CN114308150B - Feedback control type double-pulse driving liquid drop generating system and liquid drop generating method - Google Patents
Feedback control type double-pulse driving liquid drop generating system and liquid drop generating method Download PDFInfo
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Abstract
The invention provides a feedback control type double-pulse driving liquid drop generating system and a liquid drop generating method, wherein the system comprises an air pump assembly, an air pump servo, a micro-fluidic chip, an imaging assembly and a controller; the micro-fluidic chip is provided with a continuous phase flow channel, a disperse phase flow channel and a droplet flow channel, the air pump assembly comprises a continuous phase air pump and a disperse phase air pump, and the continuous phase air pump and the disperse phase air pump respectively input continuous phase liquid and disperse phase liquid into the continuous phase flow channel and the disperse phase flow channel, so that disperse phase droplets are continuously generated in the droplet flow channel on the micro-fluidic chip. The invention has the beneficial effects that: the system and the method can accurately control the liquid drop forming process, so that the liquid drop forming process is stable and controllable, and the system is convenient to build, easy to control and cost-saving.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a feedback control type double-pulse driving liquid drop generating system and a liquid drop generating method.
Background
At present, the generation methods for liquid drops in a microfluidic platform are mainly divided into an active method and a passive method.
The passive method mainly controls the generation of the liquid drops by depending on the structural design and the fluid property of the microfluidic chip, the size of the liquid drops generated by the passive generation method is unstable, the method is easily influenced by the external environment and the experimental conditions, and the robustness of the system is poor.
The active method is a liquid drop generating method for controlling the structure of the microfluidic chip and fluid by inputting external energy, wherein the external energy comprises an electric field, a magnetic field, heat, a mechanical source and the like. However, integration of external energy input in a droplet microfluidic platform inevitably increases the complexity and cost of microfluidic device fabrication. In addition, the coupling of external forces to hydrodynamic forces can complicate droplet formation dynamics too much for modeling and closed-loop feedback control, resulting in unpredictable droplet sizes or volumes when switching feed fluids or changing channel geometries.
Disclosure of Invention
In view of the above, in order to conveniently produce droplets with specified volumes and enable a droplet production system to have good system robustness, the invention provides a feedback control type double-pulse driving droplet generation system, which comprises an air pump assembly, an air pump servo, a microfluidic chip, an imaging assembly and a controller;
the micro-fluidic chip is provided with a continuous phase flow channel, a disperse phase flow channel and a droplet flow channel, the end part of the continuous phase flow channel is provided with a continuous phase inlet, the continuous phase flow channel is connected with two continuous phase sub-flow channels, the two continuous phase sub-flow channels are converged at a crossing, one end of the disperse phase flow channel is provided with the disperse phase inlet, the other end of the disperse phase flow channel extends to the crossing, one end part of the droplet flow channel is positioned at the crossing, and the other end part of the droplet flow channel is a droplet outlet;
the air pump assembly comprises a continuous phase air pump and a dispersed phase air pump which are connected with an air pump servo, a continuous phase liquid tank is arranged in the continuous phase air pump, a first input pipe is arranged on the continuous phase air pump and connected to the continuous phase inlet, a dispersed phase liquid tank is arranged in the dispersed phase air pump, a second input pipe is arranged on the continuous phase air pump and connected to the dispersed phase inlet;
the continuous phase air pump and the disperse phase air pump respectively input the continuous phase liquid and the disperse phase liquid in the continuous phase liquid tank and the disperse phase liquid tank into the continuous phase flow channel and the disperse phase flow channel, so that the disperse phase liquid forms liquid drops in the continuous phase liquid and the formed liquid drops flow out along the liquid drop flow channel;
the imaging component shoots images of the microfluidic chip in real time and transmits the images to the controller;
the controller is connected with the air pump server, calculates the volume of the liquid drop and the position of the interface of the continuous phase liquid and the disperse phase liquid according to the image information shot by the imaging assembly, and controls the air pump server to adjust the pressure and pulse pressure of the continuous phase liquid and the disperse phase liquid output by the continuous phase air pump and the disperse phase air pump, so that the volume of the liquid drop formed on the microfluidic chip is adjusted in a feedback mode.
Furthermore, a display screen is further arranged on the controller, and the display screen displays the liquid drop image shot by the electronic objective lens.
Furthermore, the liquid drop outlet is connected with a liquid drop output pipe, and the liquid drop output pipe is used for outputting the liquid drops formed on the micro-fluidic chip.
The invention also provides a liquid drop generating method based on the feed control type double-pulse driving liquid drop generating system, which comprises the following steps:
s1: inputting preset values to a controller, wherein the preset values comprise the range of the position of the two-phase intersection interface of the continuous phase liquid and the dispersed phase liquid and the required volume range of the liquid drops;
s2: the controller respectively controls the continuous phase air pump and the disperse phase air pump according to preset values of the controller to input the continuous phase liquid and the disperse phase liquid into the continuous phase flow channel and the disperse phase flow channel so as to enable the continuous phase liquid and the disperse phase liquid to be in a boundary; wherein the pressure of the dispersed phase air pump outputting the continuous phase liquid is F1, and the pressure of the continuous phase air pump outputting the dispersed phase liquid is F2;
s3: the imaging assembly shoots images of the microfluidic chip in real time and transmits the images to the controller, and the controller analyzes the images shot by the imaging assembly and calculates the junction position of the continuous phase liquid and the disperse phase liquid; the controller adjusts the sizes of the F1 and the F2 according to the analysis result until the boundary position of the continuous phase liquid and the disperse phase liquid is within a preset range;
s4: the controller controls the dispersed phase air pump to output a dispersed phase pressure pulse on the basis of the F1, the amplitude of the dispersed phase pressure pulse is Ad, the duration is Td, and the dispersed phase liquid breaks the continuous phase liquid under the action of the dispersed phase pressure pulse and enters a liquid drop flow channel; after the dispersed phase pressure pulse is finished, the controller controls the continuous phase air pump to output a continuous phase pressure pulse on the basis of the pressure value F2, the amplitude of the continuous phase pressure pulse is Ac, the duration is Tc, and the continuous phase liquid cuts off the dispersed phase liquid output process in the continuous phase pressure pulse, so that the dispersed phase liquid forms liquid drops;
s5: the controller analyzes the image shot by the imaging component, calculates the volume of the liquid drop in the step S4 and compares the calculation result with a preset value; if the calculated volume of the liquid drop is within the range of the preset value; the controller controls the amplitude Ad of the dispersed phase pressure pulse and the duration Td to be unchanged; if the calculated volume of the liquid drop is not in the range of the preset value; the controller adjusts the amplitude Ad and the duration Td of the dispersed phase pressure pulse to make the volume of the liquid drop formed by the feedback control type micro-fluidic liquid drop generating system in the preset value range.
Further, the process of the controller controlling the position of the mixing interface of the continuous phase liquid and the dispersed phase liquid in step S3 is: the process that the controller controls the size of the F1 and the F2 to adjust the boundary position to reach the preset value range is as follows: if the controller analyzes that the interface is close to the dispersed phase inlet relative to the preset value, the controller increases the interface by controlling the F1; if the controller analyzes that the interface is close to the droplet outlet relative to the preset value, the controller controls the F1 to be reduced.
Further, the step S5 of adjusting the dispersed phase pressure pulse or the size of the dispersed phase pressure pulse by the controller to make the volume of the subsequently formed droplet within the preset value range includes: if the controller analyzes that the liquid drop on the microfluidic chip is larger than a set value, the controller controls the dispersed phase pressure pulse duration time Td or the amplitude Ad output by the dispersed phase air pump next time to be reduced; if the controller analyzes that the liquid drop on the microfluidic chip is smaller than the set value, the controller controls the dispersed phase pressure pulse duration Td or the amplitude Ad of the next output of the dispersed phase air pump to be increased.
The liquid drop generating method of the feedback control type double-pulse driving liquid drop generating system has the advantages that:
(1) The system and the method use two times of feedback control to control the generation of the liquid drops, and the first time of feedback control can adjust the position of a two-phase interface so as to keep the initial state before the generation of the liquid drops consistent.
(2) The system uses dispersed phase pulse pressure and continuous phase pulse pressure to control filling and cutting respectively, and can accurately control the volume of a single liquid drop.
(3) The system monitors the generated liquid drops in real time, the volume value of the generated liquid drops is close to a preset value by utilizing the second feedback control, self-adjustment can be realized aiming at external disturbance, and the stability of the volume of the generated liquid drops is kept.
(4) The system is convenient to build, easy to control and cost-saving, can generate liquid drops according to needs, and has high system accuracy and robustness.
Drawings
FIG. 1 is a block diagram of a feedback controlled dual pulse driven droplet generation system according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a microchannel on the microfluidic chip 1 of FIG. 1;
FIG. 3 is a flow chart of a method of droplet generation for a feedback controlled dual pulse driven droplet generation system of the present invention;
fig. 4 is a schematic diagram of the pulse pressures of the outputs of the continuous phase air pump and the dispersed phase air pump in the above-described droplet generation method.
In the above figures: 1-a micro-fluidic chip, 11-a continuous phase flow channel, 12-a continuous phase branched flow channel, 13-a continuous phase inlet, 14-a fork, 15-a dispersed phase flow channel, 16-a dispersed phase inlet and 17-a droplet flow channel; 2-controller, 3-air pump servo, 4-disperse phase air pump, 41-continuous phase air pump, and 5-imaging component.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be further described with reference to the accompanying drawings.
Referring to fig. 1 and fig. 2, a feedback control type microfluidic droplet generating system of the present invention includes a microfluidic chip 1, a controller 2, an air pump assembly, an air pump servo 3, and an imaging assembly 5.
The micro-fluidic chip 1 is provided with a plurality of micro-channels, the micro-channels comprise a continuous phase flow channel 11, two continuous phase branched flow channels 12, a dispersed phase flow channel 13 and a liquid drop flow channel 17, the left end of the continuous phase flow channel 11 is provided with a continuous phase inlet, the right end of the continuous phase flow channel is connected with the two continuous phase branched flow channels 12, the two continuous phase branched flow channels 12 are converged at the tail end, the convergence position is a fork 14, the dispersed phase flow channel 12 and the liquid drop flow channel 17 extend to the left side and the right side from the fork 14, the end part of the dispersed phase flow channel 12 is provided with a dispersed phase inlet 16, the end part of the liquid drop flow channel 17 is provided with a liquid drop outlet, the liquid drop outlet is connected with a liquid drop output pipe, and the liquid drop output pipe outputs liquid drops formed on the micro-fluidic chip.
The air pump assembly comprises a continuous phase air pump 41 and a disperse phase air pump 4 which are both connected with the air pump server 3, a continuous phase liquid tank is arranged in the continuous phase air pump 41 and connected with each other, a first input pipe is arranged on the continuous phase air pump 41 and connected to the continuous phase inlet, a disperse phase liquid tank is arranged in the disperse phase air pump 4, a second input pipe is arranged on the disperse phase air pump 4 and connected to the disperse phase inlet 16; the dispersed phase liquid tank and the continuous phase liquid tank are respectively filled with dispersed phase liquid and continuous phase liquid which are not dissolved mutually, and the continuous phase air pump 41 and the dispersed phase air pump 4 respectively input the continuous phase liquid and the dispersed phase liquid into the continuous phase flow channel 11 and the dispersed phase flow channel 13 under the control of the air pump servo 3, so that the dispersed phase liquid forms liquid drops in the continuous phase liquid.
The imaging component 5 is connected with the controller 2, and the imaging component 5 is used for shooting images of a micro-channel in the micro-fluidic chip 1 and fluid (dispersed phase liquid and continuous phase liquid) on the micro-channel in real time and sending the shot images to the controller 2 in real time.
The controller 2 is connected with the air pump servo 3, the controller 2 analyzes the image shot by the imaging assembly by using a graphic analysis technology, and analyzes the position information of the interface of two phases of continuous phase liquid and disperse phase liquid on the microfluidic chip 1 and the volume size information of the droplet formed by the disperse phase liquid in the continuous phase liquid from the image, and the controller 2 adjusts the pressure of the continuous phase liquid and the disperse phase liquid output by the continuous phase air pump 41 and the disperse phase air pump 4 through the air pump servo 3 according to the analysis result, so that the positions of the two interfaces of the continuous phase liquid and the disperse phase liquid on the microfluidic chip 1 and the volume size of the droplet formed by the disperse phase liquid in the continuous phase liquid are feedback-adjusted, and finally the microfluidic chip 1 can continuously output the disperse phase droplet with the volume size in a required range.
Further, the controller 2 is further provided with a display screen, and the display screen displays the droplet image shot by the electronic objective lens.
The microfluidic droplet generation method of the feedback control type microfluidic droplet generation system comprises the following steps of:
s1: inputting preset values to the controller 2, wherein the preset values comprise the range of the position of the two-phase intersection interface of the continuous phase liquid and the dispersed phase liquid and the required volume range of the liquid drops;
s2: the controller respectively controls the continuous phase air pump 41 and the disperse phase air pump 4 according to preset values of the controllers to input the continuous phase liquid and the disperse phase liquid into the continuous phase flow channel 11 and the disperse phase flow channel 15 so that the continuous phase liquid and the disperse phase liquid are intersected near a fork; wherein the pressure of the continuous phase liquid output by the continuous phase air pump is F2, and the pressure of the dispersed phase liquid output by the dispersed phase air pump is F1;
s3: the imaging assembly 5 shoots images of the microfluidic chip in real time and transmits the images to the controller 2, and the controller 2 analyzes the images shot by the imaging assembly and calculates the junction position of the continuous phase liquid and the disperse phase liquid; the controller 2 adjusts the sizes of the F1 and the F2 according to the analysis result until the boundary position of the continuous phase liquid and the disperse phase liquid is within a preset range;
wherein; the process that the controller controls the size of the F1 and the F2 to adjust the boundary position to reach the preset value range is as follows: if the controller 2 analyzes that the interface is close to the dispersed phase inlet 16 relative to the preset value, the controller 2 increases by controlling the F1; if the controller 2 analyzes that the interface is closer to the droplet outlet than the preset value, the controller controls F1 to decrease.
S4: the controller controls the dispersed phase air pump to output a dispersed phase pressure pulse on the basis of the F1, the amplitude of the dispersed phase pressure pulse is Ad, the duration is Td, and the dispersed phase liquid breaks the continuous phase liquid under the action of the dispersed phase pressure pulse and enters the liquid drop flow channel 17; after the dispersed phase pressure pulse is finished, the controller 2 controls the continuous phase air pump to output a continuous phase pressure pulse on the basis of the pressure value F2, the amplitude of the continuous phase pressure pulse is Ac, the duration is Tc, and the continuous phase liquid cuts off the output process of the dispersed phase liquid in the continuous phase pressure pulse, so that the dispersed phase liquid forms liquid drops;
s5: the controller 2 analyzes the image photographed by the imaging module, calculates the volume of the droplet formed in step S4 and compares the calculation result with a preset value; if the calculated volume of the liquid drop is within the range of the preset value; the controller controls the dispersed phase pressure pulse amplitude Ad and the duration Td to remain unchanged during the subsequent droplet formation; if the calculated volume of the liquid drop is not in the range of the preset value; the controller adjusts the amplitude Ad or duration Td of the dispersed phase pressure pulse to make the volume of the subsequently generated liquid drop within a preset value range;
specifically, the process of the controller 2 adjusting the dispersed phase pressure pulse or the size of the dispersed phase pressure pulse so that the volume of the subsequently generated droplets is within the range of the preset value is as follows: if the controller 2 analyzes that the volume of the liquid drop formed on the micro-fluidic chip 1 is larger than a set value, the controller 2 reduces the duration Td or the amplitude Ad of the next output dispersed phase pressure pulse of the dispersed phase air pump; if the controller analyzes that the droplet generated on the microfluidic chip 1 is smaller than the set value, the controller controls the duration Td or the amplitude Ad of the disperse phase pressure pulse output by the disperse phase air pump next time to be increased.
It should be noted that the position of the imaging component remains unchanged during the above-mentioned shooting process, the imaging component 5 faces the intersection 14 of the continuous phase flow channel 11 and the dispersed phase flow channel 15 on the microfluidic chip 1, and the position of the intersection interface between the continuous phase liquid and the dispersed phase liquid and the volume of the formed droplet can be analyzed simultaneously from the image shot by the imaging component. In the method, in the process of forming the liquid drop of the first drop of the dispersed phase, the sizes of F1, F2, ad, td, ac and Tc are all determined by preset values, the volume size of the subsequent liquid drop is regulated by the feedback control of the controller 2, and the subsequent liquid drop can be stabilized in a set range after being regulated for a plurality of times, so that the effect of continuously generating the liquid drop with the fixed volume is realized. Meanwhile, the method can ensure the stability of the liquid drops in the forming process and improve the robustness of the liquid drop generating process.
In this document, the terms front, back, upper and lower are used to define the components in the drawings and the positions of the components relative to each other, and are used for clarity and convenience of the technical solution. It is to be understood that the use of the directional terms should not be taken to limit the scope of the claims.
The features of the embodiments and embodiments described herein above may be combined with each other without conflict.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.
Claims (5)
1. A liquid drop generating method based on a feedback control type double-pulse driving liquid drop generating system is characterized in that: the liquid drop generating system comprises an air pump assembly, an air pump servo, a micro-fluidic chip, an imaging assembly and a controller;
the micro-fluidic chip is provided with a continuous phase flow channel, a disperse phase flow channel and a droplet flow channel, the end part of the continuous phase flow channel is provided with a continuous phase inlet, the continuous phase flow channel is connected with two continuous phase sub-flow channels, the two continuous phase sub-flow channels are converged at a crossing, one end of the disperse phase flow channel is provided with the disperse phase inlet, the other end of the disperse phase flow channel extends to the crossing, one end part of the droplet flow channel is positioned at the crossing, and the other end part of the droplet flow channel is a droplet outlet;
the air pump assembly comprises a continuous phase air pump and a dispersed phase air pump which are connected with an air pump servo, a continuous phase liquid tank is arranged in the continuous phase air pump, a first input pipe is arranged on the continuous phase air pump and connected to the continuous phase inlet, a dispersed phase liquid tank is arranged in the dispersed phase air pump, a second input pipe is arranged on the continuous phase air pump and connected to the dispersed phase inlet;
the continuous phase air pump and the disperse phase air pump respectively input the continuous phase liquid and the disperse phase liquid in the continuous phase liquid tank and the disperse phase liquid tank into the continuous phase flow channel and the disperse phase flow channel, so that the disperse phase liquid forms liquid drops in the continuous phase liquid and the formed liquid drops flow out along the liquid drop flow channel;
the imaging component shoots images of the microfluidic chip in real time and transmits the images to the controller;
the controller is connected with the air pump server, calculates the volume of the liquid drop and the position of the interface of the continuous phase liquid and the disperse phase liquid according to the image information shot by the imaging assembly, and controls the air pump server to adjust the pressure and pulse pressure of the continuous phase liquid and the disperse phase liquid output by the continuous phase air pump and the disperse phase air pump, so that the volume of the liquid drop formed on the microfluidic chip is adjusted in a feedback manner;
the droplet generation method comprises the following steps: s1: inputting preset values to a controller, wherein the preset values comprise the range of the position of the two-phase intersection interface of the continuous phase liquid and the dispersed phase liquid and the required volume range of the liquid drops;
s2: the controller respectively controls the continuous phase air pump and the disperse phase air pump according to preset values of the controller to input the continuous phase liquid and the disperse phase liquid into the continuous phase flow channel and the disperse phase flow channel so as to enable the continuous phase liquid and the disperse phase liquid to be in a boundary; wherein the pressure of the continuous phase liquid output by the continuous phase air pump is F2, and the pressure of the dispersed phase liquid output by the dispersed phase air pump is F1;
s3: the imaging assembly shoots images of the microfluidic chip in real time and transmits the images to the controller, and the controller analyzes the images shot by the imaging assembly and calculates the junction position of the continuous phase liquid and the disperse phase liquid; the controller adjusts the sizes of the F1 and the F2 according to the analysis result until the boundary position of the continuous phase liquid and the disperse phase liquid is in a preset range;
s4: the controller controls the dispersed phase air pump to output a dispersed phase pressure pulse on the basis of the F1, the amplitude of the dispersed phase pressure pulse is Ad, the duration is Td, and the dispersed phase liquid breaks the continuous phase liquid under the action of the dispersed phase pressure pulse and enters a liquid drop flow channel; after the dispersed phase pressure pulse is finished, the controller controls the continuous phase air pump to output a continuous phase pressure pulse on the basis of the pressure value F2, the amplitude of the continuous phase pressure pulse is Ac, the duration is Tc, and the continuous phase liquid cuts off the dispersed phase liquid output process in the continuous phase pressure pulse, so that the dispersed phase liquid forms liquid drops;
s5: the controller analyzes the image shot by the imaging component, calculates the volume of the liquid drop in the step S4 and compares the calculation result with a preset value; if the calculated volume of the liquid drop is within the range of the preset value; the controller controls the amplitude Ad of the dispersed phase pressure pulse and the duration Td to be unchanged; if the calculated volume of the liquid drop is not in the range of the preset value; the controller adjusts the amplitude Ad and duration Td of the dispersed phase pressure pulse to keep the volume of the subsequently formed droplets within a preset range.
2. A method of droplet generation based on a feedback controlled dual pulse driven droplet generation system as claimed in claim 1, wherein: the controller is also provided with a display screen, and the display screen displays images shot by the electronic objective lens.
3. A method of droplet generation based on a feedback controlled dual pulse driven droplet generation system as claimed in claim 2, wherein: and the liquid drop outlet is connected with a liquid drop output pipe, and the liquid drop output pipe is used for outputting liquid drops formed on the microfluidic chip.
4. The method of claim 1, wherein the method comprises: the process of controlling the position of the mixed interface of the continuous phase liquid and the dispersed phase liquid by the controller in the step S3 is as follows: the process that the controller controls the size of the F1 and the F2 to adjust the boundary position to reach the preset value range is as follows: if the controller analyzes that the interface is close to the dispersed phase inlet relative to the preset value, the controller controls the F1 to increase; if the controller analyzes that the interface is close to the droplet outlet relative to the preset value, the controller controls F1 to be reduced.
5. A method of droplet generation based on a feedback controlled dual pulse drive droplet generation system of claim 2, wherein: step S5, the process that the controller adjusts the dispersed phase pressure pulse or the size of the dispersed phase pressure pulse to enable the volume of the subsequently formed liquid drop to be within the range of the preset value is as follows: if the volume of the liquid drop on the microfluidic chip is larger than a set value, the controller controls the dispersed phase pressure pulse duration Td or the amplitude Ad output by the dispersed phase air pump next time to be reduced; if the controller analyzes that the liquid drop on the micro-fluidic chip is smaller than the set value, the controller controls the duration Td or the amplitude Ad of the next output dispersed phase pressure pulse of the dispersed phase air pump to be increased.
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