A droplet sorting microfluidic chip and droplet sorting method based on piezoelectric perturbation

Abstract

The present invention discloses a droplet sorting microfluidic chip and a droplet sorting method based on piezoelectric perturbation; the microfluidic chip includes a chip substrate and a unilateral liquid pushing component. A main channel, an annular continuous phase flow channel, a pressure applying cavity, a pressure fluctuation flow channel, a target output flow channel and a balance flow channel are provided on the chip substrate. The annular continuous phase flow channel is connected to the main channel to form a droplet generation area; the intersection of the target output flow channel, the balance flow channel and the main channel forms a sorting area. The unilateral liquid pushing component is embedded and installed in the pressure applying cavity, and includes a mounting tube and a piezoelectric ceramic. The present invention sets a pressure applying cavity in the chip substrate, and directly integrates a unilateral liquid pushing component based on a piezoelectric ceramic structure therein, so that a unilateral thrust can be controllably generated on the droplets in the sorting area, so that the target droplets that need to be sorted separately can be separated from the main droplet queue, and the automatic sorting of the target droplets can be achieved by cooperating with the corresponding target detection device.

Description

Technical Field

[0001] The present invention belongs to the technical field of droplet microfluidic sorting, and in particular relates to a droplet sorting microfluidic chip based on piezoelectric perturbation and a droplet sorting method. Background Art

[0002] In droplet microfluidics, droplet sorting technology can be applied in fields such as biomedicine, chemical analysis, drug screening, and gene sequencing. By adjusting sorting parameters and designing different sorting devices, different types of liquid samples can be sorted and processed. Droplet sorting methods are divided into active and passive methods. Passive sorting uses the geometric properties of the channel itself to sort droplets, usually based on droplet size, while active sorting uses external energy to sort target droplets. This method can be combined with detection technology to sort the desired droplets. Compared with passive sorting, active sorting has better versatility and accuracy. Traditional active methods include electric field sorting and magnetic field sorting, but these methods require special treatment of the droplets. For example, the magnetic field method requires the addition of magnetic field materials inside the droplet, which increases the operating cost. The electric field method has requirements for the dielectric constant of the fluid, which increases the operating cost or the compatibility of the sorting, and the internal environment of the droplet can also be affected.

[0003] Droplet sorting methods based on external mechanical vibrations have higher compatibility with droplets and will not have a significant impact on the internal environment of the droplets. The channels in microfluidic chips are very small, generally at the micron level. In the field of micro-displacement vibration research, piezoelectric ceramics have the advantages of fast response speed, small size, and large load-bearing capacity, making them ideal micro-displacement vibration materials. Moreover, the process of droplet sorting using piezoelectric ceramics is contactless and does not require direct contact with the droplets, thus avoiding the contamination and damage of droplets that may be caused by traditional methods. The energy consumption of piezoelectric ceramics is relatively low, and the driving voltage and power requirements are not high. Therefore, efficient energy consumption can be achieved in the droplet sorting process, which is conducive to saving energy and reducing experimental costs. Therefore, a droplet microfluidic device based on piezoelectric perturbation, easy to process, highly integrated, low cost, and high fluid compatibility needs to be developed. Summary of the Invention

[0004] The object of the present invention is to provide a droplet sorting microfluidic chip and a droplet sorting method based on piezoelectric perturbation.

[0005] In its first aspect, the present invention provides a piezoelectric perturbation-based droplet sorting microfluidic chip, comprising a chip substrate and a single-sided liquid pusher assembly. The chip substrate is provided with a main flow channel, an annular continuous phase flow channel, a pressure application cavity, a pressure fluctuation flow channel, a target output flow channel, and a balancing flow channel.

[0006] The annular continuous phase flow channel is connected to the main flow channel to form a droplet generation region; one end of the pressure fluctuation flow channel is connected to the pressure application chamber. The other end of the pressure fluctuation flow channel, the input end of the target output flow channel, and the input end of the balancing flow channel intersect the main flow channel at the same location. The target output flow channel and the balancing flow channel are symmetrically arranged on either side of the main flow channel. The pressure fluctuation flow channel and the balancing flow channel are located on the same side of the main flow channel. The intersection of the target output flow channel, the balancing flow channel, and the main flow channel forms a sorting region.

[0007] The single-sided fluid push assembly is embedded in the pressure application chamber and includes a mounting tube and a piezoelectric ceramic. The mounting tube is fixed within the pressure application chamber. The piezoelectric ceramic is elongated and mounted within the mounting tube. The mounting tube is sealed against the sidewalls of the pressure application chamber and the mounting tube itself. The piezoelectric ceramic has two ends: a fixed end and a telescopic end. The fixed end of the piezoelectric ceramic is secured to the mounting tube.

[0008] During operation, the volume of the pressure application cavity is changed by the expansion and contraction movement of the piezoelectric ceramic, causing pressure fluctuations in the pressure application cavity, which generates a thrust on the target droplets in the sorting area toward the target output flow channel.

[0009] Preferably, the annular continuous phase flow channel is intersected with the main flow channel. A continuous phase inlet and a dispersed phase inlet are provided on the chip substrate. The continuous phase inlet communicates with the annular continuous phase flow channel. The dispersed phase inlet communicates with the input end of the main flow channel. The output ends of the main flow channel, target output flow channel, and balancing flow channel are respectively provided with a main outlet, a target droplet outlet, and a balancing outlet.

[0010] Preferably, the annular continuous phase flow channel and the main flow channel are perpendicular to each other at the intersection.

[0011] Preferably, the droplet generation area is connected to the position of the continuous phase inlet on the annular continuous phase flow channel, dividing the annular continuous phase flow channel into equal parts.

[0012] Preferably, the target output flow channel and the balancing flow channel both form an angle of 10° to 40° with the main flow channel.

[0013] Preferably, the pressure fluctuation channel and the main channel are arranged perpendicular to each other.

[0014] Preferably, the side of the pressure applying cavity away from the pressure fluctuation flow channel is connected to the cavity fluid inlet through a flow channel. The cavity fluid inlet can be closed.

[0015] Preferably, a target detection device is provided between the droplet generation area and the sorting area.

[0016] Preferably, the two electrodes of the piezoelectric ceramic are arranged at the fixed end and are led out respectively through two wires.

[0017] Preferably, a discrete phase pressure fluctuation chamber is further provided on the chip substrate. Different positions of the discrete phase pressure fluctuation chamber are connected to the discrete phase inlet and the main channel through flow channels respectively. A pressure fluctuation component is provided in the discrete phase pressure fluctuation chamber. The structure of the pressure fluctuation component is the same as that of the single-sided liquid pushing component, which is used to generate pressure fluctuations in the main channel between the discrete phase inlet and the droplet generation area; the pressure fluctuation is transmitted to the droplet generation area, so that the discrete phase fluid is pinched off by the continuous phase fluid in the droplet generation area in advance or later, thereby changing the size of the droplets generated in the droplet generation area.

[0018] In a second aspect, the present invention provides a method for sorting target droplets, which uses the aforementioned droplet sorting microfluidic chip. The process of the target droplet sorting method is as follows:

[0019] The continuous phase fluid and the discrete phase fluid are injected into the continuous phase inlet and the discrete phase inlet, respectively, so that the discrete phase fluid forms droplets separated by the continuous phase fluid in the droplet generation area. As the droplets pass through the target detection device, the target detection device detects whether the droplets contain the target substance. When the droplets containing the target substance reach the sorting area, the piezoelectric ceramic in the unilateral liquid pusher assembly is energized and extended, causing the pressure fluctuation channel to apply thrust to the target droplets in the sorting area, pushing the target droplets toward the target output channel.

[0020] The present invention has the following beneficial effects:

[0021] 1. The present invention incorporates a pressure-applying cavity within the chip substrate, directly integrating a unilateral liquid-pushing assembly based on a piezoelectric ceramic structure. This allows for a controlled unilateral thrust on droplets in the sorting area, allowing target droplets to be separated from the main droplet queue. This, combined with a corresponding target detection device, enables automatic sorting of target droplets. Furthermore, the integrated piezoelectric ceramic structure simplifies the overall structure of the present invention, making installation very convenient.

[0022] 2. The present invention can change the timing of droplet formation by providing pressure fluctuations in the droplet sorting area, thereby obtaining droplets of different sizes. In conjunction with the subsequent droplet sorting structure, droplets of different sizes encapsulating target substances can be obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of the top view of the structure of embodiment 1 of the present invention;

[0024] Figure 2 This is a bottom-view structural diagram of Example 1 of the present invention;

[0025] Figure 3 for Figure 2 Cross-sectional view of section AA;

[0026] Figure 4 Schematic diagram of the three-dimensional structure of the single-side fluid pushing assembly in Example 1 of the present invention;

[0027] Figure 5 Schematic cross-sectional view of a single-side fluid push assembly in Example 1 of the present invention;

[0028] Figure 6 This is a schematic diagram of the top view of the structure of Example 2 of the present invention. DETAILED DESCRIPTION

[0029] The present invention will be further described below with reference to the accompanying drawings.

[0030] Example 1

[0031] like Figure 1 and 2 As shown, a piezoelectric perturbation-based droplet sorting microfluidic chip includes a chip substrate 1 and a single-sided liquid pusher assembly 2. The chip substrate 1 is provided with a continuous phase inlet 3, a dispersed phase inlet 4, a main flow channel 5, an annular continuous phase flow channel 6, a pressure application cavity 7, a pressure fluctuation flow channel 8, a target output flow channel 9, a balancing flow channel 10, a main outlet 11, a target droplet outlet 12, and a balancing outlet 13.

[0032] Main outlet 11, target droplet outlet 12, and equilibrium outlet 13. The annular continuous-phase flow channel 6 intersects the main flow channel 5, forming a cross-convergent flow channel structure. The continuous-phase inlet 3 is connected to the annular continuous-phase flow channel 6. The dispersed-phase inlet 4 is connected to the input end of the main flow channel 5. The point where the annular continuous-phase flow channel 6 connects to the continuous-phase inlet 3 and the point where the dispersed-phase inlet 3 connects to the annular continuous-phase flow channel 6 divides the annular continuous-phase flow channel 6 into equal parts.

[0033] One end of the pressure fluctuation channel 8 is connected to the pressure application chamber 7. The other end of the pressure fluctuation channel 8, the input ends of the target output channel 9, and the balancing channel 10 intersect the main channel 5 at the same location. The target output channel 9 and the balancing channel 10 are symmetrically arranged on either side of the main channel 5. The pressure fluctuation channel 8 and the balancing channel 10 are located on the same side of the main channel 5. The output ends of the main channel 5, the target output channel 9, and the balancing channel 10 are connected to the main outlet 11, the target droplet outlet 12, and the balancing outlet 13, respectively.

[0034] In this embodiment, the target output flow channel 9 and the balancing flow channel 10 both form an angle of 20° with the main flow channel 5. The pressure fluctuation flow channel 8 and the main flow channel 5 are arranged perpendicular to each other.

[0035] The side of the pressure applying cavity 7 facing away from the pressure fluctuation flow channel 8 is connected to a closable cavity fluid inlet 14 through a flow channel. The cavity fluid inlet 14 is used to fill the pressure applying cavity 7 with a discrete phase liquid.

[0036] The intersection of the annular continuous phase flow channel 6 and the main flow channel 5 forms a droplet generation area. The intersection of the target output flow channel 9, the balancing flow channel 10 and the main flow channel 5 forms a sorting area. The sorting area is located on the side of the droplet generation area away from the discrete phase inlet 4. A target detection device (not shown in the figure) is provided between the droplet generation area and the sorting area; the target detection device is used to detect whether the passing droplets contain the target substance, so as to provide guidance for the droplet sorting work of the unilateral liquid pushing component 2. The target substance in this embodiment is a living cell, so that the droplets encapsulated with cells can be screened out.

[0037] like Figure 3 As shown, the unilateral liquid-pushing assembly 2 is installed in the pressure-applying chamber 7. The unilateral liquid-pushing assembly 2 can expand or contract in response to changes in input voltage, thereby changing the volume of the pressure-applying chamber 7. After the cavity fluid inlet 14 is sealed, the volume fluctuation of the pressure-applying chamber 7 causes the pressure-fluctuating flow channel 8 to apply a unilateral thrust to the sorting area, pushing the target droplets toward the target output flow channel 9.

[0038] like Figure 4 and 5 As shown, the unilateral liquid pushing component 2 includes a mounting tube 2-1, a wire 2-2 and a piezoelectric ceramic 2-3. The mounting tube 2-1 is fixed in the corresponding pressure applying cavity 7. The piezoelectric ceramic 2-3 is in an elongated shape and is installed in the mounting tube 2-1; the mounting tube 2-1 and the side wall of the pressure applying cavity 7 are sealed; the piezoelectric ceramic 2-3 and the mounting tube 2-1 are sealed. The two ends of the piezoelectric ceramic 2-3 are a fixed end and a telescopic end respectively. The fixed end of the piezoelectric ceramic 2-3 is fixed to the mounting tube 2-1. The telescopic end of the piezoelectric ceramic 2-3 extends from the end of the mounting tube 2-1. The two electrodes of the piezoelectric ceramic 2-3 are arranged at the fixed end and are respectively led out through two wires 2-1.

[0039] During operation, if the unilateral liquid pushing component 2 does not work, the droplets separated by the continuous phase fluid will only be transported along the main channel 5, and part of the continuous phase fluid will flow into the target output channel 9 and the balance channel 10. These continuous phase fluids can push the target droplets to be output from the target droplet outlet 12.

[0040] The process of using the droplet sorting microfluidic chip to sort target droplets is as follows:

[0041] The continuous phase fluid and the dispersed phase fluid are injected into the continuous phase inlet 3 and the dispersed phase inlet 4, respectively, so that the dispersed phase fluid forms droplets separated by the continuous phase fluid in the droplet generation area. When the droplets pass through the target detection device, the target detection device detects whether the droplets contain the target substance.

[0042] When droplets containing the target substance reach the sorting area, the piezoelectric ceramics 2-3 in the single-sided liquid-pushing assembly 2 are energized and extend, causing the pressure-fluctuating flow channel 8 to exert a thrust on the droplets in the sorting area, pushing the target droplets toward the target output flow channel 9. After the piezoelectric ceramics 2-3 extend, they automatically reset. Workers can then continuously collect the target droplets at the target droplet outlet 12.

[0043] When the droplets without target substances reach the sorting area, the piezoelectric ceramics 2 - 3 in the single-side liquid pushing assembly 2 are not energized. Due to the pressure balance on both sides, the droplets continue to flow along the main channel 5 and are output from the main outlet 11 .

[0044] Example 2

[0045] like Figure 6 As shown, a droplet sorting microfluidic chip based on piezoelectric perturbation is shown. This embodiment differs from Example 1 in that a discrete phase pressure fluctuation cavity is further provided on the chip substrate 1. Different positions of the discrete phase pressure fluctuation cavity are connected to the discrete phase inlet 4 and the main channel 5 through flow channels.

[0046] A pressure fluctuation component is provided in the discrete phase pressure fluctuation chamber. The structure of the pressure fluctuation component is identical to that of the unilateral liquid push component 2, and is used to generate pressure fluctuations in the main channel between the discrete phase inlet 4 and the droplet generation area. This pressure fluctuation can be transmitted to the droplet generation area, causing the discrete phase fluid to be pinched off by the continuous phase fluid in the droplet generation area earlier or later, thereby achieving droplet size control. As a result, this embodiment can obtain and sort target droplets of a specified size by adjusting the frequency of the voltage signal input to the piezoelectric ceramic in the pressure fluctuation component.

Claims

1. A droplet sorting microfluidic chip based on piezoelectric perturbation, characterized by: The chip substrate (1) comprises a chip base (1) and a single-side liquid pushing component (2); the chip base (1) is provided with a main flow channel (5), an annular continuous phase flow channel (6), a pressure application cavity (7), a pressure fluctuation flow channel (8), a target output flow channel (9) and a balance flow channel (10); The annular continuous phase flow channel (6) is connected to the main flow channel (5) to form a droplet generation area; one end of the pressure fluctuation flow channel (8) is connected to the pressure application cavity (7); the other end of the pressure fluctuation flow channel (8), the input end of the target output flow channel (9) and the balancing flow channel (10) intersect with the main flow channel (5) at the same position; the target output flow channel (9) and the balancing flow channel (10) are symmetrically arranged on both sides of the main flow channel (5); the pressure fluctuation flow channel (8) and the balancing flow channel (10) are located on the same side of the main flow channel (5); the intersection of the target output flow channel (9), the balancing flow channel (10) and the main flow channel (5) forms a sorting area; The single-sided liquid pushing component (2) is embedded and installed in the pressure applying cavity (7), and comprises a mounting tube (2-1) and a piezoelectric ceramic (2-3); the mounting tube (2-1) is fixed in the pressure applying cavity (7); the piezoelectric ceramic (2-3) is in an elongated strip shape and is installed in the mounting tube (2-1); a sealing arrangement is arranged between the mounting tube (2-1) and the side wall of the pressure applying cavity (7); a sealing arrangement is arranged between the piezoelectric ceramic (2-3) and the mounting tube (2-1); during operation, the volume of the pressure applying cavity (7) is changed by the telescopic movement of the piezoelectric ceramic (2-3), so that the pressure applying cavity (7) generates pressure fluctuations, and a thrust is generated on the target droplets in the sorting area toward the target output flow channel (9).

2. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The annular continuous phase flow channel (6) and the main flow channel (5) are arranged crosswise; a continuous phase inlet (3) and a discrete phase inlet (4) are arranged on the chip substrate (1); the continuous phase inlet (3) is connected to the annular continuous phase flow channel (6); the discrete phase inlet (4) is connected to the input end of the main flow channel (5); and the output ends of the main flow channel (5), the target output flow channel (9) and the balance flow channel (10) are respectively provided with a main outlet (11), a target droplet outlet (12) and a balance outlet (13).

3. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The droplet generation area is connected to the position of the continuous phase inlet on the annular continuous phase flow channel, dividing the annular continuous phase flow channel into equal parts.

4. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The target output flow channel (9) and the balancing flow channel (10) both form an angle of 10° to 40° with the main flow channel (5).

5. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The pressure fluctuation channel (8) and the main channel (5) are arranged perpendicular to each other.

6. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The side of the pressure applying cavity (7) facing away from the pressure fluctuation flow channel (8) is connected to the cavity fluid inlet (14) through the flow channel; the cavity fluid inlet (14) can be closed.

7. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: A target detection device is provided between the droplet generation area and the sorting area.

8. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The two electrodes of the piezoelectric ceramic (2-3) are arranged at the fixed end and are led out respectively through two wires.

9. The droplet sorting microfluidic chip based on piezoelectric perturbation according to claim 1, characterized in that: The chip substrate (1) is further provided with a discrete phase pressure fluctuation chamber (15); different positions of the discrete phase pressure fluctuation chamber (15) are connected to the discrete phase inlet (4) and the main channel (5) through flow channels respectively; a pressure fluctuation component is provided in the discrete phase pressure fluctuation chamber (15); the structure of the pressure fluctuation component is the same as that of the single-side liquid pushing component (2), and is used to generate pressure fluctuations in the main channel (5) between the discrete phase inlet (4) and the droplet generation area; the pressure fluctuations are transmitted to the droplet generation area, so that the discrete phase fluid is pinched off by the continuous phase fluid in the droplet generation area in advance or in a later manner, thereby changing the size of the droplets generated in the droplet generation area.

10. A method for sorting target droplets, characterized in that: Using the droplet sorting microfluidic chip as claimed in claim 2; the process of the target droplet sorting method is as follows: Injecting the continuous phase fluid and the dispersed phase fluid into the continuous phase inlet (3) and the dispersed phase inlet (4) respectively, so that the dispersed phase fluid forms droplets separated by the continuous phase fluid in the droplet generation area; When a droplet passes through a target detection device, the target detection device detects whether the droplet contains a target substance; when a droplet containing the target substance reaches a sorting area, the piezoelectric ceramic (2-3) in the single-side liquid pushing component (2) is energized and extended, so that the pressure fluctuation flow channel (8) applies a thrust to the target droplet in the sorting area, pushing the target droplet toward the target output flow channel (9).

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