Chip preparation method and chip
By using laser etching and a polydimethylsiloxane soft film layer during chip fabrication, the problem of damage to the substrate surface caused by traditional methods is solved, and the protection of the patterned modification of the substrate layer is achieved.
Patent Information
- Application Number
- CN202511450946.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-11
- Publication Date
- 2026-02-13
AI Technical Summary
In traditional chip fabrication methods, chemical, thermal, and plasma techniques can damage the surface of the chip's substrate layer, disrupting the patterned decoration.
A porous layer is fabricated on a glass slide using laser etching. A soft film layer made of polydimethylsiloxane is used, and the porous layer is bonded to the substrate layer with an adhesive layer to prevent damage to the surface of the substrate layer.
It effectively protects the patterned modification of the substrate layer, avoids damage, and improves the surface integrity of the substrate layer during the chip fabrication process.
Smart Images
Figure CN121513764A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of gene synthesis technology, and in particular to a method for preparing a chip and the chip itself. Background Technology
[0002] Well plate gene synthesis is a high-throughput DNA synthesis technique that utilizes well plates with a predetermined number of wells (e.g., 96-well or 384-well) as miniature reaction vessels to simultaneously and in parallel synthesize a large number of oligonucleotide fragments on a solid-phase support. Automated liquid handling workstations handle sample loading and reactions, significantly improving synthesis efficiency and reducing the cost per fragment. The synthesized short fragments can then be assembled within the well plate or after transfer to ultimately obtain longer target genes or DNA sequences. This method has significantly accelerated research and applications in synthetic biology, genetic engineering, and functional genomics. To this end, related technologies have proposed microarrays for gene synthesis; specifically, these microarrays typically consist of multi-layered structures, including a base layer and a porous layer.
[0003] Since chips are typically used for gene synthesis or as reaction chambers for other biochemical reactions, the surface of the chip's substrate layer usually requires specific patterning modifications. However, traditional chips are usually bonded using chemical, thermal, or plasma methods, all of which damage the surface of the chip's substrate layer, thereby disrupting the patterning modifications. Summary of the Invention
[0004] This application aims to at least solve one of the technical problems existing in the prior art. To this end, this application proposes a chip fabrication method that, during the chip fabrication process, helps to prevent damage to the surface of the substrate layer, thereby helping to prevent the patterning modification of the substrate layer surface from being destroyed.
[0005] This application also proposes a chip manufactured using the above-described chip fabrication method.
[0006] A method for fabricating a chip according to a first aspect embodiment of this application includes: Prepare a base layer with a patterned surface. Prepare a porous layer with multiple through holes, and bond the porous layer to the side of the substrate layer with patterned decoration; Prepare a soft film layer and bond the soft film layer to the side of the porous layer facing away from the substrate layer.
[0007] The chip fabrication method according to the embodiments of this application has at least the following beneficial effects: during the chip fabrication process, bonding the porous layer to the side of the substrate layer with patterned modification helps to prevent damage to the surface of the substrate layer, thereby helping to prevent the patterned modification of the substrate layer surface from being destroyed.
[0008] According to some embodiments of this application, the substrate layer is made of glass, and / or the porous layer is made of glass.
[0009] According to some embodiments of this application, the preparation of a porous layer having multiple through holes includes: Prepare a glass slide and use laser etching to process multiple through holes on the glass slide to form the porous layer.
[0010] According to some embodiments of this application, the soft film layer is made of polydimethylsiloxane.
[0011] According to some embodiments of this application, the preparation of the soft film layer includes: A plurality of protruding metal molds are provided on the prepared surface of the porous layer, wherein the plurality of protrusions of the metal molds correspond one-to-one with the plurality of through holes of the porous layer; Prepare a polydimethylsiloxane solution mixed with a curing agent, and apply the polydimethylsiloxane solution mixed with the curing agent to the surface of the metal mold that has multiple protrusions; Prepare a plastic film, apply external pressure to tightly adhere the plastic film to the surface of the metal mold which has multiple protrusions, and heat and cure it so that the coated polydimethylsiloxane solution mixed with curing agent adheres to the surface of the plastic film and forms a soft film layer with multiple through holes, wherein the multiple through holes of the soft film layer correspond one-to-one with the multiple through holes of the porous layer. The plastic film with the attached soft film layer is separated from the metal mold.
[0012] According to some embodiments of this application, bonding the soft film layer to the side of the porous layer opposite to the substrate layer includes: The side of the plastic film with the soft film layer attached is bonded to the side of the porous layer facing away from the substrate layer, wherein the multiple through holes of the soft film layer are aligned one-to-one with the multiple through holes of the porous layer; Remove the plastic film.
[0013] According to some embodiments of this application, the preparation of the soft film layer includes: Prepare the prefabricated membrane material; Laser cutting technology is used to process multiple through holes on the membrane material that correspond one-to-one with the multiple through holes of the porous layer to form the soft membrane layer.
[0014] According to some embodiments of this application, the step of bonding the porous layer to the patterned side of the substrate layer includes: An adhesive layer is processed on the side of the porous layer facing the substrate layer, wherein the adhesive layer is cured by heat curing or light curing; The porous layer is bonded to the patterned side of the base layer using the adhesive layer.
[0015] According to some embodiments of this application, the adhesive layer is processed by micro-droplet spraying, spray coating, screen printing, or high-precision dispensing.
[0016] According to some embodiments of this application, the adhesive layer is processed using a colloid filled with solid particles.
[0017] The chip according to the second aspect of this application is manufactured using the chip manufacturing method according to the first aspect of this application described above.
[0018] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description
[0019] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 This is a schematic flowchart of a chip fabrication method according to an embodiment of this application; Figure 2 This is a schematic diagram of the structure of a chip according to an embodiment of this application.
[0020] Figure label: The substrate layer is 100, the porous layer is 200, the soft film layer is 300, and the adhesive layer is 400. Detailed Implementation
[0021] The embodiments of this application are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this application, and should not be construed as limiting this application.
[0022] In the description of this application, it should be understood that if directional descriptions are involved, such as up, down, front, back, left, right, etc., indicating the directional or positional relationship based on the directional or positional relationship shown in the accompanying drawings, it is only for the convenience of describing this application and simplifying the description, and does not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.
[0023] In the description of this application, if words such as several, greater than, less than, exceeding, above, below, or within appear, "several" means one or more, "more than" means two or more, "greater than," "less than," "exceeding," etc. are understood to exclude the number itself, and "above," "below," "within," etc. are understood to include the number itself.
[0024] In the description of this application, the use of terms such as "first" and "second" is for the purpose of distinguishing technical features only, and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated or the order of the technical features indicated.
[0025] In the description of this application, unless otherwise expressly defined, terms such as "setup," "installation," and "connection" should be interpreted broadly, and those skilled in the art can reasonably determine the specific meaning of the above terms in this application in conjunction with the specific content of the technical solution.
[0026] Well plate gene synthesis is a high-throughput DNA synthesis technique that utilizes well plates with a predetermined number of wells (e.g., 96-well or 384-well) as miniature reaction vessels to simultaneously and in parallel synthesize a large number of oligonucleotide fragments on a solid-phase support. Automated liquid handling workstations handle sample loading and reactions, significantly improving synthesis efficiency and reducing the cost per fragment. The synthesized short fragments can then be assembled within the well plate or after transfer to ultimately obtain longer target genes or DNA sequences. This method has significantly accelerated research and applications in synthetic biology, genetic engineering, and functional genomics. To this end, related technologies have proposed microarrays for gene synthesis; specifically, these microarrays typically consist of multi-layered structures, including a base layer and a porous layer.
[0027] Since chips are typically used for gene synthesis or as reaction chambers for other biochemical reactions, the surface of the chip's substrate layer usually requires specific patterning modifications. However, traditional chips are usually bonded using chemical, thermal, or plasma methods, all of which damage the surface of the chip's substrate layer, thereby disrupting the patterning modifications.
[0028] Therefore, it is urgent to optimize the traditional chip fabrication method to solve the above-mentioned technical problems. The optimized chip fabrication method of this application will be described in detail below with reference to the accompanying drawings.
[0029] Reference Figure 1 and Figure 2 The chip fabrication method according to an embodiment of this application includes: S100: Prepare a base layer 100 with a patterned surface. S200: Prepare a porous layer 200 with multiple through holes, and bond the porous layer 200 to the side of the base layer 100 with patterned decoration. S300: Prepare the soft film layer 300 and bond the soft film layer 300 to the side of the porous layer 200 facing away from the substrate layer 100.
[0030] During chip fabrication, bonding the porous layer 200 to the patterned side of the substrate layer 100 helps prevent damage to the surface of the substrate layer 100, thus preventing the patterned decoration on the surface of the substrate layer 100 from being destroyed.
[0031] In some embodiments, the thickness of the soft film layer 300 is 20 μm to 100 μm. Specifically, the thickness of the soft film layer 300 can be 20 μm, 100 μm, 60 μm, or other values within the above range.
[0032] In some embodiments, the substrate 100 is made of glass. Specifically, the substrate 100 is made of a smooth glass sheet.
[0033] In some embodiments, the porous layer 200 is made of glass. The thickness of the porous layer 200 is 100 μm to 1000 μm. Specifically, the thickness of the porous layer 200 can be 100 μm, 1000 μm, 550 μm, or other values within the aforementioned range.
[0034] In some embodiments, a porous layer 200 having multiple through holes is prepared, including: S210: Prepare a glass sheet and use laser etching to process multiple through holes on the glass sheet to form a porous layer 200.
[0035] Specifically, the porous layer 200 is processed using laser etching technology, and its processing precision can reach the nanometer level.
[0036] The through holes processed on the glass plate can be circular, rectangular, or other shapes.
[0037] In some embodiments, the soft film layer 300 is made of polydimethylsiloxane. Polydimethylsiloxane has properties such as high transparency, biocompatibility, and ease of processing.
[0038] In some embodiments, preparing the soft film layer 300 includes: S310: A metal mold with multiple protrusions is provided on the prepared surface of the porous layer 200, wherein the multiple protrusions of the metal mold correspond one-to-one with the multiple through holes of the porous layer 200. S320: Prepare a polydimethylsiloxane solution mixed with a curing agent, and apply the polydimethylsiloxane solution mixed with a curing agent to the surface of a metal mold with multiple protrusions. S330: Prepare a plastic film, apply external pressure to tightly adhere the plastic film to the surface of a metal mold with multiple protrusions, and heat to cure it so that the coated polydimethylsiloxane solution mixed with curing agent adheres to the surface of the plastic film and forms a soft film layer 300 with multiple through holes, wherein the multiple through holes of the soft film layer 300 correspond one-to-one with the multiple through holes of the porous layer 200. S340: Separate the plastic film with the soft film layer 300 attached from the metal mold.
[0039] Specifically, the shape, size, and distribution of the protrusions in the metal mold correspond to the shape, size, and distribution of the through holes in the porous layer 200. The multiple protrusions in the metal mold are used to form multiple through holes in the soft film layer 300.
[0040] It should be noted that polydimethylsiloxane needs to be mixed with a curing agent during use. However, the curable ratio of the prepared polydimethylsiloxane solution mixed with the curing agent is not limited in this application, that is, the mixing ratio of polydimethylsiloxane and curing agent is not limited. In other words, the mixing ratio of polydimethylsiloxane and curing agent can be adjusted according to the actual situation.
[0041] Specifically, the aforementioned plastic film can be made of PC (polycarbonate), PMMA (polymethyl methacrylate), PET (polyethylene terephthalate) or other materials.
[0042] Specifically, pressure can be applied by clamping the plastic film and the metal mold with pliers to make the plastic film adhere tightly to the metal mold. Alternatively, pressure can be applied using a linear drive structure with a pressure plate, such as a cylinder, hydraulic cylinder, or electric push rod.
[0043] In some embodiments, the soft film layer 300 is bonded to the side of the porous layer 200 facing away from the substrate layer 100, including: S350: The side of the plastic film with the soft film layer 300 attached is bonded to the side of the porous layer 200 facing away from the substrate layer 100, wherein the multiple through holes of the soft film layer 300 are aligned one-to-one with the multiple through holes of the porous layer 200. S360: Remove the plastic film.
[0044] It should be noted that, based on the inherent characteristics of plastic film, there is no inseparable bond between the plastic film and the soft film layer 300 attached to the plastic film. Therefore, after the soft film layer 300 is bonded to the side of the porous layer 200 facing away from the substrate layer 100, the plastic film can be peeled off without damaging the soft film layer 300.
[0045] In some other embodiments, preparing the soft film layer 300 includes: S310: Prepare prefabricated membrane material; S320: Multiple through holes corresponding one-to-one with the multiple through holes of the porous layer 200 are processed on the membrane material using laser cutting technology to form the soft membrane layer 300.
[0046] In some embodiments, the porous layer 200 is bonded to the patterned side of the substrate layer 100, including: S220: An adhesive layer 400 is processed on the side of the porous layer 200 facing the substrate layer 100, wherein the adhesive layer 400 is cured by heat curing or light curing. S230: The porous layer 200 is bonded to the patterned side of the base layer 100 by the adhesive layer 400.
[0047] In some embodiments, the thickness of the adhesive layer 400 is 1 μm to 100 μm. Specifically, the thickness of the adhesive layer 400 can be 1 μm, 100 μm, 50 μm, or other values within the above range.
[0048] In some embodiments, a biocompatible adhesive is used to process the adhesive layer 400. This ensures that the adhesive layer 400 does not trigger an immune response or degrade the target sample when it comes into contact with biomolecules (such as DNA and proteins), while also enabling the adhesive layer 400 to withstand the biological reagents used in the experiment.
[0049] In some embodiments, the adhesive layer 400 is processed using methods such as micro-droplet spraying, spraying, screen printing, or high-precision dispensing. These methods enable precise adhesive application, allowing for accurate control of the amount of adhesive applied and thus reducing adhesive overflow.
[0050] In some embodiments, the adhesive layer 400 is processed using a colloid filled with solid particles. The filled solid particles help to suppress the flowability of the colloid, making the adhesive layer 400 less likely to spread to the edges due to gravity or pressure, thereby helping to reduce adhesive overflow.
[0051] In some embodiments, the particle size of the solid particles is 10 μm to 100 μm. Specifically, the particle size of the solid particles can be 10 μm, 100 μm, 55 μm, or other values within the above range.
[0052] Specifically, the filling solid particles can be solid glass microspheres, silica particles, calcium carbonate particles, PMMA microspheres, or other solid particles.
[0053] Reference Figure 2 The chip according to the embodiments of this application is manufactured using the chip fabrication method described above.
[0054] In the description of this specification, the use of terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," and "some examples" indicates that the specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.
[0055] Although embodiments of this application have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the claims and their equivalents.
Claims
1. A method of producing a chip, characterized by, include: Prepare a base layer with a patterned surface. Prepare a porous layer with multiple through holes, and bond the porous layer to the side of the substrate layer with patterned decoration; Prepare a soft film layer and bond the soft film layer to the side of the porous layer facing away from the substrate layer.
2. The method of claim 1, wherein the chip is prepared by a method comprising: The base layer is made of glass, and / or the porous layer is made of glass.
3. The method for producing a chip according to claim 1 or 2, wherein The preparation of the porous layer having multiple through holes includes: Prepare a glass slide and use laser etching to process multiple through holes on the glass slide to form the porous layer.
4. The method of claim 1, wherein the chip is prepared by a method comprising: The soft film layer is made of polydimethylsiloxane.
5. The method of claim 4, wherein the chip is prepared by a method comprising: The preparation of the soft film layer includes: A plurality of protruding metal molds are provided on the prepared surface of the porous layer, wherein the plurality of protrusions of the metal molds correspond one-to-one with the plurality of through holes of the porous layer; Prepare a polydimethylsiloxane solution mixed with a curing agent, and apply the polydimethylsiloxane solution mixed with the curing agent to the surface of the metal mold that has multiple protrusions; Prepare a plastic film, apply external pressure to tightly adhere the plastic film to the surface of the metal mold which has multiple protrusions, and heat and cure it so that the coated polydimethylsiloxane solution mixed with curing agent adheres to the surface of the plastic film and forms a soft film layer with multiple through holes, wherein the multiple through holes of the soft film layer correspond one-to-one with the multiple through holes of the porous layer. The plastic film with the attached soft film layer is separated from the metal mold.
6. The method of claim 5, wherein the chip is prepared by a method comprising: The step of bonding the soft film layer to the side of the porous layer opposite to the substrate layer includes: The side of the plastic film with the soft film layer attached is bonded to the side of the porous layer facing away from the substrate layer, wherein the multiple through holes of the soft film layer are aligned one-to-one with the multiple through holes of the porous layer; Remove the plastic film.
7. The method of claim 4, wherein the chip is prepared by a method comprising: The preparation of the soft film layer includes: Prepare the prefabricated membrane material; Laser cutting technology is used to process multiple through holes on the membrane material that correspond one-to-one with the multiple through holes of the porous layer to form the soft membrane layer.
8. The method for fabricating a chip as described in claim 1, characterized in that, The step of bonding the porous layer to the patterned side of the substrate layer includes: An adhesive layer is processed on the side of the porous layer facing the substrate layer, wherein the adhesive layer is cured by heat curing or light curing. The porous layer is bonded to the patterned side of the base layer using the adhesive layer.
9. The method for fabricating a chip as described in claim 8, characterized in that, The adhesive layer is processed using methods such as micro-droplet spraying, spray coating, screen printing, or high-precision dispensing.
10. The method for fabricating a chip as described in claim 8, characterized in that, The adhesive layer is processed using a colloid filled with solid particles.
11. A chip, characterized in that, It is manufactured using the chip fabrication method as described in any one of claims 1 to 10.