Micro-fluidic chip driven by acoustic excitation droplet-shaped microbubbles and manufacturing process of micro-fluidic chip driven by acoustic excitation droplet-shaped microbubbles

Abstract

The invention relates to a micro-fluidic chip driven by sound excitation droplet-shaped micro-bubbles and a manufacturing process of the micro-fluidic chip. A droplet-shaped microbubble array is obtained through the structural design of the micro-fluidic chip, microbubbles oscillate under the excitation of sound waves to generate asymmetric sound flow vortexes, and then a directional driving effect is generated on microfluid in a micro-channel. The flow velocity can be linearly controlled by adjusting the driving voltage, and the device has the advantages of non-contact, no pollution, efficient directional driving and the like. The manufacturing process is based on the MEMS technology, adopts nitrogen plasma bonding and soft photoetching processes, and is low in cost and suitable for batch production. The invention solves the problem that the traditional symmetrical acoustic streaming vortex lacks directivity, and can be widely applied to the fields of biomedicine, drug delivery, chemical analysis and the like.

Description

Technical Field

[0001] The present invention belongs to the field of microfluid drive technology, and particularly relates to a microfluidic chip and a manufacturing process thereof, in which droplet-shaped microbubbles are oscillated by acoustic wave excitation and the oscillating microbubbles drive microfluids. Background Art

[0002] Microfluidics offers advantages such as low sample consumption, high integration, and rapid response times, and has broad application prospects in the biomedical field, including drug delivery and cell analysis. Acoustofluidics, driven by acoustic vortices generated by microbubbles stimulated by sound waves, offers the advantages of being contactless and pollution-free.

[0003] In microbubble-based acoustofluidic systems, controlling the microbubble morphology is crucial for driving the microfluidics. However, existing technologies often employ symmetrical structures, such as spherical or hemispherical microbubbles, to excite acoustic waves. The resulting acoustic flow is typically a symmetrical vortex, which has a weak directional gradient and is difficult to achieve directional driving of microfluidics. This significantly limits the application of acoustically excited microbubbles in microfluidic actuation. Summary of the Invention

[0004] This invention proposes a microfluidic chip driven by acoustically stimulated droplet-shaped microbubbles and its fabrication process. By designing an array of droplet-shaped microgrooves at the bottom of the microchannel, when liquid is injected into the microchannel, surface tension causes the droplet-shaped microbubbles to self-close in the microgrooves, forming droplet-shaped microbubbles. Acoustic waves then excite the microbubbles, causing them to oscillate and generate asymmetric acoustic vortices. This asymmetry of the acoustic flow is exploited to achieve directional drive of the microfluidic system.

[0005] The present invention provides a technical solution to solve the above technical problems:

[0006] A microfluidic chip driven by acoustically excited droplet-shaped microbubbles comprises a glass substrate (1), a groove layer (2), a flow channel layer (3), a liquid inlet pipe (4), a liquid outlet pipe (5), and a piezoelectric transducer (6).

[0007] The groove layer (2) is fabricated on a glass substrate (1) by a soft photolithography process, and an array of droplet-shaped grooves (9) is designed on the groove layer (2). The large end arc radius of the droplet-shaped grooves (9) is 50-100 μm, the small end sharp angle angle is 30-90°, and the groove depth is 100-150 μm.

[0008] The flow channel layer (3) is fixed to the upper surface of the groove layer (2) through a bonding process, wherein the flow channel layer (3) is designed with a microchannel (10) structure for limiting the liquid flow area;

[0009] The liquid inlet pipe (4) and the liquid outlet pipe (5) are respectively connected to the two end ports of the microchannel (10) of the channel layer (3), wherein the liquid inlet pipe (4) is used for injecting liquid, and the liquid outlet pipe (5) is used for discharging liquid;

[0010] The piezoelectric transducer (6) is fixed on the upper surface of the glass substrate (1), wherein the piezoelectric transducer (6) is used to generate sound waves of specific frequency and amplitude, so that the microbubbles (11) oscillate under the excitation of the sound waves, thereby generating asymmetric acoustic flow vortices (12) near the microbubbles (11), and directionally driving the microfluid in the microchannel.

[0011] The microbubbles (11) are affected by the surface tension of the liquid. When the liquid flows through the drop-shaped groove (9), part of the gas is spontaneously sealed in the groove to form microbubbles (11). Under the restriction of the drop-shaped groove (9), the microbubbles (11) are drop-shaped. The large end curvature radius of the drop-shaped microbubbles (11) is 50-100 μm, the small end curvature radius is 10-20 μm, and the long axis length is 170-240 μm.

[0012] The method for using the acoustically excited droplet-shaped microbubble-driven microfluidic chip is as follows:

[0013] Liquid is injected through the liquid inlet pipe (4), and when the liquid flows through the drop-shaped groove (9) of the groove layer (2), microbubbles (11) are spontaneously formed under the action of the liquid surface tension and are confined in the drop-shaped groove;

[0014] The piezoelectric transducer (6) is connected to a driver and inputs a sinusoidal voltage that is consistent with the resonant frequency of the microbubbles (11). The driving voltage amplitude is adjusted, and the piezoelectric transducer (6) vibrates to generate sound waves. The microbubbles (11) oscillate under the excitation of the resonant sound waves, thereby generating asymmetric acoustic vortices (12) in their vicinity.

[0015] The fluid in the microchannel is acted upon by the acoustic vortex (12), thereby achieving directional driving from the large end to the small end of the droplet-shaped microbubble (11);

[0016] The speed of driving the microfluid can be controlled by adjusting the driving voltage, and the driving speed is linearly related to the driving voltage.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) The droplet-shaped microbubbles in the microfluidic chip of the present invention generate asymmetric acoustic vortices under acoustic wave excitation, breaking through the limitations of traditional symmetrical acoustic vortices and achieving directional and efficient driving of microfluids;

[0019] (2) The microfluidic chip of the present invention can accurately and dynamically control the flow rate of the directionally driven microfluid by adjusting the driving voltage;

[0020] (3) The microfluidic chip of the present invention avoids mechanical damage to biological samples through non-contact driving and can be widely used in biomedicine, chemical analysis and other fields;

[0021] (4) The manufacturing process of the microfluidic chip described in the present invention is based on MEMS technology, which can realize mass production, low cost and high reliability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 : Schematic diagram of the structure of the microfluidic chip driven by acoustically excited droplet-shaped microbubbles proposed in the present invention;

[0023] Figure 2 : Schematic diagram of the front view of the microfluidic chip driven by acoustically excited droplet-shaped microbubbles;

[0024] Figure 3 : Schematic diagram of the cross section of a microfluidic chip driven by acoustically excited droplet-shaped microbubbles Figure 1 (The cross section is a horizontal plane passing through the chip flow channel);

[0025] Figure 4 : Schematic diagram of the cross section of a microfluidic chip driven by acoustically excited droplet-shaped microbubbles Figure 2 ;

[0026] Figure 5 : A magnified partial cross-sectional view of the microchannel and microbubbles in a microfluidic chip driven by acoustically excited droplet-shaped microbubbles;

[0027] Figure 6 : Schematic diagram of microbubbles in a microfluidic chip driven by acoustically excited droplet-shaped microbubbles;

[0028] Figure 7 : Schematic cross-sectional view of acoustic vortex and directional drive of microfluidics;

[0029] Figure 8 : Flow chart of the manufacturing process of the groove layer;

[0030] Figure 9 : Flow chart of the production process of the runner layer;

[0031] In the figure: 1 glass substrate, 2 groove layer, 3 flow channel layer, 4 liquid inlet pipe, 5 liquid outlet pipe, 6 piezoelectric transducer, 7 liquid inlet, 8 liquid outlet, 9 droplet-shaped groove, 10 microfluidic channel, 11 droplet-shaped microbubble, 12 acoustic flow vortex, 13 SU-8 negative photoresist GM1070, 14 groove layer mask, 15 flow channel layer mask, 16 flow channel layer mold. DETAILED DESCRIPTION

[0032] To facilitate understanding by those skilled in the art, the present invention is further described below with reference to the accompanying drawings. The contents mentioned in the embodiment are only used to explain the present invention and are not used to limit the scope of the present invention.

[0033] The manufacturing process of a microfluidic chip for driving microfluids by acoustic wave-stimulated droplet-shaped microbubbles includes: a manufacturing process of a groove layer (2), a manufacturing process of a flow channel layer (3), and a bonding assembly process of the groove layer (2) and the flow channel layer (3).

[0034] See also Figure 8 , a flow chart of the manufacturing process of the groove layer of the microfluidic chip driven by acoustically excited droplet-shaped microbubbles of the present invention.

[0035] The manufacturing process of the groove layer (2) is specifically as follows:

[0036] a. Spin-coat a layer of SU-8 negative photoresist GM 1070 (13) with a thickness of 150 μm on a glass substrate (1); first bake on a constant temperature baking table at 65°C for 30 min, then bake on a constant temperature baking table at 95°C for 120 min, and finally cool naturally to room temperature to obtain a solidified SU-8 photoresist;

[0037] b. Place the groove layer mask (14) on the surface of the cured SU-8 photoresist and expose it with an exposure machine at a light intensity of 10 mW / cm 2 , exposure time 3.5min; then, bake on a constant temperature baking table at 65℃ for 15min, bake on a constant temperature baking table at 95℃ for 40min, and finally cool naturally to room temperature to obtain the exposed SU-8 photoresist;

[0038] c. The exposed SU-8 photoresist is rinsed with a developer, and the unexposed part is rinsed away, and then washed with deionized water, leaving a patterned SU-8 photoresist structure; then baked on a constant temperature baking table at 130°C for 120 minutes, and finally cooled naturally to room temperature to obtain a groove layer (2).

[0039] See also Figure 9 , a diagram showing the manufacturing process of the flow channel layer of the microfluidic chip driven by acoustically excited droplet-shaped microbubbles of the present invention.

[0040] The manufacturing process of the flow channel layer (3) is as follows:

[0041] a. Spin-coat a layer of SU-8 negative photoresist GM 1070 (13) with a thickness of 150 μm on a glass substrate (1); first bake the layer at a constant temperature of 65°C for 30 min, then bake the layer at a constant temperature of 95°C for 120 min, and then cool the layer naturally to room temperature to obtain a solidified SU-8 photoresist;

[0042] b. Place the channel layer mask plate (15) on the surface of the cured SU-8 photoresist and expose it through an exposure machine with a light intensity of 10mW / cm 2 , exposure time 3.5min; then, bake on a constant temperature baking table at 65℃ for 15min, then bake on a constant temperature baking table at 95℃ for 40min, and finally cool naturally to room temperature to obtain the exposed SU-8 photoresist;

[0043] c. Using a developer to rinse the exposed SU-8 photoresist, the unexposed portion is washed away, and then rinsed with deionized water, leaving a patterned SU-8 photoresist structure; then baked on a 130°C constant temperature baking table for 120 minutes, and then naturally cooled to room temperature to obtain a flow channel layer mold (16);

[0044] d. Polydimethylsiloxane and curing agent were fully mixed in a mass ratio of 10:1, and bubbles were removed in a vacuum box. Then, the mixture was poured onto the flow channel layer mold (16). After curing, the polydimethylsiloxane was peeled off from the mold to obtain the flow channel layer (3). Then, a biopsy punch was used to punch holes with a diameter of 1000 μm at both ends of the microchannel.

[0045] The bonding assembly process of the microfluidic chip is to perform nitrogen plasma surface treatment on the flow channel layer (3), and the parameters of the nitrogen plasma treatment are set to a gas pressure of 50 Pa, a power of 70 W, and a treatment time of 50 seconds; thereafter, the groove layer (2) and the flow channel layer (3) are tightly attached, and the -NH2 functional group on the surface of the flow channel layer (3) forms a covalent bond -HN-HO- with the epoxy group on the surface of the groove layer (2), so that the groove layer (2) and the flow channel layer (3) are firmly connected;

[0046] Finally, the piezoelectric transducer (6) is adhered to the glass substrate (1) using epoxy glue, and the liquid inlet pipe (4) and the liquid outlet pipe (5) are connected to the liquid inlet (7) and the liquid outlet (8) respectively, thereby completing the production of the microfluidic chip.

[0047] The working principle of the microfluidic chip driven by acoustically excited droplet-shaped microbubbles provided in the embodiment of the present invention is as follows:

[0048] The piezoelectric transducer generates an acoustic wave under the excitation of a sinusoidal signal. The frequency and amplitude of the acoustic wave can be adjusted by the frequency of the input sinusoidal signal and the driving voltage, respectively. The droplet-shaped microbubbles oscillate under the excitation of the acoustic wave at their resonant frequency, and an asymmetric acoustic vortex (12) is generated near them. The acoustic vortex (12) exerts a directional driving effect on the fluid in the microchannel.

[0049] The acoustically excited droplet-shaped microbubbles of the present invention can adjust the flow rate of the driven microfluid by regulating the driving voltage during the process of directionally driving the microfluid.

[0050] The above descriptions are merely embodiments of the present invention and are not intended to limit the scope of the present invention. Any structure or transformation made using the contents of the present invention's description and drawings, or directly or indirectly applied in other related technical fields, are also included in the scope of the present invention's patent protection.

Claims

1. A microfluidic chip driven by acoustically excited droplet-shaped microbubbles, characterized by: It comprises a glass substrate (1), a groove layer (2), a flow channel layer (3), a liquid inlet pipe (4), a liquid outlet pipe (5), and a piezoelectric transducer (6); The groove layer (2) is fabricated on a glass substrate (1) by a soft photolithography process, and an array of droplet-shaped grooves (9) is designed on the groove layer (2); the large end arc radius of the droplet-shaped grooves (9) is 50-100 μm, the small end sharp angle angle is 30-90°, and the groove depth is 100-150 μm; The flow channel layer (3) is fixed to the upper surface of the groove layer (2) through a bonding process, wherein the flow channel layer (3) is designed with a microchannel (10) structure for limiting the liquid flow area; The liquid inlet pipe (4) and the liquid outlet pipe (5) are respectively connected to the two end ports of the microchannel (10) of the channel layer (3), wherein the liquid inlet pipe (4) is used for injecting liquid, and the liquid outlet pipe (5) is used for discharging liquid; The piezoelectric transducer (6) is fixed on the upper surface of the glass substrate (1), wherein the piezoelectric transducer (6) is used to generate sound waves, so that the microbubbles (11) oscillate under the excitation of the sound waves, thereby generating asymmetric acoustic flow vortices (12) near the microbubbles (11), and directionally driving the microfluid in the microchannel.

2. The method for using the acoustically excited droplet-shaped microbubble-driven microfluidic chip according to claim 1, characterized in that: Liquid is injected through the liquid inlet pipe (4), and when the liquid flows through the drop-shaped groove (9) of the groove layer (2), microbubbles (11) are spontaneously formed under the action of the liquid surface tension and are confined in the drop-shaped groove; The piezoelectric transducer (6) is connected to a driver and inputs a sinusoidal voltage that is consistent with the resonant frequency of the microbubbles (11). The driving voltage amplitude is adjusted, and the piezoelectric transducer (6) vibrates to generate sound waves. The microbubbles (11) oscillate under the excitation of the resonant sound waves, thereby generating asymmetric acoustic flow vortices (12) in the vicinity thereof. The fluid in the microchannel is acted upon by the acoustic vortex (12), thereby achieving directional driving from the large end to the small end of the droplet-shaped microbubble (11); The speed of driving the microfluid is controlled by adjusting the driving voltage, and the driving speed is linearly related to the driving voltage.

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