Micro-fluidic chip processing method based on sacrificial printing template and application

Abstract

The invention discloses a micro-fluidic chip processing method and application based on a sacrificial printing template, and the method comprises the following steps: (1) adopting hydrolyzable photosensitive resin, and obtaining a 3D sacrificial template with a micro-channel structure through photocuring 3D printing; (2) carrying out at least two rounds of cyclic treatment on the 3D sacrificial template, and sequentially carrying out organic polar solvent cleaning, ultraviolet curing and heat treatment in each round to remove unreacted components and improve the stability of the template; (3) mixing an elastomer prepolymer with a curing agent, injecting the mixture into the obtained 3D sacrificial template, and defoaming and curing in a vacuum environment to obtain a required microstructure; and (4) hydrolyzing the obtained template by adopting an alkaline aqueous solution, and removing the template to obtain the micro-fluidic chip with the 3D micro-channel. The method has the advantages of being high in structural precision, suitable for flexible materials, controllable in template removal and the like, and effectively solves the problem that a traditional process is poor in adaptability and repeatability in flexible high-precision chip manufacturing.

Description

Technical Field

[0001] This invention relates to a method for fabricating microfluidic chips and its application, and more particularly to a method for fabricating microfluidic chips based on a sacrificial printing template and its application. Background Technology

[0002] Microfluidic chips have been widely researched and applied due to their advantages in life sciences, medical diagnostics, and drug screening, including high throughput, low sample consumption, and rapid response. Currently, PDMS (polydimethylsiloxane) has become one of the most widely used materials in microfluidic chip manufacturing due to its excellent flexibility, biocompatibility, and optical transparency. Traditional PDMS chips are mainly manufactured using soft photolithography, which involves first constructing a microstructure template on a silicon wafer using photoresist such as SU-8, followed by PDMS casting and molding.

[0003] However, this traditional molding method has the following key technical bottlenecks: (1) Limited precision: Photolithography templates are mostly two-dimensional planar structures, making it difficult to realize complex microstructures with vertical channels, suspended structures or 3D interconnections; (2) Difficult mold demolding: For complex geometry or suspended structures, PDMS is easy to adhere or tear after curing, limiting the degree of freedom of the structure; (3) Poor structural repeatability: Microstructures are easily affected by residual glue, mold deformation and other factors, resulting in poor consistency between batches; (4) Difficult to iterate quickly: Traditional mold preparation cycle is long and has poor adaptability, which is not conducive to the rapid prototyping development of structural design.

[0004] With the increasing demand for flexibility, integration of biological functions, and complex fluid control, traditional molding processes have shown their limitations. There is an urgent need to develop a processing method that can maintain high-resolution structural accuracy, be applicable to flexible materials, and have good repeatability and process versatility. Summary of the Invention

[0005] Purpose of the invention: The purpose of this invention is to provide a microfluidic chip fabrication method based on a sacrificial printing template, which can maintain high-resolution structural accuracy, is applicable to flexible materials, and has good repeatability and process versatility.

[0006] A second objective of this invention is to provide applications of the microfluidic chip obtained by the above-described method.

[0007] Technical solution: The microfluidic chip fabrication method based on a sacrificial printing template described in this invention includes the following steps:

[0008] (1) A 3D sacrificial template with a microchannel structure was obtained by photopolymerization 3D printing using a hydrolyzable photosensitive resin.

[0009] (2) The 3D sacrificial template is subjected to at least two rounds of cyclic processing, each round consisting of organic polar solvent cleaning, ultraviolet curing and heat treatment, to remove unreacted components and improve template stability;

[0010] (3) Mix the elastomer prepolymer with the curing agent and inject it into the 3D sacrificial template obtained in step (2). Degas and cure the mixture in a vacuum environment to obtain the desired microstructure.

[0011] (4) The template obtained in step (3) is hydrolyzed using an alkaline aqueous solution. After removing the template, a microfluidic chip with 3D microchannels is obtained.

[0012] In step (1), the hydrolyzable photosensitive resin is acryloyloxyethyltrimethylammonium chloride and / or polyethylene glycol diacrylate. The photosensitive resin comprises the following components: 20%–60% acrylate photosensitive monomers, preferably polyethylene glycol diacrylate (PEGDA); 10%–40% ionic monomers, preferably acryloyloxyethyltrimethylammonium chloride (AETAC); and 0.1%–10% photoinitiator, preferably 2,4-dimethylacetophenone (DMPA) or isopropylthioxanthone (Irgacure 819). The sacrificial template material can also be other hydrolyzable or water-soluble polymer materials, preferably polyvinyl alcohol (PVA), hydrogel systems, or glycosyl resins. The hydrolyzable nature of the photosensitive resin ensures the high efficiency and gentleness of subsequent template removal, while high-resolution printing technology enables the realization of complex 3D microchannel structures.

[0013] In step (1), the photopolymerization 3D printing is one of liquid crystal display printing, stereolithography printing, digital light processing printing, or two-photon polymerization printing. When using liquid crystal display printing, the exposure time is controlled at 16-18 s, and the layer thickness is 10-50 μm. When using stereolithography printing or digital light processing printing, the layer thickness is controlled at 10-50 μm, and the exposure time is 3-8 s. When using two-photon polymerization printing, the layer thickness can be controlled in the submicron to 5 μm range. When the printing parameters, such as layer thickness and exposure time, are controlled within the range, the structural stability is good. If the printing parameters are mismatched, the size of the holes and suspended structures will have excessive errors compared to the design values.

[0014] In step (2), the cleaning time with organic polar solvent is 20-40 min; the UV curing time is 0.5-1.5 h; the heat treatment temperature is 50-70 ℃ and the heat treatment time is 3-5 h.

[0015] In step (2), the organic polar solvent is at least one of ethanol, propanol, isopropanol or ethyl acetate; more preferably isopropanol.

[0016] In step (3), the mass ratio of the elastomer prepolymer to the curing agent is 5-20:1. When the ratio of the elastomer prepolymer, such as PDMS prepolymer, to the curing agent is within the specified range, the viscosity and curing speed of PDMS are moderate, ensuring the complete replication of microchannels within the template. If the proportion of the curing agent is too low, the crosslinking will be insufficient, leading to structural collapse or instability due to excessive flexibility. If the proportion of the curing agent is too high, the PDMS will be too brittle, resulting in decreased flexibility and making it difficult to meet subsequent deformation and application requirements.

[0017] In step (3), the curing temperature is 50-70 ℃ and the time is 3-6 h.

[0018] In step (3), the degassing time under vacuum is 0.5-1.5 h. Insufficient vacuum degassing time can easily lead to residual bubbles forming in the channel, resulting in microchannel blockage or defects; while excessive degassing time will no longer significantly improve the molding quality and will instead reduce process efficiency. The optimization of PDMS ratio and the vacuum degassing process together ensure the integrity and stability of the microchannel structure, realizing high-fidelity 3D microstructure replication.

[0019] In step (4), the alkaline solution is a 3-8% (w / w) NaOH, KOH, or Na2CO3 solution; more preferably, a 5% NaOH solution; the hydrolysis temperature is 80-90 °C, and the time is 5-7 h. Under these conditions, the template can be completely hydrolyzed without damaging the PDMS; if the alkaline concentration or temperature is below this range, the template will not be completely removed, leaving residues that block the channels; if the concentration or temperature is too high, or the time is too long, the PDMS surface may be damaged, roughened, or even develop microcracks, affecting the optical and mechanical properties of the microchannels. The gentle alkaline hydrolysis ensures complete template removal while avoiding damage to the PDMS chip structure, achieving high-fidelity 3D microchannel replication.

[0020] The microfluidic chips obtained by the above methods can be used in organ-on-a-chip, biosensors, wearable devices, or liquid control systems.

[0021] Beneficial effects: Compared with the prior art, the present invention achieves the following significant effects:

[0022] (1) The method of using hydrolyzable sacrificial templates eliminates the need for mechanical demolding and is suitable for complex closed or suspended structures; high-precision construction of micron-level structures is achieved by using high-resolution 3D printing, breaking through the resolution and geometric limitations of traditional planar lithography; it adapts to the processing requirements of flexible materials, and the obtained chips have good deformation capabilities and biocompatibility; the processing flow is highly versatile and suitable for rapid prototyping and large-scale replication; (2) The method of this invention has advantages such as high structural accuracy, applicability to flexible materials, and controllable template removal, and is particularly suitable for constructing flexible microfluidic chips with unidirectional liquid transport, 3D confined structure or functional integration features, and is suitable for application in cutting-edge microfluidic application scenarios such as organ-on-a-chip, biosensing, and liquid patterning manipulation; (3) This invention effectively solves the problems of poor adaptability and repeatability of traditional processes in the manufacturing of flexible high-precision chips, and provides an innovative and efficient solution for the manufacturing of microfluidic chips. Attached Figure Description

[0023] Figure 1 This is a flowchart of the method according to an embodiment of the present invention;

[0024] Figure 2 This is a diagram of a sacrificial template and a PDMS flexible capillary transistor according to an embodiment of the present invention;

[0025] Figure 3 This is a schematic diagram of the chip structure according to an embodiment of the present invention;

[0026] Figure 4 This is a diagram showing the chip structure parameters and dimensional accuracy of an embodiment of the present invention;

[0027] Figure 5 This is a diagram showing the unidirectional liquid climb of the chip in an embodiment of the present invention;

[0028] Figure 6 This is a diagram illustrating liquid transport in a complex 3D space using a chip according to an embodiment of the present invention.

[0029] Figure 7 This is a demonstration diagram of chip oil-water separation in an embodiment of the present invention;

[0030] Figure 8 This is a schematic diagram of a dual-channel membrane structure microfluidic chip that the method of the present invention is applicable to processing;

[0031] Figure 9 This is a schematic diagram of a serpentine channel structure microfluidic chip that the method of the present invention is applicable to processing;

[0032] Figure 10 This is a schematic diagram of a microfluidic chip with an infusion-type 3D network structure that is suitable for processing using the method of the present invention;

[0033] Figure 11 This is a schematic diagram of a 3D spiral structure microfluidic chip that the method of the present invention is applicable to. Detailed Implementation

[0034] The present invention will now be described in further detail.

[0035] like Figure 1 , 2 As shown, the present invention provides a microfluidic chip fabrication method based on a sacrificial template, comprising the following steps:

[0036] (1) Construction of 3D sacrificial template: A 3D sacrificial template with microchannel structure was prepared by using a photosensitive resin containing hydrolyzable material, the main components of which are polyethylene glycol diacrylate (PEGDA) 60 wt%, acryloyloxyethyltrimethylammonium chloride (AETAC) 39 wt%, and photoinitiator (DMPA) 1 wt%. The printing parameters are shown in Table 1 below.

[0037] (2) Template post-processing: The printed templates were subjected to standard post-processing in sequence. Each round included: cleaning with isopropanol (analytical grade, purity ≥99.7%, Sinopharm Chemical Reagent Co., Ltd.) for 30 min, UV curing for 1 h, and heat treatment at 60℃ for 4 h; the number of post-processing cycles is shown in Table 1 below.

[0038] (3) Casting: The polydimethylsiloxane (PDMS, Sylgard 184, Dow Corning, USA) prepolymer and curing agent were thoroughly mixed at the mass ratio and then injected into the post-treated sacrificial template. Subsequently, the mixture was degassed in a vacuum dryer (Changde Bickman Biotechnology Co., Ltd.) for 1 h and cured at 60 ℃ for 4 h to form a PDMS microstructure that is completely replicated with the sacrificial template; the mass ratio of PDMS to curing agent is shown in Table 1 below.

[0039] (4) Template removal: The cured sample was placed in an aqueous solution of 5 wt% sodium hydroxide (analytical grade, purity ≥96%, Sinopharm Chemical Reagent Co., Ltd.) at 85 ℃ for hydrolysis, thereby obtaining the required 3D channel structure in PDMS; the hydrolysis time is shown in Table 1 below.

[0040] The relevant parameters and results of each embodiment are shown in Table 1 below:

[0041] Table 1

[0042]

[0043]

[0044] Based on the results of the above embodiments, the chips of embodiments 24–68 are obtained by following the steps below:

[0045] (1) Construction of 3D sacrificial template: A 3D sacrificial template with microchannel structure was prepared by using a photosensitive resin containing hydrolyzable material, with the main components being polyethylene glycol diacrylate (PEGDA) 60 wt%, acryloyloxyethyltrimethylammonium chloride (AETAC) 39 wt%, and photoinitiator (DMPA) 1 wt%. The exposure time was 18 s and the layer thickness was 25 μm.

[0046] (2) Template post-processing: The printed template is subjected to two rounds of processing cycles, each round including: isopropanol (analytical grade, purity ≥99.7%, Sinopharm Chemical Reagent Co., Ltd.) cleaning for 30 min, UV curing for 1 h and heat treatment at 60℃ for 4 h;

[0047] (3) Casting: The polydimethylsiloxane (PDMS, Sylgard 184, Dow Corning, USA) prepolymer and curing agent are thoroughly mixed at a mass ratio of 10:1 and then injected into the post-treated sacrificial template; subsequently, the mixture is degassed in a vacuum dryer (Changde Bickman Biotechnology Co., Ltd.) for 1 h and cured at 60 ℃ for 4 h to form a PDMS microstructure that is completely replicated with the sacrificial template.

[0048] (4) Template removal: The cured sample was placed in an aqueous solution of 5 wt% sodium hydroxide (analytical grade, purity ≥96%, Sinopharm Chemical Reagent Co., Ltd.) at 85 ℃ for 6 h to hydrolyze and obtain the required 3D channel structure in PDMS.

[0049] The obtained chip was subjected to structural dimensional accuracy and repeatability verification. The chip structure is as follows: Figure 3 As shown, the chip includes a rectangular substrate on which a regularly arranged array of microstructures is mounted. The microstructure array consists of several parallel strip-shaped protrusions, each extending along the length of the chip. Each protrusion has a stepped or trapezoidal cross-section, and adjacent protrusions are spaced equidistantly, forming a periodic surface structure. Each microjunction unit has a rectangular opening. Figure 4 As shown, the chip's geometric parameters were scanned and measured, including tilt angle θ, length a, front-to-back spacing b, lateral microchannel width d, gap height e, and thickness h. The results of each embodiment are as follows:

[0050] 1. Under the conditions of fixed structure length a = 1200 μm, front-to-back structural spacing b = 1170 μm, lateral microchannel width d = 200 μm, structure thickness h = 280 μm, and structural gap e = 130 μm, the results are shown in Table 2 below:

[0051] Table 2

[0052]

[0053] 2. Under the conditions of a fixed tilt angle θ=60°, front-to-back structural spacing b=1170 μm, lateral microchannel width d=200 μm, structural thickness h=280 μm, and structural gap e=130 μm, the results are shown in Table 3 below:

[0054] Table 3

[0055]

[0056] 3. Under the conditions of a fixed tilt angle θ=60°, structural length a=1200μm, transverse microchannel width d=200μm, structural thickness h=280μm, and structural gap e=130μm, the results are shown in Table 4 below:

[0057] Table 4

[0058]

[0059] 4. Under the conditions of a fixed tilt angle θ = 60°, structural length a = 1200 μm, front-to-back structural spacing b = 1170 μm, structural gap e = 130 μm, and transverse microchannel width d = 200 μm, the results are shown in Table 5 below:

[0060] Table 5

[0061]

[0062] 5. Under the conditions of a fixed tilt angle θ=60°, structural length a=1200 μm, front-to-back structural spacing b=1170 μm, lateral microchannel width d=200 μm, and structural thickness h=280 μm, the results are shown in Table 6 below:

[0063] Table 6

[0064]

[0065] As can be seen, the chip of the present invention has good size consistency and high replication accuracy, making it suitable for microfluidic applications with high repeatability requirements.

[0066] The chips obtained in the above embodiments were tested as follows:

[0067] (1) Verification of liquid unidirectional climbing performance. For example... Figure 5 As shown, the end of a flexible capillary transistor was inserted into anhydrous ethanol, and the liquid climbing height was recorded. The results demonstrate that the chip can achieve unidirectional liquid climbing under capillary actuation. Without any external driving force, ethanol can achieve a maximum unidirectional climbing height of 37.0 mm in the chip's capillary structure, with good directional selectivity in the flow direction.

[0068] (2) Flexible curved surface liquid transport. For example... Figure 6 As shown, when the chip is bent into an "S" shape, a single spiral, or wrapped around the inner wall of a glass rod, ethanol is injected through the port, and the liquid can still achieve unidirectional transport along the suspended structure without backflow. Even in complex 3D curved surface environments, the chip can still maintain continuous liquid transport, demonstrating its high flexibility and adaptability.

[0069] (3) Oil-water separation applications. For example... Figure 7 As shown, dimethyl silicone oil and water are simultaneously dropped onto the chip surface. The oil phase rises unidirectionally along the suspended structure, while the water droplets remain in place. Further bending the chip into an arch shape and placing it between the oil and water mixture, the oil phase is self-driven and collected into a container on one side, while the water remains on the other side, achieving oil-water separation without external drive.

[0070] In addition to the flexible capillary transistors shown in the above embodiments, the method of the present invention can also be used to fabricate other types of microfluidic chips. For example, such as Figure 8 As shown, this method can fabricate dual-channel membrane structure microfluidic chips; Figure 9 As shown, microfluidic chips with serpentine channel structures can be fabricated; such as Figure 10 As shown, microfluidic chips with infused 3D network structures can be fabricated; such as Figure 11 As shown, microfluidic chips with 3D helical structures can be fabricated.

[0071] In summary, this invention successfully replicates high-precision 3D suspended microstructures in PDMS using a sacrificial printing template, forming flexible capillary transistors. Examples demonstrate that the method of this invention can stably achieve structure replication within a range of process parameters, including exposure time, layer thickness, post-processing cycle count, PDMS to curing agent mass ratio, and hydrolysis time, exhibiting good adaptability and process window. The prepared flexible chip not only demonstrates excellent performance in unidirectional liquid climbing height enhancement, complex curved surface transport, and oil-water separation, but also reliably guarantees structural dimensional accuracy and repeatability. Compared with existing technologies, this invention simultaneously possesses high-resolution molding, flexible adaptability, and multifunctional liquid control capabilities, making it suitable for various applications such as microfluidic chips, flexible liquid transport, environmental engineering, and biological detection.

Claims

1. A method for fabricating a microfluidic chip based on a sacrificial printing template, characterized in that, The method comprises the following steps: (1) using a hydrolysable photosensitive resin, a 3D sacrificial template with microchannel structure is obtained by photocuring 3D printing; (2) the 3D sacrificial template is treated by at least two cycles, each cycle comprising organic polar solvent cleaning, UV curing and heat treatment in sequence, to remove unreacted components and improve the stability of the template; (3) mixing elastomer prepolymer and curing agent, injecting into the 3D sacrificial template obtained in step (2), defoaming in vacuum environment, curing to obtain the required microstructure; (4) using alkaline aqueous solution to hydrolyze the template obtained in step (3), removing the template to obtain a microfluidic chip with 3D microchannels.

2. The sacrificial print template based microfluidic chip fabrication method according to claim 1, wherein, In step (3), the mass ratio of elastomer prepolymer to curing agent is 5-20:

1.

3. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (2), the time for organic polar solvent cleaning is 20-40 min; the time for UV curing is 0.5-1.5 h; the heat treatment temperature is 50-70 ℃, and the heat treatment time is 3-5 h.

4. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (3), the curing temperature is 50-70 ℃, and the time is 3-6 h.

5. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (3), the defoaming time in vacuum environment is 0.5-1.5 h.

6. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (4), the alkaline solution is a 3-8% NaOH solution, a KOH solution or a Na2CO3 solution by mass fraction; the hydrolysis temperature is 80-90 ℃, and the time is 5-7 h.

7. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (1), the hydrolysable photosensitive resin is acryloyloxyethyl trimethyl ammonium chloride and / or polyethylene glycol diacrylate.

8. The sacrificial print template based microfluidic chip fabrication method of claim 1, wherein, In step (1), the photocuring 3D printing is one of liquid crystal display printing, stereolithography printing, digital light processing printing or two-photon polymerization printing.

9. The sacrificial print template based microfluidic chip fabrication method of claim 8, wherein, When using liquid crystal display printing, the exposure time is controlled at 16-18 s, and the layer thickness is 10-50 μm; when using stereolithography printing or digital light processing printing, the layer thickness is controlled at 10-50 μm, and the exposure time is 3-8 s; when using two-photon polymerization printing, the layer thickness can be controlled in the range of sub-micron to 5 μm.

10. The use of a microfluidic chip obtained by the method of claim 1 in an organ chip, a biosensor, a wearable device or a liquid control system.

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