Method for preparing microfluidic chip using focused laser etching method, microfluidic chip and application thereof

Abstract

The present invention belongs to the technical field of microfluidic chip manufacturing, and discloses a method for preparing a microfluidic chip by using a focused laser etching method, a microfluidic chip and an application thereof. The method comprises the following steps: coating a photoresist on a substrate surface, forming a photoresist substrate by exposure polymerization, designing a scanning track of a focused infrared laser according to a microchannel pattern, performing microchannel laser processing on the photoresist substrate to obtain a sample, treating the sample surface by plasma, and bonding the photoresist with polydimethylsiloxane by a coupling agent to obtain a microfluidic chip. The method of the present invention simplifies the process flow, reduces the manufacturing cost, and maintains high precision at the same time.

Description

Technical Field

[0001] The invention belongs to the technical field of microfluidic chip manufacturing, and particularly relates to a method for manufacturing a microfluidic chip by using a focused laser etching method, a microfluidic chip and an application thereof. Background Art

[0002] Microfluidic technology is widely used in biomedicine, chemical analysis, materials science and other fields. The key link in its manufacturing process is the production of microfluidics. Traditional methods for producing microfluidics include chemical etching, soft lithography, ultraviolet lithography, electron beam direct writing, inkjet printing, etc.

[0003] The above methods have their own limitations in application. For example, soft lithography uses elastic molds to replicate microstructures. Although it is low-cost and easy to operate, its accuracy is limited by the accuracy of the mold. Ultraviolet lithography uses ultraviolet light to transfer patterns to photoresist through a mask. Although it has high resolution, the equipment is expensive and the process is complicated. Electron beam direct writing technology uses electron beams to directly etch patterns on photoresist. It has extremely high resolution and can be used to make nanoscale microstructures, but this method is slow and costly and is not suitable for mass production. Inkjet printing sprays liquid materials through a nozzle onto a substrate to form patterned microchannels. It is easy to operate and low-cost, but the resolution is low and high-precision microchannels cannot be made. Other methods, including femtosecond laser two-photon direct writing and screen printing, are difficult to meet the requirements of high precision, high speed and low cost at the same time.

[0004] Therefore, a microfluidic chip manufacturing method that is efficient, low-cost and high-precision is urgently needed to promote the application of microfluidic technology. Summary of the invention

[0005] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention proposes a method for preparing a microfluidic chip using a focused laser etching method, a microfluidic chip and an application thereof. The method of the present invention has the advantages of high efficiency, low cost and high precision.

[0006] The present invention proposes a method for preparing a microfluidic chip by a focused laser etching method. Traditional microfluidic technology has many limitations in terms of accuracy, cost, speed and complexity, which seriously affect its wide promotion and use in practical applications. In order to overcome these challenges, the present invention aims to develop an efficient and low-cost method for rapid prototyping and subtractive production of microfluidic chips. Pentaerythritol triacrylate, as a photoresist material with excellent performance, plays a key role in this process. Pentaerythritol triacrylate is not only inexpensive, which makes it have significant economic advantages in large-scale production, but also its excellent performance makes it an ideal choice. More importantly, pentaerythritol triacrylate has good biocompatibility, which makes it widely used in biomedical engineering and related fields. By using pentaerythritol triacrylate to subtract materials to produce microfluidic chips, the present invention can not only significantly reduce production costs, but also improve the production efficiency of microfluidic chips, thereby promoting the application and development of microfluidic technology in a wider range of fields.

[0007] The method for preparing a microfluidic chip by using focused laser etching of the present invention comprises the following steps:

[0008] The photoresist is coated on the surface of the substrate, and is polymerized through exposure to form a photoresist substrate;

[0009] Designing a scanning track of a focused infrared laser according to a microchannel pattern, and performing microchannel laser processing on the photoresist substrate to obtain a sample;

[0010] The sample surface is treated by plasma, and the photoresist and polydimethylsiloxane are bonded by a coupling agent to obtain a microfluidic chip.

[0011] Preferably, the photoresist comprises pentaerythritol triacrylate and a photoinitiator.

[0012] Preferably, in the photoresist, the mass volume ratio of the photoinitiator to pentaerythritol triacrylate is 1:(50-100).

[0013] Preferably, the photoinitiator includes photoinitiator 369. The photoinitiator has strong absorption of ultraviolet light.

[0014] Preferably, the substrate comprises indium tin oxide glass.

[0015] Preferably, the indium tin oxide glass is treated with a low-pressure air plasma cleaner (VP-R series, Guangzhou Shanzhun Technology Co., Ltd.) for 5-10 minutes, and then the indium tin oxide glass is immersed in a silane coupling agent KH570 for 20-30 minutes, and then taken out and cleaned with isopropyl alcohol.

[0016] Preferably, after the surface of the indium tin oxide glass is treated, a photoresist is spin-coated at a speed of 1500-4000 rpm for 20-30 seconds to obtain a photoresist with a thickness of several microns to tens of microns, and then irradiated with an ultraviolet lamp for 3-5 seconds to cause the photoresist to polymerize. After the polymerization is completed, the residues after polymerization on the surface of the photoresist are cleaned with a developer (propylene glycol methyl ether acetate) and isopropyl alcohol, and then dried with clean nitrogen.

[0017] Preferably, the developer comprises propylene glycol methyl ether acetate.

[0018] Preferably, a focused laser system (Aresis Tweez 305), also known as an infrared focused laser etching system, is used in the microchannel laser processing process.

[0019] Preferably, a continuous wave laser (1064 nm) with a maximum power of 5 W is used during the microchannel laser processing.

[0020] Preferably, the laser is part of a focused laser system (Aresis Tweez 305), which provides a software platform for programming and controlling the laser scanning path, an optical tweezers system, and a high-precision motorized stage (H117E1N4 / E, PriorScientific). The high-precision motorized stage is mounted on an inverted microscope (ECLIPSE Ti2-U, Nikon) equipped with objective lenses of different magnifications.

[0021] Tweez 305 uses acousto-optic deflection technology to achieve rapid changes in the position of the laser beam (100,000 Hz). Its built-in programming environment can create a variety of patterns consisting of two-dimensional dot matrices, which facilitates rapid prototyping and eliminates the mask making process in traditional photolithography.

[0022] Preferably, during the microchannel laser processing, a laser is used, and the power of the laser is 10-50% of the maximum power of the laser, and further 30-50%.

[0023] Preferably, after the microchannel laser processing is completed, ultrasonic cleaning is performed using isopropyl alcohol for 10-30 seconds and then rinsed with ultrapure water to remove residues from the etching process.

[0024] Limited by the objective lens magnification and camera size, for small-area photoresist etching, the pattern can be written directly on the two-dimensional dot matrix, and then the etching can be completed by simply turning on the laser tweezers. The laser irradiation time is 0.01 seconds and the power is 30% of the maximum power of the laser. For large-area etching, continuous etching is required by moving the electric stage to form a specific pattern. The power is 50% of the maximum power of the laser. The moving speed is usually set to 80-100 microns / second, and the etching can be completed in 10 minutes. After etching is completed, use isopropyl alcohol for ultrasonic cleaning for 10-30 seconds, and then rinse with ultrapure water to remove residues from the etching process. After cleaning, use clean nitrogen to dry the sample.

[0025] Since pentaerythritol triacrylate photoresist cannot be directly combined with polydimethylsiloxane, the surface of the photoresist needs to be specially treated, and a silane coupling agent is used as an intermediate connecting bond to bond the photoresist to the flat polydimethylsiloxane.

[0026] Preferably, first, the microchannel sample after etching is processed by plasma cleaning instrument for 10 minutes, then the substrate sample is immersed in silane coupling agent for 30 minutes, and the sample is directly dried with clean nitrogen after taking out. Then, holes are punched on polydimethylsiloxane according to the corresponding positions of the input port and output port of the microfluidic chip. Then, the flat polydimethylsiloxane after punching is processed by plasma cleaning instrument for 10 minutes. After the processing is completed, the substrate sample and polydimethylsiloxane are directly aligned and fitted, and they are bonded together in ultraviolet irradiation for 60-90 minutes. In this way, photoresist and polydimethylsiloxane are successfully bonded together, which provides necessary conditions for the use of microfluidic chip.

[0027] A microfluidic chip is prepared by the above method.

[0028] Application of the above-mentioned microfluidic chip in the field of detection.

[0029] Preferably, the detection includes detection in the fields of biomedicine, chemical analysis or material science.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0031] (1) The method of the present invention simplifies the process flow, reduces the production cost, and maintains high precision. Traditional methods such as soft lithography and ultraviolet lithography have high precision, but the equipment is expensive and the process is complicated; while inkjet printing and screen printing have low cost, but the precision and resolution are insufficient. The focused laser etching method of the present invention has the advantages of both high precision and low cost.

[0032] (2) The microfluidic structure fabricated by the method of the present invention has high biocompatibility and is suitable for the field of biomedical engineering. The conventional method may introduce incompatible substances during material selection and processing, but the present invention can avoid this problem by focusing on laser etching pentaerythritol triacrylate photoresist and ensure the biocompatibility of the microfluidic structure.

[0033] (3) The method of the present invention has a fast production speed and is suitable for rapid prototyping. Compared with high-precision but slow methods such as electron beam direct writing and femtosecond laser two-photon direct writing, the focused laser etching method of the present invention can complete the production of high-precision microfluidic channels in a relatively short time, improves production efficiency, and has wide application potential and research value. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a schematic diagram of the infrared focused laser etching system;

[0035] Figure 2 A schematic diagram of the process of making a microfluidic chip in Example 1;

[0036] Figure 3 The results of the microfluidic chip fabrication step in Example 1;

[0037] Figure 4 100x oil-immersed optical microscopic imaging of microchannels etched in photoresist at different distances from the focal plane of the objective lens. DETAILED DESCRIPTION

[0038] In order to make the technical scheme of the present invention more clearly understood by those skilled in the art, the following embodiments are listed for illustration. It should be pointed out that the following embodiments do not limit the protection scope of the present invention.

[0039] Unless otherwise specified, the raw materials, reagents or devices used in the following examples can be obtained from conventional commercial sources or by existing known methods.

[0040] The method for preparing a microfluidic chip by using focused laser etching of the present invention comprises the following steps:

[0041] The photoresist is coated on the surface of the substrate, and is polymerized through exposure to form a photoresist substrate;

[0042] Designing a scanning track of a focused infrared laser according to a microchannel pattern, and performing microchannel laser processing on the photoresist substrate to obtain a sample;

[0043] The sample surface is treated by plasma, and the photoresist and polydimethylsiloxane are bonded by a coupling agent to obtain a microfluidic chip.

[0044] The photoresist includes pentaerythritol triacrylate and a photoinitiator.

[0045] In the photoresist, the mass volume ratio of the photoinitiator to pentaerythritol triacrylate is 1:(50-100).

[0046] The photoinitiator includes photoinitiator 369. The photoinitiator has a strong absorption of ultraviolet light.

[0047] The substrate includes indium tin oxide glass.

[0048] The indium tin oxide glass was treated with a low-pressure air plasma cleaner (VP-R series, Guangzhou Shanzhun Technology Co., Ltd.) for 5-10 minutes, and then immersed in a silane coupling agent KH570 for 20-30 minutes, and then taken out and cleaned with isopropyl alcohol.

[0049] After the surface of the indium tin oxide glass is treated, the photoresist is spin-coated at a speed of 1500-4000 rpm for 20-30 seconds to obtain a photoresist with a thickness of several microns to tens of microns. It is then irradiated with an ultraviolet lamp for 3-5 seconds to cause the photoresist to polymerize. After the polymerization is completed, the residues on the surface of the photoresist are cleaned with a developer (propylene glycol methyl ether acetate) and isopropyl alcohol, and then dried with clean nitrogen gas.

[0050] The developer solution includes propylene glycol methyl ether acetate.

[0051] The microchannel laser processing process uses a focused laser system (Aresis Tweez 305), also known as an infrared focused laser etching system.

[0052] A continuous wave laser (1064nm) with a maximum power of 5W is used in the microchannel laser processing process.

[0053] The laser is part of a focused laser system (Aresis Tweez 305), which provides a software platform for programming the laser scanning path, an optical tweezers system, and a high-precision motorized stage (H117E1N4 / E, PriorScientific). The high-precision motorized stage is mounted on an inverted microscope (ECLIPSE Ti2-U, Nikon) equipped with objectives of different magnifications.

[0054] Tweez 305 uses acousto-optic deflection technology to achieve rapid changes in the position of the laser beam (100,000 Hz). Its built-in programming environment can create a variety of patterns consisting of two-dimensional dot matrices, which facilitates rapid prototyping and eliminates the mask making process in traditional photolithography.

[0055] During the microchannel laser processing, a laser is used, and the power of the laser is 10-50% of the maximum power of the laser, and further 30-50%.

[0056] After the microchannel laser processing is completed, ultrasonic cleaning is performed using isopropyl alcohol for 10-30 seconds and then rinsed with ultrapure water to remove residues from the etching process.

[0057] Limited by the objective lens magnification and camera size, for small-area photoresist etching, the pattern can be written directly on the two-dimensional dot matrix, and then the etching can be completed by simply turning on the laser tweezers. The laser irradiation time is 0.01 seconds and the power is 30% of the maximum power of the laser. For large-area etching, continuous etching is required by moving the electric stage to form a specific pattern. The power is 50% of the maximum power of the laser. The moving speed is usually set to 80-100 microns / second, and the etching can be completed in 10 minutes. After etching is completed, use isopropyl alcohol for ultrasonic cleaning for 10-30 seconds, and then rinse with ultrapure water to remove residues from the etching process. After cleaning, use clean nitrogen to dry the sample.

[0058] Since pentaerythritol triacrylate photoresist cannot be directly combined with polydimethylsiloxane, the surface of the photoresist needs to be specially treated, and a silane coupling agent is used as an intermediate connecting bond to bond the photoresist to the flat polydimethylsiloxane.

[0059] First, the etched microchannel sample is treated with a plasma cleaner for 10 minutes, and then the substrate sample is immersed in a silane coupling agent for 30 minutes. After taking it out, the sample is directly dried with clean nitrogen. Next, holes are punched on the polydimethylsiloxane according to the corresponding positions of the input and output ports of the microfluidic chip. Then, the punched flat polydimethylsiloxane is treated with a plasma cleaner for 10 minutes. After the treatment is completed, the substrate sample and the polydimethylsiloxane are directly aligned and fitted, and they are bonded together under ultraviolet irradiation for 60-90 minutes. In this way, the photoresist and polydimethylsiloxane are successfully bonded together, providing the necessary conditions for the use of the microfluidic chip.

[0060] Example 1

[0061] The method for preparing a microfluidic chip by using focused laser etching comprises the following steps:

[0062] 1) Photoresist substrate preparation

[0063] The main components of photoresist are pentaerythritol triacrylate and photoinitiator 369, which have strong absorption for ultraviolet light. The preparation process of photoresist is as follows: photoinitiator 369 and pentaerythritol triacrylate are mixed in a mass volume ratio of 1:100, and the photoinitiator 369 is completely dissolved by ultrasonic water bath heating for 30 minutes. In order to improve the adhesion of pentaerythritol triacrylate to indium tin oxide glass (size 26.5*26.5*1.1mm, film thickness 185 nanometers, provided by South China Xiangcheng Technology Co., Ltd.), a layer of silane coupling agent KH570 needs to be attached to the indium tin oxide glass. The specific process is as follows: first, use a low-pressure air plasma cleaner (VP-R series, Guangzhou Shanzhun Technology Co., Ltd.) to treat the surface of indium tin oxide glass for 10 minutes, then soak the indium tin oxide glass in silane coupling agent KH570 for 30 minutes, take it out and clean it with isopropyl alcohol, after the surface of the indium tin oxide glass is treated, spin-coat the photoresist at a speed of 3000 rpm for 30 seconds, and then use ultraviolet light to irradiate for 5 seconds to make the photoresist polymerize, after the polymerization is completed, use developer (propylene glycol methyl ether acetate) and isopropyl alcohol to clean the residue after polymerization on the surface of the photoresist, and use clean nitrogen to dry the sample;

[0064] 2) Focused infrared laser etching of microfluidic channels

[0065] A continuous wave laser (1064 nm) with a maximum power of 5 W was used. The laser used was part of a focused laser system (Aresis Tweez 305), which provided a software platform for programming and controlling the laser scanning path, an optical tweezers system, and a high-precision motorized stage (H117E1N4 / E, Prior Scientific). The high-precision motorized stage was mounted on an inverted microscope (ECLIPSE Ti2-U, Nikon) equipped with objectives of different magnifications.

[0066] Aresis Tweez 305 uses acousto-optic deflection technology to achieve rapid changes in the position of the laser beam (100,000 Hz). Its built-in programming environment can create a variety of patterns consisting of two-dimensional dot matrices, which facilitates rapid prototyping and eliminates the mask making process in traditional photolithography.

[0067] Limited by the objective lens magnification and camera size, for small-area photoresist etching, the pattern can be written directly on the two-dimensional dot matrix, and then the etching can be completed by simply turning on the laser tweezers. The laser irradiation time is 0.01 seconds, and the power is 30% of the maximum power of the laser. For large-area etching, it is necessary to move the electric stage for continuous etching to form a specific pattern. The power is 50% of the maximum power of the laser. The moving speed is usually set to 100 microns / second, and the etching can be completed in 10 minutes. After the etching is completed, use isopropyl alcohol for ultrasonic cleaning for 30 seconds, and then rinse with ultrapure water to remove the residues in the etching process. After cleaning, use clean nitrogen to dry the sample;

[0068] 3) Adhesion bonding

[0069] Since pentaerythritol triacrylate photoresist cannot be directly combined with polydimethylsiloxane, it is necessary to perform special treatment on the surface of the photoresist. The photoresist and the flat polydimethylsiloxane are bonded together using a silane coupling agent as an intermediate connecting bond. First, the microfluidic channel sample after etching in step (2) is treated with a plasma cleaner for 10 minutes, then immersed in a silane coupling agent for 30 minutes, and then taken out and directly dried with clean nitrogen. Next, holes are punched on the polydimethylsiloxane according to the corresponding positions of the input port and the output port of the microfluidic chip. Then, the flat polydimethylsiloxane after the holes are punched is treated with a plasma cleaner for 10 minutes. After the treatment is completed, the substrate sample and the polydimethylsiloxane are directly aligned and attached, and then bonded together under ultraviolet irradiation for 60-90 minutes. In this way, the photoresist and the polydimethylsiloxane are successfully bonded together, providing the necessary conditions for the use of the microfluidic chip.

[0070] Figure 1 This is a schematic diagram of the infrared focused laser etching system; Figure 2 A schematic diagram of the process of making a microfluidic chip in Example 1; Figure 3 The results of the microfluidic chip fabrication step in Example 1; Figure 4 100x oil-immersed optical microscopic imaging of microchannels etched in photoresist at different distances from the focal plane of the objective lens.

[0071] The present invention is to produce a microchannel by prototype subtraction, that is, etching a microchannel on a flat photoresist after photopolymerization, using a flat polydimethylsiloxane to bond it, eliminating the step of reverse molding, and being able to finely etch and produce a microchannel with a width of 5 microns (spin coating the photoresist at 6000 revolutions per minute and etching the microchannel with a focused infrared laser). In the entire preparation process, firstly, the indium tin oxide glass bottom plate is plasma cleaned for 10 minutes, and soaked in a silane coupling agent KH570 for 30 minutes, and at the same time, the photoresist is configured. When making a photoresist substrate, spin coating the photoresist, exposing, cleaning and drying take a total of 5 minutes. Then, etching can be completed by using laser micromachining for 10 minutes. Subsequently, the channel is cleaned, dried and plasma cleaned, which takes about 15 minutes. Then, the channel surface is soaked in the silane coupling agent KH570 for 30 minutes again. Finally, ultraviolet light irradiation packaging is performed for 60 to 90 minutes. The entire preparation process takes about 3 hours.

[0072] In order to prove the technical effect achieved by the method of the present invention, the following tests and data analysis were carried out:

[0073] 1. Resolution: Through testing, it was found that when the focal plane of the objective lens was located in the middle of the photoresist, the width of the microchannel etched by the focused infrared laser was the narrowest. Using a real-time optical microscope to measure, the width of the microchannel could reach 5 microns, which meets the requirements of high-precision microfluidic chips.

[0074] 2. Preparation time: The entire preparation process takes about 3 hours. If the photoresist and pre-treated ITO glass substrate are prepared in advance, the time can be further shortened for high-throughput production.

[0075] These data prove that the method of the present invention has the technical advantages of high precision and high efficiency in microchannel etching.

[0076] The time cost, economic cost, complexity and precision of the microfluidic chip produced by the method of the present invention and several common methods in the prior art are listed in Table 1.

[0077] Table 1

[0078]

[0079] It can be seen from Table 1 that the method of the present invention requires a short time, has a low economic cost, is easy to operate, and the microfluidic chip prepared has high precision.

Claims

1. A method for preparing a microfluidic chip using focused laser etching, characterized in that: The following steps are involved: The photoresist is coated on the surface of the substrate, and is polymerized through exposure to form a photoresist substrate; Designing a scanning track of a focused infrared laser according to a microchannel pattern, and performing microchannel laser processing on the photoresist substrate to obtain a sample; The sample surface is treated by plasma, and the photoresist and polydimethylsiloxane are bonded by a coupling agent to obtain a microfluidic chip; The photoresist comprises pentaerythritol triacrylate and a photoinitiator; The substrate comprises indium tin oxide glass; The indium tin oxide glass is treated with a low-pressure air plasma cleaning device for 5-10 minutes, and then the indium tin oxide glass is immersed in a silane coupling agent KH570 for 20-30 minutes, and then taken out and cleaned with isopropyl alcohol; After treating the surface of the indium tin oxide glass, spin-coat the photoresist at a speed of 1500-4000 rpm for 20-30 seconds to obtain a photoresist with a thickness of several microns to tens of microns. Then, irradiate the photoresist with an ultraviolet lamp for 3-5 seconds to polymerize the photoresist. After the polymerization is completed, clean the residues on the surface of the photoresist with a developer and isopropyl alcohol, and dry it with nitrogen.

2. The method according to claim 1, characterized in that In the photoresist, the mass volume ratio of the photoinitiator to pentaerythritol triacrylate is 1:(50-100).

3. The method according to claim 2, characterized in that The photoinitiator includes photoinitiator 369.

4. The method according to claim 1, characterized in that: The focused laser system Aresis Tweez 305 was used in the microchannel laser processing process.

5. A microfluidic chip, characterized in that: Prepared by the method according to any one of claims 1 to 4.

6. Application of the microfluidic chip according to claim 5 in the field of detection.

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