The first microfilament is dissolved in a specific state to control the conduction of the pores and to release the dopant by dissolving to achieve sustained release of the drug.

Benefits of technology

This design enables the semipermeable membrane to directly form a closed channel without the need for bonding surfaces, avoiding liquid leakage problems, and controlling conduction and drug release through the dissolution of microfilaments, improving the flexibility and efficiency of the system.

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Abstract

The invention discloses a semipermeable membrane, a cell culture device and a preparation method and application thereof. The semipermeable membrane comprises a membrane body and a plurality of pore channels penetrating through the membrane body; the multiple hole channels are of a hollow structure. Or at least one hole channel is filled with first microfilaments; wherein the first microfilament is configured to dissolve in a first state.
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Description

Technical Field

[0001] The embodiments of the present disclosure relate to but are not limited to semipermeable membrane technology, and in particular to a semipermeable membrane, a cell culture device, and a preparation method and application thereof. Background Art

[0002] Semipermeable membranes are often used in the fields of cell culture and microfluidics. The quality and performance of semipermeable membranes can play a key role in the research results. The inventors of this application have found that the existing semipermeable membranes are bonded to each other using two planes, which may cause leakage during use. Summary of the invention

[0003] The following is a summary of the subject matter described in detail herein. This summary is not intended to limit the scope of the claims.

[0004] The embodiments of the present disclosure provide a semipermeable membrane, a cell culture device, and a preparation method and application thereof, which can be used to solve the problem of liquid leakage risk of existing semipermeable membranes.

[0005] In a first aspect, an embodiment of the present disclosure provides a semipermeable membrane, comprising: a membrane body and a plurality of pores penetrating the membrane body; the plurality of pores are hollow structures; or, at least one of the pores is filled with a first microfilament; wherein the first microfilament is configured to dissolve in a first state.

[0006] In an exemplary embodiment, the extension directions of the plurality of channels are parallel to each other, or the extension directions of at least two channels intersect.

[0007] In an exemplary embodiment, in a plane parallel to the semipermeable membrane, a cross-sectional dimension of the pores is set to be greater than or equal to 5 micrometers and less than or equal to 30 micrometers.

[0008] In an exemplary embodiment, a first dopant is doped in the first microwire, and the first dopant is configured to be exposed as the first microwire is dissolved.

[0009] In a second aspect, the embodiments of the present disclosure also provide a method for preparing a semipermeable membrane, comprising: using a microfilament material to form a first microfilament, wherein the first microfilament is configured to dissolve in a first state; combining the first microfilament with a semipermeable membrane mold; casting a membrane material in the semipermeable membrane mold; demolding the membrane material after solidification to obtain a semipermeable membrane; cleaning the semipermeable membrane to obtain the semipermeable membrane having a plurality of hollow structural channels, or obtaining the semipermeable membrane in which at least one of the channels is filled with the first microfilament.

[0010] In an exemplary embodiment, the microfilament material comprises a soluble sugar or a protein.

[0011] In an exemplary embodiment, the microwire material is doped with a first dopant, and the first dopant is configured to be exposed as the first microwire is dissolved.

[0012] In an exemplary embodiment, the forming of the first microwire using the microwire material includes: melting the microwire material and spraying it out through a nozzle, using at least two collecting rods to collect the first microwire, and winding the first microwire between the collecting rods.

[0013] In an exemplary embodiment, before combining the first microwire with the semipermeable membrane mold, the method further includes: cutting the first microwire.

[0014] In an exemplary embodiment, before the demolding, the method further comprises: cutting the first microfilaments.

[0015] In a third aspect, the embodiments of the present disclosure further provide a cell culture device, comprising at least one semipermeable membrane as described above. In a fourth aspect, the embodiments of the present disclosure further provide an application of a cell culture device, comprising a semipermeable membrane, comprising: a membrane body and a plurality of pores penetrating the membrane body; the plurality of pores are hollow structures; the cell culture device is configured to achieve multi-cell culture through the semipermeable membrane.

[0016] In a fifth aspect, an embodiment of the present disclosure also provides an application of a cell culture device, comprising a semipermeable membrane, comprising: a membrane body and a plurality of channels passing through the membrane body; at least one of the channels is filled with a first microfilament; wherein the first microfilament is configured to dissolve in a first state; and the cell culture device is configured to achieve sustained release of drugs through the semipermeable membrane.

[0017] The semipermeable membrane provided by the embodiment of the present disclosure can directly form a closed channel by itself because the pores penetrate the membrane body, without the need to form a channel after cooperating with another bonding surface, and will not leak liquid, thus solving the risk of liquid leakage in existing semipermeable membranes.

[0018] Other aspects will be apparent upon reading and understanding the drawings and detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings are used to provide further understanding of the technical solution of the present disclosure and constitute a part of the specification. Together with the embodiments of the present disclosure, they are used to explain the technical solution of the present disclosure and do not constitute a limitation on the technical solution of the present disclosure.

[0020] Figure 1 is a top view of a semipermeable membrane in an exemplary embodiment;

[0021] Figure 2 is a top view of a semipermeable membrane in another exemplary embodiment;

[0022] Figure 3 A schematic diagram of sugar filaments collected in an exemplary embodiment;

[0023] Figure 4 A schematic diagram of cut sugar threads in an exemplary embodiment;

[0024] Figure 5 is a schematic diagram of a membrane body after casting in an exemplary embodiment;

[0025] Figure 6 is a schematic diagram after demoulding in an exemplary embodiment;

[0026] Figure 7 is a schematic diagram after cleaning in another exemplary embodiment;

[0027] Figure 8 is a schematic structural diagram of a cell culture device in an exemplary embodiment;

[0028] Fig. 9 is a schematic structural diagram of a cell culture device in another exemplary embodiment;

[0029] Fig.10 is a schematic structural diagram of a cell culture device in another exemplary embodiment;

[0030] Fig.11 is a schematic structural diagram of a cell culture device in another exemplary embodiment;

[0031] Fig.12 is a schematic structural diagram of a cell culture device in another exemplary embodiment;

[0032] Fig.13 is a schematic diagram of fixing sugar threads on a sugar plate in an exemplary embodiment;

[0033] Fig.14 This is a schematic diagram of completing the casting of the membrane body after combining the sugar plate with the sugar filaments fixed thereon with the semipermeable membrane mold in an exemplary embodiment;

[0034] Fig.15 A schematic diagram of demoulding and removing sugar filaments in an exemplary embodiment;

[0035] Fig.16 This is a schematic diagram of an exemplary embodiment in which a semipermeable membrane is used as a side wall after being spliced ​​and assembled;

[0036] Fig.17 This is a schematic diagram of an exemplary embodiment in which a semipermeable membrane is used as a side wall and a bottom wall for splicing and assembling;

[0037] Fig.18 A schematic diagram of fixing sugar threads between two sugar plates in an exemplary embodiment;

[0038] Fig.19 This is a schematic diagram of combining a sugar plate with fixed sugar filaments with a cell culture device mold in an exemplary embodiment;

[0039] Fig. 20 is a schematic diagram of a membrane body after casting in an exemplary embodiment;

[0040] Fig.21 is a schematic diagram of an exemplary embodiment after water washing;

[0041] Fig. 22 is a schematic diagram of an exemplary embodiment after the edge gap is cut off;

[0042] Fig.23 is a schematic diagram of fixing sugar threads between two sugar plates in yet another exemplary embodiment;

[0043] Fig.24 is a schematic diagram of combining a sugar plate with fixed sugar filaments with a cell culture device mold in another exemplary embodiment;

[0044] Fig.25 is a schematic diagram of a membrane body after casting in another exemplary embodiment;

[0045] Fig.26 is a schematic diagram after water cleaning in another exemplary embodiment;

[0046] Fig. 27 FIG. 1 is a schematic diagram of another exemplary embodiment after the edge gap is cut off. DETAILED DESCRIPTION

[0047] The embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings. Note that the embodiments can be implemented in a plurality of different forms. A person skilled in the art can easily understand the fact that the methods and contents can be transformed into various forms without departing from the purpose and scope of the present disclosure. Therefore, the present disclosure should not be interpreted as being limited to the contents described in the following embodiments. In the absence of conflict, the embodiments in the present disclosure and the features in the embodiments can be arbitrarily combined with each other.

[0048] The present disclosure includes and contemplates combinations of features and elements known to those of ordinary skill in the art. The embodiments, features, and elements disclosed in the present disclosure may also be combined with any conventional features or elements to form a unique invention scheme defined by the claims. Any features or elements of any embodiment may also be combined with features or elements from other invention schemes to form another unique invention scheme defined by the claims. Therefore, it should be understood that any feature shown and / or discussed in the present disclosure may be implemented individually or in any appropriate combination. Therefore, except for the limitations made according to the attached claims and their equivalents, the embodiments are not subject to other limitations. In addition, various modifications and changes may be made within the scope of protection of the attached claims.

[0049] In addition, when describing representative embodiments, the specification may have presented the method and / or process as a specific sequence of steps. However, to the extent that the method or process does not rely on the specific order of the steps described herein, the method or process should not be limited to the steps in the specific order described. As will be appreciated by those of ordinary skill in the art, other orders of steps are also possible. Therefore, the specific order of the steps set forth in the specification should not be interpreted as a limitation to the claims. In addition, the claims for the method and / or process should not be limited to the steps performed in the order written, and those skilled in the art can easily understand that these orders can be changed and still remain within the spirit and scope of the disclosed embodiments.

[0050] In the drawings, the size of one or more components, the thickness of a layer, or an area is sometimes exaggerated for the sake of clarity. Therefore, one embodiment of the present disclosure is not necessarily limited to the size, and the shape and size of one or more components in the drawings do not reflect the true proportion. In addition, the drawings schematically show ideal examples, and one embodiment of the present disclosure is not limited to the shapes or values ​​shown in the drawings.

[0051] The ordinal numbers such as "first", "second", and "third" in this specification are provided to avoid confusion of constituent elements, and are not intended to limit the quantity. The "plurality" in this disclosure means two or more.

[0052] In this specification, for the sake of convenience, the words and phrases indicating the orientation or positional relationship such as "middle", "upper", "lower", "front", "back", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like are used to illustrate the positional relationship of the constituent elements with reference to the drawings. This is only for the convenience of describing this specification and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation, and therefore cannot be understood as a limitation of the present disclosure. The positional relationship of the constituent elements is appropriately changed according to the orientation of the constituent elements being described. Therefore, it is not limited to the words and phrases described in the specification, and can be appropriately replaced according to the circumstances.

[0053] In this specification, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense. For example, it can be a fixed connection, or a detachable connection, or an integral connection; it can be a mechanical connection, or a connection; it can be a direct connection, or an indirect connection through an intermediate, or the internal communication of two elements. For ordinary technicians in this field, the meanings of the above terms in this disclosure can be understood according to the circumstances.

[0054] In this specification, "parallel" means a state where the angle formed by two straight lines is greater than -10° and less than 10°, and therefore, also includes a state where the angle is greater than -5° and less than 5°. In addition, "perpendicular" means a state where the angle formed by two straight lines is greater than 80° and less than 100°, and therefore, also includes a state where the angle is greater than 85° and less than 95°.

[0055] The triangles, rectangles, trapezoids, pentagons or hexagons in this specification are not in the strict sense, and may be approximate triangles, rectangles, trapezoids, pentagons or hexagons, etc. There may be some small deformations caused by tolerances, and there may be chamfers, arc edges and deformations.

[0056] The term "about" in the present disclosure refers to a numerical value that is not strictly limited to allow for process and measurement errors.

[0057] Polydimethylsiloxane (PDMS) is a hydrophobic silicone material that is non-toxic and tasteless, has physiological inertness, good chemical stability, hydrophobicity, electrical insulation and weather resistance, and has high shear resistance. It can still be used for a long time at an ambient temperature of -50°C to 200°C, and is often used to make microfluidic semipermeable membranes. At present, PDMS is often used to form a semipermeable membrane by molding, that is, first a mold is formed on silicon, glass, plastic and other materials by photolithography, and then the liquid PDMS is mixed with a cross-linking agent and poured on the mold, and then heated and cured and demolded to form a film with microchannels. Finally, the film with microchannels is bonded to other planes to form a closed channel in the film.

[0058] The inventor of the present application has found through research that the above method needs to use large instruments in the process of forming the mold, the preparation process is complicated, and the structure of the molding mold cannot be changed. When the semipermeable membrane is required to have different penetration properties, it is necessary to redesign the mold, and, subject to the mold turning process, the PDMS film needs to be bonded with other planes to form a closed channel, that is, the semipermeable membrane includes two parts, the PDMS film and the bonding plane, which not only needs to use a bonding machine, but also has the risk of leakage due to loose bonding. When the mold is formed by the photolithographic method, when the hole density of the mold is large or the depth and width of the hole is large, the preparation process and demoulding process of the mold are difficult, and a circular or nearly circular channel cannot be formed within a small size range, and the small size range can be less than 20 microns, for example, between 10 microns and 20 microns. In addition, although the mold can also be formed by printing, the production cost is high.

[0059] The disclosed embodiments provide a semipermeable membrane, comprising: a membrane body and a plurality of pores penetrating the membrane body; the plurality of pores are hollow; or at least one pore is filled with a first microfilament; wherein the first microfilament is configured to dissolve in a first state.

[0060] The semipermeable membrane provided by the embodiment of the present disclosure can directly form a closed channel by itself because the pores run through the membrane body, without the need to form a channel after cooperating with another bonding surface, and will not leak. By setting the first microwire, the conduction of multiple pores can be controlled to adjust the permeability of the semipermeable membrane within a certain period of time.

[0061] In an exemplary embodiment, the first microfilament is dissolved in the first state, which may refer to the first microfilament being dissolved in a solvent such as water or alcohol, or being enzymatically hydrolyzed by an enzyme, that is, the first state may refer to dissolution or enzymatic hydrolysis, and the present disclosure is not limited to this.

[0062] In an exemplary embodiment, the extension directions of the plurality of channels are parallel to each other, or the extension directions of at least two channels intersect.

[0063] In an exemplary embodiment, the extension direction of the plurality of pores may intersect two opposite side surfaces of the semipermeable membrane.

[0064] In an exemplary embodiment, the cross-sectional dimension of the pores in a plane parallel to the semipermeable membrane is set to be greater than or equal to 5 micrometers and less than or equal to 30 micrometers.

[0065] In an exemplary embodiment, the cross-sectional dimension of the pores in a plane parallel to the semipermeable membrane is set to be greater than or equal to 10 micrometers and less than or equal to 20 micrometers.

[0066] In an exemplary embodiment, the cross-sectional shape of the pores in a plane parallel to the semipermeable membrane is circular.

[0067] In an exemplary embodiment, the first microwire is doped with a first dopant, and the first dopant is configured to be exposed as the first microwire is dissolved.

[0068] In this embodiment, the semipermeable membrane can be applied to a cell culture container, the first dopant can be a drug, and as the first microwire dissolves, the first dopant can be exposed to the culture solution, and the first dopant is doped in the first microwire to achieve sustained release of the drug. In other embodiments, the first dopant can be a nutrient required by the cell, or can be other substances, such as liquid or solid substances, and the present disclosure does not limit this.

[0069] In an exemplary embodiment, the material of the membrane body includes polydimethylsiloxane.

[0070] In an exemplary embodiment, the first microfilament may be a soluble material, such as a soluble sugar; or, the material of the first microfilament may include a protein.

[0071] The embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.

[0072] Figure 1 is a top view of a semipermeable membrane in an exemplary embodiment. Figure 2 FIG. 2 is a top view of a semipermeable membrane in another exemplary embodiment. The semipermeable membrane of the disclosed embodiment comprises: a membrane body 10 and a plurality of pores 11 penetrating opposite side surfaces of the membrane body 10. Figure 1 As shown, the plurality of channels 11 may be hollow structures; or Figure 2 As shown, at least one of the channels 11 is filled with a first microwire 12, and the first microwire 12 is configured to dissolve under the action of water or an enzyme. Figure 1 and Figure 2 As shown, in a plane parallel to the semipermeable membrane, the cross-sectional shape of the pore 11 may be circular. In other embodiments, the cross-sectional shape of the pore 11 may be elliptical, triangular, quadrilateral, polygonal, or other shapes, and may also be irregular in shape, which is not limited in the present disclosure.

[0073] In an exemplary embodiment, the extension directions of the plurality of channels 11 may be parallel to each other, so that more channels 11 may be arranged within a unit area of ​​the semipermeable membrane 10, which facilitates the control of the conduction of the semipermeable membrane 10. Alternatively, the extension directions of at least two channels 11 may intersect to obtain a more flexible conduction path, and the difficulty of arranging the channels 11 may be reduced, which helps to simplify the preparation process.

[0074] In an exemplary embodiment, if Figure 1As shown, in a plane parallel to the semipermeable membrane 10, the cross-sectional size of the pore can be set to be greater than or equal to 5 microns and less than or equal to 30 microns. For example, the cross-sectional size of the pore 11 can be set to be greater than or equal to 10 microns and less than or equal to 20 microns. The cross-sectional size of the pore 11 can be set to be larger or smaller as needed, and the present disclosure does not limit this. Under the action of multiple pores 11, the semipermeable membrane 10 can allow material exchange on both sides of the membrane body, but does not allow cell exchange, and can be used for cell culture.

[0075] In an exemplary embodiment, the membrane material may include polydimethylsiloxane. The material of the first microfilament may include a soluble material or a protein, and the soluble material may be, for example, a water-soluble sugar, an alcohol-soluble sugar, etc. In the case where the semipermeable membrane is applied to a cell culture container, since both sugar and protein are natural structures, direct contact will not cause adverse effects on cells, and relative to the volume of cell culture, the volume of sugar or protein contained in the first microfilament in the semipermeable membrane is small, and the residue after dissolution is almost negligible relative to the large volume of cell culture fluid. Therefore, the use of natural structural materials such as sugar or protein to form the first microfilament will not affect cell culture.

[0076] In an exemplary embodiment, the first microfilament 12 may be doped with a first dopant, and the first dopant may be configured to be exposed as the first microfilament 12 dissolves. By doping the first dopant in the pores of the semipermeable membrane in advance, when the semipermeable membrane is used, the first dopant may be exposed as the first microfilament 12 dissolves, and permeate into the culture solution on both sides of the semipermeable membrane, so that the content of the first dopant in the culture solution can be adjusted, and by controlling the dissolution process of the first microfilament 12, the content of the first dopant can be controlled to gradually increase over time, and the content of the first dopant can be controlled more flexibly and accurately.

[0077] The preparation method of the semipermeable membrane provided in the embodiments of the present disclosure is described below with reference to the accompanying drawings.

[0078] In an exemplary embodiment, the preparation Figure 1 The semipermeable membrane shown may include steps 11 to 14. Preparation Figure 2 The semipermeable membrane shown may include steps 11 to 13 , and may further include step 14 .

[0079] (11) Forming sugar threads. In an exemplary embodiment, after the sugar is melted, sugar threads are sprayed out from the nozzle, and two collecting rods are used to rotate and collect the sugar threads so that the sprayed sugar threads can be wound around the two collecting rods. The collected sugar threads 301 can be Figure 3 As shown, Figure 3 The collecting rod is omitted in the figure. This spinning method is similar to the spinning method of cotton candy machines.

[0080] In an exemplary embodiment, the sugar filaments can be controlled to be randomly wound or orderly wound between the collecting rods to control the extension direction of the multiple channels on the semipermeable membrane that is finally formed. There are many ways to control the disorderly winding of the sugar filaments on the collecting rods, which will not be repeated here. Since the first microfilaments obtained in this embodiment are circular in shape, it can make up for the deficiency that circular or nearly circular channels cannot be formed by means such as photolithography. The diameter of the first microfilament obtained can be controlled by controlling the parameters of the sugar and the spinning process, and the present disclosure does not limit this.

[0081] In an exemplary embodiment, the sugar filaments can be controlled to be wound in an orderly manner on the collecting rod, including: when two collecting rods are used to collect the sugar filaments, the ejected sugar filaments can be controlled to be wound in the same direction between the two collecting rods. Alternatively, the number and position of the nozzles can be adjusted, for example, multiple nozzles can be arranged in a straight line so that the exit directions of the sugar filaments are parallel, which is more conducive to the orderly winding of the sugar filaments. In addition, multiple collecting rods can be used to collect the sugar filaments, and the sugar filaments can be controlled to be wound in sequence between the multiple collecting rods, and the sugar filaments located between adjacent collecting rods can be neatly arranged, similar to the winding principle of a spindle machine. The number and arrangement of the nozzles, the number and arrangement of the collecting rods, and the collection method of the sugar filaments can be set according to actual needs, and the present disclosure does not limit this.

[0082] In an exemplary embodiment, after the sugar threads 301 are collected, the sugar threads near the collecting rods may be cut off, leaving only the sugar threads 301 between the two collecting rods, so as to obtain sugar threads 301 with more uniform size and arrangement.

[0083] In an exemplary embodiment, the sugar thread 301 may include a first dopant, and the first dopant may be doped into the melted sugar to be sprayed out along with the spray head to form the sugar thread 301 with the first dopant.

[0084] In this embodiment, sugar is used to form the first microfilaments. In an exemplary embodiment, the material of the first microfilaments can be a sugar that is solid at room temperature and can switch between solid and liquid states under a first conversion condition. The first conversion condition may include temperature, pressure and other conditions. For example, sucrose can be used to form the first microfilaments, and the present disclosure does not limit this.

[0085] In an exemplary embodiment, the type of sugar can be selected as needed, the viscosity of the sugar after melting and other parameters can be adjusted, the size of the nozzle can be set, a suitable spinning method can be selected, such as electrospinning, and the composition, size and content of the first dopant in the first microfilament can be selected as needed, and the present disclosure does not limit this.

[0086] In an exemplary embodiment, the sugar filaments 301 may be replaced by protein filaments, that is, the raw material of the first microfilaments may be protein, and the formation process of the protein filaments may be similar to that of the sugar filaments, which will not be described in detail here.

[0087] (12) Combining the sugar filaments with the mold. In an exemplary embodiment, the collected sugar filaments 301 may be cut according to the size of the semipermeable membrane to be formed, and the cut sugar filaments 301 may be formed as follows. Figure 4 As shown, Figure 4 The cut sugar threads 301 are in a "U" shape, and the shape and size parameters of the cut sugar threads 301 can be selected as needed, and the present disclosure does not limit this.

[0088] Then, the cut sugar thread 301 can be placed in the mold 302, and the sugar thread 301 becomes a part of the mold 302, such as Figure 5 shown.

[0089] In an exemplary embodiment, before cutting the sugar threads 301, the collected sugar threads 301 may be pressed to adjust the distance between adjacent sugar threads 301, thereby controlling the density of the pores in the semipermeable membrane. The density of the pores in the semipermeable membrane may be set as needed, and the present disclosure does not limit this.

[0090] In an exemplary embodiment, the cut sugar threads 301 can be pressed onto the surface of the mold 302, and both ends of the sugar threads 301 can extend into the mold 302 to make the sugar threads 301 and the mold 302 more tightly combined, which helps to make the pores of the semipermeable membrane more transparent. The present disclosure does not limit this.

[0091] (13) Film casting. In an exemplary embodiment, the film material can be poured onto the mold 302, such as Figure 5 As shown, the film material can wrap the sugar threads 301 and fill the gaps between adjacent sugar threads 301. Subsequently, the mold 302 where the film is cast is heated and cured to form a film 303. The sugar threads 301 form the first microfilaments in the film 303. Then, the film can be demoulded to remove the mold 302. The demoulded film is as shown in FIG. Figure 6 shown.

[0092] In an exemplary embodiment, the membrane material may include a mixture of PDMS and a cross-linking agent (or curing agent), and the PDMS and the cross-linking agent may be mixed and degassed before being poured on the mold 302. After the cross-linking agent is added to the PDMS and cured, a transparent elastic material may be formed, which can fill in very small gaps.

[0093] In an exemplary embodiment, the mass fraction ratio of PDMS to the cross-linking agent may be 1:6 to 1:15. For example, the mass fraction ratio of PDMS to the cross-linking agent may be 1:8 to 1:15. Suitable cross-linking agents and different ratios may be selected according to actual needs, and the present disclosure is not limited thereto.

[0094] In an exemplary embodiment, the temperature for heat curing can be greater than or equal to 25°C and less than or equal to 150°C, for example, it can be set to greater than or equal to 50°C and less than or equal to 70°C, and this temperature range can ensure the safety of the curing process while ensuring a faster curing speed. The time for heat curing can be 1.5 hours to 6 hours, for example, the time for heat curing can be 2 hours to 4 hours. With the development of technology and equipment, the temperature for heat curing can be set higher or lower, and the time for heat curing can be shorter or longer, and the present disclosure does not limit this.

[0095] In an exemplary embodiment, after demoulding, the following can be obtained: Figure 2 The semipermeable membrane of the structure shown is a membrane body 303 in which the pores are filled with first microfilaments, and the material of the first microfilaments may contain sugar or protein.

[0096] In an exemplary embodiment, the collected sugar filaments or protein filaments can be first cast into a membrane body, and then the sugar filaments or protein filaments can be cut according to the shape and size of the semipermeable membrane to be formed, that is, step 12 and step 13 can be interchanged in order, and the present disclosure does not limit this. The semipermeable membrane obtained by the method of first casting the membrane body and then cutting the sugar filaments or protein filaments is not easy for cells to adhere to the surface of the semipermeable membrane during cell culture, that is, the "hanging tip" phenomenon will not occur, which is more conducive to cell culture.

[0097] In this embodiment, PDMS is used as the film material. In an exemplary embodiment, the film material may be a substance that can be transformed from a liquid to a solid state after undergoing a first change condition. The first change condition may include conditions such as light, temperature or pressure. For example, the film material may be an optical adhesive such as a UV-curable adhesive, as well as the above-mentioned PDMS and other materials. Compared with optical adhesives, PDMS has higher biosafety. The present disclosure does not limit the specific selection of the film material.

[0098] (14) Removing sugar threads. In an exemplary embodiment, since sugar threads are soluble in water, the demolded membrane body 303 can be ultrasonically cleaned in pure water to remove the sugar threads 301 and obtain a semipermeable membrane with clear pores. Figure 7 shown.

[0099] In an exemplary embodiment, after removing the sugar filaments 301, the following can be obtained: Figure 1 The semipermeable membrane of the structure shown has multiple pores with hollow structures.

[0100] In an exemplary embodiment, after removing the sugar filaments 301, the following Figure 2The semipermeable membrane of the structure shown, at least one pore of the semipermeable membrane is filled with the first microwire. The cleaning process of the membrane body after demoulding can be controlled. For example, the membrane body after demoulding can be partially cleaned to obtain a semipermeable membrane with first microwires filled in some pores. Alternatively, the cleaning time of the membrane body after demoulding can be controlled to control the dissolution degree of the first microwire in a single pore, and obtain a semipermeable membrane with different filling degrees of the first microwire in different pores, which is conducive to the subsequent flexible control of the conduction of the pores in the semipermeable membrane. The present disclosure does not limit the specific settings of the cleaning area, cleaning time, etc.

[0101] In an exemplary embodiment, when the material of the first microfilaments is protein, the membrane body can be cleaned with a solution containing an enzyme in this step, so that the protein filaments can be removed.

[0102] The disclosed embodiments further provide a cell culture device, comprising at least one semipermeable membrane, wherein the at least one semipermeable membrane is the semipermeable membrane described in any of the above embodiments.

[0103] In an exemplary embodiment, the cell culture device includes at least two cell culture units, and a side wall between adjacent cell culture units includes the semipermeable membrane.

[0104] In an exemplary embodiment, the cell culture device includes at least two cell culture units, and a bottom wall of at least one of the cell culture units includes the semipermeable membrane.

[0105] Figure 8 FIG. 1 is a schematic diagram of the structure of a cell culture device in an exemplary embodiment. Figure 8 As shown, the cell culture device 100 may include a single semipermeable membrane 10, which separates the cell culture device 100 into two cell culture units. The two cell culture units can be used to culture the same or different types of cells. The cell culture unit includes a bottom wall and a side wall. Figure 8 The side wall of the middle cell culture unit is a semipermeable membrane 10. The two cell culture units can exchange substances through the semipermeable membrane 10, but no cell exchange occurs. Figure 8 The shape of the cell culture device 100 is circular. In other embodiments, the shape of the cell culture device 100 can be elliptical, triangular, rectangular, trapezoidal, other quadrilateral and polygonal shapes, as well as irregular shapes, etc. The shape and size parameters of the semipermeable membrane 10 can be set as needed, and the present disclosure does not limit this.

[0106] Fig. 9 FIG. 4 is a schematic diagram of the structure of a cell culture device in another exemplary embodiment. Fig. 9As shown, the cell culture device 100 can be rectangular, and a plurality of semipermeable membranes 10 can be arranged in the cell culture device 100. The plurality of semipermeable membranes 10 can include four first semipermeable membranes 101 connected to each other to form a first rectangle. The first semipermeable membranes 101 and the side walls of the cell culture device 100 form an inner and outer double-layer rectangular structure, and the inner and outer two-layer rectangles can exchange substances through the first semipermeable membrane 101.

[0107] In an exemplary embodiment, the first rectangle enclosed by the first semipermeable membrane 101 can be set as a cell culture unit, and the area between the first semipermeable membrane 101 and the side wall of the cell culture device 100 can be set as a culture fluid transfer unit, which can transfer nutrients to the cell culture unit for cell growth in the cell culture unit.

[0108] In an exemplary embodiment, the cell culture device 100 may further include a second semipermeable membrane 102 that serves as the first rectangular bottom wall, and the second semipermeable membrane 102 may serve as a portion of the bottom wall of the cell culture device 100. In an exemplary embodiment, the area of ​​the second semipermeable membrane 102 may be smaller than the area of ​​the first rectangular bottom wall, and the present disclosure is not limited thereto. By providing the second semipermeable membrane 102, the cell culture device 100 may exchange substances through the bottom, thereby increasing the ways of exchanging substances and increasing the layout possibilities of the cell culture device 100.

[0109] In an exemplary embodiment, the cell culture device 100 may further include an alignment portion 103. A plurality of cell culture devices 100 may be stacked on each other in a vertical direction to form an up-and-down stacked cell culture device. The alignment portion 103 may be located at a corner of a bottom wall of the cell culture device 100, for example, to allow accurate alignment between adjacent cell culture devices 100. The shape, quantity, position, and mutual coordination relationship of the alignment portion 103 may be set as required, and the present disclosure does not limit this.

[0110] Fig.10 is a schematic diagram of the structure of a cell culture device in another exemplary embodiment, showing three Fig. 9 The structure of the cell culture device 100 after stacking is shown. Fig.10 As shown, the upper and lower adjacent cell culture devices 100 can achieve material exchange through the second semi-permeable membrane 102 of the upper cell culture device 100. For example, in a cell culture scenario where the substances produced by the cells in the upper layer can affect the cells in the lower layer, and the substances produced by the cells in the lower layer cannot affect the cells in the upper layer, the Fig.10 The cell culture device 100 of the structure shown is used for cell culture. In practical applications, the number of stacking of the cell culture devices can be set as required, and the present disclosure does not limit this.

[0111] Fig.11FIG. 4 is a schematic structural diagram of a cell culture device in another exemplary embodiment, illustrating a situation where three cell culture devices are stacked vertically. Fig.11 and Fig.10 The difference lies in the structure of the monolayer cell culture device. Fig.11 The cell culture device 100 in the embodiment includes a single first semipermeable membrane 101, which divides the single-layer cell culture device into two cell culture units, and a second semipermeable membrane 102 is arranged on the bottom wall of one of the cell culture units. Fig.10 The cell culture device shown, Fig.11 The structure in the embodiment reduces the number of semipermeable membranes and also reduces the material exchange area between the two cell culture units. In practical applications, the structure of the single-layer cell culture device can be set as needed, and the present disclosure does not limit this.

[0112] Fig.12 FIG. 4 is a schematic diagram of the structure of a cell culture device in another exemplary embodiment. Fig.12 As shown, the cell culture device 100 may be a centrally distributed single-layer structure, including a seventh culture unit 7 located in the center and the first culture unit 1 to the sixth culture unit 6 arranged in sequence in a clockwise direction around the seventh culture unit 7. The side walls of the seventh culture unit 7 are all semi-permeable membranes, so that the seventh culture unit 7 can achieve material exchange with the first culture unit 1 to the sixth culture unit 6 respectively, the side wall between the first culture unit 1 and the second culture unit 2 can be a semi-permeable membrane, so that the first culture unit 1 and the second culture unit 2 can achieve material exchange, and the side wall between the fourth culture unit 4 and the fifth culture unit 5 can be a semi-permeable membrane, so that the fourth culture unit 4 and the fifth culture unit 5 can achieve material exchange. In an exemplary embodiment, the number of cell culture units, the material exchange relationship between different cell culture units, and the area of ​​the side wall or the bottom wall occupied by the semi-permeable membrane can be set as needed, and the present disclosure is not limited to this.

[0113] In an exemplary embodiment, Figures 8 to 12 The cell culture devices in the embodiment can be combined with each other to form cell culture devices with more structures, and the present disclosure is not limited to this.

[0114] In an exemplary embodiment, since the membrane material is PDMS, the semipermeable membrane and the cell culture device in the embodiments of the present disclosure can be used for high-temperature sterilization.

[0115] In an exemplary embodiment, when cell culture is required, a cell culture fluid in which cells are suspended is added to the cell culture unit. The cells need to keep the environment as stable as possible when entering the new environment. The material of the first microfilament may include a semipermeable membrane of sugar. When the cell culture fluid is just added to the cell culture unit, the first microfilament will not dissolve immediately, and the cell culture unit cannot be connected with the surrounding chamber, thereby ensuring the stability of the culture environment in the cell culture unit. The first microfilament dissolves after contacting the cell culture fluid. By controlling the thickness of the semipermeable membrane, the length of the first microfilament in the pore, and the density of the first microfilament, etc., the time for the first microfilament to complete the dissolution can be controlled, and then the time for the cell culture unit to be connected with the surrounding chamber can be controlled, thereby achieving control of the semipermeable membrane switch.

[0116] In an exemplary embodiment, the first microfilaments may be doped with drugs, and the drugs slowly penetrate into the cell culture medium during the dissolution of the first microfilaments, thereby achieving a sustained release of the drugs.

[0117] In an exemplary embodiment, when cell culture is required, a cell culture fluid in which cells are suspended is added to the cell culture unit. When the cells enter a new environment, the environment needs to be kept as stable as possible. The material of the first microfilament can include a semipermeable membrane of protein. When the cell culture fluid is just added to the cell culture unit, the first microfilament will not dissolve immediately, and the cell culture unit cannot be connected to the surrounding chamber, which can ensure the stability of the culture environment in the cell culture unit. When the cells need to be passaged, trypsin is added to the cell culture fluid for cell digestion. At this time, the first microfilament will be digested by trypsin. By controlling the thickness of the semipermeable membrane, the length of the first microfilament in the pore, and the density of the first microfilament, the time for the first microfilament to complete dissolution can be controlled. Since the time of each cell digestion is determined, the opening time of the semipermeable membrane is related to the number of cell digestions, and then the time for the cell culture unit to be connected to the surrounding chamber can be controlled to achieve control of the semipermeable membrane switch.

[0118] The preparation process of the cell culture device provided in the embodiments of the present disclosure is described below with reference to the accompanying drawings.

[0119] In an exemplary embodiment, the cell culture device may be formed by a splicing method, that is, a semipermeable membrane is first formed, and then the semipermeable membrane is spliced ​​and combined with the side surface, bottom surface, etc. of the cell culture device, which may include the following steps 21 to 25.

[0120] (21) Forming sugar threads. In an exemplary embodiment, the process of forming sugar threads 301 may be similar to the process of forming sugar threads 301 in step 11 above, and will not be described in detail herein.

[0121] In an exemplary embodiment, the sugar filaments 301 may be provided as protein filaments, which is not limited in the present disclosure.

[0122] (22) Fixing the plurality of sugar threads on the sugar plate. In an exemplary embodiment, one end of the plurality of sugar threads 301 may be fixed on the sugar plate 310, and the arrangement of the plurality of sugar threads 301 may be the same as the distribution of the pores in the semipermeable membrane to be formed, such as Fig.13 shown.

[0123] In an exemplary embodiment, sugar can be heated into a liquid state and placed in a sugar plate mold. After the sugar cools down, a sugar plate 310 with a smooth surface can be formed. The sugar is sticky during the cooling process in the sugar plate mold, and the sugar threads 301 can be adhered to the sugar that has not yet been cooled and formed. After the sugar plate 310 is completely cooled, a sugar plate 310 with multiple sugar threads 301 fixed thereon can be obtained.

[0124] In an exemplary embodiment, the sugar plate 310 may be provided as a protein plate, but the present disclosure is not limited thereto.

[0125] (23) The sugar sheet with the sugar filaments fixed thereon is combined with the semipermeable membrane mold, and then the membrane body is cast. In an exemplary embodiment, the sugar sheet 310 with the sugar filaments 301 fixed thereon can be placed in the semipermeable membrane mold 311, and the surface of the sugar sheet 310 on the side away from the sugar filaments 301 can be in contact with the bottom surface of the semipermeable membrane mold 311, and the sugar filaments 301 and the sugar sheet 310 become part of the semipermeable membrane mold 311, and then the membrane body material is casted. The semipermeable membrane mold 311 after the membrane body material is cast is as shown in FIG. Fig.14 The membrane material and the pouring and curing process can be similar to the above step 13, and will not be described again.

[0126] In an exemplary embodiment, the film body can be cast according to the thickness of the semipermeable membrane. The thickness of the semipermeable membrane can be the distance between the opposite side surfaces of the semipermeable membrane. When casting the film body, the distance between the side surface of the film body material close to the sugar plate 310 and the side surface away from the sugar plate 310 can be controlled to be greater than or equal to the thickness of the semipermeable membrane, so that the desired thickness of the semipermeable membrane can be obtained after subsequent processing. The length of the sugar thread 301 can be greater than or equal to the size of the mold 311, and the present disclosure does not limit this.

[0127] In an exemplary embodiment, according to the research of the inventors of the present application, since the suspended cells in the cell culture fluid are in non-Brownian motion, they will not often contact the side wall of the cell culture device, so the "hanging tip" phenomenon is more likely to occur on the bottom wall of the cell culture device. The semipermeable membrane obtained by the splicing method may have a "hanging tip" phenomenon on the side of the semipermeable membrane away from the sugar plate 310. In actual use, the surface of the semipermeable membrane close to the sugar plate when the membrane is cast can be set as the cell contact surface to avoid the occurrence of the "hanging tip" phenomenon.

[0128] (24) Demolding and removing the sugar threads. In an exemplary embodiment, since the sugar threads 301 and the sugar plate 310 are soluble in water, the film body after demolding can be ultrasonically cleaned in pure water to remove the sugar threads 301 and obtain a semipermeable membrane 312 with transparent pores, such as Fig.15 Alternatively, the cleaning process of the membrane body after demoulding can be controlled so that at least one pore of the formed semipermeable membrane is filled with the first microwire, which is not limited in the present disclosure.

[0129] (25) Forming a cell culture device. In an exemplary embodiment, the semipermeable membrane 312 can be spliced ​​and combined with the bottom wall and side walls of the cell culture device according to the structure of the cell culture device to be formed, for example, by bonding. Fig.16 In the case where the semipermeable membrane 312 serves as the side wall of the culture unit, Fig.17 The semipermeable membrane 312 is used as the side wall and the bottom wall of the culture unit. Fig.16 and Fig.17 As shown, the semi-permeable membrane 312 can serve as the bottom wall or the side wall of the cell culture device, which is not limited in the present disclosure.

[0130] In an exemplary embodiment, the cell culture device can be formed by an integral casting method, that is, the cell culture device and the semipermeable membrane are formed simultaneously by an integral casting method. Taking the case where the semipermeable membrane is used as the side wall of the culture unit as an example, the cell culture device formed by the integral casting method can include the following steps 31 to 35.

[0131] (31) Forming sugar threads. In an exemplary embodiment, the process of forming sugar threads 301 may be similar to the process of forming sugar threads 301 in step 11 above, and will not be described in detail herein.

[0132] (32) Fixing a plurality of sugar threads between two sugar plates. In an exemplary embodiment, a first length of sugar thread 301 may be cut and fixed between two sugar plates 310, with both ends of the sugar thread 301 contacting a single sugar plate 310, such as Fig.18 The method of fixing the sugar thread 301 on the sugar plate 310 can refer to the description of step 22 above, which will not be repeated here. The first length can be greater than or equal to the length of the semipermeable membrane pore, so that after subsequent processing, a semipermeable membrane of desired specifications can be obtained.

[0133] In an exemplary embodiment, the lengths of the two sugar plates 310 to which the sugar threads 301 are fixed may be equal or similar.

[0134] (33) Combining the sugar sheet with the sugar filaments fixed thereon with the mold of the cell culture device. In an exemplary embodiment, the sugar sheet 310 with the sugar filaments fixed thereon 301 can be placed in the mold 313 of the cell culture device. The position of the sugar sheet 310 with the sugar filaments fixed thereon 301 is the position where the semipermeable membrane in the cell culture device is subsequently formed, such as Fig.19 The sugar plate 310 with the sugar filaments 301 fixed thereon can become a part of the mold 313 of the cell culture device.

[0135] In an exemplary embodiment, a plurality of sugar plates 310 with fixed sugar filaments 301 may be provided in the cell culture device mold 313, corresponding to the semipermeable membranes at different positions in the cell culture device, respectively, and the present disclosure is not limited thereto.

[0136] (34) Casting the membrane. In an exemplary embodiment, the membrane material can be cast in the cell culture device mold 311. The membrane material fills the gaps in the cell culture device mold 313 and fills the gaps between the sugar threads 301. The mold for casting the membrane material can be as follows: Fig. 20 The material of the cell culture device can be the same as that of the semipermeable membrane, and the membrane material and the casting and curing process can be similar to those in the above step 13, which will not be described in detail here.

[0137] (35) Demolding and removing sugar threads and margins. In an exemplary embodiment, since sugar threads 301 and sugar plates 310 are soluble in water, the demolded membrane can be ultrasonically cleaned in pure water to remove sugar threads 301. The cell culture device after water cleaning can be Fig.21 As shown in FIG. 1 , since there may be a gap between the contact portion of the sugar plate 310 and the cell culture device mold 311, during casting, the membrane material will fill the gap between the two. Therefore, after water washing, there may be gaps with residual membrane material on both sides of the semipermeable membrane. After removing the excess membrane material, the following can be obtained: Fig. 22 The cell culture apparatus is shown.

[0138] In an exemplary embodiment, taking the case where the semipermeable membrane is used as the side wall and the bottom wall of the culture unit as an example, forming the cell culture device by the integral casting method may include the following steps 41 to 45.

[0139] (41) Forming sugar threads. In an exemplary embodiment, the process of forming sugar threads 301 may be similar to the process of forming sugar threads 301 in step 11 above, and will not be described in detail herein.

[0140] (42) Fixing a plurality of sugar threads between two sugar plates. In an exemplary embodiment, a sugar thread 301 of a first length may be cut and fixed between two sugar plates 310, with both ends of the sugar thread 301 along the length direction contacting a single sugar plate 310 respectively. The first length may be greater than or equal to the length of the semipermeable membrane pore, such as Fig.23 The method of fixing the sugar thread 301 on the sugar plate 310 can refer to the description of the above step 22, which will not be repeated here.

[0141] In an exemplary embodiment, the lengths of the two sugar plates 310 to which the sugar threads 301 are fixed may be equal or similar, and the set of sugar threads 301 and sugar plates 310 may be used to form the side wall of the cell culture unit.

[0142] In an exemplary embodiment, the lengths of the two sugar plates 310 that fix the sugar filaments 301 may not be equal. The group of sugar filaments 301 and sugar plates 310 can be used to form the bottom wall of the cell culture unit. For example, the sugar plate with a longer length can be called the first sugar plate, and the other sugar plate can be called the second sugar plate. The first sugar plate can be used as the bottom surface of the cell culture device mold in subsequent steps.

[0143] In an exemplary embodiment, the sugar plate 310 may be provided as a protein plate, but the present disclosure is not limited thereto.

[0144] (43) Combining the sugar sheet with the sugar filaments fixed thereon with the mold of the cell culture device. In an exemplary embodiment, the sugar sheet 310 with the sugar filaments fixed thereon 301 can be placed in the mold 313 of the cell culture device. The position of the sugar sheet 310 with the sugar filaments fixed thereon 301 is the position where the semipermeable membrane in the cell culture device is subsequently formed, and can be located on the side wall and the bottom wall of the cell culture unit, such as Fig.24 The sugar plate 310 with the sugar filaments 301 fixed thereon can become a part of the mold 313 of the cell culture device.

[0145] In an exemplary embodiment, the sugar plate 310 having a longer length can serve as the bottom surface of the entire cell culture device mold 313 .

[0146] In an exemplary embodiment, a plurality of sugar plates 310 with fixed sugar filaments 301 may be provided in the cell culture device mold 313, corresponding to the semipermeable membranes at different positions in the cell culture device, respectively, and the present disclosure is not limited thereto.

[0147] (44) Casting the membrane. In an exemplary embodiment, the membrane material can be cast in the cell culture device mold 313. The membrane material fills the gaps in the cell culture device mold 313 and fills the gaps between the sugar threads 301. The mold for casting the membrane material can be as follows: Fig.25 The material of the cell culture device can be the same as that of the semipermeable membrane, which is convenient for casting. The membrane material and the casting and curing process can be similar to those in the above step 13, which will not be repeated here.

[0148] In an exemplary embodiment, according to the research of the inventors of the present application, when a semipermeable membrane is disposed on the bottom wall of a cell culture device, the semipermeable membrane obtained by the integral casting method is less likely to have a "hanging tip" phenomenon.

[0149] (45) Demolding and removing sugar threads and margins. In an exemplary embodiment, since sugar threads 301 and sugar plates 310 are soluble in water, the demolded film can be ultrasonically cleaned in pure water to remove sugar threads 301. The cell culture device after water cleaning can be Fig.26 As shown in the figure, there may be gaps of membrane material remaining on both sides of the semipermeable membrane. After removing the excess membrane material, the following can be obtained: Fig. 27 The cell culture apparatus is shown.

[0150] The inventors of the present disclosure have found through research that when demolding PDMS, when the cell culture device has a large depth and width or a dense structure, there will be a problem of difficulty in demolding, which may cause damage to the cell culture device or the mold. In the existing method, a silanization agent is often used to treat the surface of the cell culture device mold, but this agent is highly toxic and harmful to the human body. In the embodiment of the present disclosure, by using sugar as the base of the mold, the base can be removed by clean water, which helps the demolding process to proceed smoothly, is more conducive to obtaining a complete semipermeable membrane and cell culture device, saves production costs, and avoids the use of highly toxic agents, which is very friendly to the natural environment and the worker's operating environment.

[0151] An embodiment of the present disclosure provides a method for preparing a semipermeable membrane, comprising: using a microfilament material to form a first microfilament, wherein the first microfilament is configured to dissolve in a first state; combining the first microfilament with a semipermeable membrane mold; casting a membrane material in the semipermeable membrane mold; demolding the membrane material after solidification to obtain a semipermeable membrane; cleaning the semipermeable membrane to obtain the semipermeable membrane having a plurality of hollow structure channels, or obtaining the semipermeable membrane in which at least one of the channels is filled with the first microfilament.

[0152] In an exemplary embodiment, the microfilament material comprises a soluble sugar or a protein.

[0153] In an exemplary embodiment, the microwire material is doped with a first dopant, and the first dopant is configured to be exposed as the first microwire is dissolved.

[0154] In an exemplary embodiment, the forming of the first microwire using the microwire material includes: melting the microwire material and spraying it out through a nozzle, using at least two collecting rods to collect the first microwire, and winding the first microwire between the collecting rods.

[0155] In an exemplary embodiment, before combining the first microwire with the semipermeable membrane mold, the method further includes: cutting the first microwire.

[0156] In an exemplary embodiment, before the demolding, the method further comprises: cutting the first microfilaments.

[0157] An embodiment of the present disclosure provides an application of a cell culture device, wherein the cell culture device includes a semipermeable membrane, wherein the semipermeable membrane includes: a membrane body and a plurality of channels penetrating the membrane body; the plurality of channels are hollow structures; and the cell culture device is configured to achieve multi-cell culture through the semipermeable membrane.

[0158] An embodiment of the present disclosure provides an application of a cell culture device, wherein the cell culture device includes a semipermeable membrane, wherein the semipermeable membrane includes: a membrane body and a plurality of channels penetrating the membrane body; at least one of the channels is filled with a first microfilament; wherein the first microfilament is configured to dissolve in a first state; and the cell culture device is configured to achieve sustained release of drugs through the semipermeable membrane.

[0159] The present disclosure provides a method for preparing a cell culture device, comprising: using a microfilament material to form a first microfilament, wherein the first microfilament is configured to dissolve in a first state; using the first microfilament and a semipermeable membrane mold to form a semipermeable membrane, splicing and combining the semipermeable membrane with the bottom wall and the side wall of the cell culture device to obtain the cell culture device; or, combining the first microfilament with the cell culture device mold, casting a membrane material in the cell culture device mold, demolding the membrane material after solidification, and cleaning to obtain the cell culture device; wherein the semipermeable membrane includes a membrane body and a plurality of channels passing through the membrane body; the plurality of channels are hollow structures; or, at least one of the channels is filled with the first microfilament.

[0160] In an exemplary embodiment, the formation of a semipermeable membrane using the first microfilament includes: fixing one end of the first microfilament on a sugar plate and placing it on a semipermeable membrane mold, wherein a surface of the sugar plate away from the first microfilament is in contact with a bottom surface of the semipermeable membrane mold; pouring a membrane material in the semipermeable membrane mold; demolding the membrane material after solidification to obtain a semipermeable membrane; and cleaning the semipermeable membrane to obtain the semipermeable membrane having a plurality of hollow structural channels, or obtaining the semipermeable membrane in which at least one of the channels is filled with the first microfilament.

[0161] In an exemplary embodiment, combining the first microfilament with the cell culture device mold includes: cutting a first length of the first microfilament, the first length being greater than or equal to the channel length; fixing the first microfilament between a first sugar plate and a second sugar plate, with both ends of the first microfilament along the length direction respectively contacting a single sugar plate; and combining the fixed sugar filament and sugar plate with the cell culture device mold.

[0162] In an exemplary embodiment, the length of the first sugar plate is greater than that of the second sugar plate, and after being combined with the cell culture device mold, the first sugar plate serves as the bottom surface of the cell culture device mold.

[0163] Although the embodiments disclosed in the present invention are as above, the contents described are only embodiments adopted to facilitate understanding of the present invention and are not intended to limit the present invention. Any technician in the field to which the present invention belongs can make any modifications and changes in the form and details of implementation without departing from the spirit and scope disclosed in the present invention, but the patent protection scope of the present invention shall still be subject to the scope defined in the attached claims.

Claims

1. A semipermeable membrane, characterized in that include: A membrane body and a plurality of channels penetrating the membrane body; the plurality of channels are hollow structures; Alternatively, at least one of the channels is filled with a first microwire; wherein the first microwire is configured to dissolve in a first state.

2. The semipermeable membrane according to claim 1, characterized in that The extension directions of the plurality of channels are parallel to each other, or the extension directions of at least two channels intersect.

3. The semipermeable membrane according to claim 1, characterized in that In a plane parallel to the semipermeable membrane, a cross-sectional dimension of the pore channel is set to be greater than or equal to 5 microns and less than or equal to 30 microns.

4. The semipermeable membrane according to claim 1, characterized in that The first microwire is doped with a first dopant, and the first dopant is configured to be exposed as the first microwire is dissolved.

5. A method for preparing a semipermeable membrane, characterized in that: include: forming a first microfilament using a microfilament material, wherein the first microfilament is configured to dissolve in a first state; combining the first microfilament with a semipermeable membrane mold; Casting membrane material in the semipermeable membrane mold; After the membrane material is solidified, demoulding is performed to obtain a semipermeable membrane; The semipermeable membrane is cleaned to obtain the semipermeable membrane having a plurality of hollow structure channels, or the semipermeable membrane having at least one channel filled with the first microwires is obtained.

6. The method for preparing a semipermeable membrane according to claim 5, characterized in that: The microfilament material includes soluble sugar or protein.

7. The method for preparing a semipermeable membrane according to claim 5, characterized in that: The microwire material is doped with a first dopant, and the first dopant is configured to be exposed as the first microwire is dissolved.

8. The method for preparing a semipermeable membrane according to claim 5, characterized in that: The method of using the microwire material to form the first microwire comprises: melting the microwire material and spraying it out through a nozzle, using at least two collecting rods to collect the first microwire, and winding the first microwire between the collecting rods.

9. The method for preparing a semipermeable membrane according to claim 5, characterized in that: Before combining the first microfilament with the semipermeable membrane mold, the method further includes: cutting the first microfilament.

10. The method for preparing a semipermeable membrane according to claim 5, characterized in that: Before the demoulding, the method further comprises: cutting the first microfilaments.

11. A cell culture device, characterized in that: Comprising at least one semipermeable membrane as claimed in any one of claims 1 to 4.

12. An application of a cell culture device, characterized in that: It comprises a semipermeable membrane, comprising: a membrane body and a plurality of pores penetrating the membrane body; the plurality of pores are hollow structures; the cell culture device is configured to realize multi-cell culture through the semipermeable membrane.

13. An application of a cell culture device, characterized in that: A semipermeable membrane is provided, comprising: a membrane body and a plurality of pores penetrating the membrane body; at least one of the pores is filled with a first microfilament; wherein the first microfilament is configured to dissolve in a first state; and the cell culture device is configured to achieve sustained release of the drug through the semipermeable membrane.