CN108212231A - A kind of miniflow macrofluid control chip and preparation method thereof - Google Patents
A kind of miniflow macrofluid control chip and preparation method thereof Download PDFInfo
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- CN108212231A CN108212231A CN201810008708.XA CN201810008708A CN108212231A CN 108212231 A CN108212231 A CN 108212231A CN 201810008708 A CN201810008708 A CN 201810008708A CN 108212231 A CN108212231 A CN 108212231A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D19/00—Degasification of liquids
- B01D19/02—Foam dispersion or prevention
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
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Abstract
The invention discloses a kind of preparation methods of miniflow macrofluid control chip, include the following steps：In 3D printer, micro flow chip fluid layer and key-course formpiston are prepared using new material polysmooth；It is sprayed smooth male mold surfaces structure using alcohol；PDMS chip controls layer and fluid layer are prepared using method of molding；PDMS is spin-coated on bare silicon wafer surface and prepares pressure controlling film；Using half freezing method combination chip fluid layer and PDMS film；Using super rule of three combination key-course and the fluid layer with PDMS film；Punching, and chip bottom is sealed using PCR adhesive tapes, obtain miniflow macrofluid control chip.The fluid chip of the present invention, can realize micro-scale (cell, bacterium) and physiology, pathology and the drug Screen test of macro-scale (histotomy) simultaneously.
Description
Technical field
The present invention relates to micro fluidic chip technical fields, and in particular to a kind of miniflow macrofluid control chip and preparation side
Method, particularly a kind of preparation side that polymeric material and the PDMS miniflow macrofluid control chips of 3D printing technique are polished based on alcohol
Method.
Background technology
Microfluidic chip technology (Microfluidics) is biological, chemical, medical analysis process sample preparation, instead
Should, separation, detection etc. basic operation units be integrated on the chip of one piece of micro-meter scale, be automatically performed analysis overall process.Mainly
Using its small advantage, by that in the miniature reaction of solid chip surface construction and analytic unit, can realize to inorganic
Ion, organic substance, nucleic acid, protein and other biochemical components fast and accurately detect, and can handle picometre, nanoscale
Other fluid, therefore have the advantages of increasingly automated and integrated, can greatly reduce sample consumption, reduce biological monitoring into
Originally reaction rate, is improved, there is very big prospect to drug development, medical diagnosis on disease, micro-scale biological study.Since it is in life
The great potential in the fields such as object, chemistry, medicine has been developed as biology, chemistry, medicine, fluid, electronics, material, a machine
The brand-new research field of the subject crossings such as tool.
Traditional microfluidic chip refer to micro-meter scale structure need complex fluid condition and operation sequence chemistry or
Biology laboratory.In recent years, micro-fluidic chip is permitted in medical diagnosis on disease, drug screening, environmental monitoring, food security, judicial expertise etc.
Various aspects show very extensive application prospect.Extensively should by the micro flow chip equipment of Bureau of Drugs Supervision of the U.S. (FDA) approval
For clinical (such as Hemolink, Tassoinc, the U.S.), medical diagnosis (such as μi30Automated
Platform microfluidic-based clinical immunoanalyzer, Wako, the U.S.) and field of biological detection
(such as ClTMSingle-Cell mRNA Seq HT IFC, 10-17 μm, Fluidigm, the U.S.).
Conventional microfluidic control chip prepares material and includes monocrystalline silicon piece, glass, quartz and optical cement for photoengraving etc..Wherein
Silicon materials have good chemical inertness and thermal stability, and earliest for making micro-fluidic chip, but silicon materials are frangible, cost
Height, translucency are poor, and electrical insulation capability difference and surface chemistry behavior are complex, greatly limit its answering in micro-fluidic chip
With.Glass micro-fluidic chips have excellent optical property and support electric osmose properties of flow, are easy to surface modification, can directly use for reference biography
The capillary electrophoresis analysis technology of system, therefore more paid attention in the micro-fluidic chip early stage of development and accordingly developed, until
The present is still one of most widely used chip.Quartz is similar with glass to have good electric osmose and excellent optical property, table
Face is adsorbed and surface respond is all conducive to surface modification, but price is relatively high.Material is made to be main using glass and silicon
The manufacturing process of material relies on standard photolithography techniques, and there are of high cost, complex procedures, easy to pollute and channel geometry to be limited
Shortcoming.Although with glass material make micro-fluidic chip have many superiority, polymer material by type it is more, process
Convenient formation production method is simple, it is of low cost it is inexpensive compared with glass, the features such as disposable chip can be made, be just increasingly people
It is of interest, progressed into micro-fluidic chip field.Mainly there is poly- methyl for the polymer material of facture of microchip
Methyl acrylate (PMMA), dimethyl silicone polymer (PDMS), polypropylene (PP), polystyrene (PS), makrolon (PC) etc..
For polydimethylsiloxane as a kind of polymer material, light transmission is good, has to the ultraviolet light of more than wavelength 300nm good
Good permeability, machine-shaping is easy, is a kind of durable material, there is good thermal insulation, insulating properties and chemical stability, can
It repeatedly uses, and with good biocompatibility.The most commonly used means of photolithography of micro-fluidic chip is prepared, including light
Glue spin-on deposition, mask make, corrode and remove photoresist and etc. (thin film is covered on substrate first, in film surface
With photoresist spinner equably attached last layer optical cement, then the image on mask is transferred on optical cement layer, this step is photoetching.Again will
Image in photoetching is transferred to film, and the micro-structure of certain depth is processed on substrate, this step completes etching).Except pair
Requirement in dustless ultra-clean space, the required precision of a few micrometers of scales more cause preparation process to become extremely complex, and by ring
Border factor influences huge (such as silicon face processing procedure).Moreover, in order to realize chip automation function, the system of integrated pressure valve
The standby optical cement processing method more complicated with greater need for another kind is introduced, such as the combination of positive photoresist AZ50 and negtive photoresist SU8.This micron meter
The structure assembly of degree needs high-precision mask exposure machine, and manufacturing cost is further increased.Fluid core is prepared with means of photolithography
Another big limitation of piece is that it is limited to the scale of micron.Due to being stable at silicon chip surface using spin coating mode, tie
Structure size is largely limited to the height of structure.It is up to 500 microns using the obtained height of the method for single spin, and
Because the reasons such as surface tension and uneven heating frequently result in body structure surface out-of-flatness.Using the method for multiple multilayer of spin-on, then
It is fairly time consuming laborious.And mask exposure machine is for thickness also certain requirement (typically not greater than 1 millimeter) of optical cement.
More mature for silicon, glass, the chip technology technique of quartzy this three classes making at present, manufacture craft is based on partly leading
IC techniques in body industry, experimental period is long, technique is cumbersome, equipment and production environment is required harsh.And polymer material system
The chip of work, by its type is more, price is low, moulding process has simply become the mainstay material of current facture of microchip,
The hot spot of this analog thermoplastic elastomer of particularly PDMS, even more micro-fluidic chip research in recent years.Although there are many forming method,
Integrated control fluid carries out pressure valve necessary to complex operations (peristaltic pump, automatic fluid conveying, proportioning etc.) in the chips,
And it is still miniflow by fluid chip scale expansion to the millimeter even centimeter scale that can carry out biological pathology tissue sample operation
Control the critical issue of chip research.And the micrometer structure for PDMS chip templates complex manufacturing technology (including ultra-clean space,
Micrometer structure Preparation equipment etc.), using plasma oxidation be the bonding conditions of master chip multilayer functional structure easily by external environment shadow
The problems such as ringing (such as air environment, chemical gas etc.) also greatly limits fluid chip in biomedical aspect
Using.In consideration of it, it is simple to study a kind of preparation process, and it is of low cost, without the super-clean environment needed for photoetching, without mask equipment
With expensive devices and the tedious steps such as optical cement processing, and can prepare with micro-fluidic compared with high-aspect-ratio and complicated three-dimensional structure
The method of chip is the emphasis of the application research.
Invention content
Therefore, in view of the preparation method of existing micro-fluidic chip described above has preparation process complexity, equipment requirement
And the missing of the shortcomings of of high cost and macroscopical fluidic chip technology of preparing, it is simple the object of the present invention is to provide one kind, have
It prepares from microcosmic to macro-scale structures ability, and can be to the fluid control chip preparation method of 3D structure extensions.
The present invention provides a kind of preparation methods of miniflow macrofluid control chip, include the following steps：
Step A prepares micro-fluidic chip anode membrane：Micro-fluidic chip key-course anode membrane and fluid layer sun are prepared with 3D printing
Film carries out cleaning treatment after polishing to key-course anode membrane and fluid layer anode membrane；
Wherein, the material that 3D printing uses described in step A is polysmooth.
Wherein, it is finished to described in step A by formpiston as surface polishing is carried out in alcohol spraying, key-course formpiston is thrown
Light 30 minutes, fluid layer formpiston polish 3 hours.
Wherein, 3D printing structure is minimum 100 microns in xy directions, and the printable structure of maximum is 20 centimetres, in z-axis side
It it is 10 microns to minimal structure, the printable structure of maximum is 20 centimetres.
Wherein, in alcohol sprays polishing method, alcohol liquid-drop diameter is about 10 microns, smooth 3D printing male mold surfaces week
The polishing time of phase property linear structure is -50 minutes 30 minutes, and block structure right angle is converted into Fluid pressure valve can close arch
The polishing time of the round and smooth structure of shape is -5 hours 3 hours.
Step B prepares PDMS fluid chips, specially following steps：
Step B.a prepares PDMS chip controls layer and PDMS chip fluid layers using method of molding；
Step B.b PDMS are spin-coated on bare silicon wafer surface and prepare pressure controlling film；
Step B.c uses half freezing method combination chip fluid layer and PDMS film, obtains the fluid layer with PDMS films；
Step B.d uses super rule of three combination key-course and the fluid layer with PDMS film；
Step B.e is punched, and seals chip bottom using PCR adhesive tapes, obtains fluid control chip.
It is preferred that step B.a in, preparing PDMS chip controls layer and PDMS chip fluid layers is specially：With 20:1-5:1 is mixed
It closes PDMS substrates and curing agent, traditional vacuum removes bubble removing, mixture is poured slowly into chip fluid layer anode membrane and chip controls
In layer anode membrane, bubble is removed in vacuo；It is then placed in 80 degree of baking ovens and stands 50 minutes；
Wherein preferably, by 20：1PDMS mixtures are poured slowly into chip fluid layer formpiston, by 5：1 PDMS mixtures delay
Slowly it pours into chip controls layer formpiston.
It is preferred that step B.b in, bare silicon wafer surface carry out TMCS coating film treatments, by 20：1PDMS mixtures slowly fall
In silicon chip surface, and with 200rmp rotating speeds in silicon chip surface spin coating 20：1PDMS films, the silicon chip that then will carry PDMS film
It is put into 80 degree of baking ovens 4 minutes, prepares pressure controlling film.
It is preferred that step B.c in, be specially using half freezing method combination chip fluid layer and PDMS film：By pressure controlling
Film and chip fluid layer take out simultaneously from baking oven, remove chip fluid layer surface PDMS, and its structure is placed in not downwards
The PDMS film surface being fully cured is then placed in 80 degree of baking ovens standings and obtains the fluid layer with PDMS film in 1 hour.
It is preferred that step B.d in, be specially using super rule of three combination key-course and the fluid layer with PDMS film：It will be solid
The PDMS of change takes out from key-course formpiston, and key-course structure is placed in the fluid layer of PDMS film using micro- aligner
On, it is ensured that Fluid pressure valve can be on closing structure in fluid layer, and the fluid chip of integration is statically placed in 48 hours in 80 degree of baking ovens
It is preferred that step B.e in, punching PDMS chips feed liquor and liquid outlet are punched using hollow pipe patterning method, and
Chip bottom is sealed using biological dedicated transparent adhesive tape, obtains miniflow macrofluid control chip.
The principle of the present invention is：The present invention has excellent printing effect, equilibrium using 3D printing material PolySmooth
Mechanical performance and can polishability, can be polished using more than 75% alcohol of concentration, will such as isopropanol or ethyl alcohol
The 3D models of PolySmooth consumptive materials printing are placed in the alcohol aerosol being made of particle suspension drop, you can complete polishing
Process, process are simple to operation.Wherein particle suspension drop is that tiny alcohol hanging drop is generated by sprayer, is attached to 3D
The surface of printer model makes it more smooth.Then polysmooth microns of 3D printing and macrostructure utilize the micro- liquid of alcohol
Drop is processed by shot blasting print structure, so as to obtain round and smooth domes necessary to fluid chip pressure valve.Again with polishing
Polysmooth structures afterwards are formpiston, prepare the fluid layer and key-course of fluid control chip, and (half- is combined by semi-solid preparation
Curing) and hypergeometric example combines (off-ratio) two methods respectively in connection with fluid layer/film layer and fluid layer/key-course, it
Punching encapsulation is carried out for feed liquor and liquid outlet afterwards, obtains PDMS miniflow macroscopic view fluidic chips.
Wherein described PDMS chips curing liquid layer and PDMS semi-solid preparations film combine, and are put into 80 degree of baking ovens one hour,
Form closed fluid passages.And described 20：1PDMS mixed proportion fluid film layers, with ratio 5：1 PDMS chip controls layers
By non-stable curing agent molecule in layer and the direct diffusion bond of layer.Wherein three layers of PDMS construction joining methods, including combining
PDMS film and the semi-solid preparation method of chip fluid layer and the super ratio method of combination fluid layer and key-course.
Compared with traditional microfluidic chip formpiston preparation method, it is an advantage of the invention that：
(1) PDMS fluids control chip formpiston preparation process of the invention is integrally formed for 3D printing, and process is simple, at low cost
It is honest and clean, without the super-clean environment needed for photoetching, expensive devices and the tedious steps such as mask equipment and optical cement processing, and macroscopic view can be prepared
Mesostructure and three-dimensional structure.
(2) present invention prepares fluid control chip formpiston using 3D printing technique, can prepare with compared with high-aspect-ratio and again
Miscellaneous three-dimensional structure breaks through conventional lithography means height limitation as caused by optical cement property.
(3) present invention has excellent printing effect, balanced mechanically performance using 3D printing material PolySmooth
And can polishability, the surface of 3D printing model is more smooth, meets round and smooth domes necessary to fluid chip pressure valve
Requirement.
The preparation of miniflow (macrofluid) the control chip of the present invention is instead of the tradition side that optical cement AZ50 and SU8 is used to combine
Method, it is of low cost without lithographic equipment and ultra-clean space environment, and can prepare any form has pressure valve switching function
3 D stereo PDMS fluid chips can realize micro-scale (cell, bacterium) and physiology, the pathology of macro-scale (histotomy)
With drug Screen test.
Description of the drawings
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution of the prior art
Embodiment or attached drawing needed to be used in the description of the prior art are briefly described.
Fig. 1 is converted into smooth domes signal for 3D printing polysmooth block structures after the polishing of alcohol droplet
Figure.
Fig. 2 is the scanning that 3D printing polysmooth block structures are converted into smooth domes after the polishing of alcohol droplet
Electron microscope (SEM).
Fig. 3 is the PDMS fluid chip preparation process schematic diagrames in 1 step 2 of the embodiment of the present invention.
Fig. 4 is the macrofluid chip application schematic diagram of the embodiment of the present invention 1.
Fig. 5 is 2PDMS fluid chips preparation process of the embodiment of the present invention and application schematic diagram.
Specific embodiment
Technical scheme of the present invention is described in detail below in conjunction with the accompanying drawings.
Embodiment 1
Step 1, the preparation of PDMS miniflows macrofluid chip PLA formpistons
1.1 with 3D printing PLA polysmooth material preparation miniflow macrofluid chip controls layers and fluid layer formpiston；
1.2 by formpiston as alcohol spray in carry out surface polishing, key-course 30 minutes, fluid layer 3 hours；
1.3 pairs of key-courses and fluid layer carry out cleaning treatment；
With reference to Fig. 1, it is converted into after the polishing of alcohol droplet suitable for fluid for 3D printing polysmooth block structures
The smooth domes schematic diagram of chip pressure valve.After 3D printing, printed material polysmooth is block structure, is passed through
After crossing the polishing of alcohol droplet, block structure disappears, and is transformed into smooth domes, the surface more light of 3D printing model
Sliding, which is suitable for the use of fluid chip pressure valve.
With reference to Fig. 2, it is converted into after the polishing of alcohol droplet suitable for fluid for 3D printing polysmooth block structures
The scanning electron microscope (SEM) photograph (SEM) of the smooth domes of chip pressure valve.As shown in FIG., not only block structure is converted to smooth arch
Shape structure, while surface linear structure also becomes smooth surface caused by 3D printing.
It is the PDMS fluid chip preparation process schematic diagrames in step 2 with reference to Fig. 3.
Wherein PDMS fluids are placed on the PDMS film surface not being fully cured by (1)；(2) combining PDMS bilayers knot
Structure is put into 80 degree of baking ovens standings and is bonded for 1 hour；(3) PDMS key-courses PDMS film has been placed in using micro- aligner
Fluid layer on, it is ensured that Fluid pressure valve can be on closing structure in fluid layer；(4) fluid chip of integration is statically placed in 80 degree
It is bonded within 48 hours in baking oven.
Specifically, step 2 in the present embodiment, the preparation of PDMS miniflow macrofluid chips, specially：
2.1 with 20：1 mixing PDMS substrates and curing agent, traditional vacuum remove bubble removing；
2.2 by 20 gram 20：1PDMS mixtures are poured slowly into chip fluid layer formpiston, and bubble is removed in vacuo；It is then placed in
50 minutes are stood in 80 DEG C of baking ovens；
2.3 carry out TMCS coating film treatments on bare silicon wafer surface, and 10 grams of PDMS mixtures of total weight are slowly fallen in silicon
Piece surface, and with 200rmp rotating speeds in silicon chip surface spin coating 20：Then the silicon chip for carrying PDMS film is put by 1PDMS films
80 DEG C of baking ovens 4 minutes；
2.4 take out PDMS film and fluid layer simultaneously from baking oven, remove chip fluid layer surface PDMS, and by its
Structure is placed in the PDMS film surface not being fully cured downwards, is then placed in 80 DEG C of baking ovens and stands 1 hour；
2.5 with 5：1 mixing PDMS substrates and curing agent, traditional vacuum remove bubble removing；
2.6 by 60 gram 5：1PDMS mixtures are poured slowly into chip controls layer formpiston, and bubble is removed in vacuo；It is then placed in
50 minutes are stood in 80 DEG C of baking ovens；
2.7 take out cured PDMS from key-course formpiston, have been placed in key-course structure using micro- aligner
On the fluid layer of PDMS film, it is ensured that Fluid pressure valve can be on closing structure in fluid layer, and the fluid chip of integration is statically placed in
48 hours in 80 degree of baking ovens；
2.8 punch PDMS chips feed liquor and liquid outlet using hollow pipe patterning methods, and with biology dedicated transparent glue
Band seals chip bottom to get PDMS miniflow macroscopic view fluidic chips.
With reference to Fig. 4, using the macrofluid chip constructed by the technology, liquid not only can be controlled with micro-fluidic chip
The function of transport, proportioning and Dynamic Signal generation, and complex biological medicine can be tested (such as composition of medicine screening, bionical ring
Border structure etc.) applied to macroscopical biological sample (such as tumor biopsy sample, so as to carry out personalized diagnosis and treatment).It is specifically shown in Fig. 4, Fig. 4
(A) growing state of fibroblast (3T3) is cultivated in fluid chip；Fig. 4 (B) cultivates macrophage system in the chips
(RAW) growing state；Fig. 4 (C) builds the development detection of grade liver tumour organoid in the chips.
Embodiment 2
It is PDMS fluid chips preparation process and application schematic diagram in step 2 with reference to Fig. 5.
Fluid chip preparation process of the wherein Fig. 5 (A) based on 3D printing polishing technology：1, by the PDMS film layer of semi-solid preparation
It is combined with fluid control layer；2. being heated to 80 DEG C stablizes bonding；3. by fluid layer made of different PDMS and curing agent ratio and
Film key-course is combined；4. fluid different layers structure is integrated using hypergeometric example combined method, and complete chip preparation.
Fig. 5 (B) is using having four a diameter of 4.5 millimeters, the highly fluid chip for 1.5 millimeters of culture chambers made of the technology.It is logical
The switch for controlling each culture chamber entrance is crossed, different culture environments can be built in 4 culture chambers, so as to be directed to
The complex biological experiment of nuclear tissue.In picture the demonstration of correlation function has been carried out using food coloring agent.Fig. 5 (C)
The operating process of fluid chip：1. first by opening culture chamber (chamber 1), specified liquid (sapphirine) is passed through
Inlet is sent via fluid channel into culture chamber, closes culture chamber (chamber 1) after the completion, and the hand-manipulating of needle of going forward side by side is to other cultures
The liquid conveying of chamber；2. after the completion of the conveying of all culture chamber liquid, whole channels are closed, and by liquid displacement in channel into thin
Born of the same parents or tissue culture medium.
In the application in research process, by lot of experiments, it is found that it is following several the application critical control point mainly has
Point：
The control of 1.3D print structures scale and polishing time, the scale (including height, width etc.) of 3D printing structure and
The relevance of polishing time has vital effect for preparing the control valve for fluids with smooth arcuate structure.Specifically
For, under similary width conditions, relatively high structure needs longer alcohol polishing time to reach structural requirement；And it ties
The wide high proportion of structure also has certain limitation, and wide high proportion is best between 0.25 to 0.4.
2. the cohesive process of fluid layer and key-course, two kinds of PDMS is used to combine in the chip fabrication process of the application
Technology, including semi-solid preparation combined method and hypergeometric example combined method.How chip processing time is optimized so as to reach best knot
It is one of critical control point of the application to close effect.Specifically, when the treatment temperature that semi-solid preparation combines is 80 DEG C, film layer
Processing time is no more than 15 minutes；After semi-solid preparation combination, further it is no more than a hour in 80 DEG C of processing, then carries out
Hypergeometric example combines.The diffusion of PDMS macromoleculars is kept as far as possible, so as to be optimal combination.
3rd, common 3D printing material also has acrylonitrile-butadiene-styrene (ABS) plastics (ABS) in addition to polylactic acid (PLA), this
PLA is selected in invention, and relative to ABS, PLA is a kind of good 3D printing material of bio-compatibility, with no biotoxicity and
Convenient for the property feature of improvement.In addition, the toughness and pliability of PDMS are directly determined by the ratio of PDMS and curing agent.This is specially
1 used in profit application：5,1：10 and 1：20 confirm effective ratio by lot of experiments, change mixed proportion
Thin film physics property can be caused to change, so as to rupture under an increased pressure.
Above-described embodiment is the illustration invented, and it is special should not to describe limitation with the exemplary embodiments of specification and attached drawing
The protection domain of economic rights.
The preferred embodiments of the disclosure and embodiment are explained in detail above in conjunction with attached drawing, but it is of the invention
The above-described embodiment and examples are not limited to, in the knowledge having in those skilled in the art, can also not taken off
Various changes can be made under the premise of from present inventive concept.In the claims, should not will between bracket it is any with reference to symbol
Number be used as limitations on claims.Word "comprising" does not exclude the presence of element or step not listed in the claims.Word
First, second and the use of third etc. do not indicate that any sequence, these words can be construed to title.
The demonstration of the parameter comprising particular value can be provided herein, but these parameters are worth accordingly without being definitely equal to, but
It can be similar to analog value in acceptable error margin or design constraint.The direction term mentioned in embodiment, such as " on ",
" under ", "front", "rear", "left", "right" etc., be only refer to the attached drawing direction, be not used for limiting the scope of the invention.This
Outer above-described embodiment can be based on the considerations of design and reliability, and the collocation that is mixed with each other is used or made with other embodiment mix and match
With the technical characteristic in that is, different embodiments can freely form more embodiments.
Claims (12)
1. a kind of preparation method of miniflow macrofluid control chip, includes the following steps：
Step A prepares micro-fluidic chip anode membrane：Micro-fluidic chip key-course anode membrane and fluid layer anode membrane are prepared with 3D printing, is passed through
It crosses after alcohol polishing and cleaning treatment is carried out to key-course anode membrane and fluid layer anode membrane；
Step B prepares PDMS fluid chips, specially following steps：
Step B.a prepares PDMS chip controls layer and PDMS chip fluid layers using method of molding；
Step B.b PDMS are spin-coated on bare silicon wafer surface and prepare pressure controlling film；
Step B.c uses half freezing method combination chip fluid layer and PDMS film, obtains the fluid layer with PDMS film；
Step B.d uses super rule of three combination key-course and the fluid layer with PDMS film；
Step B.e is punched, and seals chip bottom using PCR adhesive tapes, obtains fluid control chip.
2. preparation method according to claim 1, which is characterized in that the material that 3D printing uses described in step A for
polysmooth。
3. preparation method according to claim 1, which is characterized in that be finished to described in step A by formpiston as wine
Surface polishing is carried out in essence spraying, key-course formpiston polishes 30 minutes, and fluid layer formpiston polishes 3 hours.
4. preparation method according to claim 1, which is characterized in that minimum 100 microns in xy directions of 3D printing structure,
The printable structure of maximum is 20 centimetres, and in z-axis direction, minimal structure is 10 microns, and the printable structure of maximum is 20 centimetres.
5. preparation method according to claim 1, which is characterized in that in alcohol sprays polishing method, alcohol drop is straight
Diameter is about 10 microns, and the polishing time of smooth 3D printing male mold surfaces periodicity linear structure is -50 minutes 30 minutes, will be blocky
Structure right angle be converted into Fluid pressure valve can close the round and smooth structure of arch polishing time be -5 hours 3 hours.
6. according to claim 1-5 any one of them preparation methods, which is characterized in that in step B.a, prepare PDMS chip controls
Preparative layer and PDMS chip fluid layers are specially：With 20:1-5:1 mixing PDMS substrates and curing agent, traditional vacuum remove bubble removing, will
Mixture is poured slowly into chip fluid layer anode membrane and chip controls layer anode membrane, and bubble is removed in vacuo；It is then placed in 80 degree of baking ovens
It is middle to stand 50 minutes.
7. according to claim 1-6 any one of them preparation methods, which is characterized in that in step B.a, by 20：1PDMS is mixed
Object is poured slowly into chip fluid layer formpiston, by 5：1PDMS mixtures are poured slowly into chip controls layer formpiston.
8. according to claim 1-7 any one of them preparation methods, which is characterized in that in step B.b, bare silicon wafer surface into
Row TMCS coating film treatments, by 20：1PDMS mixtures slowly fall in silicon chip surface, and with 200rmp rotating speeds in silicon chip surface spin coating
20：Then the silicon chip for carrying PDMS film is put into 80 degree of baking ovens 4 minutes, prepares pressure controlling film by 1PDMS films.
9. according to claim 1-8 any one of them preparation methods, which is characterized in that in step B.c, using half freezing method knot
It closes chip fluid layer and PDMS film is specially：Pressure controlling film and chip fluid layer from baking oven are taken out simultaneously, remove core
Piece fluid layer surface PDMS, and its structure is placed in the PDMS film surface not being fully cured downwards, it is then placed in 80 degree of bakings
Case stands 1 hour and obtains the fluid layer with PDMS film.
10. according to claim 1-9 any one of them preparation methods, which is characterized in that in step B.d, using super rule of three
Fluid layer with reference to key-course and with PDMS film is specially：Cured PDMS is taken out from key-course formpiston, utilization is micro-
Key-course structure is placed on the fluid layer of PDMS film by aligner, it is ensured that Fluid pressure valve fluid layer can closing structure it
On, the fluid chip of integration is statically placed in 80 degree of baking ovens 48 hours.
11. according to claim 1-10 any one of them preparation methods, which is characterized in that in step B.e, punching is using hollow
Pipe patterning method punches PDMS chips feed liquor and liquid outlet, and seals chip bottom using biological dedicated transparent adhesive tape, i.e.,
Miniflow macrofluid control chip is made.
12. the miniflow macrofluid control chip prepared according to any one of claim 1-11 preparation methods.
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