Biocompatible high aspect ratio porous membranes

Abstract

The porous membranes 102 provided in accordance with the present application have a desired coefficient of thermal expansion and a large surface area, such as at least about 4,000 mm 2 These porous membranes 102 can be fabricated according to an exemplary method of lithographic patterning using a photoresist 104, followed by development of the photoresist and etching. In one aspect, the etch barrier layer 104 is selected from a material that does not react with or bind metals or other contaminants into the membrane layer 102.

Description

Background Technology

[0001] Porous membranes are used in various biofiltration methods. These membranes are made of thin layers of polymer material in which pores are formed. One such material is prepared using a method called track etching, which... Figure 1 As shown, the track etching material is made using an electron gun. Electrons are directed into the film under vacuum conditions. The electrons create pores in the film, resulting in a porous film. Due to the randomness of the process, the resulting pores are randomly distributed across the film surface. There is a possibility that, due to overlap within the pores, this method results in some pores that are larger than expected.

[0002] Photolithography has been used to manufacture film materials. U.S. Patent 7,784,619, granted to Jacobsen and assigned to Baxter International, describes photolithography methods for preparing films. These methods use conventional semiconductor manufacturing techniques to fabricate films with a desired series of pores.

[0003] The inventors have discovered that standard techniques for semiconductor manufacturing cannot provide large surface area films with the desired properties. It is difficult to fabricate large surface area films that lie flat on a surface. One problem is the curling of the film material after separation from the support. Other problems include contamination of the film by a hard mask layer, which is necessary to create high aspect ratio pores in the film. In some applications, it may be desirable to produce films free of metal contaminants.

[0004] Therefore, the present invention seeks to improve microporous membranes and their manufacturing methods. Summary of the Invention

[0005] In one aspect, the invention includes a liquid filtration porous membrane comprising a polymer membrane layer having an average pore size in the range of 1 to 100 micrometers, a pore size standard deviation of less than or equal to 0.7 micrometers, and an offset ratio of 0.2 or less. The membrane ideally has a large surface area, for example, at least 4,000 mm². 2 According to one aspect of the invention, the pore size distribution can be controlled to be less than 0.3 micrometers. In another aspect, the pore size distribution has a standard deviation ranging from 0.15 to 0.7 micrometers, more preferably from 0.15 to 0.40 micrometers, or from 0.15 to 0.30 micrometers.

[0006] The polymer film can be made of various polymers, such as polyimide, polyamide, polycarbonate, polyetherimide, polyetherketone, polyurethane, synthetic polymers, low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon, Teflon (polytetrafluoroethylene), thermoplastic polyurethane (TPU), polyethylene, acrylate polymers, acrylate monomers, or acrylate elastomers. In a preferred embodiment, the polymer material is polyimide.

[0007] In another aspect, the present invention relates to a method of manufacturing a porous membrane for liquid filtration, comprising: a) depositing a photoresist layer on a top surface of a substrate, the substrate comprising a support layer, a polymer layer, and a hard mask layer, wherein the polymer layer has a thickness of 5 to 25 micrometers, and the substrate layer and the polymer layer have matched coefficients of thermal expansion relative to each other within ±25%; b) exposing the photoresist to a pattern of light; c) developing the photoresist layer to provide a first opening pattern in the photoresist layer exposing a portion of the hard mask layer; d) etching the exposed portion of the hard mask layer to provide a second opening pattern in the hard mask layer exposing a portion of the underlying polymer layer; e) removing the photoresist; f) etching the polymer layer through the openings in the hard mask layer to provide a third opening pattern in the polymer layer; g) removing the hard mask layer; and h) releasing the polymer layer from the substrate to provide the porous membrane, wherein the pore size of the porous membrane is defined by the pattern of light, and the membrane has a pore size of at least 4,000 mm. 2 Surface area.

[0008] In another aspect, the present invention relates to a porous membrane comprising a polymer layer having a diameter of at least 4,000 mm. 2 The membrane exhibits a continuous surface area, a thickness of 5 to 25 micrometers, and an opening pattern with a median aspect ratio ranging from 0.5:1 to 20:1. Furthermore, the polymer lacks detectable amounts of hard mask material or reaction products between the hard mask layer and the polymer, or the amounts present are so small as to be biologically insignificant, implying that they are non-toxic to cells, etc. In one aspect, the porous membrane has the ability to lie flat with an offset ratio of 0.2 or less.

[0009] In another aspect, the present invention relates to a method for preparing a porous membrane, comprising: a) depositing a photoresist layer on a top surface of a substrate, the substrate comprising a support layer, a polymer layer and a hard mask layer, wherein the polymer layer has a thickness of 5 to 25 micrometers and the surface area of ​​the substrate is at least 4,000 mm². 2a) wherein the hard mask and the polymer do not form a reactive layer at their interface; b) exposing the photoresist to a pattern of light; c) developing the photoresist layer to provide a first opening pattern in the photoresist layer that exposes a portion of the hard mask layer; d) etching the exposed portion of the hard mask layer to provide a second opening pattern in the hard mask layer that exposes a portion of the underlying polymer layer; e) removing the photoresist; f) etching the polymer layer through the openings in the hard mask layer, thereby forming a reactive layer in the polymer layer. A third opening pattern is provided, wherein the median aspect ratio of the third opening pattern is in the range of 0.5:1 to 20:1; g) the hard mask layer is removed, wherein after the hard mask layer is removed, the polymer layer lacks a detectable amount of hard mask material or reaction products of the hard mask layer with the polymer, or the amount present is so small that they are not biologically significant; and h) the polymer layer is released from the substrate to provide the porous membrane, wherein the pore size of the porous membrane is defined by the pattern of light, and the membrane has a pore size of at least 4,000 mm. 2 The surface area. The coefficient of thermal expansion between the polymer layer and the substrate can be controlled within ±15% relative to each other. More preferably, the CTE is controlled within ±10% relative to each other. Attached Figure Description

[0010] Figure 1 The surface of a porous membrane fabricated using a track etching method is shown.

[0011] Figure 2 The steps for manufacturing a membrane according to an embodiment of the present invention are shown.

[0012] Figure 3 An image of a membrane according to an embodiment of the present invention is shown.

[0013] Figure 4 A scanning electron microscope image of a membrane according to an embodiment of the present invention is shown.

[0014] Figure 5 A polyimide film prepared without controlling the CTE of the support layer and polymer layer is shown.

[0015] Figure 6 A polyimide film prepared according to an aspect of the invention is shown, wherein the CTE of the support layer and the polymer layer is controlled to be within 25% of each other. Detailed Implementation

[0016] This invention relates to the production of polymer films using photolithography, wherein the film material can be formed to have a thickness exceeding 4,000 mm. 2 It has a continuous surface area that can be laid flat without curling or other deformation.

[0017] The membrane of the present invention can be fabricated to have the desired pore size and distribution while maintaining a large continuous surface area.

[0018] The method of the present invention enables the production of biocompatible membranes and uses materials and techniques that avoid leaving residual components in the polymer material after processing. For example, the etching mask is selected from materials that do not react with components of the polymer, such as carbon. Avoiding these surface reactions is important for biofilms, which must not contaminate the materials they are intended to filter. Hard mask materials and etching conditions can be selected to minimize the level of residual hard mask material found in the membrane. Residual materials include elemental impurities from the hard mask material, including, for example, aluminum or silicon. In one embodiment, the membrane contains a biologically insignificant amount of residual hard mask material. In one embodiment, the amount of hard mask material on the polymer surface is preferably equal to or less than 0.15 μg / cm³. 2 More preferably, below 0.10 μg / cm 2 And the optimal value is below 0.01 μg / cm³. 2 .

[0019] like Figure 2 As shown, an exemplary method for manufacturing the film of the present invention first includes providing a base substrate layer 100. A film layer 102 is formed on the base substrate 100. A hard mask layer 103 is formed on the polymer layer 102. And a photomask layer 104 is provided on the hard mask layer 103.

[0020] The base substrate 100 can be made of glass, for example. Other suitable materials include silicon or metal. The film layer 102 is a polymer layer. In a preferred aspect of the invention, the film layer 102 and the base substrate 100 have similar coefficients of thermal expansion. The inventors have observed that when the thermal expansion characteristics of the polymer layer 102 and the base substrate 100 are matched, the resulting film resists deformation. This is a desirable property because a flat film is easier for the end user to handle. An ideal material with a CTE similar to that of glass is polyimide. In one aspect, polyimide is applied to a substrate and cured thereon, wherein the CTE of the cured polyimide substrate matches that of the glass. The inventors have found that the greater the difference between the glass and the polymer film layer (e.g., polyimide), the more likely the polymer is not flat when released from the glass.

[0021] In one embodiment, the polyimide, at a thickness of 20 micrometers, has a CTE of 3 ppm / °C between 50°C and 200°C, and the glass has a CTE of 3.2 ppm / °C between 50°C and 200°C. As mentioned above, the CTEs of the polymer and the substrate should be within ±25% of each other, more preferably within ±15% of each other, and most preferably within ±10%. For example, as mentioned above, the CTE of the glass is about 7% higher than that of the polyimide layer.

[0022] Suitable materials for membrane 102 may include polyimide, polyamide, polycarbonate, polyetherimide, polyetherketone, polyurethane, synthetic polymers, low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon, Teflon (polytetrafluoroethylene), thermoplastic polyurethane (TPU), polyethylene, acrylate polymers, acrylate monomers, or acrylate elastomers. Membrane 102 can be applied to base layer 100 using spin coating, spraying, meniscus coating, slot coating, dip coating, extrusion coating, or lamination (adhesive to the substrate). Membrane 102 can be cured using thermosetting, UV curing, or a combination of both.

[0023] The hard mask layer 103 is typically an inorganic material that can be selectively etched relative to polymeric materials such as film layers or photomask layers. Ideally, the inorganic layer is made of a material that does not react with film layer 102 in any way. For example, while aluminum is a known etching mask layer, Al may react with the polyimide of the film layer to form Al-C. This is undesirable because any metal contamination could render the membrane incompatible with biological process applications. Preferably, the hard mask layer is made of an aluminum alloy that exhibits little or no reaction with the polymer of the underlying film layer 102. The hard mask layer 103 can be deposited using one or more of physical vapor deposition, evaporation, chemical vapor deposition, and / or spraying.

[0024] Suitable hard mask materials include inorganic materials, organic materials, and multilayer inorganic and organic materials. More specifically, hard mask materials may include metals, insulators, semiconductors, photoresists, inorganic materials, organic materials, multilayer films, or combinations thereof. In some embodiments, the hard mask may include hydrogenated amorphous SiN (SiN:H) or hydrogenated amorphous SiO (SiO:H). Hard masks can be deposited using physical vapor deposition, evaporation, chemical vapor deposition, spraying, plating, lamination, spin coating, spraying, meniscus coating, slot coating, dip coating, or extrusion coating.

[0025] Ideally, the photoresist layer 104 can be patterned using lithography techniques commonly used in semiconductor and flat panel display manufacturing to expose and pattern the photoresist material. The photoresist material can be either positive or negative. Typically, a spin-coating technique is used to deposit the photoresist material to the desired thickness, followed by curing. The photoresist is then exposed to light to form a pattern, which is determined during photoresist development. Positive photoresist leaves material in areas not exposed to light and removes it during development in the light-exposed areas. Negative photoresist is the opposite; that is, negative photoresist remains in the light-exposed areas and is removed during development in the light-unexposed areas.

[0026] Figure 2 The structure shown in (a) represents a cross-section of the base layer 100, film layer 102, hard mask layer 103, and photoresist layer 104. This material can be fabricated during patterning or prefabricated and patterned at a later time. The overall shape is not critical and can be in the form of a disk, square, or rectangle. Figure 3 A disk-shaped membrane on a support structure is shown. This invention can be used to provide large-area porous membranes, including those with a surface area exceeding 4,000 mm². 2 Those.

[0027] Depend on Figure 2 The first step in fabricating the structure of the film (a) is to expose the surface of the photoresist to a light pattern and develop the photoresist to leave a pattern. Figure 2 (b) shows the photoresist pattern to provide a patterned photoresist layer 104. The location of light exposure depends on whether a positive or negative photoresist is used. Figure 2 (b) The photoresist 104 includes an opening 101 in the photoresist layer. The opening 101 in the photoresist layer 104 is formed during development after the photoresist 104 is exposed to a light pattern.

[0028] After forming the opening 101, a hard mask 103 is etched in the location of the opening 101 to form a hard mask opening 106, as shown. Figure 2 As shown in (c). The hard mask 103 can be etched using one or more of the following techniques: wet chemical etching, plasma etching, non-reactive sputtering, or a combination of these techniques. In one aspect, a combination of acetic acid, phosphoric acid, nitric acid, and water is used to etch the hard mask. In another aspect, ammonium fluoride (NH4F) and hydrofluoric acid (HF) are used to etch the hard mask layer. In another aspect, laser ablation can be used to remove the hard mask layer. Etching is typically performed at high temperatures. As described above, the material of the hard mask layer should be selected so that it does not react with the polymer beneath the film layer 102 at the temperatures encountered during the process, which includes etching the hard mask 103.

[0029] It should be understood that the hard mask layer is critical for providing a mask for subsequent etching of the holes in film layer 102. Although hard mask materials are known, many existing hard mask materials will react with carbon in the underlying film layer 102. For example, the inventors have observed that Al-C forms in the film layer when aluminum is used as a hard mask on a polyimide film. These reactions occur in part because of the increased temperature exposed to the substrate during manufacturing. For these reasons, it is desirable to use hard mask materials without potential metal contaminants, such as SiN or SiH as described above.

[0030] After patterning the hard mask layer 103 to form the opening 106, the photoresist can be removed using an NMP-based solvent or the like, and then the film layer 102 can be patterned to form the opening 107. Figure 2 (e) illustrates a patterning of the film layer 102 through the hard mask opening 106. This is an etching method designed to selectively remove the polymer film layer within the hard mask opening 106. Etching techniques may include wet chemical etching, plasma etching, non-reactive sputtering, or a combination of these techniques. It is important to note that the material must be sufficiently etched to expose the underlying substrate 100 through the film opening 107.

[0031] After patterning the film layer 102 to form the film opening 107, the hard mask layer 103 should be removed, such as... Figure 2 As shown in (f), the removal of the hard mask layer 103 is ideally performed in a selective manner relative to the film layer 102.

[0032] After removing the hard mask layer 103, as Figure 2 As shown in (g), the patterned membrane layer 102 is separated from the substrate 100. The membrane layer 102 can be released using mechanical release technology, laser release technology, solution-based release technology, thermal release technology, or a combination of these technologies.

[0033] The base layer and film layer must be selected to allow for release of the layer after patterning, but with sufficient adhesion to withstand processing. In one embodiment, the base layer 100 is made of glass, while the film layer 102 is polyimide. In a preferred embodiment, the base layer 100 and film 102 are selected to have similar coefficients of thermal expansion. The inventors have found that matching the CTE of the base layer 100 and film layer 102 is important for providing a flat film when delaminating from the base layer. In the case of mismatched CTEs, the film will tend to curl during delamination, which is undesirable.

[0034] Membrane 102 can be separated from substrate 100 using mechanical methods or a combination of chemical and mechanical methods. For example, the membrane can be removed using laser lift-off (LLO) technology. Alternatively or otherwise, the membrane may include a release layer (DBL) between membrane 102 and substrate 100. In a preferred aspect, the membrane 102 layer and substrate 100 layer are selected such that they can be easily separated without using LLO or DBL.

[0035] Figure 4 A scanning electron microscope image of a membrane according to an embodiment of the invention is shown. The holes can be patterned into regular shapes using the lithography technique described herein. Any desired pattern is possible. However, one advantage of using lithography is that the problem associated with overlapping holes caused by random processes can be avoided. Furthermore, in one embodiment, any symmetrical hole shape in the xy direction can be proportionally reproduced along the z-direction through the thickness of the membrane. For example, any symmetrical hole shape in the xy direction can be extruded along the z-direction with or without a draft angle. This can be used to avoid complex hole shapes in the z-direction and tri-point symmetry, i.e., helical geometries, which may naturally occur when a suitable hard mask cannot be used.

[0036] In one embodiment, the pores are designed to have a diameter ranging from 1 to 100 micrometers, more preferably from 1 to 10 micrometers, even more preferably from 3 to 7 micrometers, and most preferably about 5 micrometers. The membrane thickness, together with the pore diameter, determines the pore aspect ratio. The membrane thickness is typically in the range of 5 to 25 micrometers. The aspect ratio can range from 0.5:1 to a maximum of 20:1, preferably from 1:1 to 10:1, more preferably from 2:1 to 5:1, and most preferably about 3:1. In one aspect, the present invention is capable of producing membranes with a desired pore size distribution and low variability. In one aspect, variability can be characterized as a standard deviation of pore size. The standard deviation of pore size is ideally less than 0.70 micrometers, more ideally less than 0.50 micrometers, and even more ideally less than 0.30 micrometers. In another aspect, the standard deviation of pore size can range from 0.1 to 0.5 micrometers, more ideally from 0.15 to 0.4 micrometers, and more preferably from 0.15 to 0.3 micrometers. Table 1 shows the pore size and standard deviation of the membrane according to the present invention: These results are based on 15 measurement points on each 100×150 mm sheet. Some areas with smaller holes were observed, suggesting the possible presence of debris clogging the holes. The presence of some larger holes appears to be caused by defects in the mask. During production, defects in the mask can be remedied by replacing the mask.

[0037] The membranes of this invention have a pore size distribution that allows for reliable material separation based on size. The retention efficiency of the membrane is determined by challenging it with a suspension of uniform particles (polystyrene microspheres) of known size and concentration, and then quantifying the particles capable of passing through the membrane (downstream). The polystyrene beads used in these tests were unfunctionalized and unstained. Three bead size distributions with nominal sizes of 6, 10, and 12 micrometers were tested. The control membrane was a GE Healthcare TEM Nucleopore with a nominal size of 10 μm. The membranes of this invention used for testing had an accurate size of 10.3 μm ± 0.2 μm (statistical evaluation based on SEM micrographs). As shown in Table 2, the membranes of this invention exhibit a very low standard deviation in average retention compared to commercially available track-etched membranes, demonstrating the reliability of the membranes of this invention in terms of pore size reproducibility.

[0038] The porous membrane of the present invention has the desirable property of not curling after being delaminated from the support. This characteristic becomes more critical as the surface area of ​​the produced membrane increases. For example, when the surface area of ​​the membrane is 4,000 mm... 2 At or larger scales, the inventors observed a tendency for the membrane to curl after being delaminated from the substrate. Existing attempts to develop porous membranes with photolithography / etching have utilized polymer layers with indeterminate coefficients of thermal expansion, making it difficult to produce them without curling during delamination, especially at the claimed large surface areas. These limitations severely restrict the surface area size of the membrane.

[0039] The desired offset level, or when the membrane is self-supporting, is the offset ratio calculated by dividing the maximum offset of the flat plane by the ratio of the length of the membrane on the flat surface, which is 0.2 or less. Figure 5 A membrane is shown with an offset value of 0.22, calculated as 10 mm curl divided by a maximum diameter of 47 mm. This level of offset ratio is due to a lack of control over the CTE of the substrate and polymer layer, resulting in polymer layer separation leading to a curled membrane. Figure 6 A membrane according to an embodiment of the invention is shown, wherein the offset is 0.04, or in other words, the offset is less than 1 mm over a diameter of 25 mm.

[0040] Jurkat cells (human lymphoma) were cultured in RPMI medium supplemented with fetal bovine serum and an antibiotic complex (streptomycin and penicillin) and passaged twice before use in experiments. Cells were cultured as is (control) and in the presence of GE Healthcare TEM Nucleopore and the membrane of this invention for a total of 7 days, continuously monitored and maintained in the exponential growth phase (controlled directly by cell number control). Cell viability in all groups (control, track etching, and the membrane of this invention) was quantitatively inferred using a Nucleocounter 200 (Chemometec), which was a consumable via-1 box for days 1 and 7, as shown in Table 3.

[0041] The results showed no difference in the viability of Jurkat cells cultured in the presence of the membrane and the control, therefore there was no cytotoxicity.

[0042] Other embodiments and uses of the invention will be apparent to those skilled in the art upon consideration of the description and practice of the invention disclosed herein. All references cited herein, including all U.S. and foreign patents and patent applications, are expressly and entirely incorporated herein by reference. The description and examples are intended to be exemplary only, and the true scope and spirit of the invention are defined by the appended claims.

Claims

1. A porous membrane (102) comprising a polymer layer having a thickness of at least 4,000 mm. 2 The porous membrane (102) has a continuous surface area, a thickness of 5 to 25 micrometers, and an opening pattern etched through the thickness of the polymer layer using a hard mask (104), wherein the median aspect ratio of the openings is in the range of 0.5:1 to 20:1, and the porous membrane (102) contains less than or equal to 0.15 μg / cm³ on the surface of the polymer layer or within the polymer. 2 The amount of residual hard mask material, and wherein the opening has a symmetrical shape in the xy direction, wherein the hard mask is made of nonmetallic hydrogenated amorphous inorganic material.

2. The membrane (102) according to claim 1, wherein the surface area of ​​the membrane has an offset ratio of 0.2 or less.

3. The membrane (102) according to claim 1 or 2, wherein the standard deviation of the pore size is less than 0.3 micrometers.

4. The membrane (102) according to claim 1 or 2, wherein the standard deviation of the pore size is in the range of 0.15-0.40 micrometers.

5. The membrane (102) according to claim 1 or 2, wherein the standard deviation of the pore size is in the range of 0.15-0.30 micrometers.

6. The membrane (102) according to claim 1 or 2, wherein the polymer in the polymer layer is selected from polyimide, polyamide, polycarbonate, polyetherimide, polyetherketone, polyurethane, low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon, Teflon (polytetrafluoroethylene), thermoplastic polyurethane (TPU), polyethylene, acrylate polymers or acrylate elastomers.

7. The membrane (102) according to claim 1 or 2, wherein the polymer in the polymer layer is a synthetic polymer.

8. The membrane (102) according to claim 1 or 2, wherein the polymer in the polymer layer is polyimide.

9. The membrane (102) according to claim 1 or 2, wherein the membrane has an undetectable level of metallic contaminants.

10. The membrane (102) according to claim 1 or 2, wherein the pores have an aspect ratio of 0.5:1 to 20:

1.

11. A method for manufacturing the porous membrane (102) according to any one of the preceding claims, comprising: a) A photoresist layer is deposited on the top surface of a substrate (100), the substrate comprising a support layer, a polymer layer, and a hard mask layer, wherein the polymer layer has a thickness of 5 to 25 micrometers, and the surface area of ​​the substrate is at least 4,000 mm². 2 The hard mask layer and the polymer layer do not form a reactive layer at their interface; b) Expose the photoresist to the pattern of light; c) Develop the photoresist layer to provide a first opening pattern in the photoresist layer that exposes a portion of the hard mask layer; d) Etch the exposed portion of the hard mask layer to provide a second opening pattern in the hard mask layer that exposes the portion of the underlying polymer layer; e) Remove the photoresist; f) Etching the polymer layer through the opening in the hard mask layer to provide a third opening pattern in the polymer layer, wherein the median aspect ratio of the third opening pattern is in the range of 0.5:1 to 20:1; g) Remove the hard mask layer; as well as h) Release the polymer layer from the substrate to provide the porous membrane, wherein the pore size of the porous membrane (102) is defined by a pattern of light, and the membrane has a pore size of at least 4,000 mm. 2 The surface area, and the opening has a symmetrical shape in the xy direction.

12. The method of claim 11, wherein the matched coefficients of thermal expansion are within ±15% of each other.

13. The method of claim 11 or 12, wherein the matched coefficients of thermal expansion are within ±10% of each other.

14. The method according to claim 11 or 12, wherein the membrane (102) has a diameter of at least 4,000 mm. 2 Surface area.

15. The method according to claim 11 or 12, wherein the membrane (102) has a thickness of at least 0.1 μm. 2 Surface area.

16. The method according to claim 11 or 12, wherein the polymer in the polymer layer is selected from polyimide, polyamide, polycarbonate, polyetherimide, polyetherketone, polyurethane, synthetic polymer, low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon, Teflon (polytetrafluoroethylene), thermoplastic polyurethane (TPU), polyethylene, acrylate polymers, or acrylate elastomers.

17. The method according to claim 11 or 12, wherein the polymer in the polymer layer is a synthetic polymer.

18. The method according to claim 11 or 12, wherein the polymer in the polymer layer is a polyimide.

19. The method according to claim 11 or 12, wherein the membrane (102) has an undetectable level of metallic contaminants.

20. The method according to claim 11 or 12, wherein the hole has an aspect ratio of 0.5:1 to 20:

1.

21. A porous membrane (102) comprising a porous membrane having a diameter of at least 4,000 mm. 2 A polyimide with a continuous surface area, a thickness of 5 to 25 micrometers, and an opening pattern, wherein the median aspect ratio of the openings is in the range of 0.5:1 to 20:1, and the polyimide lacks a detectable amount of hard mask material or reaction products between the hard mask layer and the polyimide, or the polyimide has a content of less than or equal to 0.15 μg / cm³. 2 The amount of residual hard mask material, and wherein the opening has a symmetrical shape in the xy direction, wherein the hard mask is made of nonmetallic hydrogenated amorphous inorganic material.

22. The membrane (102) according to claim 21, wherein the standard deviation of the pore size is less than 0.3 micrometers.

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