CN117943142A - Thermal programming microfluidic control device for microfluidic complex reaction manipulation and control strategy thereof - Google Patents
Thermal programming microfluidic control device for microfluidic complex reaction manipulation and control strategy thereof Download PDFInfo
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Abstract
The invention relates to a thermal programming micro-fluid control device for micro-fluid complex reaction control, which comprises a thermal working medium, a target fluid to be controlled, a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point; the heat control working medium cavity, the fluid bearing cavity and the unified working environment reference points are sequentially arranged from upstream to downstream and are communicated through the connecting channel; the thermal working medium is positioned in the thermal control working medium cavity, and the target fluid to be controlled is positioned in the fluid bearing cavity; the controlled thermal element is used for heating up the thermal working medium, the volume of the thermal working medium is increased, and the target fluid to be controlled is pushed to the fluid receiving cavity. The control strategy comprises a single point time sharing multiplexing mode, a multipoint synchronous/asynchronous cooperation mode and an array network linkage mode. The invention realizes the movement of the target fluid to be controlled through temperature control, realizes high-efficiency compact on-chip integration and provides a widely applicable flexible and accurate fluid control treatment means.
Description
Technical Field
The invention relates to the technical field of microfluidic chips, in particular to a thermal programming microfluidic control device for microfluidic complex reaction control, and also relates to a control strategy of the thermal programming microfluidic control device for microfluidic complex reaction control.
Background
The microfluidic chip (microfluidic chip), also called lab-on-a-chip, is an emerging analytical detection technology platform capable of manipulating the functions of sampling, diluting, reagent adding, separating, reacting, detecting and the like of micro-scale (typically, scale of several micrometers to hundreds of micrometers) fluid. The basic characteristics and the greatest advantages are flexible combination and scale integration of various analysis functional units on the integrally controllable micro platform. Essentially, microfluidic chips provide a opportunity to control and process minute amounts of sample centrally in time and space.
Generally, these involve fluid handling processes requiring specific drive control means, including mechanical or pressure pump valves, optical/electrowetting, magnetic fields, electric fields, acoustic fields, capillary forces, and the like. However, the application scenes of these means have some limitations of different degrees, such as wider application range of mechanical or pressure pump valves, but more off-Chip structures, resources and equipment support are needed, the result of "Chip in a Lab" is easy to be caused, and further compact miniaturization of microfluidic Chip equipment instruments is greatly limited. Mechanisms including electro/optical wetting, magnetic, electrical, acoustic, etc. can provide a number of possibilities for flexible integrated operation of microfluidics on a chip, but there are certain requirements on the characteristics of the fluid itself being operated or still the need to combine other means to complete the full-flow operation process. The capillary force is used as a passive control strategy, can better meet the requirements of some simple fluid driving control, but is not suitable for application scenes with more complicated or higher requirements on operation accuracy.
Thus, challenges remain in terms of microfluidic chips how to achieve efficient and compact on-chip integration and to provide a flexible and accurate fluid handling approach that is widely applicable.
Disclosure of Invention
Aiming at the technical problems existing in the prior art, the invention aims at: a thermal programming microfluidic control device for controlling a microfluidic complex reaction is provided, which can be used for designing a complex flow channel for the microfluidic complex reaction.
Another object of the invention is: a control strategy for a thermally programmable microfluidic control device for the manipulation of microfluidic complex reactions is provided, which can be operated by thermally programming.
In order to achieve the above purpose, the invention adopts the following technical scheme:
A thermally programmed microfluidic control device for microfluidic complex reaction manipulation, comprising: the system comprises a thermal working medium, a target fluid to be controlled, a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point; the heat control working medium cavity, the fluid bearing cavity and the unified working environment reference points are sequentially arranged from upstream to downstream and are communicated through the connecting channel; the thermal working medium is positioned in the thermal control working medium cavity, and the target fluid to be controlled is positioned in the fluid bearing cavity; the thermal working medium is heated by the controlled thermal element, and the volume of the thermal working medium is increased, so that the target fluid to be controlled is pushed to the fluid receiving cavity.
Preferably, the device is divided into an upstream branch, a midstream branch and a downstream branch which are communicated in sequence; an upstream branch is formed by a thermal control working medium cavity and a fluid bearing cavity; a fluid receiving chamber and a unified operating environment reference point form a downstream branch.
Preferably, the midstream branch is a connection channel, and the plurality of parallel upstream branches are connected to the connection channel, and the connection channel is connected to a downstream branch.
Preferably, the midstream branch is a connecting channel or at least one fluid receiving cavity connected through the connecting channel; an upstream branch is connected to a midstream branch, and the tail end of the midstream branch is connected to a plurality of downstream branches in parallel.
Preferably, the thermal working medium is a working medium which is not miscible or reactive with the target fluid to be controlled, and comprises one or more of gas, liquid and solid with thermal response capability in form or volume, or one or more of phase change materials which can generate gas-liquid, liquid-solid and gas-solid phase interconversion under temperature regulation, or biological or chemical reaction substances which are regulated and controlled by thermal triggering and generate deformation or volume change.
Preferably, the transfer time and direction, transfer volume, transfer flow and flow rate and flow time of the target fluid to be controlled and passed through a certain position are realized by regulating and controlling the temperature of the thermal working medium and combining the geometric dimensions and topological structures of the chambers and the connecting channels. The chambers include a thermal control medium chamber, a fluid bearing chamber and a fluid receiving chamber.
Preferably, a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point form a thermal programming micro-fluid control unit; the thermal programming micro-fluid control device comprises one or more thermal programming micro-fluid control units, the thermal programming micro-fluid control units form a network, and a fluid bearing cavity or a fluid bearing cavity is shared among the thermal programming micro-fluid control units.
Control strategy for a thermally programmed microfluidic control device for microfluidic complex reaction manipulation, employing a single point time division multiplexing mode: and carrying out temperature parameter adjustment on a single thermal programming microfluidic control unit to realize timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, wherein the sample fluid is used as the target fluid to be controlled.
Control strategies for thermally programmed microfluidic control devices for microfluidic complex reaction manipulation employ a multipoint synchronous/asynchronous cooperative mode: through the combination of a plurality of thermal programming micro-fluid control units, one part of the combination is synchronously controlled to carry out multi-component synchronous addition of the micro-fluid complex reaction, the other part of the combination is synchronously controlled to carry out multi-component stepwise addition of the micro-fluid complex reaction, and the components are used as target fluids to be controlled.
The control strategy of the thermal programming micro-fluid control device for micro-fluid complex reaction control adopts an array network linkage mode: for a network structure formed by a plurality of thermal programming micro-fluid control units, a highly flexible and fluxional micro-fluid complex reaction operation system is constructed by combining a single-point time-sharing multiplexing mode and a multi-point synchronous/asynchronous cooperation mode; single point time division multiplexing mode: the temperature parameter adjustment is carried out on a single thermal programming microfluidic control unit to realize the timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, and the sample fluid is used as the target fluid to be controlled; multipoint synchronous/asynchronous collaboration mode: through the combination of a plurality of thermal programming micro-fluid control units, one part of the combination is synchronously controlled to carry out multi-component synchronous addition of the micro-fluid complex reaction, the other part of the combination is synchronously controlled to carry out multi-component stepwise addition of the micro-fluid complex reaction, and the components are used as target fluids to be controlled.
The principle of the invention is as follows:
1. The simplest thermal programming micro-fluid control unit is shown in fig. 1, and comprises a thermal working medium, a target fluid to be controlled, a thermal control working medium cavity, a fluid bearing cavity, a unified working environment reference point and a connecting channel. A thermally controlled working fluid chamber is a mechanism that receives a thermal working medium and provides it with a controlled thermal response at a desired temperature, including without limitation joule heating, plasma heating, acoustic heating, electromagnetic induction heating, and the like. The thermal working medium is a working medium that is not miscible or reactive with the fluid to be driven/controlled, and may include, but is not limited to, gases, liquids, solids, and mixtures thereof having a thermally responsive capability in form or volume, or phase change materials and combinations of materials that undergo gas-liquid, liquid-solid, gas-solid phase interconversions under temperature regulation, or the like, or biologically or chemically reactive substances that are thermally triggered to regulate and deform or change volume. In some cases, the thermal working medium and the controlled thermal element may be combined, and external energy directly acts on the thermal working medium in a non-contact manner to generate thermal response. In some cases, the fluid bearing chamber may be integrated with the thermally controlled working fluid chamber. The unified working environment reference point is a unified working environment parameter reference point established for overcoming or correcting working environment parameter drift or fluctuation to cause working condition deviation of different thermal programming micro-fluid control units, and comprises, but is not limited to, ambient air pressure, temperature, humidity and the like.
2. The basic principle of operation of a typical thermally programmed microfluidic control unit is: the thermal working medium is contained in the thermal control working medium cavity, fluid to be driven/controlled or target fluid is limited in the fluid bearing cavity through the design of the geometric dimension, the topological structure and the surface characteristics of the connecting channel, and non-target fluid is located in the fluid bearing cavity. When fluid control needs to be executed, the thermal control working medium cavity acts on the thermal working medium and performs temperature control operation (time sequence, temperature difference, temperature changing speed and the like) on the thermal working medium according to preset fluid control parameters (time sequence, volume, flow speed and the like), the thermal working medium changes in shape or volume under the condition, and target fluid in the fluid bearing cavity is extruded and pushed to be transferred to the fluid bearing cavity as required. In the process, the transfer time and direction, transfer volume, transfer flow rate and flow time of the target fluid can be realized by regulating and controlling the temperature of the thermal working medium and combining the geometric dimensions and the topological structure of each chamber and the connecting channel.
3. Several basic control strategies for thermally programming microfluidic control units include, but are not limited to: single point time division multiplexing mode, multipoint synchronous/asynchronous cooperation mode, and array network linkage mode.
The invention has the following advantages:
1. Through converting the driving and control of the microfluid on the chip into the temperature regulation and control of the corresponding thermal working medium on the chip, the control of the target fluid to be controlled can be realized without connecting an external pipeline pump valve or a mechanical structure and control, and the structure is simple and easy to control.
2. The method can form a complex flow channel structure corresponding to the complex reaction of the microfluid or multi-step time sequence operation, and realize the high efficiency and integration of the microfluidic chip.
3. The method realizes high-efficiency compact on-chip integration and provides a flexible and accurate fluid control treatment means which is widely applicable.
4. The method allows the temperature control of the thermal working medium by adopting a contact heat conduction or non-contact heat radiation mode, and further realizes the driving and control of the target fluid so as to adapt to wider application scenes.
5. The method provided by the invention provides an effective means for driving and controlling complex multi-step analysis/processing/reaction in the closed micro-channel, can greatly reduce the dependence on peripheral auxiliary supporting equipment, and is beneficial to realizing the Lab-on-a-Chip of micro integrated automation.
Drawings
Fig. 1 is a schematic diagram of a most basic thermally programmed microfluidic control unit.
Fig. 2 is a schematic diagram of a single point time division multiplexing mode according to the first embodiment.
Fig. 3 is a schematic diagram of a multipoint synchronous/asynchronous cooperation mode of the second embodiment.
Fig. 4 is a schematic diagram of an array network linkage mode of the third embodiment.
Fig. 5 is a schematic structural diagram of a thermal programming microfluidic control device according to a fourth embodiment.
Fig. 6 is a diagram of the operation of the thermal programming microfluidic control device according to the fourth embodiment.
Fig. 7 is a schematic structural diagram of a thermal programming microfluidic control device according to a fifth embodiment.
Fig. 8 is a diagram of the operation of a thermally programmed microfluidic control device according to the fifth embodiment.
The device comprises a thermal control working medium cavity 1, a fluid bearing cavity 2, a fluid bearing cavity 3, a unified working environment reference point 4, a thermal working medium 5, a target fluid to be controlled 6 and a connecting channel 7.
8 Is a bottom plate, 9 is a middle layer, 10 is a top layer, 11 is a controlled heat element, 12 is an exhaust through hole, 13 is a filling filter element, and 14 is a sealing die.
15 Is a carrier fluid control unit, 16 is a sample fluid control unit, 17 is a continuous phase fluid control unit, 18 is a main channel, 19 is a sample mixing channel, and 20 is a fluid outlet.
Detailed Description
The present invention will be described in further detail with reference to the following embodiments.
A thermally programmed microfluidic control device for microfluidic complex reaction manipulation, comprising: the system comprises a thermal working medium, a target fluid to be controlled, a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point; the heat control working medium cavity, the fluid bearing cavity and the unified working environment reference points are sequentially arranged from upstream to downstream and are communicated through the connecting channel; the thermal working medium is positioned in the thermal control working medium cavity, and the target fluid to be controlled is positioned in the fluid bearing cavity; the thermal working medium is heated by the controlled thermal element, and the volume of the thermal working medium is increased, so that the target fluid to be controlled is pushed to the fluid receiving cavity.
The thermal programming microfluidic control device for microfluidic complex reaction control is divided into an upstream branch, a midstream branch and a downstream branch which are communicated in sequence; an upstream branch is formed by a thermal control working medium cavity and a fluid bearing cavity; a fluid receiving chamber and a unified operating environment reference point form a downstream branch.
Several different configurations of the thermally programmed microfluidic control device and its thermal programming control strategies will be described below from several different embodiments.
Example 1
In the thermal programming microfluidic control device for controlling a microfluidic complex reaction, the number of upstream branches is one, the number of downstream branches is one, and the midstream branches are two fluid receiving cavities connected through a connecting channel.
Control strategy for a thermally programmed microfluidic control device for microfluidic complex reaction manipulation, employing a single point time division multiplexing mode: and carrying out temperature parameter adjustment on a single thermal programming microfluidic control unit to realize timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, wherein the sample fluid is used as the target fluid to be controlled.
As shown in fig. 2, when it is necessary to transfer a part of the fluid in the fluid-carrying chamber 2 to the fluid-carrying chamber 3-2-1 in accordance with predetermined parameters (transfer volume V1, flow rate Q1), by adjusting the temperature parameter (e.g., temperature increase Δt 1 and temperature change rate k 1) of the thermal working medium 5 in the thermally controlled working medium chamber 1; when it is necessary to transfer the target fluid entirely to the downstream other fluid receiving chamber 3-2-2, the temperature parameter (e.g., temperature increase Δt 2 and temperature change rate k 2) of the hot working medium 5 located in the thermally controlled working medium chamber 1 is again adjusted.
Example two
In the thermal programming micro-fluid control device for micro-fluid complex reaction control, the midstream branch is a connecting channel, three parallel upstream branches are connected into the connecting channel, and the connecting channel is connected into a downstream branch.
Control strategies for thermally programmed microfluidic control devices for microfluidic complex reaction manipulation employ a multipoint synchronous/asynchronous cooperative mode: through the combination of a plurality of thermal programming micro-fluid control units, one part of the combination is synchronously controlled to carry out multi-component synchronous addition of the micro-fluid complex reaction, the other part of the combination is synchronously controlled to carry out multi-component stepwise addition of the micro-fluid complex reaction, and the components are used as target fluids to be controlled.
As shown in fig. 3, when a microfluidic complex reaction needs to transport a sample fluid a located in the fluid bearing chamber 2-3-1 and a sample fluid B located in the fluid bearing chamber 2-3-2 to the fluid bearing chamber 3 at time t 1 according to a certain mixing ratio, the temperature and the temperature change rate of the thermal working medium 5 located in the thermal control working medium chambers 1-3-1 and 1-3-2 can be synchronously controlled. When the 3 rd component sample fluid C required by the microfluidic complex reaction is required to be conveyed to the fluid receiving cavity 3 according to a certain flow rate at another time t 2, the temperature and the temperature change rate of the thermal working medium 5 positioned in the thermal control working medium cavity 1-3-3 are regulated.
Example III
In the thermal programming micro-fluid control device for micro-fluid complex reaction control, the midstream branch is a connecting channel, three groups of parallel upstream branches are connected into the connecting channel, and the connecting channel is connected into a downstream branch. A set of upstream arms control sample C, a set of upstream arms control reagent a 1-Am, and a set of upstream arms control reagent B 1-Bn.
The control strategy of the thermal programming micro-fluid control device for micro-fluid complex reaction control adopts an array network linkage mode: a network structure composed of a plurality of thermal programming micro-fluid control units is used for constructing a highly flexible and fluxional micro-fluid complex reaction operation system by combining a single-point time-sharing multiplexing mode and a multi-point synchronous/asynchronous cooperation mode.
As shown in fig. 4, when the microfluidic complex reaction involves the random combination reaction test of samples C with reagents a 1-Am and B 1-Bn according to the requirement, quantitative and timed delivery of the sample fluid C, the reagents a i and B j into the fluid receiving chamber W is realized by respectively regulating and controlling the temperature parameters of the thermal working medium O located upstream of the sample fluid C carrying chamber, the thermal working medium P i located upstream of the reagent fluid a i (1.ltoreq.i.ltoreq.m) carrying chamber, and the working medium Q j located upstream of the reagent fluid B j (1.ltoreq.j.ltoreq.m) carrying chamber.
Example IV
As shown in fig. 5, a thermal programming microfluidic device in which the thermal working medium is air is a bottom plate 8, a middle layer 9, and a top layer 10 in this order from bottom to top. A controlled heating element 11 is arranged on the bottom plate and is used for heating the heat control working medium cavity. The middle layer is provided with various cavities, the top layer is provided with through holes and various top covers, so that the cavities and the through holes enclose a thermal control working medium cavity 1, and the cavities and the top covers enclose a fluid bearing cavity 2, a fluid bearing cavity 3-5-1 and a fluid bearing cavity 3-5-2. The intermediate layer is further provided with a connection channel 7 between the fluid-carrying chamber 2 and the fluid-carrying chamber 3-5-1, which connection channel is a bottom connection channel. The top layer is also provided with an exhaust through hole 12, a connecting channel between the thermal control working medium cavity 1 and the fluid bearing cavity 2, a connecting channel between the fluid bearing cavity 3-5-1 and the fluid bearing cavity 3-5-2, and a connecting channel between the fluid bearing cavity 3-5-2 and the exhaust through hole 12, wherein the connecting channels are all top connecting channels. A filling filter element 13 is arranged in the exhaust through hole 12. The top of the fluid-carrying chamber 2 is sealed by a sealing die 14.
The apparatus substantially comprises a thermally programmed microfluidic control device. The midstream branch is a fluid receiving cavity connected through a connecting channel; one upstream branch is connected to the middle upstream branch, and the tail end of the middle upstream branch is connected to three parallel downstream branches.
The control strategy of the thermal programming micro-fluid control device adopts a single-point time-sharing multiplexing mode: and carrying out temperature parameter adjustment on a single thermal programming microfluidic control unit to realize timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, wherein the sample fluid is used as the target fluid to be controlled. As shown in fig. 6:
After the bottom plate 8 and the middle layer 9 are aligned, packaged and combined, the second fluid is preloaded in the fluid bearing cavity 3-5-1, 3 different reagents are pre-stored in the bottom of the fluid bearing cavity 3-5-2 in the form of liquid or solid powder or semi-solid, and the filling filter element with air permeability and water impermeability is fixed in the top layer exhaust through hole and aligned, sealed and combined with the top of the middle layer. All the fluid contact surfaces are hydrophobic surfaces, so that the fluid pre-stored in each chamber is difficult to pass through the connecting channel without external disturbance.
And (3) adding the sample fluid to be analyzed into the fluid bearing cavity through the top before use, and then closing the upper end opening of the fluid bearing cavity by using a sealing film.
When the device is used, the temperature rising amplitude of the controlled thermal element on the bottom plate is controlled, so that the air in the thermal control working medium cavity is heated to generate volume expansion so as to squeeze the sample fluid to be analyzed in the fluid bearing cavity, and the sample fluid overcomes the surface tension of the connecting channel and enters the fluid bearing cavity 3-5-1 to be converged with the second fluid.
Similarly, in the step (III), the temperature reduction amplitude of the controlled heat element can be controlled, so that the gas in the heat control working medium cavity contracts when encountering cold, and then the liquid in the fluid bearing cavity 3-5-1 is pumped into the fluid bearing cavity. To increase the mixing rate of the first fluid sample and the second fluid, the controlled thermal element may be rapidly cycled down-up to cause the two fluids to flow back and forth between the fluid carrying chamber and the fluid receiving chamber 3-5-1 (repeating the process of steps (ii) and (iii)). When the first fluid sample is sufficiently mixed with the second fluid and the mixed liquid is located in the fluid receiving chamber 3-5-1, the fluid receiving chamber 3-5-1 can be locally heated to complete the necessary reaction.
Further heating of the controlled thermal element, as shown in step (IV), causes the liquid in the fluid receiving chamber 3-5-1 to rise to the top of the chamber and flow into the array of fluid receiving chambers 3-5-2 through the connecting channels to further react with the reagents in each chamber in the array.
In the above process, assuming that the volume of the thermally controlled working fluid chamber is V 0, the volume of the sample fluid to be analyzed in the fluid carrying chamber is V 1, the total volume of the fluid carrying chamber 3-5-1 is V 2, the volume of the fluid pre-stored in the fluid carrying chamber 3-5-1 is V 3, the initial temperature is T 0, the temperature rise required for driving the sample to be analyzed to the fluid carrying chamber 3-5-1 is DeltaT 1, and the temperature rise required for distributing the fluid obtained by mixing the sample fluid with the second fluid to the fluid carrying chamber 3-5-2 is DeltaT 2, there are
Example five
As shown in fig. 7, a thermal programming microfluidic device for automatic paired combination testing of multiple samples comprises the following main structures: a carrier fluid control unit 15, an array of sample fluid control units 16, an array of continuous phase fluid control units 17, a main channel 18, a sample mixing channel 19, a fluid receiving chamber 3 and a fluid outlet 20.
The carrier fluid control unit 15 comprises a thermal control working medium cavity 1 and a fluid bearing cavity 2, wherein the thermal control working medium cavity is communicated with the fluid bearing cavity through a top connecting channel, and fluid in the fluid bearing cavity is connected with a main channel through a bottom connecting channel of the fluid bearing cavity. The other fluid control units, including the sample fluid control unit 16 and the continuous phase fluid control unit 17, each have a similar structure to the carrier fluid control unit. The continuous phase fluid control unit 17 is located downstream of the sample fluid control unit 16 with a section of sample mixing channel 19 disposed therebetween. The fluid receiving chamber 3 is located downstream of the continuous phase fluid control unit and the fluid outlet 20 is located downstream of the fluid receiving chamber in agreement with the unified operating environment reference point parameters.
The apparatus substantially comprises a thermally programmed microfluidic control device. The midstream branch is a connecting channel and comprises a main channel and a sample mixing channel arranged in the main channel. The plurality of parallel upstream branches are divided into three groups of access connection channels, and the connection channels are accessed to one downstream branch.
The control strategy of the thermal programming micro-fluid control device for micro-fluid complex reaction control adopts an array network linkage mode: a network structure composed of a plurality of thermal programming micro-fluid control units is used for constructing a highly flexible and fluxional micro-fluid complex reaction operation system by combining a single-point time-sharing multiplexing mode and a multi-point synchronous/asynchronous cooperation mode. As shown in fig. 8:
In the preparation stage, a carrier fluid (target fluid to be controlled) which is not miscible with the reagent and the sample is preloaded in the fluid bearing cavity in the carrier fluid control unit. In the sample fluid control unit, the sample fluid to be analyzed and the required reagents (target fluid to be manipulated) are preloaded in the fluid bearing chamber, respectively. In the continuous phase fluid control unit, a continuous phase fluid (a target fluid to be controlled) is preloaded into a carrier fluid bearing cavity. And sealing all the fluid bearing cavities after the operation is finished.
When the analysis test starts, as shown in the step (I), firstly, a thermal programming micro-fluid control unit for storing the sample fluid to be tested is activated, a quantitative sample fluid a is pushed to a main channel, and the state of the unit is kept unchanged; and then activating a thermal programming micro-fluid control unit for storing the carrier fluid, driving the carrier fluid b to the main channel, and adjusting the temperature parameter of the air cavity of the carrier fluid control unit to enable the carrier fluid to continuously push the sample fluid to advance along the main channel.
As shown in step (ii), as the sample fluid passes through the test reagent c, the thermally programmed microfluidic control unit storing the test reagent fluid is activated, pushing a metered amount of test reagent c into the main channel to join the sample fluid a, maintaining the unit in a constant state. Similarly, the second or third reagent fluid may be combined with the aforementioned fluid and continuously delivered from the carrier fluid to the sample mixing channel 19 to complete the thorough mixing of the sample.
Then, the continuous phase fluid control unit is activated to continuously push the second fluid which is not miscible with the sample to the main channel, the sample mixed fluid is separated into micro reaction units by the shearing force of the two fluid interfaces, and the generated micro reaction units are further pushed to the fluid receiving cavity 3 for subsequent reaction and detection.
In the process, a certain time period can be selected, a certain amount of sample fluid to be detected and a certain reagent fluid or reagent fluids are sequentially combined, and after micro-separation of the sample mixed fluid is completed; triggering the sample fluid thermal programming control unit again, pushing out a certain amount of sample fluid to the main channel, updating carrier thermal programming control parameters, and continuously pushing out the carrier fluid to pump the sample to be converged, mixed and separated with another reagent or a plurality of other reagents until reaction detection. In the process, the carrier fluid plays a role in transporting and pumping sample reagents on one hand, and on the other hand, reagent sample pairing tests of different batches can be blocked so as to eliminate carrying pollution among different tests.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. A thermally programmable microfluidic control device for microfluidic complex reaction manipulation, comprising: the system comprises a thermal working medium, a target fluid to be controlled, a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point; the heat control working medium cavity, the fluid bearing cavity and the unified working environment reference points are sequentially arranged from upstream to downstream and are communicated through the connecting channel; the thermal working medium is positioned in the thermal control working medium cavity, and the target fluid to be controlled is positioned in the fluid bearing cavity; the thermal working medium is heated by the controlled thermal element, and the volume of the thermal working medium is increased, so that the target fluid to be controlled is pushed to the fluid receiving cavity.
2. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 1 wherein: dividing into an upstream branch, a midstream branch and a downstream branch which are communicated in sequence; an upstream branch is formed by a thermal control working medium cavity and a fluid bearing cavity; a fluid receiving chamber and a unified operating environment reference point form a downstream branch.
3. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 2 wherein: the midstream branch is a connecting channel, a plurality of parallel upstream branches are connected into the connecting channel, and the connecting channel is connected into a downstream branch.
4. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 2 wherein: the midstream branch is a connecting channel or at least one fluid receiving cavity connected through the connecting channel; an upstream branch is connected to a midstream branch, and the tail end of the midstream branch is connected to a plurality of downstream branches in parallel.
5. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 1 wherein: the thermal working medium is a working medium which is not miscible or reactive with the target fluid to be controlled, and comprises one or more of gas, liquid and solid with thermal response capability in form or volume, or one or more of phase change materials which can generate gas-liquid, liquid-solid and gas-solid phase interconversion under the control of temperature, or biological or chemical reaction substances which are controlled by thermal triggering and generate deformation or volume change.
6. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 1 wherein: the transfer time and direction, transfer volume, transfer flow and flow speed and flow time of the target fluid to be controlled are realized by regulating and controlling the temperature of the thermal working medium and combining the geometric dimensions and topological structures of each chamber and the connecting channel.
7. A thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 1 wherein: a thermal control working medium cavity, a fluid bearing cavity and a unified working environment reference point form a thermal programming micro-fluid control unit; the thermal programming micro-fluid control device comprises one or more thermal programming micro-fluid control units, the thermal programming micro-fluid control units form a network, and a fluid bearing cavity or a fluid bearing cavity is shared among the thermal programming micro-fluid control units.
8. The control strategy for a thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 7, wherein a single point time division multiplexing mode is employed: and carrying out temperature parameter adjustment on a single thermal programming microfluidic control unit to realize timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, wherein the sample fluid is used as the target fluid to be controlled.
9. The control strategy for a thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 7, wherein a multi-point synchronous/asynchronous cooperative mode is employed: through the combination of a plurality of thermal programming micro-fluid control units, one part of the combination is synchronously controlled to carry out multi-component synchronous addition of the micro-fluid complex reaction, the other part of the combination is synchronously controlled to carry out multi-component stepwise addition of the micro-fluid complex reaction, and the components are used as target fluids to be controlled.
10. The control strategy for a thermally programmed microfluidic control device for microfluidic complex reaction manipulation according to claim 7, wherein an array network linkage mode is employed: for a network structure formed by a plurality of thermal programming micro-fluid control units, a highly flexible and fluxional micro-fluid complex reaction operation system is constructed by combining a single-point time-sharing multiplexing mode and a multi-point synchronous/asynchronous cooperation mode; single point time division multiplexing mode: the temperature parameter adjustment is carried out on a single thermal programming microfluidic control unit to realize the timing and quantitative control of the same sample fluid of the microfluidic multi-step reaction, and the sample fluid is used as the target fluid to be controlled; multipoint synchronous/asynchronous collaboration mode: through the combination of a plurality of thermal programming micro-fluid control units, one part of the combination is synchronously controlled to carry out multi-component synchronous addition of the micro-fluid complex reaction, the other part of the combination is synchronously controlled to carry out multi-component stepwise addition of the micro-fluid complex reaction, and the components are used as target fluids to be controlled.
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