CN111437894A - A micro-droplet generation system and method for precisely encapsulating micro-particles - Google Patents
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Abstract
一种精确包裹微颗粒的微液滴生成系统及生成方法,含有微颗粒的离散相流体经颗粒排列装置进入微通道,通过控制第一鞘流和第二鞘流的流量及流量比,调控微通道中的总流量、颗粒间距及位置;微通道同时与第一分流微通道和第二分流微通道相连,第二分流微通道直接与出口相连,第一分流微通道经微液滴生成装置和出口微通道与出口相连;两个微通道一侧分别设计有气密性弹性膜,经气体通道,分别与气体控制装置相连,再与外界气源相连;气体控制装置分别控制气体通道中的气压,实现对气密性弹性膜的变形控制,实现对第一分流微通道和第二分流微通道中的流量精确控制;最终在微液滴生成装置中精确生成包裹指定数量微颗粒的微液滴。
A micro-droplet generation system and generation method for precisely encapsulating micro-particles. A discrete-phase fluid containing micro-particles enters a micro-channel through a particle arrangement device, and by controlling the flow rate and flow ratio of a first sheath flow and a second sheath flow, the micro-particles are regulated. The total flow, particle spacing and position in the channel; the microchannel is simultaneously connected with the first split microchannel and the second split microchannel, the second split microchannel is directly connected with the outlet, and the first split microchannel is passed through the microdroplet generation device and The outlet microchannel is connected with the outlet; one side of the two microchannels is respectively designed with an airtight elastic membrane, which is respectively connected with the gas control device through the gas channel, and then connected with the external gas source; the gas control device respectively controls the air pressure in the gas channel , realize the deformation control of the air-tight elastic film, and realize the precise control of the flow in the first shunt micro-channel and the second shunt micro-channel; finally, the micro-droplets encapsulating the specified number of micro-particles are accurately generated in the micro-droplet generating device .
Description
技术领域technical field
本发明涉及一种精确包裹微颗粒的微液滴生成方法。具体涉及一种精确包裹微颗粒的微液滴生成系统及生成方法。The invention relates to a method for generating micro-droplets that precisely wraps micro-particles. Specifically, it relates to a micro-droplet generation system and method for precisely wrapping micro-particles.
背景技术Background technique
包裹微颗粒的微液滴在生物医学、食品安全检测等领域有着重要的应用潜力。如在生物医学领域中,通过将目标细胞精确地封装在微液滴中,可实现对新研发药物的快速筛选和药效评估。已有研究发现不包裹微颗粒的简单微液滴生成尺寸与频率和离散相/连续相间的流量比直接相关。若要实现包裹微颗粒的微液滴精确生成,除了控制离散相/连续相间的流量比,还需对离散相中微颗粒运动、间距及位置进行精确控制。二者的协调控制是制约包裹微颗粒的微液滴准确生成的关键问题,目前未见相关技术报道解决这一问题。Microdroplets encapsulating microparticles have important potential applications in biomedicine, food safety testing and other fields. For example, in the field of biomedicine, rapid screening and efficacy evaluation of newly developed drugs can be achieved by precisely encapsulating target cells in microdroplets. It has been found that the size of the formation of simple microdroplets without encapsulating microparticles is directly related to the frequency and the flow ratio between the discrete phase/continuous phase. In order to realize the precise generation of micro-droplets encapsulating micro-particles, in addition to controlling the flow ratio between the discrete phase/continuous phase, it is also necessary to precisely control the movement, spacing and position of the micro-particles in the discrete phase. The coordinated control of the two is the key problem that restricts the accurate generation of microdroplets encapsulating microparticles, and there is no relevant technical report to solve this problem.
发明内容SUMMARY OF THE INVENTION
为解决上述关键问题,本发明目的在于提供一种精确包裹微颗粒的微液滴生成系统及生成方法,通过结合鞘流和微通道流动阻力控制,实现对微颗粒运动、分布及微通道中流体流量的协调控制,为包裹微颗粒的微液滴精确生成提供了一种新的方法和技术手段。具有结构简单、易操作、控制精确度高等优点,在生物医学、食品安全检测等领域有着很好的应用前景。In order to solve the above-mentioned key problems, the purpose of the present invention is to provide a micro-droplet generation system and method for precisely encapsulating micro-particles. By combining sheath flow and micro-channel flow resistance control, the movement and distribution of micro-particles and the fluid in the micro-channel can be controlled. The coordinated control of the flow provides a new method and technical means for the precise generation of micro-droplets encapsulated by micro-particles. It has the advantages of simple structure, easy operation and high control accuracy, and has a good application prospect in the fields of biomedicine, food safety detection and the like.
为了达到上述目的,本发明采用如下技术方案:In order to achieve the above object, the present invention adopts the following technical solutions:
一种精确包裹微颗粒的微液滴生成系统,包括颗粒排列装置1,与颗粒排列装置1连通的微通道2,设置在微通道2两侧的用于调控微通道2中的流体总流量、颗粒间距及位置的第一鞘流3和第二鞘流4;微通道2末端分流为第一分流微通道6和第二分流微通道7,第一分流微通道6和第二分流微通道7一侧分别连通第一气体通道9和第二气体通道8,第一分流微通道6和第二分流微通道7与第一气体通道9和第二气体通道8连通处分别设置有第一气密性弹性膜16和第二气密性弹性膜15,第一气体通道9和第二气体通道8分别连接与外界气源相连的第一气体控制装置11和第二气体控制装置10;所述第一分流微通道6末端依次通过微液滴生成装置13和出口微通道14与出口12相连通,第二分流微通道7末端直接与出口12相连通;第一气体控制装置11和第二气体控制装置10分别控制第一气体通道9和第二气体通道8中的气压,实现对第一气密性弹性膜16和第二气密性弹性膜15的变形控制,进而分别控制第一分流微通道6和第二分流微通道7的流量,最后在微液滴生成装置13中生成精确包裹微颗粒的微液滴。A micro-droplet generation system for precisely wrapping micro-particles, comprising a
所述第一鞘流3和第二鞘流4对称设置在微通道2两侧,需进行协同控制,实现对微通道2的流体总流量、微颗粒间距及位置的精确调控。The
所述第一密性弹性膜16和第二密性弹性膜15在第一气体控制装置11和第二气体控制装置10的协同控制下发生形变,改变第一分流微通道6和第二分流微通道7的横截面积及流体流速,以实现对微通道中流体流量的准确控制。The first dense
所述的精确包裹微颗粒的微液滴生成系统生成微液滴的方法,含有微颗粒的离散相流体在颗粒排列装置1中实现单个微颗粒的链式排列后进入微通道2,通过控制第一鞘流3和第二鞘流4的流量及流量比,调控微通道2中的流体总流量、颗粒间距及位置;微通道2末端同时与第一分流微通道6和第二分流微通道7相连通,其中第二分流微通道7为了分流调控第一分流微通道6中的流体流量;第一气体控制装置11和第二气体控制装置10分别控制第一气体通道9和第二气体通道8中的气压,实现对第一密性弹性膜16和第二密性弹性膜15的变形控制,进而分别控制第一分流微通道6和第二分流微通道7的流量;最终实现对微颗粒运动、分布及微液滴生成微通道中流体流量的协同调控,在微液滴生成装置13中生成精确包裹微颗粒的微液滴。In the method for generating micro-droplets by the micro-droplet generation system that precisely wraps micro-particles, the discrete-phase fluid containing micro-particles enters the micro-channel 2 after realizing the chain arrangement of single micro-particles in the
本发明具有如下优点:The present invention has the following advantages:
1)结构简单。通过简单的对称鞘流设计,可有效实现对离散相流体内微颗粒间距和位置的有效调控,便于装置的加工制作。1) Simple structure. Through a simple symmetrical sheath flow design, the effective regulation of the spacing and position of microparticles in the discrete phase fluid can be effectively achieved, which facilitates the fabrication of the device.
2)易操作。耦合气体控制和气密性弹性膜,通过弹性膜的可逆变形,可方便实现对微通道结构和流体流速的有效调控,从而控制进入微液滴生成装置中的离散相流体流量。2) Easy to operate. Coupling gas control and air-tight elastic membrane, through the reversible deformation of the elastic membrane, it is convenient to realize the effective regulation of microchannel structure and fluid flow rate, so as to control the flow rate of discrete phase fluid into the microdroplet generation device.
3)控制精确度高。通过对称鞘流作用,可实现对微颗粒的运动和分布的精确控制;通过弹性膜的变形,可实现对进入微液滴生成装置的离散相流量的精确控制,同时保证微颗粒进入微液滴生成装置。通过对微液滴运动、分布及微通道内流体流量的协调控制,最终可实现对包裹微颗粒的微液滴生成的精确控制。3) High control accuracy. Through the action of symmetrical sheath flow, precise control of the movement and distribution of micro-particles can be achieved; through the deformation of the elastic membrane, precise control of the flow rate of discrete phases entering the micro-droplet generation device can be achieved, while ensuring that micro-particles enter the micro-droplets Generate device. Through the coordinated control of the microdroplet movement, distribution, and fluid flow in the microchannel, the precise control of the generation of microdroplets encapsulating the microparticles can finally be achieved.
附图说明Description of drawings
图1为本发明用于精确包裹微颗粒的微液滴生成方法示意图。FIG. 1 is a schematic diagram of the method for generating microdroplets for precisely wrapping microparticles according to the present invention.
具体实施方式Detailed ways
下面结合附图和具体实施方式对本发明作进一步详细的说明:The present invention will be described in further detail below in conjunction with the accompanying drawings and specific embodiments:
如图1所示,本发明一种精确包裹微颗粒的微液滴生成系统,含有微颗粒的离散相流体经颗粒排列装置1进入微通道2,通过控制第一鞘流3和第二鞘流4的流量及流量比,调控微通道2中的总流量、颗粒间距及位置。微通道2同时与第一分流微通道6和第二分流微通道7相连,第二分流微通道7直接与出口12相连,第一分流微通道6经微液滴生成装置13和出口微通道14与出口12相连。第一分流微通道6和第二分流微通道7一侧分别设计有第一气密性弹性膜16和第二气密性弹性膜15,经第一气体通道9与第二气体通道8,分别与第一气体控制装置11和第二气体控制装置10相连,再与外界气源相连。第一气体控制装置10与第二气体控制装置11分别控制第一气体通道9与第二气体通道8中的气压,实现对第一气密性弹性膜16和第二气密性弹性膜15的变形控制,分别调控第一分流微通道6和第二分流微通道7的流量。最终实现对微颗粒运动、分布及微液滴生成微通道中流体流量的协同调控,在微液滴生成装置13中生成精确包裹微颗粒的微液滴。As shown in Figure 1, the present invention is a micro-droplet generation system that precisely encapsulates micro-particles. The discrete-phase fluid containing micro-particles enters the micro-channel 2 through the
作为本发明的优选实施方式,本发明中所述第一鞘流3和第二鞘流4对称设置在微通道2两侧,流量需进行协同控制,实现对微通道2的流体总流量、微颗粒间距及位置的精确调控。As a preferred embodiment of the present invention, the
作为本发明的优选实施方式,本发明中所述第一气密性弹性膜16和第二气密性弹性膜15在第一气体控制装置11和第二气体控制装置10的协同控制下发生形变,改变第一分流微通道6和第二分流微通道7的横截面积及流体流速,以实现对微通道中流体流量的准确控制。As a preferred embodiment of the present invention, the first air-tight
下面以一实施例说明本发明的实施过程:Describe the implementation process of the present invention with an embodiment below:
采用本发明生成包裹单个微颗粒的微液滴具体步骤如下。包裹微颗粒的离散相流体在颗粒排列装置1中实现微颗粒单一位置处的链式排列,或对于较低颗粒浓度的离散相流体可直接进入微通道2中。按照合适的流量比,调控第一鞘流3和第二鞘流4的流量,在微通道2中实现对微颗粒位置及相邻颗粒间距离的调控。根据微液滴生成装置13中连续相的流量,通过第一气体控制装置11和第二气体控制装置10分别控制第一气体通道9与第二气体通道8中的气体压强,使第一气密性弹性膜16和第二气密性弹性膜15发生相应的形变,从而改变第一分流微通道6和第二分流微通道7中的流动阻力,调控第一分流微通道6和第二分流微通道7中的流体流量,使第一分流微通道6中的流量满足微液滴生成所需的离散型/连续相流量比,同时保证微颗粒以合适间距进入微液滴生成装置13中,最终在微液滴生成装置13中生成包裹单个微颗粒的微液滴,而后经出口微通道14进入出口12。上述过程中微通道2中进入第一分流微通道6之外的流体则经第二分流微通道7进入出口12。综上,通过鞘流实现对微颗粒运动和分布的准确调控,通过耦合气体控制与弹性膜变形,实现对离散相流量的精确调控,通过对颗粒运动、分布和流体流量的协调控制,最终精确生成包裹指定颗粒数的微液滴。在生物医学、食品安全检测等领域有着重要的应用价值。The specific steps of using the present invention to generate micro-droplets encapsulating a single micro-particle are as follows. The discrete phase fluid encapsulating the microparticles can achieve chain arrangement of the microparticles at a single location in the
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CN112755933A (en) * | 2021-01-13 | 2021-05-07 | 广东工业大学 | Multi-stage reaction micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
CN112755933B (en) * | 2021-01-13 | 2023-12-26 | 广东工业大学 | Multistage reaction micro-channel structure, micro-fluidic chip and heterogeneous reaction method |
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