CN211190233U - A microfluidic structure and microfluidic chip for quantitative heterogeneous reactions - Google Patents
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Abstract
Description
技术领域technical field
本实用新型属于微流控技术领域,尤其涉及一种用于定量非均相反应的微流道结构和微流控芯片。The utility model belongs to the technical field of microfluidics, in particular to a microfluidic channel structure and a microfluidic control chip for quantitative heterogeneous reaction.
背景技术Background technique
近年来,生物、化学、能源、环保等多个领域越来越多地使用微型化反应手段进行微量精准的操作,微流控技术便是其中最重要的技术手段之一。微流控技术利用微尺度通道和装置对微量液体(或样品)进行操控,可以将样品制备、化学反应以及检测等集成到微小的芯片上进行系统化、程序化、规范化的操作。In recent years, many fields such as biology, chemistry, energy, and environmental protection have increasingly used miniaturized reaction methods for micro-precision operations, and microfluidic technology is one of the most important technical methods. Microfluidic technology utilizes micro-scale channels and devices to manipulate trace amounts of liquids (or samples), and can integrate sample preparation, chemical reactions, and detection into tiny chips for systematic, programmed, and standardized operations.
常规的微液滴制备,目前主要是通过机械搅拌法,这种方法并不能准确的对粒径尺寸进行控制且由于不能对反应物量进行精准控制而不能确保反应的有效充分进行。微流控技术进样量极小,且反应快速准确易自动化控制,尤其是微尺寸通道带来的比表面积大、操作距离缩短且全程可控以及可对精确的复杂液流进行控制等特点,使之成为某些领域替代常规反应的热门技术。Conventional microdroplet preparation is currently mainly carried out by mechanical stirring method. This method cannot accurately control the particle size and cannot ensure the effective and sufficient progress of the reaction due to the inability to precisely control the amount of reactants. Microfluidic technology has a very small injection volume, and the reaction is fast, accurate and easy to automate control, especially the characteristics of large specific surface area, shortened operating distance and controllable whole process brought by micro-sized channels, and can control precise and complex liquid flow, etc. Making it a popular alternative to conventional reactions in some fields.
使用微流控生成微液滴的方法主要可分为主动式和被动式两大类。主动式方法是指通过施加气压、电场等外力改变液体的流动从而得到微液滴。被动式方法通过对微通道的流道形状改变与流体的流动特性控制液相流动产生微液滴,操作简单方便且制作成本低廉。采用被动迪恩流是目前微流控聚焦微球最有效的方式之一,通过被动迪恩流能够将在微流道中紊乱散布的微球聚焦成等间距排布的微球队列,其原理是利用流体在螺旋聚焦弯微流道中的离心力引发二次涡流,对液相中的微球施加迪恩拖曳力,同时微球还受到惯性流的惯性升力,微球在同时受二种力的共同作用下,最终在流道截面上的固定位置保持不变。The methods of generating microdroplets using microfluidics can be mainly divided into two categories: active and passive. The active method refers to obtaining micro droplets by applying external forces such as air pressure and electric field to change the flow of the liquid. The passive method controls the flow of the liquid phase by changing the shape of the flow channel of the microchannel and the flow characteristics of the fluid to generate microdroplets, which is simple and convenient to operate and has a low production cost. Passive Dean flow is one of the most effective ways to focus microspheres in microfluidics. Passive Dean flow can focus the chaotically dispersed microspheres in the microchannel into an array of microspheres arranged at equal intervals. It uses the centrifugal force of the fluid in the spiral focusing curved microchannel to induce secondary eddy currents, and exerts a Dean drag force on the microspheres in the liquid phase. At the same time, the microspheres are also subjected to the inertial lift force of the inertial flow, and the microspheres are simultaneously affected by the two forces. Under the combined action, the final fixed position on the flow channel section remains unchanged.
虽然通过被动迪恩流聚焦后的等间距排布的微球队列在一定程度上实现分散,但是如何实现精准定量控制微球的数量再与反应液充分混合进行非均相精确高效反应,成为本领域技术亟待解决的问题之一。Although the uniformly spaced array of microspheres after passive Dean flow focusing can achieve dispersion to a certain extent, how to achieve precise and quantitative control of the number of microspheres and then fully mix them with the reaction solution for heterogeneous, accurate and efficient reaction has become a problem. One of the problems to be solved urgently in the art.
实用新型内容Utility model content
有鉴于此,本申请提供了一种用于定量非均相反应的微流道结构和微流控芯片,用于解决现有技术在进行非均相反应时,无法精准定量控制微球的数量的问题。In view of this, the present application provides a microfluidic channel structure and a microfluidic chip for quantitative heterogeneous reactions, which are used to solve the problem that the prior art cannot accurately and quantitatively control the number of microspheres during heterogeneous reactions. The problem.
本实用新型的具体技术方案如下:The concrete technical scheme of the present utility model is as follows:
一种微流道结构,包括:微球聚焦单元、主动阀定量控制单元和同轴流非均相反应单元;A microfluidic channel structure, comprising: a microsphere focusing unit, an active valve quantitative control unit and a coaxial flow heterogeneous reaction unit;
所述微球聚焦单元包括第一液相进样口和涡旋聚焦弯道,所述第一液相进样口和所述涡旋聚焦弯道的第一端连通;The microsphere focusing unit includes a first liquid phase injection port and a vortex focusing curve, and the first liquid phase injection port is communicated with the first end of the vortex focusing curve;
所述主动阀定量控制单元包括第一液相流道、气相进样口和气相流道,所述第一液相流道和所述涡旋聚焦弯道的第二端连通,所述第一液相流道的内壁设置有阀块,所述气相进样口与所述气相流道的第一端连通,所述气相流道与所述第一液相流道非连通设置,所述气相流道用于调节设置有所述阀块的所述第一液相流道处的开闭;The active valve quantitative control unit includes a first liquid-phase flow channel, a gas-phase injection port and a gas-phase flow channel, the first liquid-phase flow channel is communicated with the second end of the vortex focusing curve, and the first liquid-phase flow channel is in communication with the second end of the vortex focusing curve. The inner wall of the liquid-phase flow channel is provided with a valve block, the gas-phase injection port is communicated with the first end of the gas-phase flow channel, the gas-phase flow channel is not communicated with the first liquid-phase flow channel, and the gas-phase flow channel is not communicated with the first liquid-phase flow channel. The flow channel is used to adjust the opening and closing of the first liquid-phase flow channel provided with the valve block;
所述同轴流非均相反应单元包括第一液相流道、第二液相流道、第三液相流道和第四液相流道,所述第二液相流道的出口和所述第三液相流道的出口连通所述第四液相流道并位于所述第一液相流道的外侧,所述第一液相流道和所述第四液相流道同轴且所述第一液相流道的出口设置于所述第四液相流道的中心处。The coaxial flow heterogeneous reaction unit includes a first liquid-phase flow channel, a second liquid-phase flow channel, a third liquid-phase flow channel and a fourth liquid-phase flow channel, the outlet of the second liquid-phase flow channel and the The outlet of the third liquid-phase flow channel is connected to the fourth liquid-phase flow channel and is located outside the first liquid-phase flow channel, and the first liquid-phase flow channel and the fourth liquid-phase flow channel are the same as the first liquid-phase flow channel. axis and the outlet of the first liquid phase flow channel is disposed at the center of the fourth liquid phase flow channel.
优选的,所述阀块和所述气相流道的数量相同;Preferably, the valve blocks and the gas-phase flow passages have the same number;
所述阀块的数量为两个以上。The number of the valve blocks is two or more.
优选的,所述主动阀定量控制单元还包括气体缓冲室;Preferably, the active valve quantitative control unit further includes a gas buffer chamber;
所述气体缓冲室与所述气相流道的第二端连通,所述气相流道可通过所述气体缓冲室调节设置有所述阀块的所述第一液相流道处的开闭。The gas buffer chamber communicates with the second end of the gas-phase flow channel, and the gas-phase flow channel can be opened and closed at the first liquid-phase flow channel provided with the valve block through the gas buffer chamber.
优选的,所述阀块为长方体阀块;Preferably, the valve block is a cuboid valve block;
所述气体缓冲室在工作状态时与所述第一液相流道的接触面为曲面。The contact surface of the gas buffer chamber and the first liquid phase flow channel is a curved surface in a working state.
优选的,所述涡旋聚焦弯道、所述第一液相流道和所述气相流道的横截面形状相同;Preferably, the cross-sectional shapes of the vortex focusing curve, the first liquid phase flow channel and the gas phase flow channel are the same;
所述涡旋聚焦弯道、所述第一液相流道和所述气相流道的高度相同且为100μm~200μm。The heights of the vortex focusing curve, the first liquid-phase flow channel and the gas-phase flow channel are the same and are 100 μm˜200 μm.
优选的,所述涡旋聚焦弯道的总长度为100mm~1000mm;Preferably, the total length of the vortex focusing curve is 100mm-1000mm;
所述涡旋聚焦弯道的宽度为100μm~200μm;The width of the vortex focusing curve is 100 μm˜200 μm;
所述涡旋聚焦弯道的相邻两流道的间距为100μm~300μm;The distance between two adjacent flow channels of the vortex focusing curve is 100 μm˜300 μm;
所述涡旋聚焦弯道的最内侧流道的曲率半径为20mm~30mm。The radius of curvature of the innermost flow channel of the vortex focusing curve is 20mm˜30mm.
本实用新型还提供了一种微流控芯片,包括:芯片本体和上述技术方案所述微流道结构;The utility model also provides a microfluidic chip, comprising: a chip body and the microfluidic channel structure described in the above technical solution;
所述微流道结构设置于所述芯片本体内;The micro-channel structure is arranged in the chip body;
所述第一液相进样口、所述气相进样口、所述第二液相流道的进口、所述第三液相流道的进口和所述第四液相流道的出口均开设于所述芯片本体的上表面。The first liquid phase inlet, the gas phase inlet, the inlet of the second liquid phase flow channel, the inlet of the third liquid phase flow channel and the outlet of the fourth liquid phase flow channel are all is opened on the upper surface of the chip body.
优选的,还包括:输送装置和提取装置;Preferably, it also includes: a conveying device and an extracting device;
所述输送装置包括与所述第一液相进样口连通的第一输送泵、与所述气相进样口连通的第二输送泵、与所述第二液相流道的进口连通的第三输送泵以及与所述第三液相流道的进口连通的第四输送泵;The delivery device includes a first delivery pump communicated with the first liquid phase inlet, a second delivery pump communicated with the gas phase inlet, and a second delivery pump communicated with the inlet of the second liquid phase flow channel. three delivery pumps and a fourth delivery pump communicated with the inlet of the third liquid phase flow channel;
所述提取装置与所述第四液相流道的出口连通。The extraction device communicates with the outlet of the fourth liquid phase flow channel.
优选的,所述芯片本体包括基板和盖板;Preferably, the chip body includes a substrate and a cover;
所述基板上表面设置有所述微流道结构;The upper surface of the substrate is provided with the micro-channel structure;
所述盖板覆盖在所述基板的上表面,且所述第一液相进样口、所述气相进样口、所述第二液相流道的进口、所述第三液相流道的进口和所述第四液相流道的出口开设于所述盖板上。The cover plate covers the upper surface of the substrate, and the first liquid phase inlet, the gas phase inlet, the inlet of the second liquid phase flow channel, and the third liquid phase flow channel The inlet and the outlet of the fourth liquid phase flow channel are opened on the cover plate.
综上所述,本实用新型提供了一种微流道结构,包括:微球聚焦单元、主动阀定量控制单元和同轴流非均相反应单元;所述微球聚焦单元包括第一液相进样口和涡旋聚焦弯道,所述第一液相进样口和所述涡旋聚焦弯道的第一端连通;所述主动阀定量控制单元包括第一液相流道、气相进样口和气相流道,所述第一液相流道和所述涡旋聚焦弯道的第二端连通,所述第一液相流道的内壁设置有阀块,所述气相进样口与所述气相流道的第一端连通,所述气相流道与所述第一液相流道非连通设置,所述气相流道用于调节设置有所述阀块的所述第一液相流道处的开闭;所述同轴流非均相反应单元包括第一液相流道、第二液相流道、第三液相流道和第四液相流道,所述第二液相流道和所述第三液相流道的出口连通所述第四液相流道并位于所述第一液相流道的外侧,所述第一液相流道和所述第四液相流道同轴且所述第一液相流道的出口设置于所述第四液相流道的中心处。In summary, the present invention provides a micro-channel structure, including: a micro-sphere focusing unit, an active valve quantitative control unit and a coaxial flow heterogeneous reaction unit; the micro-sphere focusing unit includes a first liquid phase The injection port and the vortex focusing curve are in communication with the first liquid phase injection port and the first end of the vortex focusing curve; the active valve quantitative control unit includes a first liquid phase flow channel, a gas phase inlet A sample port and a gas-phase flow channel, the first liquid-phase flow channel is communicated with the second end of the vortex focusing bend, the inner wall of the first liquid-phase flow channel is provided with a valve block, and the gas-phase injection port communicated with the first end of the gas-phase flow channel, the gas-phase flow channel is not communicated with the first liquid-phase flow channel, and the gas-phase flow channel is used to adjust the first liquid-phase flow channel provided with the valve block The opening and closing of the phase flow channel; the coaxial flow heterogeneous reaction unit includes a first liquid phase flow channel, a second liquid phase flow channel, a third liquid phase flow channel and a fourth liquid phase flow channel, and the first liquid phase flow channel Outlets of the second liquid phase flow channel and the third liquid phase flow channel communicate with the fourth liquid phase flow channel and are located outside the first liquid phase flow channel. The first liquid phase flow channel and the third liquid phase flow channel The four liquid phase flow channels are coaxial and the outlet of the first liquid phase flow channel is arranged at the center of the fourth liquid phase flow channel.
本实用新型微流道结构包括微球聚焦单元、主动阀定量控制单元和同轴流非均相反应单元,微球聚焦单元包括涡旋聚焦弯道,微球聚焦单元将微球聚焦形成直线微球队列并保持等间距排布,主动阀定量控制单元包括第一液相流道、气相进样口和气相流道,第一液相流道的内壁设置有阀块,气相流道用于调节设置有阀块的第一液相流道处的开闭,主动阀定量控制单元对聚焦成等间距排列的微球进行定量分散,第二液相流道和第三液相流道的出口连通第四液相流道并位于第一液相流道的外侧,第一液相流道和第四液相流道同轴且第一液相流道的出口设置于第四液相流道的中心处,再通过第二液相流道和第三液相流道中的反应液对定量分散的微球进行充分包裹,实现微球的定量非均相反应,且该微流道结构密闭,气相流道和第一液相流道未连通,对微液滴内含物的理化学性质不会产生任何影响。本实用新型微流道结构可打破传统方法固液非均相反应中,微球数量无法精准控制导致的反应不充分、不均匀等限制,可快速大量生成精准调控的微液滴,实现定量非均相反应。常温常压条件下,通过调节主动阀定量控制单元中第一液相流道的微球就可以快速准确控制,并且该微流道结构的结构简单,易于大批量制作,可推广应用于生物医药和轻工化工等众多领域。The microfluidic channel structure of the utility model comprises a microsphere focusing unit, an active valve quantitative control unit and a coaxial flow heterogeneous reaction unit. The microsphere focusing unit includes a vortex focusing curve, and the microsphere focusing unit focuses the microspheres to form a linear microsphere. The teams are arranged at equal intervals. The active valve quantitative control unit includes a first liquid-phase flow channel, a gas-phase injection port and a gas-phase flow channel. The inner wall of the first liquid-phase flow channel is provided with a valve block, and the gas-phase flow channel is used for Adjust the opening and closing of the first liquid phase flow channel provided with the valve block, the active valve quantitative control unit quantitatively disperses the microspheres focused into equal spacing, and the outlets of the second liquid phase flow channel and the third liquid phase flow channel The fourth liquid-phase flow channel is connected to and is located outside the first liquid-phase flow channel, the first liquid-phase flow channel and the fourth liquid-phase flow channel are coaxial, and the outlet of the first liquid-phase flow channel is arranged in the fourth liquid-phase flow channel At the center of the microspheres, the quantitatively dispersed microspheres are fully wrapped by the reaction solution in the second liquid phase flow channel and the third liquid phase flow channel to realize the quantitative heterogeneous reaction of the microspheres, and the microfluidic channel structure is airtight, The gas-phase flow channel and the first liquid-phase flow channel are not connected, and will not have any influence on the physicochemical properties of the contents of the droplets. The micro-flow channel structure of the utility model can break the limitation of insufficient and uneven reaction caused by the inability to precisely control the number of microspheres in the solid-liquid heterogeneous reaction of the traditional method, and can quickly generate a large number of precisely controlled micro-droplets, thereby realizing quantitative non-uniformity. Homogeneous reaction. Under the conditions of normal temperature and pressure, it can be quickly and accurately controlled by adjusting the microspheres of the first liquid phase flow channel in the quantitative control unit of the active valve, and the structure of the microchannel structure is simple, easy to manufacture in large quantities, and can be widely used in biomedicine. and light industry and chemical industry and many other fields.
附图说明Description of drawings
为了更清楚地说明本实用新型实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。In order to illustrate the embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that are required to be used in the description of the embodiments or the prior art.
图1为本实用新型实施例中提供的一种微流道结构的示意图;1 is a schematic diagram of a micro-channel structure provided in an embodiment of the present invention;
图2为本实用新型实施例中提供的一种微流道结构中的涡旋聚焦弯道的示意图;2 is a schematic diagram of a vortex focusing curve in a microfluidic channel structure provided in an embodiment of the present invention;
图3为本实用新型实施例中提供的一种微流道结构中主动阀定量控制单元的工作原理示意图;3 is a schematic diagram of the working principle of an active valve quantitative control unit in a micro-channel structure provided in an embodiment of the present invention;
图4为本实用新型实施例中提供的一种微流控芯片的整体结构示意图;4 is a schematic diagram of the overall structure of a microfluidic chip provided in an embodiment of the present invention;
图示说明:100.微球聚焦单元;101.第一液相进样口;102.涡旋聚焦弯道;200.主动阀定量控制单元;201.第一液相流道;202.阀块;203.气相进样口;204.气相流道;205.气体缓冲室;300.同轴流非均相反应单元;301.第一液相流道的出口;302.第四液相流道;303.第二液相流道;304.第三液相流道;305.第三液相流道的进口;306.第二液相流道的进口;307.第四液相流道的出口;41.第一输送泵;42.第二输送泵;43.第三输送泵;44.第四输送泵;45.提取装置;46.盖板;47.基板。Illustration description: 100. Microsphere focusing unit; 101. First liquid phase inlet; 102. Vortex focusing curve; 200. Active valve quantitative control unit; 201. First liquid phase flow channel; 202.
具体实施方式Detailed ways
本实用新型提供了一种微流道结构、微流控芯片和定量非均相反应的方法,用于解决现有技术在进行非均相反应时,无法精准定量控制微球的数量的问题。The utility model provides a microfluidic channel structure, a microfluidic control chip and a quantitative heterogeneous reaction method, which are used to solve the problem that the quantity of microspheres cannot be accurately and quantitatively controlled when the heterogeneous reaction is performed in the prior art.
下面将对本实用新型实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本实用新型一部分实施例,而不是全部的实施例。基于本实用新型中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本实用新型保护的范围。The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present invention.
请参阅图1和图2,图1为本实用新型实施例中提供的一种微流道结构的示意图,图2为本实用新型实施例中提供的一种微流道结构中的涡旋聚焦弯道的示意图。Please refer to FIG. 1 and FIG. 2 , FIG. 1 is a schematic diagram of a micro-channel structure provided in an embodiment of the present invention, and FIG. 2 is a vortex focusing in a micro-channel structure provided in an embodiment of the present invention Schematic diagram of the bend.
本实用新型实施例提供的一种微流道结构的一个实施例,包括:微球聚焦单元100、主动阀定量控制单元200和同轴流非均相反应单元300;An example of a microfluidic structure provided by the embodiment of the present invention includes: a
微球聚焦单元100包括第一液相进样口101和涡旋聚焦弯道102,第一液相进样口101和涡旋聚焦弯道102的第一端连通;The
主动阀定量控制单元200包括第一液相流道201、气相进样口203和气相流道204,第一液相流道201和涡旋聚焦弯道102的第二端连通,第一液相流道201的内壁设置有阀块202,气相进样口203与气相流道204的第一端连通,气相流道204与第一液相流道201非连通设置,气相流道204用于调节设置有阀块202的第一液相流道201处的开闭;The active valve
同轴流非均相反应单元300包括第一液相流道201、第二液相流道303、第三液相流道304和第四液相流道302,第二液相流道303的出口和第三液相流道304的出口连通第四液相流道302并位于第一液相流道201的外侧,第一液相流道201和第四液相流道302同轴且第一液相流道的出口301设置于第四液相流道302的中心处。The coaxial flow
本实用新型微流道结构包括微球聚焦单元100、主动阀定量控制单元200和同轴流非均相反应单元300,微球聚焦单元100包括涡旋聚焦弯道102,微球聚焦单元100将微球聚焦形成直线微球队列并保持等间距排布,主动阀定量控制单元200包括第一液相流道201、气相进样口203和气相流道204,第一液相流道201的内壁设置有阀块202,气相流道204用于调节设置有阀块202的第一液相流道201处的开闭,主动阀定量控制单元200对聚焦成等间距排列的微球进行定量分散,第二液相流道303和第三液相流道304的出口连通第四液相流道302并位于第一液相流道201的外侧,第一液相流道201和第四液相流道302同轴且第一液相流道的出口301设置于第四液相流道302的中心处,再通过第二液相流道303和第三液相流道304中的反应液对定量分散的微球进行充分包裹,实现微球的定量非均相反应,且该微流道结构密闭,气相流道204和第一液相流道201未连通,对微液滴内含物的理化学性质不会产生任何影响。本实用新型微流道结构可打破传统方法固液非均相反应中,微球数量无法精准控制导致的反应不充分、不均匀等限制,可快速大量生成精准调控的微液滴,实现定量非均相反应。常温常压条件下,通过调节主动阀定量控制单元200中第一液相流道201的微球就可以快速准确控制,并且该微流道结构的结构简单,易于大批量制作,可推广应用于生物医药和轻工化工等众多领域。The microfluidic channel structure of the present invention includes a
本实用新型实施例中,第一液相进样口101可外接微球悬浮液,为了保持微球悬浮液浓度相对均匀,制样过程中可以采用溶剂分散或持续磁力搅拌和超声分散等方法。微球悬浮液通过第一液相进样口101进入涡旋聚焦弯道102使微球悬浮液分散稳定。In the embodiment of the present invention, the first
本实用新型实施例中,阀块202和气相流道204的数量相同;In the embodiment of the present invention, the valve blocks 202 and the gas-
阀块202的数量为两个以上,优选为两个。The number of valve blocks 202 is two or more, preferably two.
本实用新型实施例中,主动阀定量控制单元200还包括气体缓冲室205;In the embodiment of the present invention, the active valve
气体缓冲室205与气相流道204的第二端连通,气相流道204可通过气体缓冲室205调节设置有阀块202的第一液相流道201处的开闭。The
本实用新型实施例中,气体缓冲室205和第一液相流道201的材料为弹性材料,优选为聚二甲基硅氧烷(PDMS)、橡胶或聚乙烯(PE)。In the embodiment of the present invention, the material of the
本实用新型实施例气体缓冲室205的设置为了避免气相流道204直接与第一液相流道201的壁面接触导致第一液相流道201壁面破损。在气体缓冲室205不在工作状态时,气体缓冲室205和第一液相流道201壁保持距离,气体缓冲室205和第一液相流道201壁的距离为30μm~100μm。The setting of the
请参阅图3,为本实用新型实施例中提供的一种微流道结构中主动阀定量控制单元200的工作原理示意图。气相进样口203外接气动泵,使用惰性气体,气相流道204的一端与气相进样口203直接相通,气相流道204的另一端连通至气体缓冲室205。通过气动泵调节气流的流量,当惰性气体充斥整个气相流道204,再持续充入气体会导致气体缓冲室205压力增大,从而对第一液相流道201壁面形成压力,迫使第一液相流道201壁面弯曲与阀块202相接触达到阻断液流的作用;一段时间过后,气动泵停止输出气体并进行相应放气处理,则第一液相流道201壁面恢复,微球悬浮液可以继续通过,进而实现定量控制。Please refer to FIG. 3 , which is a schematic diagram of the working principle of the active valve
第二液相流道303和第三液相流道304的入口外接反应液,与定量控制完成的微球悬浮液进行充分混合,实现精准控制的定量非均相反应。The inlets of the second liquid-
本实用新型实施例中,定量控制后的微球悬浮液通过第一液相流道201进入更大管径的第四液相流道302,第二液相流道303和第三液相流道304的出口连通第四液相流道302并位于第一液相流道201的外侧。优选的,第二液相流道303和第三液相流道304与第一液相流道201的夹角呈45°。In the embodiment of the present invention, the quantitatively controlled microsphere suspension enters the fourth liquid
本实用新型实施例中,阀块202为长方体阀块;In the embodiment of the present invention, the
气体缓冲室205在工作状态时与第一液相流道201的接触面为曲面。曲面可以增大气体缓冲室205与第一液相流道201的接触面积,减小压强,可以有效地防止第一液相流道201的流道壁面因受力集中而破裂,并可实现与长方体阀块充分接触,从而保证精准的微球数量控制。The contact surface of the
本实用新型实施例中,涡旋聚焦弯道102、第一液相流道201和气相流道204的横截面形状相同;In the embodiment of the present invention, the cross-sectional shapes of the
涡旋聚焦弯道102、第一液相流道201和气相流道204的高度相同且为100μm~200μm。The heights of the
进一步的,涡旋聚焦弯道102、第一液相流道201、气相流道204、第二液相流道303、第三液相流道304和第四液相流道302的横截面形状相同,横截面形状优选为矩形;Further, the cross-sectional shapes of the
涡旋聚焦弯道102、第一液相流道201、气相流道204、第二液相流道303、第三液相流道304和第四液相流道302的的高度相同且为100μm~200μm。The heights of the
本实用新型实施例中,涡旋聚焦弯道102的总长度为100mm~1000mm;In the embodiment of the present invention, the total length of the
涡旋聚焦弯道102的宽度为100μm~200μm;The width of the
涡旋聚焦弯道102的相邻两流道的间距为100μm~300μm;The distance between two adjacent flow channels of the
涡旋聚焦弯道102的最内侧流道的曲率半径为20mm~30mm。The radius of curvature of the innermost flow channel of the
本实用新型实施例中,第二液相流道303和第三液相流道304与第一液相流道201在第四液相流道302形成同轴流,第一液相流道201的宽度为100μm~200μm,第二液相流道303和第三液相流道304的宽度均为50μm~150μm,第四液相流道302的宽度为200μm~300μm。In the embodiment of the present invention, the second liquid
气相流道204的宽度为50μm~100μm。The width of the gas-
微球悬浮液中的微球粒径与第一液相流道201的高度之比不大于0.4。The ratio of the particle size of the microspheres in the microsphere suspension to the height of the first liquid
以上是对本实用新型实施例提供的一种微流道结构的一个实施例进行详细的描述,以下将对本实用新型实施例提供的一种微流控芯片的一个实施例进行详细的描述。The above is a detailed description of an embodiment of a microfluidic channel structure provided by an embodiment of the present invention, and an embodiment of a microfluidic chip provided by an embodiment of the present invention will be described in detail below.
本实用新型实施例提供的一种微流控芯片的一个实施例,包括:芯片本体和上述技术方案微流道结构;An embodiment of a microfluidic chip provided by the embodiment of the present invention includes: a chip body and a microfluidic channel structure of the above technical solution;
微流道结构设置于芯片本体内;The micro-channel structure is arranged in the chip body;
第一液相进样口101、气相进样口203、第二液相流道的进口306、第三液相流道的进口305和第四液相流道的出口307均开设于芯片本体的上表面。The first liquid
本实用新型实施例中,还包括:输送装置和提取装置45;In the embodiment of the present utility model, it also includes: a conveying device and an extracting
输送装置包括与第一液相进样口101连通的第一输送泵41、与气相进样口203连通的第二输送泵42、与第二液相流道的进口306连通的第三输送泵43以及与第三液相流道的进口305连通的第四输送泵44;The delivery device includes a
提取装置45与第四液相流道的出口307连通。The
通过输送装置和提取装置45,可以以恒定的速度进行样品输入并稳定提取微流控芯片中的流体,从而保证稳定的聚焦效果,使得微流控芯片的各相入口及所有出口压力保持连贯且一致,使芯片装置中的流体的压力、流速保持恒定。Through the delivery device and the
本实用新型实施例中,芯片本体包括基板47和盖板46;In the embodiment of the present invention, the chip body includes a
基板47上表面设置有微流道结构;The upper surface of the
盖板46覆盖在基板47的上表面,且第一液相进样口101、气相进样口203、第二液相流道的进口306、第三液相流道的进口305和第四液相流道的出口307开设于盖板46上。The
以上是对本实用新型实施例提供的一种微流控芯片的一个实施例进行详细的描述,以下将对本实用新型实施例提供的一种定量非均相反应的方法的一个实施例进行详细的描述。The above is a detailed description of an embodiment of a microfluidic chip provided by the embodiment of the present invention, and an embodiment of a quantitative heterogeneous reaction method provided by the embodiment of the present invention will be described in detail below. .
本实用新型实施例提供的一种微流控芯片的一个应用例,采用上述技术方案微流道结构,包括以下步骤:An application example of a microfluidic chip provided by the embodiment of the present invention adopts the microfluidic channel structure of the above technical solution, and includes the following steps:
S1:将微球悬浮液通过涡旋聚焦弯道102分散并流入主动阀定量控制单元200的第一液相流道201;S1: Disperse the microsphere suspension through the
S2:通过气相流道204调节设置有阀块202的第一液相流道201处的开闭,控制流入同轴流非均相反应单元300的微球悬浮液中的微球数量;S2: adjusting the opening and closing of the first liquid
S3:将反应液通过第二液相流道303和第三液相流道304进入与第一液相流道201同轴的第四液相流道302,与第一液相流道201出口的定量微球进行非均相反应,得到微液滴。S3: The reaction solution enters the fourth liquid
本实用新型应用例中,通过第一液相进样口101将微球悬浮液通过涡旋聚焦弯道102分散,通过第二液相流道303和第三液相流道304的入口向第二液相流道303和第三液相流道304通入反应液,使用气动泵通过气相进样口203向气相流道204通入气体,定量微液滴从提取装置45出口流出。In the application example of the present invention, the microsphere suspension is dispersed through the
气相流道204和第一液相流道201之间有气体缓冲室205隔开,气相流道204受到气动泵输入的气体压力作用,由气体缓冲室205向第一液相流道201有压力产生,促使第一液相流道201壁面弯曲与壁面上的阀块202接触,阻断液流从而达到分散控制微球的作用,通过调节气相流道204和第一液相流道201的流量,可以精准定量控制微球的数量。A
微球在涡旋聚焦弯道102中受到迪恩拖曳力与惯性升力的共同作用,在涡旋聚焦弯道102内形成直线微球队列并在固定位置等间距排列,微球队列悬浮液经过主动阀定量控制单元200控制后与第二液相流道303和第三液相流道304的反应液汇合流入更大管径的第四液相流道302,第二液相流道303和第三液相流道304的反应液先进入第四液相流道302,再与经过主动阀定量控制单元200精准控制的微球混合,定量微球在汇合点被充满第四液相流道302的反应液充分包裹,进行非均相反应,得到微液滴。可经第四液相流道的出口307,通过提取装置45收集所制备的微液滴。The microspheres are subjected to the combined action of Dean's drag force and inertial lift force in the
本实用新型微流控芯片高度集成,整个芯片面积小,仅有数个立方厘米;微流控芯片成本低廉、结构简单,易于批量生产。使用本实用新型微流控芯片进行非均相反应,试剂消耗量小,仅为微升级别。本实用新型定量非均相反应的方法控制精准,经过涡旋聚焦弯道102的微球队列均一高度和间距值,且通过调节气动泵,可精确控制微球悬浮液中微球的数量,实现精准可控的定量控制;该定量非均相反应的方法环境友好,操作过程中均是通过力学原理对微球聚焦分散、定量控制进行操纵,不会对微球的功能活性和理化性质等产生影响;微流控芯片的制造材料对环境均无害;该微流控芯片可选用透明材质制备,可以直接使用显微镜进行观察,同时也可以利用高速摄影仪进行图形记录,操作简便,便于观察;由于气体与微球悬浮液之间隔开,气体不会对微球悬浮液有任何影响的同时进行精准控制,适于用大量非均相反应,适应性强;涡旋聚焦弯道102每秒钟可实现数百颗分散排布微球的输出,且过程连续,单位时间产量高,连续快速。The microfluidic chip of the utility model is highly integrated, the entire chip area is small, only a few cubic centimeters; the microfluidic chip has low cost, simple structure and easy mass production. Using the microfluidic chip of the utility model to carry out heterogeneous reaction, the consumption of reagents is small, only at the microliter level. The quantitative heterogeneous reaction method of the present invention is precisely controlled, the height and spacing of the microsphere array passing through the
为了进一步理解本实用新型,下面结合具体实施例对本实用新型进行详细阐述。In order to further understand the present utility model, the present utility model will be described in detail below with reference to specific embodiments.
实施例1Example 1
本实施例微流控芯片的材质为聚二甲基硅氧烷(PDMS),其中,涡旋聚焦弯道的总长度为400mm,涡旋聚焦弯道的相邻两流道的间距为150μm,涡旋聚焦弯道的最内侧流道的曲率半径为20mm,气相流道、第二液相流道和第三液相流道的宽度均为50μm,第一液相流道的宽度为100μm,第四液相流道的宽度为200μm,气体缓冲室在非工作状态时与第一液相流道壁距离为40μm,所有流道高度为100μm。The material of the microfluidic chip in this embodiment is polydimethylsiloxane (PDMS), wherein the total length of the vortex focusing curve is 400 mm, and the distance between two adjacent flow channels of the vortex focusing curve is 150 μm. The radius of curvature of the innermost flow channel of the vortex focusing curve is 20mm, the width of the gas-phase flow channel, the second liquid-phase flow channel and the third liquid-phase flow channel are all 50 μm, and the width of the first liquid-phase flow channel is 100 μm. The width of the fourth liquid phase flow channel is 200 μm, the distance between the gas buffer chamber and the wall of the first liquid phase flow channel is 40 μm in the non-working state, and the height of all the flow channels is 100 μm.
采用本实施例微流控芯片进行定量非均相反应,具体包括:选用氮气作为气相,微球悬浮液的固相为粒径30μm二氧化钛微球,甲基蓝水溶液作为反应液,同时使用外部光源进行持续光照处理。使用聚四氟乙烯毛细软管分别将微球悬浮液和反应液注入芯片,并利用气动泵控制气相流体。微球悬浮液的流量为30μl/min,气相流量为50μl/min,第二液相流道和第三液相流道的反应液流量均为30μl/min,调节气相和微球悬浮液流量可以使得微球悬浮液中的定量二氧化钛微球与甲基蓝在光照条件下进行精准高效充分的非均相反应,得到亚甲基蓝或次甲基蓝。The microfluidic chip of this embodiment is used to perform quantitative heterogeneous reaction, which specifically includes: selecting nitrogen gas as the gas phase, the solid phase of the microsphere suspension being titania microspheres with a particle size of 30 μm, the methyl blue aqueous solution as the reaction solution, and using an external light source at the same time Perform continuous light treatment. The microsphere suspension and the reaction solution were injected into the chip using a Teflon capillary tube, and the gas phase fluid was controlled by a pneumatic pump. The flow rate of the microsphere suspension is 30 μl/min, the gas phase flow rate is 50 μl/min, and the flow rate of the reaction liquid in the second liquid phase flow channel and the third liquid phase flow channel are both 30 μl/min. The quantitative titanium dioxide microspheres in the microsphere suspension and the methyl blue are accurately, efficiently and fully reacted heterogeneously under light conditions to obtain methylene blue or methylene blue.
实施例2Example 2
本实施例微流控芯片的材质为聚二甲基硅氧烷(PDMS),其中涡旋聚焦弯道部分总长度为600mm,涡旋聚焦弯道的相邻两流道的间距为200μm,涡旋聚焦弯道的最内侧流道的曲率半径为20mm,气相流道的宽度为50μm,第二液相流道和第三液相流道的宽度均为20μm,第一液相流道的宽度为50μm,第四液相流道的宽度为90μm,气体缓冲室在非工作状态时与第一液相流道壁距离为40μm,所有流道的高度为80μm。The material of the microfluidic chip in this embodiment is polydimethylsiloxane (PDMS), wherein the total length of the vortex focusing curve is 600 mm, and the distance between two adjacent flow channels of the vortex focusing curve is 200 μm. The radius of curvature of the innermost flow channel of the rotary focusing curve is 20mm, the width of the gas phase flow channel is 50μm, the width of the second liquid phase flow channel and the third liquid phase flow channel are both 20μm, and the width of the first liquid phase flow channel is 20μm. is 50 μm, the width of the fourth liquid phase flow channel is 90 μm, the distance between the gas buffer chamber and the wall of the first liquid phase flow channel is 40 μm in the non-working state, and the height of all the flow channels is 80 μm.
采用本实施例微流控芯片进行定量非均相反应,具体包括:选用氮气作为气相,含有粒径为20μm碳球的氢氧化钙[Ca(OH)2]溶液即碳球悬浮液作为微球悬浮液(碳球与氢氧化钙不发生反应),形成分散相,碳酸铵溶液作为反应液,形成连续液相。使用聚四氟乙烯毛细软管分别将碳球悬浮液和碳酸铵溶液注入芯片,利用气动泵控制气相流体。其中微球悬浮液的注入第一液相流道流量为40μL/min,气相注入流量为50μL/min,碳酸铵溶液注入第二液相流道和第三液相流道的流量为80μL/min,调节气相和微球悬浮液流量可以得到各种定量碳球含量的微球悬浮液,通过同轴流与碳酸铵连续相充分混合进行非均相精确高效反应,在碳球表面析出碳酸钙[CaCO3]沉淀均匀包裹碳球,同时非均相反应均匀,能得到定量碳球含量的微液滴。The microfluidic chip of this embodiment is used to perform quantitative heterogeneous reaction, which specifically includes: selecting nitrogen gas as gas phase, and calcium hydroxide [Ca(OH) 2 ] solution containing carbon spheres with a particle size of 20 μm, that is, carbon sphere suspension as microspheres Suspension (carbon balls do not react with calcium hydroxide) to form a dispersed phase, and ammonium carbonate solution is used as a reaction solution to form a continuous liquid phase. The carbon sphere suspension and the ammonium carbonate solution were injected into the chip using a Teflon capillary tube, respectively, and the gas-phase fluid was controlled by a pneumatic pump. The flow rate of the microsphere suspension injected into the first liquid phase flow channel is 40 μL/min, the gas phase injection flow rate is 50 μL/min, and the flow rate of the ammonium carbonate solution injected into the second liquid phase flow channel and the third liquid phase flow channel is 80 μL/min , by adjusting the flow rate of the gas phase and the microsphere suspension, various microsphere suspensions with quantitative carbon sphere content can be obtained, and the coaxial flow is fully mixed with the continuous phase of ammonium carbonate for a heterogeneous, accurate and efficient reaction, and calcium carbonate is precipitated on the surface of the carbon spheres [ CaCO 3 ] precipitation evenly wrapped the carbon spheres, and at the same time the heterogeneous reaction was uniform, and microdroplets with quantitative carbon sphere content could be obtained.
以上所述仅是本实用新型的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本实用新型原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本实用新型的保护范围。The above are only the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, several improvements and modifications can be made. These improvements and Retouching should also be regarded as the protection scope of the present invention.
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CN112755934A (en) * | 2021-01-13 | 2021-05-07 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
CN112755935A (en) * | 2021-01-13 | 2021-05-07 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
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CN110605148A (en) * | 2019-10-18 | 2019-12-24 | 广东工业大学 | A microfluidic channel structure, a microfluidic chip and a method for quantifying heterogeneous reactions |
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CN112755934A (en) * | 2021-01-13 | 2021-05-07 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
CN112755935A (en) * | 2021-01-13 | 2021-05-07 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
CN112755935B (en) * | 2021-01-13 | 2023-11-24 | 广东工业大学 | Micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
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