A multifunctional microfluidic chip based on bulk acoustic wave

Abstract

The present invention belongs to the technical field of microfluidic chips, and provides a multifunctional microfluidic chip based on bulk acoustic waves, which is a microfluidic chip based on bulk acoustic waves for particle concentration, cleaning and liquid replacement. The system includes a microchannel structure and a piezoelectric transducer disposed in the chip body. The microchannel structure includes an inlet region, a focusing region, a sorting region and an outlet region, and the piezoelectric transducer is bonded to the bottom of the chip. Sample liquids containing particles are introduced through the two side inlets of the inlet region, and another sample liquid without particles is introduced through the central inlet; the focusing region is used to achieve particle focusing and replacement of the solution where the particles are located; the sorting region is used to achieve sorting of target particles and high-magnification concentration of liquids; the liquids in the outlet region flow into different flow paths for collection. The present invention can efficiently achieve cleaning and high-magnification concentration of biochemical sample particles, can be applicable to rapid processing of various complex samples, and can be widely applied in fields such as biopharmaceuticals and environmental monitoring.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidic chips, and particularly relates to a multifunctional microfluidic chip based on bulk acoustic waves. Background Art

[0002] Acoustofluidics technology is a technology that uses acoustic radiation force generated inside microfluidics by acoustic waves to manipulate and separate substances such as fluids, particles, and cells. When acoustic waves interact with a medium on a chip, acoustic streaming drag force and acoustic radiation force will be generated. The combined action of these acoustic forces on particles will cause them to move towards the nodes of the standing wave field. Using this principle, cell sorting can be carried out.

[0003] The Zweich Fung effect refers to the fact that when a particle is located at a flow channel bifurcation, if the flow velocities of the two bifurcated flow channels are different, the particle will be affected by the shear force and flow towards the faster-flowing channel, and the larger the particle, the greater the shear force it receives. When performing particle sorting, the larger the particle size, the greater the acoustic field force it receives, and the greater the shear force it receives. Therefore, by combining the above two effects, efficient sorting can be achieved.

[0004] Existing sorting technologies need to set multiple piezoelectric transducers or interdigital electrodes on the same chip to separately achieve pretreatment and sorting. This not only makes the manufacturing process more complex, but also different transducers may interfere with each other, lacking a simple and efficient solution to simultaneously achieve high-throughput sorting and high-fold concentration of particles. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to propose a multifunctional microfluidic chip based on bulk acoustic waves for the replacement of the liquid to which the particles belong, the sorting of different particles, and the high-fold concentration of the solution by combining the acoustic field force and the Zweifach-Fung effect.

[0006] To solve the above technical problems, the technical solution adopted by the present invention is:

[0007] A multifunctional microfluidic chip based on bulk acoustic waves for enriching particles, replacing the liquid to which the particles belong, and highly concentrating the particles in a solution. The multifunctional microfluidic chip includes a flow channel structure 9 in a chip body 1 and a piezoelectric transducer 8 for driving the movement of particles. Along the particle flow direction on the main flow channel of the flow channel structure 9, an inlet area 2, a focusing area 3, a sorting area 4, and an outlet area 5 that are interconnected are sequentially arranged. The chip body 1 includes a substrate 7 and a cover plate 6. A square concave channel is processed on the upper surface of the substrate 7, and the cover plate 6 is hermetically attached to the substrate 7 so that the channel between the cover plate 6 and the substrate 7 forms the flow channel structure 9. The piezoelectric transducer 8 can generate a bulk acoustic wave standing wave perpendicular to the particle flow direction. The chip flow channel structure is symmetric about the center line.

[0008] The described inlet area 2 includes three inlets. After the three inlets converge, they are connected to the main channel 13 of the focusing area 3. The two side inlets 10 and 12 are used to introduce the sample liquid containing particles, where the particles include large particles and small particles. The central inlet 11 is used to introduce another sample liquid without particles. The present invention can transfer the large particles in the two side sample liquids into the other pure sample liquid in the center.

[0009] The described focusing area 3 is used to achieve the focusing of particles to the center position of the flow channel and the replacement of the solution in which the particles are located; specifically: it is used to achieve the focusing of particles in the main channel 13. At the entrance of the main channel 13, the two sides of the fluid are the sample liquid containing particles, and the center is another sample liquid without particles. As the fluid flows, the large particles in the sample liquids on both sides of the main channel 13 are transferred and focused into the central sample liquid under the action of the larger acoustic field force generated by the piezoelectric transducer 8, while the small particles are subjected to a smaller acoustic field force and remain in the liquids on both sides of the main channel 13, thereby realizing the replacement of the solution in which the large particles are located.

[0010] The described sorting area 4 is used to achieve the sorting of particles with different particle sizes and the high magnification concentration of the liquid in the main channel. The intersection of the focusing area 3 and the sorting area 4 is connected to the separation channels 24 / 25 through two side channels on both sides of the main channel 13. The separation channels 24 / 25 are located on both sides of the main channel 13 and are parallel to the main channel 13. In the sorting area, the main channel is connected to the separation channels on both sides through the side channels arranged at equal intervals. Due to the combined action of the Zweifach-Fung effect and the acoustic field force, the sample liquid outside the central main channel 13 and the small particles contained therein will flow into the separation channels from the side channels, while the large particles located at the center position of the central main channel 13 flow out from the central outlet.

[0011] The described outlet area 5 also includes three outlets, corresponding to the three inlets of the inlet area 2; its two side outlets collect the sample liquid containing small particles, and the central outlet collects the high-concentration sample liquid containing large particles.

[0012] Further, the piezoelectric transducer 8 is bonded to the lower surface of the substrate 7 or the upper surface of the cover sheet 6.

[0013] Further, the width of the main channel 13 is equal to half of the wavelength of the bulk acoustic wave excited by the piezoelectric transducer 8 on the substrate, and the acoustic pressure node of the standing wave field inside the focusing channel coincides with the center line of the central main channel 13.

[0014] Further, the width of the separation channel in the sorting area 4 is greater than that of the central main channel 13, and the width of the central main channel 13 is greater than that of each side channel. The center main channel 13 in the sorting area 4 has the same size as the main channel 13 in the focusing area 3.

[0015] Further, a plurality of side channels are provided on both sides of the central main channel 13 in the sub-selection area, and the side channels jointly lead to the separation channel.

[0016] Further, the piezoelectric transducer 8 is a piezoelectric ceramic.

[0017] Further, the substrate 7 is made of a silicon wafer, and the cover sheet 6 can be made of materials such as glass, plastic, or polymer.

[0018] Further, in the sample liquid containing particles, the particles include fine particles made of organic or inorganic materials, or biological cells.

[0019] Further, at least one piezoelectric transducer 8 is provided in the focusing area 3 for aggregating the particles to the center of the main channel 13.

[0020] The beneficial effects of the present invention are as follows:

[0021] (1) The present invention can simultaneously achieve the replacement of the liquid to which the particles belong, the sorting of different particles, and the high-magnification concentration of the liquid in which the particles are located. The liquid particle concentration collected from the central outlet can be increased by 9 - 10 times compared with the liquid particle concentration flowing in at the inlet.

[0022] (2) The present invention only needs one piezoelectric transducer to control the movement of the particles, and the acoustic radiation force always plays a focusing role on the particles located in the main channel, enabling a high sample processing throughput.

[0023] (3) The present invention combines acoustic fluidics and a channel structure, and through the combined action of the acoustic field force and the Zweifach-Fung effect, it can non-contact control the movement of the particles and is well applicable to various biological cells. Description of the Drawings

[0024] Figure 1 is a schematic diagram of the principle of the multifunctional microfluidic chip based on bulk acoustic waves of the present invention.

[0025] Figure 2 is a partial schematic diagram of the principle of the sub-selection area of the multifunctional microfluidic chip based on bulk acoustic waves of the present invention.

[0026] Figure 3 is a schematic diagram of the structure of the multifunctional microfluidic chip based on bulk acoustic waves of the present invention.

[0027] Figure 4 is a schematic diagram of the side view structure of the multifunctional microfluidic chip based on bulk acoustic waves of the present invention.

[0028] Figure 5 is a regional division diagram of the multifunctional microfluidic chip based on bulk acoustic waves of the present invention.

[0029] Figure 6It is a schematic diagram of the microchannel structure of the multi-functional microfluidic chip based on bulk acoustic waves of the present invention.

[0030] Explanation of reference numerals: 1 Chip body; 2 Inlet area; 3 Focusing area; 4 Sorting area; 5 Outlet area; 6 Cover plate; 7 Substrate; 8 Piezoelectric transducer; 9 Channel structure; 10, 11, 12 Sampling ports; 13 Main channel; 14 - 23 Side channels, 24, 25 Separation channels; 26, 27, 28 Collection ports. Detailed implementation manners

[0031] The following further elaborates on the present invention in conjunction with embodiments, so that those skilled in the art can implement it with reference to the text of the specification.

[0032] Refer to Figure 1 , Figure 2 , Figure 3 A multi-functional microfluidic chip based on bulk acoustic waves in this embodiment includes a piezoelectric transducer 8 for driving the movement of particles and a channel structure 9 provided in the chip body 1. Along the particle flow direction on the main channel of the channel structure 9, an inlet area 2, a focusing area 3, a sorting area 4, and an outlet area 5 are sequentially arranged.

[0033] The depth of the chip channel structure 9 is 100 microns, the width of the main channel 13 is 375 microns, and the length is 23 mm; the width of the side channels in the sorting area is 200 microns, the length is 1 mm, the distance between each side channel is 4 mm, the width of the separation channel is 3.5 mm, and the length is 6 mm; the resonance frequency of the piezoelectric transducer is 2 MHz.

[0034] The focusing area 3 is used to achieve the focusing of particles in the main channel and the replacement of the solution in which they are located, and the sorting area 4 is used to achieve the sorting of target particles and the high - magnification concentration of the liquid in the main channel 13.

[0035] The piezoelectric transducer 8 can generate a bulk acoustic wave standing wave perpendicular to the particle flow direction, so that the large particles in the liquids on both sides are focused into another sample liquid located in the center, realizing the replacement of the liquid in which they are located. The small particles remain on both sides due to the relatively small acoustic radiation force they receive; the solution on both sides of the central channel and the small particles in the solution in the sorting area 4 flow into the separation channels 14 - 23, and the solution and large particles located in the center will remain in the central channel 13. The above is the overall concept of the present invention. The following provides more specific embodiments for further illustration.

[0036] In this embodiment, the chip body 1 includes a substrate 7 and a cover plate 6. The substrate 7 is made of a silicon wafer. A square groove is etched on the top of the substrate 7. The cover plate 6 is hermetically attached to the substrate 7, so that the pipe groove between the cover plate 7 and the substrate 6 forms the channel structure 9. The cover plate 6 can be made of glass material.

[0037] The microfluidic chip can be used to separate blood cells and pathogens in human blood. The size of human blood cells is generally 6 - 10 microns, and the size of pathogens is generally 1 - 2 microns. Before the experiment, a certain amount of phosphate buffered saline (PBS) is first added to the blood sample to ensure its activity. The processed blood sample is introduced through the two side inlets 10 and 12 on both sides of the inlet area 2, and pure PBS buffer solution is introduced through the central inlet 11. Since the channel size is in the micron range, the Reynolds number of the fluid is very low, and the flow of the fluid in the channel exhibits laminar flow characteristics. The blood and the PBS buffer solution basically do not mix.

[0038] A piezoelectric transducer 8 is provided on the lower surface of the substrate 7 or the upper surface of the cover plate 6. When the piezoelectric transducer 8 vibrates, standing wave nodal lines are generated in the width direction of the central channel 13, and the particles in the blood move towards the center position of the channel under the action of the acoustic radiation force. The blood cells in the blood introduced from both sides are subjected to a larger acoustic field force and are transferred into the central PBS buffer solution, while the pathogens are subjected to a smaller acoustic field force and remain in the blood on both sides of the channel.

[0039] Affected by the Zweifach - Fung effect, particles tend to flow into the faster - flowing channel at the bifurcated channel. At the bifurcations on both sides of the chip sorting area, the size of the main channel is wider than that of the side channels. Therefore, the flow resistance of the main channel is less than that of the side channels, and the flow rate is greater than that of the side channels. The blood cells located at the bifurcation are subjected to the shear force perpendicular to the channel direction and flow into the faster - flowing main channel. A large amount of solution will flow into the side channels 14 - 23, and high - magnification concentration of the liquid in the main channel can be achieved.

[0040] In the sorting area 4, under the combined action of the acoustic field force and the Zweifach - Fung effect, the blood cells located in the main channel are subjected to a larger acoustic field force and shear force pointing towards the center of the channel, while the pathogens are subjected to smaller acoustic field force and shear force. The fluid on both sides of the central channel 13 and the pathogens in the fluid will flow into the separation channels 24 - 25 from the side channels 14 - 23, and the blood cells located in the central channel 13 will remain in the central channel.

[0041] When at the bifurcations of the side channels 14 - 23, due to a large amount of liquid flowing into the two side channels on both sides, the blood cells located at the center of the central channel 13 will diffuse to both sides along with the liquid. The piezoelectric transducer 8 still generates an acoustic radiation force in the central channel 13 of the sorting area. The blood cells gather at the center position of the central channel under the action of the acoustic field force and the shear force. The blood cells experience a cycle of diffusion and focusing in the sorting area 4. The pathogens are subjected to smaller acoustic field force and shear force, are more difficult to be gathered to the center of the channel 13, and are more likely to flow into the separation channels 24 - 25 from the side channels 14 - 23, thus being separated from the blood cells.

[0042] Finally, a solution containing only blood cells will be collected at the outlet 27, and the concentration of blood cells is 10 times higher than that of the blood flowing in at the inlet 10, which is convenient for subsequent applications such as disease detection. Solutions containing only germs will be collected at the outlets 26 and 28.

[0043] In summary, based on acoustofluidics and the Zweifach-Fung effect, through the design of the bulk acoustic wave standing wave pressure field and the flow channel structure of the sorting area, the present invention can not only achieve the sorting of particles with different particle sizes, but also achieve the focusing and high magnification concentration of particles.

[0044] The above are only the embodiments of the present invention, and do not limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the specification and drawings of the present invention, or directly or indirectly applied in other related technical fields, shall be equally included in the patent protection scope of the present invention.

Claims

1. A multifunctional microfluidic chip based on bulk acoustic wave, characterized in that, The described multifunctional microfluidic chip is used for enriching particles, replacing the liquid to which the particles belong, and highly concentrating the particles in the solution. The multifunctional microfluidic chip includes a flow channel structure (9) in a chip body (1) and a piezoelectric transducer (8) for driving the movement of particles. The described chip body (1) includes a substrate (7) and a cover plate (6). A square concave channel is machined on the upper surface of the substrate (7), and the cover plate (6) is hermetically attached to the substrate (7) so that the channel between the cover plate (6) and the substrate (7) forms a flow channel structure (9). The piezoelectric transducer (8) can generate a bulk acoustic wave standing wave perpendicular to the particle flow direction. The chip flow channel structure is symmetric along the center line. In the described flow channel structure (9), an inlet area (2), a focusing area (3), a sorting area (4), and an outlet area (5) that are interconnected are sequentially arranged on the main channel (13) along the particle flow direction. The described focusing area (3) is used to achieve the focusing of particles to the center position of the flow channel and the replacement of the solution in which the particles are located, and transfer the large particles in the sample liquids on both sides to another pure sample liquid in the center. The described sorting area (4) is used to achieve the sorting of particles with different particle sizes and the high magnification concentration of the liquid in the main channel. The described inlet area (2) includes three inlets. After the three inlets converge, they are connected to the main channel (13) of the focusing area (3). The two side inlets (10), (12) on both sides are used to introduce the sample liquid containing particles, where the particles include large particles and small particles, and the central inlet (11) is used to introduce another sample liquid without particles. In the described focusing area (3): at the inlet of the main channel (13), the fluids on both sides are the sample liquid containing particles, and the center is another sample liquid without particles. As the fluid flows, the large particles in the sample liquids on both sides of the main channel (13) are transferred and focused into the central sample liquid by the acoustic field force generated by the piezoelectric transducer (8), while the small particles remain in the liquids on both sides of the main channel (13), thereby realizing the replacement of the solution in which the large particles are located. At the intersection of the focusing area (3) and the sorting area (4), two side channels are connected to the separation channels (24 / 25) on both sides of the main channel (13). The separation channels (24 / 25) are located on both sides of the main channel (13) and are parallel to the main channel (13). In the sorting area, the main channel is connected to the separation channels on both sides through side channels arranged at equal intervals. Due to the combined action of the Zweifach-Fung effect and the acoustic field force, the sample liquid outside the central main channel (13) and the small particles contained therein will flow into the separation channels from the side channels, while the large particles located at the center position of the central main channel (13) flow out from the central outlet. The described outlet area (5) also includes three outlets, corresponding to the three inlets of the inlet area (2). The two side outlets collect the sample liquid containing small particles, and the central outlet collects the high-concentration sample liquid containing large particles.

2. The multifunctional microfluidic chip based on bulk acoustic wave according to claim 1, wherein The described piezoelectric transducer (8) is bonded to the lower surface of the substrate (7) or the upper surface of the cover plate (6).

3. A multifunctional microfluidic chip based on bulk acoustic waves according to claim 1, characterized in that, The width of the main channel (13) is equal to half of the wavelength of the bulk acoustic wave excited by the piezoelectric transducer (8) on the substrate, and the sound pressure node of the standing wave field inside the focusing channel coincides with the center line of the central main channel (13).

4. A multifunctional microfluidic chip based on bulk acoustic waves according to claim 1, characterized in that The width of the separation channel in the selected separation area (4) is greater than that of the central main channel (13), and the width of the central main channel (13) is greater than that of each side channel; the central main channel (13) in the selected separation area (4) has the same size as the main channel (13) in the focusing area (3).

5. A multifunctional microfluidic chip based on bulk acoustic waves according to claim 1, characterized in that, The piezoelectric transducer (8) is a piezoelectric ceramic.

6. A multifunctional microfluidic chip based on bulk acoustic wave according to claim 1, characterized in that, The substrate (7) is a silicon wafer, and the cover plate (6) is glass, plastic or polymer.

7. A multifunctional microfluidic chip based on bulk acoustic waves according to claim 1, characterized in that In the sample liquid containing particles, the particles include fine particles made of organic or inorganic materials, or biological cells.

8. A multifunctional microfluidic chip based on bulk acoustic waves according to claim 1, characterized in that, At least one piezoelectric transducer (8) is arranged in the focusing area (3) for aggregating the particles to the center of the main channel (13).

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