CN115069318B - Liquid drop component regulating and controlling device and method based on bypass microinjection technology - Google Patents

Liquid drop component regulating and controlling device and method based on bypass microinjection technology Download PDF

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CN115069318B
CN115069318B CN202210760396.4A CN202210760396A CN115069318B CN 115069318 B CN115069318 B CN 115069318B CN 202210760396 A CN202210760396 A CN 202210760396A CN 115069318 B CN115069318 B CN 115069318B
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unit
channel
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CN115069318A (en
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岳涛
张长清
张鑫业
姜宁
钟宋义
张泉
李龙
李恒宇
谢少荣
罗均
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University of Shanghai for Science and Technology
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P90/00Enabling technologies with a potential contribution to greenhouse gas [GHG] emissions mitigation
    • Y02P90/02Total factory control, e.g. smart factories, flexible manufacturing systems [FMS] or integrated manufacturing systems [IMS]

Abstract

The invention belongs to the field of microfluidic droplet preparation, and particularly relates to a droplet component regulating and controlling device and method based on a bypass microinjection technology, wherein the droplet component regulating and controlling device comprises a multilayer microfluidic chip and a control module, and the control module is matched with the multilayer microfluidic chip; the multi-layer microfluidic chip comprises a fluid channel layer and a pneumatic control layer which are sequentially arranged from top to bottom; an elastic film layer is arranged between the fluid channel layer and the pneumatic control layer; the fluid channel layer is provided with an input unit, the input unit is connected with a liquid drop generating module, an outlet of the liquid drop generating module is connected with a liquid drop output unit, and an outlet of the liquid drop output unit is connected with a mixing channel; the liquid drop output unit is also provided with a microinjection module which is arranged at the downstream of the liquid output unit; the invention aims to disclose a droplet component regulating device and a droplet component regulating method based on bypass microinjection technology, which can not damage the biological activity of reactants.

Description

Liquid drop component regulating and controlling device and method based on bypass microinjection technology
Technical Field
The invention belongs to the field of microfluidic droplet preparation, and particularly relates to a droplet component regulating and controlling device and method based on bypass microinjection technology.
Background
In recent years, microfluidic chips have been increasingly used in fields of biochemistry, medicine, materials, etc., including therapeutics, pathology, drug delivery and diagnosis, tissue engineering, biosensors, etc.; the liquid drop generated by the microfluidic chip is used as a micro-reactor, has the advantages of microminiaturization, blocking, parallelization and the like, and is widely applied to various fields such as 3D cell culture, tissue engineering, drug screening and detection, biochemical analysis, material synthesis and the like;
in the technology of preparing liquid drops through a microfluidic chip, the traditional preparation method of the liquid drops adopts the principle of emulsification to form discrete liquid drops, but the generated liquid drops have high polydispersity and poor volume uniformity among the liquid drops; at present, the droplet microfluidic technology creates discrete volumes by using two immiscible phases, can realize accurate control of fluid, has better operability, and generates droplets with better monodispersity and high uniformity;
the reagent is injected into the liquid drop, so that the composition of the liquid drop can be accurately controlled and optimized, and obvious advantages are provided for multi-step reaction and screening; for adding reagents to a droplet, the reagent is injected into the droplet from the measurement channel, typically by disrupting the stability of the droplet oil/water interface with the aid of an electric field, thereby achieving pairing and fusion of droplets of two different compositions and volumes; however, external power input makes the system more complex, and furthermore, the introduction of an electric field may impair the biological activity of biological components in the droplets and reagents.
Disclosure of Invention
The invention aims to provide a droplet component regulating device and a droplet component regulating method which do not damage the biological activity of reactants and are used in bypass microinjection technology.
Based on the above purpose, the invention adopts the following technical scheme: the droplet component regulating and controlling device based on the bypass microinjection technology comprises a multi-layer microfluidic chip and a control module, wherein the control module is matched with the multi-layer microfluidic chip; the multi-layer microfluidic chip comprises a fluid channel layer and a pneumatic control layer which are sequentially arranged from top to bottom; an elastic film layer is arranged between the fluid channel layer and the pneumatic control layer; the fluid channel layer is provided with an input unit, the input unit is connected with a liquid drop generating module, an outlet of the liquid drop generating module is connected with a liquid drop output unit, and an outlet of the liquid drop output unit is connected with a mixing channel; the liquid drop output unit is also provided with a microinjection module which is arranged at the downstream of the liquid output unit.
Preferably, the droplet generation module comprises a continuous phase channel and a discrete phase channel; the input ends of the continuous phase channel and the discrete phase channel are respectively provided with a continuous phase input port and a discrete phase input port, and the input unit is communicated with the continuous phase input port and the discrete phase input port; the output port of the continuous phase channel is communicated with the output port of the discrete phase channel to form a droplet generation unit.
Preferably, the input unit comprises a plurality of liquid storage bottles filled with liquid, and the liquid storage bottles are respectively connected to the continuous phase input port and the discrete phase input port which are respectively corresponding through liquid supply pipes.
Preferably, the continuous communication channel comprises a first channel and a second channel; the first channel and the second channel are symmetrically distributed by taking the discrete phase channel as a symmetry axis, the output ports of the first channel and the second channel are communicated with the discrete communicated output ports, and the channels of the output ports of the first channel and the second channel are perpendicular to the discrete communicated channels.
Preferably, the microinjection module comprises a microinjection unit arranged on the fluid channel layer, the microinjection unit being in communication with the droplet output unit; the pneumatic control layer is provided with a pneumatic control chamber matched with the microinjection unit; the elastic film layer is arranged between the microinjection unit and the pneumatic control chamber.
Preferably, the pneumatic control chamber comprises an air cavity, the air cavity is a square groove, and the air cavity is arranged at the joint of the microinjection unit and the liquid drop output unit; the air cavity is connected with an air inlet through an air passage.
Preferably, the control module comprises an upper computer; the upper computer is connected with an electromagnetic proportional control valve; the continuous phase input port, the discrete phase input port and the pneumatic control chamber are respectively connected with an air pump, and the air pump is connected with an electromagnetic proportional control valve in a matching way; the upper computer is also connected with an acquisition card, and the acquisition card is connected with a photoelectric sensor; the photoelectric sensor is matched with the liquid drop input unit, and liquid drops in the liquid drop input unit are monitored through the photoelectric sensor.
Preferably, the liquid drop output unit is connected with a serpentine mixing channel.
Preferably, the fluid channel layer and the pneumatic control layer are provided with cross alignment marks which are matched with each other, and the alignment accuracy of the fluid channel layer and the pneumatic control layer can be improved through the cross alignment marks.
Preferably, the microinjection unit is rectangular, one end of the microinjection unit connected with the liquid drop output unit is conical, and one end of the microinjection unit far away from the liquid drop output unit is hemispherical.
Preferably, the method for regulating and controlling the droplet composition by using the droplet composition regulating and controlling device based on the bypass microinjection technology is characterized by comprising the following steps:
(1): the liquid in the liquid storage bottle is respectively sent into the continuous phase input port and the discrete phase input port through the control of the upper computer and the electromagnetic proportional control valve and the air pump connected with the continuous phase input port and the discrete phase input port;
(2): the liquid in the liquid storage bottle enters the multi-layer microfluidic chip through the continuous phase input port and the discrete phase input port respectively and then is converged in the liquid drop generating unit, and the continuous phase liquid and the discrete phase liquid enter the liquid drop conveying sheet after being converged in the liquid drop generating unit;
(3): when the liquid drop output unit passes through liquid drops, the photoelectric sensor transmits collected signals to the collecting card, the collecting card transmits the signals to the upper computer, the upper computer and the electromagnetic proportional control valve control an air pump connected with the pneumatic control chamber to work, and liquid in the microinjection unit is injected into the liquid drop output unit.
Preferably, the flow rate of the continuous phase liquid, the flow rate of the discrete phase liquid, and the liquid injection amount of the microinjection unit are controlled by controlling the air pressure output from the air pump.
Preferably, the continuous phase liquid flow rate, the discrete phase liquid flow rate and the liquid injection amount of the microinjection unit are controlled by controlling the air pressure output by the air pump, and the specific steps are as follows: converting the flow signal into air pressure through the upper computer, wherein the voltage of the electromagnetic proportional control valve and the air pressure are in linear proportional relation, and then converting the air pressure signal into a voltage signal through the upper computer and transmitting the voltage signal to the electromagnetic proportional control valve;
since the input signal is a flow signal, the flow signal is converted into an air pressure signal by a formula, and the relationship between the driving pressure Δp and the volume flow Q can be expressed as:
ΔP=R H Q
R H total fluid resistance for microchannel and reservoir pump
Figure BDA0003720837700000031
Wherein: l, h, w, η are the length, height, width, and viscosity of the liquid, respectively, of the microchannel.
Compared with the prior art, the invention has the following beneficial effects:
the invention takes the air pump as a drive, and can avoid damaging the biological activity of biological components in the reactant; the continuous phase liquid and the discrete phase liquid are respectively pumped into the multilayer microfluidic chip through the continuous phase input port and the discrete phase input port by controlling the air pump through the upper computer and the electromagnetic proportional control valve to form liquid drops; after the liquid drops enter the liquid drop output unit, the photoelectric sensor monitors that the liquid drops in the liquid drop output unit pass through, and then signals are transmitted to the acquisition card; the signal is fed back to the upper computer by the acquisition card, the air pump is controlled by the upper computer and the electromagnetic proportional control valve, the air is filled in the cavity of the whole pneumatic control layer, the elastic film between the pneumatic control cavity and the microinjection unit is pushed by the air to extrude the liquid in the microinjection unit, and the liquid in the microinjection unit is injected into the liquid drop in the liquid drop output unit, so that the reagent is added into the liquid drop, the volume of the added reagent can be accurately controlled by adjusting the air pressure of the pneumatic control cavity, and the accurate regulation and control of the liquid drop components are realized.
Drawings
Fig. 1 is a schematic structural diagram of a microfluidic device in embodiment 1 of the present invention;
fig. 2 is a schematic structural diagram of a multi-layer microfluidic chip according to embodiment 1 of the present invention;
fig. 3 is a schematic structural diagram of a fluid channel layer in embodiment 2 of the present invention.
In the figure: a fluid channel layer 1; an elastic film layer 2; a pneumatic control layer 3; a continuous phase input port 4; a discrete phase input port 5; a droplet generation unit 6; a droplet output unit 7; a pneumatic control chamber 8; a microinjection unit 9; a cross alignment mark 10; mixing channel 11.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail below by way of examples with reference to the accompanying drawings; it should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
The droplet component regulating and controlling device based on the bypass microinjection technology comprises a multi-layer microfluidic chip and a control module, wherein the control module is matched with the multi-layer microfluidic chip; the multi-layer micro-fluidic chip comprises a fluid channel layer 1 and a pneumatic control layer 3 which are sequentially arranged from top to bottom; an elastic film layer 2 is arranged between the fluid channel layer 1 and the pneumatic control layer 3; an input unit is arranged on the fluid channel layer 1, the input unit is connected with a liquid drop generating module, an outlet of the liquid drop generating module is connected with a liquid drop output unit 7, and an outlet of the liquid drop output unit 7 is connected with a mixing channel 11; the droplet output unit 7 is also provided with a microinjection module which is arranged at the downstream of the liquid output unit; the fluid channel layer 1, the elastic film layer 2 and the pneumatic control layer 3 are sequentially connected through the itch plasma treatment bonding.
The mixing channel 11 is a serpentine channel, the mixing channel 11 can fully mix reactants in synthetic liquid drops, and reaction parameters can be controlled by keeping injection volume and mixing time, so that monodisperse nanoparticle synthesis and the like are realized; the fluid channel layer 1 and the pneumatic control layer 3 are respectively provided with cross alignment marks 10 which are matched with each other; the cross alignment marks 10 on the fluid passage layer 1 and the pneumatic control layer 3 correspond to each other, and the alignment accuracy of the fluid passage layer 1 and the pneumatic control layer 3 can be improved by the cross alignment marks 10.
The droplet generation module comprises a continuous phase channel and a discrete phase channel; the input ends of the continuous phase channel and the discrete phase channel are respectively provided with a continuous phase input port 4 and a discrete phase input port 5, and the input unit is communicated with the continuous phase input port 4 and the discrete phase input port 5; the output port of the continuous phase channel is communicated with the output port of the discrete phase channel to form a liquid drop generating unit 6; the input unit comprises a plurality of liquid storage bottles filled with liquid, and the liquid storage bottles are respectively connected to the continuous phase input port 4 and the discrete phase input port 5 which are respectively corresponding to each other through liquid supply pipes; in this embodiment, the continuous phase input port 4 and the discrete phase input port 5 are connected with a liquid storage bottle containing continuous phase liquid and a liquid storage bottle containing discrete phase liquid through liquid supply pipes respectively.
The continuous communication channel comprises a first channel and a second channel; the first channel and the second channel are symmetrically distributed by taking the discrete phase channel as a symmetry axis, the output ports of the first channel and the second channel are communicated with the discrete communicated output ports, and the channels of the output ports of the first channel and the second channel are vertical to the discrete communicated channels; the input ports of the first and second channels are connected and communicate with the continuous phase input port 4.
The microinjection module comprises a microinjection unit 9 arranged on the fluid channel layer 1, and the microinjection unit 9 is communicated with the liquid drop output unit 7; the microinjection unit 9 is rectangular, one end of the microinjection unit 9 connected with the liquid drop output unit 7 is conical, and one end of the microinjection unit 9 far away from the liquid drop output unit 7 is hemispherical; the pneumatic control layer 3 is provided with a pneumatic control chamber matched with the microinjection unit 9; the elastic film layer 2 is arranged between the microinjection unit 9 and the pneumatic control chamber; the microinjection unit 9 is filled with a reagent to be added.
The pneumatic control chamber 8 comprises an air cavity, the air cavity is a square groove, and the air cavity is arranged at the joint of the microinjection unit 9 and the liquid drop output unit 7; the air cavity is connected with an air inlet through an air passage.
The control module comprises an upper computer; the upper computer is connected with an electromagnetic proportional control valve; the continuous phase input port 4, the discrete phase input port 5 and the pneumatic control chamber 8 are respectively connected with an air pump, and the air pump is connected with an electromagnetic proportional control valve in a matching way; the upper computer is also connected with an acquisition card, and the acquisition card is connected with a photoelectric sensor; the photoelectric sensor is matched with the liquid drop input unit, and liquid drops in the liquid drop input unit are monitored through the photoelectric sensor.
The connection mode of the air pump connected with the continuous phase input port 4: the air pump is connected with a liquid storage bottle connected with the continuous phase input port 4, an air channel connected with the air pump penetrates into the liquid storage bottle, and the liquid storage bottle is connected with the continuous phase input port 4 through a liquid supply pipe; when in operation, the device comprises: the air pump sends air into the liquid storage bottle through the air circuit, the air pressure in the liquid storage bottle increases and then the liquid is conveyed into the continuous phase input port 4 through the liquid supply pipe.
The connection mode of the air pump connected with the discrete phase input port 5: the air pump is connected with a liquid storage bottle connected with the discrete phase input port 5, an air path connected with the air pump extends into the liquid storage bottle, and the liquid storage bottle is connected with the discrete phase input port 5 through a liquid supply pipe; when in operation, the device comprises: the air pump sends air into the liquid storage bottle through the air circuit, the air pressure in the liquid storage bottle increases and then the liquid is conveyed into the discrete phase input port 5 through the liquid supply pipe.
The connection mode of the air pump connected with the pneumatic control chamber is as follows: the air pump is connected with an air inlet of the pneumatic control chamber 8 through an air circuit; when in operation, the device comprises: the gas is sent into the pneumatic control chamber 8 through the air pump, and the elastic film is extruded after the pneumatic control chamber 8 is filled with the gas, so that the reagent in the injection unit is injected into the liquid drops of the liquid drop output unit 7.
Wherein: the elastic film layer 2 adopts a PDMS elastic film; the elastic deformation of the PDMS elastic film has better accuracy and stability; the fluid channel layer 1 and the pneumatic control layer 3 are made of PDMS material; the diameter of the continuous phase input port 4 and the discrete phase input port 5 is 250 μm; the continuous communication channel width is 67-73 μm, the continuous communication channel width of this embodiment is 70 μm, and the depth is 100 μm; the width of the discrete communication channel is 48-52 μm, the width of the discrete communication channel is 50 μm, and the depth is 100 μm in the embodiment; the droplet output unit 7 is a channel having a width of between 48 and 52 μm, and the droplet output unit 7 of this embodiment has a width of 50 μm and a depth of 100 μm.
The working principle of the control module is that an upper computer controls an electromagnetic proportional control valve, an air pump connected with a continuous phase input port 4 and a discrete phase input port 5 is controlled to work through the electromagnetic proportional control valve, and continuous phase liquid and discrete phase liquid in a liquid storage bottle respectively connected with the continuous phase input port 4 and the discrete phase input port 5 are sent into a multilayer microfluidic chip through a liquid supply pipe; the continuous phase liquid and the discrete phase liquid enter a liquid drop output unit 7 after being fused by a liquid drop generating unit 6; when the liquid drops pass through the liquid drop output unit 7, the refractive index and the wavelength of the laser facula are changed, the photoelectric sensor captures the signals and then converts the signals into electric signals to be fed back to the acquisition card, the acquisition card transmits the signals to the upper computer, the upper computer sends out signals to the electromagnetic proportional control valve, the air pump connected with the pneumatic control chamber 8 works, the whole pneumatic control chamber 8 is filled with air, and when the air is redundant, the air pushes the elastic film on the upper layer to squeeze the liquid in the microinjection unit 9, so that the liquid in the microinjection unit 9 is injected into the liquid drop output unit 7, and then the liquid drops in the microinjection unit 9 are injected into the flowing liquid drops.
The mixing channel 11 is a serpentine channel, the mixing channel 11 can fully mix reactants in synthetic liquid drops, and reaction parameters can be controlled by keeping injection volume and mixing time, so that monodisperse nanoparticle synthesis and the like are realized; the fluid channel layer 1 and the pneumatic control layer 3 are respectively provided with cross alignment marks 10 which are matched with each other; the cross alignment marks 10 on the fluid passage layer 1 and the pneumatic control layer 3 correspond to each other, and the alignment accuracy of the fluid passage layer 1 and the pneumatic control layer 3 can be improved by the cross alignment marks 10.
The method for regulating and controlling the liquid drop components by using the liquid drop component regulating and controlling device based on the bypass microinjection technology comprises the following steps:
(1): the liquid in the liquid storage bottle is respectively sent into the continuous phase input port 4 and the discrete phase input port 5 through the control of the upper computer and the electromagnetic proportional control valve and the air pump connected with the continuous phase input port 4 and the discrete phase input port 5;
the flow rate of continuous phase liquid entering the multi-layer micro-fluidic chip, the flow rate of discrete phase liquid entering the multi-layer micro-fluidic chip and the quantity of liquid injected into the liquid drop output unit 7 of the micro-injection unit 9 are controlled by controlling the air pressure output by the air pump; the flow rate of the continuous phase liquid, the flow rate of the discrete phase liquid and the liquid injection amount of the microinjection unit 9 are controlled by controlling the air pressure output by the air pump, and the specific steps are as follows: converting the flow signal into air pressure through Labview program of the upper computer, wherein the voltage of the electromagnetic proportional control valve and the air pressure are in linear proportional relation, and then converting the air pressure signal into a voltage signal through the upper computer to be transmitted to the electromagnetic proportional control valve;
since the input signal is a flow signal, the flow signal is converted into an air pressure signal by a formula, and the relationship between the driving pressure Δp and the volume flow Q can be expressed as:
ΔP=R H Q
R H total fluid resistance for microchannel and reservoir pump
Figure BDA0003720837700000061
Wherein: l, h, w, η are the length, height, width of the microchannel and the viscosity of the liquid, respectively;
electromagnetic proportional control valves connected with the continuous phase input port 4, the discrete phase input port 5 and the air pumps of the microinjection units 9 are controlled by Labview program of the upper computer; the output air pressure of an air pump connected with the continuous phase input port 4, the discrete phase input port 5 and the microinjection unit 9 is controlled through an electromagnetic proportional control valve, so that the frequency and the volume of liquid drops are controlled;
(2): the continuous phase liquid and the discrete phase liquid in the liquid storage bottle enter the multi-layer microfluidic chip through the continuous phase input port 4 and the discrete phase input port 5 respectively and then are converged in the liquid drop generating unit 6, and the continuous phase liquid and the discrete phase liquid enter the liquid drop conveying sheet after being converged in the liquid drop generating unit 6;
(3): the liquid drop output unit 7 is monitored through the photoelectric sensor, when the liquid drop output unit 7 has liquid drops to pass through, the photoelectric sensor transmits collected signals to the collecting card, the collecting card transmits the signals to the upper computer, the upper computer and the electromagnetic proportional control valve control an air pump connected with the pneumatic control chamber 8 to work, and liquid in the microinjection unit 9 is injected into the liquid output unit.
Example 2
The difference from the embodiment 1 is that a plurality of channels of the microinjection unit 9 are added on the basis of the embodiment 1, the number of the injection channels can be adjusted according to actual needs, and the microinjection units 9 in the embodiment are three and are used for multi-step chemical reaction without cross contamination; the multi-layer micro-fluidic chip is provided with a pneumatic control chamber 8 matched with each micro-injection unit 9, and each pneumatic control chamber 8 is connected with an air pump matched with the pneumatic control chamber; the air pump connected with the pneumatic control chamber 8 is controlled by the upper computer, so that reagents are sequentially added into the liquid drops.
An electromagnetic proportional control valve controlled by Labview program of the upper computer; the air pump connected with each microinjection unit 9 is controlled through an electromagnetic proportional control valve; the photoelectric sensor detects that the liquid drop output unit 7 transmits signals to the acquisition card after the liquid drop passes through, the acquisition card transmits signals to the upper computer, the upper computer transmits signals to the electromagnetic proportional control valve, the electromagnetic proportional control valve controls the air pump connected with each microinjection unit 9 to work, further different reagents can be sequentially added into the liquid drop, the volume of the added reagents can be accurately controlled by adjusting the air pressure of the microinjection units 9, and therefore accurate regulation and control of liquid drop components are achieved.
The remaining parts are the same as in example 1.

Claims (7)

1. The droplet component regulating and controlling device based on the bypass microinjection technology is characterized by comprising a multi-layer microfluidic chip and a control module, wherein the control module is matched with the multi-layer microfluidic chip; the multilayer microfluidic chip comprises a fluid channel layer and a pneumatic control layer which are sequentially arranged from top to bottom, wherein cross alignment marks which are matched with each other are arranged on the fluid channel layer and the pneumatic control layer; an elastic film layer is arranged between the fluid channel layer and the pneumatic control layer; the fluid channel layer is provided with an input unit, the input unit is connected with a liquid drop generating module, an outlet of the liquid drop generating module is connected with a liquid drop output unit, and an outlet of the liquid drop output unit is connected with a mixing channel; the liquid drop output unit is also provided with a microinjection module, and the microinjection module is arranged at the downstream of the liquid output unit; the micro-injection module comprises a micro-injection unit arranged on the fluid channel layer, and the micro-injection unit is communicated with the liquid drop output unit; the pneumatic control layer is provided with a pneumatic control chamber matched with the microinjection unit; the elastic film layer is arranged between the microinjection unit and the pneumatic control chamber; the pneumatic control cavity comprises an air cavity, the air cavity is a square groove, and the air cavity is arranged at the joint of the microinjection unit and the liquid drop output unit; the air cavity is connected with an air inlet through an air passage; the control module comprises an upper computer; the upper computer is connected with an electromagnetic proportional control valve; the continuous phase input port, the discrete phase input port and the pneumatic control chamber are respectively connected with an air pump, and the air pump is connected with an electromagnetic proportional control valve in a matching way; the upper computer is also connected with an acquisition card, and the acquisition card is connected with a photoelectric sensor; the photoelectric sensor is matched with the liquid drop input unit, and liquid drops in the liquid drop input unit are monitored through the photoelectric sensor.
2. The droplet composition control device according to claim 1, wherein: the droplet generation module comprises a continuous phase channel and a discrete phase channel; the input ends of the continuous phase channel and the discrete phase channel are respectively provided with a continuous phase input port and a discrete phase input port, and the input unit is communicated with the continuous phase input port and the discrete phase input port; the output port of the continuous phase channel is communicated with the output port of the discrete phase channel to form a droplet generation unit.
3. The droplet component control device according to claim 2, wherein: the input unit comprises a plurality of liquid storage bottles filled with liquid, and the liquid storage bottles are respectively connected to the continuous phase input port and the discrete phase input port which are respectively corresponding through liquid supply pipes.
4. A droplet component control device according to claim 3, characterized in that: the continuous communication channel comprises a first channel and a second channel; the first channel and the second channel are symmetrically distributed by taking the discrete phase channel as a symmetry axis, the output ports of the first channel and the second channel are communicated with the discrete communication output ports, and the channels of the output ports of the first channel and the second channel are perpendicular to the discrete communication channels.
5. A method for regulating a droplet composition using the apparatus of claim 4, comprising the steps of:
(1): the liquid in the liquid storage bottle is respectively sent into the continuous phase input port and the discrete phase input port through the control of the upper computer and the electromagnetic proportional control valve and the air pump connected with the continuous phase input port and the discrete phase input port;
(2): the liquid in the liquid storage bottle enters the multi-layer microfluidic chip through the continuous phase input port and the discrete phase input port respectively and then is converged in the liquid drop generating unit, and the continuous phase liquid and the discrete phase liquid enter the liquid drop conveying unit after being converged in the liquid drop generating unit;
(3): when the liquid drop output unit passes through liquid drops, the photoelectric sensor transmits collected signals to the collecting card, the collecting card transmits the signals to the upper computer, the upper computer and the electromagnetic proportional control valve control an air pump connected with the pneumatic control chamber to work, and liquid in the microinjection unit is injected into the liquid drop output unit.
6. The method according to claim 5, wherein the flow rate of the continuous phase liquid, the flow rate of the discrete phase liquid, and the liquid injection amount of the microinjection unit are controlled by controlling the air pressure output from the air pump.
7. The method according to claim 6, wherein the control of the flow rate of the continuous phase liquid, the flow rate of the discrete phase liquid, and the liquid injection amount of the microinjection unit by controlling the air pressure output from the air pump comprises the specific steps of: converting the flow signal into air pressure through the upper computer, wherein the voltage of the electromagnetic proportional control valve and the air pressure are in linear proportional relation, and then converting the air pressure signal into a voltage signal through the upper computer and transmitting the voltage signal to the electromagnetic proportional control valve; because the input signal is a flow signal, the flow signal is converted into an air pressure signal through a formula, and the relation between the driving pressure delta P and the volume flow Q is expressed as follows:
ΔP=R H Q
R H total fluid resistance for microchannel and reservoir pump
Figure QLYQS_1
Wherein: l, h, w, η are the length, height, width, and viscosity of the liquid, respectively, of the microchannel.
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