CN112691709A - Fluid driving device, preparation method of fluid driving device and surface treatment method - Google Patents
Fluid driving device, preparation method of fluid driving device and surface treatment method Download PDFInfo
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Abstract
The fluid driving device provided by the invention comprises N layers of interconnected fluid channels, wherein N is an integer more than or equal to 2, any layer of the fluid channel comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid, and the fluid driving mode provided by the invention integrates basic operation flows of sample preparation, separation, reaction, detection and the like on the same chip, so that various fluid operation and control flows required in sample treatment and detection are completed, and the application is wide.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a fluid driving device, a preparation method of the fluid driving device and a surface treatment method.
Background
The microfluidic chip is also called a Lab-on-a-chip (Lab-on-a-chip) and is used for integrating basic operation units related to the fields of biology, chemistry, medicine and the like, such as sample preparation, reaction, separation, detection and the like, on one chip to automatically complete the whole process of reaction and analysis.
The driving and controlling of the fluid in the microfluidic chip can be realized by a micropump, and in the research aspect of the micropump, the micropump comprises a mechanical micropump and a non-mechanical micropump. The mechanical micropump is simple and convenient to operate, easy to realize and low in cost, but miniaturization and integration are not easy to realize on a chip; rather than a mechanical micropump, the fluid is converted or applied to the driven fluid by other forms of energy (optical, electrical, magnetic, thermal, etc.) to impart kinetic energy to the fluid. Since non-mechanical micropumps are generally of valveless construction, they are often referred to as dynamic continuous flow pumps.
In recent years, a method for conveying and processing fluid in a microfluidic chip by using hydrophilic and hydrophobic characteristics or capillary force of a surface of a material or a structure becomes a difficult problem in the technology of the microfluidic chip. For example, in the microfluidic chip made of paper, plastic, etc., the method has the advantages that the fluid can be spontaneously driven without additional energy, but has the disadvantages that it is difficult to implement a complex fluid control function or system, it is impossible to complete various fluid operation and control processes required when the microfluidic chip is used for sample processing and detection, and basic operation processes of sample preparation, separation, reaction, detection, etc. cannot be integrated on the same chip.
Disclosure of Invention
In view of the above, it is desirable to provide a fluid driving device having multiple functions and high integration degree, which overcomes the drawbacks of the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
in one aspect, the invention provides a fluid driving device, which includes N layers of interconnected fluid channels, where N is an integer greater than or equal to 2, any one of the fluid channels includes a fluid sample introduction module and a functional module connected to the fluid sample introduction module, where fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can achieve different types of fluid mixing and/or accurately measure and/or self-drive the fluid, and the fluid includes at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagent.
In some preferred embodiments, the fluid injection module comprises at least one injection port and an injection port fluid channel connected to any one of the injection ports, and the fluid enters the functional module from the injection port through the injection port fluid channel.
In some preferred embodiments, the functional module includes a control unit, the control unit includes a micro valve structure and an etching fluid channel connected to the micro valve structure, and the opening and closing of the etching fluid channel and the switching of the fluid flow direction can be realized through the micro valve structure.
In some preferred embodiments, the functional module comprises a mixing unit comprising at least one mixing fluid channel through which the fluids can be mixed.
In some preferred embodiments, the functional module comprises a mixing unit comprising at least two mixed fluid channels, the fluids in the mixed fluid channels passing sequentially one after the other at the location of the junction.
In some preferred embodiments, the mixing fluid channel comprises a straight line, a serpentine, an S-shape, or a spiral shape.
In some preferred embodiments, the width of the mixing fluid channel is 10-5000 microns.
In some preferred embodiments, the functional module includes a measuring unit, the measuring unit includes at least one measuring fluid channel and a micro valve structure connected to the measuring fluid channel, and the micro valve structure can stop or block the measuring fluid channel, so as to accurately measure the fluid.
In some preferred embodiments, the functional module includes a power unit, the power unit includes at least one power fluid channel and a power assembly disposed on the power fluid channel, and the power assembly includes micro-pillars disposed at intervals and having different heights.
In some preferred embodiments, the height of the microcolumn is 10 to 5000 micrometers.
In some preferred embodiments, the cross-section of the microcolumn is circular, parallelogram, regular polygon or ellipse.
In some preferred embodiments, when the cross-section of the microcolumns is circular, the radius of the microcolumns is less than 5000 micrometers, and the shortest distance between two adjacent microcolumns is 1 to 2000 micrometers.
In some preferred embodiments, when the diameter of the circular shape of the microcolumn is 20 to 500 micrometers, the shortest distance between two adjacent microcolumns is 10 to 1500 micrometers.
In some preferred embodiments, the sample outlet unit further comprises at least one sample outlet fluid channel, and the fluid after passing through the functional module flows out of the sample outlet fluid channel.
In another aspect, the present invention further provides a method for manufacturing the fluid driving device, including the following steps:
forming a protective layer on a substrate;
etching the protective layer to form a plurality of first windows;
etching the protective layer and the substrate to form a plurality of second windows;
and etching the substrate through the first window and the second window by using the protective layer as a mask to form a first layer of the fluid channel and a second layer of the fluid channel, wherein the fluid channel comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents.
In some preferred embodiments, the step of forming the protective layer on the substrate specifically includes: forming a protective layer and a first mask layer on the protective layer on a substrate;
the substrate comprises silicon, silicon oxide or silicon nitride and the protective layer comprises silicon dioxide or a metal mask.
In some preferred embodiments, in the step of etching the protective layer to form the plurality of first windows, the step specifically includes:
forming a first micro-channel male die layer on the first mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process;
and etching the protective layer by taking the first micro-channel male mold layer as a mask to form a plurality of first windows, and removing the first micro-channel male mold layer.
In some preferred embodiments, the protective layer and the substrate are etched to form a plurality of second windows, specifically:
forming a second mask layer on the protective layer of the first window;
forming a second micro-channel male die layer on the second mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process;
and etching the protective layer and the substrate by taking the second micro-channel male die layer as a mask to form a plurality of second windows.
In a third aspect, the present invention further provides a method for manufacturing a fluid driving device, including the steps of:
forming an anode mould layer of an N-layer fluid channel on a substrate, wherein N is an integer more than or equal to 2;
turning over the fluid channel male die layer to form N layers of interconnected fluid channels, wherein N is an integer more than or equal to 2;
any layer of the fluid channel comprises a fluid sample feeding module and a functional module connected with the fluid sample feeding module, wherein fluid can enter the functional module through the fluid sample feeding module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measuring and/or self-driving of the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents.
In some preferred embodiments, the step of forming an N-layer positive mold layer of the fluid channel on the substrate, where N is an integer greater than or equal to 2, specifically includes:
when the substrate is made of silicon-based materials or quartz or glass, the N-layer micro-channel male mold layer is prepared by adopting the processes of deep ultraviolet lithography or laser direct writing lithography and the like;
when the substrate is cycloolefin copolymer or cyclic olefin copolymer, preparing N layers of fluid channel male die layers by adopting a carving process and laser cutting;
when the substrate is polylactic acid, polyhydroxybutyrate or polyhydroxyalkanoate, the N-layer fluid channel positive mold layer is prepared by selecting a 3D printing mode.
In some preferred embodiments, in the step of overmolding the fluid channel male mold layer to form N layers of fluid channels, N being an integer ≧ 2,
the material selected by the turnover mould comprises polydimethylsiloxane or room temperature vulcanization type silicon rubber.
In a fourth aspect, the present invention further provides a method for manufacturing a fluid driving device, including the steps of:
the method comprises the steps of forming N layers of interconnected fluid channels on a substrate in a machining mode, wherein N is an integer larger than or equal to 2, any layer of the fluid channels comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can achieve different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid, the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, tissue fluid and detection reagents, and the machining comprises numerical control machining, laser engraving machine or 3D printing.
In some preferred embodiments, the substrate is polymethylmethacrylate or plastic.
In addition, the invention also provides a surface treatment method of the fluid driving device, which comprises the following steps:
and treating the surface of the fluid driving device by using a chemical reagent, and keeping the contact angle of the surface stable.
In some preferred embodiments, the agent comprises (3-aminopropyl) triethoxysilane or polyethylene glycol.
In some preferred embodiments, the surface treatment includes a chemical treatment, a spin coating treatment, or a coating treatment.
In some preferred embodiments, the contact angle is in the range of 20 DEG to 70 DEG, and the surface contact angle of the fluid driving device can be maintained for a stabilization time of at least N days, wherein N is an integer greater than or equal to 3.
The invention adopts the technical scheme that the method has the advantages that:
the fluid driving device provided by the invention integrates basic operation processes of preparation, separation, reaction, detection and the like of a sample into the same chip, completes various fluid operation and control processes required during sample treatment and detection, can be widely applied to the fields of immunodetection, biochemical analysis and molecular diagnosis based on a microfluidic chip technology, the kit mainly focuses on immune protein detection, cell recognition and diagnosis, nucleic acid amplification and detection, blood sugar detection, blood gas and electrolyte analysis, rapid hemagglutination detection, rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, and detection of blood fat items such as triglyceride and cholesterol, and is widely used.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without any creative effort.
Fig. 1 is a schematic structural diagram of a fluid driving device according to an embodiment of the present invention.
Fig. 2 is a schematic structural diagram of the fluid sample injection module according to an embodiment of the present invention.
Fig. 3 is a partially enlarged view of a control unit according to an embodiment of the present invention.
Fig. 4A is a partially enlarged view of a mixing unit according to an embodiment of the invention.
Fig. 4B is a partially enlarged view of a mixing unit according to an embodiment of the invention.
Fig. 5 is a partially enlarged view of the measuring unit according to the embodiment of the present invention.
Fig. 6 is a partially enlarged view of a power unit provided in an embodiment of the present invention.
Fig. 7 is a partially enlarged view of a sample outlet unit according to an embodiment of the present invention.
Fig. 8 is a flowchart illustrating steps of a method for manufacturing a fluid driving device according to an embodiment of the present invention.
Fig. 9 is a flowchart illustrating steps of a method for manufacturing a fluid driving device according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example one
Referring to fig. 1, a schematic structural diagram of a fluid driving device according to an embodiment of the present invention is shown, including: the device comprises N layers of interconnected fluid channels 10, wherein N is an integer larger than or equal to 2, any layer of the fluid channels 10 comprises a fluid sample injection module 11 and a functional module 20 connected with the fluid sample injection module, fluid can enter the functional module 20 through the fluid sample injection module 11, and the functional module 20 can control the flow direction of the fluid and/or realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid. The fluid includes at least one of buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagents.
It is to be understood that the fluid channels are not limited to two layers, but may be extended to a multi-layer structure, and the geometric relationship between the first layer of fluid channels and the second layer of fluid channels in the horizontal direction is not limited to vertical, as long as it is satisfied that the first layer of fluid channels is connected to the second layer of fluid channels at a certain position.
The structure, function, and interconnection of the various modules are described in detail below.
Referring to fig. 2, a schematic structural diagram of the fluid sample injection module 11 according to an embodiment of the present invention includes: at least one sample inlet 111 and a sample inlet fluid channel 112 connected to any one of the sample inlets 111, wherein the fluid enters the functional module 20 through the sample inlet 111 and the sample inlet fluid channel 112.
It is to be understood that the sample inlet 111 of the fluid sample module 11 provided by the present invention is not limited to one, and the inlet may be designed to be multiple, and each inlet may be respectively introduced with buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagent, including but not limited to the above combinations.
Referring to fig. 3, the functional module 20 includes a control unit 21, the control unit 21 includes a micro valve structure 210 and an etching fluid channel 211 connected to the micro valve structure 210, and the opening and closing of the etching fluid channel 211 and the switching of the fluid flow direction can be realized through the micro valve structure 210. The fluid includes at least one of a buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and a test agent.
It will be appreciated that the microvalve structure 210 may be rectangular or square in cross-section or otherwise shaped. The microvalve structures 210 include trigger microvalve structures, static microvalve structures, depth microvalve structures, and shut-off microvalve structures or other types of microvalves.
Referring to fig. 4A, the functional module 20 further includes a mixing unit 22, and the mixing unit 22 includes at least one mixing fluid channel 221, and the fluids can be mixed through the mixing fluid channel 221. The fluid includes at least one of buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and a test agent.
Referring to fig. 4B, the functional module 20 includes a mixing unit 22, and the mixing unit 22 includes at least two mixing fluid channels 221(222), and the fluids in the mixing fluid channels are mixed after passing through the combined position.
It can be understood that, in practice, one fluid a (such as blood and tissue fluid with relatively high viscosity) is allowed to pass through the mixing fluid channel 221 (such as by arranging a series of serpentine fluid channels to increase the flow resistance and reduce the flow rate of the fluid passing through the mixing fluid channel), and another fluid channel 222 is allowed to rapidly introduce another fluid B (such as buffer solution), so that when the buffer solution reaches the combining position, the fluid stays at the combining position of the two fluid channels due to the existence of the control unit, and the fluid B can be triggered to pass through the combining position after the fluid a passes through the combining position.
In some preferred embodiments, the mixing fluid channel 221 is straight, serpentine, S-shaped, spiral, or not limited to the above; the cross-section of the mixing fluid channel 221 is rectangular, square, or not limited to the above combinations; the width of the mixing fluid channel 221 is 10-5000 microns, and different types of fluid mixing can be achieved by the mixing module.
Referring to fig. 5, the functional module 20 further includes a measuring unit 23, the measuring unit 23 includes at least one measuring fluid channel 231 and a micro valve structure 232 connected to the measuring fluid channel 231, and the micro valve structure 232 can stop or block the measuring fluid channel 231, so as to accurately measure the fluid. The fluid includes at least one of buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagents.
Referring to fig. 6, the functional module 20 further includes a power unit 24, the power unit 24 includes at least one power fluid channel 241 and a power assembly 242 disposed on the power fluid channel 241, and the power assembly 242 includes microcolumns 243 spaced apart and having different heights. It can be appreciated that self-actuation of the fluid is achieved by differential design of the different silicon-based pillar heights. The fluid includes at least one of buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagents.
In some preferred embodiments, the height of the microcolumns 243 is 10 to 5000 micrometers, and the cross-section of the microcolumns 243 is circular, parallelogram, regular polygon or ellipse and includes but is not limited to the above shapes.
Further, when the cross-section of the microcolumns 243 is circular, the radius thereof is less than 5000 micrometers, and the shortest distance between two adjacent microcolumns 243 is 1 to 2000 micrometers. More preferably, when the diameter of the circle is 20 to 500 μm, the shortest distance between two adjacent microcolumns 243 is 10 to 1500 μm.
Referring to fig. 7, the fluid driving apparatus further includes a sample outlet unit 30, the sample outlet unit 30 includes at least one sample outlet fluid channel 31, and the fluid passing through the functional module 20 flows out of the sample outlet fluid channel 31. The fluid includes at least one of buffer, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid, and detection reagents.
It is understood that the functional module 20 of the fluid driving apparatus provided by the present invention includes one or more different units or a plurality of identical units among the control unit 21, the mixing unit 22, the measuring unit 23, and the power unit 24, and when the plurality of different units or the plurality of identical units are included, any two of them may be connected to each other.
The fluid driving device provided by the invention integrates basic operation processes of sample preparation, separation, reaction, detection and the like into the same chip, finishes various fluid operation and control processes required during sample treatment and detection, can be widely applied to the fields of immunoassay, biochemical analysis and molecular diagnosis based on a microfluidic chip technology, mainly focuses on the fields of immune protein detection, cell recognition and diagnosis, nucleic acid amplification and detection, blood sugar detection, blood gas and electrolyte analysis, rapid hemagglutination detection, rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, detection of blood fat items such as triglyceride, cholesterol and the like, and is widely used.
Example two
Referring to fig. 8, a flow chart of steps of a method for manufacturing a fluid driving device according to a second embodiment of the present invention includes the following steps:
step S110: forming a protective layer on a substrate;
in this embodiment, a protective layer and a first mask layer on the protective layer are formed on a substrate.
Specifically, the substrate material is not limited to silicon, silicon oxide, silicon nitride, and other silicon-based materials.
Further, the protective layer is silicon dioxide, a metal mask and includes but is not limited to the above two; the first mask layer is a photoresist, including a positive photoresist, a negative photoresist and including but not limited to the above two.
Step S120: and etching the protective layer to form a plurality of first windows.
In this embodiment, etching the protection layer to form a plurality of first windows specifically includes the following steps:
step S121: and forming a first micro-channel male die layer on the first mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process.
Step S122: and etching the protective layer by taking the first micro-channel male mold layer as a mask to form a plurality of protective layers of first windows, and removing the first micro-channel male mold layer.
Specifically, the first microchannel anode mold layer is used as a mask, the protective layer is etched by adopting reactive plasma etching or deep silicon etching or wet etching to form a plurality of first windows, and the first microchannel anode mold layer is removed by utilizing concentrated sulfuric acid and hydrogen peroxide water.
Step S130: etching the protective layer and the substrate to form a plurality of second windows;
in this embodiment, etching the protection layer to form a plurality of second windows includes the following steps:
step S131: forming a second mask layer on the protective layer of the first window;
step S132: and forming a second micro-channel male die layer on the second mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process.
Step S133: and etching the protective layer and the substrate by taking the second micro-channel male mold layer as a mask to form a plurality of second windows, and removing the second micro-channel male mold layer.
Specifically, the second microchannel anode mold layer is used as a mask, the protective layer and the substrate are etched by adopting reactive plasma etching or deep silicon etching or wet etching to form a plurality of second windows, and the second microchannel anode mold layer is removed by utilizing concentrated sulfuric acid and hydrogen peroxide.
Step S140: and etching the substrate through the first window and the second window by using the protective layer as a mask to form a first layer of the fluid channel and a second layer of the fluid channel.
The fluid channel comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, wherein fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving of the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents.
It can be understood that the fluid driving device can be obtained by forming a first layer of fluid channels and a second layer of fluid channels by the above-mentioned preparation method, wherein the first layer of fluid channels and the second layer of fluid channels are connected with each other; in practice, a similar approach may be used to prepare a third or more layer of fluid channels.
In some preferred embodiments, the first layer of fluidic channels have a different height than the second layer of fluidic channels, the second layer of fluidic channels have a height of 20-5000 microns, and the first layer of fluidic channels have a height of 10-3000 microns.
The fluid driving device prepared in the second embodiment of the invention integrates basic operation processes of sample preparation, separation, reaction, detection and the like into the same chip, completes various fluid operation and control processes required in sample treatment and detection, can be widely applied to the fields of immunoassay, biochemical analysis and molecular diagnosis based on a microfluidic chip technology, mainly focuses on the detection of immune proteins, cell identification and diagnosis, nucleic acid amplification and detection, blood glucose detection, blood gas and electrolyte analysis, rapid hemagglutination detection, rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, detection of blood lipids such as triglyceride and cholesterol and the like, and is widely used.
EXAMPLE III
Referring to fig. 9, a flow chart of steps of a method for manufacturing a fluid driving device according to a third embodiment of the present invention includes the following steps:
step S210: an anode mould layer of N layers of fluid channels is formed on the substrate, and N is an integer more than or equal to 2.
Specifically, when the substrate is made of a silicon-based material or quartz or glass, an N-layer micro-channel male mold layer is prepared by a deep ultraviolet lithography or laser direct writing lithography process;
when the substrate is cycloolefin copolymer or cyclic olefin copolymer, preparing N layers of fluid channel male die layers by adopting a carving process or laser cutting;
when the substrate is polylactic acid, polyhydroxybutyrate or polyhydroxyalkanoate, the N-layer fluid channel positive mold layer is prepared by selecting a 3D printing mode.
Step S230: turning over the fluid channel male die layer to form N layers of interconnected fluid channels, wherein N is an integer more than or equal to 2;
any layer of the fluid channel comprises a fluid sample feeding module and a functional module connected with the fluid sample feeding module, wherein fluid can enter the functional module through the fluid sample feeding module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measuring and/or self-driving of the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents.
Specifically, the material selected by the turnover mold comprises polydimethylsiloxane or room temperature vulcanization type silicon rubber.
The fluid driving device prepared in the third embodiment of the invention integrates basic operation processes of sample preparation, separation, reaction, detection and the like into the same chip, completes various fluid operation and control processes required in sample treatment and detection, can be widely applied to the fields of immunoassay, biochemical analysis and molecular diagnosis based on a microfluidic chip technology, mainly focuses on the detection of immune proteins, cell identification and diagnosis, nucleic acid amplification and detection, blood sugar detection, blood gas and electrolyte analysis, rapid hemagglutination detection, rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, detection of blood lipids such as triglyceride and cholesterol and the like, and is widely used.
Example four
In this embodiment, a method for manufacturing a fluid driving device includes the following steps:
the method comprises the steps of forming N layers of interconnected fluid channels on a substrate in a machining mode, wherein N is an integer larger than or equal to 2, any layer of the fluid channels comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can achieve different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid, the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, tissue fluid and detection reagents, and the machining comprises numerical control machining, laser engraving machine or 3D printing.
Specifically, the machining includes numerical control machining, laser engraving machine or 3D printing. The substrate is polymethyl methacrylate or plastic.
The fluid driving device prepared in the fourth embodiment of the present invention integrates basic operation processes of sample preparation, separation, reaction, detection, etc. into a same chip, completes various fluid operation and control processes required for sample treatment and detection, can be widely applied to the fields of immunoassay, biochemical analysis, and molecular diagnosis based on a microfluidic chip technology, mainly focuses on detection of immune proteins, cell identification and diagnosis, nucleic acid amplification and detection, blood glucose detection, blood gas and electrolyte analysis, rapid hemagglutination detection, rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, detection of blood lipids such as triglyceride and cholesterol, etc., and is widely used.
EXAMPLE five
In this embodiment, a surface treatment method of a fluid driving device includes the following steps: and treating the surface of the fluid driving device by using a chemical reagent, and keeping the contact angle of the surface stable.
In particular, the agent comprises (3-aminopropyl) triethoxysilane or polyethylene glycol or other agents.
Specifically, the surface treatment means includes a chemical treatment, a spin coating treatment, or a coating treatment.
Specifically, the contact angle ranges from 20 degrees to 70 degrees, the surface contact angle of the fluid driving device can be kept for a stable time of at least N days, and N is an integer more than or equal to 3.
The fifth embodiment of the invention processes the surface of the fluid driving device, can integrate the basic operation processes of sample preparation, separation, reaction, detection and the like into the same chip, completes the operation and control processes of various fluids required by sample processing and detection, can be widely applied to the fields of immunodetection, biochemical analysis and molecular diagnosis based on the microfluidic chip technology, mainly focuses on immune protein detection, cell identification and diagnosis, nucleic acid amplification and detection, blood sugar detection, blood gas and electrolyte analysis and rapid hemagglutination detection, the kit is widely used for rapid diagnosis of cardiac markers, drug abuse screening, urine analysis, dry biochemical detection, pregnancy test, fecal occult blood analysis, food pathogen screening, hemoglobin detection, infectious disease detection, and detection of triglyceride, cholesterol and other blood lipid items.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
Of course, the fluid driving device of the present invention may have various changes and modifications, and is not limited to the specific structure of the above-described embodiment. In conclusion, the scope of the present invention should include those changes or substitutions and modifications which are obvious to those of ordinary skill in the art.
Claims (27)
1. A fluid driving device is characterized by comprising N layers of interconnected fluid channels, wherein N is an integer greater than or equal to 2, any layer of the fluid channels comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving on the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents.
2. The fluid driving device as claimed in claim 1, wherein the fluid injection module comprises at least one injection port and an injection port fluid channel connected to any one of the injection ports, and the fluid enters the functional module from the injection port through the injection port fluid channel.
3. The fluid driving device as claimed in claim 1, wherein the functional module comprises a control unit, the control unit comprises a micro valve structure and an etching fluid channel connected to the micro valve structure, and the etching fluid channel can be opened and closed and the fluid flow direction can be switched by the micro valve structure.
4. A fluid driving device as defined in claim 1, wherein the functional module comprises a mixing unit including at least one mixing fluid channel through which the fluids may be mixed.
5. A fluid driving device according to claim 4, wherein the functional module comprises a mixing unit comprising at least two mixed fluid channels, the fluids in the mixed fluid channels being sequentially passable through one another at the location of the junction.
6. The fluid actuated device of claim 4, wherein the mixed fluid channel comprises a straight line, a serpentine, an S-shape, or a spiral.
7. The fluid driven device of claim 6, wherein the width of the mixing fluid channel is between 10 and 5000 microns.
8. The fluid driving device as claimed in claim 1, wherein the functional module comprises a measuring unit, the measuring unit comprises at least one measuring fluid channel and a micro valve structure connected to the measuring fluid channel, and the micro valve structure can stop or intercept the measuring fluid channel, so as to accurately measure the fluid.
9. The fluid driving device according to claim 1, wherein the functional module comprises a power unit, the power unit comprises at least one power fluid channel and a power assembly disposed on the power fluid channel, and the power assembly comprises micro-pillars disposed at intervals and having different heights.
10. The fluid driving device according to claim 9, wherein the height of the microcolumn is 10 to 5000 μm.
11. The fluid driving device according to claim 10, wherein the cross-section of the microcolumn is circular, parallelogram, regular polygon or ellipse.
12. The fluid driving device as defined in claim 10, wherein when said microcolumn has a circular cross-section, its radius is less than 5000 micrometers, and the shortest distance between two adjacent microcolumns is 1-2000 micrometers.
13. The fluid driving device as defined in claim 12, wherein when said microcolumn has a circular diameter of 20 to 500 μm, a shortest distance between adjacent two of said microcolumns is 10 to 1500 μm.
14. The fluid driving device according to claim 1, further comprising a sample output unit, wherein the sample output unit comprises at least one sample output fluid channel, and the fluid passing through the functional module flows out of the sample output fluid channel.
15. A method of manufacturing a fluid driving device according to any one of claims 1 to 14, comprising the steps of:
forming a protective layer on a substrate;
etching the protective layer to form a plurality of first windows;
etching the protective layer and the substrate to form a plurality of second windows;
etching the substrate through the first window and the second window by using the protective layer as a mask to form a first layer of the fluid channel and a second layer of the fluid channel;
the fluid channel comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, wherein fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measurement and/or self-driving of the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagent.
16. The method for manufacturing a fluid driving device according to claim 15, wherein the step of forming the protective layer on the substrate specifically comprises:
forming a protective layer and a first mask layer on the protective layer on a substrate;
the substrate comprises silicon, silicon oxide or silicon nitride and the protective layer comprises silicon dioxide or a metal mask.
17. The method for manufacturing a fluid driving device according to claim 16, wherein in the step of etching the protective layer to form the plurality of first windows, specifically:
forming a first micro-channel male mold layer on the first mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process;
and etching the protective layer by taking the first micro-channel male mold layer as a mask to form a plurality of first windows, and removing the first micro-channel male mold layer.
18. The method of manufacturing a fluid driving device according to claim 17, wherein the protective layer and the substrate are etched to form a plurality of second windows, specifically:
forming a second mask layer on the protective layer of the first window;
forming a second micro-channel male mold layer on the second mask layer by adopting a deep ultraviolet lithography, laser direct writing lithography or plasma super-resolution lithography process;
and etching the protective layer and the substrate by taking the second micro-channel male die layer as a mask to form a plurality of second windows.
19. A method of manufacturing a fluid driven device as defined in claim 1, comprising the steps of:
forming an anode mould layer of an N-layer fluid channel on a substrate, wherein N is an integer more than or equal to 2;
turning over the fluid channel male die layer to form N layers of interconnected fluid channels, wherein N is an integer more than or equal to 2;
any layer of the fluid channel comprises a fluid sample feeding module and a functional module connected with the fluid sample feeding module, wherein fluid can enter the functional module through the fluid sample feeding module, the functional module can control the flow direction of the fluid and/or can realize different types of fluid mixing and/or accurate fluid measuring and/or self-driving of the fluid, and the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagent.
20. The method for manufacturing a fluid driving device according to claim 19, wherein the step of forming an anode layer of N fluid channels on a substrate, N being an integer of 2 or more, specifically comprises:
when the substrate is made of silicon-based materials or quartz or glass, an N-layer micro-channel male mold layer is prepared by adopting a deep ultraviolet lithography or laser direct writing lithography process;
when the substrate is cycloolefin copolymer or cyclic olefin copolymer, preparing N layers of fluid channel male die layers by adopting a carving process or laser cutting;
when the substrate is polylactic acid, polyhydroxybutyrate or polyhydroxyalkanoate, the N-layer fluid channel positive mold layer is prepared by selecting a 3D printing mode.
21. The method of manufacturing a fluid driving device according to claim 19, wherein in the step of forming N-layer fluid channels by overmolding the fluid channel male mold layer, N being an integer of 2 or more, the material selected for the overmolding comprises polydimethylsiloxane or room temperature vulcanizing silicone rubber.
22. A method of manufacturing a fluid driven device as defined in claim 1, comprising the steps of:
the method comprises the steps of forming N layers of interconnected fluid channels on a substrate in a machining mode, wherein N is an integer larger than or equal to 2, any one layer of the fluid channels comprises a fluid sample introduction module and a functional module connected with the fluid sample introduction module, fluid can enter the functional module through the fluid sample introduction module, the functional module can control the flow direction of the fluid and/or can achieve different types of fluid mixing and/or accurate fluid measurement and/or self-driving of the fluid, the fluid comprises at least one of buffer solution, whole blood, plasma, serum, sweat, urine, cell suspension, interstitial fluid and detection reagents, and the machining comprises numerical control machining, laser engraving machine or 3D printing.
23. A method of manufacturing a fluid actuated device as claimed in claim 22 wherein said substrate is polymethylmethacrylate or plastic.
24. A surface treatment method for a fluid driven device according to claim 1, 15, 19 or 22, comprising the steps of:
and treating the surface of the fluid driving device by using a chemical reagent, and keeping the contact angle of the surface stable.
25. The surface treatment method for a fluid driven device according to claim 24, wherein the reagent comprises (3-aminopropyl) triethoxysilane or polyethylene glycol.
26. The surface treatment method for a fluid driving device according to claim 25, wherein the surface treatment is performed by a chemical treatment, a spin coating treatment, or a coating treatment.
27. The method of claim 26, wherein the contact angle ranges from 20 ° to 70 °, and the contact angle of the surface of the fluid driving device is stable for at least N days, where N is an integer greater than or equal to 3.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090233810A1 (en) * | 2008-03-12 | 2009-09-17 | The Mitre Corporation | Multi-Modal surface plasmon polariton-raman scattering based bio-detection |
| CN102059161A (en) * | 2009-11-18 | 2011-05-18 | 中国科学院化学研究所 | Microfluidic chip and manufacturing method thereof |
| CN203816649U (en) * | 2014-02-26 | 2014-09-10 | 深圳市第二人民医院 | Micro-fluidic chip with multilayered structure |
| CN108295913A (en) * | 2018-04-08 | 2018-07-20 | 东莞东阳光科研发有限公司 | A kind of micro-fluidic chip |
| CN209188809U (en) * | 2018-08-08 | 2019-08-02 | 苏州含光微纳科技有限公司 | The structure of improvement low flow velocity liquid flow interface and immune micro-fluidic chip |
-
2019
- 2019-12-14 CN CN201911287062.4A patent/CN112691709B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090233810A1 (en) * | 2008-03-12 | 2009-09-17 | The Mitre Corporation | Multi-Modal surface plasmon polariton-raman scattering based bio-detection |
| CN102059161A (en) * | 2009-11-18 | 2011-05-18 | 中国科学院化学研究所 | Microfluidic chip and manufacturing method thereof |
| CN203816649U (en) * | 2014-02-26 | 2014-09-10 | 深圳市第二人民医院 | Micro-fluidic chip with multilayered structure |
| CN108295913A (en) * | 2018-04-08 | 2018-07-20 | 东莞东阳光科研发有限公司 | A kind of micro-fluidic chip |
| CN209188809U (en) * | 2018-08-08 | 2019-08-02 | 苏州含光微纳科技有限公司 | The structure of improvement low flow velocity liquid flow interface and immune micro-fluidic chip |
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