CN106513068B - The solution and its application that micro-fluidic chip bonding for polymerizable material is modified with surface - Google Patents
The solution and its application that micro-fluidic chip bonding for polymerizable material is modified with surface Download PDFInfo
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- CN106513068B CN106513068B CN201610941525.4A CN201610941525A CN106513068B CN 106513068 B CN106513068 B CN 106513068B CN 201610941525 A CN201610941525 A CN 201610941525A CN 106513068 B CN106513068 B CN 106513068B
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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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Abstract
The invention discloses a kind of solution that the micro-fluidic chip bonding for polymerizable material is modified with surface comprising solution buffer components, linked component and surface-modifying component；The buffer components, linked component and surface-modifying component dissolve each other, and do not react, while will not corrode chip.The micro-fluidic chip bonding of the present invention is suitble to monster chip to be bonded with the solution that surface is modified, and production flux is high；It is few to be bonded blind area, intensity is high；Equipment is simple, and production cost is low；After bonding, the deformation of pipeline is small.
Description
Technical field
The present invention relates to a kind of micro-fluidic chip fields, and in particular to a kind of micro-fluidic chip key for polymerizable material
Close the solution being modified with surface and its application.
Background technology
Microfluidic chip technology feature is will to realize sample feeding, mixing, reaction and detection based on micro-processing technology
Etc. functions structure assembly in several square centimeters of chip.In field of biochemistry detection, microfluidic chip technology has logical
Amount is high, detection sensitivity is high, at low cost and be easy to the potential advantages such as automation, thus with very wide application prospect.
Chip bonding is an important link in micro-fluidic chip process of manufacture.Chip bonding refers to will be by micro-
The structures such as the micro- raceway groove obtained, micro- hole and through-hole are processed, closed microchannel, microcavity body and sample inlet and outlet etc. are packaged into.With
Polymer, which is the common bonding method of micro-fluidic chip of material, thermocompression bonding, the bonding of mono-/bis-face glue and organic solution auxiliary
Bonding.
(1) mode of thermocompression bonding is suitble to the bonding between polymer chip, is by applying certain temperature to bonding face
Degree, temperature is closed on or is reached polymer glass temperature, bonding face is allowed to reach the state of softening, while applying certain pressure,
It allows bonding face to merge, completes chip bonding.Thermocompression bonding has bond strength high, is not necessarily to additional auxiliary reagent, thus
Noresidue in pipeline.But it is disadvantageous in that and needs higher temperature；And the problem of being transmitted due to heat, often thermocompression bonding are needed
Longer time；Pressure control also has certain requirement.
(2) mono-/bis-face glue bonding refers to being acted on bonding face using mono-/bis-face glue, makes the method for chip bonding.It is this
Requirement of the method to mono-/bis-face glue is relatively more, such as the requirements such as compatibility, hydrophilic and hydrophobic of intensity, biological sample being bonded.This
Kind method bonding process is simple, is easy to mass produce.But compared with other bonding patterns, bond strength is not often high；Glue
Ingredient is easy to form biochemical reaction and interfere；Most of glue all easy tos produce background fluorescence, is formed and is interfered to optical detection.
(3) bonding of organic solution auxiliary is that have the function of infiltration, softening to polymer chip substrate using organic solution,
So that bonding face permeates each other in bonding process, after organic solvent volatilization, bonding face is hardened and is bonded together again, is completed
Bonding.Organic solution auxiliary bonding has bond strength high, and bonding blind area is few, and bonding speed is fast, at low cost and remained without reagent
The advantages that, it is particularly suitable for large-scale production process.But traditional organic solvent easily corrodes chip structure so that chip structure is sent out
Raw deformation, influences the work of chip.
It is another important link in micro-fluidic chip production that surface, which is modified,.It refers to keeping chip material that surface, which is modified,
Under the premise of originality energy, assign its surface new performance.Due to the characteristic of chip base material, such as hydrophobe characteristic, often without
Method is met the requirements, thus needs to carry out surface modification to its pipe surface, and the common process for modifying surface of micro-fluidic chip has wet
Method modification and vapor deposition both methods.
(1) wet-process modified by liquid reagent processing chip pipeline, change its hydrophobe characteristic.This method has very extensively
Application, especially in micro-fluidic chip academic research field, principle is that liquid reagent is injected the micro-fluidic chip made
It is interior, so that it is formed hydrophilic or hydrophobic functional layer in inner wall of the pipe, achievees the purpose that change surface characteristic.This method has
Reagent cost is low, the advantages that being suitble to be manually operated.But in large-scale production, wet-treating needs reagent leading to every chip
Pipeline in, this just becomes very inefficient, limits production flux.
(2) vapor deposition be using occur in gas phase physics, chemical process, chip pipe surface formed it is functional or
Decorative metal, nonmetallic or compound coat.Vapor deposition can handle large batch of chip simultaneously, thus relatively be suitble to big
Scale processes.But since vapor deposition generally requires the environment of vacuum, equipment cost is very high.Meanwhile to control
The consistency that good surface everywhere is modified, it is also desirable to very complicated control.
Invention content
The present invention to solve the above-mentioned problems, provides a kind of micro-fluidic chip for polymerizable material and is bonded and change with surface
The solution of property, the solution includes following components：Buffer components, linked component and surface-modifying component, the buffer components, key
It is combined point and surface-modifying component dissolves each other, and do not react, while chip will not be corroded；The buffer components control key is combined
Point to the softening rate of chip so that can realize chip bonding and not soften chip excessively, the buffer components be with it is described molten
The volume ratio range of liquid is 20%~90%, it is therefore preferable to 30%~80%, more preferably 40%-70%；The bonding group
Divide so that chip surface becomes to soften, after its evaporation, bonding, the linked component and the solution are realized in chip bonding face
Volume ratio range is 10%~90%, it is therefore preferable to 20%~80%, more preferably 30%-60%；It is modified with the surface
Group is divided into hydrophobic silane, and molecular structure isWherein halogen can be F, Cl, Br, I atom, halogen
Prime number amount is 1 to 3, and the carbon atom number of alkane chain is 1 to 20, and the H atom of alkane chain can partly or entirely be replaced by halogen；Institute
The volume ratio range for stating surface-modifying component and the solution is 0%~20%；Preferably 5%~15%, more preferably
8%-12%.
In one embodiment, buffer components are selected from pentane, hexane, octane, amylene, hexene, octene and nonene one
Kind is a variety of.
In one embodiment, linked component is one in acetone, dichloromethane, chloroform, toluene, benzene
Kind is a variety of.
In one embodiment, surface-modifying component is selected from dimethylchlorosilane, trim,ethylchlorosilane, diformazan bromide
Silane, bromotrimethylsilane, dimethyl iodine silane, Iodotrimethylsilane, hexadecyl trichlorosilane, trichlorine (octyl) silane and
It is one or more in trichlorine (1H, 1H, 2H, 2H- perfluoro capryl) silane.
In one embodiment, polymerizable material is makrolon, polymethyl methacrylate, polydimethylsiloxanes
Alkane or polystyrene.
In one embodiment, the present invention provides a kind of micro-fluidic chip for polymerizable material and is bonded and changes with surface
Property method, the described method comprises the following steps：
Step 1：Configure the solution that the above-mentioned micro-fluidic chip bonding for polymerizable material is modified with surface；
Step 2：By the micro-fluidic chip of polymerizable material need bonding face fully infiltrate configured in step 1 it is molten
In liquid；
Step 3：By the chip bonding infiltrated in step 2 in face of neat assembling, be bonded, control bonding temperature 10~
120 DEG C, bonding time is controlled at 10 seconds~20 minutes；
Step 4：After the completion of bonding, remaining solution in chip is blown off with dry air.Beneficial effects of the present invention：
1. it is high to produce flux, it is suitble to monster chip bonding.Since in monster chip production process, surface is modified past
It is past more time-consuming.Polymer chip bonding is modified the two important processing environments with surface and is combined into one by the present invention,
The problem of carrying out surface modification while bonding, not only solve wet-process modified unsuitable large-scale production process, simultaneously also
The production link for individually carrying out chip surface modification is eliminated, therefore greatly improves the flux of production.
2 bonding blind areas are few, and intensity is high.The method of the bonding chip of the present invention is the side based on organic solution auxiliary bonding
Method, thus also inherit its be bonded blind area it is few, the high advantage of bond strength.
3 equipment are simple, and production cost is low.The present invention assists the wet-process modified organic solution that is integrated in during being bonded,
Device systems needed for thus are fairly simple.Simultaneously as the auxiliary bonding of wet-process modified and organic solution all has production cost
Low advantage, thus the present invention similarly has the advantages that production cost is low.
After 4 bondings, the deformation of pipeline is small.Due to containing buffer components in the present invention, chip pipeline configuration can be formed and be protected
Shield reduces influence of the linked component to pipeline form so that the deformation of pipeline is small after bonding.
Description of the drawings
It in order to more clearly explain the technical solutions in the embodiments of the present application, below will be to needed in the embodiment
Attached drawing is briefly described, it should be apparent that, the accompanying drawings in the following description is only some embodiments described in the application, right
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings
Its attached drawing.
Fig. 1 is the Contact-angle measurement figure of the PMMA chip surfaces handled without mixed solution in embodiment 1；
Fig. 2 is the Contact-angle measurement figure of the PMMA chip surfaces by mixed solution processing in embodiment 1；
Fig. 3 is the result figure of the drop formation chip production drop by mixed solution A bonding in embodiment 2；With
Fig. 4 is the result figure by the mixed solution B drop formation chip production drops being bonded in embodiment 2.
Specific implementation mode
In order to make art technology field personnel more fully understand the technical solution in the application, below in conjunction with following knot
Closing embodiment, the invention will be further described, it is clear that and described embodiments are only a part of embodiments of the present application, without
It is whole embodiment.Based on the embodiment in the application, those of ordinary skill in the art are not before making creative work
The all other embodiment obtained is put, shall fall within the protection scope of the present application.Below in conjunction with the accompanying drawings and specific example
The invention will be further described.
Change of one mixed solution of embodiment to PMMA material hydrophilic and hydrophobics
Step 1：It is about respectively 3cm, thickness 5mm to take the PMMA chips of two panels surfacing, length and width；It is positioned in pure water,
It is cleaned, and dried with supersonic cleaning machine.
Step 2：Configure 1ml mixed solutions, wherein 500 μ l of buffer components, 400 μ l of linked component, surface-modifying component
100μl.Wherein, buffer components ingredient is n-hexane, and linked component is chloroform, surface-modifying component be trichlorine (1H, 1H,
2H, 2H- perfluoro capryl) silane, structural formula isThen it stirs evenly.
Step 3：Oxygen plasma processing, 60 seconds processing times are carried out to the two panels PMMA chips in step 1.
Step 4：Two panels PMMA chips are kept flat, 1ml mixed solutions are uniformly smeared into a piece of PMMA chip lists wherein
Face, another is not handled.Two panels chip is respectively positioned in ventilated container, temperature setting is 50 DEG C in container.Wait for 30 points
It is taken out after clock, is used in combination dry air to blow away remaining solution on processed chip, stands 10 minutes.
Step 5：Two panels chip is positioned on contact angle measurement, the distilled water water droplet of 2 μ l is added dropwise respectively, is clapped after 5 seconds
Contact angle photo is taken the photograph, goniometry is used in combination to measure.Untreated PMMA chip surfaces contact angle is 72 °, as a result such as Fig. 1.It is mixed
The PMMA chip surface contact angles for closing solution treatment are 113 °, and contact angle increases 41 °, as a result such as Fig. 2.
Embodiment two realizes the generation of drop using mixed solution bonding PC chips
Step 1：It is 3cm to take the PC chip two panels with cross pipeline, chip length and width, and pipeline is 100 μm deep, wide 100 μ
M, four branches ends of cross pipeline have been all connected with through-hole, and through-hole can be used by the entrance as fluid.It is another to take without containing pipe
The PC chips in road and through-hole structure, length and width are 3cm.Four chips are cleaned with supersonic cleaning machine, and are dried.
Step 2：Configure mixed solution A 1ml, including 500 μ l of buffer components, 400 μ l of linked component, surface-modifying component
100μl.Wherein, buffer components ingredient is 1- hexenes, and linked component is dichloromethane, surface-modifying component be trichlorine (1H, 1H,
2H, 2H- perfluoro capryl) silane.Configure the mixed solution B1ml without surface treatment component, including 600 μ l of buffer components, bonding
400 μ l of component.Wherein, buffer components are 1- hexenes, and linked component is dichloromethane.
Step 3：Oxygen plasma processing, 60 seconds processing times are carried out to four PC chips in step 1.
Step 4：PC chip of the two panels without containing pipeline configuration is kept flat, 1ml mixed solution As are uniformly smeared wherein
A piece of PC chip surfaces, mixed solution B are uniformly applied to another surface.After standing 10 seconds, by other two panels PC chip belt pipes
Downwards, the face that mixed solution is smeared with other two panels PC chips closely forces together road structure, pressure 50N.It keeps
Pressure simultaneously places them in ventilated container, and temperature setting is 80 DEG C in container.It is taken out after ten minutes.Chip has been at this time
Bonding finishes, and obtains two complete chips.
Step 5：Remaining solution in chip is blown away with dry air, stands 10 minutes.
Step 6：Water and mineral oil are injected into two panels chip for generating drop respectively using syringe.Wherein, cross
One pipeline of pipeline injects water, and flow velocity is 800 μ l/h, and adjacent two pipelines inject mineral oil, and flow velocity is 600 μ l/
H, water and mineral oil converge at cross, then flow to remaining pipeline together, and flow out from outlet.In such cases, drop
Generation need pipeline have certain hydrophobicity.The interaction process of cross intersection water and mineral oil is used under the microscope
High speed camera records, as a result such as Fig. 3, Fig. 4.The chip being bonded with mixed solution A is due to containing surface treatment agent, inner wall of the pipe
It is that there is drop that is hydrophobic, therefore can generating size uniformity.And do not carry out pipeline with the chip of mixed solution B bondings
Surface is modified, and unmodified pipeline hydrophobicity is inadequate, thus can not generate drop.Whole process chip leakproofness is good, and mixed
Surface modification can be carried out to pipeline by closing the chip of solution A bonding, illustrate that the present invention is provided simultaneously with bonding chip and is modified with surface
Ability.Through measuring, the chip bonding intensity of mixed solution A bonding is up to 113N/cm2, the chip bonding of mixed solution B bondings
Intensity is up to 152N/cm2。
It should be understood that the present invention disclosed is not limited only to specific method, scheme and the substance of description, because these
It is alterable.It will also be understood that purpose of the terminology used here just for the sake of the specific embodiment scheme of description, rather than
It is intended to limit the scope of the invention, the scope of the present invention is limited solely by the attached claims.
Those skilled in the art, which will also be appreciated that or be able to confirm that, uses no more than routine experiment, institute herein
Many equivalents of the specific embodiment of the present invention stated.These equivalents are also contained in the attached claims.
Claims (11)
1. for polymerizable material micro-fluidic chip bonding with surface be modified solution, it is characterised in that the solution include with
Lower component：Buffer components, linked component and surface-modifying component, the buffer components, linked component and surface-modifying component are mutual
It is molten, and do not react, while chip will not be corroded；
Softening rate of the buffer components control linked component to chip so that can realize chip bonding and not soften core excessively
Piece, it is 20%~90% that the buffer components, which are with the volume ratio range of the solution,；
The linked component makes chip surface become to soften, and after its evaporation, bonding, the bonding group are realized in chip bonding face
It is 10%~90% to divide with the volume ratio range of the solution；With
The surface-modifying component is hydrophobic silane, and molecular structure isWherein halogen can be
F, Cl, Br, I atom, halogen quantity are 1 to 3, and the carbon atom number of alkane chain is 1 to 20, the H atom of alkane chain can part or
All replaced by halogen；The volume ratio range of the surface-modifying component and the solution is 5%~15%.
2. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the buffering group
It is divided into one or more in pentane, hexane, octane, amylene, hexene, octene and nonene.
3. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the bonding group
It is divided into one or more in acetone, dichloromethane, chloroform, toluene, benzene.
4. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the surface changes
Property group be divided into selected from dimethylchlorosilane, trim,ethylchlorosilane, dimethyl bromo-silicane, bromotrimethylsilane, dimethyl iodine silane,
Iodotrimethylsilane, hexadecyl trichlorosilane, trichlorine (octyl) silane and trichlorine (1H, 1H, 2H, 2H- perfluoro capryl) silane
In the middle one or more.
5. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the polymer
Material is makrolon, polymethyl methacrylate, dimethyl silicone polymer or polystyrene.
6. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the buffering group
It is 30%~80% to be divided into the volume ratio range of the solution.
7. the solution that the micro-fluidic chip bonding according to claim 6 is modified with surface, it is characterised in that the buffering group
It is 40%-70% to be divided into the volume ratio range of the solution.
8. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the bonding group
It is 20%~80% to divide with the volume ratio range of the solution.
9. the solution that the micro-fluidic chip bonding according to claim 8 is modified with surface, it is characterised in that the bonding group
The volume ratio range with the solution is divided to be 30%-60%.
10. the solution that the micro-fluidic chip bonding according to claim 1 is modified with surface, it is characterised in that the surface changes
Property component and the solution volume ratio range be 8%-12%.
11. a kind of micro-fluidic chip bonding and surface modifying method for polymerizable material, it is characterised in that the method packet
Include following steps：
Step 1：Configure the solution of claim 1；
Step 2：Bonding face is needed fully to infiltrate the solution configured in step 1 the micro-fluidic chip of polymerizable material
In；
Step 3：By the chip bonding infiltrated in step 2 in face of neat assembling, be bonded, control bonding temperature at 10~120 DEG C,
Bonding time is controlled at 10 seconds~20 minutes；
Step 4：After the completion of bonding, remaining solution in chip is blown off with dry air.
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| CN101643701A (en) * | 2009-07-23 | 2010-02-10 | 清华大学 | Cell sorter micro-fluidic chip based on immunomagnetic separation technology and application thereof in aspect of enrichment of rare cells |
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Address after: 100084 Tsinghua Yuan, Beijing, Haidian District Co-patentee after: Beijing Xinyi Biotechnology Co., Ltd. Patentee after: Tsinghua University Address before: 100084 Tsinghua Yuan, Beijing, Haidian District Co-patentee before: Beijing Tianjian Wellcome Biotechnology Co. Ltd. Patentee before: Tsinghua University |