CN105363503A - Multicomponent micro droplet microfluidic chip and processing method thereof - Google Patents

Multicomponent micro droplet microfluidic chip and processing method thereof Download PDF

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CN105363503A
CN105363503A CN201510733141.9A CN201510733141A CN105363503A CN 105363503 A CN105363503 A CN 105363503A CN 201510733141 A CN201510733141 A CN 201510733141A CN 105363503 A CN105363503 A CN 105363503A
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microlayer model
layer
chip
multicomponent
aqueous phase
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CN105363503B (en
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白志山
王炳捷
赵双良
宣晋
古文全
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East China University of Science and Technology
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502715Containers 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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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 means or forces applied to move the fluids

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Abstract

The invention relates to a multicomponent micro droplet microfluidic chip and a processing method thereof. The provided multicomponent micro droplet microfluidic chip is formed by a covering layer (A), a hydrophobic chip layer (B), a hydrophilic layer chip layer (C) and a base layer (D) which are stacked sequentially. The invention further provides a processing method of the multicomponent micro droplet microfluidic chip.

Description

Multicomponent microlayer model micro-fluidic chip and processing method thereof
Technical field
The invention belongs to the technical field of integrated chip, relate to a kind of multicomponent microlayer model micro-fluidic chip and processing method thereof.
Background technology
Microlayer model is a kind of technology manipulating very low volume fluids grown up on micro-fluidic chip in recent years, its principle is: by two kinds of immiscible liquid, with one wherein for continuous phase, another kind is decentralized photo, continuous phase and decentralized photo enter chip by different entrance respectively, in microchannel, decentralized photo is cut into the microlayer model of the uniform particle sizes of series of discrete under the effect of shearing force by continuous phase.Each drop is independently wrapped up by continuous phase, forms a closed system with extraneous without mass exchange, therefore as a microreactor, can complete one group of chemistry or biological respinse, and stable reaction conditions, reliable results.
At present, the preparation of multicomponent microlayer model has become the study hotspot in this field, and the design of the labyrinth micro-fluidic chip arisen at the historic moment also develops rapidly.The making material of micro-fluidic chip mainly contains silicon, glass, dimethyl silicone polymer, polymethyl methacrylate etc., and wherein silicon and glass material are due to difficult processing, high in cost of production shortcoming, significantly limit its application.By contrast, the organic polymer such as dimethyl silicone polymer, polymethyl methacrylate has that cost is low, lightweight, transparency high, and good resistance to ag(e)ing, corrosion resistance and machining property, become the main material instantly preparing micro-fluidic chip.The fluid channel of various complexity can be processed by laser engraving machine on different organic polymer plates, then successively plate stacked combination is got up, the final channel network configuration forming three-dimensional.In addition, by to the design of MCA and surface treatment, not only in same chip, water-in-oil type or oil-in-water type microlayer model can be gone out by continuous production, more can prepare and comprise the more complicated multicomponent microlayer model such as Janus drop, O/W/O (Water-In-Oil oil-in) drop.
But this area not yet to solve in current microlayer model facture of microchip technique about microchannel processing and the key technology difficult problem such as chip bonding, and the multicomponent microlayer model of preparation complexity cannot be made can to realize on one piece of micro-fluidic chip.
Summary of the invention
The invention provides a kind of multicomponent microlayer model micro-fluidic chip and processing method thereof of novelty, thus solve problems of the prior art.
On the one hand, the invention provides a kind of multicomponent microlayer model micro-fluidic chip, it is made up of capping layer stacked successively, hydrophobic chip layer, hydrophilic chip layer and basalis.
In one preferred embodiment, described capping layer comprises 5 reagent inlet, i.e. 1 aqueous phase A entrance, 2 aqueous phase B entrances, and 2 oil phase entrances;
Described hydrophobic chip layer is that focused flow declines channel design, and comprise 1 aqueous phase A introduction passage, 2 oil phase introduction passages and 1 water-in-oil type microlayer model and generate chamber, they generate channel connection by 1 right-angled intersection focused flow microlayer model; Also comprise 2 aqueous phase B entrances, match with capping layer;
Described hydrophilic chip layer is that focused flow declines channel design, comprise 1 microlayer model introduction passage, 2 aqueous phase B introduction passages and 1 water-in-oil type multicomponent microlayer model and generate chamber, they generate channel connection by 1 right-angled intersection focused flow water-in-oil type multicomponent microlayer model;
Described basalis comprises 1 water-in-oil type multicomponent microlayer model and collects outlet.
Another preferred embodiment in, described capping layer comprises the reagent inlet that 5 diameters are about 2-4mm;
In described hydrophobic chip layer, the size of aqueous phase A introduction passage is about (10-20mm) × (2-4mm), the size of 2 oil phase introduction passages is about (10-20mm) × (2-4mm), the size of 1 water-in-oil type microlayer model generation chamber is about (10-20mm) × (2-4mm), and the width that focused flow microlayer model generates passage is about 0.5-1mm; The diameter of 2 aqueous phase B entrances is all about 2-4mm;
In described hydrophilic chip layer, the size of 1 microlayer model introduction passage is about (5-10mm) × (2-4mm), the size of 2 aqueous phase B introduction passages is about (10-20mm) × (2-4mm), the size of 1 water-in-oil type multicomponent microlayer model generation chamber is about (10-30mm) × (2-4mm), and the width that focused flow water-in-oil type multicomponent microlayer model generates passage is about 0.5-1mm;
In described basalis, 1 water-in-oil type multicomponent microlayer model is collected the diameter exported and is about 2-4mm;
The thickness of described capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis is all about 1-2mm.
Another preferred embodiment in, the size of described multicomponent microlayer model micro-fluidic chip is about (100-150mm) × (60-100mm); Prepared by the polymeric material being selected from lower group by one or more: polymethyl methacrylate, dimethyl silicone polymer and polystyrene.
Another preferred embodiment in, the operation principle of described multicomponent microlayer model micro-fluidic chip is: use external pump valve system respectively aqueous phase solution A, aqueous phase B solution, oil-phase solution to be injected chip from the entrance of correspondence, aqueous phase A is cut into a series of microlayer model by oil phase in hydrophobic chip layer, subsequently, described microlayer model is cut into the water-in-oil type multicomponent microlayer model of uniform particle sizes further in hydrophilic chip layer by follow-up aqueous phase B, and finally derives collection from outlet; Wherein, the flow-rate ratio of described aqueous phase solution A, oil-phase solution and aqueous phase B solution is about 1:(4-5): (20-30).
On the other hand, the invention provides a kind of processing method of multicomponent microlayer model micro-fluidic chip, the method comprises the following steps:
I (), by stacked successively to capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis, forms the channel network configuration of interior three-dimensional, and the Primary Location utilizing ultraviolet cured adhesive to carry out between each layer; And
(ii) each layer after Primary Location is carried out thermocompression bonding, form the multicomponent microlayer model micro-fluidic chip be made up of capping layer stacked successively, hydrophobic chip layer, hydrophilic chip layer and basalis.
In one preferred embodiment, the method is further comprising the steps of: described capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis are all utilized CO 2laser engraving machine is processed, and processes rear Ultrasonic Cleaning, dry for standby, wherein,
Control Laser Processing power and the speed of each layer respectively, wherein, Laser Processing power when processing capping layer and basalis controls at 90-100%, and process velocity controls at 50-60%; Laser Processing power when processing hydrophobic chip layer and hydrophilic chip layer controls at 70-80%, and process velocity controls at 90-100%; The Ultrasonic Cleaning time is 5-10 minute.
Another preferred embodiment in, the method is further comprising the steps of: use sol-gel process surface hydrophilic modification is carried out to described hydrophilic chip layer, modification procedure is as follows:
(1) chip layer of non-modified is carried out ultrasonic cleaning, dry for standby;
(2) chip layer obtained in step (1) is put into isopropyl alcohol to embathe, taking-up is dried;
(3) chip layer obtained in step (2) is put into teos solution, soak time is no less than 3 hours; And
(4) chip layer obtained in step (3) is taken out from teos solution, also dry with deionized water rinsing.
Another preferred embodiment in, described teos solution is by ethyl orthosilicate, deionized water, watery hydrochloric acid and isopropyl alcohol by volume about (1-2): (3-4): (1-2): (2-4) mixes, wherein watery hydrochloric acid concentration is 0.1-0.15mol/L.
Another preferred embodiment in, the described UV-irradiation time is 1-2 minute; Thermocompression bonding temperature controls between 80-90 DEG C, hot pressing for several times, each hot pressing 30-60 second.
Accompanying drawing explanation
Fig. 1 is the perspective exploded view according to multicomponent microlayer model micro-fluidic chip of the present invention.
Fig. 2 prepares the cross section structure of Water-In-Oil oil-in (O/W/O) multicomponent microlayer model micro-fluidic chip and the schematic diagram of drop formation according to of the present invention.
Detailed description of the invention
Present inventor finds after extensive and deep research, for in microlayer model facture of microchip technique in prior art about microchannel processing and the key technology difficult problem such as chip bonding, the multicomponent microlayer model of preparation complexity cannot be made can to realize on one piece of micro-fluidic chip, by forming micro-fluidic chip by stacked for four-layer structure by thermocompression bonding, wherein this micro-fluidic chip comprises capping layer, hydrophobic chip layer, hydrophilic chip layer, basalis; Capping layer comprises 3 aqueous phase entrances and 2 oil phase entrances; Hydrophobic chip layer is provided with focused flow and declines channel design and 2 aqueous phase entrances matching with capping layer; Hydrophilic chip layer is provided with the focused flow identical with hydrophobic chip layer and declines channel design, and carries out hydrophilic modifying process by sol-gel process to chip surface; Basalis is provided with 1 multicomponent microlayer model and collects outlet, can realize the continuous production of water-in-oil type multicomponent microlayer model, has the features such as with low cost, processing is simple, technique environmental protection simultaneously; By changing the surperficial hydrophobe characteristic of chip layer and the component of each phase solution, the preparation of Water-In-Oil oil-in (O/W/O) multicomponent microlayer model more can be realized, significant in the preparation of multicomponent drop and labyrinth particulate.Based on above-mentioned discovery, the present invention is accomplished.
In a first aspect of the present invention, provide a kind of multicomponent microlayer model micro-fluidic chip, it is made up of capping layer stacked successively, hydrophobic chip layer, hydrophilic chip layer and basalis.
Preferably, described micro-fluidic chip can be prepared from by one or more in the polymeric materials such as polymethyl methacrylate, dimethyl silicone polymer, polystyrene.
Preferably, described micro-fluidic chip size is about (100-150mm) × (60-100mm), preferred 100mm × 60mm.
Preferably, the thickness of described capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis is all about 1-2mm, preferred 2mm.
Preferably, described capping layer comprises 5 reagent inlet, i.e. 1 aqueous phase A entrance, 2 aqueous phase B entrances, and 2 oil phase entrances.
Preferably, described hydrophobic chip layer is that focused flow declines channel design, and comprise 1 aqueous phase A introduction passage, 2 oil phase introduction passages and 1 water-in-oil type microlayer model and generate chamber, they generate channel connection by 1 right-angled intersection focused flow microlayer model; Also comprise 2 aqueous phase B entrances, match with capping layer.
Preferably, described hydrophilic chip layer is that focused flow declines channel design, comprise 1 microlayer model introduction passage, 2 aqueous phase B introduction passages and 1 water-in-oil type multicomponent microlayer model and generate chamber, they generate channel connection by 1 right-angled intersection focused flow water-in-oil type multicomponent microlayer model.
Preferably, described basalis comprises 1 water-in-oil type multicomponent microlayer model collection outlet.
Preferably, described capping layer comprises 5 diameters and is about 2-4mm, the reagent inlet of preferred 4mm.
Preferably, in described hydrophobic chip layer, the size of aqueous phase A introduction passage is about (10-20mm) × (2-4mm), preferred 20mm × 4mm, the size of 2 oil phase introduction passages is about (10-20mm) × (2-4mm), preferred 20mm × 4mm, the size of 1 water-in-oil type microlayer model generation chamber is about (10-20mm) × (2-4mm), preferred 20mm × 4mm, the width that focused flow microlayer model generates passage is about 0.5-1mm, preferred 1mm; The diameter of 2 aqueous phase B entrances is all about 2-4mm, preferred 4mm.
Preferably, in described hydrophilic chip layer, the size of 1 microlayer model introduction passage is about (5-10mm) × (2-4mm), preferred 10mm × 4mm, the size of 2 aqueous phase B introduction passages is about (10-20mm) × (2-4mm), preferred 20mm × 4mm, the size of 1 water-in-oil type multicomponent microlayer model generation chamber is about (10-30mm) × (2-4mm), preferred 30mm × 4mm, the width that focused flow water-in-oil type multicomponent microlayer model generates passage is about 0.5-1mm, preferred 1mm.
Preferably, in described basalis, 1 water-in-oil type multicomponent microlayer model is collected the diameter exported and is about 2-4mm, preferred 4mm.
The operation principle of multicomponent microlayer model micro-fluidic chip of the present invention is: use external pump valve system respectively aqueous phase solution A, aqueous phase B solution, oil-phase solution to be injected chip from the entrance of correspondence, aqueous phase A is cut into a series of microlayer model by oil phase in hydrophobic chip layer, subsequently, described microlayer model is cut into the water-in-oil type multicomponent microlayer model of uniform particle sizes further in hydrophilic chip layer by follow-up aqueous phase B, and finally derives collection from outlet; Wherein, the flow-rate ratio of described aqueous phase solution A, oil-phase solution and aqueous phase B solution is about 1:(4-5): (20-30), preferred 1:5:20.
In a second aspect of the present invention, provide a kind of processing method of multicomponent microlayer model micro-fluidic chip, the method comprises the following steps:
I (), by stacked successively to capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis, forms the channel network configuration of interior three-dimensional, and the Primary Location utilizing ultraviolet cured adhesive to carry out between each layer; And
(ii) each layer after Primary Location is carried out thermocompression bonding, form the multicomponent microlayer model micro-fluidic chip be made up of capping layer stacked successively, hydrophobic chip layer, hydrophilic chip layer and basalis.
Preferably, the method is further comprising the steps of: described capping layer, hydrophobic chip layer, hydrophilic chip layer and basalis are all utilized CO 2laser engraving machine is processed, and processes rear Ultrasonic Cleaning, dry for standby.
Preferably, need the Laser Processing power and the speed that control each layer respectively, wherein, Laser Processing power when processing capping layer and basalis controls at 90-100%, and process velocity controls at 50-60%; Laser Processing power when processing hydrophobic chip layer and hydrophilic chip layer controls at 70-80%, and process velocity controls at 90-100%.
Preferably, the Ultrasonic Cleaning time is 5-10 minute.
Preferably, the method is further comprising the steps of: use sol-gel process to carry out surface hydrophilic modification to described hydrophilic chip layer, modification procedure is as follows:
(1) chip layer of non-modified is carried out ultrasonic cleaning, dry for standby;
(2) chip layer obtained in step (1) is put into isopropyl alcohol to embathe, taking-up is dried;
(3) chip layer obtained in step (2) is put into teos solution, soak time is no less than 3 hours; And
(4) chip layer obtained in step (3) is taken out from teos solution, also dry with deionized water rinsing.
Preferably, described teos solution is by ethyl orthosilicate, deionized water, watery hydrochloric acid and isopropyl alcohol by volume about (1-2): (3-4): (1-2): (2-4), preferred 1:4:1.5:4 mixes, and wherein watery hydrochloric acid concentration is 0.1-0.15mol/L.
Preferably, the described UV-irradiation time is 1-2 minute.
Preferably, thermocompression bonding temperature controls between 80-90 DEG C, hot pressing for several times, each hot pressing 30-60 second.
Below referring to accompanying drawing.
Fig. 1 is the perspective exploded view according to multicomponent microlayer model micro-fluidic chip of the present invention.As shown in Figure 1, capping layer A is processed with aqueous phase A entrance a, aqueous phase B entrance m, oil phase entrance g; Hydrophobic chip layer B is processed with oil phase introduction passage b, aqueous phase A introduction passage c, water-in-oil type microlayer model generates chamber d, aqueous phase B entrance k, focused flow microlayer model generates passage l; Hydrophilic chip layer C is processed with aqueous phase B introduction passage e, water-in-oil type microlayer model introduction passage f, water-in-oil type multicomponent microlayer model generates chamber i, focused flow water-in-oil type multicomponent microlayer model generates passage j; Basalis D is processed with water-in-oil type multicomponent microlayer model and collects outlet h.
Fig. 2 prepares the cross section structure of Water-In-Oil oil-in (O/W/O) multicomponent microlayer model micro-fluidic chip and the schematic diagram of drop formation according to of the present invention.As shown in Figure 2, described micro-fluidic chip is made up of capping layer A stacked successively, hydrophobic chip layer B, hydrophilic chip layer C and basalis D; Oil phase and the deionized water that is added with water soluble dyestuffs are carried out high-speed stirred and as aqueous phase A using volume ratio 1:4; Three syringe pumps are used respectively aqueous phase A, oil phase, aqueous phase B to be injected micro-fluidic chip of the present invention with flow-rate ratio 1:5:25 by the solution inlet of correspondence; In hydrophobic chip layer B, oil phase shears aqueous phase A from both sides, and being sheared by aqueous phase A becomes a series of water-in-oil type microlayer model; This water-in-oil type microlayer model generates the hydrophilic chip layer C of chamber with continuous phase inflow lower floor by the microlayer model in hydrophobic chip layer B, and under the shear action of aqueous phase B, the final O/W/O microlayer model forming uniform particle sizes; This O/W/O microlayer model is collected outlet from the drop of micro-fluidic chip basalis D and is flowed out, and conduit or beaker etc. can be used to carry out the collection of drop.
Major advantage of the present invention is:
(1) chip material that the present invention is used is organic polymer, have that cost is low, lightweight, transparency is high, and the feature such as good resistance to ag(e)ing, corrosion resistance and machining property, can with at a high speed online microscope experiment platform coupling, convenient real-time observation and manipulation are carried out to sample.
(2) processing technology of micro-fluidic chip microchannel involved in the present invention is laser engraving method, and simple to operate, flexibility is high, at the MCA of chip material surface engraving complexity, and can ensure the size of microchannel.
(3) the chip layer hydrophilic modifying process that the present invention relates to utilizes sol-gel process, easy to operate, effective, and can realize the modification to chip layer local.By changing the hydrophilic and hydrophobic on different flaggy surface, not only can prepare water-in-oil type or oil-in-water type multicomponent microlayer model, and the preparation of O/W/O multicomponent microlayer model or more complicated microlayer model structure can be realized.
embodiment
The present invention is set forth further below in conjunction with specific embodiment.But, should be understood that these embodiments only do not form limitation of the scope of the invention for illustration of the present invention.The test method of unreceipted actual conditions in the following example, usually conveniently condition, or according to the condition that manufacturer advises.Except as otherwise noted, all percentage and number are by weight.
embodiment 1: the micro-fluidic chip of preparation O/W/O multicomponent microlayer model
This multicomponent microlayer model micro-fluidic chip uses laser engraving to be prepared from conjunction with sol-gel surface modification and thermocompression bonding method by polymethyl methacrylate base sheet, and its structure as shown in Figure 1.
Above-mentioned micro-fluidic chip is utilized to prepare Water-In-Oil oil-in (O/W/O) multicomponent microlayer model.Preparation process as shown in Figure 2.Oil phase (normal octane) and the deionized water that is added with water soluble dyestuffs (0.1% methyl orange solution) are carried out high-speed stirred (for 25000rpm, mixing time is 5 minutes to mixing speed) with volume ratio 1:4 and as aqueous phase A.Use three syringe pumps respectively by aqueous phase A, oil phase (normal octane), aqueous phase B (deionized water) with flow-rate ratio 1:5:25 by micro-fluidic chip described in the solution inlet of correspondence; In hydrophobic chip layer, oil phase shears aqueous phase A from both sides, and being sheared by aqueous phase A becomes a series of water-in-oil type microlayer model; This water-in-oil type microlayer model generates the hydrophilic chip layer of chamber with continuous phase inflow lower floor by the microlayer model in hydrophobic chip layer, and under the shear action of aqueous phase B, the final O/W/O multicomponent microlayer model forming uniform particle sizes; This O/W/O multicomponent microlayer model is collected outlet from the drop of micro-fluidic chip basalis and is flowed out, and uses conduit or beaker etc. to carry out the collection of drop.
embodiment 2: the micro-fluidic chip of preparation O/W/O multicomponent magnetic response microlayer model
By Fe 3o 4nano particle (3g) and deionized water (5mL) carry out high-speed stirred, and mixing speed is 18000rpm, and mixing time is 5 minutes, obtains aqueous phase A.1 of surfactant castor oil polyglycerol ester PGPR90 (Shanghai Aladdin biochemical technology limited company) will be added with, 6-hexanediyl ester solution (1,6-hexanediyl ester solution 10mL, PGPR900.5g) as oil phase, be added with glycerin solution (the deionized water 20mL of surfactant F-127 (Sigma-AldrichCo.LLC.), glycerine 1g, F-1270.2g) as aqueous phase B.Three syringe pumps are used respectively above-mentioned aqueous phase A, oil phase, aqueous phase B to be injected this micro-fluidic chip with velocity ratio 1:4:16; In hydrophobic chip layer, aqueous phase A is become a series of by oil phase shearing and includes Fe 3o 4the microlayer model of nano particle; Above-mentioned microlayer model generates the hydrophilic chip layer of chamber with continuous phase oil phase inflow lower floor by the microlayer model in hydrophobic chip layer, and under the shear action of aqueous phase B, the final O/W/O multicomponent magnetic response microlayer model forming uniform particle sizes.Experiment proves, this O/W/O multicomponent magnetic response microlayer model has good magnetic response characteristic.
embodiment 3: the micro-fluidic chip preparing porous polymer microsphere
Ammonium bicarbonate soln (the deionized water 5mL of surfactant F-127 (Sigma-AldrichCo.LLC.) will be added with, carbonic hydroammonium 0.75g, F-1270.05g) as aqueous phase A, be added with GDMA EGDMA (Shanghai Aladdin biochemical technology limited company) solution (the GDMA 10mL of surfactant castor oil polyglycerol ester PGPR90 (Shanghai Aladdin biochemical technology limited company) and light trigger HMPP (Shanghai Aladdin biochemical technology limited company), PGPR900.5g, HMPP0.1g) as oil phase, be added with glycerin solution (the deionized water 20mL of surfactant F-127, glycerine 1g, F-1270.2g) as aqueous phase B.Three syringe pumps are used respectively above-mentioned aqueous phase A, oil phase, aqueous phase B to be injected this micro-fluidic chip with velocity ratio 1:5:20; In hydrophobic chip layer, aqueous phase A is sheared by oil phase becomes a series of water-in-oil type microlayer model; Above-mentioned microlayer model generates the hydrophilic chip layer of chamber with continuous phase oil phase inflow lower floor by the microlayer model in hydrophobic chip layer, and under the shear action of aqueous phase B, the final O/W/O multicomponent microlayer model forming uniform particle sizes; This O/W/O multicomponent microlayer model is collected outlet from the drop of micro-fluidic chip basalis and is flowed out, and uses and is added with the collection that the culture dish accepting phase (deionized water 20mL, glycerine 1g, F-1270.2g) with aqueous phase B same composition carries out drop.Subsequently, this O/W/O multicomponent microlayer model to be placed on thermostatic platform ultraviolet light (400W, 365nm) under 45 degree of constant temperatures and to irradiate 30 minutes.Finally, the porous polymer microsphere of uniform particle sizes is obtained with washed with de-ionized water drying, average grain diameter 870 μm.
Use micro-fluidic chip provided by the invention and processing technology thereof can realize the continuous production of water-in-oil type multicomponent microlayer model, thus improve the production efficiency of water-in-oil type multicomponent microlayer model significantly.Micro-fluidic chip provided by the present invention and processing technology thereof, except having the features such as with low cost, processing is simple, technique environmental protection, more can prepare requirement in conjunction with different drops, surface modification is carried out to the local of chip layer or chip layer, prepares needs with what meet multicomponent drop and labyrinth particulate.
Above-mentioned listed embodiment is only preferred embodiment of the present invention, is not used for limiting practical range of the present invention.Namely all equivalences done according to the content of the present patent application the scope of the claims change and modify, and all should be technology category of the present invention.
The all documents mentioned in the present invention are quoted as a reference all in this application, are just quoted separately as a reference as each section of document.In addition should be understood that those skilled in the art can make various changes or modifications the present invention, and these equivalent form of values fall within the application's appended claims limited range equally after having read above-mentioned instruction content of the present invention.

Claims (10)

1. a multicomponent microlayer model micro-fluidic chip, it is made up of capping layer (A) stacked successively, hydrophobic chip layer (B), hydrophilic chip layer (C) and basalis (D).
2. multicomponent microlayer model micro-fluidic chip as claimed in claim 1, it is characterized in that, described capping layer (A) comprises 5 reagent inlet, i.e. 1 aqueous phase A entrance (a), 2 aqueous phase B entrance (m), and 2 oil phases entrance (g);
Described hydrophobic chip layer (B) to decline channel design for focused flow, comprise 1 aqueous phase A introduction passage (c), 2 oil phases introduction passage (b) and 1 water-in-oil type microlayer model and generate chamber (d), they generate passage (l) by 1 right-angled intersection focused flow microlayer model and are communicated with; Also comprise 2 aqueous phase B entrance (k), match with capping layer (A);
Described hydrophilic chip layer (C) to decline channel design for focused flow, comprise 1 microlayer model introduction passage (f), 2 aqueous phase B introduction passage (e) and 1 water-in-oil type multicomponent microlayer model and generate chamber (i), they generate passage (j) by 1 right-angled intersection focused flow water-in-oil type multicomponent microlayer model and are communicated with;
Described basalis (D) comprises 1 water-in-oil type multicomponent microlayer model and collects outlet (h).
3. multicomponent microlayer model micro-fluidic chip as claimed in claim 2, it is characterized in that, it is the reagent inlet of 2-4mm that described capping layer (A) comprises 5 diameters;
In described hydrophobic chip layer (B), aqueous phase A introduction passage (c) is of a size of (10-20mm) × and (2-4mm), 2 oil phases introduction passage (b) are of a size of (10-20mm) × (2-4mm), 1 water-in-oil type microlayer model generates chamber (d) and is of a size of (10-20mm) × (2-4mm), and the width that focused flow microlayer model generates passage (l) is 0.5-1mm; The diameter of 2 aqueous phase B entrance (k) is 2-4mm;
In described hydrophilic chip layer (C), 1 microlayer model introduction passage (f) is of a size of (5-10mm) × (2-4mm), 2 aqueous phase B introduction passage (e) are of a size of (10-20mm) × (2-4mm), 1 water-in-oil type multicomponent microlayer model generates chamber (i) and is of a size of (10-30mm) × (2-4mm), and the width that focused flow water-in-oil type multicomponent microlayer model generates passage (j) is 0.5-1mm;
In described basalis (D), it is 2-4mm that 1 water-in-oil type multicomponent microlayer model collects the diameter exporting (h);
The thickness of described capping layer (A), hydrophobic chip layer (B), hydrophilic chip layer (C) and basalis (D) is 1-2mm.
4. the multicomponent microlayer model micro-fluidic chip according to any one of claim 1-3, is characterized in that, it is of a size of (100-150mm) × (60-100mm); Prepared by the polymeric material being selected from lower group by one or more: polymethyl methacrylate, dimethyl silicone polymer and polystyrene.
5. the multicomponent microlayer model micro-fluidic chip according to any one of claim 1-3, it is characterized in that, the operation principle of described multicomponent microlayer model micro-fluidic chip is: use external pump valve system respectively by aqueous phase solution A, aqueous phase B solution, oil-phase solution injects chip from the entrance of correspondence, aqueous phase A is cut into a series of microlayer model by oil phase in hydrophobic chip layer (B), subsequently, described microlayer model is cut into the water-in-oil type multicomponent microlayer model of uniform particle sizes further in hydrophilic chip layer (C) by follow-up aqueous phase B, and finally derive collection from outlet, wherein, the flow-rate ratio of described aqueous phase solution A, oil-phase solution and aqueous phase B solution is 1:(4-5): (20-30).
6. a processing method for multicomponent microlayer model micro-fluidic chip, the method comprises the following steps:
I () is by stacked successively to capping layer (A), hydrophobic chip layer (B), hydrophilic chip layer (C) and basalis (D), form the channel network configuration of interior three-dimensional, and the Primary Location utilizing ultraviolet cured adhesive to carry out between each layer; And
(ii) each layer after Primary Location is carried out thermocompression bonding, form the multicomponent microlayer model micro-fluidic chip be made up of capping layer (A) stacked successively, hydrophobic chip layer (B), hydrophilic chip layer (C) and basalis (D).
7. method as claimed in claim 6, it is characterized in that, the method is further comprising the steps of: described capping layer (A), hydrophobic chip layer (B), hydrophilic chip layer (C) and basalis (D) are all utilized CO 2laser engraving machine is processed, and processes rear Ultrasonic Cleaning, dry for standby, wherein,
Control Laser Processing power and the speed of each layer respectively, wherein, Laser Processing power during processing capping layer (A) and basalis (D) controls at 90-100%, and process velocity controls at 50-60%; Laser Processing power when processing hydrophobic chip layer (B) and hydrophilic chip layer (C) controls at 70-80%, and process velocity controls at 90-100%; The Ultrasonic Cleaning time is 5-10 minute.
8. method as claimed in claim 6, it is characterized in that, the method is further comprising the steps of: use sol-gel process to carry out surface hydrophilic modification to described hydrophilic chip layer (C), modification procedure is as follows:
(1) chip layer of non-modified is carried out ultrasonic cleaning, dry for standby;
(2) chip layer obtained in step (1) is put into isopropyl alcohol to embathe, taking-up is dried;
(3) chip layer obtained in step (2) is put into teos solution, soak time is no less than 3 hours; And
(4) chip layer obtained in step (3) is taken out from teos solution, also dry with deionized water rinsing.
9. method as claimed in claim 8, it is characterized in that, described teos solution is by ethyl orthosilicate, deionized water, watery hydrochloric acid and isopropyl alcohol by volume (1-2): (3-4): (1-2): (2-4) mixes, wherein watery hydrochloric acid concentration is 0.1-0.15mol/L.
10. the method according to any one of claim 6-9, is characterized in that, the described UV-irradiation time is 1-2 minute; Thermocompression bonding temperature controls between 80-90 DEG C, hot pressing for several times, each hot pressing 30-60 second.
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