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微流控装置越来越广泛的应用于生物医学诊断学研究,小型化微流控和纳流控生物传感器的开发,DNA分析,化学合成和基因组学研究等方面。其内部通道尺寸仅几微米,大幅度降低表面体积比,降低样品/试剂的损耗。微流控装置内物料流动性是层流而非湍流,其雷诺值较小,即两种液体之间没有湍流混合。化学反应混合的快速可控对试剂和样品的分析以及微流控装置的优化至关重要。(见图1)
层流中,流体主要通过分子扩散进行混合,通过增强流体之间的扩散以增加混合效果。一般将微流控芯体设置为多孔结构,增强流体在内部的分流和并流效果。
也可以通过增加流体间的接触面积和接触时间(即“被动”微流体混合)。通过优化通道几何形状来增加接触面积和接触时间。根据被动微混合器的类型不同,混合时间可能会从几十毫秒到几百毫秒不等(见图2)。
Microfluidic devices are widely used in biomedical diagnostics research, the development of miniaturized microfluidic and nanofluidic biosensors, DNA analysis, chemical synthesis and genomics research. The internal channel size is only a few microns, which greatly reduces the surface volume ratio and reduces the sample/reagent loss. The flow of the material in the microfluidic device is laminar flow rather than turbulent flow, and its Reynolds value is small, that is, there is no turbulent mixing between the two liquids. The rapid and controllable mixing of chemical reactions is essential for the analysis of reagents and samples and for the optimization of microfluidic devices.
In laminar flow, fluids are mixed mainly through molecular diffusion, so the mixing effect should be increased by enhancing the diffusion between fluids. Generally, the microfluidic core is set up as a multi-space structure to enhance the separation and merging effect of the fluid in the interior.
It can also be done by increasing the contact area and contact time between the fluids (so-called "passive" microfluidic mixing). This can be achieved by optimizing the channel geometry. Depending on the type of passive micromixer, mixing times can range from tens to hundreds of milliseconds (see Figure 2).
图1 微流控装置
Figure 1 Microfluidic device
图2 不同类型微混合器的混合所需时间
Fig. 2 Mixing time required for different types of micro-mixers
图3左侧为T形微流体混合器示例,图3右侧为在通道中引入凹槽提高混合效率。
T形或Y形通道微混合器结构。由两个入口和一个出口组成。T形微通道中流体分别从对向设置的入口逆流进入混合器,在垂直方向上汇流混合(如图3)。
传统上的混合器中,混合主要发生在接触面上,主要在界面处进行扩散,其混合时间长,效果差。微混合器中则可以通过改变流速或增加阻碍物,增加扰动来提高混合效果。
图4为多层平行通道微流体混合器。也叫层压型微混合器。通过在微流体芯片内创建多个微小平行通道,对两个或多个流体进行多次分流和并流来增加流体的接触面积。微小平行通道越多混合越快。
An example of a T-shaped micro-fluidic mixer is shown on the left side of Figure 3, and a groove is introduced into the channel on the right side of Figure 3 to improve mixing efficiency.
T- or Y-channel micro-fluidic mixer construction consists of two entrances and one exit. In the T-shaped microchannel, the fluid enters the mixer in the opposite direction, respectively, from the inlet set in the opposite direction, and is mixed in a vertical direction (Fig.3).
In the mixer used before, the mixing mainly occurred on the contact surface, and the diffusion was carried out at the interface, and the mixing took longer and the heat transfer efficiency is reduced. In the micromixer, the mixing efficiency can be improved by changing the flow rate or increasing the obstruction and increasing the disturbance.
Figure 4 shows a multi-parallel channel micro-fluidic mixer. Also called laminated micro-mixer. The contact area of the fluid is increased by creating several tiny parallel channels in the micro-fluidic chip and diverting and merging two or more fluids several times. The more tiny parallel channels, the faster the mixing.
图3 T形微流体混合器示意图
FIG. 3 Schematic diagram of T-shaped micro-fluidic mixer
图4 多层平行通道微流体混合器
FIG. 4 Multi-layer parallel channel micro-fluidic mixer
图5a为微流控混合器内水力聚焦原理图。图5中b,由a到d分别为侧流流速对中心流宽度的影响。
混合路径是影响混合效率的重要参数,混合路径越短设备紧凑度越高。通过流动聚焦进行混合是能提高设备紧凑度。可通过水力聚焦来优化微流控混合器的通道数量。
水力聚焦型微流控混合器的基本原理如图5a所示,设计三个入口和一个出口,物料由三个入口进入,水平流出。中间入口(聚焦流)由两侧进料的(裹挟流)的流体裹挟着向前流动。中心流宽度可通过调节裹挟流的流量来控制,如图5b所示,中心流参数取决于内外流的流量比,流速相差越大,聚焦流越细,混合时间越短。微流控混合器通常配置需要会每个进料速率进行独立控制。
FIG.5a is the hydraulic focusing principle diagram in the microfluidic mixer. In FIG.5b, from a to d, are the effects of lateral flow velocity on the width of central flow.
The mixing path is an important parameter that affects the mixing efficiency. The shorter the mixing path, the higher the compactness of the device. Flow focusing can improve equipment compactness. The number of channels in the micro-fluidic mixer can be optimized by hydraulic focusing.
The basic principle of the hydraulic focused microfluidic mixer is shown in Figure 5a. It is designed with three entrances and one outlet, and the material has three entrances to enter and horizontal outflow. The middle inlet (focus flow) is carried forward by fluid fed on both sides (sheath flow). The center flow width can be controlled by adjusting the sheath flow rate. As shown in Figure 5b, the center flow parameters depend on the flow ratio between the inside and the outside. The larger the flow rate difference, the finer the focused flow and the shorter the mixing time. Microfluidic mixers are usually configured to require individual control of each feed rate.
图5 微流控混合器内水力聚焦原理图
FIG. 5 Schematic diagram of hydraulic focusing in a microfluidic mixer
主动型微流控微混合器。通过特定的机械方式(如声波、压力扰动、磁场、加热等)对流体施加外力达到主动混合的效果。增加声波可促进物料间的混合,然而外力的施加可能影响试样,如导致试样升温、副反应或沉淀等。
图6为不同类型的主动微流控微混合器对比表。可以通过主动与被动结合的方式来设计微流控微混合器,形成复合通道,进一步提高混合效率。压力扰动是通过在层流中产生局部扰动的达到主动混合的效果。
例如通过微型泵交替推动来实现压力扰动。同时,流速突变也可达到优化混合的效果。格拉斯哥大学的一个研究小组发现,如果两种流速以180°相移变化并且彼此垂直,则混合效率会提高。
Active micro-fluidic mixer. Active mixing is achieved by applying external forces to the fluid through specific mechanical means (such as sound waves, pressure perturbations, magnetic fields, thermal methods, etc.). Increasing the sound wave can increase the mixing between the materials, but the application of external forces may affect the sample, such as causing the sample to heat up, side reactions or precipitation.
Figure 6 shows a comparison table of different types of active micro-fluidic mixers. The micro-fluidic mixer can be designed by combining active and passive methods to form a composite channel and further improve the mixing efficiency. The pressure disturbance achieves the effect of active mixing by generating local disturbance in laminar flow.
For example, pressure perturbation is achieved by alternating pushes of micro-pumps. At the same time, velocity mutation can also achieve the optimal mixing effect. A team of researchers in Glasgow found that mixing efficiency is improved if two flow rates vary at 180° phase shift and are perpendicular to each other.
图6 不同类型的主动微流控微混合器对比表
FIG. 6 Comparison table of different types of active micro-fluidic mixers
图7为电驱动主动微型混合器的原理图。电驱动主动微型混合器,通过电场的波动激活混合器内的流体混合。图8为基于声驱动侧壁捕获微气泡的微流控混合器示意图。
将压电陶瓷换能器集成到微流控芯片中,通过超声波驱动流体沿垂直于流动方向的方向混合。同时,在混合区引入小气泡,增加声波的暴露面,进一步提高混合效率。
FIG. 7 shows the schematic diagram of an electrically driven active micro-fluidic mixers. The active micro-fluidic mixers is electrically driven and the fluid mixing in the mixer is activated by fluctuations in the electric field.
FIG. 8 is a schematic diagram of a micro-fluidic mixers based on acoustically driven side-wall capture of microbubbles.
A piezoelectric ceramic transducer is integrated into a micro-fluidic chip and the fluid is driven by ultrasound in a direction perpendicular to the direction of flow. At the same time, small bubbles are introduced into the mixing zone to increase the exposed surface of the sound wave and further improve the mixing efficiency.
图7 电驱动主动微型混合器的原理图
FIG. 7 Schematic diagram of an electrically driven active micro mixer
来源:https://www.elveflow.com/microfluidic-reviews/microfluidic-flow-control/microfluidic-mixers-a-short-review/
图8 基于声驱动侧壁捕获微气泡的微流控混合器示意图
FIG. 8 Schematic diagram of a microfluidic mixer based on acoustically driven side-wall capture of microbubbles
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