CN110928146A - Arc-section blood vessel network microchannel template based on back-surface divergent lithography technology and manufacturing method - Google Patents
Arc-section blood vessel network microchannel template based on back-surface divergent lithography technology and manufacturing method Download PDFInfo
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- CN110928146A CN110928146A CN201911268757.8A CN201911268757A CN110928146A CN 110928146 A CN110928146 A CN 110928146A CN 201911268757 A CN201911268757 A CN 201911268757A CN 110928146 A CN110928146 A CN 110928146A
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/20—Exposure; Apparatus therefor
- G03F7/2002—Exposure; Apparatus therefor with visible light or UV light, through an original having an opaque pattern on a transparent support, e.g. film printing, projection printing; by reflection of visible or UV light from an original such as a printed image
- G03F7/2004—Exposure; Apparatus therefor with visible light or UV light, through an original having an opaque pattern on a transparent support, e.g. film printing, projection printing; by reflection of visible or UV light from an original such as a printed image characterised by the use of a particular light source, e.g. fluorescent lamps or deep UV light
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/0035—Multiple processes, e.g. applying a further resist layer on an already in a previously step, processed pattern or textured surface
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Abstract
The invention discloses a method for manufacturing an arc-shaped section blood vessel network micro-channel template based on a back-surface divergent lithography technology, which is based on the lithography technology and consists of SU-8 photoresist, a blood vessel network graph, a lithography mask, a diffuse scattering ultraviolet light source and a light-transmitting glass substrate, and can realize the template manufacturing of the arc-shaped micro-channel with the diameter within 5 mu m-4mm, thereby constructing a micro-channel model similar to a human blood vessel network. The method breaks through the limitation that the common photoetching technology can only manufacture the microchannels with consistent height, provides a new way for manufacturing the models with the circular cross sections of real blood vessels and the like, has simple principle and easy manufacture, and has important significance for researching the human hemodynamics characteristics, applying clinical medical experiments and the like.
Description
Technical Field
The method is a novel back-surface divergent photoetching technical method and a novel back-surface divergent photoetching technical template which can be used for manufacturing a blood vessel network microchannel template with an arc-shaped section, and belongs to the technical field of microfluidics.
Background
With the advent of the precise medical age, research and prevention of diseases of human blood and blood vessels become important contents of current medical treatment, wherein the exploration of the hemodynamic characteristics of the human body is an important means for understanding blood vessel diseases, so that the establishment of a model as similar as possible to a real human blood vessel network becomes the key to the experimental research on whether the experimental research has medical reference value.
Many techniques are currently available to reconstruct the human blood network. As in the conventional photolithography, a microchannel template is manufactured by placing SU-8 photoresist under a photolithography mask and projecting ultraviolet rays from the front of the mask to cure the SU-8 photoresist in a specific shape, but it can only manufacture a channel structure with a uniform height at each location, and a natural blood vessel of a human body consists of circular portions of different diameters, so that the conventional photolithography cannot sufficiently reproduce the geometric shape of a blood vessel network; in addition, although the 3D printing technology which has been developed very rapidly can reproduce the actual three-dimensional geometry of the vascular network, due to the limitation of materials and printing technology, the printing mold does not have enough spatial resolution and low surface roughness, and the error is large for the micrometer-scale experimental condition.
The photoetching technology is a chip processing and manufacturing technology widely applied at present, and the effect of manufacturing a micro-channel model which is close to the geometric shape of a real human vascular network can be achieved by slightly improving the traditional front photoetching technology.
Disclosure of Invention
The method aims to manufacture the template with the blood vessel network microchannel with the arc-shaped section, and the microchannel chip for the hemodynamics experiment can be further manufactured by using the template. A method for preparing the microchannel template of blood vessel network based on back-surface divergent photoetching technique features that the template prepared by said method can fully reproduce the geometric shape of blood vessel network, i.e. it has arc cross-section instead of rectangular cross-section. And the blood vessel network micro-channel chip manufactured by the template has lower surface roughness and higher scientific research and clinical application values.
The technical scheme adopted by the invention is an arc-shaped cross section blood vessel network micro-channel template based on a back-surface divergent lithography technology, and the template comprises SU-8 photoresist 1, a solidified blood vessel network micro-channel 2, a blood vessel network pattern 3, a lithography mask 4, a diffuse scattering ultraviolet light source 5 and a light-transmitting glass substrate 6.
Specifically, SU-8 photoresist 1, a photoetching mask 4 and a transparent glass substrate 6 are closely contacted and placed to form a main structure of the template; the blood vessel network pattern 3 is a hollow structure on the photoetching mask 4, and the graphic shape of the blood vessel network pattern 3 is a two-dimensional shape of a target real blood vessel; the diffuse scattering ultraviolet light source 5 emits ultraviolet rays with specific wavelength, the ultraviolet rays penetrate through the glass substrate 6, most of the ultraviolet rays are absorbed by the photoetching mask 4, part of the diffuse scattering ultraviolet rays pass through the vascular network pattern 3 to cure the SU-8 photoresist in the shape within the depth range, the curing depth is related to the light transmission width, the principle is shown in figure 2, if the width of the vascular pattern 3 is smaller, as shown in a left channel of figure 2, the ultraviolet rays emitted by the diffuse scattering ultraviolet light source 5 can only pass through a small amount, and cure a small amount of the SU-8 photoresist, on the contrary, if the width of the vascular pattern 3 is larger, as shown in a right channel of figure 2, more ultraviolet rays can pass through, so that more and thicker SU-8 photoresist is cured, in addition, because the ultraviolet light source is in a diffuse scattering mode, different from a general direct-irradiation mode (figure 3), which can only cure SU-8 photoresist with the same height, the intensity of the diffuse scattering ultraviolet light passing through, therefore, SU-8 glue with an arc-shaped section can be cured, namely SU-8 glue with different arc-shaped sectional areas can be cured according to the size requirement of the blood vessel model, so that templates with different sizes from common blood vessels to capillary networks and the like can be manufactured, the shape limitation of the current blood vessel experiment is broken through, the research range of the future blood vessel experiment is expanded, and the accuracy of the experiment is improved. And then washing away the uncured SU-8 photoresist by using a developing solution, and leaving the cured blood vessel network microchannel 2.
The SU-8 photoresist 1, the photoetching mask 4 and the light-transmitting glass substrate 6 are tightly connected, and the diffuse scattering ultraviolet light source 5 is arranged at the lower part of the main body structure 1 to cure the SU-8 photoresist on the upper part of the photoetching mask;
the overall implementation process of the method is as follows:
first, a template substrate is fabricated. Selecting a glass substrate 5 with a proper size, cleaning the glass substrate by using a piranha solution in advance, depositing a chromium layer with the thickness of about 100nm on the surface of the glass substrate by using electron beam physical vapor deposition, coating the chromium layer with a layer of AZ1518 photoresist in a spinning mode, and prebaking the coating for about 1 minute at 110 ℃. The vascular microchannel pattern 3 was transferred by contact photolithography and the photoresist was developed in an alkaline solution, then the mask was defined by a wet etch process (chrome etch solution) that produced a transparent network pattern. Finally, the remaining photoresist was ashed off with acetone and oxygen plasma. To this end, a template substrate consisting of a photolithographic mask 4 with a network pattern 3 of blood vessel microchannels and a glass substrate 5 has been fabricated.
Then, a blood vessel micro-channel template is manufactured. SU-82010 photoresist 1 was poured on the template substrate surface without spin coating. Since the exposure is done through the backside, a regular and completely flat photoresist layer is not required. This process only requires that the thickness of SU-8 be greater than the thicker channel 2 to be made. After 30 minutes of standing, the thick SU-8 layer is heated (3 to 4 ℃ C. min)-1) To 95 ℃ and pre-baked for 30 minutes, then slowly lowered to room temperature. The time to fall to room temperature exceeds one hour due to the thermal inertia of the heating plate.
The exposure is then carried out by diffuse scattering uv 5 in direct contact with the back of the glass. The samples were inverted on dark plastic plates to avoid optical reflections. The exposure time, the ultraviolet dose and the like are related to the setting of the ultraviolet device, and the like need to be tested, optimized and the like according to data provided by different manufacturers, for the mask plate, the proper exposure time is about 16s, and the irradiance of the mask plate is 10mW cm-2Therefore, an equivalent dose of 160 mJ. cm was used-2This dose is generally suitable for conventional front exposure of a 50 μm thick SU-8 layer.
The samples were then slowly baked (3 to 4 ℃ C. min)-1) Baking at 95 deg.C for 30 min, and slowly cooling to room temperature. Development was carried out with Propylene Glycol Methyl Ether Acetate (PGMEA) until completion. Since the initial thickness of the resin is about several hundred microns, it usually takes more than 30 minutes. Finally, a hard bake step was performed to soften the surface (ramping up to 160 ℃ for 30 minutes, then slowly cooling to room temperature). Thus, the blood vessel micro-channel template 2 is manufactured.
Drawings
FIG. 1 is a three-dimensional schematic view of an apparatus used in the present process.
FIG. 2 is a schematic diagram of a backside lithography technique.
FIG. 3 is a schematic diagram of front-side direct lithography
In the figure:
1, SU-8 photoresist, 2, cured blood vessel network SU-8 photoresist, 3, blood vessel network pattern, 4, photoetching mask, 5, diffuse scattering ultraviolet light source, and 6, light-transmitting glass substrate.
Detailed Description
The working process and effect of the invention will be further explained with reference to the structure drawings.
Fig. 1 is a schematic diagram of an arc-section blood vessel network microchannel template based on a back-surface divergent lithography technology and a manufacturing method thereof.
A method for manufacturing an arc-section blood vessel network micro-channel template based on a back-surface divergent lithography technology. The template comprises SU-8 photoresist 1, a solidified blood vessel network micro-channel 2, a blood vessel network pattern 3, a photoetching mask 4, a diffuse scattering ultraviolet light source 5 and a light-transmitting glass substrate 6. The SU-8 photoresist 1, the photoetching mask 4 and the transparent glass substrate 6 are closely contacted with each other to form a main structure of the template; the blood vessel network pattern 3 is a hollow structure on the photoetching mask 4, and the graphic shape of the blood vessel network pattern 3 is a two-dimensional shape of a target real blood vessel; the diffuse scattering ultraviolet light source 5 emits ultraviolet rays with specific wavelength, the ultraviolet rays penetrate through the glass substrate 6, most of the ultraviolet rays are absorbed by the photoetching mask 4, part of the diffuse scattering ultraviolet rays pass through the vascular network pattern 3 to cure the SU-8 photoresist in the shape within the depth range, the curing depth is related to the light transmission width, the principle is shown in figure 2, if the width of the vascular pattern 3 is smaller, as shown in a left channel of figure 2, the ultraviolet rays emitted by the diffuse scattering ultraviolet light source 5 can only pass through a small amount, and cure a small amount of the SU-8 photoresist, on the contrary, if the width of the vascular pattern 3 is larger, as shown in a right channel of figure 2, more ultraviolet rays can pass through, so that more and thicker SU-8 photoresist is cured, in addition, because the ultraviolet light source is in a diffuse scattering mode, different from a general direct-irradiation mode (figure 3), which can only cure SU-8 photoresist with the same height, the intensity of the diffuse scattering ultraviolet light passing through, therefore, SU-8 glue with an arc-shaped section can be cured, namely SU-8 glue with different arc-shaped sectional areas can be cured according to the size requirement of the blood vessel model, so that templates with different sizes from common blood vessels to capillary networks and the like can be manufactured, the shape limitation of the current blood vessel experiment is broken through, the research range of the future blood vessel experiment is expanded, and the accuracy of the experiment is improved. And then washing away the uncured SU-8 photoresist by using a developing solution, and leaving the cured blood vessel network microchannel 2.
The SU-8 photoresist 1, the photoetching mask 4 and the light-transmitting glass substrate 6 are tightly connected, and the diffuse scattering ultraviolet light source 5 is arranged at the lower part of the main body structure 1 to cure the SU-8 photoresist at the upper part of the photoetching mask.
The working process of the device is as follows: first, a template substrate is fabricated. Selecting a glass substrate 5 with a proper size, cleaning the glass substrate by using a piranha solution in advance, depositing a chromium layer with the thickness of about 100nm on the surface of the glass substrate by using electron beam physical vapor deposition, coating the chromium layer with a layer of AZ1518 photoresist in a spinning mode, and prebaking the coating for about 1 minute at 110 ℃. The vascular microchannel pattern 3 was transferred by contact photolithography and the photoresist was developed in an alkaline solution, then the mask was defined by a wet etch process (chrome etch solution) that produced a transparent network pattern. Finally, the remaining photoresist was ashed off with acetone and oxygen plasma. To this end, a template substrate consisting of a photolithographic mask 4 with a network pattern 3 of blood vessel microchannels and a glass substrate 5 has been fabricated.
Then, a blood vessel micro-channel template is manufactured. SU-82010 photoresist 1 was poured on the template substrate surface without spin coating. Since the exposure is done through the backside, a regular and completely flat photoresist layer is not required. This process only requires that the thickness of SU-8 be greater than the thicker channel 2 to be made. After 30 minutes of standing, the thick SU-8 layer is heated (3 to 4 ℃ C. min)-1) To 95 ℃ and pre-baked for 30 minutes, then slowly lowered to room temperature. The time to fall to room temperature exceeds one hour due to the thermal inertia of the heating plate.
The exposure is then carried out by diffuse scattering uv 5 in direct contact with the back of the glass. The samples were inverted on dark plastic plates to avoid optical reflections. Exposure time andthe ultraviolet dose and the like are related to the setting of the ultraviolet device, and the ultraviolet dose and the like need to be tested, optimized and the like according to data provided by different manufacturers, and for a mask plate, the proper exposure time is about 16s, and the irradiance of the mask plate is 10mW cm-2Therefore, an equivalent dose of 160 mJ. cm was used-2This dose is generally suitable for conventional front exposure of a 50 μm thick SU-8 layer.
The samples were then slowly baked (3 to 4 ℃ C. min)-1) Baking at 95 deg.C for 30 min, and slowly cooling to room temperature. Development was carried out with Propylene Glycol Methyl Ether Acetate (PGMEA) until completion. Since the initial thickness of the resin is about several hundred microns, it usually takes more than 30 minutes. Finally, a hard bake step was performed to soften the surface (ramping up to 160 ℃ for 30 minutes, then slowly cooling to room temperature). Thus, the blood vessel micro-channel template 2 is manufactured.
Claims (6)
1. A back-divergent lithography-based arc-section blood vessel network microchannel template is characterized in that: the template comprises SU-8 photoresist (1), cured blood vessel network SU-8 photoresist (2), a blood vessel network graph (3), a photoetching mask (4), a diffuse scattering ultraviolet light source (5) and a light-transmitting glass substrate (6);
the SU-8 photoresist (1), the photoetching mask (4) and the light-transmitting glass substrate (6) are placed in close contact, and are of a template main body structure;
the blood vessel network graph (3) is a hollow structure on the photoetching mask (4), and the shape of the graph is a two-dimensional shape of a target real blood vessel;
the diffuse scattering ultraviolet light source (5) emits ultraviolet rays with specific wavelength, the ultraviolet rays penetrate through the glass substrate (6), most of the ultraviolet rays are absorbed by the photoetching mask (4), partial diffuse scattering ultraviolet rays enable the SU-8 photoresist in the shape to be solidified in a depth range through the blood vessel network graph (3), the solidified depth is related to the light transmission width, the solidified SU-8 photoresist (2) of the blood vessel network is formed, and then the uncured SU-8 photoresist is cleaned through developing solution;
the SU-8 photoresist (1), the photoetching mask (4) and the light-transmitting glass substrate (6) are tightly connected, and the diffuse scattering ultraviolet light source (5) is arranged at the lower part of the main body structure to cure the SU-8 photoresist at the upper part of the photoetching mask.
2. The arc-shaped cross-section blood vessel network micro-channel template based on back-surface divergent lithography, as claimed in claim 1, wherein: the diffuse scattering ultraviolet light source (5) is positioned at the lower part of the photoetching mask (4), and the depth and the thickness of the cured SU-8 photoresist are determined by the opening width of the vascular network, so that the diameter of the cured vascular network model is determined.
3. The arc-shaped cross-section blood vessel network micro-channel template based on back-surface divergent lithography, as claimed in claim 1, wherein: the SU-8 photoresist (1), the photoetching mask (4) and the light-transmitting glass substrate (6) are sequentially and closely contacted from top to bottom.
4. The microstructure groove-based circulating tumor cell sorting chip device of claim 1, wherein: the device comprises the following working process that a photoetching mask (4) containing a target blood vessel network shape (3) is manufactured and is tightly connected with a light-transmitting glass substrate (5), SU-8 photoresist with a certain thickness is coated on the upper part of the photoetching mask (4) to form a main body structure, the whole body is arranged on the upper part of a diffuse scattering ultraviolet light source (5), the ultraviolet light source is started to cure the SU-8 photoresist with a specific shape to form cured blood vessel network SU-8 photoresist (2), then developer is used to wash out the uncured SU-8 photoresist, and the photoetching mask (4) is removed, namely the preparation of the micro-channel template of the near blood vessel network is completed.
5. A manufacturing method of a circulating tumor cell sorting chip device based on a microstructure groove is characterized in that:
firstly, manufacturing a template substrate; selecting a glass substrate with a proper size, cleaning the glass substrate by using a piranha solution in advance, depositing a 100 nm-thick chromium layer on the surface by using electron beam physical vapor deposition, then coating the chromium layer with a layer of AZ1518 photoresist in a spinning mode, and prebaking the photoresist for 1 minute at 110 ℃; transferring the blood vessel microchannel pattern by contact photolithography, developing the photoresist in an alkaline solution, and then defining a mask by a wet etching process that generates a transparent network pattern; finally, ashing and stripping the residual photoresist by using acetone and oxygen plasma; thus, the template substrate consisting of the photoetching mask with the blood vessel micro-channel network pattern and the glass substrate is manufactured;
then, manufacturing a blood vessel micro-channel template; pouring SU-82010 photoresist on the surface of the template substrate without spin coating; since the exposure is done through the backside, a regular and completely flat photoresist layer is not required; the thickness of SU-82010 photoresist is required to be larger than the channel to be made; standing for 30 minutes, heating the SU-82010 photoresist layer to 95 ℃, pre-baking for 30 minutes, and then reducing the temperature to room temperature; the time for dropping to the room temperature exceeds one hour due to the thermal inertia of the heating plate;
exposing by diffuse scattering ultraviolet rays in direct contact with the back surface of the glass; inverting the sample on a dark plastic plate;
slowly baking the sample to 95 ℃, baking for 30 minutes, and then slowly cooling to room temperature; developing with propylene glycol methyl ether acetate until the completion; finally, hard baking is carried out to soften the surface; and finishing the manufacturing of the blood vessel micro-channel template.
6. The method for manufacturing a chip device for sorting circulating tumor cells based on the microstructure grooves according to claim 4, wherein the chip device comprises: since the initial thickness of the resin is several hundred micrometers, it takes 30 minutes or more.
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Citations (4)
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| CN101281365A (en) * | 2007-04-04 | 2008-10-08 | 韩国科学技术院 | Material pattern, and mold, metal thin-film pattern, metal pattern using thereof, and methods of forming the same |
| US20090092934A1 (en) * | 2007-10-09 | 2009-04-09 | The Govt. Of The United States Of America, As Represented By The Secretary Of The Navy | Gray-tone lithography using optical diffusers |
| CN101636671A (en) * | 2007-03-26 | 2010-01-27 | 木本股份有限公司 | Method for manufacturing surface unevenness |
| CN102520591A (en) * | 2011-12-15 | 2012-06-27 | 东南大学 | Negative photoresist-based diffuser photo-etching process |
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- 2019-12-11 CN CN201911268757.8A patent/CN110928146A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101636671A (en) * | 2007-03-26 | 2010-01-27 | 木本股份有限公司 | Method for manufacturing surface unevenness |
| CN101281365A (en) * | 2007-04-04 | 2008-10-08 | 韩国科学技术院 | Material pattern, and mold, metal thin-film pattern, metal pattern using thereof, and methods of forming the same |
| US20090092934A1 (en) * | 2007-10-09 | 2009-04-09 | The Govt. Of The United States Of America, As Represented By The Secretary Of The Navy | Gray-tone lithography using optical diffusers |
| CN102520591A (en) * | 2011-12-15 | 2012-06-27 | 东南大学 | Negative photoresist-based diffuser photo-etching process |
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Application publication date: 20200327 |