CN110013891B - Microfluidic system based on bionic responsive liquid gating and control method - Google Patents
Microfluidic system based on bionic responsive liquid gating and control method Download PDFInfo
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- CN110013891B CN110013891B CN201910070035.5A CN201910070035A CN110013891B CN 110013891 B CN110013891 B CN 110013891B CN 201910070035 A CN201910070035 A CN 201910070035A CN 110013891 B CN110013891 B CN 110013891B
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- 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
- B01L3/502707—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 manufacture of the container or its components
Abstract
The invention belongs to the field of bionic responsive microfluidic systems, and discloses a microfluidic system based on bionic responsive liquid gating, which is provided with a microchannel; conveying liquid is introduced into the microchannel, and the microchannel is combined with the responsive substance through physical adsorption or chemical action; a porous matrix is arranged between the micro-channel and the responsive substance; the responsive substance is encapsulated with the microchannel within the containment device. The bionic responsive liquid gated microfluidic system releases and absorbs liquid, and the liquid is used as a gated substrate to realize intelligent regulation and control of liquid conveying behavior of a microchannel; the invention breaks through the limitation of the traditional solid/liquid material interface design, brings excellent pollution resistance and solvent swelling resistance by applying a brand new dynamic solid/liquid interface design, and is beneficial to prolonging the cycle service life of the microfluidic chip.
Description
Technical Field
The invention belongs to the field of bionic responsiveness microfluidic systems, and particularly relates to a microfluidic system based on bionic responsiveness liquid gating and a control method.
Background
Currently, the current state of the art commonly used in the industry is such that:
the microfluidic technology relates to the cross fields of multiple subjects such as chemistry, materials science, fluid physics, physical chemistry, microelectronics, engineering, new materials, biomedicine, micro-nano processing technology and the like, and has huge application prospects in the aspects of biochemical reaction, personalized medical detection, clinical diagnosis and the like. The microfluidic industry has been rapidly developed in recent years, and the microfluidic industry is expected to reach 230 billion dollars by 2022 in a report of the current state of the Chinese microfluidic industry-2018 edition. However, how to realize the intellectualization of the channel under the micro scale in the micro-fluidic chip, the limitation of the application of the micro-fluidic system with single function is distinguished, and the performances of pollution resistance, solvent swelling resistance and the like of the micro-fluidic device are improved, so that the micro-fluidic chip always faces huge challenges and a bottleneck restricting the rapid development of the micro-fluidic chip.
In recent years, the intellectualization of channels under the microscale is deeply explored, and two design ideas are generally available. One is to modify the surface of the microchannel with a responsive molecule. After external field stimulation, the modified microchannel surface generates hydrophilic and hydrophobic conversion, or response to the unfolding and collapsing of molecular chains. However, this approach is very sensitive to the size of the channel, and the effect of this response will disappear when the size of the channel is orders of magnitude higher than the chain length of the responding molecule. Meanwhile, the method inevitably generates channel pollution, and the service life of the micro-channel is limited. The other is a substance that modifies the response deformation in/out of the channel, which can solve the response to the channel in the large size. However, contamination of the microchannels is still unavoidable and deformation of the microchannels does not completely close the channels.
In summary, the problems of the prior art are as follows:
(1) when the size of the channel is orders of magnitude higher than the chain length of the responsive molecule, the effect of this response will disappear; meanwhile, the mode inevitably generates channel pollution, and the service life of the micro channel is limited.
(2) In modifying the material inside/outside the channel in response to the deformation, contamination of the microchannel is still unavoidable and the deformation of the microchannel does not completely close the channel.
The difficulty of solving the technical problems is as follows:
by using the techniques such as atom transfer radical polymerization, the molecular chain length of the responsive molecule constructed on the surface of the channel can reach a stable value (micron level), so that the effect of the response can be eliminated when the size order of the channel is far higher than the chain length of the responsive molecule under the control of the size of the micro-channel. When the intelligent regulation is realized by utilizing the action of the response generating force on the micro-channel, the pollution problem cannot be avoided, and the deformation of the micro-channel cannot completely close the channel. Therefore, such conventional solid/solid interface has difficulty in solving the problems of dimensional effect and contamination resistance.
The significance of solving the technical problems is as follows:
the design of the interface has been a hot spot of the research of the microfluidic system. The invention applies a brand new dynamic solid/liquid interface design, and the responsive substance releases and absorbs liquid. The liquid is used as a gating liquid and acts on the microchannel through the porous matrix, so that the intellectualization of the channel under the microscale and the high adaptability under the dynamic environmental change are realized, and a brand new thought and research platform is provided for the drug release of the microfluidic technology and the cell behavior research in the microchip. Meanwhile, the excellent anti-pollution and anti-solvent swelling performance is brought, the cycle service life of the micro-fluidic chip is greatly prolonged, and the use cost is reduced.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a micro-fluidic system based on bionic responsiveness liquid gating and a control method. The invention combines the responsive substances with light, magnetism, heat, pH, sound, force or chemistry and the like with the micro-channel through physical adsorption or chemical action, and under the combined action of any one or more external fields mentioned, the responsive substances release and absorb liquid. The liquid is used as a gating liquid, acts on a micro-channel through a porous substrate, realizes the intellectualization of the channel under the micro-scale and high adaptability under the dynamic environment change, and brings excellent anti-pollution and anti-solvent swelling performance.
The invention is realized in such a way that a microfluidic system based on bionic responsive liquid gating is provided with:
a microchannel;
conveying liquid is introduced into the microchannel, and the microchannel is combined with the responsive substance through physical adsorption or chemical action;
a porous matrix is arranged between the micro-channel and the responsive substance; the responsive substance is encapsulated with the microchannel within the containment device.
Another object of the present invention is to provide a microfluidic system device based on bionic responsive liquid gating, comprising: and the upper part and the lower part of the packaging shell are fixed through screws, and the packaging shell is provided with an incoming line and an outgoing line.
Further, the gating liquid can be an aqueous solution, an organic solvent, a fluorine-containing solution, or low surface energy oils such as gasoline, kerosene, olive oil, lubricating oil, sesame oil and silicone oil.
Furthermore, the bionic responsive liquid-gated microfluidic system is used for preparing responsive substances, and the responsive substances are compounded with the microchannel through physical adsorption, van der waals force, hydrogen bond action or covalent mode, so that the bionic responsive liquid-gated microfluidic system can be used for multiple times and is flexibly assembled.
Furthermore, the material for preparing the channel in the microfluidic system based on the bionic responsive liquid gate control can be a high molecular organic film such as cellulose derivatives, polysulfones, polyimides, silicon-containing polymers, polyamides, polyolefins, chitin, polyesters, vinyl polymers, fluorine-containing polymers and the like, and can also be an elastomer material such as PDMS, VHB, rubber, nylon and the like.
Furthermore, in the microfluidic system based on bionic responsive liquid gating, the micro-channel can use micro-processing technologies such as laser engraving, chemical corrosion, soft etching, hot pressing, blade cutting and the like, the size of the channel is accurate and controllable, and meanwhile, large-scale batch industrial production can be realized.
The invention also aims to provide a micro-fluidic manufacturing method based on bionic responsive liquid gating, which comprises the following steps:
designing micro-channels with various sizes and shapes by using computer-aided software;
step two, processing the microfluidic substrate material into the size and the shape of a channel required by design through a micro-processing technology, wherein the size of the channel is accurate and controllable;
thirdly, compounding the prepared responsive substance with the microchannel through physical adsorption or chemical action;
step four, encapsulating the responsive substance and the micro-channel in a closed device to form an intelligent responsive micro-fluidic system based on liquid gating;
and fifthly, applying external field stimulation, releasing and absorbing liquid by the responsive substance, and acting on the micro-channel through the porous matrix to realize the intelligent regulation and control of liquid conveying behavior of the micro-channel.
In summary, the advantages and positive effects of the invention are:
the micro-fluidic system based on the bionic responsive liquid gate can accurately design and prepare the micro-channel with the required size by the micro-processing technology, such as the micro-channel with the size from 200 microns to 800 microns in figures 5 and 6; after external field stimulation (e.g., temperature), the filling and removal of gated liquid in the microchannel can be rapidly achieved (fig. 5). The invention utilizes liquid with fluidity as gating liquid, and can realize intelligent regulation and control of liquid conveying behavior of the microchannel even if the size of the microchannel is in the order of millimeter (figure 6). The invention breaks through the limitation of the traditional solid/liquid material interface design, applies the brand-new dynamic solid/liquid interface design, converts the solid/liquid interface into the liquid/liquid interface, and brings excellent anti-pollution performance (figure 7).
Drawings
Fig. 1 is a schematic structural diagram of a microfluidic system based on bionic responsive liquid gating according to an embodiment of the present invention.
In the figure: 1. a responsive substance; 2. a porous matrix; 3. a microchannel; 4. external field stimulation; 5. a gating fluid; 6. and (5) packaging the material.
Fig. 2 is a schematic structural diagram of a microfluidic system device based on bionic responsive liquid gating according to an embodiment of the present invention.
Fig. 3 is a schematic diagram and an object of an incoming line, an outgoing line and a screw arrangement structure provided by an embodiment of the invention.
Fig. 4 is a flow chart of a microfluidic control method based on bionic responsive liquid gating, provided by an embodiment of the invention.
Fig. 5 is a fluorescence image process of a gated liquid entering and aspirating a pore channel after the gated liquid is heated and responded in the microfluidic system based on bionic responsive liquid gating provided by the embodiment of the invention.
Fig. 6 is a schematic and fluorescent picture of a microfluidic system based on bionic responsive liquid gating, which is provided by the embodiment of the invention and can realize intelligent regulation and control of liquid conveying behavior in a large-scale microchannel.
Fig. 7 is a micro-fluidic system based on bionic responsive liquid gating, which is provided by the embodiment of the invention, and the detection and evaluation of the anti-pollution performance of the micro-fluidic system are carried out.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
As shown in fig. 1, a microfluidic system based on biomimetic responsive liquid gating according to an embodiment of the present invention includes: response substance 1, porous matrix 2, microchannel 3, external field stimulus 4, gated liquid 5, encapsulating material 6;
conveying liquid is introduced into the microchannel 3, a porous matrix 2 is arranged between the microchannel 3 and the response substance 1, and the porous matrix 2 is combined with the response substance 1 through physical adsorption or chemical action; the responsive substance is encapsulated with the microchannel within the containment device.
As shown in fig. 2 and fig. 3, a microfluidic system device based on biomimetic responsive liquid gating according to an embodiment of the present invention includes: packaging a shell, incoming wires, outgoing wires and screws;
the upper and lower parts pass through the screw fixation in the encapsulation shell, and the encapsulation shell is provided with inlet wire, is qualified for the next round of competitions.
As shown in fig. 4, the microfluidic control method based on biomimetic responsive liquid gating provided by the embodiment of the present invention includes the following steps:
s101: designing microchannels with various sizes and shapes by using computer-aided software;
s102: the microfluidic substrate material is processed into the size and the shape of a channel required by design through a micro-processing technology, and the size of the channel is accurate and controllable;
s103: after the responsive substance is prepared, the responsive substance is compounded with the microchannel through physical adsorption or chemical action;
s104: the responsive substance and the micro-channel are encapsulated in a closed device to form an intelligent responsive micro-fluidic system based on liquid gating;
s105: and applying external field stimulation, releasing and absorbing liquid by the responsive substance, and acting on the microchannel through the porous matrix to realize the intelligent regulation and control of liquid conveying behavior of the microchannel.
As a preferred embodiment of the present invention, the gating liquid may be an aqueous solution, an organic solvent, a fluorine-containing solution, or a low surface energy oil such as gasoline, kerosene, olive oil, lubricating oil, sesame oil, silicone oil, etc.
As a preferred embodiment of the invention, the responsive substance is prepared in the microfluidic system based on bionic responsive liquid gating, and is compounded with the microchannel through physical adsorption, van der Waals force, hydrogen bond action or covalent mode, so that the microfluidic system can be used for multiple times and is flexibly assembled.
As a preferred embodiment of the present invention, the material used for preparing the channel in the microfluidic system based on the biomimetic responsive liquid gate may be a polymer organic film such as cellulose derivatives, polysulfones, polyimides, silicon-containing polymers, polyamides, polyolefins, chitin, polyesters, vinyl polymers, fluoropolymers, or an elastomer material such as PDMS, VHB, rubber, nylon, or the like.
As a preferred embodiment of the invention, in the microfluidic system based on bionic responsive liquid gating, the micro-channel can use micro-processing technologies such as laser engraving, chemical corrosion, soft etching, hot pressing, blade cutting and the like, the size of the channel is accurate and controllable, and meanwhile, the micro-channel can be produced industrially in large scale.
As a preferred embodiment of the present invention, as shown in fig. 1, the present invention is based on a biomimetic responsive liquid gated microfluidic system, comprising a responsive substance and a microchannel. The method comprises the steps of preparing a micro-channel with a required shape and size by using a laser etching technology, preparing a responsive substance, compounding the micro-channel with the responsive substance by using a physical adsorption or chemical crosslinking mode, and releasing and absorbing liquid by the responsive substance under the stimulation of an external field. The liquid is used as a gating liquid, so that the intelligent regulation and control of liquid conveying behaviors of the micro-channel are realized. The invention acts on the microchannel through the porous substrate, breaks through the limitation of the traditional solid/liquid material interface design, brings excellent anti-pollution and anti-solvent swelling performance by applying a brand new dynamic solid/liquid interface design, and has good anti-pollution effect on inorganic matters, organic matters, compounds and even blood. In addition, the invention can control the responsive substance to release the drug or the small molecule into the microchannel, and provides a brand-new research platform for the drug release of the microfluidic technology and the cell behavior research in the microchip.
As a preferred embodiment of the present invention, the present invention is based on a bionic responsive liquid-gated microfluidic system, when the responsive substance release and absorption gating liquid is an aqueous solution, the responsive substance may be a light responsive gel, a magnetic responsive gel, a thermal responsive gel, a pH responsive gel, an acoustic responsive gel, a force responsive gel, an electric responsive gel, a chemical responsive gel, etc., and the thermal responsive gel is taken as an example, and other responsive gels are included. The thermal response gel includes poly-N-isopropylacrylamide gel (PNIPAM), poly-N, N-diethylacrylamide gel, poly-N-ethylacrylamide gel, poly-N-N-propylacrylamide gel, and the like. Taking PNIPAM as an example, the prepared PNIPAM is compounded with the porous matrix in a hydrogen bond mode. The macromolecular side chain of the polymer has two parts of hydrophilic amide group and hydrophobic isopropyl group simultaneously. At normal temperature, the PNIPAM molecular chain wraps a large amount of water due to strong hydrogen bond action between the hydrophilic group and water molecules. With increasing temperature, part of the hydrogen bonding force gradually weakens, and the hydrophobic force in the chain continuously increases. When a certain temperature is reached, under the interaction of hydrophobic groups, polymer chains are mutually aggregated, volume phase transformation occurs, and a large amount of liquid is released. The liquid is used as a gate liquid, acts on the micro-channel through the porous substrate, and the gate liquid is filled in the channel to enable the channel to be in a closed state. When the temperature of the aqueous solution is reduced, the water-soluble polymer micro-channel can reversibly absorb water to enable the channel to be in an open state, so that the intelligent regulation and control of the micro-channel under thermal regulation and control for liquid transportation are realized, and meanwhile, excellent pollution resistance and solvent swelling resistance are brought.
As a preferred embodiment of the present invention, when the gated liquid for releasing and absorbing the responsive substance is a fluorine-containing solution, an organic solvent, a low surface energy oil (gasoline, kerosene, olive oil, lubricating oil, sesame oil, silicone oil), the responsive substance may be a light-responsive gel, a magnetic-responsive gel, a thermal-responsive gel, a pH-responsive gel, an acoustic-responsive gel, a force-responsive gel, an electric-responsive gel, a chemical-responsive gel, etc., taking a light-responsive gel as an example, and other corresponding gels are included in the microfluidic system based on biomimetic responsive liquid gating of the present invention. The light response gel includes but is not limited to azobenzene, stilbenes, spiropyrans and other gels. Taking azobenzene as an example, the prepared azobenzene is compounded with the porous matrix material. The trans conformation of azobenzene is more stable than the cis conformation, and trans-cis isomeric transformation can occur under the condition of ultraviolet illumination to cause reversible transformation of gel release liquid-absorption liquid. The liquid is used as a gate liquid, acts on the micro-channel through the porous substrate, and the gate liquid is filled in the channel to enable the channel to be in a closed state. When the liquid is adsorbed, the channel is in an open state. The intelligent regulation and control of the liquid transportation behavior of the micro-channel under thermal regulation and control are realized, and meanwhile, excellent pollution resistance and solvent swelling resistance are brought.
As a preferred embodiment of the present invention, in the microfluidic system based on biomimetic responsive liquid gating according to the present invention, the responsive substance may be a light response, a magnetic response, a thermal response, a pH response, an acoustic response, a force response, a chemical response, or the like, and may be a multi-response, such as a random combination of two or more of light-heat, light-pH, and heat-pH, for example, the heat-pH response, PNIPAM and acrylic copolymer gel have a certain proportion of hydrophilic groups and hydrophobic groups, and the hydrophobic groups have a larger effect than the hydrophilic groups at high temperature, thereby releasing liquid. Under acidic conditions, weakly acidic groups on molecular chains are ionized to form anions with points, and large osmotic pressure is generated in gel to adsorb a large amount of liquid. Under alkaline conditions, liquid can be released reversibly, the liquid is used as a gating liquid, the gating liquid acts on the micro-channel through the porous matrix, and the gating liquid is filled in the channel to enable the channel to be in a closed state. When the liquid is adsorbed, the channel is in an open state. The intelligent regulation and control of the liquid transportation behavior of the micro-channel under thermal regulation and control are realized, and meanwhile, excellent pollution resistance and solvent swelling resistance are brought.
The working principle of the invention is as follows:
firstly, designing micro-channels with various sizes and shapes by using computer-aided software; the microfluidic substrate material is processed into the size and the shape of a channel required by design through a micro-processing technology, and the size of the channel is accurate and controllable;
then, preparing a responsive substance, and compounding the responsive substance with the microchannel through physical adsorption or chemical action; the responsive substance and the micro-channel are encapsulated in a closed device to form an intelligent responsive micro-fluidic system based on liquid gating;
and finally, applying external field stimulation, releasing and absorbing liquid by the responsive substance, and acting on the microchannel through the porous substrate to realize the intelligent regulation and control of liquid delivery behavior of the microchannel.
The invention is further described below with reference to thermal response as an example.
The invention can precisely design and prepare the micro-channel with the required size by micro-processing technology, such as the micro-channel with the size of 200 microns to 800 microns in figures 5 and 6;
preparing a responsive substance PNIPAM, and compounding the responsive substance PNIPAM and the micro-channel in a hydrogen bond mode; the PNIPAM and the micro-channel are packaged in a closed device to form an intelligent responsiveness micro-fluidic system based on liquid gating;
as shown in fig. 5, after the temperature is increased, the responsive substance releases liquid, and is adsorbed on the porous matrix under the action of capillary force, and when the liquid is increased, the released gated liquid enters the micro-channel due to instability; after the temperature is reduced, the hydrogen bond separating acting force in the PNIPAM is gradually enhanced, the hydrophobic acting force in the chain is continuously weakened, the gated liquid in the channel is reversibly absorbed through the porous matrix, and the intelligent regulation and control liquid conveying behavior of the micro-channel is realized.
As shown in fig. 6, the conventional responsive channel is controlled by the size of the microchannel, and the effect of this response will disappear when the size of the channel is orders of magnitude higher than the chain length of the responsive molecule. The invention uses liquid with fluidity as gate control liquid, and can realize intelligent regulation and control of liquid conveying behavior of the micro-channel even if the size of the micro-channel is in the order of millimeter.
Referring to fig. 7, when fluorescence-labeled cyclohexane is introduced into the channel, and then water is introduced for cleaning, the traditional material still has a fluorescence signal, but the present invention breaks through the limitation of the traditional solid/liquid material interface design, and the brand new dynamic solid/liquid interface design is applied to convert the solid/liquid interface into the liquid/liquid interface, so as to bring excellent anti-pollution performance.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (4)
1. The utility model provides a micro-fluidic system based on bionical responsiveness liquid gate, its characterized in that, micro-fluidic system based on bionical responsiveness liquid gate be provided with: a microchannel; conveying liquid is introduced into the microchannel, and the microchannel is combined with the responsive substance through physical adsorption or chemical action; a porous matrix is arranged between the micro-channel and the responsive substance; the responsive substance and the micro-channel are encapsulated in the closed device;
the responsive substance is a light responsive gel, a magnetic responsive gel, a thermal responsive gel, a pH responsive gel, an acoustic responsive gel, a force responsive gel, an electrical responsive gel, or a chemical responsive gel.
2. The biomimetic-responsive liquid-gated-based microfluidic system of claim 1, wherein the gated liquid is one of an aqueous solution, an organic solvent, a fluorine-containing solution, gasoline, kerosene, olive oil, lubricating oil, sesame oil, and silicone oil.
3. The biomimetic-responsive liquid-gate based microfluidic system of claim 1, wherein the micro-channels are fabricated using laser engraving, chemical etching, soft lithography, hot pressing, and cutting with a blade.
4. The microfluidic control method based on bionic-response liquid gating of the microfluidic control system based on bionic-response liquid gating of claim 1, wherein the microfluidic control method based on bionic-response liquid gating comprises the following steps: designing micro-channels with various sizes and shapes by using computer-aided software; step two, processing the microfluidic substrate material into the size and the shape of a channel required by design through a micro-processing technology; thirdly, compounding the prepared responsive substance with the microchannel through physical adsorption or chemical action; step four, encapsulating the responsive substance and the micro-channel in a closed device to form an intelligent responsive micro-fluidic system based on liquid gating; and fifthly, applying external field stimulation, releasing and absorbing liquid by the responsive substance, and acting on the micro-channel through the porous matrix to realize the intelligent regulation and control of liquid conveying behavior of the micro-channel.
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