Composite membrane structure

Abstract

A composite membrane structure includes a middle layer and at least one surface layer. The middle layer has a plurality of holes, and the at least one surface layer is disposed on one side of the middle layer. The material of the surface layer is different from the material of the middle layer. A plurality of holes in the middle layer pass through the middle layer and open on opposite sides of the middle layer.

Description

[Technical Field]

[0001] This invention relates to a biomimetic technology, and more particularly to a membrane structure that can be used in biomimetic organ devices. [Previous Technology]

[0002] Traditional cell culture methods struggle to reflect the complex physiological functions of tissues and organs in organisms, while animal experiments suffer from drawbacks such as long cycles and high costs. Organ wafers reconstruct the physiological environment of organs in vivo, simulating the structure, microenvironment, and physiological functions of biological organs, and allowing for precise parameter control. They also offer advantages such as miniaturization, integration, high efficiency, and reduced costs. However, current organ wafers are limited by the hydrophilic nature of their porous membranes, making it impossible to accurately reflect the microenvironment and conditions within organisms, and thus failing to achieve certain desired effects in practical use. [Summary of the Invention]

[0003] The present invention provides a composite membrane structure that can be used for cell or tissue attachment or culture to simulate the microenvironment in a living organism, and can also be used in biomimetic organ devices.

[0004] To achieve one, some, or all of the above objectives, or other objectives, an 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 pores, 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 pores 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 at least one of the surface layers is a hydrophobic material. The hydrophobic material is biocompatible.

[0006] Because the present invention employs a composite structure with an intermediate layer and a surface layer, and the materials of the intermediate layer and the surface layer are different, the membrane can possess appropriate hydrophilic and / or hydrophobic properties and air permeability. When used for cell or tissue attachment or culture, it helps to better simulate the microenvironment in vivo, and can be applied in different ways to meet the needs of experiments or simulations.

[0007] In order to make the above and other objects, features and advantages of the present invention more apparent and understandable, embodiments are described below in detail with reference to the accompanying drawings.

Implementation Method

[0008] The foregoing descriptions and other technical contents, features, and effects of this invention will be clearly presented in the following detailed description of one embodiment with reference to the accompanying drawings. The directional terms mentioned in the following embodiments are only for reference to the directions in the accompanying drawings. Therefore, the directional terms used are for illustrative purposes and not for limiting the invention. Furthermore, the terms "first," "second," etc., mentioned in this specification or the claims are only used to name elements or distinguish different embodiments or scopes, and are not used to limit the upper or lower limit of the number of elements.

[0009] Figure 1 is a perspective view of a composite membrane structure according to an embodiment of the present invention, and Figure 2 is a cross-sectional view along aa' in Figure 1. As shown in Figures 1 and 2, 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 pores 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 that of the intermediate layer 200. Furthermore, 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, while the intermediate layer 200 may have a thickness T2 in micrometers (μm), such as several micrometers, tens of micrometers, or tens of micrometers. In the embodiments shown in Figures 1 and 2, the number of surface layers 300 is one. However, in other embodiments (described later), the number of surface layers 300 may be, for example, two, and the two surface layers 300 may be further disposed on opposite sides of the intermediate layer 200, that is, forming a sandwich structure in which the two surface layers 300 sandwich the intermediate layer 200.

[0010] As shown in Figure 2, multiple holes 250 pass through the intermediate layer 200 and form openings 251 and 252 on opposite sides of the intermediate layer 200. The diameters of the openings 251 and 252 may be the same as or different from the pore diameter D of the holes 250. The holes 250 may have a pore diameter D in nanometers (nm), for example, tens of nanometers or hundreds of nanometers. In one embodiment of the present invention, the pore diameter D of the holes 250 is, for example, 200 to 800 nm, such as 200 nm, 300 nm, 400 nm, 500 nm, 600 nm, 700 nm, or 800 nm, but is not limited thereto. As shown in Figure 1, the multiple holes 250 may be further uniformly distributed in the intermediate 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 pores 250 is, for example, 5*10⁵ to 8*10⁶ pores / square centimeter, such as 500,000, 1,000,000, 2,000,000, 3,000,000, 4,000,000, 5,000,000, 6,000,000, 7,000,000, or 8,000,000 pores per square centimeter, but is not limited thereto. The density and size of the pores 250 can be matched to provide an appropriate range of opening ratios, thereby giving the intermediate layer 200 and the composite membrane structure 10 appropriate air permeability.

[0011] In embodiments of the present invention, the intermediate layer 200 and the surface layer 300 are, for example, prepared from biocompatible materials. The materials used can be polymeric materials. For the intermediate layer 200, selectable materials include, for example, polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), polyurethane, styrene-ethylene-butene-styrene (SEBS), polyhydroxyethyl methacrylate (pHEMA), polyethylene glycol or polyvinyl alcohol, and polycarbonate (PC), but are not limited thereto. The thickness T2 is commonly, for example, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 35 μm, 40 μm, 45 μm, and 50 μm in embodiments of the present invention, but is not limited thereto. The surface layer 300 is generally thinner than the intermediate layer 200 (thickness T2) in terms of thickness T1, and also has stronger hydrophobicity than the intermediate layer 200. For example, if the intermediate layer 200 is hydrophilic, then the surface layer 300 is hydrophobic; or when both the intermediate layer 200 and the surface layer 300 are hydrophobic, the surface layer 300 is more hydrophobic than the intermediate layer 200. As shown in Figure 2, the droplet angle A formed by liquid L on the surface layer 300 (the upper side in Figure 2) is greater than the droplet angle A' formed on the intermediate layer 200 (the lower side in Figure 2). In one embodiment of the present invention, the surface layer 300 can cause liquid L to form a droplet angle A greater than 90 degrees, while the droplet angle A' of the intermediate layer 200 is less than 90 degrees, for example, 20 to 40 degrees, but not limited thereto. Thus, the composite membrane structure 10 of the embodiments of the present invention can have different hydrophobicities on both sides.

[0012] The material of the surface layer 300 may be selected from the above-mentioned polymeric materials such as polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), polyurethane, styrene-ethylene-butene-styrene (SEBS), poly(hydroxyethyl methacrylate) (pHEMA), polyethylene glycol or polyvinyl alcohol, polycarbonate (PC), or as appropriate for the selection of the material of the intermediate layer 200, but is not limited thereto. In several embodiments of the present invention, when PET is used as the material of the intermediate layer 200, parylene or its analogues are used as the material of the surface layer 300. The surface layer 300 may be formed directly on one side or opposite sides of the intermediate layer 200, or it may be prepared first and then bonded to the intermediate layer 200. In one embodiment of the present invention, the surface layer 300 is formed directly on the intermediate layer 200, and the surface layer 300 may be formed by, for example, coating, vapor deposition, or printing. In one embodiment of the present invention, the surface layer 300 is formed by vapor deposition, where material molecules are deposited on the intermediate layer 200.

[0013] As shown in Figures 1 and 2, the surface layer 300 further has a plurality of holes 350, and the plurality of holes 350 correspond to the plurality of pores 250 of the intermediate layer 200. In an embodiment of the present invention, the plurality of holes 350 are formed simultaneously, for example, during the forming of the surface layer 300. Furthermore, in one embodiment of the present invention, the position of the plurality of holes 350 can be determined based on the position of the plurality of pores 250 on the intermediate layer 200. For example, when the surface layer 300 material is deposited on the intermediate layer 200 by vapor deposition, gaps may be left because the material molecules are not deposited at the pores 250, thus forming the holes 350 of the surface layer 300.

[0014] In this embodiment of the invention, the thickness T1 of the surface layer 300 can be further designed according to the size of the aperture 250. For example, the thickness T1 of the surface layer 300 is a certain percentage of the aperture D of the aperture 250, wherein, for example, it does not exceed 100%, and in one embodiment of the invention, for example, but not limited to, 20% to 60%. Thus, when the aperture D of the aperture 250 is, for example, 200 nm, the thickness T1 of the surface layer 300 can be, for example, 40 to 120 nm; when the aperture D of the aperture 250 is, for example, 500 nm, the thickness T1 of the surface layer 300 can be, for example, 100 to 300 nm; when the aperture D of the aperture 250 is, for example, 800 nm, the thickness T1 of the surface layer 300 can be, for example, 160 to 480 nm. Furthermore, the upper and lower limits of the percentage may vary depending on the different materials of the surface layer 300 and the intermediate layer 200.

[0015] The present invention selects a specific material, such as parylene or its analogues, as the material of the surface layer 300, and the thickness T1 is a lower limit value, for example, at least 20% of the pore diameter D of the hole 250, which can ensure that the formed water droplet angle A is greater than 90 degrees. Increasing the thickness T1 of the surface layer 300 can effectively improve the water droplet angle A, for example, to 95 degrees, 100 degrees, 105 degrees, 110 degrees or more. However, in some embodiments, ensuring that the thickness T1 of the surface layer 300 does not exceed the upper limit value, for example, 60% of the pore diameter D of the hole 250, helps to ensure that the gap left at the hole 250 is sufficient to become a suitable hole 350, and its size allows the composite membrane structure 10 to have an appropriate range of aperture ratio, but is not limited thereto. For example, even if the integrity of the pores 250 may be affected during, for example, material deposition, such as material deposition within or around the pores 250, the present invention ensures the hydrophobicity and aperture ratio of the composite membrane structure 10 by designing upper and lower limits for the surface layer thickness T1 of 300 and an appropriate degree of deposition. The surface hydrophobicity of the composite membrane structure 10 causes liquid to condense into droplets, making it less likely for liquid to pass through the composite membrane structure 10, while the pores 250 allow gas to pass through. Therefore, the composite membrane structure 10 of the embodiments of the present invention is both hydrophobic and permeable.

[0016] Figure 3 shows a cross-sectional schematic diagram of a composite membrane structure according to another embodiment of the present invention. As shown in Figure 3, 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 will not be repeated here. The thickness T1 of the first surface layer 310 and the thickness T1 of the second surface layer 320 may be designed according to the size of the hole 250, and are a certain percentage of the hole diameter 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 embodiments of the present invention, the materials of the first surface layer 310 and the second surface layer 320 are the same, but this is not a limitation. Furthermore, 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 of these surface layers 300 can be the same or different.

[0017] The first surface layer 310 and the second surface layer 320 have stronger hydrophobicity than the intermediate layer 200, and as mentioned above, the first surface layer 310 and the second surface layer 320 can cause liquid L to form a droplet angle A greater than 90 degrees. Furthermore, when the materials of the first surface layer 310 and the second surface layer 320 are different, the hydrophobicity between them may differ, and the resulting droplet angles A may differ, but are not limited thereto. Thus, the composite membrane structure 10' of this embodiment of the invention can have different hydrophobicities on both sides. The first surface layer 310 and the second surface layer 320 also further have a plurality of pores 350, and the plurality of pores 350 correspond to the plurality of holes 250 of the intermediate layer 200, respectively. For example, the openings 251 and 252 on both sides of any hole 250 correspond to the hole 350 in the first surface layer 310 and the hole 350 in the second surface layer 320, respectively. In embodiments of the invention, the plurality of holes 350 in the first surface layer 310 and / or the second surface layer 320 are formed simultaneously, for example, during the forming of the first surface layer 310 and / or the second surface layer 320. Furthermore, the first surface layer 310 and the second surface layer 320 are not limited to being formed simultaneously. For example, different materials can be deposited sequentially on different sides of the intermediate layer 200 to form the first surface layer 310 and the second surface layer 320.

[0018] The composite membrane structures 10 and 10' of the embodiments of the present invention can be used for cell or tissue attachment or culture, and / or for biomimetic organ devices. The hydrophobicity of the composite membrane structures 10 and 10' helps to create an interface layer, such as a gas-liquid interface layer, which allows gas to pass through while hindering liquid passage. Furthermore, the different hydrophobicities on both sides of the composite membrane structures 10 and 10' can further give the interface layer directionality, for example, hindering the passage of liquid in a specific direction.

[0019] Figure 4 shows an operational schematic diagram of the composite membrane structure 10 / 10' used in a biomimetic organ device according to an embodiment of the present invention. As shown in Figure 4, the biomimetic organ device 1 may include a shell 50 and a composite membrane structure 10 / 10'. The space within the shell 50 may be further divided into multiple 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' can be used to attach or culture a cell C on the side facing the first chamber 510 (first side 11), and can be used to attach or culture another cell (not shown) on the side facing the second chamber 520 (second side 12). Furthermore, different liquids (not shown) can be placed in the first chamber 510 and the second chamber 520, such as culture media with different compositions. Alternatively, liquid and gas can be placed in the first chamber 510 and the second chamber 520 respectively, for example, liquid in the first chamber 510 and gas in the second chamber 520, or vice versa. In this way, the biomimetic organ device 1 can simulate the microenvironment within a living organism, and can also be used to further test or simulate the interactions between different cells.

[0020] In several 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 vivo, including the introduction of a specific gas, such as an oxygen-containing gas. The second side 12 can be used to attach other cells, such as vascular endothelial cells, but the invention is not limited thereto. In this case, the second chamber 520 is configured to simulate the environment of vascular endothelial cells in vivo, including the introduction of a culture liquid. Based on the 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' restricts or prevents the passage of liquid.

[0021] In summary, the composite membrane structures 10 and 10' of the embodiments of the present invention are breathable, allowing attached / cultured cells to exchange gases across the membrane structure. On the other hand, the composite membrane structures 10 and 10' can serve as selective membranes. As selective membranes, the composite membrane structures 10 and 10' can be used to simulate the function of natural barriers, such as simulating the lack of fluid exchange between tissues in a living organism, or can be designed for use in biomimetic organ devices.

[0022] Although the present invention has been disclosed above by way of embodiments, it is not intended to limit the present invention. Those skilled in the art to which the present invention pertains may make some modifications and refinements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims. [Simplified Explanation of the Diagram]

[0023] Figure 1 is a perspective view of the composite membrane structure according to the first embodiment of the present invention. Figure 2 is a cross-sectional view of Figure 1 along aa'. Figure 3 is a cross-sectional view of the composite membrane structure according to the second embodiment of the present invention. Figure 4 is an operational schematic diagram of the composite membrane structure according to an embodiment of the present invention.

Claims

1. A composite membrane structure comprising: an intermediate layer having a plurality of pores having a pore size of 200–800 nm; and at least one surface layer disposed on one side of the intermediate layer; the material of the at least one surface layer being different from the material of the intermediate layer, and the thickness of the at least one surface layer being less than the pore size; wherein the pores of the intermediate layer pass through the intermediate layer and open on opposite sides of the intermediate layer.

2. The composite membrane structure as claimed in claim 1, wherein the at least one surface layer further includes 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 intermediate layer.

3. The composite membrane structure as claimed in claim 1, wherein the pores are further uniformly distributed in the intermediate layer, and the distribution density in the intermediate layer is 5*105 to 8*106 pores / square centimeter.

4. The composite membrane structure as claimed in claim 1, wherein the thickness of the at least one surface layer is 20% to 60% of the pore diameter.

5. The composite membrane structure as claimed in claim 1, wherein the material of the at least one surface layer is a hydrophobic material; the hydrophobic material is biocompatible.

6. The composite membrane structure as claimed in claim 5, wherein the at least one surface layer is further adapted for liquid to form a droplet angle greater than 90 degrees.

7. The composite membrane structure as described in claim 5, wherein the hydrophobicity of the at least one surface layer is higher than that of the intermediate layer.

8. The composite membrane structure as claimed in claim 1, wherein the at least one surface layer further has a plurality of pores; the pores correspond to the holes, and the pores are less than or equal to the holes.

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