A glass-based microfluidic chip and a method for manufacturing the same

Abstract

The present application relates to a kind of glass-based microfluidic chip and its preparation method, comprising the following steps: the glass substrate of bare photolithography pattern is prepared, the photolithography pattern includes solution inflow channel, reaction channel, solution outflow channel, the reaction channel is provided with weir structure;The pattern of the bare photolithography pattern glass substrate except reaction channel is respectively protected according to different etching channel depth, to obtain the glass substrate of step-by-step protection;Make wet etching liquid in the surface of the glass substrate of step-by-step protection constant speed flow, according to etching channel target depth, the protection of the glass substrate of step-by-step protection is removed respectively in corresponding time, so that each channel is exposed in corresponding time in constant speed flow wet etching liquid, to prepare the chip bottom plate with different depth-width ratio microchannel;Chip cover plate is prepared, the chip bottom plate and the chip cover plate are bonded, to prepare glass-based microfluidic chip.

Description

Technical Field

[0001] This invention relates to the field of glass-based microfluidic chips, specifically to a glass-based microfluidic chip and its fabrication method. Background Technology

[0002] Microfluidic chip technology is a technique that utilizes microchannels to process or manipulate tiny fluids, characterized by its small size, fast reaction speed, low energy consumption, and small sample and reagent usage. Microfluidic chip technology has become one of the most promising cutting-edge analytical techniques, with broad application prospects in medicine, biochemical analysis, and chemical synthesis. Commonly used materials in the fabrication of microfluidic chips include glass, quartz, PDMS (polydimethylsiloxane), PS (polystyrene), PP (polypropylene), PE (polyethylene), and PMMA (polymethyl methacrylate). Finished microfluidic chips commonly use PDMS chips, glass chips, and PMMA chips. Currently, PDMS is the preferred material for rapid fabrication of microfluidic devices due to its low cost, good biocompatibility, and ease of manufacturing. However, in practical applications, the chemical inertness, softening temperature, transmittance, molding performance, and bonding performance of microfluidic chips must be comprehensively considered. When microfluidic chips are used as reactors in chemical synthesis, the chip material must be able to withstand corrosion from organic solvents or acid / alkali reagents such as DMF (N,N-dimethylformamide), DIC (N,N-diisopropylcarbodiimide), and TFA (trifluoroacetic acid). In such cases, PDMS chips are often unsuitable. Glass, as an important substrate for microfluidic chips, has excellent resistance to organic solvents and possesses unique advantages such as not reacting chemically with other substances, good electrical insulation and heat dissipation, excellent optical properties, high voltage resistance, and good biocompatibility.

[0003] In practical applications, micromachining on glass substrates is typically required. The processes used generally include micromachining (such as electrochemical discharge, ultrasonic drilling, and laser etching), dry etching, and wet etching. Among these three methods, wet etching with hydrofluoric acid solution can be used, but the etching depth achievable with current glass wet etching technology is relatively shallow. The bottleneck in deep wet etching of glass is that the highly corrosive etchant is more likely to cause the mask protective layer to collapse, erode, or even peel off during the etching process. Furthermore, the timely removal of reaction products on the etched surface and the controllability of the etching rate and time are crucial to the success of deep etching and are problems that need to be solved in the application of wet etching in the fabrication of glass microchannels of different depths.

[0004] Most existing microfluidic chips used in the pharmaceutical and biological fields are polymer-based (PC, PMMA, PDMS, etc.), which have the following drawbacks when used in chemical synthesis:

[0005] (1) The chip is hydrophobic: It is difficult to introduce aqueous solution into the channel. Hydrophobic substances will be adsorbed on the surface of the PDMS chip, thus interfering with the subsequent reaction or analysis and detection.

[0006] (2) Chips made of elastic materials are not resistant to high pressure: When the pressure inside the channel increases, it will change the geometry of the channel, which will easily cause leakage of the reaction liquid, affecting the experiment or causing the experiment to fail.

[0007] (3) The chip is not resistant to organic solvents: When the synthesis experiment is carried out, the chip will dissolve due to the inability of the material to withstand the reaction environment, thus losing the functionality of the chip reactor.

[0008] In existing technologies, most glass wet etching processes employ static etching, which easily leads to the deposition of substances such as metal oxides on the surface (the reaction products on the etching surface are not easy to remove in time), resulting in a significant increase in the surface roughness and unevenness of the etching channel, which in turn affects deeper etching.

[0009] Existing wet etching techniques have shallow depths, making it difficult to obtain etching channels with high aspect ratios.

[0010] In existing wet etching techniques, the etching rate of the etching solution used is too fast or too slow and is difficult to control. Severe lateral etching often leads to over-etching, making the etching process uncontrollable and difficult to obtain stable etching results.

[0011] Existing technologies for drilling glass often employ diamond drilling or relatively coarse laser drilling, resulting in holes with varying upper and lower diameters, numerous burrs on the edges, and uneven surfaces. When such cover plates are bonded to the substrate, they can easily generate air bubbles near the chip's microchannels, leading to chip fabrication failure.

[0012] Existing technologies for high-temperature glass-to-glass bonding typically employ a direct heating bonding method. However, excessively rapid heating can easily cause cracks on the surface of the glass chip, leading to chip fabrication failure.

[0013] The purpose of this invention is to design a glass-based microfluidic chip and its fabrication method to address one or more of the problems existing in the prior art. Summary of the Invention

[0014] To address the problems existing in the prior art, the present invention provides a glass-based microfluidic chip and its fabrication method, which can effectively solve the problems existing in the prior art.

[0015] The technical solution of this invention is:

[0016] A method for fabricating a glass-based microfluidic chip includes the following steps:

[0017] A glass substrate with an exposed photolithographic pattern is prepared by means of chromium plating, spin coating, photolithography, development, hardening, and chromium removal processes. The photolithographic pattern includes a solution inflow channel, a reaction channel, and a solution outflow channel. The reaction channel is provided with a weir structure.

[0018] The exposed photolithographic pattern on the glass substrate, excluding the reaction channels, is protected according to different etching channel depths to obtain a glass substrate with step-by-step protection.

[0019] The wet etching solution is made to flow at a constant speed on the surface of the step-protected glass substrate. According to the target depth of the etching channel, the protection of the step-protected glass substrate is removed at the corresponding time, so that each channel is exposed in the wet etching solution with a constant speed for a corresponding time, thereby obtaining a chip substrate with microchannels with different aspect ratios.

[0020] A chip cover plate is prepared, and the chip substrate and the chip cover plate are bonded together to obtain a glass-based microfluidic chip.

[0021] Furthermore, the solution inflow channel, the reaction channel, the dam structure, and the solution outflow channel are sequentially and intermittently arranged on the glass substrate. After each channel is exposed to a wet etching solution flowing at a constant speed for a corresponding time, the solution inflow channel, the reaction channel, and the solution outflow channel are sequentially connected, and the reaction channel is connected to the dam structure.

[0022] Furthermore, the wet etching solution is prepared by mixing 40% HF, HNO3, and H2O (v / v) in the ratio of (8-12):(5-10):(25-40), and the etching rate of the wet etching solution is stable.

[0023] Furthermore, the target depth of the etching channel in the solution inflow channel is 200-250 μm, the target depth of the etching channel in the reaction channel is 400-500 μm, the target depth of the etching channel in the dam structure is 8-12 μm, and the target depth of the etching channel in the solution outflow channel is 60-100 μm.

[0024] The glass substrate with exposed photolithographic patterns, excluding the reaction channels, is protected according to different etching channel depths to obtain a glass substrate with step-by-step protection, including protecting the solution inflow channel, the dam structure, and the solution outflow channel respectively.

[0025] Furthermore, the step-by-step removal of the protective glass substrate at corresponding times according to the target depth of the etching channel includes:

[0026] The stepwise protected glass substrate exposing the reaction channel is placed in the wet etching solution to etch the reaction channel;

[0027] When the current depth of the reaction channel is within ±3 μm of the target depth of the etching channel of the solution inflow channel, the protection of the solution inflow channel is removed, and the reaction channel and the solution inflow channel are etched.

[0028] When the current depth of the reaction channel and / or the solution inflow channel is within ±3 μm of the target depth of the etching channel of the solution outflow channel, the protection of the solution outflow channel is removed, and the reaction channel, the solution inflow channel, and the solution outflow channel are etched.

[0029] When the current depth of the reaction channel and / or the solution inflow channel and / or the solution inflow channel is within ±1 μm of the target depth of the etching channel of the cofferdam structure, the protection of the cofferdam structure is removed, and the reaction channel, the solution inflow channel, the solution outflow channel, and the cofferdam structure are etched.

[0030] When the cofferdam structure reaches the target depth, wet etching is stopped.

[0031] Furthermore, before removing the protection of the step-by-step protected glass substrate at corresponding times according to the target depth of the etching channel, the step includes: measuring the etching rate of the wet etching solution;

[0032] During wet etching, the current depth of each channel is calculated based on the etching rate multiplied by the etching time.

[0033] Furthermore, the step of maintaining a constant flow rate of the wet etching solution on the surface of the step-protected glass substrate includes:

[0034] The glass substrate with the photolithographic pattern is placed face down in the stirring mechanism. The wet etching solution is placed in the stirring mechanism. The temperature of the wet etching solution is controlled by the stirring mechanism. The wet etching solution is stirred at a constant speed by the stirring mechanism to form a gentle eddy.

[0035] Further, the fabrication of the chip cover plate, including bonding the chip substrate and the chip cover plate, comprises:

[0036] The solution inflow channel includes an inlet port, and the solution outflow channel includes an outlet port. A UV nanosecond laser is used to drill holes in the chip cover plate at positions corresponding to the inlet port and the outlet port.

[0037] Align the sample inlet and outlet holes of the chip substrate with the holes of the chip cover plate, apply pressure and lock them, then raise the temperature to 130°C at 2°C / min, hold at 130°C for 50 min, then raise the temperature to 600°C at 2°C / min, hold at 600°C for 16 h for bonding, and then cool down to room temperature at a rate of 1°C / min.

[0038] A further glass-based microfluidic chip is provided, which is prepared by the aforementioned method for preparing a glass-based microfluidic chip;

[0039] The solution inflow channel includes an inlet port and an inlet channel, and the solution outflow channel includes an outlet channel and an outlet port. The inlet port, the inlet channel, the reaction channel, the outlet channel, and the outlet port are sequentially connected.

[0040] The sample inlet channel can be one or more, each of which has an inlet hole at its end. If there are multiple sample inlet channels, they are spaced at equal angles; and / or

[0041] The sample outlet channel can be a straight line or a serpentine winding structure.

[0042] Furthermore, the cofferdam structure is a columnar array structure with three or more rows.

[0043] Therefore, the present invention provides the following effects and / or advantages:

[0044] This application utilizes an etching solution flowing on the surface of a glass substrate. The reactants from the reaction between the etching solution and the glass substrate are immediately carried away by the water flow. Simultaneously, the flowing etching solution continuously delivers the desired concentration to the glass substrate for further reaction. Throughout the reaction process, the constant flow rate ensures a constant reaction rate. Based on the target etching depth, the desired structure on the glass substrate can be exposed to the etching solution for a specific time to achieve the corresponding etching depth.

[0045] This application provides protection for all patterns on the glass substrate except for the reaction channels. During wet etching, the invention applies stepwise protection measures to different channel locations on the chip substrate using polyimide tape and polyvinyl chloride film at different etching time points. After etching, microchannels with different aspect ratios can be fabricated, enabling a single glass microfluidic chip to possess different reactive functional characteristics. Applying stepwise protection measures to different channel locations on the chip substrate allows for the fabrication of microchannels with different aspect ratios, enabling a single glass microfluidic chip to possess different reactive functional characteristics.

[0046] In processing chip cover plates, this invention explores processing techniques by adapting to different ultraviolet nanosecond lasers. The final processing method can produce cover plate round holes with uniform upper and lower diameters and no burrs or defects on the edges in batches.

[0047] This invention has developed a programmed temperature and pressure bonding process for chip bonding, which effectively reduces the breakage rate of glass chips during the heating process. There are no air bubbles in the chip bonding interlayer or only a small number of air bubbles far away from the channel (which does not affect the normal performance of the chip). This method effectively improves the success rate of glass chip bonding in the laboratory.

[0048] This invention uses a stirring mechanism to make the etching solution flow slowly on the chip channel surface during the etching process, so that the metal oxides or reaction products deposited on the chip surface can be removed in time. The resulting chip channel surface is smooth and flat with uniform depth, which can achieve deeper etching.

[0049] This invention applies protective measures to the plane of the chip other than the etched channels, alleviates lateral etch near the chip channels, and improves the flatness of the chip surface.

[0050] It should be understood that the above summary and the following detailed description of the invention are exemplary and explanatory, and are intended to provide further explanation of the invention as claimed. Attached Figure Description

[0051] Figure 1 This is a flowchart illustrating the method provided by the present invention.

[0052] Figure 2 This is a schematic diagram of a photolithographic pattern according to one embodiment of the present invention.

[0053] Figure 3 This is a schematic diagram showing the photolithographic pattern after protection.

[0054] Figure 4 This is a schematic diagram of the temperature change during the heating thermal bonding process.

[0055] Figure 5 A schematic diagram showing the removal of the protection for the solution inflow channel.

[0056] Figure 6 A schematic diagram illustrating the protection measures for removing the inflow and outflow channels of the solution.

[0057] Figure 7 A schematic diagram illustrating the protection of the solution inflow channel, solution outflow channel, and cofferdam structure.

[0058] Figure 8 This is a schematic diagram of a glass-based microfluidic chip with one sample inlet channel.

[0059] Figure 9 This is a schematic diagram of a glass-based microfluidic chip with a serpentine, meandering structure for the sample outlet channel.

[0060] Figure 10This is a schematic diagram of a glass-based microfluidic chip with a linear sample outlet channel. Detailed Implementation

[0061] To facilitate understanding by those skilled in the art, the structure of the present invention will now be described in further detail with reference to the accompanying drawings. It should be understood that, unless otherwise specified, the order of the steps mentioned in this embodiment can be adjusted according to actual needs, and they can even be executed simultaneously or partially simultaneously.

[0062] refer to Figure 1 A method for fabricating a glass-based microfluidic chip includes the following steps:

[0063] S1, through chromium plating, spin coating, photolithography, development, hardening, and chromium removal processes, a glass substrate with exposed photolithographic patterns is prepared, such as... Figure 2 As shown, the photolithographic pattern includes a solution inflow channel 1, a reaction channel 2, a dam structure 3, and a solution outflow channel 4; wherein, the solution inflow channel 1 includes an inlet port 101 and an inlet channel 102, and the solution outflow channel 4 includes an outlet channel 401 and an outlet port 402.

[0064] In this step, the chromium plating process, the spin coating process, the photolithography process, the developing process, the hard coating process, and the chromium removal process are all direct adoptions of existing technologies and do not involve the core improvements of this application.

[0065] Before wet etching, the chip substrate underwent chromium plating, photoresist coating, photolithography, development, hardening, and chromium removal. The chip substrate is made of B270 glass with a 120nm chromium layer deposited on its surface. The photoresist used is AZ1500 with a thickness of 500nm. Laser direct-write lithography was used to perform photolithography on the chip substrate, followed by 30 seconds of development. The developed chip substrate was then placed on a 120°C heated plate for hardening. After hardening, the chip substrate was placed in a chromium removal solution to etch away the chromium layer on the microchannel surface, exposing the glass substrate with the photolithographic pattern.

[0066] Among them, the cofferdam structure 3 is set at three-quarters of the distance from the solution outflow channel of the reaction channel 2.

[0067] S2, the exposed photolithographic pattern of the glass substrate, excluding the reaction channel, is protected according to different etching channel depths to obtain a glass substrate with step-by-step protection;

[0068] Since the required etching depth varies for each exposed structure on the glass substrate, but all exposed structures will be etched after the glass substrate is immersed in the etching solution, different structures can be protected separately. For example, in this embodiment, the required etching depth can be set as follows: 200 μm for the solution inflow channel, 450 μm for the reaction channel, 10 μm for the dam structure, and 60 μm for the solution outflow channel. Therefore, each channel is different, and the reaction channel is the deepest. Thus, each structure outside the reaction channel is protected by a shield 5 in each channel.

[0069] In this embodiment, the protection 5 for each channel uses polyimide tape and polyvinyl chloride film, which can be well attached to each structure, and the polyimide tape and polyvinyl chloride film have a certain thickness. Figure 3 As shown, protective layer 5 is affixed to the solution inflow channel, the confinement structure, and the solution outflow channel. Furthermore, protective layer 5 is tearable, meaning that the corresponding structure is exposed after the protective layer is removed. The polyimide tape and polyvinyl chloride film used to protect the chip in this invention are common laboratory tapes and films, and can be replaced with other solvent-resistant tapes or protective films that do not easily leave residue after removal.

[0070] S3, the wet etching solution is made to flow at a constant speed on the surface of the step-protected glass substrate. According to the target depth of the etching channel, the protection of the step-protected glass substrate is removed at the corresponding time, so that each channel is exposed in the wet etching solution with a constant speed for a corresponding time, and a chip substrate with microchannels with different aspect ratios is obtained.

[0071] In this embodiment, wet etching is a technique that involves immersing the material to be etched in a wet etching solution to remove the material from the etched area through a chemical reaction process. The wet etching solution is a buffer solution composed of HF, HNO3, and H2O in a specific ratio. At a constant temperature, the etching rate depends on the ratio of the wet etching solution and the SiO2 doping level. The SiO2 etching rate is most sensitive to temperature; the higher the temperature, the faster the etching.

[0072] The core technological improvement of this application lies in maintaining a constant flow rate of the wet etching solution on the surface of the step-protected glass substrate. Existing technologies mostly employ static etching, where reactants deposit within channels or structures during the contact between the etching solution and the glass substrate. Furthermore, the concentration of reactants in the etching solution around the glass substrate decreases after the reaction, affecting further reactions. By allowing the etching solution to flow across the glass substrate surface, the reactants from the reaction are immediately carried away by the water flow. Simultaneously, the continuous flow of the etching solution brings in the required concentration to react with the glass substrate. Throughout the entire reaction process, the constant flow rate ensures a constant reaction rate.

[0073] Because the reaction rate is constant, the structure of the glass substrate to be etched can be exposed to the etching solution for a certain period of time according to the target depth of the etching channel, thus obtaining the corresponding depth. Since a protective layer is provided on the glass substrate in step S2, after the deepest target channel has reacted for a certain period, the protection is removed to expose the protected portion, allowing it to be etched together with the deepest target channel. Ultimately, channels of different depths and locations can be obtained, resulting in a chip substrate with microchannels of different aspect ratios.

[0074] This embodiment can also be achieved by constructing a dynamic uniform wet etching apparatus and etching the chip in an inverted position. The dynamic uniform wet etching apparatus can be a carrier plate with numerous through holes, allowing the glass substrate to be both exposed to the etching solution and raised by the carrier plate, enabling the etching solution to flow fully on the surface of the glass substrate. In other embodiments, the components providing uniform kinetic energy, the reactor vessel, and the chip support holder can take many different forms, which are not limited here.

[0075] Because the etching requirements for different chip microchannels vary, a suitable etching rate is needed. Therefore, the wet etching solution formulation needs to be changed simultaneously, specifically a mixture of 40% HF, HNO3, and H2O, while still maintaining full control over the etching process. The specific proportions of the wet etching solution are not limited here.

[0076] S4, fabricating a chip cover plate, bonding the chip substrate and the chip cover plate together to obtain a glass-based microfluidic chip. Further, the fabrication of the chip cover plate, including bonding the chip substrate and the chip cover plate, comprises:

[0077] The solution inflow channel includes an inlet port, and the solution outflow channel includes an outlet port. A UV nanosecond laser is used to drill holes in the chip cover plate at positions corresponding to the inlet port and the outlet port.

[0078] Align the sample inlet and outlet holes of the chip substrate with the holes of the chip cover plate, apply pressure and lock them, then raise the temperature to 130°C at 2°C / min, hold at 130°C for 50 min, then raise the temperature to 600°C at 2°C / min, hold at 600°C for 16 h for bonding, and then cool down to room temperature at a rate of 1°C / min.

[0079] In this step, a programmed temperature and pressure bonding method is used to bond the chip substrate and cover plate. The circular holes on the chip substrate are aligned with the circular holes on the chip cover plate, and after being secured with a steel plate under pressure, the chip is placed in a muffle furnace. The programmed temperature and pressure process is as follows: Figure 4As shown. The heating rate was 2℃ / min, equilibrated at 130℃ for 50 min, then increased to 600℃ at 2℃ / min, held at 600℃ for 16 h for bonding, and then cooled to room temperature at 1℃ / min. The equilibration process at 130℃ serves as a pre-bonding process, ensuring initial bonding. The prolonged holding at 600℃ helps eliminate large areas of Newton's rings (air bubbles) near the channels during pre-bonding. The slow heating / cooling process prevents internal stress-induced chip breakage during annealing. Experimental results show that this bonding process effectively reduces the chip breakage rate during heating, resulting in no air bubbles in the chip bonding interlayer or only a small number of air bubbles far from the channels (not affecting normal chip performance). This method effectively improves the success rate of glass chip bonding in the laboratory.

[0080] The method of using an ultraviolet nanosecond laser to process the round holes of the chip cover plate can produce round holes of the cover plate with uniform upper and lower diameters and no burrs or defects on the edges in batches.

[0081] The chip bonding process in this invention consists of four steps: low-temperature equilibration, slow and uniform heating, high-temperature holding and slow and uniform cooling. When performing thermal bonding of glass with different compositions, the bonding pattern can follow this trend, but the low-temperature equilibration temperature, high-temperature holding temperature and heating and cooling rates will be slightly different.

[0082] Furthermore, the solution inflow channel 1, the reaction channel 2, the dam structure 3, and the solution outflow channel 4 are sequentially and intermittently arranged on the glass substrate. After each channel is exposed to a wet etching solution flowing at a constant speed for a corresponding time, the solution inflow channel 1, the reaction channel 2, and the solution outflow channel 4 are sequentially connected, and the reaction channel 2 is connected to the dam structure 3.

[0083] like Figure 2 As shown, the photolithographic pattern is initially set with gaps between each channel. This is because, during the wet etching process, the etching solution not only etches the channel downwards but also etches it outwards. In order to ensure the accuracy of the shape and width of the connection between each channel, the pattern of each channel is initially set with gaps between them. During the wet etching process, the ends of each channel extend outwards and then connect together.

[0084] Furthermore, the wet etching solution is prepared by mixing 40% HF, HNO3, and H2O (v / v) in the ratio of (8-12):(5-10):(25-40), and the etching rate of the wet etching solution is stable.

[0085] In this embodiment, the wet etching solution is prepared with a ratio of 40% HF, HNO3, and H2O (v / v) of 11:9:30. The etching rate at this ratio is 2.54 μm / min, exhibiting stable etching performance and controllable etching throughout the process, thus preventing over-etching or insufficient etching depth. In other embodiments, any value within this range can be used; the etching rate simply needs to be determined based on this ratio.

[0086] Furthermore, the target depth of the etching channel in the solution inflow channel is 200-250 μm, the target depth of the etching channel in the reaction channel is 400-500 μm, the target depth of the etching channel in the dam structure is 8-12 μm, and the target depth of the etching channel in the solution outflow channel is 60-100 μm.

[0087] The glass substrate with exposed photolithographic patterns, excluding the reaction channels, is protected according to different etching channel depths to obtain a glass substrate with step-by-step protection, including protecting the solution inflow channel, the dam structure, and the solution outflow channel respectively.

[0088] In this embodiment, the target depth of the etching channel for the solution inflow channel is 200 μm, the target depth of the etching channel for the reaction channel is 450 μm, the target depth of the etching channel for the cofferdam structure is 10 μm, and the target depth of the etching channel for the solution outflow channel is 60 μm.

[0089] Since the reaction channels require the deepest etching depth, etching can begin immediately without the need for protection. The glass substrate can then be directly immersed in the etching solution, allowing the reaction channels to come into immediate contact with the etching solution.

[0090] Furthermore, the step-by-step removal of the protective glass substrate at corresponding times according to the target depth of the etching channel includes:

[0091] The stepwise protected glass substrate exposing the reaction channel is placed in the wet etching solution to etch the reaction channel;

[0092] refer to Figure 5 When the current depth of the reaction channel is within ±3 μm of the target depth of the etching channel of the solution inflow channel, the protection of the solution inflow channel is removed, and the reaction channel and the solution inflow channel are etched.

[0093] refer to Figure 6When the current depth of the reaction channel and / or the solution inflow channel is within ±3 μm of the target depth of the etching channel of the solution outflow channel, the protection of the solution outflow channel is removed, and the reaction channel, the solution inflow channel, and the solution outflow channel are etched.

[0094] refer to Figure 7 When the current depth of the reaction channel and / or the solution inflow channel and / or the solution inflow channel is within ±1 μm of the target depth of the etching channel of the cofferdam structure, the protection of the cofferdam structure is removed, and the reaction channel, the solution inflow channel, the solution outflow channel, and the cofferdam structure are etched.

[0095] When the cofferdam structure reaches the target depth, wet etching is stopped.

[0096] Because this application employs a constant-speed flow of wet etching solution on the surface of the step-protected glass substrate, it avoids variations in the concentration of the reaction solution around the glass substrate and the deposition of reactants that could obstruct the exposure of the reaction surface. Therefore, the reaction rate is constant, and the reaction depth is controllable. This application initiates the reaction at the deepest channel. When the remaining required reaction depth of the deepest channel is the same as that of the second deepest channel, the protection of the second deepest channel is removed, allowing both to begin reacting simultaneously. The principle of the reaction timing for other channels is similar. The overall etching rate is constant, and the exposure points of different channels can be artificially controlled, thus enabling multiple channels to begin etching at different points, ultimately achieving the required etching depth simultaneously for multiple channels.

[0097] Furthermore, before removing the protection of the step-by-step protected glass substrate at corresponding times according to the target depth of the etching channel, the step includes: measuring the etching rate of the wet etching solution;

[0098] During wet etching, the current depth of each channel is calculated based on the etching rate multiplied by the etching time.

[0099] In this step, the etching solution was prepared as described above. With this etching solution, the etching rate was 2.54 μm / min when the etching temperature was maintained at 25℃, the etching was stable, and the entire etching process was controllable.

[0100] Due to the requirement of a solution inflow channel depth of 200 μm, a reaction channel depth of 450 μm, a dam structure depth of 10 μm, and a solution outflow channel depth of 60 μm, and an etching rate of 2.54 μm / min, after 99 min of etching, the protection at the solution inflow channel was removed, and etching continued for 54 min. Then, the protection at the solution outflow channel was removed, and etching continued for 20 min. Finally, the protection at the dam structure was removed, and etching continued for 4 min to complete the etching of the chip substrate. After etching, (1) the protection measures on the chip plane effectively alleviated the lateral etching near the chip channel, improving the flatness of the chip surface; (2) microchannels with different aspect ratios can be fabricated simultaneously, with a maximum depth of 450 μm and a minimum depth of 10 μm, realizing that a glass microfluidic chip has different reaction functional characteristics.

[0101] Furthermore, the step of maintaining a constant flow rate of the wet etching solution on the surface of the step-protected glass substrate includes:

[0102] The glass substrate with the photolithographic pattern is placed face down in the stirring mechanism. The wet etching solution is placed in the stirring mechanism. The temperature of the wet etching solution is controlled by the stirring mechanism. The wet etching solution is stirred at a constant speed by the stirring mechanism to form a gentle eddy.

[0103] In this step, the glass substrate with the photolithographic pattern is placed face down in the stirring mechanism because the etched reactants tend to sink under gravity. With the photolithographic pattern face down, the reactants can naturally detach from the photolithographic pattern and be carried away better by the flow of the etching solution.

[0104] In this step, the magnetic stirrer speed is adjusted to 500 r / min. At this speed, the etching solution surface in the etching container forms a gentle vortex, and the etching temperature is maintained at 25℃. The patterned side of the protected glass substrate is placed face down on the PTFE holder. The distance between the chip substrate and the PTFE holder is raised by attaching PVC films to both ends of the glass substrate, allowing the etching solution to fully contact and react with the chip surface. The flow of the solution promptly removes any build-up on the chip surface. The etched chip channel surface is smooth and flat with consistent depth, enabling deeper etching.

[0105] A further glass-based microfluidic chip is provided, which is prepared by the aforementioned method for preparing a glass-based microfluidic chip;

[0106] refer to Figure 2The solution inflow channel 1 includes an inlet port 101 and an inlet channel 102, and the solution outflow channel 4 includes an outlet channel 401 and an outlet port 402. The inlet port 101, the inlet channel 102, the reaction channel 2, the outlet channel 401, and the outlet port 402 are connected in sequence.

[0107] In this embodiment, solution inflow channel 1 serves as the inflow channel for etching solution and solidified material, reaction channel 2 serves as the main reactor for reaction, dike structure 3 is used to enclose the solidified material in the reaction channel, and solution outflow channel 4 serves as the outflow channel for products and waste liquid.

[0108] The sample inlet channel 102 can be one or more, and each sample inlet channel is provided with a sample inlet hole at its end. If there are multiple sample inlet channels, the multiple sample inlet channels are arranged at equal angular intervals.

[0109] like Figure 8 The glass-based microfluidic chip shown includes a sample inlet channel. For example... Figure 9 The glass-based microfluidic chip shown contains two sample entry channels.

[0110] And / or the sample outlet channel may be a straight line or a serpentine meandering structure;

[0111] like Figure 8 or Figure 9 The sample outlet channel of the glass-based microfluidic chip shown is a serpentine, meandering structure. For example... Figure 10 The sample outlet channel of the glass-based microfluidic chip shown is a straight structure.

[0112] The cofferdam structure is a columnar array structure with three or more rows.

[0113] like Figure 2 The glass-based microfluidic chip shown has a three-row or higher columnar array structure for enclosing the solidified material within the reaction channel. Figure 2 In the diagram, the white portion of the cofferdam structure 3 is a columnar structure, and the black shaded portion is unetched glass. The reacting liquid drains through the gaps in the columnar structure, which serves to hold back the flow. In this embodiment, a 10-row columnar array structure is used. The more rows of columnar structures there are, the better the interception effect.

[0114] It should be noted that any reference signs placed between parentheses in the claims should not be construed as limiting the claims. The word "comprising" does not exclude the presence of components or steps not listed in the claims. The word "a" or "an" preceding a component does not exclude the presence of a plurality of such components. The invention can be implemented by means of hardware comprising several different components and by means of a suitably programmed computer. In a unit claim enumerating several means, several of these means may be embodied by the same item of hardware. The use of the words first, second, and third, etc., does not indicate any order. These words can be interpreted as names.

[0115] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0116] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

[0117] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0118] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms should not be construed as necessarily referring 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. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

Claims

1. A method for fabricating a glass-based microfluidic chip, characterized by: The method comprises the following steps: A glass substrate with exposed photoetching patterns is prepared by a chrome plating process, a uniform glue process, a photoetching process, a developing process, a hardening process, and a chrome removing process, wherein the photoetching patterns comprise a solution inflow channel, a reaction channel, and a solution outflow channel, and the reaction channel is provided with a cofferdam structure; The glass substrate with exposed photoetching patterns is protected by a protective layer according to different etching channel depths, and a glass substrate with step-by-step protection is obtained; A wet etching liquid is made to flow at a constant speed on the surface of the glass substrate with step-by-step protection, and the protective layer of the glass substrate with step-by-step protection is removed at a corresponding time according to the target depth of the etching channel, so that each channel is exposed to the wet etching liquid for a corresponding time, and a chip bottom plate with micro-channels of different aspect ratios is prepared; A chip cover plate is prepared, the chip bottom plate and the chip cover plate are bonded, and a glass-based micro-fluidic chip is prepared. 2.The method of claim 1, wherein: The solution inflow channel, the reaction channel, the cofferdam structure, and the solution outflow channel are sequentially arranged in the glass substrate, and after each channel is exposed to the wet etching liquid for a corresponding time, the solution inflow channel, the reaction channel, and the solution outflow channel are sequentially connected, and the reaction channel is connected with the cofferdam structure. 3.The method of claim 1, wherein: The wet etching liquid is 40% HF, HNO3, and H2O (v / v) with a ratio of (8-12):(5-10):(25-40), and the etching speed of the wet etching liquid is stable.

4. The method of claim 3, wherein the glass-based microfluidic chip is prepared by: The target depth of the etching channel of the solution inflow channel is 200-250 μm, the target depth of the etching channel of the reaction channel is 400-500 μm, the target depth of the etching channel of the cofferdam structure is 8-12 μm, and the target depth of the etching channel of the solution outflow channel is 60-100 μm. The glass substrate with exposed photoetching patterns is protected by a protective layer according to different etching channel depths, and a glass substrate with step-by-step protection is obtained.

5. The method of claim 4, wherein the glass-based microfluidic chip is prepared by: The target depth of the etching channel of the solution inflow channel is 200-250 μm, the target depth of the etching channel of the reaction channel is 400-500 μm, the target depth of the etching channel of the cofferdam structure is 8-12 μm, and the target depth of the etching channel of the solution outflow channel is 60-100 μm. The glass substrate with exposed photoetching patterns is protected by a protective layer according to different etching channel depths, and a glass substrate with step-by-step protection is obtained. The glass substrate with exposed photoetching patterns is protected by a protective layer according to different etching channel depths, and a glass substrate with step-by-step protection is obtained. When the current depth of the reaction channel and / or the solution inflow channel is within ±3 μm of the target depth of the solution outflow channel, the protective layer of the solution outflow channel is removed, and the reaction channel, the solution inflow channel, and the solution outflow channel are etched. When the current depth of the reaction channel and / or the solution inflow channel and / or the solution inflow channel is within ±1 μm of the target depth of the etching channel of the cofferdam structure, the protective layer of the cofferdam structure is removed, and the reaction channel, the solution inflow channel, the solution outflow channel, and the cofferdam structure are etched; When the cofferdam structure reaches the target depth, the wet etching is stopped.

6. The method of claim 5, wherein: Before the protective layer of the step-by-step protected glass substrate is removed at the corresponding time according to the etching channel target depth, the etching speed of the wet etching solution is measured. During the wet etching process, the current depth of each channel is calculated according to the etching speed * etching time.

7. The method for fabricating a glass-based microfluidic chip according to claim 1, characterized in that: The constant-speed flow of the wet etching solution on the surface of the step-by-step protected glass substrate comprises: The side of the step-by-step protected glass substrate provided with the photolithography pattern is placed downward in the stirring mechanism, the wet etching solution is placed in the stirring mechanism, the temperature of the wet etching solution is controlled by the stirring mechanism, and the wet etching solution is stirred at a constant speed by the stirring mechanism to form a gentle vortex. 8.The method of claim 1, wherein: The preparation of the chip cover plate and the bonding of the chip bottom plate and the chip cover plate comprise: The solution inflow channel comprises a sample inlet hole, and the solution outflow channel comprises a sample outlet hole, and the positions of the sample inlet hole and the sample outlet hole corresponding to the chip cover plate are punched by a ultraviolet nanosecond laser instrument; After the sample inlet hole, the sample outlet hole of the chip bottom plate, and the hole position of the chip cover plate are aligned and locked under pressure, the temperature is raised to 130°C at a rate of 2°C / min, and after maintaining at 130°C for 50 min, the temperature is raised to 600°C at a rate of 2°C / min, and the bonding is maintained at 600°C for 16 h, and then the temperature is lowered to room temperature at a rate of 1°C / min.

9. A glass-based microfluidic chip, characterized by, A glass-based microfluidic chip prepared by the method of any one of claims 1-8; The solution inflow channel comprises a sample inlet hole and a sample inlet channel, the solution outflow channel comprises a sample outlet channel and a sample outlet hole, and the sample inlet hole, the sample inlet channel, the reaction channel, the sample outlet channel, and the sample outlet hole are sequentially connected; The sample inlet channel is one or more, each sample inlet channel is provided with a sample inlet hole at the end thereof, and if the sample inlet channel is multiple, the multiple sample inlet channels are arranged at equal angles; and / or The sample outlet channel is a straight line or a serpentine structure.

10. The glass-based microfluidic chip of claim 9, wherein, The cofferdam structure is a columnar array structure of three rows or more. The cofferdam structure is a columnar array structure of three rows or more.

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