CN107754960B - A microfluidic chip for asymmetric splitting of double emulsion droplets based on additional flow - Google Patents
A microfluidic chip for asymmetric splitting of double emulsion droplets based on additional flow Download PDFInfo
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- 239000000839 emulsion Substances 0.000 title claims abstract description 284
- 239000007787 solid Substances 0.000 claims abstract description 36
- 239000004205 dimethyl polysiloxane Substances 0.000 claims abstract description 22
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims abstract description 22
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract description 22
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims abstract description 20
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 claims description 68
- 238000002347 injection Methods 0.000 claims description 22
- 239000007924 injection Substances 0.000 claims description 22
- 239000012530 fluid Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 9
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 12
- 238000013268 sustained release Methods 0.000 abstract description 6
- 239000012730 sustained-release form Substances 0.000 abstract description 6
- 239000003094 microcapsule Substances 0.000 description 4
- 241000270295 Serpentes Species 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000011258 core-shell material Substances 0.000 description 2
- 238000001723 curing Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- -1 polydimethylsiloxane Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003848 UV Light-Curing Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0883—Serpentine channels
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Abstract
本发明涉及一种基于附加流量实现双乳液滴非对称分裂的微流控芯片。本发明特征是利用主体固体结构跟PDMS底板键合固定，利用双乳液滴径向固定通道维持双乳液滴内核及外壳的同轴性，利用聚焦缩口将液滴喷射出，使其接触双乳液滴分裂岔口发生分裂。利用支路附加流量调节单侧支路流阻，实现双乳液滴的非对称分裂。本发明能够在不改变通道几何结构的情况下，利用单侧支路附加流量产生的非对称支路压力，使得双乳液滴在经过Y型微通道时发生非对称分裂。通过以上功能，可为胶囊型缓释药物提供尺寸大小可控的双乳液滴模板，提高缓释性药物的应用范围。
The invention relates to a microfluidic chip for realizing asymmetric splitting of double emulsion droplets based on additional flow. The feature of the present invention is that the solid structure of the main body is bonded and fixed with the PDMS bottom plate, and the radial fixed channel of the double emulsion droplet is used to maintain the coaxiality of the inner core and the outer shell of the double emulsion droplet, and the droplet is sprayed out by using the focusing constriction, so that it contacts the double emulsion Splitting occurs at the fork where the drop splits. The flow resistance of the unilateral branch is adjusted by using the additional flow of the branch to realize the asymmetric splitting of the double emulsion droplet. The invention can make use of the asymmetric branch pressure generated by the additional flow of the unilateral branch without changing the geometric structure of the channel, so that the double emulsion droplet can be asymmetrically split when passing through the Y-shaped microchannel. Through the above functions, a double emulsion droplet template with controllable size can be provided for capsule-type sustained-release drugs, and the application range of sustained-release drugs can be improved.
Description
技术领域technical field
本发明涉及一种基于附加流量实现双乳液滴非对称分裂的微流控芯片。本发明属于基于微流控芯片的液滴微流控技术领域。The invention relates to a microfluidic chip for realizing asymmetric splitting of double emulsion droplets based on additional flow. The invention belongs to the technical field of droplet microfluidics based on microfluidic chips.
背景技术Background technique
随着药物研制水平的不断发展，许多新型药物被研制出来以应对不同种类的疾病，但传统给药方法在释放过程中通常使患者体内的血药浓度在短时间内迅速上升并快速下降。在治疗过程中，血药浓度无论是超过患者的最高耐受剂量还是低于有效剂量，都无法得到有效的治疗效果，有时还会对患者产生不良的副作用。频繁的小剂量给药虽然可以一定程度上解决以上情况，但往往使患者难以接受，实施起来有很多困难。因此，能够缓慢释放药物成分的缓释性药物应运而生。With the continuous development of drug research and development, many new drugs have been developed to deal with different types of diseases, but the traditional drug delivery method usually causes the blood drug concentration in the patient's body to rise and fall rapidly in a short period of time during the release process. During the course of treatment, no matter whether the blood drug concentration exceeds the patient's maximum tolerated dose or is lower than the effective dose, no effective therapeutic effect can be obtained, and sometimes adverse side effects will be produced on the patient. Although frequent small-dose administration can solve the above situation to a certain extent, it often makes it difficult for patients to accept it, and there are many difficulties in implementation. Therefore, sustained-release drugs that can slowly release drug components have emerged.
液滴微流控技术是近些年发展起来的一种研究微米尺度微液滴生成、操控及应用的新技术。该技术具有稳定、易操作和适用范围广等特点，目前已广泛应用于药物运输、疾病防护、细胞研究及功能材料制备等诸多领域，是目前国内外各相关学科的研究热点。该技术基于玻璃微毛细管装置可以生成单分散性良好的双乳液滴，这些液滴能够为后续利用化学聚合、紫外光固化等方式生成的微胶囊提供高质量的模板。在药物缓释领域，厚度决定了微胶囊壳层在患者体内的溶解速率，通过将多种壳厚的微胶囊注入患者体内，使得不同核壳尺寸的微胶囊在不同时间点实现分批释放，可以控制药物在患者体内以给定的速率缓慢释放，维持有效的血药浓度。Droplet microfluidic technology is a new technology developed in recent years to study the generation, manipulation and application of micron-scale micro-droplets. This technology has the characteristics of stability, easy operation and wide application range. It has been widely used in many fields such as drug delivery, disease prevention, cell research and preparation of functional materials. It is currently a research hotspot in various related disciplines at home and abroad. This technology is based on a glass microcapillary device that can generate double emulsion droplets with good monodispersity. These droplets can provide high-quality templates for subsequent microcapsules generated by chemical polymerization, UV curing, and other methods. In the field of drug sustained release, the thickness determines the dissolution rate of the microcapsule shell in the patient's body. By injecting microcapsules with various shell thicknesses into the patient's body, the microcapsules with different core-shell sizes can be released in batches at different time points. The drug can be controlled to release slowly at a given rate in the patient's body to maintain an effective blood drug concentration.
相关文献指出，双乳液滴的尺寸很大程度上依赖于毛细管生成装置的几何参数，由于毛细管生成装置制作工艺的难度和复杂性，使得精确生成不同核壳尺寸，特别是100微米以下的双乳液滴模板还相对困难。Related literature points out that the size of the double emulsion droplet depends largely on the geometric parameters of the capillary generation device. Due to the difficulty and complexity of the manufacturing process of the capillary generation device, it is possible to accurately generate double emulsions with different core-shell sizes, especially below 100 microns. Drop templates are also relatively difficult.
发明内容Contents of the invention
基于目前的背景，本发明是为了在不改变通道几何结构的情况下，利用单侧支路附加流量产生的非对称支路压力，使得双乳液滴在经过Y型微通道时发生非对称分裂。通过以上功能，可为胶囊型缓释药物提供尺寸大小可控的双乳液滴模板，提高缓释性药物的应用范围。Based on the current background, the present invention is to make use of the asymmetric branch pressure generated by the additional flow of the unilateral branch without changing the geometric structure of the channel, so that the double emulsion droplets are asymmetrically split when passing through the Y-shaped microchannel. Through the above functions, a double emulsion droplet template with controllable size can be provided for capsule-type sustained-release drugs, and the application range of sustained-release drugs can be improved.
本发明提供一种基于附加流量实现双乳液滴非对称分裂的微流控芯片。该微流控芯片包括双乳液滴注射入口1、蛇形增压通道2、双乳液滴运动速度调节入口3、第一子双乳液滴出口4、双乳液滴分裂岔口5、第一双乳液滴分裂支路6、单侧支路附加流量入口7、第一出口蛇形增压通道8、稳流主通道9、第二子双乳液滴出口10、双乳液滴径向固定通道11、双乳液滴分裂聚焦缩口12、第二双乳液滴分裂支路13、第二出口蛇形增压通道14、主体固体结构15和PDMS底板16。The invention provides a microfluidic chip for realizing asymmetric splitting of double emulsion droplets based on additional flow. The microfluidic chip includes a double-emulsion droplet injection inlet 1, a serpentine pressurization channel 2, a double-emulsion droplet movement speed adjustment inlet 3, a first sub-double emulsion droplet outlet 4, a double-emulsion droplet splitting fork 5, a first double-emulsion droplet Split branch 6, unilateral branch additional flow inlet 7, first outlet serpentine pressurized channel 8, steady flow main channel 9, second sub-double emulsion drop outlet 10, double emulsion drop radial fixed channel 11, double emulsion Droplet splitting focusing constriction 12 , second double emulsion droplet splitting branch 13 , second outlet serpentine pressurization channel 14 , main body solid structure 15 and PDMS bottom plate 16 .
具体而言，双乳液滴注射入口1、双乳液滴运动速度调节入口3、单侧支路附加流量入口7、第二子双乳液滴出口10、第一子双乳液滴出口4为主体固体结构15上的孔洞结构。蛇形增压通道2、第二出口蛇形增压通道14、第一出口蛇形增压通道8、双乳液滴径向固定通道11、稳流主通道9、第二双乳液滴分裂支路13、第一双乳液滴分裂支路6则为体固体结构1上的凹槽结构。Specifically, the double emulsion droplet injection inlet 1, the double emulsion droplet movement speed adjustment inlet 3, the single-side branch additional flow inlet 7, the second sub-double emulsion droplet outlet 10, and the first sub-double emulsion droplet outlet 4 are the main solid structure 15 hole structure. Serpentine pressurization channel 2, second exit serpentine pressurization channel 14, first exit serpentine pressurization channel 8, double emulsion drop radial fixed channel 11, steady flow main channel 9, second double emulsion drop splitting branch 13. The first double emulsion droplet splitting branch 6 is a groove structure on the bulk solid structure 1 .
所述主体固体结构15和PDMS底板16通过上下键合固定，PDMS底板16置于主体固体结构15之下，用以支撑主体固体结构15并闭合主体固体结构15表面的沟槽结构，形成流体的流动区域。The main body solid structure 15 and the PDMS bottom plate 16 are fixed by bonding up and down, and the PDMS bottom plate 16 is placed under the main body solid structure 15 to support the main body solid structure 15 and close the groove structure on the surface of the main body solid structure 15 to form a fluid flow area.
所述双乳液滴注射入口1用于连接导管，双乳液滴注射入口1直接连接稳流主通道9，双乳液滴运动速度调节入口3连接蛇形增压通道2，蛇形增压通道2接入在稳流主通道9的一侧。The double-emulsion droplet injection inlet 1 is used to connect the catheter, the double-emulsion droplet injection inlet 1 is directly connected to the steady flow main channel 9, the double-emulsion droplet movement speed adjustment inlet 3 is connected to the serpentine booster channel 2, and the serpentine booster channel 2 is connected to Into the side of the steady flow main channel 9.
所述稳流主通道9的尾部接入了双乳液滴径向固定通道11，在双乳液滴径向固定通道11的尾部是双乳液滴分裂聚焦缩口12以及双乳液滴分裂岔口5。The tail of the steady flow main channel 9 is connected to the radial fixed channel 11 of the double emulsion droplet, and at the tail of the radial fixed channel 11 of the double emulsion droplet is the double emulsion droplet split focusing constriction 12 and the double emulsion droplet split fork 5 .
所述双乳液滴分裂岔口5的两侧分别是第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，第二双乳液滴分裂支路13尾部接入了第二出口蛇形增压通道14。第一双乳液滴分裂支路6尾部接入了第一出口蛇形增压通道8，在第一双乳液滴分裂支路6以及第一出口蛇形增压通道8之间接有单侧支路附加流量入口7。The two sides of the double emulsion droplet splitting fork 5 are respectively the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and the tail of the second double emulsion droplet splitting branch 13 is connected to the second outlet snake Shaped pressurization channel 14. The tail of the first double-emulsion droplet splitting branch 6 is connected to the first outlet serpentine pressurization channel 8, and a single-side branch is connected between the first double emulsion droplet splitting branch 6 and the first outlet serpentine pressurization channel 8 Additional flow inlet 7.
第一双乳液滴分裂支路6末端经过第一出口蛇形增压通道8接入第一子双乳液滴出口4。所述第二双乳液滴分裂支路13末端分别经过第二出口蛇形增压通道14、接入第二子双乳液滴出口10；第二子双乳液滴出口10、第一子双乳液滴出口4将接连导管。The end of the first double-emulsion droplet splitting branch 6 is connected to the first sub-double-emulsion droplet outlet 4 through the first outlet serpentine pressurization channel 8 . The end of the second double-emulsion drop splitting branch 13 passes through the second outlet serpentine pressurized passage 14, and is connected to the second sub-double emulsion drop outlet 10; the second sub-double emulsion drop outlet 10, the first sub-double emulsion drop Outlet 4 will be followed by a conduit.
2.应用如权利要求1中所述芯片的方法，其特征在于：2. Apply the method for the chip as claimed in claim 1, characterized in that:
将制备好的双乳液滴通过导管输入双乳液滴注射入口1，随着流体流动，双乳液滴流入稳流主通道9于蛇形增压通道2交汇处。另一方面，流体从双乳液滴运动速度调节入口3流入主体固体结构15和PDMS底板16制作成的微流控芯片，经过蛇形增压通道2，与双乳液滴同时进入稳流主通道9。通过调节流体从双乳液滴运动速度调节入口3的流量大小，控制双乳液滴的运动速度，调节分裂稳定性。The prepared double-emulsion droplets are fed into the double-emulsion droplet injection inlet 1 through the catheter, and as the fluid flows, the double-emulsion droplets flow into the steady-flow main channel 9 at the junction of the serpentine pressurized channel 2 . On the other hand, the fluid flows into the microfluidic chip made of the main body solid structure 15 and the PDMS bottom plate 16 from the double emulsion droplet velocity adjustment inlet 3, passes through the serpentine pressurized channel 2, and enters the steady flow main channel 9 at the same time as the double emulsion droplet . By adjusting the moving speed of the fluid from the double emulsion droplet, the flow rate of the inlet 3 is adjusted, the moving speed of the double emulsion droplet is controlled, and the splitting stability is adjusted.
随后，双乳液滴流入稳流主通道9的末端，进入双乳液滴径向固定通道11，双乳液滴径向固定通道11将双乳液滴径向固定起来，经过双乳液滴分裂聚焦缩口12，双乳液滴射入双乳液滴分裂岔口5发生分裂。另一方面，单侧支路附加流量入口7接入附加流量，引起第二双乳液滴分裂支路13、第一双乳液滴分裂支路6内部的压力差。最终，双乳液滴在双乳液滴分裂岔口5发生非对称分裂，通过调节单侧支路附加流量入口7的流量大小，调节双乳液滴的分裂比。Subsequently, the double-emulsion droplets flow into the end of the steady-flow main channel 9 and enter the double-emulsion droplet radially fixed channel 11. The double-emulsion droplet radially fixed channel 11 fixes the double-emulsion droplet in the radial direction. , the double-emulsion droplet is injected into the double-emulsion droplet splitting fork 5 to split. On the other hand, the additional flow inlet 7 of the single-side branch is connected with the additional flow, causing a pressure difference inside the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6 . Finally, the double-emulsion droplet splits asymmetrically at the double-emulsion droplet splitting fork 5, and the splitting ratio of the double-emulsion droplet is adjusted by adjusting the flow rate of the additional flow inlet 7 of the unilateral branch.
在完成非对称分裂之后，子双乳液滴流经第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，分别进入第二出口蛇形增压通道14，第一出口蛇形增压通道8。最终，从第二子双乳液滴出口10、第一子双乳液滴出口4输入，流入外接导管。After completing the asymmetric splitting, the sub-double emulsion droplets flow through the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and enter the second outlet serpentine pressurization channel 14 respectively, and the first outlet serpentine Boost channel 8. Finally, it is input from the second sub-double emulsion drop outlet 10 and the first sub-double emulsion drop outlet 4, and flows into the external conduit.
更具体的，该微流控芯片包括双乳液滴注射入口1、蛇形增压通道2、双乳液滴运动速度调节入口3、第一子双乳液滴出口4、双乳液滴分裂岔口5、第一双乳液滴分裂支路6、单侧支路附加流量入口7、第一出口蛇形增压通道8、稳流主通道9、第二子双乳液滴出口10、双乳液滴径向固定通道11、双乳液滴分裂聚焦缩口12、第二双乳液滴分裂支路13、第二出口蛇形增压通道14、主体固体结构15、PDMS底板16。More specifically, the microfluidic chip includes a double-emulsion droplet injection inlet 1, a serpentine pressurized channel 2, a double-emulsion droplet movement speed adjustment inlet 3, a first sub-double emulsion droplet outlet 4, a double-emulsion droplet splitting fork 5, a second A double emulsion droplet splitting branch 6, a single side branch additional flow inlet 7, a first outlet serpentine pressurized channel 8, a steady flow main channel 9, a second sub-double emulsion droplet outlet 10, a double emulsion droplet radial fixed channel 11. Double emulsion droplet splitting focusing constriction 12, second double emulsion droplet splitting branch 13, second outlet serpentine pressurization channel 14, main body solid structure 15, PDMS bottom plate 16.
具体而言，双乳液滴注射入口1、双乳液滴运动速度调节入口3、单侧支路附加流量入口7、第二子双乳液滴出口10、第一子双乳液滴出口4为主体固体结构15上的孔洞结构。蛇形增压通道2、第二出口蛇形增压通道14、第一出口蛇形增压通道8、双乳液滴径向固定通道11、稳流主通道9、第二双乳液滴分裂支路13、第一双乳液滴分裂支路6则为体固体结构1上的凹槽结构。其中，各结构为微流控芯片工作时流体的流动区域。Specifically, the double emulsion droplet injection inlet 1, the double emulsion droplet movement speed adjustment inlet 3, the single-side branch additional flow inlet 7, the second sub-double emulsion droplet outlet 10, and the first sub-double emulsion droplet outlet 4 are the main solid structure 15 hole structure. Serpentine pressurization channel 2, second exit serpentine pressurization channel 14, first exit serpentine pressurization channel 8, double emulsion drop radial fixed channel 11, steady flow main channel 9, second double emulsion drop splitting branch 13. The first double emulsion droplet splitting branch 6 is a groove structure on the bulk solid structure 1 . Wherein, each structure is a fluid flow area when the microfluidic chip works.
所述主体固体结构15和PDMS底板16通过上下键合固定，PDMS底板16置于主体固体结构15之下，用以支撑主体固体结构15并闭合主体固体结构15表面的沟槽结构，形成流体的流动区域。The main body solid structure 15 and the PDMS bottom plate 16 are fixed by bonding up and down, and the PDMS bottom plate 16 is placed under the main body solid structure 15 to support the main body solid structure 15 and close the groove structure on the surface of the main body solid structure 15 to form a fluid flow area.
所述主体固体结构15和PDMS底板16均通过聚二甲基硅氧烷浇筑并加热固化制成，具有良好的透明性，可方便利用显微镜观测微流控芯片内部双乳液滴分裂状况。Both the main body solid structure 15 and the PDMS bottom plate 16 are made by pouring polydimethylsiloxane and heating and curing, which have good transparency and can be conveniently observed by a microscope for the splitting of double emulsion droplets inside the microfluidic chip.
所述双乳液滴注射入口1用于连接导管，以注入已制备好的尺寸均一的双乳液滴，双乳液滴注射入口1直接连接稳流主通道9，用于双乳液滴的输送。双乳液滴运动速度调节入口3连接蛇形增压通道2，蛇形增压通道2接入在稳流主通道9的一侧，用于调节双乳液滴间隔距离以及运输速度。The double-emulsion droplet injection inlet 1 is used to connect a catheter to inject the prepared double-emulsion droplet with uniform size. The double-emulsion droplet injection inlet 1 is directly connected to the steady flow main channel 9 for the delivery of the double-emulsion droplet. The double-emulsion droplet movement speed adjustment inlet 3 is connected to the serpentine booster channel 2, which is connected to one side of the steady-flow main channel 9, and is used to adjust the distance between the double-emulsion droplets and the transport speed.
所述稳流主通道9的尾部接入了双乳液滴径向固定通道11，用于维持双乳液滴内核及外壳的同轴性，在双乳液滴径向固定通道11的尾部是双乳液滴分裂聚焦缩口12以及双乳液滴分裂岔口5，用于双乳液滴的实际分裂。The afterbody of described steady-flow main channel 9 is connected with double emulsion droplet radially fixed channel 11, is used for maintaining the coaxiality of double emulsion droplet inner core and shell, and the afterbody of double emulsion droplet radially fixed channel 11 is double emulsion droplet The split focusing constriction 12 and the double emulsion droplet splitting fork 5 are used for the actual splitting of the double emulsion droplet.
所述双乳液滴分裂岔口5的两侧分别是第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，第二双乳液滴分裂支路13尾部接入了第二出口蛇形增压通道14。第一双乳液滴分裂支路6尾部接入了第一出口蛇形增压通道8，在第一双乳液滴分裂支路6以及第一出口蛇形增压通道8之间接有单侧支路附加流量入口7，用于改变附加流量，引起第二双乳液滴分裂支路13、第一双乳液滴分裂支路6内部的压力差。The two sides of the double emulsion droplet splitting fork 5 are respectively the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and the tail of the second double emulsion droplet splitting branch 13 is connected to the second outlet snake Shaped pressurization channel 14. The tail of the first double-emulsion droplet splitting branch 6 is connected to the first outlet serpentine pressurization channel 8, and a single-side branch is connected between the first double emulsion droplet splitting branch 6 and the first outlet serpentine pressurization channel 8 The additional flow inlet 7 is used to change the additional flow to cause the pressure difference inside the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6 .
所述第二双乳液滴分裂支路13、第一双乳液滴分裂支路6末端分别经过第二出口蛇形增压通道14、第一出口蛇形增压通道8接入第二子双乳液滴出口10、第一子双乳液滴出口4。第二子双乳液滴出口10、第一子双乳液滴出口4将接连导管，用于输出分裂获得的子双乳液滴。The second double-emulsion droplet splitting branch 13 and the end of the first double-emulsion droplet splitting branch 6 respectively pass through the second outlet serpentine pressurization channel 14 and the first outlet serpentine pressurization channel 8 to access the second sub-double emulsion Drop outlet 10, the first sub-double emulsion drop outlet 4. The second sub-double-emulsion outlet 10 and the first sub-double-emulsion outlet 4 will be connected with conduits for outputting sub-double-emulsion droplets obtained by splitting.
本发明的工作过程如下，将制备好的双乳液滴通过导管输入双乳液滴注射入口1，随着流体流动，双乳液滴流入稳流主通道9于蛇形增压通道2交汇处。另一方面，流体从双乳液滴运动速度调节入口3流入主体固体结构15和PDMS底板16制作成的微流控芯片，经过蛇形增压通道2，与双乳液滴同时进入稳流主通道9。通过调节流体从双乳液滴运动速度调节入口3的流量大小，可以控制双乳液滴的运动速度，调节分裂稳定性。The working process of the present invention is as follows, the prepared double emulsion droplets are input into the double emulsion droplet injection inlet 1 through the catheter, and as the fluid flows, the double emulsion droplets flow into the steady flow main channel 9 at the junction of the serpentine pressurized channel 2 . On the other hand, the fluid flows into the microfluidic chip made of the main body solid structure 15 and the PDMS bottom plate 16 from the double emulsion droplet velocity adjustment inlet 3, passes through the serpentine pressurized channel 2, and enters the steady flow main channel 9 at the same time as the double emulsion droplet . By adjusting the moving speed of the fluid from the double emulsion droplet to adjust the flow rate of the inlet 3, the moving speed of the double emulsion droplet can be controlled and the splitting stability can be adjusted.
随后，双乳液滴流入稳流主通道9的末端，进入双乳液滴径向固定通道11，双乳液滴径向固定通道11将双乳液滴径向固定起来，经过双乳液滴分裂聚焦缩口12，双乳液滴射入双乳液滴分裂岔口5发生分裂。另一方面，单侧支路附加流量入口7接入附加流量，引起第二双乳液滴分裂支路13、第一双乳液滴分裂支路6内部的压力差。最终，双乳液滴在双乳液滴分裂岔口5发生非对称分裂，通过调节单侧支路附加流量入口7的流量大小，可以进一步调节双乳液滴的分裂比。Subsequently, the double-emulsion droplets flow into the end of the steady-flow main channel 9 and enter the double-emulsion droplet radially fixed channel 11. The double-emulsion droplet radially fixed channel 11 fixes the double-emulsion droplet in the radial direction. , the double-emulsion droplet is injected into the double-emulsion droplet splitting fork 5 to split. On the other hand, the additional flow inlet 7 of the single-side branch is connected with the additional flow, causing a pressure difference inside the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6 . Finally, the double-emulsion droplet splits asymmetrically at the double-emulsion droplet splitting fork 5, and the splitting ratio of the double-emulsion droplet can be further adjusted by adjusting the flow rate of the additional flow inlet 7 of the unilateral branch.
在完成非对称分裂之后，子双乳液滴流经第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，分别进入第二出口蛇形增压通道14，第一出口蛇形增压通道8。最终，从第二子双乳液滴出口10、第一子双乳液滴出口4输入，流入外接导管。由于系统外部压力的微小波动会引起分裂比的不稳定，第二出口蛇形增压通道14，第一出口蛇形增压通道8可用于提高微流控芯片内部压力，减小系统外部微小压力波动的相对大小，降低其影响。After completing the asymmetric splitting, the sub-double emulsion droplets flow through the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and enter the second outlet serpentine pressurization channel 14 respectively, and the first outlet serpentine Boost channel 8. Finally, it is input from the second sub-double emulsion drop outlet 10 and the first sub-double emulsion drop outlet 4, and flows into the external conduit. Since the small fluctuation of the external pressure of the system will cause the instability of the split ratio, the second outlet serpentine pressurization channel 14 and the first outlet serpentine pressurization channel 8 can be used to increase the internal pressure of the microfluidic chip and reduce the micro pressure outside the system The relative size of the fluctuation, reducing its impact.
与现有技术相比，本发明具有如下有益效果。Compared with the prior art, the present invention has the following beneficial effects.
1、本发明的新颖之处是区别于利用不同尺寸参数的生成装置制备不同尺寸双乳液滴的传统双乳液滴制备方式，在不改变装置几何参数的情况下获得不同尺寸的双乳液滴。1. The novelty of the present invention is that it is different from the traditional double-emulsion droplet preparation method in which double-emulsion droplets of different sizes are prepared by means of generating devices with different size parameters, and double-emulsion droplets of different sizes can be obtained without changing the geometric parameters of the device.
2、本发明的新颖之处是结合以往单乳液滴的分裂方式，利用支路附加流量调节单侧支路流阻，实现双乳液滴的非对称分裂，控制双乳液滴的尺寸。2. The novelty of the present invention is to combine the splitting method of the single emulsion droplet in the past, and use the additional flow of the branch to adjust the flow resistance of the single side branch, realize the asymmetric splitting of the double emulsion droplet, and control the size of the double emulsion droplet.
附图说明Description of drawings
图1是本发明基于附加流量实现双乳液滴非对称分裂的微流控芯片的三维透视图。Fig. 1 is a three-dimensional perspective view of a microfluidic chip that realizes asymmetric splitting of double emulsion droplets based on additional flow in the present invention.
图2是本发明基于附加流量实现双乳液滴非对称分裂的微流控芯片的俯视图。Fig. 2 is a top view of a microfluidic chip for asymmetric splitting of double emulsion droplets based on additional flow in the present invention.
图中包括了双乳液滴注射入口1、蛇形增压通道2、双乳液滴运动速度调节入口3、第一子双乳液滴出口4、双乳液滴分裂岔口5、第一双乳液滴分裂支路6、单侧支路附加流量入口7、第一出口蛇形增压通道8、稳流主通道9、第二子双乳液滴出口10、双乳液滴径向固定通道11、双乳液滴分裂聚焦缩口12、第二双乳液滴分裂支路13、第二出口蛇形增压通道14、主体固体结构15、PDMS底板16。The figure includes double emulsion droplet injection inlet 1, serpentine booster channel 2, double emulsion droplet movement speed adjustment inlet 3, first sub-double emulsion droplet outlet 4, double emulsion droplet splitting fork 5, first double emulsion droplet splitting branch Road 6, single-side branch additional flow inlet 7, first outlet serpentine pressurized channel 8, steady flow main channel 9, second sub-double emulsion droplet outlet 10, double emulsion droplet radial fixed channel 11, double emulsion droplet splitting Focusing constriction 12, second double emulsion droplet splitting branch 13, second outlet serpentine pressurization channel 14, main body solid structure 15, PDMS bottom plate 16.
具体实施方式Detailed ways
下面结合附图对发明的工作原理及效果作进一步说明和验证。The working principle and effect of the invention will be further described and verified below in conjunction with the accompanying drawings.
图1是本发明基于附加流量实现双乳液滴非对称分裂的微流控芯片的三维透视图。该微流控芯片包括主体固体结构15、双乳液滴注射入口1、双乳液滴运动速度调节入口3、单侧支路附加流量入口7、第二子双乳液滴出口10、第一子双乳液滴出口4、蛇形增压通道2、第二出口蛇形增压通道14、第一出口蛇形增压通道8、双乳液滴径向固定通道11、双乳液滴分裂聚焦缩口12、双乳液滴分裂岔口5、稳流主通道9、第二双乳液滴分裂支路13、第一双乳液滴分裂支路6、PDMS底板16。Fig. 1 is a three-dimensional perspective view of a microfluidic chip that realizes asymmetric splitting of double emulsion droplets based on additional flow in the present invention. The microfluidic chip includes a main body solid structure 15, a double emulsion droplet injection inlet 1, a double emulsion droplet movement speed adjustment inlet 3, a single-side branch additional flow inlet 7, a second sub-double emulsion droplet outlet 10, a first sub-double emulsion droplet outlet Drip outlet 4, serpentine booster channel 2, second outlet serpentine booster channel 14, first outlet serpentine booster channel 8, double emulsion droplet radial fixed channel 11, double emulsion droplet split focusing constriction 12, double emulsion droplet Emulsion droplet splitting fork 5 , steady flow main channel 9 , second double emulsion droplet splitting branch 13 , first double emulsion droplet splitting branch 6 , PDMS bottom plate 16 .
具体而言，双乳液滴注射入口1、双乳液滴运动速度调节入口3、单侧支路附加流量入口7、第二子双乳液滴出口10、第一子双乳液滴出口4为主体固体结构15上的孔洞结构。蛇形增压通道2、第二出口蛇形增压通道14、第一出口蛇形增压通道8、双乳液滴径向固定通道11、稳流主通道9、第二双乳液滴分裂支路13、第一双乳液滴分裂支路6则为体固体结构1上的凹槽结构。其中，各结构为微流控芯片工作时流体的流动区域。Specifically, the double emulsion droplet injection inlet 1, the double emulsion droplet movement speed adjustment inlet 3, the single-side branch additional flow inlet 7, the second sub-double emulsion droplet outlet 10, and the first sub-double emulsion droplet outlet 4 are the main solid structure 15 hole structure. Serpentine pressurization channel 2, second exit serpentine pressurization channel 14, first exit serpentine pressurization channel 8, double emulsion drop radial fixed channel 11, steady flow main channel 9, second double emulsion drop splitting branch 13. The first double emulsion droplet splitting branch 6 is a groove structure on the bulk solid structure 1 . Wherein, each structure is a fluid flow area when the microfluidic chip works.
所述主体固体结构15和PDMS底板16通过上下键合固定，PDMS底板16置于主体固体结构15之下，用以支撑主体固体结构15并闭合主体固体结构15表面的沟槽结构，形成流体的流动区域。The main body solid structure 15 and the PDMS bottom plate 16 are fixed by bonding up and down, and the PDMS bottom plate 16 is placed under the main body solid structure 15 to support the main body solid structure 15 and close the groove structure on the surface of the main body solid structure 15 to form a fluid flow area.
所述主体固体结构15和PDMS底板16均通过聚二甲基硅氧烷浇筑并加热固化制成，具有良好的透明性，可方便利用显微镜观测微流控芯片内部双乳液滴分裂状况。Both the main body solid structure 15 and the PDMS bottom plate 16 are made by pouring polydimethylsiloxane and heating and curing, which have good transparency and can be conveniently observed by a microscope for the splitting of double emulsion droplets inside the microfluidic chip.
所述双乳液滴注射入口1用于连接导管，以注入已制备好的尺寸均一的双乳液滴，双乳液滴注射入口1直接连接稳流主通道9，用于双乳液滴的输送。双乳液滴运动速度调节入口3连接蛇形增压通道2，蛇形增压通道2接入在稳流主通道9的一侧，用于调节双乳液滴间隔距离以及运输速度。The double-emulsion droplet injection inlet 1 is used to connect a catheter to inject the prepared double-emulsion droplet with uniform size. The double-emulsion droplet injection inlet 1 is directly connected to the steady flow main channel 9 for the delivery of the double-emulsion droplet. The double-emulsion droplet movement speed adjustment inlet 3 is connected to the serpentine booster channel 2, which is connected to one side of the steady-flow main channel 9, and is used to adjust the distance between the double-emulsion droplets and the transport speed.
所述稳流主通道9的尾部接入了双乳液滴径向固定通道11，用于维持双乳液滴内核及外壳的同轴性，在双乳液滴径向固定通道11的尾部是双乳液滴分裂聚焦缩口12以及双乳液滴分裂岔口5，用于双乳液滴的实际分裂。The afterbody of described steady-flow main channel 9 is connected with double emulsion droplet radially fixed channel 11, is used for maintaining the coaxiality of double emulsion droplet inner core and shell, and the afterbody of double emulsion droplet radially fixed channel 11 is double emulsion droplet The split focusing constriction 12 and the double emulsion droplet splitting fork 5 are used for the actual splitting of the double emulsion droplet.
所述双乳液滴分裂岔口5的两侧分别是第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，第二双乳液滴分裂支路13尾部接入了第二出口蛇形增压通道14。第一双乳液滴分裂支路6尾部接入了第一出口蛇形增压通道8，在第一双乳液滴分裂支路6以及第一出口蛇形增压通道8之间接有单侧支路附加流量入口7，用于改变附加流量，引起第二双乳液滴分裂支路13、第一双乳液滴分裂支路6内部的压力差。The two sides of the double emulsion droplet splitting fork 5 are respectively the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and the tail of the second double emulsion droplet splitting branch 13 is connected to the second outlet snake Shaped pressurization channel 14. The tail of the first double-emulsion droplet splitting branch 6 is connected to the first outlet serpentine pressurization channel 8, and a single-side branch is connected between the first double emulsion droplet splitting branch 6 and the first outlet serpentine pressurization channel 8 The additional flow inlet 7 is used to change the additional flow to cause the pressure difference inside the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6 .
所述第二双乳液滴分裂支路13、第一双乳液滴分裂支路6末端分别接入第二子双乳液滴出口10、第一子双乳液滴出口4。第二子双乳液滴出口10、第一子双乳液滴出口4将接连导管，用于输出分裂获得的子双乳液滴。The ends of the second double-emulsion droplet splitting branch 13 and the first double-emulsion droplet splitting branch 6 are connected to the second sub-double-emulsion droplet 10 and the first sub-double-emulsion droplet 4 respectively. The second sub-double-emulsion outlet 10 and the first sub-double-emulsion outlet 4 will be connected with conduits for outputting sub-double-emulsion droplets obtained by splitting.
本发明的工作过程如下，将制备好的双乳液滴通过导管输入双乳液滴注射入口1，随着流体流动，双乳液滴流入稳流主通道9于蛇形增压通道2交汇处。另一方面，流体从双乳液滴运动速度调节入口3流入主体固体结构15和PDMS底板16制作成的微流控芯片，经过蛇形增压通道2，与双乳液滴同时进入稳流主通道9。通过调节流体从双乳液滴运动速度调节入口3的流量大小，可以控制双乳液滴的运动速度，调节分裂稳定性。The working process of the present invention is as follows, the prepared double emulsion droplets are input into the double emulsion droplet injection inlet 1 through the catheter, and as the fluid flows, the double emulsion droplets flow into the steady flow main channel 9 at the junction of the serpentine pressurized channel 2 . On the other hand, the fluid flows into the microfluidic chip made of the main body solid structure 15 and the PDMS bottom plate 16 from the double emulsion droplet velocity adjustment inlet 3, passes through the serpentine pressurized channel 2, and enters the steady flow main channel 9 at the same time as the double emulsion droplet . By adjusting the moving speed of the fluid from the double emulsion droplet to adjust the flow rate of the inlet 3, the moving speed of the double emulsion droplet can be controlled and the splitting stability can be adjusted.
随后，双乳液滴流入稳流主通道9的末端，进入双乳液滴径向固定通道11，双乳液滴径向固定通道11将双乳液滴径向固定起来，经过双乳液滴分裂聚焦缩口12，双乳液滴射入双乳液滴分裂岔口5发生分裂。另一方面，单侧支路附加流量入口7接入附加流量，引起第二双乳液滴分裂支路13、第一双乳液滴分裂支路6内部的压力差。最终，双乳液滴在双乳液滴分裂岔口5发生非对称分裂，通过调节单侧支路附加流量入口7的流量大小，可以进一步调节双乳液滴的分裂比。Subsequently, the double-emulsion droplets flow into the end of the steady-flow main channel 9 and enter the double-emulsion droplet radially fixed channel 11. The double-emulsion droplet radially fixed channel 11 fixes the double-emulsion droplet in the radial direction. , the double-emulsion droplet is injected into the double-emulsion droplet splitting fork 5 to split. On the other hand, the additional flow inlet 7 of the single-side branch is connected with the additional flow, causing a pressure difference inside the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6 . Finally, the double-emulsion droplet splits asymmetrically at the double-emulsion droplet splitting fork 5, and the splitting ratio of the double-emulsion droplet can be further adjusted by adjusting the flow rate of the additional flow inlet 7 of the unilateral branch.
在完成非对称分裂之后，子双乳液滴流经第二双乳液滴分裂支路13、第一双乳液滴分裂支路6，分别进入第二出口蛇形增压通道14，第一出口蛇形增压通道8。最终，从第二子双乳液滴出口10、第一子双乳液滴出口4输入，流入外接导管。由于系统外部压力的微小波动会引起分裂比的不稳定，第二出口蛇形增压通道14，第一出口蛇形增压通道8可用于提高微流控芯片内部压力，减小系统外部微小压力波动的相对大小，降低其影响。After completing the asymmetric splitting, the sub-double emulsion droplets flow through the second double emulsion droplet splitting branch 13 and the first double emulsion droplet splitting branch 6, and enter the second outlet serpentine pressurization channel 14 respectively, and the first outlet serpentine Boost channel 8. Finally, it is input from the second sub-double emulsion drop outlet 10 and the first sub-double emulsion drop outlet 4, and flows into the external conduit. Since the small fluctuation of the external pressure of the system will cause the instability of the split ratio, the second outlet serpentine pressurization channel 14 and the first outlet serpentine pressurization channel 8 can be used to increase the internal pressure of the microfluidic chip and reduce the micro pressure outside the system The relative size of the fluctuation, reducing its impact.
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