CN103586093B - Microfluidic chip and manufacturing method thereof - Google Patents
Microfluidic chip and manufacturing method thereof Download PDFInfo
- Publication number
- CN103586093B CN103586093B CN201310571537.9A CN201310571537A CN103586093B CN 103586093 B CN103586093 B CN 103586093B CN 201310571537 A CN201310571537 A CN 201310571537A CN 103586093 B CN103586093 B CN 103586093B
- Authority
- CN
- China
- Prior art keywords
- sacrifice layer
- substrate
- layer
- runner
- integument
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention discloses a microfluidic chip which comprises a substrate, a coating layer, insulating layers and flow passages, wherein a sacrificial layer is arranged on the substrate 1, channels which penetrate through the sacrificial layer and enter deeply into the substrate are formed in the sacrificial layer which is covered with the coating layer, the insulating layers are arranged in the channels and divide the sacrificial layer into different zones, passages communicating the outside with the sacrificial layer are arranged in the substrate and/or the coating layer, and the flow passages are formed after the sacrificial layer is corroded or dissolved. The invention further discloses a manufacturing method of the microfluidic chip. The microfluidic chip is easy to manufacture, high in finished product ratio and low in cost, and has low flatness requirements for the substrate surface. By means of the sacrificial layer arranged on the substrate, the depth of the flow passages is controlled conveniently through thickness control of the sacrificial layer; and the channels are formed in the sacrificial layer, and the insulating layers are arranged in the channels and divide the sacrificial layer into different zones, so that complex flow passages with controllable shapes are generated conveniently.
Description
Technical field
The invention belongs to biochip technology field, be specifically related to a kind of facture of microchip method.
Background technology
Micro-full analytical system (Miniaturized Total Analysis Systems, μ TAS) be one of the Technological research field in forward position, the world today, its objective is by the microminiaturization of chemical analysis apparatus and integrated, to greatest extent the function i ntegration of assay laboratory in portable analytical equipment, even be integrated on the chip of heart size, i.e. " Lab on a chip ".Micro-fluidic chip is one of research direction of μ TAS current most active, its architectural feature is turned to microchannel network and the integrated of numerous analytic function element, not only make the consumption of sample and reagent significantly decline, and have efficiently, at a high speed, high-throughout analysis ability.Micro-fluidic chip is mainly used in the fields such as biology, medical science, food security, environmental protection, chemical analysis.
Existing facture of microchip method, generally first make runner and punching (beat hole as liquid storage pool or the interface being connected external component as chip) substrate (substrate of substrate and chip) is upper, then by substrate and smooth cover plate bonding (being mainly divided into chemical bonding and physical bond), thus form the runner closed, this preparation method be difficult to make high-precision nanoscale runner, be also difficult in same chip, make the runner simultaneously comprising nanoscale and micro-meter scale, and cost of manufacture is very high and yield rate is extremely low.Its main cause is substrate and cover plate is not definitely smooth, nanoscale may be irregular, and existing bonding technology can not ensure the abundant laminating on nanoscale of substrate and cover plate, thus makes flow channel shape and seal there is open defect; Need to apply pressure in bonding process, substrate and cover plate can deform, the runner of nanoscale may be caused to be destroyed, or need in bonding process to carry out chemical treatment, also the runner of nanoscale may be caused to be destroyed, or need in bonding process to use adhesive, the runner of nanoscale equally also may be caused to be destroyed; When needs during Integrated electrode, often need the integrated high-precision electrode of technique ability by complexity on micro-fluidic chip.Prior art, such as application number is 201010614403.7, name is called " a kind of nano-fluidic control chip and based on the processing method of AFM and application ", application number is 200810060845.4, name is called " preparation method of the two-dimensional nano passage of micro--nano-fluidic control chip ", application number is " 201210558821.8 ", name is called " a kind of method utilizing inverted fluorescence microscope to manufacture micro-nano-fluidic control chip ", these Chinese patent application, all can not solve the problem.
Therefore, need a kind of new facture of microchip method to solve the problem.
Summary of the invention
The present invention is directed to the defect of facture of microchip in prior art, a kind of micro-fluidic chip making micron and nanoscale runner is provided.
For solving the problems of the technologies described above, the technical scheme that micro-fluidic chip of the present invention adopts is:
A kind of micro-fluidic chip, it is characterized in that, comprise substrate, integument, separation layer and runner, described substrate is provided with sacrifice layer, described sacrifice layer be provided with through described sacrifice layer and go deep into the raceway groove of described substrate inside, described sacrifice layer covers described integument, described separation layer is provided with in described raceway groove, described sacrifice layer is divided into different regions by described separation layer, described substrate and/or integument are provided with the passage being communicated with extraneous and described sacrifice layer, described sacrifice layer is corroded, dissolved or fusing state under be removed after obtain described runner.
Further, also comprise functional structure, the part that described separation layer surrounds is not corroded, do not dissolved and not removed described sacrifice layer formation functional structure under the state of fusing.Convenient while generation runner, produce other functional structure, wherein, functional structure can be electrode.
Further, also comprise supporting construction, the part that described separation layer surrounds is not corroded, do not dissolved and not removed described sacrifice layer is supporting construction under the state of fusing.Convenient while generation runner, produce supporting construction.
Further, described sacrifice layer is conductive material or soluble material.Simultaneously by optionally retaining the sacrifice layer of specific region, electric conductivity functional structure can be produced; Electric conductivity functional structure refers to that for connecting the circuit of chip exterior, electrode is conventional electric conductivity functional structure in the process using chip.Soluble material is can by the material of dissolution with solvents, and specific material has corresponding specific solvent (such as polyethylene glycol is as sacrificial layer material, and water is exactly the solvent of polyethylene glycol).
Further, described sacrifice layer is arranged on the substrate by the mode of plated film or rotary coating.Use the sacrifice layer that plated film mode convenient generation thickness is controlled, thus control the degree of depth of runner.Also can generate the sacrifice layer in different-thickness region on same substrate, thus on same chip, produce the runner of different depth, and the inner surface of runner is smooth, the resistance of runner to fluid is little.Sacrifice layer is generated by the mode of spin coated: be fixed on by substrate on photoresist spinner, substrate adds the solution of sacrificial layer material or liquid sacrificial layer material, the centrifugal force rotating generation is utilized to be uniformly coated on substrate by the solution of sacrificial layer material or liquid sacrificial layer material, then liquid sacrificial layer material or is solidified by the removal of solvents (such as being removed by the mode of evaporation) in solution, then just form solid-state sacrifice layer.
Further, described sacrifice layer is generated by the mode of repeatedly plated film or rotary coating.The convenient region producing different-thickness on sacrifice layer.Thickness needed for can producing in zones of different as required.
Further, described raceway groove is generated by the mode etching or carve.
Further, described integument and separation layer are resin, plastics or the rubber that can be cured, and described integument and separation layer obtain after solidification respectively by covering on described sacrifice layer by liquid resin, liquid plastic or liquid rubber and infiltrating in described raceway groove.By using resin, plastics or the rubber that can be cured and curing molding in position, resin, plastics or rubber and raceway groove, sacrifice layer are fully fitted, thus achieve the high stringency of runner, the good fastness of runner, and not needing bonding process, the flow passage structure of nanoscale can not be destroyed because of not needing bonding.The materials such as liquid towards resin, liquid plastic or liquid rubber are cured, and can adopt interpolation chemical solvent, curing agent, be heating and curing and/or photo-curable.Wherein, the resin that can be cured, plastics or rubber are composite material.Namely be made up of at least two kinds of resins, plastics or rubber, or be made up of at least one resin, plastics or rubber and additive.
Further, described sacrifice layer is metal material, corrodes described sacrifice layer and adopts electrochemical etching method.Adopt electrochemical corrosion mode, sacrifice layer connects the positive pole of dc source, places the negative electrode of a connection DC power cathode in a liquid, the material of sacrifice layer to enter in electrolyte with the form of ion and gathers negative electrode, electrolyte is constantly filled up sacrifice layer and to be corroded the space produced in process, and sacrifice layer corrosion falls the most at last.
Beneficial effect: micro-fluidic chip of the present invention, easily makes, and yield rate is high is with low cost, low to the flatness requirement of substrate surface.By being provided with sacrifice layer on substrate, the degree of depth of the convenient THICKNESS CONTROL runner by controlling sacrifice layer, by generating raceway groove on sacrifice layer, and arranges separation layer in channels, sacrifice layer is isolated into zones of different by separation layer, the convenient complicated runner producing controlled shape.
The invention also discloses the preparation method of above-mentioned micro-fluidic chip, comprise the following steps:
1), on substrate generate sacrifice layer, described sacrifice layer generates through described sacrifice layer and gos deep into the raceway groove of described substrate inside;
2), on described sacrifice layer and raceway groove, cover liquid resin, liquid plastic or the liquid rubber that can be cured, liquid resin, liquid plastic or liquid rubber cover described sacrifice layer and infiltrate described raceway groove;
3), to step 2) liquid resin, liquid plastic or liquid rubber be cured, cover the resin of described sacrifice layer, plastics or rubber and form integument, infiltrate the resin of described raceway groove, plastics or rubber and form separation layer, obtain the substrate that surface coverage has sacrifice layer and integument;
4) on described substrate and/or integument, generate the passage being communicated with extraneous and described sacrifice layer;
5), the substrate of sacrifice layer and integument surface coverage is had to be dipped in corrosive medium, dissolve medium or electrolyte, by corrosive medium erode can touch sacrifice layer, to be dissolved the sacrifice layer that can touch by dissolve medium or erode sacrifice layer by electrochemical etching method, corrosion or the sacrifice layer dissolved form runner, after cleaning, obtain micro-fluidic chip of the present invention; Or under surface coverage being had the substrate of sacrifice layer and integument to be positioned over the phase change conditions of fusing sacrificial layer material, after sacrifice layer is melted, introduces extraneous pressure and liquid or gas by passage, after being removed by sacrifice layer, form runner, after cleaning, obtain micro-fluidic chip of the present invention.
Beneficial effect: the technology that facture of microchip method of the present invention uses is all ripe industrial technology, easy enforcement, yield rate is high, cost is low, obtained micro-fluidic chip by being provided with sacrifice layer on substrate, the degree of depth of the convenient THICKNESS CONTROL runner by controlling sacrifice layer, by generating raceway groove on sacrifice layer, and separation layer is set in channels, sacrifice layer is isolated into zones of different by separation layer, the convenient complicated runner producing controlled shape, by using the resin that can be cured and in-situ solidifying is shaping, resin and raceway groove, sacrifice layer is fully fitted, thus achieve the high stringency of runner, the good fastness of runner, and do not need bonding process, flow channel depth can be nanoscale, flow passage structure can not be destroyed because of not needing bonding.
Accompanying drawing explanation
Fig. 1 and Fig. 2 is schematic diagram, how produces the sacrifice layer of different-thickness for illustration of a specific embodiment of the present invention at same substrate;
Fig. 3 is 3 D stereo perspective view, for illustration of the shape obtained after the operating procedure shown in Fig. 1 and Fig. 2;
Fig. 4 is 3 D stereo perspective view, for illustration of etching the result shown in Fig. 3 and producing raceway groove;
Fig. 5 is the top view of Fig. 4;
Fig. 6 pours into a mould curable liquid resin, liquid plastic or liquid rubber for illustration of after the operating procedure shown in Fig. 4, and is cured the result obtained;
Fig. 7 punches for illustration of on the resin solidified, plastics or rubber, and the hole produced is for corroding the sacrifice layer of specific region;
Fig. 8 punches for illustration of on substrate, and the hole produced, for corroding the sacrifice layer of specific region, also connects the interface of external component as chip;
Fig. 9 is the top view of Fig. 8;
Figure 10 is the sectional view obtained along the A-A line cutting shown in Fig. 9, for illustration of internal structure;
Figure 11 is partial enlarged drawing, for illustration of the details of the local J A shown in Figure 10;
Figure 12 is the sectional view obtained along the B-B line cutting shown in Fig. 9, for illustration of internal structure;
Figure 13 is the front view of Fig. 8;
Figure 14 is the sectional view obtained along the C-C line cutting shown in Figure 13, for illustration of internal structure;
Figure 15 is schematic diagram, for illustration of how to produce runner by the mode of electrochemical corrosion;
Figure 16 is sectional view, for illustration of the internal structure after electrochemical corrosion, and the corresponding Figure 10 of slice location;
Figure 17 is partial enlarged drawing, for illustration of the details of the local J B shown in Figure 17;
Figure 18 is sectional view, for illustration of the internal structure after electrochemical corrosion, and the corresponding Figure 12 of slice location;
Figure 19 is sectional view, for illustration of the internal structure after electrochemical corrosion, and the corresponding Figure 14 of slice location;
Figure 20 is partial enlarged drawing, for illustration of the details of the local J C shown in Figure 19;
Wherein, 1-substrate, 2-metal film one, 3-metal film two, 4-raceway groove, 5-galvanic anode, 6-dc source, 7-raceway groove, 8-integument, 9-passage one, 10-passage two, 11-separation layer, 12-separation layer, 13-sacrifice layer, 14-electroplate liquid, 15-electrochemical corrosion negative electrode, 16-electrolyte, 17-runner, the sacrifice layer one that 18-is not corroded, sacrifice layer two, the 20-runner that 19-is not corroded, the sacrifice layer three that 22-is not corroded.
Detailed description of the invention
Below in conjunction with the drawings and specific embodiments, illustrate the present invention further, these embodiments should be understood only be not used in for illustration of the present invention and limit the scope of the invention, after having read the present invention, the amendment of those skilled in the art to the various equivalent form of value of the present invention has all fallen within the application's claims limited range.
The invention discloses a kind of micro-fluidic chip, comprise substrate 1, integument 8, separation layer 11; 12 and runner 17; 20, substrate 1 is provided with sacrifice layer 13, sacrifice layer 13 is provided with through sacrifice layer 13 and gos deep into the raceway groove 4 of substrate 1 inside; 7, sacrifice layer 13 covers integument 8, raceway groove 4; Separation layer 11 is provided with in 7; 12, separation layer 11; Sacrifice layer 13 is divided into different regions by 12.Like this, 1, when corroding sacrifice layer 13 or dissolve, the scope that sacrifice layer is corroded and path are controlled (if do not have the constraint of separation layer, corrosion scope can spread towards periphery), cause the shape of runner and size to be controlled; In existing published technology, separation layer is not had to retrain, corrosion scope can spread towards periphery, try hard to recommend dynamic corrosive liquid if outer or lysate enter (as application number be 201110394190.6, name is called the patent application of " a kind of closed-type microfluidic channel etching method and automatic etching device "), corrosion scope can spread and not controlled towards periphery; 2, in use, if do not have the constraint of separation layer, fluid can permeate along the interface between the sacrifice layer on runner both sides and integument and/or the interface between sacrifice layer and substrate toward periphery under the promotion of pump.
Substrate 1 and/or integument 8 are provided with the passage 9 being communicated with extraneous and sacrifice layer 13; 10, sacrifice layer 13 is corroded, dissolved or fusing state under be removed after obtain runner 17; 20.Wherein, substrate 1, integument 8 and separation layer 11; Sacrifice layer 13 is enclosed in inside by 12.Also comprise electrode, the part that separation layer 11 surrounds is not corroded and the sacrifice layer 13 that dissolves forms electrode.Also comprise supporting construction, separation layer 11; 12 parts of surrounding are not corroded and the sacrifice layer 13 that dissolves is supporting construction.Wherein, separation layer also plays some special effects, as: separation layer stretches into substrate inside just as " claw ", and by integument together with substrate riveting, when liquid logical in runner, the pressure of liquid can not make integument softened (local struts); Material in sacrifice layer and runner is kept apart by separation layer, if sacrifice layer is soluble material, if there is no the isolation of separation layer, will in use do not dissolved by the sacrifice layer dissolved away, if sacrifice layer is metal material, if do not have the isolation of separation layer, metal material can touch fluid, if fluid is biological substance or corrosive substance, sacrifice layer will pollute fluid; If there is no separation layer, if sacrifice layer is metal material, and use as electrode, in use, the liquid in electrode meeting electrolysis runner.
Passage 9; The sacrifice layer 13 of specific region, passage 9 are arrived in one end of 10; The other end of 10 is communicated with outside air, passage 9; 10 guide corrosive medium or dissolve medium to contact with the sacrifice layer 13 of specific region; Optionally corrosion or dissolve the sacrifice layer of specific region, is corroded or space left by the sacrifice layer that dissolves forms runner 17; 20, runner 17; The degree of depth of 20 is determined by the thickness of sacrifice layer 13, runner 17; The width of 20 is by surrounding runner 17; The separation layer 11 of 20; Distance between 12 determines.
Sacrifice layer 13 is conductive material.By optionally retaining the sacrifice layer of specific region, electric conductivity functional structure can be produced; Electric conductivity functional structure refers to that for connecting the circuit of chip exterior, electrode is conventional electric conductivity functional structure in the process using chip.Sacrifice layer 13 is arranged on the substrate 1 by the mode of plated film.Sacrifice layer 13 adopts repeatedly the mode of plated film to produce, the thickness needed for can producing in zones of different as required.Wherein, the mode of plated film comprises one or more in plating, vacuum ion membrane plating, vacuum evaporation or plated film.Use the sacrifice layer that plated film mode convenient generation thickness is controlled, thus control the degree of depth of runner.Also can generate the sacrifice layer in different-thickness region on same substrate, thus on same chip, produce the runner of different depth, and the inner surface of runner is smooth, the resistance of runner to fluid is little.
When sacrifice layer 13 adopts conductive material, by optionally retaining the sacrifice layer of specific region, electric conductivity functional structure can be produced; Electric conductivity functional structure refers to that for connecting the circuit of chip exterior, electrode is conventional electric conductivity functional structure in the process using chip.
Sacrifice layer 13 also can adopt soluble material.Soluble material is can by the material of dissolution with solvents, such as use polyethylene glycol as sacrificial layer material, use water as the solvent of polyethylene glycol, polyethylene glycol can be adopted as sacrificial layer material when making the runner of micro-meter scale, at dissolving sacrifice layer to be formed in the process of runner, ultrasonic assistant can be applied and accelerate to dissolve.Sacrifice layer 13 is the phase-change material solid-state, fusion temperature is not high under also can adopting normal temperature, phase-change material refers to and varies with temperature and change the material that physical property also can provide latent heat, such as use agarose as sacrificial layer material, pass through passage 9 in temperature higher than when 85 DEG C; (sacrifice layer 13 is isolated layer 11 by specific region for the pressure that 10 introducings are extraneous and water; 12 are separated to form zones of different) agarose drive away, the space stayed just forms runner.Sacrifice layer 13 is generated by the mode of spin coated, such as: substrate is fixed on photoresist spinner, substrate adds the solution of polyethylene glycol or liquid agarose, the centrifugal force rotating generation is utilized to be uniformly coated on substrate by the solution of polyethylene glycol or liquid agarose, then the water in polyglycol solution is removed (such as being removed by the mode of evaporation) or temperature is reduced to less than 32 DEG C liquid towards agaroses and be cured, then just form solid-state sacrifice layer.
Raceway groove 4; 7 are generated by the mode etching or carve.Wherein, etching comprises Ultra-Violet Laser etching, X-ray etching or electron beam lithography, and engraving comprises laser engraving or mechanical engraving.
Integument 8 and separation layer 11; 12 are the resin that can be cured, integument 8 and separation layer 11; 12 respectively by being covered by liquid resin on sacrifice layer 13 and infiltrating raceway groove 4; Obtain after solidification in 7.Namely resin is for liquid before being cured, and is solid-state after being cured.By using the resin that can be cured and curing molding in position, resin and raceway groove, sacrifice layer are fully fitted, thus achieve the high stringency of runner, the good fastness of runner, and do not need bonding process, the flow passage structure of nanoscale can not be destroyed because of not needing bonding.Liquid towards resin is cured, and can adopt and be heating and curing or photo-curable.The resin that can be cured is hybrid resin.Namely be made up of at least two kinds of resins, or be made up of at least one resin and non-tree lipid additive.
In existing published technology, majority uses " bonding ", namely first on substrate, runner is produced, and then bonding one piece of cover plate, the surface of substrate and cover plate is actually rough (from micro-meter scale or nanoscale), be difficult to when bonding accomplish that the position of substrate and cover plate this bondings all is all really bonded together, some region can produce gap, and under nanoscale, the material deformation caused during bonding may make nanochannel be destroyed (or being blocked).Technology of the present invention does not need bonding, and the sacrifice layer produced by plated film mode and then can be risen and fallen along with the fluctuating on the surface of substrate, when producing integument, integument is liquid before curing, integument can be followed the fluctuating of sacrifice layer and fit together, and overcomes the rough problem of substrate material at micro-scale completely.In existing published technology (as application number be 200810060845.4, name is called the patent application of " preparation method of the two-dimensional nano passage of micro--nano-fluidic control chip "), the runner that substrate makes the nanoscale degree of depth also has difficulties, because substrate surface is actually rough (from micro-meter scale or nanoscale), the runner made, the runner possibility difference in the degree of depth being distributed in substrate zones of different is very large, and the region that even should form runner at some can not form runner because of substrate surface out-of-flatness at all.Therefore, the present invention can also prepare micro-channel structure on non-smooth substrate surface, even curved surface.
When sacrifice layer 13 is metal material, corrosion sacrificial layer 13 adopts electrochemical etching method.Adopt electrochemical corrosion mode, sacrifice layer connects the positive pole of dc source, places the negative electrode of a connection DC power cathode in a liquid, the material of sacrifice layer to enter in electrolyte with the form of ion and gather negative electrode under the driving of electric field force, electrolyte is constantly filled up sacrifice layer and to be corroded the space produced in process, and sacrifice layer corrosion falls the most at last.In existing disclosed technology, corrosive liquid or lysate by the natural flow of liquid spread (as application number be 200710158204.8, name is called the patent application of " water-soluble sacrificial layer micro-flow control chip preparation method "), very difficult under the natural flow of liquid is diffused in nanoscale, corrosive liquid or lysate are difficult to natural flow corrosion removal or dissolving sacrifice layer in the runner of nanoscale, under nanoscale, do not possess operability.
The invention also discloses the preparation method of above-mentioned micro-fluidic chip, comprise the following steps:
1), on the substrate 1 generate sacrifice layer 13, sacrifice layer 13 generates through sacrifice layer 13 and gos deep into the raceway groove 4 of substrate 1 inside; 7;
2), at sacrifice layer 13 and raceway groove 4; Cover liquid resin, liquid plastic or the liquid rubber that can be cured on 7, liquid resin, liquid plastic or liquid rubber cover sacrifice layer 13 and infiltrate raceway groove 4; 7;
3) liquid resin, to step 2, liquid plastic or liquid rubber are cured, and cover the resin of sacrifice layer 13, plastics or rubber and form integument 8, infiltrate raceway groove 4; The resin of 7, plastics or rubber form separation layer 11; 12, obtain the substrate 1 that surface coverage has sacrifice layer 13 and integument 8;
4) on substrate 1 and/or integument 8, generate the passage 9 being communicated with extraneous and sacrifice layer 13; 10; 5, the substrate 1 of sacrifice layer 13 and integument 8 surface coverage is had to be dipped in corrosive medium, dissolve medium or electrolyte, by corrosive medium erode can touch sacrifice layer 13, to be dissolved the sacrifice layer 13 that can touch by dissolve medium or erode sacrifice layer 13 by electrochemical etching method, to corrode or the sacrifice layer 13 that dissolves forms runner 17; 20; Or under surface coverage being had the substrate 1 of sacrifice layer 13 and integument 8 to be positioned over the phase change conditions of fusing sacrifice layer 13 material, after sacrifice layer 13 is melted, by passage 9; 10 introduce extraneous pressure and liquid or gas, and sacrifice layer 13 is removed rear formation runner 17; 20.Chip obtained above is put in cleaning fluid and/or by cleaning fluid and inject runner 17; 20 li, chip is cleaned, drying or drying and processing are carried out to chip, obtain micro-fluidic chip of the present invention.In the process using chip, the passage 9 on substrate 1 or integument 8; 10 as the liquid storage pool of chip, or as connecting the interface of external devices, or keeps and do not use.
The present invention produces the controlled sacrifice layer of thickness by using plated film mode, thus produce the controlled runner of the degree of depth, the sacrifice layer in different-thickness region also can be generated on same substrate, thus on same chip, produce the runner of different depth, and the inner surface of runner is smooth, the resistance of runner to fluid is little; By separation layer, sacrifice layer is isolated into zones of different, the complicated runner of controlled shape can be produced, also synchronously can produce other critical function structure, as electrode; By using the resin that can be cured and in-situ solidifying is shaping, resin and raceway groove, sacrifice layer are fully fitted, thus achieve the high stringency of runner, the good fastness of runner, and do not need bonding process, the flow passage structure of nanoscale can not be destroyed because of not needing bonding; The technology that the present invention uses is all ripe industrial technology, and easily implement, yield rate is high, and cost is low.The present invention obtains good technique effect, has substantial advance.The present invention can prepare the fluid channel of nm deep easily, builds and receives fluid chip.
embodiment 1
One as shown in Fig. 1 to Figure 20 specific embodiment optimized.This specific embodiment is for a kind of micro-fluidic chip realizing operating individual cells, and this embodiment has the runner of nanoscale and the micro-meter scale degree of depth, is also integrated with electrode.Substrate 1 adopts glass material, and the thickness of substrate 1 is 500 microns, and the smooth surface of substrate 1 is smooth; Use the mode of plated film to produce sacrifice layer 13 on the substrate 1, sacrifice layer 13 adopts nickel metal.The mode of Ultra-Violet Laser etching is used to produce raceway groove; Solidify at sacrifice layer 13 and raceway groove upper PDMS resin; Ultra-Violet Laser is used to punch on substrate 1 and PDMS material; The mode of electrochemical corrosion is used to corrode generation runner.
Manufacturing process below with regard to this specific embodiment is described:
Step one, plates one deck nickel metal film on the substrate 1 by vacuum evaporation coating machine, i.e. metal film 1, and thickness is 150 nanometers; The thickness of metal film determines primarily of the power of coating machine, plated film duration, plated film area.
Further plated film, uses plating mode on the basis of the above, metal film 1 produces the nickel metal film region that two pieces of thickness are 50 microns, i.e. metal film 23; Slope shape transition region is had, for generation of the transitional runner of slope shape between metal film 1 and metal film 23; The production method of this slope shape transition region has multiple, in this specific embodiment, slowly to be promoted on plating limit, substrate 1 limit realize by using a miniature slow hoister at the uniform velocity; In electroplating process, galvanic anode 5 adopts nickel metal material and is connected to the positive pole of dc source 6, and the nickel metal film on substrate 1 is connected to the negative pole of dc source 6, and galvanic anode 5 and substrate 1 are all partly dipped in electroplate liquid 14; The thickness of metal film 23 determines primarily of the composition of the voltage of plating, electric current, duration, temperature and electroplate liquid; Metal film 1 forms sacrifice layer 13 together with metal film 23.After plating is good, carry out cleaning and drying.
The surface of the nickel metal film that vacuum evaporation and plating produce is very smooth.
Step 2, on the basis of step one, etches mesa etch generation by using high-precision Ultra-Violet Laser and penetrates sacrifice layer 13 and the raceway groove of through substrate 1 inside; Trench bottom arrives inner 200 micrometer depth of substrate 1, and raceway groove does not penetrate substrate 1, and sacrifice layer 13 is divided into zones of different by raceway groove; Raceway groove 27 is wherein shorter, and raceway groove 1 is long curve-like.After having etched, ethanol and deionized water is used to carry out cleaning and drying.Use the mode of Ultra-Violet Laser etching, the raceway groove of complicated shape can be produced, and shape is controlled.
Step 3, at sacrifice layer 13 and raceway groove 4; Cover the liquid resin that can be cured on 7, liquid resin covers sacrifice layer 13 and infilters in raceway groove; In this specific embodiment, liquid resin is hybrid resin, adopts PDMS and curing agent (additive) mixing to produce.
Step 4, is cured liquid resin (become solid-state by liquid state, namely harden), is cured by the mode of heating; The resin be covered on sacrifice layer 13 forms integument 8, and the resin being positioned at raceway groove forms separation layer, i.e. separation layer 1 and separation layer 2 12, and sacrifice layer 13 surrounds with separation layer by substrate 1, integument 8 jointly.Liquid resinous solidification belongs to in-situ solidifying, i.e. the resin rear invariant position with solidification before curing.Belong to liquid before solidification, there is good mobility, achieve resin and raceway groove, fully the contacting (contact on molecular scale) of sacrifice layer, through in-situ solidifying, resin after solidification fully contacts with raceway groove, sacrifice layer, the combination guaranteeing separation layer and raceway groove is tight, ensure that integument 8 is tight with the combination of sacrifice layer 13 equally.
Step 5, use the mode ad-hoc location on the substrate 1 of Ultra-Violet Laser etching and the ad-hoc location generation passage on integument 8, the sacrifice layer region needing to be corroded is arrived in the bottom of passage; Passage 1 on integument 8 produces runner channel 2 10 for corroding generation runner for corroding, and connects external component (such as pump) for chip.
Step 6, as shown in figure 15, is connected to the sacrifice layer of the bottom of the passage 2 10 of substrate 1 one end, is dipped in electrolyte 16 by the passage 2 10 of the other end of substrate 1 by circuit (positive pole of dc source 6), the copper metal that electrochemical corrosion negative electrode 15 adopts chemical activity more weak than nickel metal, electrolyte 16 main component is hydrochloric acid, nickelous sulfate and nickel chloride, in electrochemical corrosion course, need to adjust the height of substrate 1 in electrolyte 16 according to the progress of corrosion, electrolyte 16 through passage 2 10 guiding and contact with sacrifice layer, the nickel ion that sacrifice layer produces constantly is assembled toward electrochemical corrosion negative electrode 15 under the driving of electric field, electrolyte 16 is constantly filled up sacrifice layer and to be corroded the space produced in process, electrolyte 16 erodes its sacrifice layer that can touch, need the sacrifice layer corrosion be corroded to fall the most at last, the space stayed after the sacrifice layer that substrate 1, integument 8 and separation layer surround is corroded just forms runner, after corrosion produces runner, then corrosion is guided to produce another runner by the passage 1 on integument 8, Corrosion results is as shown in Figure 16 to Figure 20, the sacrifice layer 1 be not corroded is for connecting substrate 1 and integument 8, the sacrifice layer 2 19 be not corroded uses (for generation of electric field) as electrode, the sacrifice layer 3 22 be not corroded uses (for detecting the large particulate matter in runner as electrode, as cell), runner 1 is that (50 microns dark for the runner of micro-meter scale, by some complete human body cell in this specific embodiment of the present invention), runner 2 20 is that (150 nanometers are dark for the runner of nanoscale, cell can be squeezed flat in this specific embodiment of the present invention), separation layer 1 is formed by the resin infiltrated in raceway groove 1, the sacrifice layer that separation layer 1 surrounds runner and is not corroded, separation layer 2 12 is formed by the resin infiltrating raceway groove 27, and separation layer 2 12 is an array (in this specific embodiment of the present invention, cell cutting can be fragmentated under the promotion of external force).
PDMS material is non-conductive, can not corrode by electrolyte 16.Electrolyte 16, under the constraint of separation layer, can only contact with the sacrifice layer of specific region, and the sacrifice layer due to zones of different is also isolated layer isolation, and electric current can only arrive the sacrifice layer of specific region, thus realizes optionally corroding.After PDMS material is cured, dimensionally stable, can not subside, produce runner by forms of corrosion, and the degree of depth of runner is determined by the thickness of sacrifice layer, and the width of runner is determined by the distance between the separation layer surrounding runner.
In the use procedure of chip, the passage 2 10 on substrate 1 connects the interface of external devices as chip, and the passage 1 on integument 8 is not used.
Step 7, is dipped in deionized water by above-mentioned result, repeatedly cleans chip; Use Micropump deionized water to be advanced in runner to clean runner; Vibration and heating is used to accelerate cleaning progress.
Step 8, finally dries.
Know from above-mentioned manufacturing process: the seal of runner and fastness are very excellent; The inner surface of runner is unusual light; The degree of depth of runner is controlled, can produce the runner of different depth on same chip; Produce complex-shaped raceway groove by etching and just can produce complex-shaped separation layer, and then the complicated runner of controlled shape can be produced, also synchronously can produce other critical function structure, conventional critical function structure as this in electrode; The generation of raceway groove does not need to make mask in advance, but uses Ultra-Violet Laser direct etching, and making is quick and simple.
When using the electrode in chip, need to use micro metal body (the micro metal body of such as needle-like) wear out integument 8 and arrive electrode, micro metal body and electrode contact, the part that micro metal body is exposed to outside chip is connected with external circuitry.
Claims (9)
1. a micro-fluidic chip, is characterized in that, comprises substrate (1), integument (8), separation layer (11; 12) and runner (17; 20), described substrate (1) is provided with sacrifice layer (13), described sacrifice layer (13) is provided with through described sacrifice layer (13) and gos deep into the inner raceway groove (4 of described substrate (1); 7), described sacrifice layer (13) is upper covers described integument (8), described raceway groove (4; 7) described separation layer (11 is provided with in; 12), described separation layer (11; 12) described sacrifice layer (13) is divided into different regions, described substrate (1) and/or integument (8) are provided with the passage (9 being communicated with extraneous and described sacrifice layer (13); 10), described sacrifice layer (13) obtains described runner (17 after being corroded, being dissolved or being removed under the state of fusing; 20), described integument (8) and separation layer (11; 12) resin, plastics or the rubber that can be cured is, described integument (8) and separation layer (11; 12) respectively by liquid resin, liquid plastic or liquid rubber being covered on described sacrifice layer (13) and infiltrating described raceway groove (4; 7) obtain after solidification in.
2. micro-fluidic chip as claimed in claim 1, is characterized in that, also comprise functional structure, described separation layer (11; 12) part of surrounding is not corroded, do not dissolved and not removed described sacrifice layer (13) forms functional structure under the state of fusing.
3. micro-fluidic chip as claimed in claim 1, is characterized in that, also comprise supporting construction, described separation layer (11; 12) part of surrounding is not corroded, do not dissolved and not removed described sacrifice layer (13) is supporting construction under the state of fusing.
4. micro-fluidic chip as claimed in claim 1, it is characterized in that, described sacrifice layer (13) is conductive material or soluble material.
5. micro-fluidic chip as claimed in claim 1, it is characterized in that, described sacrifice layer (13) is arranged on described substrate (1) by the mode of plated film or rotary coating.
6. micro-fluidic chip as claimed in claim 5, is characterized in that, described sacrifice layer (13) is generated by the mode of repeatedly plated film or rotary coating.
7. micro-fluidic chip as claimed in claim 1, is characterized in that, described raceway groove (4; 7) mode by etching or carving generates.
8. micro-fluidic chip as claimed in claim 1, it is characterized in that, described sacrifice layer (13) is metal material, corrodes described sacrifice layer (13) and adopts electrochemical etching method.
9. the preparation method of the micro-fluidic chip as described in any one of claim 1-8, is characterized in that, comprises the following steps:
1), on substrate (1) generate sacrifice layer (13), above generate through described sacrifice layer (13) at described sacrifice layer (13) and go deep into the inner raceway groove (4 of described substrate (1); 7);
2), at described sacrifice layer (13) and raceway groove (4; 7) above cover liquid resin, liquid plastic or the liquid rubber that can be cured, liquid resin, liquid plastic or liquid rubber cover described sacrifice layer (13) and infiltrate described raceway groove (4; 7);
3), to step 2) liquid resin, liquid plastic or liquid rubber be cured, cover the resin of described sacrifice layer (13), plastics or rubber formed integument (8), infiltrate described raceway groove (4; 7) resin, plastics or rubber form separation layer (11; 12) substrate (1) that surface coverage has sacrifice layer (13) and integument (8), is obtained;
4), at described substrate (1) and/or the upper passage (9 generating the connection external world and described sacrifice layer (13) of integument (8); 10);
5) substrate (1) of sacrifice layer (13) and integument (8), surface coverage is had to be dipped in corrosive medium, dissolve medium or electrolyte, by corrosive medium erode can touch sacrifice layer (13), to be dissolved the sacrifice layer (13) that can touch by dissolve medium or erode sacrifice layer (13) by electrochemical etching method, the sacrifice layer corroding or dissolve (13) forms runner (17; 20), after cleaning, micro-fluidic chip is obtained; Or under surface coverage being had the substrate (1) of sacrifice layer (13) and integument (8) to be positioned over the phase change conditions of fusing sacrifice layer (13) material, after sacrifice layer (13) is melted, by passage (9; 10) introduce extraneous pressure and liquid or gas, after being removed by sacrifice layer (13), form runner (17; 20), after cleaning, micro-fluidic chip is obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310571537.9A CN103586093B (en) | 2013-11-13 | 2013-11-13 | Microfluidic chip and manufacturing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310571537.9A CN103586093B (en) | 2013-11-13 | 2013-11-13 | Microfluidic chip and manufacturing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103586093A CN103586093A (en) | 2014-02-19 |
| CN103586093B true CN103586093B (en) | 2015-07-01 |
Family
ID=50076531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310571537.9A Expired - Fee Related CN103586093B (en) | 2013-11-13 | 2013-11-13 | Microfluidic chip and manufacturing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103586093B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105413546B (en) * | 2015-12-14 | 2020-02-14 | 沈阳理工大学 | Microfluid mixing process and mixing device |
| CN107058291B (en) * | 2017-05-03 | 2020-08-25 | 东南大学 | Whole genome amplification method based on elongated reaction cavity |
| CN111229335B (en) * | 2020-01-17 | 2021-11-30 | 上海新微技术研发中心有限公司 | Method for manufacturing optical waveguide microfluid chip |
| CN111239897B (en) * | 2020-01-17 | 2022-02-11 | 上海新微技术研发中心有限公司 | Method for manufacturing optical waveguide microfluid chip |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004167607A (en) * | 2002-11-15 | 2004-06-17 | Tama Tlo Kk | Microfluid element and its manufacturing method |
| CN101149364A (en) * | 2007-11-10 | 2008-03-26 | 大连理工大学 | Water-soluble sacrificial layer micro-flow control chip preparation method |
| CN101382555A (en) * | 2008-09-19 | 2009-03-11 | 厦门大学 | Method for producing glass microflow control chip |
| CN103265179A (en) * | 2013-05-27 | 2013-08-28 | 苏州扬清芯片科技有限公司 | Manufacture method of glass micro-channel |
-
2013
- 2013-11-13 CN CN201310571537.9A patent/CN103586093B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN103586093A (en) | 2014-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103586093B (en) | Microfluidic chip and manufacturing method thereof | |
| CN103894248A (en) | Micro-fluidic chip and micro-fluidic chip system for single cell analysis and single cell analyzing method | |
| JPH05507793A (en) | Microfluid structure and its manufacturing method | |
| Tanzi et al. | Fabrication of combined-scale nano-and microfluidic polymer systems using a multilevel dry etching, electroplating and molding process | |
| CN103231518A (en) | Polydimethylsiloxane array micropore film preparation method | |
| Coltro et al. | Rapid prototyping of polymeric electrophoresis microchips with integrated copper electrodes for contactless conductivity detection | |
| CN100507569C (en) | Process for preparing polymer microfluidic chips | |
| CN110496657B (en) | Microfluidic chip capable of forming liquid metal droplets and preparation method thereof | |
| Li | Fundamentals of microfluidics and lab on a chip for biological analysis and discovery | |
| Guan et al. | Topographic design and application of hierarchical polymer surfaces replicated by microinjection compression molding | |
| CN103723676A (en) | Manufacturing method of micro-fluid channel | |
| CN111974471A (en) | 3D printing-based microfluidic electrical detection chip processing method | |
| Gabardo et al. | Deposition, patterning, and utility of conductive materials for the rapid prototyping of chemical and bioanalytical devices | |
| Martinez‐Duarte | A critical review on the fabrication techniques that can enable higher throughput in dielectrophoresis devices | |
| JP5054824B2 (en) | Method for producing a three-dimensional structure having a hydrophobic outer surface | |
| CN101970726B (en) | Method for fabricating 3d structure having hydrophobic surface using metal foil | |
| Lim et al. | Effect of nanostructures orientation on electroosmotic flow in a microfluidic channel | |
| JP3984557B2 (en) | Electrophoresis device | |
| Meng et al. | Additive processes for polymeric materials | |
| WO2021115047A1 (en) | Microfluidic chip and whole blood separation method based on microfluidic chip | |
| Darboui et al. | Microfluidics chip inspired by fish gills for blood cells and serum separation | |
| CN115007231B (en) | Microfluidic chip for cell-microbead capturing pairing | |
| CN207271276U (en) | A kind of micro-fluidic chip of the PLC technology based on liquid-liquid electrowetting effect | |
| CN105567547B (en) | A kind of preparation method of the high gradient cell capture chip such as non-homogeneous | |
| CN105092555A (en) | Micro-fluidic surface enhanced Raman test chip and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150701 Termination date: 20171113 |