CN109307102B - Micro valve device for micro-fluidic chip and preparation method and application thereof - Google Patents
Micro valve device for micro-fluidic chip and preparation method and application thereof Download PDFInfo
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
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Abstract
Description
技术领域technical field
本发明涉及一种用于微流控芯片的微阀装置及其制备方法和应用,属于微流控芯片技术领域。The invention relates to a microvalve device for a microfluidic chip, a preparation method and application thereof, and belongs to the technical field of microfluidic chips.
背景技术Background technique
微流控芯片概念于20世纪末产生,通过设计、制作小型化芯片器件来达到自动化、集成化完成实验操作的目的。微流控芯片技术利用微加工技术在材料表面加工出一定的图形,经过封装等步骤,使其成为一定的流道结构,控制流体在芯片中的流动,从而完成某些反应,最终达到取代常规实验平台的目的。微流控芯片已经在药物筛选、细胞培养、免疫分析等多个领域有了广泛的应用。The concept of microfluidic chip was born at the end of the 20th century, through the design and manufacture of miniaturized chip devices to achieve the purpose of automation and integration to complete experimental operations. Microfluidic chip technology uses micromachining technology to process a certain pattern on the surface of the material. After packaging and other steps, it becomes a certain flow channel structure to control the flow of fluid in the chip, so as to complete certain reactions, and finally replace the conventional Purpose of the experimental platform. Microfluidic chips have been widely used in many fields such as drug screening, cell culture, and immunoassays.
对于微流控芯片中流体的流动路径与是否进行流动的控制可以通过阀结构来实现。近年来,随着微流控技术的发展,出现了多种微阀结构。现有的微阀结构多通过向微流控芯片中加入可以平移或旋转的组件,组件内部打孔连通流道的上下游,通过外界控制组件的移动,使得其内部的孔与芯片中的流道对齐或错开,以达到阀结构开合的效果,如球阀、电磁阀。The control of the flow path and whether to flow of the fluid in the microfluidic chip can be realized by the valve structure. In recent years, with the development of microfluidic technology, various microvalve structures have appeared. In the existing micro-valve structure, components that can translate or rotate are added to the microfluidic chip, and the inside of the component is perforated to connect the upstream and downstream of the flow channel. The channels are aligned or staggered to achieve the effect of valve structure opening and closing, such as ball valves and solenoid valves.
然而这种阀结构存在着缺陷。首先,由于需要向较小的微流控芯片中加入可移动的组件,该结构较难组装;其次,由于流道壁由多个部分组成,装配过程中的误差容易引发微流控芯片的流道堵塞、漏液等问题;并且,该结构需要根据不同的微流控芯片尺寸定制不同尺寸的组件,难以批量化生产。这些缺陷都使得这种微阀结构难以在微流控芯片中有广泛的应用。另一些微阀利用外力引发微流道的形变从而控制流道的开合,如通过控制气道中气体的压力,利用高压时气道的充盈挤压与之垂直的液体流道,使得流道闭合,低压时气道干瘪并重新开放液体流道。这类微阀具有易于组装、不对原有流道结构进行改变,且易于接受外界信号控制等优点。现有的基于形变的微阀,通过控制外力在流道的外壁上的施加和撤除,实现对流道的压合和复原,流道为单一流道,使其形变所需的外力较大,且常发生压合不严等情况。However, this valve structure has drawbacks. First, the structure is difficult to assemble due to the need to add movable components to the smaller microfluidic chip; secondly, since the flow channel wall is composed of multiple parts, errors in the assembly process can easily cause the flow of the microfluidic chip In addition, the structure needs to customize components of different sizes according to different microfluidic chip sizes, which is difficult to mass-produce. These defects make it difficult for this microvalve structure to be widely used in microfluidic chips. Other microvalves use external force to cause the deformation of the microchannel to control the opening and closing of the channel. For example, by controlling the pressure of the gas in the airway, the filling of the airway at high pressure is used to squeeze the liquid channel perpendicular to it, so that the channel is closed. , at low pressure the airway shriveles and re-opens the fluid flow path. This kind of microvalve has the advantages of easy assembly, no change to the original flow channel structure, and easy acceptance of external signal control. The existing deformation-based microvalve realizes the pressing and restoring of the flow channel by controlling the application and removal of external force on the outer wall of the flow channel. The flow channel is a single flow channel, and the external force required for its deformation is large, and Often there are situations such as lax pressing.
发明内容SUMMARY OF THE INVENTION
发明目的:本发明的目的是提供一种用于微流控芯片的微阀装置及其制备方法和应用,该微阀结构易于组装、不对原有流道结构进行改变且活动部件不直接接触流体。Purpose of the Invention: The purpose of the present invention is to provide a microvalve device for a microfluidic chip and a preparation method and application thereof, the microvalve structure is easy to assemble, does not change the original flow channel structure, and the moving parts do not directly contact the fluid .
技术方案:为达到上述目的,本发明采用以下技术方案:Technical scheme: in order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme:
一种用于微流控芯片的微阀装置,包括盖片、弹性材料层和可变形装置层,弹性材料层位于盖片和可变形装置层中间,并且弹性材料层与盖片的中间设有独立的通液流道和空腔,空腔位于通液流道的两侧,弹性材料层能够在可变形装置层的挤压或者牵拉下进行弹性形变,从而控制通液流道的闭合和开启。A microvalve device for a microfluidic chip, comprising a cover sheet, an elastic material layer and a deformable device layer, the elastic material layer is located between the cover sheet and the deformable device layer, and the middle of the elastic material layer and the cover sheet is provided with Independent liquid passage and cavity, the cavities are located on both sides of the liquid passage, and the elastic material layer can be elastically deformed under the extrusion or pulling of the deformable device layer, thereby controlling the closing and closing of the liquid passage. on.
此外,还包括设于盖片表面的两个圆孔,其分别与通液流道的两端开口相连。In addition, it also includes two circular holes arranged on the surface of the cover sheet, which are respectively connected with the openings at both ends of the liquid passage.
所述可变形装置层为压电膜,其与电信号发生装置相连接。The deformable device layer is a piezoelectric film, which is connected to the electrical signal generating device.
所述用于微流控芯片的微阀装置的制备方法,包括以下步骤:The preparation method of the microvalve device for the microfluidic chip comprises the following steps:
(1)使用PDMS材料(聚二甲基硅氧烷),将预聚体与固化剂混合,倒入制作好的模具上,将PDMS脱气,然后加热使其固化,形成包含一条较长凹槽与两侧较短凹槽的结构;(1) Using PDMS material (polydimethylsiloxane), mix the prepolymer with the curing agent, pour it into the prepared mold, degas the PDMS, and then heat it to cure it to form a long concave The structure of grooves and shorter grooves on both sides;
(2)将上述PDMS有图案的一侧与盖片键合,形成一条可以进行通液操作的通液流道和流道两侧的密闭空腔;(2) bonding the patterned side of the PDMS with the cover sheet to form a liquid-passing flow channel that can perform liquid-passing operation and a closed cavity on both sides of the flow channel;
(3)利用PDMS自身的粘性贴合,将一片大小能够覆盖两个空腔区域的可变形装置层覆盖在PDMS芯片下表面,即得。(3) Using the adhesive bonding of PDMS itself, a deformable device layer with a size that can cover two cavity regions is covered on the lower surface of the PDMS chip, that is, it is obtained.
步骤(2)中盖片与PDMS键合前,先在盖片上雕刻出两个圆孔,两圆孔中心相对位置与PDMS表面直线图案的两个端点相对应。In step (2), before the cover sheet is bonded to the PDMS, two circular holes are carved on the cover sheet, and the relative positions of the centers of the two circular holes correspond to the two end points of the linear pattern on the PDMS surface.
本发明最后还提供了所述微流控芯片的微阀装置检测聚合酶链式反应效率的应用。Finally, the invention also provides the application of the microvalve device of the microfluidic chip to detect the efficiency of polymerase chain reaction.
本发明微阀的主要结构由包含三个平行空腔的软质材料和可变形装置组成。使用具有弹性的软质材料制备微流道,软质材料中共包含三个平行的空腔,其中中央的空腔作为通液流道,两侧的空腔不通液,为流道可能产生的形变提供形变空间。上述两侧的空腔可以是密闭空腔也可以不是密闭空腔。上述软质材料的外表面平整光滑,贴合一片平整的可变形装置,该装置在空腔面的投影面积与通液流道有重叠。上述可变形装置可以受控变形,可以在软质材料外侧对空腔施加形变作用,形变作用发生后,驱动与之相连的流道壁与另一侧流道壁贴合,两侧平行的空腔为形变提供了空间,降低了流道壁贴合所需的驱动力。通过控制可变形装置的形变与否,可以改变微阀的开合状态。形变发生后,空腔流道两壁的贴合状态改变,可以由贴合改变为分离,也可以由分离改变为贴合。流道两壁贴合时,流道闭合、流体不能通过,流道两壁分离时,流道开放,流体正常流动。通过控制可变形装置以改变中间空腔两壁的贴合与否,可以是可变形装置形变时中间空腔两壁贴合,形变撤除时中间空腔两壁分离,也可以是变形装置形变时中间空腔两壁分离,形变撤除时中间空腔两壁贴合。The main structure of the microvalve of the present invention consists of a soft material containing three parallel cavities and a deformable device. The microfluidic channel is prepared by using an elastic soft material. The soft material contains three parallel cavities in total, of which the central cavity is used as a liquid flow channel, and the cavities on both sides do not pass liquid, which is the possible deformation of the flow channel. Provide room for deformation. The cavities on both sides may be closed cavities or not. The outer surface of the above-mentioned soft material is flat and smooth, and is fitted with a flat deformable device, and the projected area of the device on the cavity surface overlaps with the liquid passage. The above-mentioned deformable device can be deformed in a controlled manner, and can exert a deformation effect on the cavity on the outside of the soft material. The cavity provides room for deformation, reducing the driving force required for runner wall fit. By controlling the deformation of the deformable device, the opening and closing states of the microvalve can be changed. After the deformation occurs, the bonding state of the two walls of the cavity flow channel changes, which can be changed from bonding to separation, and can also be changed from separation to bonding. When the two walls of the flow channel are attached, the flow channel is closed and the fluid cannot pass through. When the two walls of the flow channel are separated, the flow channel is open and the fluid flows normally. By controlling the deformable device to change whether the two walls of the intermediate cavity fit together, it can be that when the deformable device is deformed, the two walls of the intermediate cavity are attached, and when the deformation is removed, the two walls of the intermediate cavity are separated, or when the deformable device is deformed The two walls of the middle cavity are separated, and the two walls of the middle cavity fit together when the deformation is removed.
本发明微阀易于组装、不对原有流道结构进行改变且活动部件不直接接触流体的阀结构。同时,该微阀形变时所需的外力较小,适用于压电膜等电驱动装置,易于接受外界信号控制,可以通过调整信号输入实时准确地改变阀的开合状态,从而精确控制微流控芯片中的流体运动。并且,该微阀在闭合时较之传统形变微阀更加紧密。The micro-valve of the invention is easy to assemble, does not change the original flow channel structure, and has a valve structure that the movable parts do not directly contact the fluid. At the same time, the external force required for the deformation of the microvalve is small, which is suitable for electric drive devices such as piezoelectric membranes, and is easy to accept external signal control. The opening and closing states of the valve can be accurately changed in real time by adjusting the signal input, thereby accurately controlling the microflow. fluid movement in the control chip. Moreover, the microvalve is tighter than the traditional deformable microvalve when closed.
有益效果:相对于现有技术,本发明微阀装置无需复杂的装配过程,易于批量生产。制备流道时,在需要设置阀结构的流道左右各留出一空腔,并在流道外侧覆盖可变形装置,两侧空腔的设计为流道形变提供了空间,使得流道发生形变更加容易,降低了流道闭合状态改变所需的驱动力变化幅度,扩展了可形变装置的选择面,使一些易于控制的有限形变装置能够用于微阀的装配,并且两侧流道的设计使得通液流道闭合时更加彻底,不易发生闭合不全的情况。同时,该结构可以通过调整输入信号,实时准确地改变阀的开合状态,从而精确控制微流控芯片中的流体运动。Beneficial effects: Compared with the prior art, the micro-valve device of the present invention does not need a complicated assembly process, and is easy to produce in batches. When preparing the flow channel, a cavity is left on the left and right of the flow channel where the valve structure needs to be set, and the deformable device is covered on the outside of the flow channel. It is easy to reduce the driving force change range required for changing the closed state of the flow channel, expand the selection surface of deformable devices, and enable some easy-to-control limited deformation devices to be used in the assembly of microvalves, and the design of the flow channels on both sides makes When the liquid passage is closed, it is more complete, and it is not easy to cause incomplete closure. At the same time, the structure can accurately change the opening and closing state of the valve in real time by adjusting the input signal, so as to precisely control the fluid movement in the microfluidic chip.
附图说明Description of drawings
图1:本发明微阀装置(打开状态)剖面示意图;Fig. 1: sectional schematic diagram of the microvalve device of the present invention (open state);
图2:本发明微阀装置(闭合状态)剖面示意图;Fig. 2: sectional schematic diagram of the microvalve device of the present invention (closed state);
图3:本发明微阀装置组成示意图;Figure 3: a schematic diagram of the composition of the microvalve device of the present invention;
图4:本发明微阀装置组成示意图(俯视图)。Figure 4: Schematic diagram of the composition of the microvalve device of the present invention (top view).
具体实施方式Detailed ways
下面结合具体实施例对本发明方法进行进一步说明。The method of the present invention will be further described below in conjunction with specific embodiments.
实施例1:Example 1:
一种用于微流控芯片的微阀装置,如图1、2、3和4所示,包括盖片1、弹性材料层2和可变形装置层5,弹性材料层2位于盖片1和可变形装置层5中间,并且弹性材料层2与盖片1的中间设有独立的通液流道3和空腔4,空腔4位于通液流道3的两侧,弹性材料层2能够在可变形装置层5的挤压或者牵拉下进行弹性形变,从而控制通液流道3的闭合和开启。A microvalve device for a microfluidic chip, as shown in Figures 1, 2, 3 and 4, comprises a cover sheet 1, an
此外,还包括设于盖片1表面的两个圆孔6,其分别与通液流道3的两端开口相连。In addition, it also includes two circular holes 6 arranged on the surface of the cover sheet 1 , which are respectively connected with the openings at both ends of the
所述可变形装置层5为压电膜7,其与电信号发生装置8相连接。The
实施例2:Example 2:
如图3所示,使用PDMS材料,将预聚体与固化剂按10:1的比例混合,倒入制作好的模具上,模具表面平整,中央位置有直线型状的凸起,其两侧对称分布两个矩形凸起,上述凸起高度可以相同也可以不同。将PDMS脱气,然后加热至85℃使其固化,形成包含一条较长凹槽与两侧较短凹槽的结构。使用激光雕刻机在一片玻璃片上雕刻出两个圆孔6,两圆孔6中心相对位置与上述PDMS表面直线图案的两个端点相对应。As shown in Figure 3, using PDMS material, mix the prepolymer and the curing agent in a ratio of 10:1, and pour it into the prepared mold. Two rectangular protrusions are symmetrically distributed, and the heights of the protrusions may be the same or different. The PDMS was degassed and then heated to 85°C to cure it, forming a structure containing a long groove with shorter grooves on both sides. Two circular holes 6 are engraved on a piece of glass by a laser engraving machine, and the relative positions of the centers of the two circular holes 6 correspond to the two end points of the above-mentioned PDMS surface linear pattern.
将玻璃片上的圆孔与PDMS上直线的两端相对齐,上述PDMS有图案的一侧与玻璃片键合,形成一条可以进行通液操作的直流道(通液流道3)和流道两侧的密闭空腔4。将一片大小能够覆盖两个空腔区域的可形变装置5(在本具体实施例中采用薄型压电器件,即压电膜7)覆盖在PDMS芯片表面,利用PDMS自身的粘性贴合,压电膜7外接电信号发生装置8,可以调节施加在压电膜7上的电压。Align the circular hole on the glass sheet with the two ends of the straight line on the PDMS, and the patterned side of the PDMS is bonded to the glass sheet to form a straight channel (liquid flow channel 3) and two flow channels that can perform liquid-passing operations. side closed cavity 4. Cover the surface of the PDMS chip with a piece of deformable device 5 (a thin piezoelectric device, namely the piezoelectric film 7) with a size that can cover the two cavity regions, and the piezoelectric The membrane 7 is connected to an electrical
这种阀结构是常开的。在需要微阀开启时,压电膜7两极不施加电压,此时压电膜7不产生形变,流道3畅通、流体正常流动,如图1所示。在需要微阀闭合时,调整电信号发生装置8,使得压电膜两极存在电势差,此时压电膜7向流道3方向隆起,挤压流道3并使其闭合,以阻碍流体的流动。如图2所示,流道3对应压电膜7的区域被挤压塌陷而处于关闭状态,流道3两侧的空腔4因压电膜7的形变而部分塌陷;空腔4为流道3与可形变装置5(压电膜7)发生形变提供活动空间。This valve structure is normally open. When the micro-valve needs to be opened, no voltage is applied to the two poles of the piezoelectric film 7. At this time, the piezoelectric film 7 is not deformed, the
实施例3:Example 3:
按照实施例1方法,用胶水将可形变装置5(压电膜7)与PDMS表面黏合,并预先将压电膜7调整为向通液流道3方向弯曲,制成常闭的阀结构。未向压电膜7施加电压时,压电膜7挤压流道,通液流道3上下表面贴合,流体不能通过。使用电信号发生装置8向压电膜7施加与实施例1相反的电势差时,压电膜7中央背向流道变形,使得流道3上下表面分开,此时流体能够正常流动。According to the method of Example 1, the deformable device 5 (piezoelectric film 7 ) is bonded to the surface of PDMS with glue, and the piezoelectric film 7 is adjusted to bend in the direction of the
实施例4:Example 4:
按照实施例2方法,使用该结构检测聚合酶链式反应(PCR)效率。芯片一端的孔作为进样孔,在进样孔下放置一控温装置。另一个孔作为检测孔,预先在孔的底部固定PicoGreen染料。将配置好的PCR体系滴入进样孔,利用控温装置调整温度,使得滴入的溶液进行PCR反应。反应结束后,向压电膜7通电,通电后压电膜7会背向通液流道3方向变形,使得微阀打开。液体依靠毛细作用流向检测孔,检测孔中的染料会与液体中的DNA相结合并发出荧光,使用仪器检测其荧光强度即可定量得到反应后溶液中的DNA浓度。This construct was used to test polymerase chain reaction (PCR) efficiency according to the method of Example 2. The hole at one end of the chip is used as the injection hole, and a temperature control device is placed under the injection hole. The other well serves as a detection well, and PicoGreen dye is pre-immobilized on the bottom of the well. The configured PCR system was dropped into the injection hole, and the temperature was adjusted by a temperature control device, so that the dropped solution was subjected to PCR reaction. After the reaction, the piezoelectric film 7 is energized, and the piezoelectric film 7 will deform in the direction away from the
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