CN103386336A - Microfluidic chip for producing droplets with concentration gradients - Google Patents
Microfluidic chip for producing droplets with concentration gradients Download PDFInfo
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- CN103386336A CN103386336A CN2013103416974A CN201310341697A CN103386336A CN 103386336 A CN103386336 A CN 103386336A CN 2013103416974 A CN2013103416974 A CN 2013103416974A CN 201310341697 A CN201310341697 A CN 201310341697A CN 103386336 A CN103386336 A CN 103386336A
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Abstract
The invention provides a microfluidic chip for producing droplets with concentration gradients. The microfluidic chip is characterized by comprising a sample solution inlet and channel, a concentration gradient generating unit, a water phase import hole, an oil phase inlet and channel, a droplet generating unit and a droplet outlet, wherein the droplets with concentration gradients are formed by injecting products which are exported from the concentration gradient generating unit and have concentration gradients into a flowing oil phase in the droplet generating unit, thus continuously obtaining water-in-oil droplets with corresponding concentrations. By using the microfluidic chip provided by the invention, plenty of droplets of inclusions with concentration gradients can be generated on line in real time and are expected to be applied to the fields such as drug screening, chemical synthesis, material preparation, chemical production and the like.
Description
Technical field
The present invention relates to the microflow control technique field, particularly relate to a kind of micro-fluidic chip for the production of the little drop of concentration gradient.
Background technology
Little drop micro-fluidic (droplet-based microfluidics) is a kind of technology platform of controlling micro volume liquid that grows up on micro-fluidic chip in recent years, its principle is: with two kinds of immiscible liquid, a kind of as continuous phase take wherein, another kind is decentralized photo, after continuous phase and decentralized photo enter microchannel simultaneously, under the effect of microchannel, decentralized photo is with micro volume (10
-15～10
-9L) formal distribution of unit in continuous phase, forms little drop of series of discrete, and each drop, as a microreactor, is completed one group of chemistry or biological respinse.Little drop is used for screening and has following advantage: 1) sample consumption is atomic, greatly reduces the screening cost; 2) drop is wrapped up by oil, exchanges the stable reaction conditions in drop, reliable results without material with the external world.Therefore the aspect such as, enzyme reaction analyzing and testing synthetic in drug screening, micro Nano material has important and application prospect widely.
When little drop was applied to high flux screening, little drop formation of different component, different inclusion or variable concentrations was a very important basic content.At present, the generation technique of drop mainly is based on the design of chip microchannel and realizes, namely utilizes MCA T-shaped or the flow focusing type, produces continuously little drop; In addition, the pneumatic operated valve technology also is applied to the drop formation of different component.But existing drop technology still is difficult to realize generating simultaneously large batch of, as to have variable concentrations little drop.Therefore, if can develop a kind of new technology, can generate simultaneously the little drop that has in a large number concentration gradient, have foreseeable using value and market prospects widely.
Summary of the invention
For the problems referred to above, for the online little drop with concentration gradient inclusion that generates, the present invention proposes a kind of micro-fluidic chip for the production of the little drop of concentration gradient, it is characterized in that, this micro-fluidic chip is comprised of sample solution entrance and passage, concentration gradient generation unit, water entrance hole, oil phase entrance and passage, drop formation unit and drop outlet.
Drop micro-fluidic chip provided by the present invention, is characterized in that, described micro-fluidic chip is to be formed by materials processings such as silicon, glass, dimethyl silicone polymer, polymethyl methacrylate, Merlon, polystyrene.
Drop micro-fluidic chip provided by the present invention, is characterized in that, described concentration gradient generation unit is based on lamina flow principle, by the microchannel network of constructing " Christmas tree " type on micro-fluidic chip, realizes, is used for the online product that generates concentration gradient.
Drop micro-fluidic chip provided by the present invention, it is characterized in that, described sample solution entrance and passage and concentration gradient generation unit are on the same layer substrate, and oil phase entrance and passage and drop formation unit are on another layer substrate, and the water entrance hole is through-hole structure, on above-mentioned substrate between two-layer.
Drop micro-fluidic chip provided by the present invention, is characterized in that, described concentration gradient generation unit and drop formation unit connect by the water entrance hole, and the water entrance hole is positioned at the ad-hoc location in the downstream of oil phase entrance and passage.
Drop micro-fluidic chip provided by the present invention, is characterized in that, the drop formation unit is a kind of T-shaped structure that consists of oil phase passage and perpendicular crossing water entrance hole; Also can be formed by oil phase passage and perpendicular another crossing passage, and this passage and water entrance hole link.
Drop micro-fluidic chip provided by the present invention, it is characterized in that, the operation principle of described micro-fluidic chip is: the little drop of concentration gradient injects with the product of deriving, having concentration gradient from the concentration gradient generation unit oil phase that the drop generation unit flows, thereby obtains continuously the little drop of water-in-oil type of corresponding concentration.
Use micro-fluidic chip provided by the present invention, can generate a large amount of, little drop that have the concentration gradient inclusion in real-time online ground, be expected to be applied to the fields such as drug screening, chemical synthesis, material preparation, Chemical Manufacture.
Description of drawings
Fig. 1. the structural representation of a kind of micro-fluidic chip for the production of the little drop of concentration gradient provided by the present invention.Wherein, A is the cover plate with fluid passing hole, and B is the substrate with drop formation unit, and C is the substrate with water entrance hole, D is the substrate with concentration gradient generation unit, E1 and E2 are the entrance of sample solution and retarder thinner, and F is the oil phase entrance, and G is the drop outlet, H is oil phase and drop passage, I is the water entrance hole, and J is the channel network that " Christmas tree " type concentration gradient generates, and K is the taphole of concentration gradient.
Fig. 2. the substrate structure schematic diagram of the drop formation unit in micro-fluidic chip.Wherein, a is that the oil phase entrance reaches, and b is sample channel, and c is the water entrance hole, and d is the water-in-oil type drop.
Specific embodiments
The following examples are further described the present invention in connection with Figure of description.
A kind of micro-fluidic chip for the production of the little drop of concentration gradient of embodiment
In order to realize producing in batches the little drop with concentration gradient inclusion, the present invention proposes a kind of micro-fluidic chip of PDMS for the production of the little drop of concentration gradient, as shown in Figure 1, this micro-fluidic chip consists of four layers of substrate, be respectively the cover plate A with fluid passing hole, substrate B with drop formation unit, have the substrate C of water entrance hole, has the substrate D of concentration gradient generation unit.Wherein, be processed with fluid inlet E1 and E2, oil phase entrance F and drop outlet G in A; Be processed with oil phase passage H in B; Be processed with water entrance hole I in C; D always is processed with the channel network J of concentration gradient generation and the taphole K of concentration gradient.
Use above-mentioned micro-fluidic chip to carry out drop while preparing, pass into sample solution and pure water in E1 and E2, regulate certain flow velocity, sample solution and current after concentration gradient forms unit, form respectively the sample solution of concentration from the concentration gradient of 100%～0% extension rate in sample export.
Be used for the substrate of drop formation as shown in Figure 2, when above-mentioned concentration gradient generates, oil phase entrance a place (corresponding to the F in Fig. 1) uses syringe pump constantly to inject hexadecane, mineral wet goods oil phase, from the above-mentioned concentration gradient solution b water entrance hole c (corresponding to the I Fig. 1) that flows through, enter in oil phase passage (corresponding to the H in Fig. 1), under the acting in conjunction of two kinds of hydrodynamic shears and viscous force, generate continuously little drop d in the oil phase passage, the final little drop preparation that realizes having concentration gradient.
Use micro-fluidic chip provided by the present invention, can generate a large amount of, little drop that have the concentration gradient inclusion in real-time online ground, be expected to be applied to the fields such as drug screening, chemical synthesis, material preparation, Chemical Manufacture.
Claims (8)
1. micro-fluidic chip for the production of the little drop of concentration gradient, it is characterized in that, this micro-fluidic chip is comprised of sample solution entrance and passage, concentration gradient generation unit, water entrance hole, oil phase entrance and passage, drop formation unit and drop outlet.
2. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, described micro-fluidic chip is to be formed by materials processings such as silicon, glass, dimethyl silicone polymer, polymethyl methacrylate, Merlon, polystyrene.
3. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, described concentration gradient generation unit is based on lamina flow principle, realize by the microchannel network of constructing " Christmas tree " type on micro-fluidic chip, be used for the online product that generates concentration gradient.
4. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, described sample solution entrance and passage and concentration gradient generation unit are on the same layer substrate, and oil phase entrance and passage and drop formation unit are on another layer substrate, and the water entrance hole is through-hole structure, on above-mentioned substrate between two-layer.
5. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, described concentration gradient generation unit and drop formation unit connect by the water entrance hole, and the water entrance hole is positioned at the ad-hoc location in the downstream of oil phase entrance and passage.
6., according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, the drop formation unit is a kind of T-shaped structure that consists of oil phase passage and perpendicular crossing water entrance hole; Also can be formed by oil phase passage and perpendicular another crossing passage, and this passage and water entrance hole link.
7. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, the operation principle of described micro-fluidic chip is: the little drop of concentration gradient injects with the product of deriving, having concentration gradient from the concentration gradient generation unit oil phase that the drop generation unit flows, thereby obtains continuously the little drop of water-in-oil type of corresponding concentration.
8. according to a kind of micro-fluidic chip for the production of the little drop of concentration gradient claimed in claim 1, it is characterized in that, use micro-fluidic chip provided by the present invention, can generate a large amount of, little drop that have the concentration gradient inclusion in real-time online ground, be expected to be applied to the fields such as drug screening, chemical synthesis, material preparation, Chemical Manufacture.
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106110340A (en) * | 2016-07-12 | 2016-11-16 | 陈传品 | A kind of method and device preparing target drug-carrying microbubble |
| CN106669513A (en) * | 2017-01-10 | 2017-05-17 | 中国科学院苏州纳米技术与纳米仿生研究所 | Concentration gradient generating device and method for generating concentration gradient in one step |
| CN107271706A (en) * | 2017-07-05 | 2017-10-20 | 大连理工大学 | A kind of micro-fluidic chip of the dynamic Some Circulating Factors concentration of real-time and precise control observation point |
| CN107597221A (en) * | 2017-09-30 | 2018-01-19 | 深圳市博瑞生物科技有限公司 | Drop formation device and drop formation system |
| CN108893411A (en) * | 2018-06-15 | 2018-11-27 | 杭州电子科技大学 | Micro-fluidic chip and its manufacturing method based on photocuring printing |
| CN110029063A (en) * | 2019-03-04 | 2019-07-19 | 杭州电子科技大学 | A kind of double-deck microlayer model co-culture device and its application method with concentration gradient |
| CN110038656A (en) * | 2019-05-31 | 2019-07-23 | 中国科学技术大学 | A kind of aqueous two-phase system and its drop formation module for emulsification |
| CN111971378A (en) * | 2018-05-21 | 2020-11-20 | 深圳华大生命科学研究院 | High-flux organ chip and preparation method and application thereof |
| CN112844501A (en) * | 2019-11-28 | 2021-05-28 | 中国科学院大连化学物理研究所 | Multi-liquid-core hydrogel microcapsule chip based on double aqueous phases and application thereof |
| CN113588896A (en) * | 2021-07-30 | 2021-11-02 | 中山大学 | Micro-channel device and method for establishing high-flux programmable multi-concentration medicine |
| CN113578404A (en) * | 2021-07-19 | 2021-11-02 | 杭州电子科技大学 | Multi-concentration micro-droplet chip for drug microspheres and manufacturing method thereof |
| CN114931988A (en) * | 2022-06-28 | 2022-08-23 | 苏州大学 | Nanoliter molecular concentration gradient droplet generation microfluidic chip and use method thereof |
| CN115521882A (en) * | 2021-06-24 | 2022-12-27 | 清华大学 | Micro-upgrading single-cell droplet generation and culture method and device |
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| US8189186B2 (en) * | 2007-12-27 | 2012-05-29 | Lawrence Livermore National Security, Llc. | Signal enhancement using a switchable magnetic trap |
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| CN101132853A (en) * | 2004-11-17 | 2008-02-27 | 万罗赛斯公司 | Process for making or treating an emulsion using microchannel technology |
| US8189186B2 (en) * | 2007-12-27 | 2012-05-29 | Lawrence Livermore National Security, Llc. | Signal enhancement using a switchable magnetic trap |
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Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106110340A (en) * | 2016-07-12 | 2016-11-16 | 陈传品 | A kind of method and device preparing target drug-carrying microbubble |
| CN106110340B (en) * | 2016-07-12 | 2019-09-03 | 陈传品 | A kind of method and device preparing target drug-carrying microbubble |
| CN106669513B (en) * | 2017-01-10 | 2019-08-23 | 中国科学院苏州纳米技术与纳米仿生研究所 | The method that concentration gradient generating means and a step generate concentration gradient |
| CN106669513A (en) * | 2017-01-10 | 2017-05-17 | 中国科学院苏州纳米技术与纳米仿生研究所 | Concentration gradient generating device and method for generating concentration gradient in one step |
| CN107271706A (en) * | 2017-07-05 | 2017-10-20 | 大连理工大学 | A kind of micro-fluidic chip of the dynamic Some Circulating Factors concentration of real-time and precise control observation point |
| CN107597221A (en) * | 2017-09-30 | 2018-01-19 | 深圳市博瑞生物科技有限公司 | Drop formation device and drop formation system |
| CN111971378A (en) * | 2018-05-21 | 2020-11-20 | 深圳华大生命科学研究院 | High-flux organ chip and preparation method and application thereof |
| CN108893411A (en) * | 2018-06-15 | 2018-11-27 | 杭州电子科技大学 | Micro-fluidic chip and its manufacturing method based on photocuring printing |
| CN108893411B (en) * | 2018-06-15 | 2024-03-08 | 杭州电子科技大学 | Microfluidic chip based on photo-curing printing and manufacturing method thereof |
| CN110029063A (en) * | 2019-03-04 | 2019-07-19 | 杭州电子科技大学 | A kind of double-deck microlayer model co-culture device and its application method with concentration gradient |
| CN110038656A (en) * | 2019-05-31 | 2019-07-23 | 中国科学技术大学 | A kind of aqueous two-phase system and its drop formation module for emulsification |
| CN112844501A (en) * | 2019-11-28 | 2021-05-28 | 中国科学院大连化学物理研究所 | Multi-liquid-core hydrogel microcapsule chip based on double aqueous phases and application thereof |
| CN115521882A (en) * | 2021-06-24 | 2022-12-27 | 清华大学 | Micro-upgrading single-cell droplet generation and culture method and device |
| CN113578404A (en) * | 2021-07-19 | 2021-11-02 | 杭州电子科技大学 | Multi-concentration micro-droplet chip for drug microspheres and manufacturing method thereof |
| CN113578404B (en) * | 2021-07-19 | 2022-05-31 | 杭州电子科技大学 | Multi-concentration micro-droplet chip for drug microspheres and manufacturing method thereof |
| CN113588896A (en) * | 2021-07-30 | 2021-11-02 | 中山大学 | Micro-channel device and method for establishing high-flux programmable multi-concentration medicine |
| CN114931988A (en) * | 2022-06-28 | 2022-08-23 | 苏州大学 | Nanoliter molecular concentration gradient droplet generation microfluidic chip and use method thereof |
| CN114931988B (en) * | 2022-06-28 | 2024-03-29 | 苏州蜜思肤化妆品股份有限公司 | Micro-fluidic chip for generating nano-scale molecular concentration gradient liquid drops and application method thereof |
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Application publication date: 20131113 |