技术领域technical field
本发明属于数字微流技术领域，具体涉及基于介质上电润湿的数字微流技术芯片，尤其涉及一种基于电润湿数字微流体芯片的液滴混合单元。The invention belongs to the technical field of digital microfluidics, and in particular relates to a digital microfluidic technology chip based on electrowetting on a medium, in particular to a droplet mixing unit based on an electrowetting digital microfluidic chip.
背景技术Background technique
芯片实验室（Lab-on-a-chip，LOC）作为一项新兴的技术，由于具有高集成性、高精度、低耗性等许多优点，正受到越来越多的关注，具有很好的研究及应用前景。而所谓芯片实验室是指能够完成生物化学处理各个过程，将能自动完成传统实验室任务的复杂功能微小化、集成化的MEMS系统。其目标是在单个器件上集成完全的分析过程，能够完成样品提取、 样品预处理、分解分离、生物化学反应、分析检测、数据处理等操做。作为芯片实验室的动力部分，微流控技术起着至关重要的作用。而基于电润湿的数字微流技术是指通过施加电压来控制单个液滴的一项微流技术，由于具有相对简单、较好的可控性及驱动能力，被认为是LOC应用中最可行，最具发展前景的技术。As an emerging technology, Lab-on-a-chip (LOC) is attracting more and more attention due to its high integration, high precision, low consumption and many other advantages. Research and application prospects. The so-called lab-on-a-chip refers to a miniaturized and integrated MEMS system that can complete various biochemical processes and automatically complete traditional laboratory tasks. Its goal is to integrate a complete analysis process on a single device, which can complete operations such as sample extraction, sample pretreatment, decomposition and separation, biochemical reactions, analysis and detection, and data processing. As the power part of lab-on-a-chip, microfluidic technology plays a vital role. The digital microfluidic technology based on electrowetting refers to a microfluidic technology that controls a single droplet by applying a voltage. Due to its relatively simple, good controllability and driving ability, it is considered to be the most feasible in LOC applications. , the most promising technology.
目前基于电润湿的数字微流技术在实用芯片上的功能主要集中在对液体样品的分配、输运、混合、提取、分离等多种处理，而样品的混合这一功能至关重要，是数字微流芯片应用的基础部分，是芯片实验室微型化、自动化、商用化的关键。At present, the functions of digital microfluidic technology based on electrowetting on practical chips mainly focus on the distribution, transportation, mixing, extraction, and separation of liquid samples, and the function of sample mixing is very important. The basic part of the digital microfluidic chip application is the key to the miniaturization, automation and commercialization of the chip laboratory.
在目前的电润湿数字微流芯片中，样品的混合主要两大类方法：第一类是芯片上简单直接混合，即通过驱动两种样品液滴合并，其后使合并液滴输运一段路径，在输运过程中，两种样品实现慢慢混合。这种方法其实就是利用数字微流芯片的液滴合并和输运功能，可以直接利用芯片的驱动电极，方法直接简单，不需额外功能单元。但这种方法也存在明显缺点，首先是混合速率很慢，因为它是依靠传统芯片的液滴输运过程来完成的，而传统的液滴输运只能走直线路径，这样液滴的混合效率很低，需要较长的液滴输运路径或较长的混合时间。其次，由于液滴的混合没有专用的功能单元，而液滴较长时间的混合输运会造成芯片的污染。最后，由于受芯片普通驱动电极的约束，所混合液滴的大小尺寸受限制。而第二类混合方法是采用额外的辅助方法，例如在数字微流芯片上集成声波振荡、磁力搅拌等方法进行混合，这类混合方法可以得到较好的混合效率及效果，但是需要额外的功能单元，增加了芯片的复杂度及商用成本，而且集成度低限制了微流芯片的微型化。In the current electrowetting digital microfluidic chip, there are two main methods for sample mixing: the first type is simple and direct mixing on the chip, that is, by driving two sample droplets to merge, and then transporting the combined droplet for a period of time. During the transport process, the two samples are slowly mixed. This method actually uses the droplet merging and transport functions of the digital microfluidic chip, and can directly use the driving electrodes of the chip. The method is straightforward and simple, and does not require additional functional units. But this method also has obvious disadvantages. First, the mixing rate is very slow, because it is completed by the droplet transport process of the traditional chip, and the traditional droplet transport can only follow a straight line path, so the mixing of droplets Very inefficient, requiring long droplet transport paths or long mixing times. Secondly, since there is no dedicated functional unit for the mixing of droplets, the mixing and transportation of droplets for a long time will cause contamination of the chip. Finally, the size of the mixed droplets is limited due to the constraints of the common drive electrodes on the chip. The second type of mixing method uses additional auxiliary methods, such as integrating acoustic wave oscillation and magnetic stirring on the digital microfluidic chip for mixing. This type of mixing method can obtain better mixing efficiency and effect, but requires additional functions. The unit increases the complexity and commercial cost of the chip, and the low level of integration limits the miniaturization of the microfluidic chip.
因此，需要一种简单易行，混合效果好、混合效率高、集成度高、成本低的液滴混合功能装置以集成在数字微流芯片中，以满足芯片实验室的应用要求。Therefore, there is a need for a droplet mixing functional device that is simple and easy to implement, has good mixing effect, high mixing efficiency, high integration, and low cost to be integrated in a digital microfluidic chip to meet the application requirements of a lab-on-a-chip.
发明内容Contents of the invention
本发明旨在提供一种基于电润湿数字微流芯片的液滴混合单元，以集成在数字微流芯片中，能够实现液滴的简单、高效混合。The present invention aims to provide a droplet mixing unit based on an electrowetting digital microfluidic chip, which can be integrated in the digital microfluidic chip and can realize simple and efficient mixing of droplets.
本发明的混合原理是基于液滴的输运，即通过将液滴以一定方式快速输运一定路径以达到自动混合的目的。The mixing principle of the present invention is based on the transport of liquid droplets, that is, the purpose of automatic mixing is achieved by quickly transporting liquid droplets to a certain path in a certain way.
本发明提供的基于电润湿数字微流芯片的液滴混合单元，包括三个部分：The droplet mixing unit based on the electrowetting digital microfluidic chip provided by the present invention includes three parts:
第一部分是混合单元的入口区；该部分主要是牵引液滴进入混合单元，入口部分的驱动电极可以是独立电极，也可以是混合单元内部驱动电极电极的一部分，电极的形状大小并不限定，只要满足能将混合单元外液滴输运到混合单元内的混合驱动电极即可。入口的位置和数目也并不限定。The first part is the entrance area of the mixing unit; this part is mainly to pull liquid droplets into the mixing unit, the driving electrode of the entrance part can be an independent electrode, or a part of the driving electrode inside the mixing unit, and the shape and size of the electrode are not limited. As long as the mixing drive electrode capable of transporting the liquid droplets outside the mixing unit to the inside of the mixing unit is satisfied. The positions and numbers of the entrances are also not limited.
第二部分是混合单元的混合区；该部分是混合单元的主要功能部分，实施对液滴的高效混合。这一部分由单向驱动电极组成。每个驱动电极首尾相靠、相互嵌套形成封闭的环状结构，使液滴的混合路径为圆环曲线。利用该设计，使液滴无论在单个电极的运动上还是整条混合路径上运动均为曲线，这样可以大大地提高液滴的混合效率；而且该部分使用精简电极相连，把相间电极电气相连，这样使整个混合单元的最小控制信号可以为两个，极大地精简了控制系统。在该部分中，混合单元的驱动电极至少为4个，但并无上限，只要能保证电极排布成环状封闭结构即可。The second part is the mixing zone of the mixing unit; this part is the main functional part of the mixing unit and implements efficient mixing of the droplets. This part consists of unidirectional drive electrodes. Each driving electrode is close to each other and nested with each other to form a closed ring structure, so that the mixing path of the droplet is a circular curve. Utilizing this design, the liquid droplets can be curved no matter on the movement of a single electrode or the entire mixing path, which can greatly improve the mixing efficiency of the liquid droplets; and this part is connected with simplified electrodes, and the phase electrodes are electrically connected. In this way, the minimum control signals of the entire mixing unit can be two, which greatly simplifies the control system. In this part, the number of driving electrodes of the hybrid unit is at least four, but there is no upper limit, as long as the electrodes can be arranged in a ring-shaped closed structure.
该部分的单向驱动电极可采用如下结构方式。电极形状是不对称的分立电极，每个电极分为3个部分：一是呈短棒状且顶端为圆弧的电极头部（E41），该部分用来在开始时牵引邻近电极液滴到该电极上，顶端为圆弧形，以增加液滴驱动力；二是带有圆型缺口的电极中部（E42），该部分是液滴开始接触驱动电极到液滴稳定在驱动电极的过度部分，圆形缺口的作用是增加液滴驱动能力及单向性；三是方块圆弧状且尾部有缺口的电极尾部（E43），该部分是液滴在驱动电极上的稳定部分，尾部缺口是便于和相邻电极的头部嵌套；整体的电极结构满足如下条件：对于一定大小的液滴，无论其处于电极上任何位置，只要能有效覆盖电极某一部分，对电极施加驱动信号，它都能最终到达电极尾部的稳定部分；The unidirectional driving electrodes of this part can adopt the following structure. The shape of the electrode is an asymmetric discrete electrode, and each electrode is divided into 3 parts: one is the electrode head (E41) in the shape of a short rod with a circular arc at the top, which is used to pull the adjacent electrode droplet to the electrode at the beginning. On the electrode, the top is arc-shaped to increase the driving force of the droplet; the second is the middle part of the electrode (E42) with a circular notch, which is the transition part from when the droplet starts to contact the driving electrode to when the droplet stabilizes on the driving electrode. The role of the circular notch is to increase the driving ability and unidirectionality of the droplet; the third is the electrode tail (E43) with a square arc shape and a notch at the tail. This part is the stable part of the droplet on the driving electrode. The notch at the tail is convenient Nested with the head of the adjacent electrode; the overall electrode structure meets the following conditions: for a droplet of a certain size, no matter where it is on the electrode, as long as it can effectively cover a certain part of the electrode and apply a driving signal to the electrode, it can finally reach the stable part of the electrode tail;
第三部分是混合单元的出口区；该部分主要是将混合单元的液滴输出，出口部分的驱动电极可以是独立电极，也可以是混合单元内部驱动电极电极的一部分，电极的形状大小并不限定，但要满足处于该部分的液滴能有效接触到混合驱动电极从而使液滴能输入混合单元进行混合。出口的位置和数目也并不限定。The third part is the outlet area of the mixing unit; this part is mainly to output the droplets of the mixing unit, and the driving electrode of the outlet part can be an independent electrode, or a part of the driving electrode inside the mixing unit, and the shape and size of the electrode are different. Limit, but it must be satisfied that the droplets in this part can effectively contact the mixing driving electrode so that the droplets can be input into the mixing unit for mixing. The location and number of outlets are also not limited.
应当指出，传统的数字微流芯片的混合单元并未明确界定入口、出口，本发明的定义有利于液滴快速进出混合单元，并能与微流芯片的其它功能单元有效结合。这是本发明的创新点之一。It should be pointed out that the mixing unit of the traditional digital microfluidic chip does not clearly define the inlet and outlet. The definition of the present invention is conducive to the rapid entry and exit of droplets into the mixing unit, and can be effectively combined with other functional units of the microfluidic chip. This is one of the innovative points of the present invention.
而且，在本发明中，利用不对称驱动电极以及封闭的环形路径使液滴混合时的输运路径不为直线，这样能大大提高混合效率，这又是本发明的创新点。Moreover, in the present invention, the asymmetric driving electrodes and the closed circular path are used to make the transportation path of the droplets mixed not be a straight line, which can greatly improve the mixing efficiency, which is another innovation of the present invention.
另外，在本发明中，由于使用单向驱动电极及精简电极连接方式，不需要事先知道液滴位置，只需对两个驱动电极轮流施加驱动信号即可以实现液滴的高速自动输运混合。In addition, in the present invention, due to the use of unidirectional driving electrodes and a simplified electrode connection method, it is not necessary to know the droplet position in advance, and only need to apply driving signals to the two driving electrodes in turn to realize high-speed automatic transportation and mixing of droplets.
本发明中，所述“单元”是指具有一定功能的多个部件的有机组合。In the present invention, the "unit" refers to an organic combination of multiple components with certain functions.
本发明中，所述“液滴”是指能用于电润湿驱动的溶液滴，其成分可以是单一的生物样品、化学溶液等，也可以是多成分组成，如外面包裹着一层油膜的液滴等，其大小并不限定，可以为次微微升到若干毫升之间。In the present invention, the "droplet" refers to a solution drop that can be driven by electrowetting, and its composition can be a single biological sample, chemical solution, etc., or it can be composed of multiple components, such as a layer of oil film wrapped outside The size of the liquid droplets is not limited, and can be between subpicoliters and several milliliters.
本发明中，所述“驱动电极”是指芯片实施时对应电极的电压被置成不为0以使电润湿驱动能够发生，所述“接地电极”是指芯片实施时对应电极的电压被置成0或与0足够接近。In the present invention, the "driving electrode" means that the voltage of the corresponding electrode is set to be non-zero when the chip is implemented so that the electrowetting drive can occur, and the "ground electrode" means that the voltage of the corresponding electrode is set to 0 when the chip is implemented. Set to 0 or close enough to 0.
本发明中，所述“相互嵌套”是指驱动电极之间有一部分几何包含区，但在电气上并不相连，以保证单液滴接触到某一驱动电极的某一部分时，其也能接触相应邻近电极的一部分。In the present invention, the "mutual nesting" means that there is a part of the geometric inclusion area between the driving electrodes, but they are not connected electrically, so as to ensure that when a single droplet touches a certain part of a certain driving electrode, it can also A portion of the corresponding adjacent electrode is contacted.
本发明提供的液滴混合单元具有如下显著优势：The droplet mixing unit provided by the present invention has the following significant advantages:
1. 直接利用液滴输运功能，简单方便、易于集成；1. Directly use the droplet transport function, which is simple, convenient and easy to integrate;
2. 具有进出口部分，能实现液滴快速进出，并能与其它部分有效结合；2. It has an inlet and outlet part, which can realize the rapid entry and exit of liquid droplets, and can be effectively combined with other parts;
3. 与传统混合方法相比，具有更快的混合速率及更好的混合效果；3. Compared with traditional mixing methods, it has faster mixing speed and better mixing effect;
4. 混合部分只需两个驱动信号，大大降低了控制复杂度；4. The mixing part only needs two driving signals, which greatly reduces the control complexity;
5. 利用独特的单向电极，可实现全自动混合，具有较高的可靠性；5. With unique unidirectional electrodes, fully automatic mixing can be realized with high reliability;
6. 利用独特的电极配置，可使混合驱动电极数目任意增加却不影响芯片的控制。6. Using the unique electrode configuration, the number of hybrid driving electrodes can be increased arbitrarily without affecting the control of the chip.
附图说明Description of drawings
图1为本发明的液滴混合单元的一种电润湿数字微流体芯片结构示意图。Fig. 1 is a schematic structural diagram of an electrowetting digital microfluidic chip of the droplet mixing unit of the present invention.
图2为本发明的基于电润湿数字微流体芯片的液滴混合单元示意图。Fig. 2 is a schematic diagram of the droplet mixing unit based on the electrowetting digital microfluidic chip of the present invention.
图3是本发明的一种单向驱动电极结构图示。Fig. 3 is a structural diagram of a unidirectional driving electrode of the present invention.
具体实施方式Detailed ways
本发明提供的基于电润湿数字微流体芯片的液滴混合单元可以有多种具体的芯片实现方式，本实施方式只列举一种常见的数字芯片结构以说明其实施原理。应当指出，本实施方式是为了说明目的而提供，而不在意以任何方式限制本发明的范围。The droplet mixing unit based on the electrowetting digital microfluidic chip provided by the present invention can have various specific chip implementation methods. This embodiment only lists a common digital chip structure to illustrate its implementation principle. It should be noted that this embodiment is provided for illustrative purposes and is not intended to limit the scope of the present invention in any way.
基于本发明的一种电润湿数字微流体芯片结构如图1所示。在衬底11上为本发明的混合单元驱动电极1-4。用作基板的材料并不固定，只要绝缘即可，如可以为石英、玻璃、绝缘的硅片等；而电极（包括下面所述的接地电极）可以由任何导电材料组成。应当说明，示意图的混合驱动电极只以4个为例，但其实际数目并不限定，而且图中驱动电极只是简单表示电极在芯片中的位置，并不详细反映其具体排布及连接方式，并不详细描述芯片结构。电极1-4上为介质层12，其上为疏水层13。应当指出，介质层应为绝缘介质材料但并不限定，优选为介电常数较高、抗击穿能力较强的材料。衬底11、驱动电极1-4、介质层12、疏水层13共同构成了芯片的下极板1。在下极板上为驱动液滴D；液滴上为疏水层23，介质22，及基本21，它们共同构成了芯片的上极板2。整个芯片的结构是液滴夹在上下极板之间，当下极板驱动电极1-4按要求施加电压信号，而上极板接地电极接地时，液滴就会相应发生驱动输运，从而实现高速混合。The structure of an electrowetting digital microfluidic chip based on the present invention is shown in FIG. 1 . On the substrate 11 are the hybrid cell drive electrodes 1-4 of the present invention. The material used as the substrate is not fixed, as long as it is insulating, such as quartz, glass, insulating silicon wafer, etc.; and the electrodes (including the ground electrode described below) can be made of any conductive material. It should be noted that the hybrid driving electrodes in the schematic diagram only take 4 as an example, but the actual number is not limited, and the driving electrodes in the figure simply indicate the positions of the electrodes in the chip, and do not reflect their specific arrangement and connection methods in detail. The chip structure is not described in detail. On the electrodes 1-4 is a dielectric layer 12, on which is a hydrophobic layer 13. It should be pointed out that the dielectric layer should be an insulating dielectric material, but is not limited thereto. It is preferably a material with a high dielectric constant and strong breakdown resistance. The substrate 11, the driving electrodes 1-4, the dielectric layer 12, and the hydrophobic layer 13 together constitute the lower plate 1 of the chip. On the lower plate is the driving droplet D; on the droplet are the hydrophobic layer 23, the medium 22, and the base 21, which together constitute the upper plate 2 of the chip. The structure of the whole chip is that the droplet is sandwiched between the upper and lower plates, and the driving electrodes 1-4 of the lower plate apply voltage signals as required, and when the grounding electrode of the upper plate is grounded, the droplets will be driven and transported accordingly, thus realizing Mix at high speed.
图2为本发明的基于电润湿数字微流体芯片的液滴混合单元示意图。混合单元由4个驱动电极1-4组成嵌套闭环结构，用以输运液滴实现混合；混合单元包含一个入口5，应当指出，入口电极5的形式并不限定，可以为独立的电极且电极形状根据具体而改变，本说明只以精简方式配置，将某一形状的入口电极5与输运驱动电极1相连，以实现共同控制，并不影响混合单元的功能实现。此外，混合单元还包含一个出口6，出口的形式也是不限定的，本发明以电极2的部分凹陷作为出口，用以与外部电极连接以方便输出混合后的液滴。整个混合单元采用精简方式连接，最终引出两个驱动信号连接电极A、B。当混合单元采用图1的芯片结构配置时，若液滴位于驱动单元入口处，如D1，通过对连接电极A时间电压驱动信号，同时芯片上极板接地，那么液滴将会进入混合单元，最终处于混合单元内某一混合输运电极的稳定处，如D2。其后，若保持芯片上极板接地，通过对连接电极B时间电压驱动信号，而A撤销驱动信号，液滴将会往电极2运动并最终稳定在电极2的稳定处，如D3。以此轮流对A、B连接电极施加驱动信号，液滴将会以此在电极1、2、3、4做环形输运，从而实现液滴混合。若当液滴位于电极2的稳定处时，如D3，同时撤销电极A、B的驱动信号，液滴将会一直保持不动，此时通过出口6可以将液滴输出混合单元。按照这种实施方式，整个混合单元可以快速实现液滴的输入、混合、输出功能，具有较高效率和较好效果。Fig. 2 is a schematic diagram of the droplet mixing unit based on the electrowetting digital microfluidic chip of the present invention. The mixing unit is composed of 4 drive electrodes 1-4 to form a nested closed-loop structure for transporting droplets to achieve mixing; the mixing unit includes an inlet 5, and it should be noted that the form of the inlet electrode 5 is not limited, it can be an independent electrode and The shape of the electrode varies according to the specific conditions. This description only configures in a simplified manner. The entrance electrode 5 of a certain shape is connected to the transport driving electrode 1 to achieve common control without affecting the function realization of the mixing unit. In addition, the mixing unit also includes an outlet 6, and the form of the outlet is not limited. In the present invention, a part of the electrode 2 is recessed as the outlet to connect with an external electrode to facilitate the output of mixed droplets. The whole mixing unit is connected in a simplified way, and finally leads to two driving signals to connect electrodes A and B. When the mixing unit adopts the chip structure configuration shown in Figure 1, if the droplet is located at the entrance of the drive unit, such as D1, the droplet will enter the mixing unit through the time voltage drive signal connected to the electrode A, and at the same time the plate on the chip is grounded. Finally, it is at the stable place of a mixed transport electrode in the mixed unit, such as D2. Afterwards, if the plate on the chip is kept grounded, the voltage drive signal is connected to electrode B for a time, and A cancels the drive signal, the droplet will move to electrode 2 and finally stabilize at the stable position of electrode 2, such as D3. In this way, driving signals are applied to the connecting electrodes A and B in turn, and the droplets will be transported circularly on electrodes 1, 2, 3, and 4, thereby realizing droplet mixing. If the droplet is at the stable position of the electrode 2, such as D3, and the driving signals of the electrodes A and B are canceled at the same time, the droplet will remain still, and the droplet can be output from the mixing unit through the outlet 6 at this time. According to this embodiment, the entire mixing unit can quickly realize the functions of input, mixing, and output of droplets, with higher efficiency and better effect.
| Application Number | Priority Date | Filing Date | Title |
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| CN201210351244.5ACN102836653B (en) | 2012-09-20 | 2012-09-20 | Liquid drop mixing unit based on electro-wetting digital micro-fluid chip |
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| CN201210351244.5ACN102836653B (en) | 2012-09-20 | 2012-09-20 | Liquid drop mixing unit based on electro-wetting digital micro-fluid chip |
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