CN101590389A - Drop formation and catching method and application thereof based on three-layer sandwich disc-type chip - Google Patents
Drop formation and catching method and application thereof based on three-layer sandwich disc-type chip Download PDFInfo
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- CN101590389A CN101590389A CNA2009100122031A CN200910012203A CN101590389A CN 101590389 A CN101590389 A CN 101590389A CN A2009100122031 A CNA2009100122031 A CN A2009100122031A CN 200910012203 A CN200910012203 A CN 200910012203A CN 101590389 A CN101590389 A CN 101590389A
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Abstract
A kind of drop formation and catching method and application thereof based on three-layer sandwich disc-type chip, designed a kind of by the main channel, the chip of the geometry micro-structural that wing passage and capture region are formed utilizes the interior capillary difference of passage of different in width to induce the original position of drop to form and catch; The invention has the advantages that and adopt a kind of simple structure to realize that the original position of drop forms and catches; The formation of drop does not need to use surfactant, has avoided the influence of surfactant to the drop internal reaction; The formation of drop is not subjected to the influence of channel surface character, can realize oil-in-water drop on the PDMS of unmodified chip; The formation of drop does not need fluid flow rate to control accurately, and the mode that the mobile employing liquid storage tank of fluid vacuumizes has been avoided the use of precise injection pump, has reduced the cost of experiment; The drop of catching has been realized the chemical reaction of solution-air two-phase first as the array microreactor in drop.
Description
Technical field
The present invention relates to the micro-fluidic chip technology, a kind of drop formation and catching method and application thereof based on three-layer sandwich disc-type chip is provided especially.
Background technology
Micro-fluidic chip is a kind of emerging scientific and technical platform, and it relies on more than one square centimeters chip, forms network by the microchannel, runs through whole system with controlled fluid, can replace the various functions of conventional chemical or biology laboratory.Its essential characteristic is that consumption sample amount is extremely low, and sample treatment speed is fast, comprise the multiple monotechnics of reaction, detection can be on small platform flexible combination, scale integrated.Develop so far, the field that micro-fluidic chip relates to is more and more wider, constantly derives from the branch that makes new advances.
A kind of drop (droplet) technology recently grows up on micro-fluidic chip, the basic point of this technology is to utilize immiscible two phase flow, under the effect of hydrodynamic shear and interfacial tension, wherein one be dispersed in mutually another mutually in, form a series of monodispersed drops, each drop comprises specific chemical reaction or biological respinse, forms parallel microreactor.Have the rapid mixing of reactant based on the microreactor of drop, the accurate control in reaction time, high flux, advantages such as small size are potential high flux screening platforms.But the quick flowability of drop has increased the detection difficulty of drop, particularly needs monitoring reaction in real time, needs the analysis of dynamics data.At the problem that exists, the capture technique of drop more and more is much accounted of recently.At present the capture technique of drop mainly is based on catching of physical dimension, and the stream of liquid droplets that the upstream produces under the effect of various power, enters capture region when capture region, is characterized in that drop produces earlier, after catch.This characteristics have determined the accurately size and the capture region coupling of control drop, cross conference and cause drop can not enter capture region, too small then can catching incessantly.In addition, the minor fluctuations of rate of flow of fluid can cause the variation of drop size, causes the capture rate of drop low.
Set up and a kind ofly simply, the droplet capture method becomes exigence efficiently especially the needs real-time online is detected, need the analysis of kinetic parameter.
At present the reaction of carrying out in the drop mainly is a liquid-liquid reactions, comprising: enzyme reaction, nano material or micro particulate materials synthetic, crystallization of protein etc.; Reason that gas-liquid reaction in the drop not have to realize is that oil phase has been blocked contacting of gas phase and water, reacts to be difficult to generation.How to allow the interior water of drop fully contact, become the bottleneck of realizing gas-liquid reaction in the drop with gas phase.
Summary of the invention
Having the purpose of this invention is to provide a kind of drop based on three-layer sandwich disc-type chip forms and catches and use.
The invention provides a kind of three-layer sandwich disc-type chip, this chip is made up of upper, middle and lower-ranking; The upper strata is the chip with how much micro-structurals, is made up of liquid storage tank 1, liquid storage tank 2, how much micro-structurals; The middle level is a thin layer; Lower floor is the gas passage chip; Described how much micro-structurals are by the main channel, and wing passage and capture region are formed.
Three-layer sandwich disc-type chip provided by the invention, the material on described chip upper strata is a glass, and middle layer film is high polymer (preferred PDMS), and the material of chip lower floor is a glass.
The present invention also provides a kind of method that forms and catch based on the drop of three-layer sandwich disc-type chip, and concrete steps are as follows:
The PDMS-glass hybridization hybrid chip that will have how much micro-structurals outgased in vacuum desiccator 3-5 minute, took out then, added water in liquid storage tank 1, take out vacuum in the liquid storage tank 2, make the aqueous solution be full of the main channel, leave standstill, under the ventilative effect of PDMS, the aqueous solution enters capture region, treat that capture region is full of after, vacuumize at liquid storage tank 2, solution in the main channel is taken away, add oil phase then in liquid storage tank 1, oil phase soaks into the main channel, forms water in oil drop;
Oil-in-water drop formation method is the same substantially on the PDMS-glass hybridization hybrid chip, because water does not soak into PDMS, after the oil phase in the main channel is taken away, adds water in liquid storage tank 1, vacuumizes at liquid storage tank 2 then, impels water sealing oil droplet.
The method that forms and catch based on the drop of three-layer sandwich disc-type chip provided by the invention can form different big or small drops easily by the area that changes capture region, and the size height of the size of drop and capture region is consistent; By changing the shape of capture region, the shape of the drop of formation also can change accordingly, can form circle, square, polygon and irregular shape or the like.
The method that forms and catch based on the drop of three-layer sandwich disc-type chip provided by the invention, by using a plurality of array drops to form the eccentric circle disc type chip of unit, with centrifugal force is driving force, in close each liquid storage tank in the center of circle, add the different aqueous solution of component, the method that adopts above-mentioned drop to form and catch, the array drop of formation different component.
Chip application provided by the invention is in the formation of pH gradient and the gas-liquid reaction in the drop.
The formation of pH gradient provided by the invention, concrete steps are as follows: with the pH indicator is water, fluorinated oil Fc40 is an oil phase, forms the drop of pH indicator on the chip upper strata, continues to feed NH then in the lower floor gas passage
3, NH
3See through the PDMS film and enter drop, and with drop in indicator reaction, the alkalescence of drop increases, and darkens; Along with the increase of ammonia diffusion length, the concentration of ammonia reduces, and the ammonia amount that drop absorbs reduces, and the increasing degree of alkalescence reduces, and forming with the drop directly over the gas passage is the center, the pH gradient that gradually changes to the both sides drop.
The formation of pH gradient provided by the invention, described pH indicator is for to mix concentration 0.05～0.5mol/L (being preferably 0.25mol/L) methyl red aqueous solution, concentration 0.05～0.5mol/L (being preferably 0.25mol/L) bromocresol green aqueous solution and 0.05～0.5mol/L (being preferably 0.25mol/L) bromthymol blue aqueous solution 1: 1: 1 by volume～1: 1: 30 (being preferably 1: 1: 30), be adjusted to acidity with hydrochloric acid, be the pH indicator.
The present invention adopts three-layer sandwich disc-type chip, reaction reagent is dispersed into the drop array, formation comprises the array microreactor of reaction reagent, the reaction reagent of different component is dispersed into different drop arrays, lower floor's passage feeds the reagent that another kind participates in reaction, diffuses into participation reaction in the array microreactor through striding film.
Gas-liquid reaction in the drop provided by the invention, concrete steps are as follows: adopting different metal ion salt solutions is water, and Fc40 is an oil phase, the array drop of the different component of formation with stride gas (ammonia, HCl, the H that film spreads
2O
2Deng) complex reaction takes place, realized the gas-liquid reaction in the drop.
Advantage of the present invention:
1, adopt a kind of simple structure to realize that the original position of drop forms and catches;
2, drop forms the accurate control that does not need fluid flow rate, has avoided the use of precise injection pump;
3, do not need to add surfactant in the drop forming process, avoided the influence of surfactant;
4, drop forms does not need chip channel is carried out surface treatment, can realize oil-in-water drop on the PDMS of unmodified chip;
5, catching of drop do not need to control drop size and is complementary the capture rate height with capture region;
6, make gas and water mediate contact by the PDMS film, realized the gas liquid reaction in the microfluidic chip liquid drop first;
7, on chip piece, a plurality of reactants have been realized, the gas-liquid reaction of a plurality of concentration.
Description of drawings
Fig. 1 PDMS-glass hybridization hybrid chip schematic diagram, wherein: 1,2 is liquid storage tank, and 3 is the main channel, and 4 is capture region, and 5 is wing passage;
The geometry micro-structural schematic diagram that Fig. 2 drop forms and catches, wherein: 1 is wing passage, and 2 is capture region, and 3 is the main channel;
The process generalized section that Fig. 3 drop forms and catches, wherein: a represents the PDMS chip, and b represents glass substrate, and A represents water, and B represents air, and C represents oil phase, and 1 represents the main channel, and 2 represent capture region;
The process that Fig. 4 drop forms and catches photo in kind, wherein: A represents air, and B represents methylene blue solution, and C represents mineral oil;
Array drop (Water-In-Oil) photo in kind of the different sizes of Fig. 5, shape;
Array drop (oil-in-water) photo in kind of the different sizes of Fig. 6, shape;
The disk chip of Fig. 7 multicomponent array drop and array drop photo in kind;
Fig. 8 three-layer sandwich disc-type chip schematic diagram, wherein on behalf of the upper strata drop, A form and capturing unit, and B represents middle level PDMS film, and C represents the lower floor gas passage;
The pH gradient that Fig. 9 forms on three-layer sandwich disc-type chip photo in kind;
Figure 10 NiCl
2Drop and ammonia gas react result's photo in kind;
Figure 11 CuSO
4Drop and ammonia gas react result's photo in kind;
Figure 12 Fe (NO
3)
3Drop and ammonia gas react result's photo in kind.
The specific embodiment
Following examples will give further instruction to the present invention, but not thereby limiting the invention.
The original position of embodiment 1 array drop forms and catches
PDMS chip shown in Figure 1 is put into vacuum desiccator, vacuum outgas 3-5 minute, take out the back and in liquid storage tank 1, add aqueous solution of methylene blue, take out at liquid storage tank 2 usefulness vavuum pumps, aqueous solution of methylene blue is full of the main channel, the air bubble of formation capture region (see Fig. 3-1,4-1), because PDMS has gas permeability, the air of capture region slowly enters the PDMS body, methylene blue solution in the main channel is full of capture region (seeing Fig. 3-2, Fig. 4-2) gradually, treat that the blue solution of subunit is full of capture region fully after, vacuumize at liquid storage tank 2, the blue solution of subunit in the main channel is taken away, and the blue solution of the subunit of capture region forms water droplet (seeing Fig. 3-3, Fig. 4-3), and then add mineral oil in the liquid storage tank 1, mineral oil is full of the main channel under capillarity, form water in oil drop (seeing Fig. 3-4, Fig. 4-4).By changing the interpolation order of water and oil phase, can form water in oil drop (see figure 5) and oil-in-water drop (see figure 6) respectively.Employing has the disc-type chip that a plurality of array drops form the unit, can form the array drop (see figure 7) of multiple different component.
The formation of pH gradient in the embodiment 2 array drops
Three-layer sandwich disc-type chip shown in Figure 8 is put into vacuum desiccator, vacuum outgas 3-5 minute, take out the back and in the close liquid storage tank in the center of circle, add the pH indicator solution, take out with vavuum pump at liquid storage tank away from the center of circle, the pH indicator solution enters the main channel, leaves standstill to treat that the pH indicator solution is full of capture region, then with centrifugal 55 seconds of chip (2500 rev/mins), and then add Fc40 (fluorinated oil) respectively in the close liquid storage tank in the center of circle, form the pH indicator solution drop of Fc40 parcel.Lower floor's passage continues to feed ammonia, strides the ammonia and the reaction of pH indicator solution of film diffusion, causes pH indicator solution change color (see figure 9).Because the pH indicator solution is to the absorption of ammonia, the concentration of ammonia reduces along dispersal direction, causes the ammonia amount difference of pH indicator solution drop absorption, has formed the graded of color, i.e. the graded (see figure 9) of pH.
The complex reaction of multiple metal ion and ammonia in the embodiment 3 array drops
Adopt chip shown in Figure 8 and embodiment 2 described methods, form NiCl respectively
2/ Fc40, CuSO
4/ Fc40 and Fe (NO
3)
3/ Fc40 array drop, in lower floor's passage, continue to feed ammonia, the ammonia of striding the film diffusion is absorbed by metal salt solution, with metal ion generation complex reaction, the ammonia amount difference that each drop absorbs, the crystal that has caused forming metal ion-ammonia complex (is seen Figure 10-3,10-4), different shapes such as solution, precipitation (see Figure 10,11,12).
Claims (10)
1, a kind of three-layer sandwich disc-type chip is characterized in that: this chip is made up of upper, middle and lower-ranking; The upper strata is the chip with how much micro-structurals, is made up of liquid storage tank 1, liquid storage tank 2, how much micro-structurals; The middle level is a thin layer; Lower floor is the gas passage chip;
Described how much micro-structurals are by the main channel, and wing passage and capture region are formed.
2, according to the described three-layer sandwich disc-type chip of claim 1, it is characterized in that: the material on described chip upper strata is a glass, and middle layer film is a high polymer, and the material of chip lower floor is a glass.
3, according to the described three-layer sandwich disc-type chip of claim 2, it is characterized in that: layer film is PDMS in described.
4, a kind of method that forms and catch based on the drop of claim 1,2 described chips is characterized in that:
The PDMS-glass hybridization hybrid chip that will have how much micro-structurals outgased in vacuum desiccator 3-5 minute, took out then, added water in liquid storage tank 1, take out vacuum in the liquid storage tank 2, make the aqueous solution be full of the main channel, leave standstill, under the ventilative effect of PDMS, the aqueous solution enters capture region, treat that capture region is full of after, vacuumize at liquid storage tank 2, solution in the main channel is taken away, add oil phase then in liquid storage tank 1, oil phase soaks into passage, forms water in oil drop;
Oil-in-water drop formation method is the same substantially on the PDMS-glass hybridization hybrid chip, because water does not soak into PDMS, after the oil phase in the main channel is taken away, adds water in liquid storage tank 1, vacuumizes at liquid storage tank 2 then, impels water sealing oil droplet.
5, the method that forms and catch according to the described drop of claim 4 is characterized in that: by changing the area and the shape of capture region, form the array drop of different sizes and shape; Have the disc-type chip of a plurality of array structures unit by use, form the array drop of different component.
6, the described chip application of claim 1 is in the formation of pH gradient and the gas-liquid reaction in the drop.
7, according to the formation of the described pH gradient of claim 5, it is characterized in that: with the pH indicator is water, and fluorinated oil Fc40 is an oil phase, forms the drop of pH indicator on the chip upper strata, continues to feed NH then in the lower floor gas passage
3, NH
3See through the PDMS film and enter drop, and with drop in indicator reaction, the alkalescence of drop increases, and darkens; Along with the increase of ammonia diffusion length, the concentration of ammonia reduces, and the ammonia amount that drop absorbs reduces, and the increasing degree of alkalescence reduces, and forming with the drop directly over the gas passage is the center, the pH gradient that gradually changes to the both sides drop.
8, according to the formation of the described pH gradient of claim 6, it is characterized in that: described pH indicator is for to mix 0.05～0.5mol/L methyl red aqueous solution, 0.05～0.5mol/L bromocresol green aqueous solution and 0.05～0.5mol/L bromthymol blue aqueous solution in 1: 1: 1 by volume～1: 1: 30, be adjusted to acidity with hydrochloric acid, be the pH indicator.
9, according to the gas-liquid reaction in the described drop of claim 5, it is characterized in that: adopting different metal ion salt solutions is water, Fc40 is an oil phase, and the array drop of the different component of formation and the gas generation complex reaction of striding the film diffusion have been realized the gas-liquid reaction in the drop.
10, according to the gas-liquid reaction in the described drop of claim 9, it is characterized in that: described gas of striding the film diffusion is ammonia, HCl, H
2O
2In at least a.
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| CN105233888A (en) * | 2015-10-12 | 2016-01-13 | 浪潮(北京)电子信息产业有限公司 | Glass-PDMS film-glass sandwich microfluidic chip manufacturing method |
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| CN101034080B (en) * | 2007-04-10 | 2010-05-19 | 南京大学 | Simple sampling method suitable for portable microchip capillary electrophoresis |
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| CN104415801B (en) * | 2013-08-28 | 2016-03-09 | 中国科学院青岛生物能源与过程研究所 | A kind of portable microlayer model generator based on self energizing vacuum Micropump |
| CN103495440A (en) * | 2013-09-25 | 2014-01-08 | 中国科学院长春光学精密机械与物理研究所 | Reagent pre-packaged structure of centrifugal type micro-fluidic chip as well as manufacturing method and application method of reagent pre-packaged structure |
| CN103495440B (en) * | 2013-09-25 | 2015-04-22 | 中国科学院长春光学精密机械与物理研究所 | Reagent pre-packaged structure of centrifugal type micro-fluidic chip as well as manufacturing method and application method of reagent pre-packaged structure |
| CN105233888A (en) * | 2015-10-12 | 2016-01-13 | 浪潮(北京)电子信息产业有限公司 | Glass-PDMS film-glass sandwich microfluidic chip manufacturing method |
| CN106268563A (en) * | 2016-08-19 | 2017-01-04 | 清华大学 | The method of gradient substrate induction droplet growth |
| CN106423315A (en) * | 2016-09-26 | 2017-02-22 | 东北大学 | Multi-material gradient mixed liquid drop formation device based on micro-fluidic chip |
| CN106423315B (en) * | 2016-09-26 | 2019-05-21 | 东北大学 | A kind of more substance gradients mixing drop forming devices based on micro-fluidic chip |
| CN107583692A (en) * | 2017-05-23 | 2018-01-16 | 深圳市博瑞生物科技有限公司 | Drop micro-fluidic chip and preparation method thereof |
| CN116425190A (en) * | 2023-04-04 | 2023-07-14 | 华东师范大学 | Method for in-situ growth of zinc oxide nanorods based on microfluidic chip |
| CN116425190B (en) * | 2023-04-04 | 2024-04-12 | 华东师范大学 | Method for in-situ growth of zinc oxide nanorods based on microfluidic chip |
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