CN114471762B - Design and implementation method of micro-fluidic chip capable of controlling ultralow flow velocity - Google Patents

Design and implementation method of micro-fluidic chip capable of controlling ultralow flow velocity Download PDF

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CN114471762B
CN114471762B CN202210160163.0A CN202210160163A CN114471762B CN 114471762 B CN114471762 B CN 114471762B CN 202210160163 A CN202210160163 A CN 202210160163A CN 114471762 B CN114471762 B CN 114471762B
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peristaltic pump
peristaltic
pipeline
control valve
stage
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CN114471762A (en
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王松伟
车丙晨
张策
孙聃
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Northwest University
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/50273—Containers 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 the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502746—Containers 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 the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers

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Abstract

The invention provides a design and implementation method of a micro-fluidic chip with controllable ultra-low flow velocity, wherein the chip comprises: independent peristaltic pump system of variable speed, the independent peristaltic pump system of basis, flow field regulation and control module, peristaltic pipeline output control valve one, peristaltic pipeline output control valve two, solution collecting pipe, independent peristaltic pump system, the independent peristaltic pump system of basis and flow field regulation and control module carry out two liang of connections through solution collecting pipe, flow field regulation and control module includes buffering output channel, multistage reposition of redundant personnel passageway, concentrates and observes the passageway, the independent peristaltic pump unit of variable speed gathers the peristaltic pipeline collecting pipe through output pipeline is unified. The invention controls the working logic of the onboard peristaltic pump system through a self-defined program, can generate stable ultralow flow rate, simplifies the control mode, ensures that the flow rate is more stable, can simultaneously generate multi-stage flow rate, and does not need an external flow field generating device.

Description

Design and implementation method of micro-fluidic chip capable of controlling ultra-low flow velocity
Technical Field
The invention relates to the technical field of microfluidics, in particular to a design and implementation method of a microfluidic chip capable of controlling ultralow flow velocity.
Background
At present, the micro-fluidic chip is widely applied to the field of scientific research by the characteristics of miniaturization, integration and the like, and the biological or chemical basic or application research is carried out through the control on micro-nano-scale fluid. The traditional micro-fluidic chip and platform mostly adopt an external injection pump or a peristaltic pump to control liquid to be input into a micro-channel of the micro-fluidic chip, and the flow speed are controlled by adjusting the propelling speed of the injection pump and the rotating speed of the peristaltic pump; the full-automatic microfluidic analyzers (Yang Shuaitao, chen Mingfeng, wang Qingsong and the like, full-automatic microfluidic analyzers, CN 111650168A) disclosed by Shenzhen Shang national Spanish Biotechnology Limited company only relate to the characteristic of micro-flow of a micro-channel, and liquid is guided in and analyzed through an uncontrolled capillary phenomenon; baidao medical science and technology ltd, suzhou, discloses a microfluidic chip cell detection device (Guo Jincheng, liu Yang, a microfluidic chip cell detection device, CN 111748445A), which utilizes an external injection pump to input liquid and detect cells in the chip. The liquid flow velocity in the chip is limited by the design performance and effective parameters of an external injection pump or a pressure pump, is influenced by external environmental conditions and operation modes (such as the connection mode, the movement and the switching port of a pipeline and the like), easily causes the problems of large flow velocity and flow fluctuation, poor repeatability of experimental results and the like, cannot meet the requirement of high-precision experiments, and in addition, the price of part of external flow velocity and flow control equipment is overhigh and can reach hundreds of thousands of yuan RMB.
Disclosure of Invention
The invention provides a design and implementation method of a micro-fluidic chip with controllable ultra-low flow rate, which is used for solving the problem that the flow rate of liquid in the chip is limited by the design performance of an externally-connected injection pump or a pressure pump.
As an embodiment of the invention: a microfluidic chip for controllable ultra-low flow rates, comprising: the system comprises an on-board peristaltic pump control system, a flow field regulation and control module, a peristaltic pipeline output control valve I, a peristaltic pipeline output control valve II and a solution collecting pipeline;
wherein, the onboard peristaltic pump control system consists of an independent peristaltic pump system and a basic independent peristaltic pump system, the basic independent peristaltic pump system and the flow field regulation and control module are connected in pairs through a solution collecting pipe I, the flow field regulation and control module comprises a buffer output channel, a multi-stage flow distribution channel and a centralized observation channel, wherein,
the buffer output channel includes: the variable-speed independent peristaltic pump system comprises a first buffer output channel, a second buffer output channel and a third buffer output channel, wherein 6 variable-speed independent peristaltic pump units connected in parallel are arranged in the variable-speed independent peristaltic pump system, and the variable-speed independent peristaltic pump units are collected to a peristaltic pipeline collecting pipeline through an output pipeline in a unified mode.
As an embodiment of the present invention: the microfluidic chip comprises two layers of structures, namely a chip fluid layer and a chip control layer, which are combined in a plasma bonding manner,
the chip fluid layer comprises a peristaltic pipeline of an onboard peristaltic pump control system, a solution collecting pipeline I, a solution collecting pipeline II, a buffer output channel, a multistage diversion channel, a centralized observation channel and a chip liquid outlet;
the chip control layer comprises a control valve of an onboard peristaltic pump control system, a chip liquid inlet and outlet control valve, a peristaltic pump liquid inlet selection control valve, a control valve liquid inlet channel and a control valve liquid outlet channel;
wherein, peristaltic pump feed liquor selection control valve includes: the liquid inlet selection control valve of the first peristaltic pump, the liquid inlet selection control valve of the second peristaltic pump and the liquid inlet selection control valve of the third peristaltic pump.
As an embodiment of the present invention: the variable-speed independent peristaltic pump system is formed by connecting 6 basic variable-speed independent peristaltic pump units in parallel, wherein each basic variable-speed independent peristaltic pump unit comprises a first liquid inlet, a selectable peristaltic pipeline output pipeline, a peristaltic pump liquid inlet selection control valve and a selectable peristaltic pump control valve, the basic variable-speed independent peristaltic pump units are connected in parallel to a peristaltic pipeline collecting pipeline, and whether a generated flow field is output or not is controlled by the first peristaltic pipeline output control valve; wherein the content of the first and second substances,
the selectable peristaltic pipelines at least comprise two types, each type at least comprises two liquid inlet channels, the number of the peristaltic pipelines participating in work is selected through a peristaltic pump liquid inlet selection control valve, the speed of the generated fluid is directly regulated and controlled, the peristaltic pump control valves of the selectable peristaltic pump control valves are three groups of independent control valves, each group comprises at least two types of control valves, each type of control valve at least comprises two control channels, the number and the types of the control valves contained in each type are the same, and the corresponding forms of circulation control are performed through selecting the number of the control pipelines of the peristaltic pumps providing peristaltic control; wherein the content of the first and second substances,
the selectable peristaltic pipelines are connected into the basic variable-speed independent peristaltic pump units in parallel and are converged to a selectable peristaltic pipeline output pipeline through the basic variable-speed independent peristaltic pump units; wherein the selectable peristaltic tubing; wherein the content of the first and second substances,
the selectable peristaltic tubing comprises: the peristaltic pipeline comprises a first-stage selectable peristaltic pipeline, a second-stage first selectable peristaltic pipeline, a second-stage second selectable peristaltic pipeline, a third-stage first selectable peristaltic pipeline, a third-stage second selectable peristaltic pipeline and a third-stage third selectable peristaltic pipeline;
the system comprises a first-stage first selectable peristaltic pump control valve, a second-stage first selectable peristaltic pump control valve, a first-stage second selectable peristaltic pump control valve, a second-stage second selectable peristaltic pump control valve, a first-stage third selectable peristaltic pump control valve, a second-stage third selectable peristaltic pump control valve and a second-stage third selectable peristaltic pump control valve.
As an embodiment of the present invention: the selectable peristaltic pump control valve comprises three different modes, wherein the first-stage mode is only provided with one control pipeline, the second-stage mode is that two control pipelines are connected in parallel, and the third-stage mode is that three control pipelines are connected in parallel; wherein the content of the first and second substances,
the control pipeline in the primary mode comprises a primary first selectable peristaltic pump control valve, a primary second selectable peristaltic pump control valve and a primary third selectable peristaltic pump control valve;
the control conduit of the secondary mode comprises: a second-stage first selectable peristaltic pump control valve, a second-stage second selectable peristaltic pump control valve and a third-stage selectable peristaltic pump control valve;
the control pipeline of the three-stage mode comprises: a two-stage first selectable peristaltic pump control valve, a two-stage second selectable peristaltic pump control valve, and a two-stage third selectable peristaltic pump control valve.
As an embodiment of the invention: the basic independent peristaltic pump system is formed by connecting 6 basic independent peristaltic pump units in parallel, and each basic independent peristaltic pump unit comprises a liquid inlet II, a peristaltic pipeline, a peristaltic pump control valve and a peristaltic pipeline output pipeline; the basic independent peristaltic pump unit is connected into a peristaltic pipeline collecting pipeline in a parallel mode, and a peristaltic pipeline output control valve II is used for controlling whether a generated flow field is output or not; wherein, the first and the second end of the pipe are connected with each other,
the basic independent peristaltic pump system comprises at least two parallel peristaltic pipelines and three groups of independently controlled peristaltic pump control valves; the peristaltic pipeline is used for increasing the total amount of liquid inlet in the peristaltic process, and the peristaltic pump control valve is used for performing circulation logic control;
the peristaltic tubing includes: a peristaltic pipeline I and a peristaltic pipeline II;
the peristaltic pump control valve includes: a basically independent peristaltic pump control valve 1, a basically independent peristaltic pump control valve 2 and a basically independent peristaltic pump control valve 3.
As an embodiment of the invention: the first solution collecting pipeline and the second solution collecting pipeline are connected in series with the first peristaltic pipeline collecting pipeline and the second peristaltic pipeline collecting pipeline, and whether the solution is output to the solution collecting pipeline and the buffer output channel is controlled through the first peristaltic pipeline output control valve and the second peristaltic pipeline output control valve;
the buffer output channel is used for performing stable filtering processing on the flow field of the solution collecting pipeline and filtering the fluctuation generated by the working mode of the peristaltic pump system;
each stage of the multi-stage flow distribution channel generates a pair of stable flow velocities which are equal to each other in size and are half of the input flow velocity of the previous stage, a multi-stage flow field from low to high is generated in the centralized observation channel, and the multi-stage flow fields are converged into the multi-stage flow distribution output channel and output to the chip through the liquid outlet;
the centralized observation channel consists of at least two flow velocity flow distribution output channels, and each 2 flow channels are a group of flow fields and are ultra-low flow velocity collection and sample control areas; the flow speed distribution output channel comprises a first output channel, a second output channel, a third output channel, a fourth output channel, a fifth output channel, a sixth output channel, a seventh output channel, an eighth output channel, a ninth output channel, a tenth output channel, an eleventh output channel and a twelfth output channel.
As an embodiment of the present invention: the onboard peristaltic pump control system performs peristaltic motion through a preset program, drives a peristaltic pump control valve to work by controlling a pneumatic miniature electromagnetic valve, pumps liquid into a chip fluid layer according to a preset execution logic, and controls the pneumatic miniature electromagnetic valve to be switched on and off by connecting a hollow metal pipe to an inlet of a chip control valve through the tail end of a liquid pipeline and driving the liquid in the liquid pipeline to enter the control valve of the chip through compressed gas;
the on-off state of pneumatic miniature solenoid valve is controlled through predetermined procedure, when the valve state is for opening, compressed gas and liquid pipeline and chip control valve inlet UNICOM, drive liquid makes control valve department film deformation make the pipeline that the fluid layer corresponds the position close, when the valve state is for closing, the input of interruption compressed gas, excessive gas in the pipeline is discharged by the solenoid valve hole of losing heart simultaneously, and communicate liquid pipeline and chip control valve inlet and atmosphere, pressure is applyed in the release, control valve department film resumes the relaxed state, the pipeline that the fluid layer corresponds the position switches on.
As an embodiment of the present invention: the method comprises the following steps:
step 1: placing the prepared chip on an inverted fluorescence microscope objective table, and sequentially connecting a pneumatic control valve to a liquid inlet of a chip control layer according to the serial number of the control valve;
step 2: the driving air pressure of the pneumatic miniature electromagnetic valve is adjusted to 25psi through a digital air pressure meter, all control valves are opened through a preset program, and control layer degassing is carried out;
and step 3: after the control layer is degassed, closing peristaltic pump control valves and peristaltic pipeline output control valves of all the channels, and closing a total liquid inlet control valve of any channel;
and 4, step 4: driving a fluorescent particle solution by using 2.5psi air pressure to degas the chip from a liquid inlet for closing the main liquid inlet control valve, and closing the main liquid outlet control valve when liquid flows out from the main liquid outlet;
and 5: after degassing of the fluid layer is finished, performing basic ultra-low flow rate test;
step 6: the parameters of the test were selected to achieve the target ultra low flow rate and then long time application of force to the sample was initiated while imaging was performed with the microscope.
As an embodiment of the present invention: the step of the basic ultra low flow rate test comprises:
s101: a control valve for opening a liquid inlet of the fluorescent particle solution and a peristaltic pump control valve of the passage;
s102: 2.5psi of air pressure is used for driving phosphate buffer solution to be input into the chip from the other total liquid inlets;
s103: closing the connected liquid inlet control valve;
s104: setting cycle parameters through a preset program, inputting the time interval of the control logic of the peristaltic pump system, the peristaltic time and the waiting time for starting the next cycle, and clicking to start the peristaltic cycle;
s105: observing a second-stage shunting input channel and a last-stage shunting input channel of the centralized observation channel through a fluorescence microscope, comparing the current particle flow rate, and stabilizing a flow field and reducing the relative flow rate through a switch buffer output channel control valve; the second-stage shunting input channel corresponds to a first channel, and the last-stage shunting input channel corresponds to a last channel;
s106: and obtaining system parameters of the target flow field, including the number of the selected buffer output channels, the working time interval of a peristaltic pump control valve and the waiting time for starting the next cycle.
As an embodiment of the invention: in the basic ultra-low flow rate test process, the method further comprises the following steps:
when testing is carried out aiming at basic ultra-low flow velocity, recording system parameters under different flow fields in real time, and synchronously storing the system parameters of the different flow fields to a cloud database;
acquiring parameter data of the cloud database, constructing a flow rate control model according to the parameter data, acquiring flow field parameter change characteristics based on the flow rate control model, and performing multi-dimensional data analysis on the flow field parameter characteristics to acquire a primary data processing result; the flow rate control model is used for determining a target flow field according to system parameters in different flow fields;
performing visualization processing on the primary data processing result to obtain a secondary data processing result;
and performing fault detection on the microfluidic chip based on the secondary data processing result to obtain a fault detection result, judging the fault reason when the fault detection result shows that the microfluidic chip has a fault problem, and determining the judgment result.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and drawings.
The technical solution of the present invention is further described in detail by the accompanying drawings and embodiments.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:
FIG. 1 is a schematic diagram of a basic cell design of a controllable ultra-low flow rate microfluidic chip according to an embodiment of the present invention;
FIG. 2 is a flow rate range diagram generated by a basic independent peristaltic pump system in a controllable ultra-low flow rate microfluidic chip according to an embodiment of the present invention;
fig. 3 is a flow field stability test chart generated by using a basic independent peristaltic pump system in a controllable ultra-low flow rate microfluidic chip according to an embodiment of the present invention.
FIG. 1, 1-a variable speed independent peristaltic pump system; 2-a substantially independent peristaltic pump system; 3-a flow field regulation module; 4-a peristaltic pipeline output control valve I and 5-a peristaltic pipeline output control valve II; 6-solution collecting pipeline I;
the basic unit parts of the variable speed independent peristaltic pump system 1 are respectively: 101-liquid inlet; 102-one stage of selectable peristaltic pipelines; 103-a second level first selectable peristaltic tubing, 104-a second level second selectable peristaltic tubing; 105-three stages of first selectable peristaltic pipelines, 106-three stages of second selectable peristaltic pipelines and 107-three stages of third selectable peristaltic pipelines; 108-a first peristaltic pump feed liquid selection control valve; 109-a liquid inlet selection control valve of a second peristaltic pump; 110-a third peristaltic pump liquid inlet selection control valve; 111-a first selectable peristaltic pump control valve of the stage one; 112-a two-stage first selectable peristaltic pump control valve; 113-a two-stage first selectable peristaltic pump control valve; 114-a stage one second selectable peristaltic pump control valve; 115-a two-stage second selectable peristaltic pump control valve; 116-a second selectable peristaltic pump control valve; 117-a primary third selectable peristaltic pump control valve; 118-a second stage third selectable peristaltic pump control valve; 119-a second stage third selectable peristaltic pump control valve; 120-an optional peristaltic tubing output tubing; 6 groups of basic units are connected in parallel and then collected by a first collecting pipeline of a 121-peristaltic pipeline;
the basic unit parts of the basic independent peristaltic pump system 2 are respectively: 201-peristaltic pipeline one and 203-peristaltic pipeline two; 202-liquid inlet; 204-substantially independent peristaltic pump control valve 1; 205-substantially independent peristaltic pump control valve 2; 206-substantially independent peristaltic pump control valve 3; 207-peristaltic tubing output tubing; 6 groups of basic units are connected in parallel and then are gathered by a 208-peristaltic pipeline gathering pipeline II.
301-a first buffered output channel, 302-a second buffered output channel, 303-a third buffered output channel; 304-solution collecting pipe two; 305-first-stage flow distribution channel one, 338-second-stage flow distribution channel one; 306-a first-stage flow distribution channel II and 337-a second-stage flow distribution channel II; 307-first-stage flow distribution channel III and 336-second-stage flow distribution channel III; 308-first-stage shunting channel IV and 335-second-stage shunting channel IV; 309-a first-stage flow distribution channel five and 334-a second-stage flow distribution channel five; 310-first-stage flow splitting channel six, 311-second-stage flow splitting channel six, 312-third-stage flow splitting channel six, 313-fourth-stage flow splitting channel six, 314-fifth-stage flow splitting channel six, 315-sixth-stage flow splitting channel six, 328-seventh-stage flow splitting channel six, 329-eighth-stage flow splitting channel six, 330-ninth-stage flow splitting channel six, 331-tenth-stage flow splitting channel six, 332-eleventh-stage flow splitting channel six, 333-twelfth-stage flow splitting channel six; 316-first output channel, 317-second output channel, 318-third output channel, 319-fourth output channel, 320-fifth output channel, 321-sixth output channel, 322-seventh output channel, 323-eighth output channel, 324-ninth output channel, 325-tenth output channel, 326-eleventh output channel, 327-twelfth output channel; 339-a liquid outlet;
in fig. 3, flow field stability generated with a basic independent peristaltic pump system: a. the natural fluctuation flow field generated by the peristaltic pump system presents a stable output flow field like a solid line after filtering the fluctuation by a specific method; b. after the input and output velocities are normalized, the stability of the flow field after passing through the process can be found to be high.
Detailed Description
The preferred embodiments of the present invention will be described in conjunction with the accompanying drawings, and it will be understood that they are described herein for the purpose of illustration and explanation and not limitation.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Example 1:
the embodiment of the invention provides a design and implementation method of a microfluidic chip with controllable ultra-low flow rate, as shown in figure 1, comprising the following steps: the system comprises an on-board peristaltic pump control system, a flow field regulation and control module 3, a peristaltic pipeline output control valve I4, a peristaltic pipeline output control valve II 5 and a solution collecting pipeline 6;
wherein the onboard peristaltic pump control system consists of an independent peristaltic pump system 1 and a basic independent peristaltic pump system 2, the independent peristaltic pump system 1, the basic independent peristaltic pump system 2 and a flow field regulation and control module 3 are connected in pairs through a solution collecting pipeline I6, the flow field regulation and control module 3 comprises a buffer output channel, a multi-stage flow dividing channel and a centralized observation channel, wherein,
the buffer output channel includes: the variable-speed independent peristaltic pump system comprises a first buffer output channel 301, a second buffer output channel 302 and a third buffer output channel 303, wherein 6 parallel variable-speed independent peristaltic pump units are arranged in the variable-speed independent peristaltic pump system 1, and the variable-speed independent peristaltic pump units are collected to a peristaltic pipeline collecting pipeline 121 through output pipelines;
when the system is implemented, two independent onboard peristaltic pump control systems are adopted, a peristaltic pump unit of any one peristaltic pump system is driven to operate in a linkage manner through an automatic control program, an input liquid is driven to generate a flow field mode required by an experiment, meanwhile, any one independent peristaltic pump unit can also work independently, the independent peristaltic pump system is divided into a basic independent peristaltic pump system and a variable-speed independent peristaltic pump system, and the variable-speed independent peristaltic pump system comprises a total liquid inlet, a peristaltic pipeline with the width of 100 micrometers and a peristaltic pump control valve with the width of 100 micrometers, and the variable-speed independent peristaltic pump system further comprises a peristaltic pump liquid inlet selection valve with the width of 100 micrometers;
preferably, the basic independent peristaltic pump system is provided with at least two peristaltic pipelines (with the width of 100 μm) for increasing the total amount of liquid fed in the peristaltic process, and three groups of independently controlled peristaltic pump control valves (with the width of 200 μm) for realizing the circulating peristaltic control;
preferably, the variable-speed independent peristaltic pump system is composed of a selectable peristaltic pipeline (with the width of 100 μm), a peristaltic pump liquid inlet selection control valve (with the width of 100 μm) and a selectable peristaltic pump control valve (with the width of 100 μm);
the beneficial effects of the above technical scheme are: the two independent onboard peristaltic pump control systems drive the peristaltic pump units of any one peristaltic pump system to operate in a linkage manner through an automatic control program, so that the individualized experiment requirements are favorably met, and rich smooth mode selection is provided; in addition, various peristaltic pipelines can be selected, each type of peristaltic liquid inlet channels comprises different numbers, and the number of the peristaltic pipelines participating in the work is selected through the peristaltic pump liquid inlet selection control valve, so that the speed of the generated fluid can be directly regulated and controlled.
Example 2:
in one embodiment, as shown in fig. 1, the microfluidic chip is composed of two layers, namely a chip fluidic layer and a chip control layer, which are bonded by means of plasma bonding, wherein,
the chip fluid layer comprises a peristaltic pipeline of an on-board peristaltic pump control system, a solution collecting pipeline I6, a solution collecting pipeline II 304, a buffer output channel, a multi-stage flow dividing channel, a centralized observation channel and a chip liquid outlet 339;
the chip control layer comprises a control valve of an on-board peristaltic pump control system, a chip liquid inlet and outlet control valve, a peristaltic pump liquid inlet selection control valve, a control valve liquid inlet channel and a control valve liquid outlet channel;
wherein, peristaltic pump feed liquor selection control valve includes: a first peristaltic pump liquid inlet selection control valve 108, a second peristaltic pump liquid inlet selection control valve 109 and a third peristaltic pump liquid inlet selection control valve 110;
when the method is implemented, firstly, degassing treatment is carried out on a chip fluid layer and a control layer, and a flow field regulating and controlling module 3 inputs a flow field in a solution collecting pipeline 6 from a solution collecting pipeline 304; firstly, filtering a flow field through a buffer output channel; then outputting the filtered flow field to a next stage of flow distribution channel in a grading manner through the flow distribution channel; the graded flow field flows through the observation channel, is converged to the shunt channel, is converged by the shunt channel, and is output from the liquid outlet 339 to a system or provides a required flow field for a downstream chip;
the beneficial effects of the above technical scheme are: the flow field is filtered in the buffer output channel, so that more stable ultralow flow rate can be generated, and when the flow rate is stable, multistage flow rate can be generated at the same time, so that a downstream chip can quickly acquire a target flow field.
Example 3:
in one embodiment, as shown in fig. 1, the variable speed independent peristaltic pump system 1 is composed of 6 basic variable speed independent peristaltic pump units connected in parallel, wherein the basic variable speed independent peristaltic pump units include a first liquid inlet 101, a selectable peristaltic pipeline output pipeline 120, a peristaltic pump liquid inlet selection control valve, and a selectable peristaltic pump control valve, the basic variable speed independent peristaltic pump units are connected in parallel to a peristaltic pipeline collection pipeline 121, and whether a generated flow field is output or not is controlled by a first peristaltic pipeline output control valve 4; wherein the content of the first and second substances,
the selectable peristaltic pipelines at least comprise two types, each type at least comprises two liquid inlet channels, the number of the peristaltic pipelines participating in the work is selected through a peristaltic pump liquid inlet selection control valve, the generated fluid speed is directly regulated and controlled, the peristaltic pump control valves of the selectable peristaltic pump control valves are three groups of independent control valves, each group comprises at least two types of control valves, each type of control valve at least comprises two control channels, the number and the types of the control valves contained in each type are the same, and the corresponding forms of circulation control are performed through selecting the number of the control pipelines of the peristaltic pumps providing peristaltic control; wherein the content of the first and second substances,
the selectable peristaltic pipelines are connected into the basic variable-speed independent peristaltic pump units in parallel and are collected to a selectable peristaltic pipeline output pipeline 120 through the basic variable-speed independent peristaltic pump units; wherein the selectable peristaltic tubing; the selectable peristaltic pump control valves are arranged in a parallel manner;
when the invention is implemented, when a flow field is generated by the variable speed independent peristaltic pump system 1, firstly, liquid is driven by compressed gas to flow in a shunt way from the liquid inlet 101 to enter the peristaltic pipeline, the opened peristaltic pump control valve blocks the liquid, the selection of the peristaltic pipeline is carried out according to the selection, for example, the liquid inlet selection control valve 108 is closed, so that the selectable peristaltic pipeline 102 can carry out liquid input, thereby participating in peristaltic circulation, at the moment, the states of 6 liquid inlets are the same, but through the control logic of the peristaltic pump system, the liquid is controlled and input into a chip, and the basic circulation control logic corresponds to six steps: 100. 110, 010, 011, 001, 101 respectively control a selectable peristaltic pump control valve 1, a selectable peristaltic pump control valve 2, and a selectable peristaltic pump control valve 3, the solution is collected from a selectable peristaltic pipe output pipe 120 to a closed peristaltic pipe collection pipe 121 of a peristaltic pipe output control valve 4 through a coordinated control flow field, and is conveyed to a solution collection pipe 304 through a solution collection pipe 6, at this time, since the peristaltic pipe output control valve 5 is opened, the liquid is not conveyed to a selectable peristaltic pipe collection pipe 208, filtering processing is performed according to whether a buffer output channel is opened, the filtered liquid is continuously conveyed to a first-stage diversion channel one 305 through a solution collection pipe two 304, flows into a first-stage diversion channel two 306 and a first-stage diversion channel six 310 after being shunted, is shunted to a first output channel 316 through the first-stage diversion channel six 310, and is collected to a twelfth-stage diversion channel six 333 through a second output channel 317, and is then collected to a second-stage diversion channel one 338; the flow is divided by a first-stage flow dividing channel II 306, flows into a first-stage flow dividing channel III 307 and a sixth-stage flow dividing channel VI 315, is divided by the sixth-stage flow dividing channel VI 315 into an eleventh output channel 326, a twelfth output channel 327 and is converged into a seventh-stage flow dividing channel VI 328, and is converged into a second-stage flow dividing channel 337; the flow is split by the first-stage flow splitting channel three 307, flows into the first-stage flow splitting channel four 308 and the fifth-stage flow splitting channel six 314, is split by the fifth-stage flow splitting channel six 314 to the ninth output channel 324, is converged by the tenth output channel 325 to the eighth-stage flow splitting channel six 329, and is converged by the second-stage flow splitting channel three 336; the flow is split by the first-stage splitting channel four 308, flows into the ninth-stage splitting channel six 330 and the fourth-stage splitting channel six 313, is split by the fourth-stage splitting channel six 313 to the seventh output channel 322, is converged by the eighth output channel 323 to the ninth-stage splitting channel six 330, and is converged by the second-stage splitting channel four 335; the flow is split by a first-stage flow splitting channel five 309, then flows into a second-stage flow splitting channel six 311 and a third-stage flow splitting channel six 312, is converged into a tenth-stage flow splitting channel six 331 and an eleventh-stage flow splitting channel six 332 by a third output channel 318, a fourth output channel 319, a fifth output channel 320 and a sixth output channel 321, is converged into a second-stage flow splitting channel four 335 by a second-stage flow splitting channel five 334, is converged into a flow field of the other part of the second-stage flow splitting channel four 335, is converged into a second-stage flow splitting channel three 336 and is converged into a flow field of the second-stage flow splitting channel three 336, is output into a second-stage flow splitting channel two 337, and is converged into the other part of the flow field, and the variable-speed independent peristaltic pump system needs to perform additional operation:
(1) selecting one group of a first peristaltic pump liquid inlet selection control valve 108, a second peristaltic pump liquid inlet selection control valve 109 and a third peristaltic pump liquid inlet selection control valve 110 to work, so as to select the number of peristaltic pipelines participating in peristaltic work;
(2) the number of control pipelines for peristaltic work is selected through a selectable peristaltic pump control valve, so that different liquid peristaltic speeds are provided;
in this embodiment, the number of peristaltic pipelines of the basic independent peristaltic pump system and the number of control pipelines of the peristaltic pump control valve are constant values, and flow rate selection by selecting pipeline parameters cannot be performed; wherein, the first and the second end of the pipe are connected with each other,
the number of the peristaltic pipelines is that after being input from the liquid inlet 202, the peristaltic pipelines are divided into 9 paths of peristaltic pipelines, are output to the peristaltic pipeline output pipeline 207 through a peristaltic pump control valve, are converged to the peristaltic pipeline convergence pipeline 208 and are output to the next stage;
a first-stage peristaltic pump control valve 204, a second-stage peristaltic pump control valve 205 and a third-stage peristaltic pump control valve 206, which are three groups as shown in fig. 1, but the number of control pipelines of each stage is 4, and the control pipelines of each stage are connected in parallel, and each stage is independently and centrally controlled by a control valve liquid inlet channel;
each independent peristaltic pump unit operates according to the same six steps (100, 110, 010, 011, 001, 101);
the six steps work in 6 independent peristaltic pump units in a manner of starting at the same time as the next step of the previous step, and each path is set to run at the same time interval, namely:
the initial state of the 6 peristaltic pump units is that all valves are in a closed state, namely all valves are 1;
the first independent peristaltic unit operates the step 1, and the second to the sixth independent peristaltic units do not act;
the first independent peristaltic unit runs step 2 110, the second independent peristaltic unit runs step 1 and step 100, and the third to sixth independent peristaltic units do not act;
the first independent peristaltic unit runs step 3 010, the second independent peristaltic unit runs step 2, the third independent peristaltic unit runs step 1, step 110, and the fourth to sixth independent peristaltic units do not act;
the first independent peristaltic unit runs through the 4 th step 011, the second independent peristaltic unit runs through the 3 rd step 010, the third independent peristaltic unit runs through the 2 nd step 110, the fourth independent peristaltic unit runs through the 1 st step 100, and the fifth to sixth independent peristaltic units do not act;
the first independent peristaltic unit operates in the 5 th step 001, the second independent peristaltic unit operates in the 4 th step 011, the third independent peristaltic unit operates in the 3 rd step 010, the fourth independent peristaltic unit operates in the 2 nd step 110, the fifth independent peristaltic unit operates in the 1 st step 100, and the sixth independent peristaltic unit does not act;
the first independent peristaltic unit runs in the 6 th step 101, the second independent peristaltic unit runs in the 5 th step 001, the third independent peristaltic unit runs in the 4 th step 011, the fourth independent peristaltic unit runs in the 3 rd step 010, the fifth independent peristaltic unit runs in the 2 nd step 110, and the sixth independent peristaltic unit runs in the 1 st step 100; … …
The first independent peristaltic unit operates in step 1 and step 110, the second independent peristaltic unit operates in step 2, the third independent peristaltic unit operates in step 3 and step 010, the fourth independent peristaltic unit operates in step 4 and step 011, the fifth independent peristaltic unit operates in step 5 and step 001, and the sixth independent peristaltic unit operates in step 6 and step 101;
when the sixth independent peristaltic unit finishes the step 6, a complete cycle is finished;
the self-defined control program needs to input a time interval Int between each step in the six steps in a unit of ms, a time Dur to wait for a new cycle to start after the six steps are finished, a unit of s, a cycle total number Cyc and a unit of times, and then clicks to start the cycle to creep to generate the ultra-low flow rate;
the beneficial effects of the above technical scheme are: the invention drives the compressed gas to enter the peristaltic pipeline from the liquid inlet, which is beneficial to the selectable peristaltic pipeline to input liquid, thereby participating in peristaltic circulation, and in addition, the basic circulation control logic respectively controls the basically independent peristaltic pump control valves, which is beneficial to preventing the liquid from being conveyed to the selectable peristaltic pipeline collecting pipeline; the peristaltic cycle is performed by custom control logic, which facilitates the production of ultra-low flow rates.
Example 4:
in one embodiment, as shown in FIG. 1, the selectable peristaltic pump control valve comprises three different modes, wherein a primary mode has only one control conduit, a secondary mode has two control conduits connected in parallel, and a tertiary mode has three control conduits connected in parallel; wherein the content of the first and second substances,
the control pipeline of the primary mode comprises a primary first selectable peristaltic pump control valve 111, a primary second selectable peristaltic pump control valve 114 and a primary third selectable peristaltic pump control valve 117;
the control conduit of the secondary mode comprises: a secondary first selectable peristaltic pump control valve 112, a secondary second selectable peristaltic pump control valve 115, a secondary third selectable peristaltic pump control valve 118;
the control pipeline of the three-stage mode comprises: a two-stage first selectable peristaltic pump control valve 113, a two-stage second selectable peristaltic pump control valve 116, a two-stage third selectable peristaltic pump control valve 119;
when the invention is implemented, any mode needing to participate in work in the three groups of control valves can be selected according to the required flow rate, so that 9 combinations can be generated, the lowest driving pressure is the mode 1 of the three groups of control valves, the corresponding three groups of control valves are respectively the control valve 111, the control valve 114 and the control valve 117, the highest driving pressure is the mode 3 of the three groups of control valves, and the corresponding three groups of control valves are respectively the control valve 113, the control valve 116 and the control valve 119;
in the embodiment, the number of control pipelines of the selectable peristaltic pump control valve is respectively 1 control pipeline, 2 control pipelines and 3 control pipelines;
when 1 peristaltic pipeline is selected to participate in peristaltic work and 1 control pipeline provides drive, the generated minimum flow rate provided for the current speed change system is set as a, and when 3 peristaltic pipelines are selected to participate in peristaltic work and 3 control pipelines provide drive, the generated maximum flow rate provided for the current speed change system is theoretically 9 times a;
finally, the water is collected into a first secondary flow-dividing channel 338 and flows out through a liquid outlet 339;
the beneficial effects of the above technical scheme are: according to the invention, different working modes are selected according to different flow rates, so that an ultra-low flow field is generated by the onboard peristaltic pump system, the flow field is stable, and other external injection pumps are not needed.
Example 5:
in one embodiment, as shown in fig. 1, the basic independent peristaltic pump system 2 is composed of 6 basic independent peristaltic pump units connected in parallel, and the basic independent peristaltic pump units include a second liquid inlet 202, a peristaltic pipeline, a peristaltic pump control valve, and a peristaltic pipeline output pipeline 207; the basic independent peristaltic pump unit is connected into a peristaltic pipeline collecting pipeline 208 in a parallel mode, and whether a generated flow field is output or not is controlled by a peristaltic pipeline output control valve II 5; wherein the content of the first and second substances,
the basic independent peristaltic pump system 2 comprises at least two parallel peristaltic pipelines and three groups of independently controlled peristaltic pump control valves; the peristaltic pipeline is used for increasing the total amount of liquid inlet in the peristaltic process, and the peristaltic pump control valve is used for performing circulation logic control;
the peristaltic tubing includes: a peristaltic pipeline I201 and a peristaltic pipeline II 203;
the peristaltic pump control valve includes: a substantially independent peristaltic pump control valve 1 204, a substantially independent peristaltic pump control valve 2 205, a substantially independent peristaltic pump control valve 3 206;
when the invention is implemented, when the flow field is generated by the basic independent peristaltic pump system 2, firstly the liquid is driven by compressed gas to flow into the peristaltic pipelines 201 and 203 from the liquid inlet 202, the opened peristaltic pump control valve 204 blocks the liquid, at this time, the states of the 6 liquid inlets are the same, but through the control logic of the peristaltic pump system, the liquid is controlled and input into the chip, and the basic circulation control logic correspondingly comprises: 100. 110, 010, 011, 001, 101, respectively controlling a first-stage basic independent peristaltic pump control valve 1, a second-stage basic independent peristaltic pump control valve 2, and a third-stage basic independent peristaltic pump control valve 3, so that the solution is collected from the peristaltic tube output tube 207 to the peristaltic tube collecting tube 208 of the closed peristaltic tube output control valve 5, and is delivered from the solution collecting tube 6 to the solution collecting tube 304, and since the peristaltic tube output control valve 4 is opened at this time, the liquid is not delivered to the selectable peristaltic tube collecting tube one 121. According to whether the buffer output channel is opened for filtering processing, liquid after filtering processing is continuously conveyed to the first-stage flow dividing channel 305 through the solution collecting pipeline 304, flows into the second first-stage flow dividing channel 306 and the sixth first-stage flow dividing channel 310 after being divided, is divided into a first output channel 316 through the sixth first-stage flow dividing channel 310, is collected to the sixth twelve-stage flow dividing channel 333 through the second output channel 317, and is collected to the first second-stage flow dividing channel 338; the flow is divided by a first-stage flow dividing channel II 306, flows into a first-stage flow dividing channel III 307 and a sixth-stage flow dividing channel VI 315, is divided by the sixth-stage flow dividing channel VI 315 into an eleventh output channel 326, a twelfth output channel 327 and is converged into a seventh-stage flow dividing channel VI 328, and is converged into a second-stage flow dividing channel 337; the flow is split by the first-stage flow splitting channel three 307, flows into the first-stage flow splitting channel four 308 and the fifth-stage flow splitting channel six 314, is split by the fifth-stage flow splitting channel six 314 to the ninth output channel 324, is converged by the tenth output channel 325 to the eighth-stage flow splitting channel six 329, and is converged by the second-stage flow splitting channel three 336; the flow is divided by the first-stage flow dividing channel four 308, flows into the first-stage flow dividing channel five 309 and the fourth-stage flow dividing channel six 313, is divided by the fourth-stage flow dividing channel six 313 to the seventh output channel 322, is collected by the eighth output channel 323 to the ninth-stage flow dividing channel six 330, and is collected to the second-stage flow dividing channel four 335; the flow is divided by a first-stage flow dividing channel five 309, flows into a second-stage flow dividing channel six 311 and a third-stage flow dividing channel six 312, is converged into a tenth-stage flow dividing channel six 331 and an eleventh-stage flow dividing channel six 332 by a third output channel 318, a fourth output channel 319, a fifth output channel 320 and a sixth output channel 321, is converged into a second-stage flow dividing channel four 335 by a second-stage flow dividing channel five 334, is converged with the flow field of the other second-stage flow dividing channel four 335, is converged into a second-stage flow dividing channel three 336, is converged with the flow field of the second-stage flow dividing channel three 336, is output into a second-stage flow dividing channel two 337, is converged with the other flow field of the second-stage flow dividing channel three 336, and finally is converged into a first second-stage flow dividing channel 338 and flows out through a liquid outlet 339
The beneficial effects of the above technical scheme are: when the flow field is generated by the basic independent peristaltic pump system, the basic independent peristaltic pump system 2 is formed by expanding 6 basic independent peristaltic pump units, so that liquid discontinuity caused by time intervals between each step is compensated, the continuous flow field can be stably provided while the interval time is increased, the ultra-low flow field is favorably generated, and other external injection pumps are not needed.
Example 6:
in one embodiment, as shown in fig. 1, the first solution collecting pipe 6 and the second solution collecting pipe 304 are connected in series to the first peristaltic pipe collecting pipe 121 and the second peristaltic pipe collecting pipe 208, and whether the first peristaltic pipe collecting pipe and the second peristaltic pipe collecting pipe are output to the solution collecting pipe and the buffer output channel is controlled by the first peristaltic pipe output control valve 4 and the second peristaltic pipe output control valve 5;
the buffer output channel is used for performing stable filtering processing on the flow field of the solution collecting pipeline 304 and filtering the fluctuation generated by the working mode of the peristaltic pump system;
each stage of flow of the multistage shunting channel generates a pair of stable flow velocities which are equal in size and are half of the input flow velocity of the previous stage, a multistage flow field from low to high is generated in the centralized observation channel, and the multistage flow fields are converged to the multistage shunting output channel and output to the chip through the liquid outlet 339;
the centralized observation channel consists of at least two flow velocity distribution output channels, and each 2 flow channels are a group of flow fields and are collection and sample control areas with ultralow flow velocity; the flow rate split output channels comprise a first output channel 316, a second output channel 317, a third output channel 318, a fourth output channel 319, a fifth output channel 320, a sixth output channel 321, a seventh output channel 322, an eighth output channel 323, a ninth output channel 324, a tenth output channel 325, an eleventh output channel 326, and a twelfth output channel 327;
when the invention is implemented, the solution collecting pipeline 6 is used for collecting the output solutions of the peristaltic pipelines 208 and 121 of the basic independent peristaltic pump system 2 and the variable-speed independent peristaltic pump system 1; the buffer output channel is positioned at the side edge of the solution collecting pipeline, 10 output ports are arranged in the embodiment, 4 control valves are used for controlling, and each control valve respectively controls 1, 2, 3 and 4 output ports; the flow dividing channels 1, 2, 3, 4, 5 and 6 of the multistage flow dividing channel are shown in the figure, but the flow dividing channels are correspondingly expanded, so that 14 stages of flow dividing channels are arranged in total, 42 flow speed channels are used as centralized observation channels, the width of the centralized observation channels is 140 micrometers, the centralized observation channels consist of a plurality of flow speed flow dividing output channels, wherein the flow field modes in the 2 parallel observation channels are the same, and the flow speed flow dividing output channels are an ultra-low flow speed collection region and an experimental observation region. In addition, the chip can also guide the ultra-low flow field from the liquid outlet to other independent chips through a micro pipeline and serve as a flow velocity generating device;
the liquid is collected from the centralized observation channel and then conveyed to a chip total liquid outlet, and 5 total liquid outlets which are symmetrically distributed are arranged in the embodiment;
the beneficial effects of the above technical scheme are: the multi-stage flow dividing channel is arranged, so that the parameters can be controlled by a user-defined program, and the flow field is more stable.
Example 7:
in one embodiment, the onboard peristaltic pump control system performs peristaltic action through a preset program, drives a peristaltic pump control valve to work by controlling a pneumatic micro electromagnetic valve, pumps liquid into a chip fluid layer according to a preset execution logic, and controls the pneumatic micro electromagnetic valve to be connected with a hollow metal pipe through the tail end of a liquid pipeline to be connected with a liquid inlet of a chip control valve, so as to control the switch of the pneumatic micro electromagnetic valve, and drives the liquid in the liquid pipeline to enter the control valve of the chip through compressed gas;
the on-off state of the pneumatic miniature electromagnetic valve is controlled through a preset program, when the valve state is on, compressed gas is communicated with the liquid pipeline and the liquid inlet of the chip control valve, liquid is driven to enable the membrane at the position of the control valve to deform, so that the pipeline at the position corresponding to the fluid layer is closed, when the valve state is off, the input of the compressed gas is interrupted, meanwhile, excessive gas in the pipeline is discharged through the air leakage hole of the electromagnetic valve, the liquid pipeline and the liquid inlet of the chip control valve are communicated with the atmosphere, the applied pressure is released, the membrane at the position of the control valve is restored to the relaxed state, and the pipeline at the position corresponding to the fluid layer is conducted;
when the method is implemented, liquid is pumped into a chip fluid layer according to a preset execution logic, the preset execution logic comprises six steps of 100, 110, 010, 011, 001 and 101, in the six steps, each step has 3 digital logics which indicate the working state (101: a first group of valves are opened, a second group of valves are closed and a third group of valves are opened) of each valve of 3 peristaltic pump control valves, a fixed time interval is arranged between each step, the total volume of the pumped liquid can be changed by adjusting the time interval between each step, the flow rate in a solution collecting pipeline can be directly regulated and controlled, wherein,
the shorter the time interval is, the more the total volume of the liquid pumped in unit time is increased, the relative flow rate in the solution collecting pipeline is increased, and the more continuous the liquid is;
the larger the time interval is, the smaller the total volume pumped by the liquid in unit time is, and the smaller the relative flow rate in the solution collecting pipeline is, the worse the whole continuity is;
the limit value of the time interval reduction depends on the highest response frequency of the pneumatic miniature electromagnetic valve, once the maximum response frequency is exceeded, the electromagnetic valve cannot be controlled by a program and cannot complete corresponding switching action, and the fastest response time of the high-frequency pneumatic miniature electromagnetic valve is 1ms;
furthermore, the total liquid inlet of the chip is M, wherein M is more than or equal to 1 and less than or equal to 100, the number of the buffer output channels is N, wherein N is more than or equal to 1 and less than or equal to 200, the number of the total liquid outlets is K, the distribution positions of K are required to be mutually symmetrical so as to not influence the flow dividing effect of the multi-stage flow dividing channels, wherein K is more than or equal to 1 and less than or equal to 20, and the number of the control valves is determined according to the number of the liquid inlets and the buffer output channels and the number of the standard control valves of the variable speed independent peristaltic pump system;
preferably, the peristaltic pump units are uniformly expanded while the liquid inlet is expanded, a new peristaltic pump system is controlled in a linkage manner to generate a continuous and stable flow field according to the expanded control logic, and the two peristaltic pump systems can be expanded independently or simultaneously;
preferably, the expanded independent peristaltic pump systems are connected in parallel in a unified mode and are connected to a solution collecting pipeline for collecting and outputting, and the flow field generated by the peristaltic pump systems is collected and output;
further, the peristaltic pump control system realizes the peristaltic function through a self-defined control program, drives the peristaltic pump control valve to work by controlling the pneumatic miniature electromagnetic valve, and pumps liquid into the chip fluid layer according to a specific logic;
the pneumatic miniature electromagnetic valve is connected with a hollow metal pipe (with the outer diameter of 0.7mm and the inner diameter of 0.5 mm) through the tail end of a liquid pipeline (with the inner diameter of 0.508mm and the outer diameter of 1.524 mm) and is connected to a liquid inlet of the chip control valve to control the opening and closing of the pneumatic miniature electromagnetic valve, and liquid in the liquid pipeline is driven to enter the control valve of the chip through compressed gas;
the on-off state of the pneumatic miniature electromagnetic valve is controlled through a self-defined program, compressed gas is communicated with a liquid pipeline and a chip control valve liquid inlet in a valve state opening (corresponding to logic number 1), liquid is driven to enable a film at the control valve to deform so that the pipeline at the corresponding position of a fluid layer is closed, the valve state closing (corresponding to logic number 0) interrupts the input of the compressed gas, meanwhile, excessive gas in the pipeline is discharged from an electromagnetic valve air leakage hole, the liquid pipeline and the chip control valve liquid inlet are communicated with the atmosphere, applied pressure is released, the film at the control valve is restored to a relaxed state, and the pipeline at the corresponding position of the fluid layer is communicated;
the beneficial effects of the above technical scheme are: according to the invention, through adopting six steps to carry out program control, the linkage work of any one independent onboard peristaltic pump control system can be controlled, the generated ultra-low flow rate is more stable, meanwhile, two peristaltic pump systems can be independently or simultaneously expanded, and the realization of various complex functional designs in the same chip is facilitated.
Example 8:
in one embodiment, the method performs steps comprising:
step 1: placing the prepared chip on an inverted fluorescence microscope objective table, and sequentially connecting a pneumatic control valve to a liquid inlet of a chip control layer according to the serial number of the control valve;
step 2: the driving air pressure of the pneumatic miniature electromagnetic valve is adjusted to 25psi through a digital air pressure meter, all control valves are opened through a preset program, and control layer degassing is carried out;
and step 3: after the control layer is degassed, closing peristaltic pump control valves and peristaltic pipeline output control valves of all the channels, and closing a total liquid inlet control valve of any channel;
and 4, step 4: driving a fluorescent particle solution by using 2.5psi air pressure to degas the chip from a liquid inlet for closing the main liquid inlet control valve, and closing the main liquid outlet control valve when liquid flows out from the main liquid outlet;
and 5: after degassing of the fluid layer is finished, as shown in figure 2, a basic ultra-low flow rate test is carried out;
and 6: selecting tested parameters to obtain target ultra-low flow rate, then starting to apply force to the sample for a long time, and simultaneously imaging by using a microscope;
when the method is implemented, firstly, the prepared chip is placed on an inverted fluorescence microscope objective table, and a pneumatic control valve is sequentially connected to a liquid inlet of a chip control layer according to the serial number of the control valve; the driving air pressure of the pneumatic miniature electromagnetic valve is adjusted to 25psi through a digital air pressure meter, and all control valves are opened through a program to degas a control layer; after the control layer is degassed, closing peristaltic pump control valves and peristaltic pipeline output control valves of all the channels, and closing a total liquid inlet control valve of any channel; driving a fluorescent particle solution by using 2.5psi air pressure to degas the chip from a liquid inlet for closing the main liquid inlet control valve, and closing the main liquid outlet control valve when liquid flows out from the main liquid outlet; after degassing of a fluid layer is finished, a basic ultra-low flow rate test is carried out, a flow field test flow rate graph generated by using a basic independent peristaltic pump system is shown in figure 2, the abscissa is corresponding pumping time of the basic independent peristaltic pump, and the ordinate is corresponding test flow rate; finally, selecting tested parameters to obtain a target ultralow flow rate, then starting to apply force to the sample for a long time, and simultaneously imaging by using a microscope;
the beneficial effects of the above technical scheme are: the invention is beneficial to improving the stability in the flow field test process by carrying out the basic ultra-low flow rate test after degassing the fluid layer, and can carry out real-time data collection while providing the flow field by adopting the microscopic imaging system.
Example 9:
in one embodiment, the step of base ultra low flow rate testing comprises:
s101: opening a control valve of a fluorescent particle solution inlet and a peristaltic pump control valve of the passage;
s102: 2.5psi of air pressure is used for driving phosphate buffer solution to be input into the chip from the other total liquid inlets;
s103: closing the connected liquid inlet control valve;
s104: setting cycle parameters through a preset program, inputting a time interval of control logic of a peristaltic pump system, peristaltic time and waiting time for starting the next cycle, and clicking to start the peristaltic cycle;
s105: observing a second-stage shunting input channel and a last-stage shunting input channel of the centralized observation channel through a fluorescence microscope, comparing the current particle flow rate, and stabilizing a flow field and reducing the relative flow rate through a switch buffer output channel control valve; the second-stage shunting input channel corresponds to a first channel, and the last-stage shunting input channel corresponds to a last channel;
s106: obtaining system parameters of a target flow field, including the number of selected buffer output channels, the working time interval of a peristaltic pump control valve and the waiting time for starting the next cycle;
when the method is implemented, when an ultra-low flow rate test is carried out and circulation parameters are set, the time interval Int between every two steps which is required to be input into a control program is preferably set to be 100ms, the time Dur which needs to wait for the start of a new cycle after the six steps are finished is set to be 0s, the total cycle number Cyc is set to be 9000 times, and then the cycle is started by clicking to creep so as to generate the ultra-low flow rate;
the beneficial effects of the above technical scheme are: according to the invention, the working mode of the onboard peristaltic pump system is controlled by introducing the circulating parameters to generate the flow field, the current flow rate is observed in the centralized observation channel through the microscopic imaging system, and meanwhile, the flow field can be stably generated for a long time, so that the liquid input is directly driven by air pressure for long-time contrast experiment research.
Example 10:
in one embodiment, the basic ultra-low flow rate test process further comprises:
when testing is carried out aiming at basic ultra-low flow velocity, recording system parameters in different flow fields in real time, and synchronously storing the system parameters in the different flow fields to a cloud database;
acquiring parameter data of the cloud database, constructing a flow rate control model according to the parameter data, acquiring flow field parameter change characteristics based on the flow rate control model, performing multi-dimensional data analysis aiming at the flow field parameter characteristics, and acquiring a primary data processing result; the flow rate control model is used for determining a target flow field according to system parameters under different flow fields;
performing visualization processing on the primary data processing result to obtain a secondary data processing result;
performing fault detection on the microfluidic chip based on the secondary data processing result to obtain a fault detection result, judging the fault reason when the fault detection result shows that the microfluidic chip has a fault problem, and determining a judgment result;
when the method is implemented, the method is independent of a microscope imaging system in the imaging process, so that data are acquired in real time when a flow field is provided, and the acquired data are processed without delay, so that target parameters of the flow field are acquired, and when a flow rate control test is performed, the stability of the flow rate test is relatively abstract and cannot be visually displayed, in order to visually display the stability variation range of the control flow rate of the microfluidic chip in the invention, the stability test is performed on the flow rate, for example, fig. 3 shows a flow field stability test result graph generated by using a basic independent peristaltic pump system, wherein a shows that a naturally fluctuating flow field generated by the peristaltic pump system presents a stable output flow field like a black solid line after filtering fluctuation by a specific method, and b shows that the stability of the flow field after processing is higher after normalizing input and output speeds, and comprehensive judgment is performed from multiple dimensions based on a large data processing platform according to the stability detection result of flow rate control; the method comprises the steps of firstly, acquiring the number and the type of peristaltic liquid inlet channels by adopting a flow rate self-adaptive control method, intelligently controlling the speed of a fluid based on a data mapping relation preset in a system according to the number and the type of the corresponding channels, and storing data and results of each control to a cloud end in the control process; the centralized observation channel comprises a plurality of flow fields, so that a plurality of flow field effects can be simultaneously performed in an area range, and under the action of the plurality of flow fields, the simultaneously generated data volume is large, so that certain difficulty can be generated during data analysis;
the beneficial effects of the above technical scheme are: according to the method, the flow field data are collected in real time, the collected data are processed without delay, so that the efficiency and the reliability of obtaining the target parameters of the flow field are high, the stability change amplitude is visually displayed, the stability test result of the flow rate can be visually checked, in addition, the data and the result which are regulated and controlled each time are stored to the cloud, the storage mode does not need to worry about the data loss, and the cloud server carries out automatic analysis according to the received regulation and control data and the result, so that the intelligent regulation and control result is synchronously obtained.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (2)

1. A microfluidic chip for controllable ultra-low flow rates, comprising: the system comprises an on-board peristaltic pump control system, a flow field regulation and control module (3), a peristaltic pipeline output control valve I (4), a peristaltic pipeline output control valve II (5) and a solution collecting pipeline I (6);
the onboard peristaltic pump control system comprises a variable-speed independent peristaltic pump system (1) and a basic independent peristaltic pump system (2), wherein the variable-speed independent peristaltic pump system (1) and the basic independent peristaltic pump system (2) are respectively connected with a solution collecting pipeline I (6), the solution collecting pipeline I (6) is connected with a flow field regulation and control module (3), the flow field regulation and control module (3) comprises a buffer output channel, a solution collecting pipeline II (304), a multi-stage flow dividing channel and a centralized observation channel, the variable-speed independent peristaltic pump system (1) is formed by connecting 6 basic variable-speed independent peristaltic pump units in parallel, the basic variable-speed independent peristaltic pump unit comprises a liquid inlet I (101), a selectable peristaltic pipeline output pipeline (120), a peristaltic pump liquid inlet selection control valve and a selectable pump control valve, and is connected into the peristaltic pump collecting pipeline I (121) in parallel, and whether the output is controlled by a peristaltic pipeline output control valve I (4) to generate a flow field; wherein the content of the first and second substances,
the selectable peristaltic pipelines are connected into the basic variable-speed independent peristaltic pump units in parallel and are converged to a selectable peristaltic pipeline output pipeline (120) through the basic variable-speed independent peristaltic pump units; wherein the selectable peristaltic tubing comprises: the peristaltic pump comprises a first-stage selectable peristaltic pipeline (102), a second-stage first selectable peristaltic pipeline (103), a second-stage selectable peristaltic pipeline (104), a third-stage first selectable peristaltic pipeline (105), a third-stage second selectable peristaltic pipeline (106) and a third-stage third selectable peristaltic pipeline (107);
the peristaltic pump liquid inlet selection control valves are arranged in a parallel mode in an arrangement mode; wherein, peristaltic pump feed liquor selection control valve includes: a first peristaltic pump liquid inlet selection control valve (108), a second peristaltic pump liquid inlet selection control valve (109) and a third peristaltic pump liquid inlet selection control valve (110);
the selectable peristaltic pump control valves are arranged in a parallel mode, wherein the selectable peristaltic pump control valves comprise three different modes, wherein the first-stage mode only has one control pipeline, the second-stage mode is that two control pipelines are connected in parallel, and the third-stage mode is that three control pipelines are connected in parallel; wherein the content of the first and second substances,
the control pipeline of the primary mode comprises a primary first selectable peristaltic pump control valve (111), a primary second selectable peristaltic pump control valve (114) and a primary third selectable peristaltic pump control valve (117);
the control conduit of the secondary mode comprises: a two-stage first selectable peristaltic pump control valve (112), a two-stage second selectable peristaltic pump control valve (115), a two-stage third selectable peristaltic pump control valve (118);
the control pipeline of the three-stage mode comprises: a three-stage first selectable peristaltic pump control valve (113), a three-stage second selectable peristaltic pump control valve (116), and a three-stage third selectable peristaltic pump control valve (119);
the basic independent peristaltic pump system (2) is formed by connecting 6 basic independent peristaltic pump units in parallel, and each basic independent peristaltic pump unit comprises a second liquid inlet (202), a peristaltic pipeline, a peristaltic pump control valve and a peristaltic pipeline output pipeline (207); the basic independent peristaltic pump unit is connected into a second peristaltic pipeline collecting pipeline (208) in a parallel connection mode, and whether a generated flow field is output or not is controlled by a second peristaltic pipeline output control valve (5); wherein the peristaltic tubing comprises: a peristaltic pipeline I (201) and a peristaltic pipeline II (203); the peristaltic pump control valve includes: a first basically independent peristaltic pump control valve (204), a second basically independent peristaltic pump control valve (205) and a third basically independent peristaltic pump control valve (206);
the first solution collecting pipeline (6) and the second solution collecting pipeline (304) are connected in series with the first peristaltic pipeline collecting pipeline (121) and the second peristaltic pipeline collecting pipeline (208), and whether the solution is output to the solution collecting pipeline is controlled through the first peristaltic pipeline output control valve (4) and the second peristaltic pipeline output control valve (5);
the buffer output channel is used for performing stable filtering processing on a flow field of the solution collecting pipe II (304) and filtering fluctuation generated by a working mode of the peristaltic pump system; the buffer output channel includes: a first buffer output channel (301), a second buffer output channel (302), and a third buffer output channel (303);
each stage of flow of the multistage shunting channel generates a pair of stable flow velocities which are equal in size and are half of the input flow velocity of the previous stage, a multistage flow field from low to high is generated in the centralized observation channel, and the multistage flow fields are converged to the multistage shunting output channel and output to the chip through a liquid outlet (339);
the centralized observation channel consists of at least two flow velocity distribution output channels, and each 2 flow channels are a group of flow fields and are collection and sample control areas with ultralow flow velocity; the flow rate distribution output channel comprises a first output channel (316), a second output channel (317), a third output channel (318), a fourth output channel (319), a fifth output channel (320), a sixth output channel (321), a seventh output channel (322), an eighth output channel (323), a ninth output channel (324), a tenth output channel (325), an eleventh output channel (326) and a twelfth output channel (327).
2. The microfluidic chip of claim 1, wherein said microfluidic chip comprises a two-layer structure, comprising a chip fluidic layer and a chip control layer, said chip fluidic layer and chip control layer being bonded by plasma bonding, wherein,
the chip fluid layer comprises a peristaltic pipeline of an on-board peristaltic pump control system, a solution collecting pipeline I (6), a solution collecting pipeline II (304), a buffer output channel, a multi-stage flow distribution channel, a centralized observation channel and a chip liquid outlet (339).
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