Composite membrane structure

Abstract

A composite membrane structure comprises a middle layer and at least one surface layer. The middle layer is provided with a plurality of holes, and at least one surface layer is arranged on one side of the middle layer. The surface layer and the middle layer are made of different materials. A plurality of holes of the middle layer pass through the middle layer and are opened at two opposite sides of the middle layer.

Description

Technical Field

[0001] The present invention relates to a bionic technology, in particular to a membrane structure which can be used for a bionic organ device. Background Art

[0002] Traditional cell culture is difficult to reflect the complex physiological functions of biological tissues and organs, and animal experiments have disadvantages such as long cycles and high costs. Organ chips reconstruct the physiological environment of organs in the body, simulate the structure, microenvironment and physiological functions of biological organs, and can accurately control parameters. They have the advantages of miniaturization, integration, high efficiency and low cost. However, the current organ chips are limited by the hydrophilic nature of their porous membranes and cannot properly reflect the microenvironment and conditions in the body, and cannot achieve certain desired effects in use. Summary of the invention

[0003] The invention provides a composite membrane structure which can be used for the attachment or cultivation of cells or tissues, for simulating the microenvironment in a living body, and for bionic organ devices.

[0004] To achieve one or part or all of the above purposes or other purposes, one embodiment of the present invention provides a composite membrane structure, comprising an intermediate layer and at least one surface layer. The intermediate layer has a plurality of holes, and at least one surface layer is disposed on one side of the intermediate layer. The material of the surface layer is different from that of the intermediate layer. The plurality of holes in the intermediate layer pass through the intermediate layer and open on opposite sides of the intermediate layer.

[0005] In one embodiment of the present invention, the material of the at least one surface layer is a hydrophobic material having biocompatibility.

[0006] The present invention adopts a composite structure with an intermediate layer and a surface layer, and the materials between the intermediate layer and the surface layer are different, so the membrane can have appropriate hydrophilic and / or hydrophobic properties and air permeability. When used for the attachment or cultivation of cells or tissues, it helps to better simulate the microenvironment in the body, and can have different applications according to the needs of experiments or simulations.

[0007] In order to make the above and other purposes, features and advantages of the present invention more clearly understood, embodiments are given below with reference to the accompanying drawings for detailed description as follows. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 FIG. 1 is a three-dimensional schematic diagram of a composite membrane structure according to a first embodiment of the present invention.

[0009] Figure 2 Shown Figure 1 Schematic cross-sectional view along aa'.

[0010] Figure 3FIG. 1 is a schematic cross-sectional view of a composite membrane structure according to a second embodiment of the present invention.

[0011] Figure 4 It is a schematic diagram showing the operation of the composite membrane structure according to an embodiment of the present invention.

[0012] Wherein, the reference numerals are:

[0013] 1: Bionic organ device

[0014] 10, 10': Composite membrane structure

[0015] 11: Side 1

[0016] 12: Side 2

[0017] 200: Middle layer

[0018] 250: Holes

[0019] 251, 252: Opening

[0020] 300: Surface

[0021] 310: First surface

[0022] 320: Second surface

[0023] 350: Hole

[0024] 50: Shell

[0025] 510: First cavity

[0026] 520: Second cavity

[0027] T1, T2: thickness

[0028] D: Aperture

[0029] A, A': Water drop angle

[0030] L: Liquid

[0031] C: Cell DETAILED DESCRIPTION

[0032] The aforementioned and other technical contents, features and effects of the present invention will be clearly presented in the following detailed description of an embodiment with reference to the drawings. The directional terms mentioned in the following embodiments are only with reference to the directions of the attached drawings. Therefore, the directional terms used are used to illustrate and not to limit the present invention. In addition, the terms "first", "second", etc. mentioned in this specification or the scope of the patent application are only used to name the name of the element or to distinguish different embodiments or scopes, and are not used to limit the upper or lower limit of the number of elements.

[0033] Figure 1 FIG. 1 is a three-dimensional schematic diagram of a composite membrane structure according to an embodiment of the present invention. Figure 2 for Figure 1 Schematic diagram of the cross section along aa'. Figures 1-2 As shown, the composite membrane structure 10 of the embodiment of the present invention includes an intermediate layer 200 and at least one surface layer 300. The intermediate layer 200 has a plurality of holes 250, and the surface layer 300 is disposed on one side of the intermediate layer 200. The material of the surface layer 300 is different from the material of the intermediate layer 200. In addition, in the embodiment of the present invention, the thickness T1 of the surface layer 300 is generally thinner than the thickness T2 of the intermediate layer 200. For example, the surface layer 300 may have a thickness T1 in nanometers (nm), such as tens of nanometers or hundreds of nanometers, and the intermediate layer 200 may have a thickness T2 in micrometers (μm), such as several micrometers, more than ten micrometers, or tens of micrometers. Figures 1-2 In the illustrated embodiment, the number of the surface layer 300 is one, but in other embodiments (described later), the number of the surface layers 300 may be, for example, two, and the two surface layers 300 may be further disposed on opposite sides of the middle layer 200, respectively, to form a sandwich structure in which the two surface layers 300 sandwich the middle layer 200.

[0034] like Figure 2 As shown, a plurality of holes 250 pass through the middle layer 200 and form openings 251 and 252 on opposite sides of the middle layer 200. The diameters of the openings 251 and 252 may be the same as or different from the aperture D of the hole 250. The hole 250 may have an aperture D in nanometers (nm), such as tens of nanometers or hundreds of nanometers. In one embodiment of the present invention, the aperture D of the hole 250 is, for example, 200 to 800 nm, such as 200 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, and 800 nm, but is not limited thereto. Figure 1 As shown, the plurality of holes 250 may be further evenly distributed in the middle layer 200. The distribution density may be, for example, tens of thousands, hundreds of thousands, or millions per square centimeter. In one embodiment of the present invention, the distribution density of the holes 250 is, for example, 5*10 5 ~8*10 6 The density of the holes 250 and the size of the holes 250 can be matched with each other to provide an appropriate range of opening ratios, so that the intermediate layer 200 and the composite membrane structure 10 have appropriate air permeability.

[0035] In the embodiment of the present invention, the middle layer 200 and the surface layer 300 are made of biocompatible materials, for example. The materials used can be polymer materials. For the middle layer 200, the optional materials are polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), polyurethane, styrene-ethylene-butylene-styrene (SEBS), polyhydroxyethyl methacrylate (pHEMA), polyethylene glycol or polyvinyl alcohol, polycarbonate (PC), but not limited thereto. The thickness T2 in the embodiment of the present invention is commonly 10μm, 15μm, 20μm, 25μm, 30μm, 35μm, 40μm, 45μm, 50μm, but not limited thereto. In addition to the thickness T1 of the surface layer 300 being generally thinner than the thickness T2 of the middle layer 200, it is also more hydrophobic than the middle layer 200. For example, if the middle layer 200 is hydrophilic, the surface layer 300 is hydrophobic, or when the middle layer 200 and the surface layer 300 are both hydrophobic, the hydrophobicity of the surface layer 300 is higher than that of the middle layer 200. Figure 2 As shown, the liquid L is on the surface layer 300 (such as Figure 2 The water drop angle A formed on the middle layer 200 (such as Figure 2 In one embodiment of the present invention, the surface layer 300 can make the liquid L form a water drop angle A greater than 90 degrees, while the water drop angle A' of the middle layer 200 is less than 90 degrees, such as 20 to 40 degrees, but not limited thereto. In this way, the composite membrane structure 10 of the embodiment of the present invention can have different hydrophobicity on both sides.

[0036] The material of the surface layer 300 can be selected from the above-mentioned polymer materials such as polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), polyurethane, styrene-ethylene-butylene-styrene (SEBS), poly(hydroxyethyl methacrylate) (pHEMA), polyethylene glycol or polyvinyl alcohol, polycarbonate (PC), or selected according to the selection of the material of the middle layer 200, but not limited thereto. In some embodiments of the present invention, when PET is used as the material of the middle layer 200, polyparaxylene or its analogue is used as the material of the surface layer 300. The surface layer 300 can be directly formed on one side or two opposite sides of the middle layer 200, or prepared in advance and then bonded to the middle layer 200. In one embodiment of the present invention, the surface layer 300 is directly formed on the middle layer 200, and the method of forming the surface layer 300 can be, for example, coating, evaporation, and printing. In one embodiment of the present invention, the material molecules are deposited on the middle layer 200 by evaporation to form the surface layer 300.

[0037] like Figures 1-2As shown, the surface layer 300 further has a plurality of holes 350, and the plurality of holes 350 correspond to the plurality of holes 250 of the middle layer 200, respectively. In an embodiment of the present invention, the plurality of holes 350 are, for example, formed simultaneously when the surface layer 300 is formed. In addition, in an embodiment of the present invention, the positions of the plurality of holes 350 can be determined based on the positions of the plurality of holes 250 on the middle layer 200. For example, when the surface layer 300 material is deposited on the middle layer 200 by evaporation, a gap may be left because the material molecules are not deposited at the holes 250, thereby forming the holes 350 of the surface layer 300.

[0038] In the embodiment of the present invention, the thickness T1 of the surface layer 300 can be further designed according to the size of the hole 250. For example, the thickness T1 of the surface layer 300 is a certain percentage of the hole diameter D of the hole 250, wherein for example, it does not exceed 100%, and in one embodiment of the present invention, for example, but not limited to 20% to 60%, so that when the hole diameter D of the hole 250 is, for example, 200nm, the thickness T1 of the surface layer 300 can be, for example, 40 to 120nm; when the hole diameter D of the hole 250 is, for example, 500nm, the thickness T1 of the surface layer 300 can be, for example, 100 to 300nm; when the hole diameter D of the hole 250 is, for example, 800nm, the thickness T1 of the surface layer 300 can be, for example, 160 to 480nm. In addition, the upper and lower limits of the percentage may be different due to different materials of the surface layer 300 and the intermediate layer 200.

[0039] The present invention selects a specific material such as polyparaxylene or the like as the material of the surface layer 200, and the thickness T1 is the lower limit value, such as at least 20% of the hole diameter D of the hole 250, which can ensure that the water drop angle A formed is greater than 90 degrees. The increase in the thickness T1 of the surface layer 200 can effectively increase the water drop angle A, such as to 95 degrees, 100 degrees, 105 degrees, 110 degrees or more. However, if the thickness T1 of the surface layer 200 does not exceed the upper limit value, such as 60% of the hole diameter D of the hole 250, in some embodiments, it helps to ensure that the gap left at the hole 250 is sufficient to become an appropriate hole 350, and its size can make the composite membrane structure 10 have an appropriate range of opening ratio, but it is not limited to this. For example, even if the integrity of the hole 250 may be affected during the process of material deposition, such as material deposition in the hole 250 or its periphery, the present invention ensures the hydrophobicity and opening ratio of the composite membrane structure 10 by designing the upper and lower limits of the thickness T1 of the surface layer 200 and the appropriate degree of deposition. The surface hydrophobicity of the composite membrane structure 10 causes the liquid to condense into liquid beads and is less likely to pass through the composite membrane structure 10 . The pores 250 allow gas to pass through. Therefore, the composite membrane structure 10 of the embodiment of the present invention is both hydrophobic and breathable.

[0040] Figure 3 FIG. 2 is a cross-sectional schematic diagram of a composite membrane structure according to another embodiment of the present invention. Figure 3As shown, the surface layer 300 of the composite membrane structure 10' may further include a first surface layer 310 and a second surface layer 320, and the first surface layer 310 and the second surface layer 320 are respectively disposed on opposite sides of the intermediate layer 200. The thickness T1 of the first surface layer 310, the thickness T1 of the second surface layer 320 and the thickness T2 of the intermediate layer 200 are as described above, and are not repeated here, wherein the thickness T1 of the first surface layer 310 and the thickness T1 of the second surface layer 320 can be respectively designed as described above, that is, according to the size of the hole 250, and are a certain percentage of the aperture D of the hole 250. The materials of the first surface layer 310 and the second surface layer 320 are as described above. In addition, in the embodiment of the present invention, the materials of the first surface layer 310 and the second surface layer 320 are the same, but not limited thereto. In addition, the number of surface layers 300 is not limited to one or two. For example, multiple surface layers 300 can be stacked on the same side of the intermediate layer 200, and the materials between the surface layers 300 can be the same or different.

[0041] The first surface layer 310 and the second surface layer 320 have stronger hydrophobicity than the middle layer 200, and as mentioned above, the first surface layer 310 and the second surface layer 320 can make the liquid L form a water drop angle A greater than 90 degrees. In addition, when the materials of the first surface layer 310 and the second surface layer 320 are different, the hydrophobicity between the two may be different, wherein the different water drop angles A formed may be different, but not limited to this. In this way, the composite membrane structure 10' of the embodiment of the present invention can have different hydrophobicity on both sides. The first surface layer 310 and the second surface layer 320 also further have a plurality of holes 350, and the plurality of holes 350 correspond to the plurality of holes 250 of the middle layer 200 respectively. For example, the openings 251 and 252 on both sides of any hole 250 correspond to the holes 350 in the first surface layer 310 and the holes 350 in the second surface layer 320 respectively. In the embodiment of the present invention, the plurality of holes 350 of the first surface layer 310 and / or the second surface layer 320 are formed simultaneously when the first surface layer 310 and / or the second surface layer 320 are formed. In addition, the first surface layer 310 and the second surface layer 320 are not limited to being formed simultaneously. For example, different materials may be deposited on different sides of the intermediate layer 200 to form the first surface layer 310 and the second surface layer 320.

[0042] The composite membrane structures 10, 10' of the embodiments of the present invention can be used for attachment or culture of cells or tissues, and / or for bionic organ devices, wherein the hydrophobicity of the composite membrane structures 10, 10' helps to create an interface layer, such as a gas-liquid interface layer, which allows gas to pass through and blocks liquid from passing through. In addition, the different hydrophobicity of the composite membrane structures 10, 10' on both sides can make the interface layer further directional, such as blocking the passage of liquid in a specific direction.

[0043] Figure 4 The composite membrane structure 10 / 10' of the embodiment of the present invention is used in a bionic organ device. Figure 4 As shown, the bionic organ device 1 may include a housing 50 and a composite membrane structure 10 / 10'. The space in the housing 50 may be further divided into a plurality of spaces, such as a first chamber 510 and a second chamber 520, and the first chamber 510 and the second chamber 520 are separated by the composite membrane structure 10 / 10'. The composite membrane structure 10' may be used to attach or culture a type of cell C on the side (first side 11) facing the first chamber 510, and may be used to attach or culture another type of cell (not shown) on the side (second side 12) facing the second chamber 520. In addition, different liquids (not shown) such as culture fluids with different components may be further arranged in the first chamber 510 and the second chamber 520, or liquids and gases may be arranged in the first chamber 510 and the second chamber 520, respectively, such as liquids in the first chamber 510 and gases in the second chamber 520, or conversely gases in the first chamber 510 and liquids in the second chamber 520. Thereby, the bionic organ device 1 can simulate the microenvironment in a living body, and can further test or simulate the interaction between different cells.

[0044] In some embodiments, one side of the composite membrane structure 10 / 10', such as the first side 11, can be used to attach or culture, for example, lung epithelial cells, and the first chamber 510 is configured to simulate the environment of lung epithelial cells in a living body, including the introduction of specific gases such as oxygen-containing gases. The second side 12 can be used to attach other cells, such as vascular endothelial cells, but the present invention is not limited to this. At this time, the second chamber 520 is configured to simulate the environment of vascular endothelial cells in a living body, including the introduction of culture liquid. Based on the air permeability of the composite membrane structure 10 / 10', gas can penetrate the composite membrane structure 10 / 10' and travel between the first chamber 510 and the second chamber 520, while the hydrophobicity of the composite membrane structure 10 / 10' limits or prevents the passage of liquid.

[0045] In summary, the composite membrane structures 10, 10' of the embodiments of the present invention are gas permeable, and can allow attached / cultured cells to achieve gas exchange on both sides of the membrane structure. On the other hand, the composite membrane structures 10, 10' can be used as a selective membrane. As a selective membrane, the composite membrane structures 10, 10' can be used to simulate the role of natural barriers, such as simulating the situation where fluids between tissues in a biological body are not intercommunication, or can be used in bionic organ devices according to experimental design.

[0046] Of course, the present invention may have many other embodiments. Without departing from the spirit and essence of the present invention, technicians familiar with the field may make various corresponding changes and deformations based on the present invention, but these corresponding changes and deformations should all fall within the scope of protection of the claims of the present invention.

Claims

1. A composite membrane structure, characterized in that: Include: a middle layer; the middle layer having a plurality of holes; and At least one surface layer is disposed on one side of the middle layer; the material of the surface layer is different from that of the middle layer; The holes in the middle layer pass through the middle layer and open at two opposite sides of the middle layer.

2. The composite membrane structure as claimed in claim 1, wherein the at least one surface layer further comprises a first surface layer and a second surface layer; the material of the first surface layer and the material of the second surface layer are hydrophobic materials and are respectively disposed on opposite sides of the middle layer. 3 . The composite membrane structure as claimed in claim 1 , wherein the pores have a pore diameter of 200-800 nm.

4. The composite membrane structure as claimed in claim 1, wherein the holes are further evenly distributed in the middle layer, and the distribution density in the middle layer is 5*10 5 ~8*10 6 Pieces / square centimeter. The composite membrane structure as claimed in claim 3 , wherein the thickness of the at least one surface layer is smaller than the diameter of the holes. 6 . The composite membrane structure as claimed in claim 5 , wherein a thickness of the at least one surface layer is 20% to 60% of a diameter of the holes. 7 . The composite membrane structure as claimed in claim 1 , wherein the material of the at least one surface layer is a hydrophobic material; and the hydrophobic material has biocompatibility. 8 . The composite membrane structure as claimed in claim 7 , wherein the at least one surface layer is further suitable for the liquid to form a water drop angle; the water drop angle is greater than 90 degrees. 9 . The composite membrane structure as claimed in claim 7 , wherein the hydrophobicity of the at least one surface layer is higher than the hydrophobicity of the middle layer. 10 . The composite membrane structure as claimed in claim 1 , wherein the at least one surface layer further has a plurality of holes; the holes correspond to the holes, and the holes are smaller than or equal to the holes.

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