CN117376787A - An audio-driven microfluidic control system, method and related equipment - Google Patents
An audio-driven microfluidic control system, method and related equipment Download PDFInfo
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Abstract
Description
技术领域Technical field
本发明涉及微流控技术领域,更具体地说,它涉及一种基于音频驱动的微流体控制系统、方法及相关设备。The present invention relates to the field of microfluidic technology, and more specifically, to an audio-driven microfluidic control system, method and related equipment.
背景技术Background technique
微流控技术作为一种新兴的科学技术已经发展了二三十年,已经应用于化学、生物学、工程学和物理学等诸多领域,学科交叉性强,在时间、空间和分析对象的精密操控上进行了突破,能够解决生命分析的许多关键问题。比如,在分析检测方面,微流控技术能够将原本只能在实验室才能完成的检测实验集成到一小块芯片上,不仅节约了耗材成本和时间成本,更重要的是能够集成多种检测技术于一体,提高检测效率;在生命科学研究方面,器官芯片技术的发展越来越得到科学家的关注,因为其在未来探究生命科研研究方面具有广大的应用前景,包括人体微环境,血液系统及淋巴免疫系统的模拟,同时让人体生物分子的信号通路研究也有了更加细化的实验平台,使理论依据更加充分,推动人类生命科学研究的革命性进展。As an emerging science and technology, microfluidic technology has been developed for 20 to 30 years. It has been applied in many fields such as chemistry, biology, engineering and physics. It has strong interdisciplinary nature and can control the precision of time, space and analysis objects. It has made breakthroughs in control and can solve many key problems in life analysis. For example, in terms of analysis and detection, microfluidic technology can integrate detection experiments that could only be completed in the laboratory onto a small chip. This not only saves the cost of consumables and time, but more importantly, it can integrate multiple detection methods. technology to improve detection efficiency; in life science research, the development of organ-on-a-chip technology has attracted more and more attention from scientists, because it has broad application prospects in exploring life science research in the future, including the human microenvironment, blood system and The simulation of the lymphatic immune system also provides a more detailed experimental platform for the study of signaling pathways of human biomolecules, making the theoretical basis more sufficient and promoting revolutionary progress in human life science research.
然而,虽然微流控芯片本身体积较小,但用于微流体控制的外置设备却庞大、笨重、昂贵,这大大制约了微流控芯片的应用场景。目前现有的微流体控制系统及其存在的问题如下:注射泵系统,成本高,体积大,便携性差,不适合即时检测环境;离心驱动系统,芯片设计门槛高,灵活度弱,难以结合温度控制模块;按压驱动系统,精度较低,自动化程度差;毛细力驱动系统,芯片设计门槛高,精度较低,流体控制能力较弱;压电式驱动系统,需要高电压,难以实用化。However, although the microfluidic chip itself is small, the external equipment used for microfluidic control is large, bulky, and expensive, which greatly restricts the application scenarios of microfluidic chips. The current existing microfluidic control systems and their existing problems are as follows: the syringe pump system has high cost, large volume, poor portability, and is not suitable for real-time detection environments; the centrifugal drive system has high chip design threshold, weak flexibility, and difficulty in combining temperature Control module; press drive system, which has low accuracy and poor automation; capillary drive system, which has high chip design threshold, low accuracy, and weak fluid control capability; piezoelectric drive system, which requires high voltage and is difficult to be practical.
有基于此,本发明提供一种基于音频驱动的微流体控制系统、方法及相关设备,实现微流体高精度、低成本、便捷的控制。Based on this, the present invention provides an audio-driven microfluidic control system, method and related equipment to achieve high-precision, low-cost and convenient control of microfluidics.
发明内容Contents of the invention
本申请的目的是提供一种基于音频驱动的微流体控制系统、方法及相关设备,解决现有微流体控制外设结构复杂、成本较高的问题,通过动圈与装配外壳箱的配合,实现音频电信号驱动的微流体控制系统。The purpose of this application is to provide an audio-driven microfluidic control system, method and related equipment to solve the problems of complex structure and high cost of existing microfluidic control peripherals. Through the cooperation of the moving coil and the assembly housing box, the Microfluidic control system driven by audio electrical signals.
本申请第一方面提供一种基于音频驱动的微流体控制系统,包括:动圈,用于将电信号转化为声信号;和装配外壳箱,所述装配外壳箱与所述动圈配合形成气腔,所述装配外壳箱内部设置连通所述气腔和微流控制芯片的第一气路,所述第一气路的支路数量与所述微流控芯片内的流道数量相适应;其中,所述装配外壳箱与所述动圈配合形成的气腔,用于当所述动圈向第一方向动作时,所述气腔体积增大,所述第一气路内的流体向靠近所述气腔的方向移动;当所述动圈向与所述第一方向相对的第二方向动作时,所述气腔体积缩小,所述第一气路内的流体向远离所述气腔的方向移动。The first aspect of this application provides a microfluidic control system based on audio drive, including: a moving coil for converting electrical signals into acoustic signals; and an assembly housing box that cooperates with the moving coil to form a gas Cavity, a first air path connecting the air chamber and the microfluidic control chip is provided inside the assembly housing box, and the number of branches of the first air path is adapted to the number of flow channels in the microfluidic chip; Wherein, the air cavity formed by the cooperation between the assembly housing box and the moving coil is used to increase the volume of the air cavity when the moving coil moves in the first direction, and the fluid in the first air path moves toward Move closer to the air chamber; when the moving coil moves in the second direction opposite to the first direction, the volume of the air chamber shrinks, and the fluid in the first air path moves away from the air chamber. direction of the cavity.
采用上述技术方案,将动圈与装配外壳箱组装密封,形成特殊的气路结构,实现基于音频驱动的微流体控制系统。通过改变输入音频电信号的波形、频率、幅值等参数,改变动圈的运动方向及速度,进而改变第一气路的压力状态,从而实现对微流控芯片内的微流体进行精确的操控,包括微流体的方向、流速及流量。基于音频驱动实现微流体高精度、低成本、便捷的控制。Using the above technical solution, the moving coil and the assembly housing box are assembled and sealed to form a special gas circuit structure to realize a microfluidic control system based on audio drive. By changing the waveform, frequency, amplitude and other parameters of the input audio electrical signal, the movement direction and speed of the moving coil are changed, thereby changing the pressure state of the first air path, thereby achieving precise control of the microfluid in the microfluidic chip. , including the direction, flow rate and flow rate of microfluidics. Realize high-precision, low-cost, and convenient control of microfluidics based on audio drive.
在一种可能的实施方式中,所述装配外壳箱内部还设置连通所述气腔和大气的第二气路,用于当所述动圈向第一方向动作时,所述气腔体积增大,所述第二气路内的流体与所述第一气路内的流体一同向靠近所述气腔的方向移动;当所述动圈向与所述第一方向相对的第二方向动作时,所述气腔体积缩小,所述第二气路内的流体与所述第一气路内的流体一同向远离所述气腔的方向移动。In a possible implementation, a second air path connecting the air chamber and the atmosphere is also provided inside the assembly housing box, so that when the moving coil moves in the first direction, the volume of the air chamber increases. When the moving coil moves in the second direction opposite to the first direction, the fluid in the second air path and the fluid in the first air path move together toward the air chamber. , the volume of the air cavity is reduced, and the fluid in the second air path moves away from the air chamber together with the fluid in the first air path.
在一种可能的实施方式中,所述装配外壳箱内部还包括:电磁阀,所述电磁阀与所述第一气路的各个支路连接,用于通断所述第一气路的各个支路;所述装配外壳箱表面嵌设:用于插接微流控芯片的插槽,所述插槽底部设置气口,所述气口与所述第一气路的支路连通。In a possible implementation, the assembly housing box further includes: a solenoid valve, which is connected to each branch of the first air path and is used to switch on and off each branch of the first air path. Branch circuit; embedded in the surface of the assembly housing box: a slot for inserting the microfluidic chip, a gas port is provided at the bottom of the slot, and the gas port is connected to the branch of the first gas circuit.
在一种可能的实施方式中,所述装配外壳箱包括:相互连通且垂直设置的第一壳体和第二壳体;所述第一壳体的表面与所述动圈配合连接,形成气腔,所述第一壳体内部设置连通所述气腔并延伸至第二壳体内部的第一气路以及连通所述气腔和大气的第二气路;所述第二壳体的表面凹陷嵌设插槽,当所述微流控芯片插接于所述插槽时,所述微流控芯片与所述第一壳体平行,所述插槽底部设置气口,所述气口与所述第一气路的支路连通。In a possible implementation, the assembly housing box includes: a first housing and a second housing that are interconnected and arranged vertically; the surface of the first housing is matingly connected with the moving coil to form a gas A cavity, a first air path connecting the air chamber and extending to the inside of the second housing and a second air path connecting the air chamber and the atmosphere are provided inside the first housing; the surface of the second housing A slot is embedded in the recess. When the microfluidic chip is plugged into the slot, the microfluidic chip is parallel to the first housing. An air port is provided at the bottom of the slot, and the air port is connected to the first housing. The branches of the first air path are connected.
在一种可能的实施方式中,所述第一壳体靠近微流控芯片的表面还设置有荧光激发模块、加热模块以及磁珠控制模块;所述荧光激发模块用于发出激发光,激发微流控芯片中的荧光化合物产生荧光发射光;所述温度控制模块用于维持设定温度,维持微流控芯片中的样本反应;所述磁珠控制模块用于控制微流控芯片中的磁珠位置,实现样本提取。In a possible implementation, the first housing is also provided with a fluorescence excitation module, a heating module and a magnetic bead control module on a surface close to the microfluidic chip; the fluorescence excitation module is used to emit excitation light to excite the microfluidic chip. The fluorescent compound in the fluidic chip generates fluorescent emission light; the temperature control module is used to maintain the set temperature and maintain the sample reaction in the microfluidic chip; the magnetic bead control module is used to control the magnetic field in the microfluidic chip. bead position to achieve sample extraction.
本申请第二方面提供一种基于音频驱动的微流体控制方法,应用于如上任一所述的一种基于音频驱动的微流体控制系统,包括:输入电信号,所述电信号为正项电压信号、负向电压信号、正向锯齿波、反向锯齿波、三角波、正弦波、方波中的任意一种或多种的组合,驱动所述动圈向第一方向或第二方向动作,控制微流控芯片内的流体移动;其中,当微流控芯片存在多个流道时,通过电磁阀控制第一气路的单个支路导通,控制微流控芯片内单个流道的流体移动。The second aspect of the present application provides an audio-driven microfluidic control method, which is applied to an audio-driven microfluidic control system as described above, including: inputting an electrical signal, and the electrical signal is a positive voltage. Any one or a combination of signals, negative voltage signals, forward sawtooth waves, reverse sawtooth waves, triangle waves, sine waves, square waves, drives the moving coil to move in the first direction or the second direction, Control the movement of fluid in the microfluidic chip; wherein, when there are multiple flow channels in the microfluidic chip, the solenoid valve is used to control the conduction of a single branch of the first air path to control the fluid in a single flow channel in the microfluidic chip. move.
本申请第三方面提供一种基于音频驱动的微流体控制系统的设备,包括:如上任一所述的基于音频驱动的微流体控制系统和微流控芯片;其中,所述基于音频驱动的微流体控制系统中,所述第一气路的支路数量为1;所述微流控芯片包括依次连通的:进样孔、微反应器和连接管,所述进样孔用于接入待测样本,所述微反应器用于完成各种生物化学反应,所述连接管与所述第一气路连通。The third aspect of the present application provides a device based on an audio-driven microfluidic control system, including: an audio-driven-based microfluidic control system and a microfluidic chip as described above; wherein, the audio-driven microfluidic control system In the fluid control system, the number of branches of the first gas path is 1; the microfluidic chip includes a sampling hole, a microreactor and a connecting tube that are connected in sequence, and the sampling hole is used to access the fluid to be processed. To measure samples, the microreactor is used to complete various biochemical reactions, and the connecting tube is connected to the first gas path.
本申请第四方面提供一种基于音频驱动的微流体控制系统的设备,包括:如上任一所述的基于音频驱动的微流体控制系统和微流控芯片;其中,所述基于音频驱动的微流体控制系统中,所述第一气路的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀控制通断;所述微流控芯片包括:液滴收集腔、T型液滴发生器、油进口、水进口、第一连接管和第二连接管,所述液滴收集腔与所述T型液滴发生器的第一端连通,所述T型液滴发生器的第二端和第三端分别与所述油进口和水进口连通,所述油进口与第一连接管连通,所述水进口与所述第二连接管连通,所述第一连接管和所述第二连接管分别与所述支路A和支路B连通。The fourth aspect of the present application provides a device based on an audio-driven microfluidic control system, including: the audio-driven-based microfluidic control system and a microfluidic chip as described in any one of the above; wherein the audio-driven microfluidic control system In the fluid control system, the number of branches of the first gas path is 2, including branch A and branch B. The branch A and branch B are controlled on and off by solenoid valves; the microfluidic chip includes : droplet collection cavity, T-shaped droplet generator, oil inlet, water inlet, first connecting pipe and second connecting pipe, the droplet collection cavity is connected with the first end of the T-shaped droplet generator, The second end and the third end of the T-shaped droplet generator are respectively connected with the oil inlet and the water inlet. The oil inlet is connected with the first connecting pipe, and the water inlet is connected with the second connecting pipe. , the first connecting pipe and the second connecting pipe are connected to the branch A and the branch B respectively.
本申请第五方面提供一种基于音频驱动的微流体控制系统的设备,包括:如上任一所述的基于音频驱动的微流体控制系统和微流控芯片;其中,所述基于音频驱动的微流体控制系统中,所述第一气路的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀控制通断;所述微流控芯片包括:检测区、样本、裂解液、清洗液、洗脱液、微柱、第一连接管和第二连接管,所述样本、裂解液、清洗液通过各自的管道汇合至微柱,所述微柱一端连通检测区和第二连接管,所述微柱的另一端通过洗脱液连通第一连接管,所述第一连接管和所述第二连接管分别与所述支路A和支路B连通。The fifth aspect of the present application provides a device based on an audio-driven microfluidic control system, including: an audio-driven-based microfluidic control system and a microfluidic chip as described in any one of the above; wherein, the audio-driven microfluidic control system In the fluid control system, the number of branches of the first gas path is 2, including branch A and branch B. The branch A and branch B are controlled on and off by solenoid valves; the microfluidic chip includes : detection area, sample, lysis solution, cleaning solution, eluent, micro-column, first connecting tube and second connecting tube, the sample, lysing solution and cleaning solution are merged into the micro-column through their respective pipelines, and the micro-column is One end of the column is connected to the detection area and the second connecting pipe, and the other end of the micro column is connected to the first connecting pipe through the eluent. The first connecting pipe and the second connecting pipe are connected to the branch A and the branch respectively. Road B is connected.
本申请第六方面提供一种基于音频驱动的微流体控制系统的设备,包括:如上任一所述的基于音频驱动的微流体控制系统和微流控芯片;其中,所述基于音频驱动的微流体控制系统中,所述第一气路的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀控制通断;所述微流控芯片包括:培养器官腔室、第一流管、第二流管、转换中心、第一连接管和第二连接管,所述培养器官腔室的上端通过第一流管与转换中心的上端连通,所述转换中心的下端通过第二流管与所述培养器官腔室的下端连通,所述转换中心的上端和下端分别通过第一连接管和第二连接管与支路A和支路B连通。The sixth aspect of this application provides a device based on an audio-driven microfluidic control system, including: the audio-driven-based microfluidic control system and a microfluidic chip as described above; wherein, the audio-driven microfluidic control system In the fluid control system, the number of branches of the first gas path is 2, including branch A and branch B. The branch A and branch B are controlled on and off by solenoid valves; the microfluidic chip includes : a culture organ chamber, a first flow tube, a second flow tube, a conversion center, a first connecting pipe and a second connecting pipe, the upper end of the cultured organ chamber is connected to the upper end of the conversion center through the first flow pipe, and the conversion center The lower end of the center is connected to the lower end of the cultured organ chamber through a second flow tube, and the upper end and lower end of the conversion center are connected to branch A and branch B through first connecting pipes and second connecting pipes respectively.
与现有技术相比,本申请具有以下有益效果:Compared with the existing technology, this application has the following beneficial effects:
1、本发明提供了一种基于音频驱动的微流体控制系统,将动圈与特殊结构的装配外壳箱组装密封,形成特殊的气路结构,以较低的成本实现音频电信号驱动微流体;同时集成了荧光激发模块、加热模块以及磁珠控制模块,可以精确化地完成微流控技术所需的各种微流体控制需求;1. The present invention provides an audio-driven microfluidic control system, which assembles and seals the moving coil with a special-structured assembly housing box to form a special air path structure, and realizes audio-electric signal-driven microfluidics at a lower cost; At the same time, it integrates the fluorescence excitation module, heating module and magnetic bead control module, which can accurately complete various microfluidic control requirements required by microfluidic technology;
2、本发明提供了一种基于音频驱动的微流体控制方法,通过不同旋律的音频电信号输入即可完成微流体在芯片内方向、流速及流量的控制,可以配合实现液体顺序进样、液体混合、液体循环、定量分配及液滴生成等多种功能;2. The present invention provides an audio-driven microfluidic control method. The control of the direction, flow rate and flow rate of the microfluid in the chip can be completed through the input of audio electrical signals of different melodies, and can be used to realize sequential liquid sampling and liquid flow control. Various functions such as mixing, liquid circulation, quantitative distribution and droplet generation;
3、本发明提供了基于音频驱动的微流体控制系统的相关设备,基于音频驱动的微流体控制方法,设计匹配的气路结构和微流控芯片结构,可以集成在芯片内,或成为独立组件与芯片进行连接,可重复使用;采用其构成的设备具有智能化、便携化、微型化及低成本等优势。3. The present invention provides related equipment for an audio-driven microfluidic control system. Based on the audio-driven microfluidic control method, the matching gas path structure and microfluidic chip structure are designed, which can be integrated into the chip or become an independent component. It is connected to the chip and can be used repeatedly; the equipment composed of it has the advantages of intelligence, portability, miniaturization and low cost.
附图说明Description of the drawings
此处所说明的附图用来提供对本发明实施例的进一步理解,构成本申请的一部分,并不构成对本发明实施例的限定。在附图中:The drawings described here are used to provide a further understanding of the embodiments of the present invention, constitute a part of this application, and do not constitute a limitation to the embodiments of the present invention. In the attached picture:
图1为本发明实施例1提供的基于音频驱动的微流体控制系统的正视图;Figure 1 is a front view of an audio-driven microfluidic control system provided in Embodiment 1 of the present invention;
图2为本发明实施例1提供的基于音频驱动的微流体控制系统的俯视图;Figure 2 is a top view of the audio-driven microfluidic control system provided in Embodiment 1 of the present invention;
图3为本发明实施例1提供的基于音频驱动的微流体控制系统的侧视图;Figure 3 is a side view of the audio-driven microfluidic control system provided in Embodiment 1 of the present invention;
图4为本发明实施例2提供的电信号为正向锯齿波和反向锯齿波时的示意图;Figure 4 is a schematic diagram when the electrical signal provided by Embodiment 2 of the present invention is a forward sawtooth wave and a reverse sawtooth wave;
图5为本发明实施例2提供的电信号为正弦波时的示意图;Figure 5 is a schematic diagram when the electrical signal provided by Embodiment 2 of the present invention is a sine wave;
图6为本发明实施例2提供的电信号驱动微流体后退的示意图;Figure 6 is a schematic diagram of the electrical signal driving the microfluid to retreat according to Embodiment 2 of the present invention;
图7为本发明实施例2提供的电信号驱动微流体前进的示意图;Figure 7 is a schematic diagram of electrical signals driving microfluidic advancement provided in Embodiment 2 of the present invention;
图8为本发明实施例2提供的电信号控制流道A的示意图;Figure 8 is a schematic diagram of the electrical signal control flow channel A provided in Embodiment 2 of the present invention;
图9为本发明实施例2提供的电信号控制流道B的示意图;Figure 9 is a schematic diagram of the electrical signal control flow channel B provided in Embodiment 2 of the present invention;
图10为本发明实施例3提供的基于音频驱动的微流体控制系统集成在芯片内的示意图;Figure 10 is a schematic diagram of an audio-driven microfluidic control system integrated into a chip according to Embodiment 3 of the present invention;
图11为本发明实施例4提供的基于音频驱动的微流体控制系统应用于液滴生成的示意图;Figure 11 is a schematic diagram of the audio-driven microfluidic control system applied to droplet generation in Embodiment 4 of the present invention;
图12为本发明实施例5提供的基于音频驱动的微流体控制系统应用于全自动化核酸提取及检测的示意图;Figure 12 is a schematic diagram of the application of the audio-driven microfluidic control system provided in Embodiment 5 of the present invention to fully automated nucleic acid extraction and detection;
图13为本发明实施例6提供的基于音频驱动的微流体控制系统应用于器官芯片研究的示意图;Figure 13 is a schematic diagram of the application of the audio-driven microfluidic control system provided in Embodiment 6 of the present invention to organ chip research;
附图中标记及对应的零部件名称:Marks and corresponding parts names in the attached drawings:
1、动圈;2、装配外壳箱;21、第一壳体;22、第二壳体;23、气腔;24、第一气路;25、第二气路;26、电磁阀;27、插槽;3、微流控芯片;4、荧光激发模块;5、加热模块;6、磁珠控制模块;71、进样孔;72、微反应器;73、连接管;81、液滴收集腔;82、T型液滴发生器;83、油进口;84、水进口;91、检测区;92、样本;93、裂解液;94、清洗液;95、洗脱液;96、微柱;101、培养器官腔室;102、第一流管;103、第二流管;104、转换中心。1. Moving coil; 2. Assembly shell box; 21. First housing; 22. Second housing; 23. Air chamber; 24. First air path; 25. Second air path; 26. Solenoid valve; 27 , slot; 3. Microfluidic chip; 4. Fluorescence excitation module; 5. Heating module; 6. Magnetic bead control module; 71. Injection hole; 72. Microreactor; 73. Connecting tube; 81. Droplet Collection chamber; 82. T-shaped droplet generator; 83. Oil inlet; 84. Water inlet; 91. Detection area; 92. Sample; 93. Lysis solution; 94. Cleaning solution; 95. Eluent; 96. Micro Column; 101, culture organ chamber; 102, first flow tube; 103, second flow tube; 104, conversion center.
具体实施方式Detailed ways
为使本申请的目的、技术方案和优点更加清楚明白,下面结合实施例和附图,对本申请作进一步的详细说明,本申请的示意性实施方式及其说明仅用于解释本申请,并不作为对本申请的限定。In order to make the purpose, technical solutions and advantages of the present application more clear, the present application will be further described in detail below in conjunction with the embodiments and drawings. The schematic embodiments of the present application and their descriptions are only used to explain the present application and do not As a limitation of this application.
实施例1提供一种基于音频驱动的微流体控制系统,请参见图1-3所示,系统包括:动圈1,用于将电信号转化为声信号;和装配外壳箱2,所述装配外壳箱2与所述动圈1配合形成气腔23,所述装配外壳箱2内部设置连通所述气腔23和微流控制芯片3的第一气路24,所述第一气路24的支路数量与所述微流控芯片3内的流道数量相适应;Embodiment 1 provides an audio-driven microfluidic control system, as shown in Figures 1-3. The system includes: a moving coil 1 for converting electrical signals into acoustic signals; and an assembly housing box 2. The housing box 2 cooperates with the moving coil 1 to form an air chamber 23. A first air path 24 is provided inside the assembled housing box 2 to connect the air chamber 23 and the microfluidic control chip 3. The first air path 24 is The number of branches is adapted to the number of flow channels in the microfluidic chip 3;
其中,所述装配外壳箱2与所述动圈1配合形成的气腔23,用于当所述动圈1向第一方向动作时,所述气腔23体积增大,所述第一气路24内的流体向靠近所述气腔23的方向移动;当所述动圈1向与所述第一方向相对的第二方向动作时,所述气腔23体积缩小,所述第一气路24内的流体向远离所述气腔23的方向移动。Among them, the air chamber 23 formed by the cooperation between the assembly housing box 2 and the moving coil 1 is used to increase the volume of the air chamber 23 when the moving coil 1 moves in the first direction, and the first air chamber 23 increases in volume. The fluid in the path 24 moves in the direction closer to the air chamber 23; when the moving coil 1 moves in the second direction opposite to the first direction, the volume of the air chamber 23 shrinks, and the first air chamber 23 The fluid in the path 24 moves away from the air chamber 23 .
具体地,动圈1用于将音频电信号转化为振动声信号,例如,可以采用现有的扬声器、喇叭等器件,或者自制的其他具备将音频电信号转化为振动声信号的结构;装配外壳箱2为壳体结构,其内可以设置气路、固定多种器件;装配外壳箱2与动圈1配合组装,两者之间形成一个空腔,称为气腔23。为保证装配外壳箱2与动圈1连接处的气密性,可以采用压缩垫、密封胶、O型圈等密封方式,避免流体从连接处渗出,构建密闭的气腔23环境。进一步,为了实现电信号驱动微流体,本系统设置连通气腔23和微流控制芯片的第一气路24;微流控芯片3可以选择常见的受气压操控的微流控芯片3,其内含有流道,流道开口与第一气路24连接,实现第一气路24与流道的连通。本系统的目的在于,控制微流控芯片3内微流的移动,具体是通过动圈1动作改变气腔23内的气压,经第一气路24调整微流控芯片3内流体的移动。Specifically, the moving coil 1 is used to convert audio electrical signals into vibrating sound signals. For example, existing speakers, horns and other devices can be used, or other self-made structures capable of converting audio electrical signals into vibrating sound signals; assemble the shell The box 2 is a shell structure, in which air paths can be set and various devices can be fixed; the assembly shell box 2 is assembled with the moving coil 1, and a cavity is formed between the two, which is called the air cavity 23. In order to ensure the airtightness of the connection between the assembly housing box 2 and the moving coil 1, sealing methods such as compression gaskets, sealants, and O-rings can be used to prevent fluid from seeping from the connection and create a sealed air cavity 23 environment. Furthermore, in order to realize the electrical signal driving microfluid, this system is provided with a first air path 24 that connects the air chamber 23 and the microfluidic control chip; the microfluidic chip 3 can choose a common microfluidic chip 3 controlled by air pressure, in which It contains a flow channel, and the opening of the flow channel is connected with the first air path 24 to realize the communication between the first air path 24 and the flow channel. The purpose of this system is to control the movement of the microfluid in the microfluidic chip 3, specifically by changing the air pressure in the air chamber 23 through the action of the moving coil 1, and adjusting the movement of the fluid in the microfluidic chip 3 through the first air path 24.
请参见图6-7所示。本系统通过音频电信号驱动微流体的原理为:音频电信号驱动动圈1振动,通过动圈1振动改变气腔23内的压力状态,第一气路24内的压力状态随之改变,进而控制与之连通的微流控芯片3内微流的移动。以系统水平放置为例,受音频电信号的影响,动圈1可能向上动作或向下动作,当动圈1向上动作时,气腔23体积增大,第一气路24产生向气腔23方向移动的压力,进而实现微流控芯片3内微流向流道开口方向移动,当动圈1向下动作时,气腔23体积减小,第一气路24产生向远离气腔23方向移动的压力,进而实现微流控芯片3内微流向远离流道开口方向移动。See Figure 6-7. The principle of this system to drive microfluidics through audio electrical signals is as follows: the audio electrical signals drive the moving coil 1 to vibrate, and the vibration of the moving coil 1 changes the pressure state in the air chamber 23, and the pressure state in the first air path 24 changes accordingly, and then Control the movement of the microfluid in the microfluidic chip 3 connected to it. Taking the system placed horizontally as an example, due to the influence of the audio electrical signal, the moving coil 1 may move upward or downward. When the moving coil 1 moves upward, the volume of the air chamber 23 increases, and the first air path 24 generates a flow toward the air chamber 23 The pressure of the movement in the direction of the microfluidic chip 3 enables the microflow in the microfluidic chip 3 to move toward the opening of the flow channel. When the moving coil 1 moves downward, the volume of the air chamber 23 decreases, and the first air path 24 moves away from the air chamber 23. pressure, thereby realizing the movement of the microflow in the microfluidic chip 3 away from the opening of the flow channel.
需要说明的是,本发明将音频电信号与微流体控制相结合,将动圈1与装配外壳箱2组装密封,形成特殊的气路结构,实现基于音频驱动的微流体控制系统。通过改变输入音频电信号的波形、频率、幅值等参数,改变动圈1的运动方向及速度,进而改变第一气路24的压力状态,从而实现对微流控芯片3内的微流体进行精确的操控,包括微流体的方向、流速及流量。通过动圈1与装配外壳箱2即可实现微流体控制,整体结构便携、成本低廉且具有较高的控制精度,可广泛应用于受气压控制的微流控芯片3,以实现微流控芯片3所需的液体顺序进样、液体混合、液体循环、定量分配及液滴生成等功能。It should be noted that the present invention combines audio electrical signals with microfluidic control, assembles and seals the moving coil 1 and the assembly housing box 2, forms a special gas circuit structure, and realizes a microfluidic control system based on audio drive. By changing the waveform, frequency, amplitude and other parameters of the input audio electrical signal, the movement direction and speed of the moving coil 1 are changed, thereby changing the pressure state of the first air path 24, thereby realizing the microfluidic control in the microfluidic chip 3. Precise control of microfluidic direction, flow rate and flow rate. Microfluidic control can be realized through the moving coil 1 and the assembled housing box 2. The overall structure is portable, low-cost and has high control accuracy. It can be widely used in microfluidic chips 3 controlled by air pressure to realize microfluidic chips. 3. Required functions such as liquid sequential injection, liquid mixing, liquid circulation, quantitative distribution, and droplet generation.
在一种可能的实施方式中,所述装配外壳箱2内部还设置连通所述气腔23和大气的第二气路25,用于当所述动圈1向第一方向动作时,所述气腔23体积增大,所述第二气路25内的流体与所述第一气路24内的流体一同向靠近所述气腔23的方向移动;当所述动圈1向与所述第一方向相对的第二方向动作时,所述气腔23体积缩小,所述第二气路25内的流体与所述第一气路24内的流体一同向远离所述气腔23的方向移动。In a possible implementation, a second air passage 25 connecting the air chamber 23 and the atmosphere is also provided inside the assembly housing box 2 so that when the moving coil 1 moves in the first direction, the second air path 25 is provided. The volume of the air chamber 23 increases, and the fluid in the second air path 25 and the fluid in the first air path 24 move toward the direction of the air chamber 23 together; when the moving coil 1 moves toward the air chamber 23 When moving in the second direction opposite to the first direction, the volume of the air chamber 23 is reduced, and the fluid in the second air path 25 and the fluid in the first air path 24 move away from the air chamber 23 together. move.
设置第二气路25的原因在于,当使用锯齿波进行流体控制时,可以使用第二气路进行排气,当使用方波或者正弦波进行流体控制时,可以封堵住第二气路,仅采用第一气路控制微流控芯片内的流体移动。The reason for providing the second air path 25 is that when a sawtooth wave is used for fluid control, the second air path can be used for exhaust, and when a square wave or sine wave is used for fluid control, the second air path can be blocked. Only the first gas path is used to control fluid movement within the microfluidic chip.
在一种可能的实施方式中,所述装配外壳箱2内部还包括:电磁阀26,所述电磁阀26与所述第一气路24的各个支路连接,用于通断所述第一气路24的各个支路。In a possible implementation, the assembly housing box 2 also includes: a solenoid valve 26 connected to each branch of the first air path 24 for switching on and off the first gas path. Each branch of the air path 24.
具体地,当微流控芯片3内存在多个流道,需要对多个流道内的微流体进行分别控制时,第一气路24需具备与流道数量对应的分支,各个分支均通过电磁阀26控制选通。例如,微流控芯片3包含两个流道,具有两个流道开口时,系统内的第一气路24需要设置两个分支,两个分支与两个流道开口对应连接,实现两个分支与两个流道的对应连通;当需要控制流道A内的微流体时,打开分支A对应的电磁阀26即可。Specifically, when there are multiple flow channels in the microfluidic chip 3 and it is necessary to control the microfluids in the multiple flow channels respectively, the first gas path 24 needs to have branches corresponding to the number of flow channels, and each branch passes through the electromagnetic Valve 26 controls the gating. For example, when the microfluidic chip 3 contains two flow channels and has two flow channel openings, the first gas path 24 in the system needs to be provided with two branches, and the two branches are correspondingly connected to the two flow channel openings to achieve two The branches are connected to the corresponding ones of the two flow channels; when it is necessary to control the microfluid in flow channel A, just open the solenoid valve 26 corresponding to branch A.
优选地,本系统中第一气路24可以采用分支的结构实现多流道的控制,即第一气路24靠近气腔23的一端为主路,靠近微流控芯片3的一端根据微流控芯片3内的流道数量拆分为多个分支,各个分支通过电磁阀26控制选通。Preferably, the first gas path 24 in this system can adopt a branched structure to realize the control of multiple flow channels, that is, one end of the first gas path 24 close to the air chamber 23 is the main channel, and the end close to the microfluidic chip 3 is based on the microfluidic flow. The number of flow channels in the control chip 3 is divided into multiple branches, and each branch is controlled by a solenoid valve 26.
可选地,第一气路24设置为多个,其数量根据微流控芯片3内的流道数量而定。多个第一气路24,一端连接气腔23,另一端连接对应的微流控芯片3流道开口,实现气腔23到流道的连通。各个第一气路24通过电磁阀26控制选通。Optionally, multiple first gas channels 24 are provided, and their number is determined according to the number of flow channels in the microfluidic chip 3 . One end of the plurality of first air passages 24 is connected to the air chamber 23, and the other end is connected to the corresponding flow channel opening of the microfluidic chip 3 to realize communication between the air chamber 23 and the flow channel. Each first air path 24 is controlled by a solenoid valve 26.
需要说明的是,电磁阀26可以采用集成多个通道的单个电磁阀26或者多个独立的电磁阀26。It should be noted that the solenoid valve 26 may be a single solenoid valve 26 integrating multiple channels or a plurality of independent solenoid valves 26 .
进一步地,所述装配外壳箱2表面嵌设:用于插接微流控芯片3的插槽27,所述插槽27底部设置气口,所述气口与所述第一气路24的支路连通。Further, the assembly housing box 2 is embedded with a slot 27 for inserting the microfluidic chip 3 on the surface. An air port is provided at the bottom of the slot 27. The branch of the air port and the first air path 24 is Connected.
具体地,为了固定微流控芯片3,且保证微流控芯片3内的流道与系统的第一气路24连通,因此在装配外壳箱2表面嵌设插槽27,且插槽27底部设置与第一气路24的支路连通的气口。Specifically, in order to fix the microfluidic chip 3 and ensure that the flow channel in the microfluidic chip 3 is connected with the first air path 24 of the system, a slot 27 is embedded on the surface of the assembly housing box 2, and the bottom of the slot 27 An air port connected to the branch of the first air path 24 is provided.
在一种可能的实施方式中,所述装配外壳箱2包括:相互连通且垂直设置的第一壳体21和第二壳体22;所述第一壳体21的表面与所述动圈1配合连接,形成气腔23,所述第一壳体21内部设置连通所述气腔23和大气的第二气路25以及连通所述气腔23并延伸至第二壳体22内部的第一气路24;所述第二壳体22的表面凹陷嵌设插槽27,当所述微流控芯片3插接于所述插槽27时,所述微流控芯片3与所述第一壳体21平行,所述插槽27底部设置气口,所述气口与所述第一气路24的支路连通。In a possible implementation, the assembly housing box 2 includes: a first housing 21 and a second housing 22 that are interconnected and arranged vertically; the surface of the first housing 21 is in contact with the moving coil 1 Fittingly connected to form an air chamber 23, a second air path 25 connecting the air chamber 23 and the atmosphere is provided inside the first housing 21, and a first air path 25 connecting the air chamber 23 and extending to the inside of the second housing 22 is provided. Air path 24; the recessed surface of the second housing 22 is embedded with a slot 27. When the microfluidic chip 3 is inserted into the slot 27, the microfluidic chip 3 and the first The housing 21 is parallel, and an air port is provided at the bottom of the slot 27 . The air port is connected to the branch of the first air path 24 .
具体地,本实施例示例性地给出一种装配外壳箱2可能的实现结构,如图3所示,包括相互连通且垂直设置的第一壳体21和第二壳体22。图3中,第一壳体21水平设置,其上连接动圈1,第二壳体22垂直设置,侧壁凹陷嵌设插槽27,微流控芯片3插接于插槽27时,微流控芯片3与第一壳体21平行。该结构简单易实现。Specifically, this embodiment exemplifies a possible implementation structure of assembling the housing box 2, as shown in FIG. 3, including a first housing 21 and a second housing 22 that are connected to each other and arranged vertically. In Figure 3, the first housing 21 is arranged horizontally, with the moving coil 1 connected to it, and the second housing 22 is arranged vertically, with a recessed side wall embedded in a slot 27. When the microfluidic chip 3 is inserted into the slot 27, the microfluidic chip 3 is inserted into the slot 27. The fluidic chip 3 is parallel to the first housing 21 . The structure is simple and easy to implement.
需要说明的是,当动圈1为图3所示的类圆锥形结构时,该类圆锥形结构内部本身具有一定空间,因此可以直接与水平设置的第一壳体21连接,自然形成气腔23。如动圈1自身不具备空间或空间过小时,可以将第一壳体21的一部分表面向内凹陷,通过凹陷部分与动圈1配合,形成气腔23。It should be noted that when the moving coil 1 is a quasi-conical structure as shown in Figure 3, the conical structure itself has a certain space inside, so it can be directly connected to the horizontally arranged first housing 21 to naturally form an air cavity. twenty three. If the moving coil 1 itself does not have space or the space is too small, a part of the surface of the first housing 21 can be recessed inward, and the recessed portion cooperates with the moving coil 1 to form an air cavity 23 .
在一种可能的实施方式中,所述第一壳体21靠近微流控芯片3的表面还设置有荧光激发模块4、加热模块5以及磁珠控制模块6;所述荧光激发模块4用于发出激发光,激发微流控芯片3中的荧光化合物产生荧光发射光;所述温度控制模块用于维持设定温度,维持微流控芯片3中的样本92反应;所述磁珠控制模块6用于控制微流控芯片3中的磁珠位置,实现样本92提取。In a possible implementation, the first housing 21 is also provided with a fluorescence excitation module 4, a heating module 5 and a magnetic bead control module 6 on the surface close to the microfluidic chip 3; the fluorescence excitation module 4 is used for Emit excitation light to excite the fluorescent compound in the microfluidic chip 3 to produce fluorescent emission light; the temperature control module is used to maintain the set temperature and maintain the reaction of the sample 92 in the microfluidic chip 3; the magnetic bead control module 6 Used to control the position of the magnetic beads in the microfluidic chip 3 to achieve sample 92 extraction.
具体地,为了拓展系统的应用场景,可以在第一壳体21靠近微流控芯片3的表面设置荧光激发模块4、加热模块5以及磁珠控制模块6。荧光激发模块4用于发出激发光,激发光使得待检测的荧光化合物发出荧光发射光;温度控制模块可以使温度维持到特定值,使得样本92发生相应反应,比如核酸扩增;磁珠控制模块6可以固定磁珠,将核酸提取出来。Specifically, in order to expand the application scenarios of the system, the fluorescence excitation module 4, the heating module 5 and the magnetic bead control module 6 can be disposed on the surface of the first housing 21 close to the microfluidic chip 3. The fluorescence excitation module 4 is used to emit excitation light, which causes the fluorescent compound to be detected to emit fluorescent emission light; the temperature control module can maintain the temperature to a specific value, so that the sample 92 undergoes corresponding reactions, such as nucleic acid amplification; the magnetic bead control module 6. Magnetic beads can be fixed and nucleic acids extracted.
需要说明的是,上述内容仅作为一种示例性的拓展,不构成对本系统的限制,本系统可以根据实际使用需要增添删改一些现有模块,以满足微流控技术的常用功能。It should be noted that the above content is only an exemplary expansion and does not constitute a restriction on this system. This system can add or delete some existing modules according to actual needs to meet the common functions of microfluidic technology.
可以理解的是,本例提供的基于音乐驱动的微流体控制系统具有便携、成本低,控制精度高等特点。同时集成了荧光激发模块4、加热模块5以及磁珠控制模块6,可以精确化地完成微流控技术所需的各种微流体控制需求,包括流体方向,流速及流量等,实现液体顺序进样、样本92的定量分配、流体混合、液体循环、液滴生产、核酸扩增等功能。It can be understood that the music-driven microfluidic control system provided in this example has the characteristics of portability, low cost, and high control accuracy. At the same time, the fluorescence excitation module 4, the heating module 5 and the magnetic bead control module 6 are integrated, which can accurately complete various microfluidic control requirements required by microfluidic technology, including fluid direction, flow rate and flow rate, etc., to achieve sequential liquid flow. It has functions such as quantitative distribution of samples and samples 92, fluid mixing, liquid circulation, droplet production, and nucleic acid amplification.
实施例2提供一种基于音频驱动的微流体控制方法,请参见图4-9所示,应用于如上所述的一种基于音频驱动的微流体控制系统,方法包括:输入电信号,所述电信号为正项电压信号、负向电压信号、正向锯齿波、反向锯齿波、三角波、正弦波、方波中的任意一种或多种的组合,驱动所述动圈1向第一方向或第二方向动作,控制微流控芯片3内的流体移动;Embodiment 2 provides an audio-driven microfluidic control method, as shown in Figures 4-9, applied to the audio-driven microfluidic control system as described above. The method includes: inputting an electrical signal, The electrical signal is any one or a combination of positive voltage signal, negative voltage signal, forward sawtooth wave, reverse sawtooth wave, triangle wave, sine wave, and square wave, driving the moving coil 1 to the first direction. The movement in one direction or the second direction controls the movement of fluid in the microfluidic chip 3;
其中,当微流控芯片3存在多个流道时,通过电磁阀26控制第一气路24的支路单个导通,控制微流控芯片3内单个流道的流体移动。When there are multiple flow channels in the microfluidic chip 3 , the solenoid valve 26 is used to control the branch of the first gas channel 24 to be individually conductive to control the movement of fluid in a single flow channel in the microfluidic chip 3 .
具体地,请参见图6-7所示,当输入电信号为负向电压时,动圈1上缩,吸动流体向后流动;当输入电信号为正向电压时,动圈1下压,推动流体向前流动。Specifically, please refer to Figure 6-7. When the input electrical signal is a negative voltage, the moving coil 1 shrinks upward, sucking the fluid to flow backward; when the input electrical signal is a positive voltage, the moving coil 1 presses downward. , pushing the fluid forward.
当给定不同波形时,流体的运动方式也将不同,当使用正向锯齿波对动圈1进行驱动时,前进力道大于后退力道,流体向前推进;当使用反向锯齿波对动圈1进行驱动时,后退力道大于前进力道,流体后退;当使用三角波时,流体不断先前进,然后后退,此时,微流控芯片3内的微流体可以在具有特殊结构的混合腔室,比如具有鱼鳞状通道的混合腔室,不断混合;当使用正弦波对动圈1进行驱动时,可以在微流控芯片3内的流道上集成单向阀,使液体在微流控芯片3上可以单向流动,此时动圈1运动变化平缓,流体流动也同样平缓,适用于对流体流动速度较敏感的细胞等样本92;当使用方波时,驱动力道大,流体运动速度快。When different waveforms are given, the movement of the fluid will also be different. When a forward sawtooth wave is used to drive the moving coil 1, the forward force is greater than the backward force, and the fluid advances forward; when a reverse sawtooth wave is used to drive the moving coil 1 When driving, the backward force is greater than the forward force, and the fluid retreats; when using a triangle wave, the fluid continuously advances first and then retreats. At this time, the microfluid in the microfluidic chip 3 can be mixed in a mixing chamber with a special structure, such as a The mixing chamber of the fish scale-shaped channel is continuously mixed; when a sine wave is used to drive the moving coil 1, a one-way valve can be integrated on the flow channel in the microfluidic chip 3, so that the liquid can flow on the microfluidic chip 3 in a single direction. At this time, the movement of the moving coil 1 changes slowly, and the fluid flow is also gentle, which is suitable for samples such as cells that are sensitive to the fluid flow speed. When square waves are used, the driving force is large and the fluid movement speed is fast.
请参见图8-9所示,当微流控芯片3存在多个流道时,通过动圈1配合电磁阀26,可以控制微流控芯片3内单个流道的流体移动。当动圈1下压时,电磁阀26打开A通道,当动圈1上缩时,电磁阀26打开B通道,就可以在A与B通道实现各自的单向流动。Referring to Figures 8-9, when there are multiple flow channels in the microfluidic chip 3, the moving coil 1 cooperates with the solenoid valve 26 to control the movement of fluid in a single flow channel in the microfluidic chip 3. When the moving coil 1 is pressed down, the solenoid valve 26 opens the A channel. When the moving coil 1 is retracted, the solenoid valve 26 opens the B channel, so that each one-way flow can be achieved in the A and B channels.
本例还示例性地给出了电信号为正向锯齿波、反向锯齿波以及正弦波时的示意图,请参见图4-5所示。This example also provides an exemplary schematic diagram when the electrical signal is a forward sawtooth wave, a reverse sawtooth wave, and a sine wave, as shown in Figure 4-5.
需要说明的是,通过改变输入音频电信号的波形、频率、幅值等参数,即可改变动圈1的运动方向及速度,进而改变第一气路24的压力状态,从而实现对微流控芯片3内的微流体进行精确的操控,包括微流体的方向、流速及流量。It should be noted that by changing the waveform, frequency, amplitude and other parameters of the input audio electrical signal, the movement direction and speed of the moving coil 1 can be changed, thereby changing the pressure state of the first air path 24, thereby realizing microfluidic control. The microfluid in chip 3 is precisely controlled, including the direction, flow rate and flow rate of the microfluid.
实施例3提供一种基于音频驱动的微流体控制系统的设备,请参见图10所示,图10为基于音频驱动的微流体控制系统集成在芯片内的示意图(基于音频驱动的微流体控制系统简易示出)。设备包括:实施例1所述的基于音频驱动的微流体控制系统和微流控芯片3;Embodiment 3 provides a device based on an audio-driven microfluidic control system, as shown in Figure 10 , which is a schematic diagram of an audio-driven microfluidic control system integrated in a chip (audio-driven microfluidic control system shown briefly). The equipment includes: the audio-driven microfluidic control system and microfluidic chip 3 described in Embodiment 1;
其中,所述基于音频驱动的微流体控制系统中,所述第一气路24的支路数量为1;所述微流控芯片3包括依次连通的:进样孔71、微反应器72和连接管73,所述进样孔71用于接入待测样本92,所述微反应器72用于完成各种生物化学反应,所述连接管73与所述第一气路24连通。Wherein, in the audio-driven microfluidic control system, the number of branches of the first gas path 24 is 1; the microfluidic chip 3 includes sequentially connected: sampling holes 71, microreactors 72 and The connecting pipe 73 , the sampling hole 71 is used to access the sample 92 to be tested, the microreactor 72 is used to complete various biochemical reactions, the connecting pipe 73 is connected with the first gas path 24 .
具体地,基于音频驱动的微流体控制系统可以作为微泵与芯片集成为一体,对微流体进行控制,设备主要包括进样孔71,微反应器72、微泵。进样孔71内可以添加所需的试剂,通过微泵提供负压动力,将液体引流进微反应器72内,通过微反应器72内的设计完成各种生物化学反应,微泵可以提供所需微流体混合、微流体方向的改变及流速变化等功能需求。Specifically, the audio-driven microfluidic control system can be integrated with the chip as a micropump to control the microfluid. The equipment mainly includes a sampling hole 71, a microreactor 72, and a micropump. The required reagents can be added to the sampling hole 71, and the micropump can provide negative pressure power to guide the liquid into the microreactor 72. Various biochemical reactions can be completed through the design in the microreactor 72. The micropump can provide all the necessary reagents. Functional requirements such as microfluidic mixing, microfluidic direction change, and flow rate change are required.
实施例4提供一种基于音频驱动的微流体控制系统的设备,请参见图11随时,图11为基于音频驱动的微流体控制系统应用于液滴生成的示意图(其中,基于音频驱动的微流体控制系统简易示出)。设备包括:如实施例1所述的基于音频驱动的微流体控制系统和微流控芯片3;Embodiment 4 provides a device based on an audio-driven microfluidic control system. Please refer to FIG. 11 at any time. FIG. 11 is a schematic diagram of the audio-driven microfluidic control system applied to droplet generation (wherein, the audio-driven microfluidic control system The control system is briefly shown). The equipment includes: the audio-driven microfluidic control system and microfluidic chip 3 as described in Example 1;
其中,所述基于音频驱动的微流体控制系统中,所述第一气路24的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀26控制通断;所述微流控芯片3包括:液滴收集腔81、T型液滴发生器82、油进口83、水进口84、第一连接管和第二连接管,所述液滴收集腔81与所述T型液滴发生器82的第一端连通,所述T型液滴发生器82的第二端和第三端分别与所述油进口83和水进口84连通,所述油进口83与第一连接管连通,所述水进口84与所述第二连接管连通,所述第一连接管和所述第二连接管分别与所述支路A和支路B连通。Wherein, in the audio-driven microfluidic control system, the number of branches of the first gas path 24 is 2, including branch A and branch B, and the branch A and branch B pass through the solenoid valve 26 Control on-off; the microfluidic chip 3 includes: a droplet collection chamber 81, a T-shaped droplet generator 82, an oil inlet 83, a water inlet 84, a first connecting pipe and a second connecting pipe. The cavity 81 is connected to the first end of the T-shaped droplet generator 82, and the second end and the third end of the T-shaped droplet generator 82 are connected to the oil inlet 83 and the water inlet 84 respectively. The oil inlet 83 is connected to the first connecting pipe, the water inlet 84 is connected to the second connecting pipe, and the first connecting pipe and the second connecting pipe are connected to the branch A and the branch B respectively.
具体地,基于音频驱动的微流体控制系统可以成为芯片外微泵重复使用,只需通过连接管将第一气路24与芯片对应的进口相连接,即可完成芯片内的微流体控制,具有便携性高,可重复使用,成本低等优势。设备整体包括液滴收集腔81,T型液滴发生器82,油进口83、水进口84、连接管及微泵。通过电磁阀26的转换,先推进一部分水,关闭水进口84,连通油进口83,推进一部分油,依此不断切换可以快速生成多个液滴,同时可以通过音频信号频率的大小来控制液滴的大小,液滴的大小也受通道的限制,因此,微液滴的大小可以达到纳升到毫升级别之间转换。例如,当T型液滴发生器82为纳米级别时,可以产生纳升级液滴,当为毫米级别时,可以产生微升级液滴。同时液滴的产生不受开始流速调节的影响,可以尽量避免试剂的损失,或在刚开始调节流速时产生大小不均一的液滴,因为其液滴大小可以通过频率进行精确的控制。Specifically, the audio-driven microfluidic control system can be reused as an off-chip micropump. Simply connect the first air path 24 to the corresponding inlet of the chip through a connecting tube to complete the microfluidic control within the chip. High portability, reusable, low cost and other advantages. The overall equipment includes a droplet collection chamber 81, a T-shaped droplet generator 82, an oil inlet 83, a water inlet 84, connecting pipes and a micropump. Through the switching of the solenoid valve 26, a part of the water is first pushed, the water inlet 84 is closed, the oil inlet 83 is connected, a part of the oil is pushed, and multiple droplets can be quickly generated by continuous switching. At the same time, the droplets can be controlled by the frequency of the audio signal. The size of the droplets is also limited by the channel, so the size of the microdroplets can be converted from nanoliter to milliliter levels. For example, when the T-shaped droplet generator 82 is at the nanometer level, it can generate nanoliter droplets, and when it is at the millimeter level, it can produce microliter droplets. At the same time, the generation of droplets is not affected by the initial flow rate adjustment, which can avoid the loss of reagents or the generation of unevenly sized droplets when the flow rate is first adjusted, because the droplet size can be precisely controlled by frequency.
实施例5提供一种基于音频驱动的微流体控制系统的设备,请参见图12所示,图12为基于音频驱动的微流体控制系统应用于全自动化核酸提取及检测的示意图(其中,基于音频驱动的微流体控制系统简易示出)。设备包括:如实施例1所述的基于音频驱动的微流体控制系统和微流控芯片3;Embodiment 5 provides a device based on an audio-driven microfluidic control system, as shown in Figure 12. Figure 12 is a schematic diagram of an audio-driven microfluidic control system applied to fully automated nucleic acid extraction and detection (wherein, the audio-based microfluidic control system The driven microfluidic control system is briefly shown). The equipment includes: the audio-driven microfluidic control system and microfluidic chip 3 as described in Example 1;
其中,所述基于音频驱动的微流体控制系统中,所述第一气路24的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀26控制通断;所述微流控芯片3包括:检测区91、样本92、裂解液93、清洗液94、洗脱液95、微柱96、第一连接管和第二连接管,所述样本92、裂解液93、清洗液94通过各自的管道汇合至微柱96,所述微柱96一端连通检测区91和第二连接管,所述微柱96另一端通过洗脱液95连通第一连接管,所述第一连接管和所述第二连接管分别与所述支路A和支路B连通。Wherein, in the audio-driven microfluidic control system, the number of branches of the first gas path 24 is 2, including branch A and branch B, and the branch A and branch B pass through the solenoid valve 26 Control on-off; the microfluidic chip 3 includes: detection area 91, sample 92, lysis solution 93, cleaning solution 94, eluent 95, micro-column 96, first connecting tube and second connecting tube, the sample 92. The lysis solution 93 and the cleaning solution 94 are merged into the micro-column 96 through their respective pipelines. One end of the micro-column 96 is connected to the detection area 91 and the second connecting tube, and the other end of the micro-column 96 is connected to the first connecting pipe through the eluent 95. Connecting pipes, the first connecting pipe and the second connecting pipe are connected to the branch A and the branch B respectively.
具体地,基于音频驱动的微流体控制系统可以作为微泵,连接一种适配的核酸提取及检测芯片,可以通过微流体控制系统完成自动化核酸全提取及数字化检测全过程。设备包括检测区91、样本92、裂解液93、清洗液94、洗脱液95、微柱96、连接管及微泵。可以将裂解液93、清洗液94及洗脱液95提前封装在芯片内,当加入样本92时,支路B提供负压,将样本92及裂解液93同时引流进入微柱96,并通过音频信号频率的控制完成样本92溶液及裂解液93在微柱96上的来回混合,当完成核酸吸附之后,将液体引流走;同时开放清洗液94,通过同样的操作完成微柱96上多余杂质的清洗,随后关闭支路B,连通支路A,将洗脱液95注入微柱96,对核酸进行清洗混合,最后提供正压,将混合好的核酸溶液注入检测区91,检测区91可以设计多个微孔阵列,通过液体的推动,完成定量分配,最后进行密封,完成核酸数字化检测。Specifically, the audio-driven microfluidic control system can be used as a micropump, connected to an adapted nucleic acid extraction and detection chip, and the entire process of automated nucleic acid extraction and digital detection can be completed through the microfluidic control system. The equipment includes a detection area 91, a sample 92, a lysis solution 93, a cleaning solution 94, an eluent 95, a micro-column 96, connecting tubes and a micro-pump. The lysis solution 93, the cleaning solution 94 and the eluent 95 can be packaged in the chip in advance. When the sample 92 is added, branch B provides negative pressure to simultaneously drain the sample 92 and the lysis solution 93 into the micro-column 96, and through the audio The control of the signal frequency completes the back-and-forth mixing of the sample 92 solution and the lysis solution 93 on the micro-column 96. After the nucleic acid adsorption is completed, the liquid is drained away; at the same time, the cleaning solution 94 is opened, and the excess impurities on the micro-column 96 are removed through the same operation. Clean, then close branch B, connect branch A, inject the eluent 95 into the micro-column 96, clean and mix the nucleic acid, and finally provide positive pressure to inject the mixed nucleic acid solution into the detection area 91. The detection area 91 can be designed Multiple microwell arrays are driven by liquid to complete quantitative distribution and are finally sealed to complete digital detection of nucleic acids.
实施例6提供一种基于音频驱动的微流体控制系统的设备,请参见图13所示,图13为基于音频驱动的微流体控制系统应用于器官芯片研究的示意图(其中,基于音频驱动的微流体控制系统简易示出)。设备包括:如实施例1所述的基于音频驱动的微流体控制系统和微流控芯片3;Embodiment 6 provides a device based on an audio-driven microfluidic control system, as shown in Figure 13. Figure 13 is a schematic diagram of an audio-driven microfluidic control system applied to organ chip research (wherein, the audio-driven microfluidic control system The fluid control system is briefly shown). The equipment includes: the audio-driven microfluidic control system and microfluidic chip 3 as described in Example 1;
其中,所述基于音频驱动的微流体控制系统中,所述第一气路24的支路数量为2,包括支路A和支路B,所述支路A和支路B通过电磁阀26控制通断;所述微流控芯片3包括:培养器官腔室101、第一流管102、第二流管103、转换中心、第一连接管和第二连接管,所述培养器官腔室101的上端通过第一流管102与转换中心104的上端连通,所述转换中心104的下端通过第二流管103与所述培养器官腔室101的下端连通,所述转换中心104的上端和下端分别通过第一连接管和第二连接管与支路A和支路B连通。Wherein, in the audio-driven microfluidic control system, the number of branches of the first gas path 24 is 2, including branch A and branch B, and the branch A and branch B pass through the solenoid valve 26 Control on-off; the microfluidic chip 3 includes: a culture organ chamber 101, a first flow tube 102, a second flow tube 103, a conversion center, a first connection tube and a second connection tube. The culture organ chamber 101 The upper end of the conversion center 104 is connected to the upper end of the conversion center 104 through the first flow tube 102, and the lower end of the conversion center 104 is connected to the lower end of the cultured organ chamber 101 through the second flow tube 103. The upper end and the lower end of the conversion center 104 are respectively It is connected to branch A and branch B through the first connecting pipe and the second connecting pipe.
具体地,基于音频驱动的微流体控制系统可以连接一种适配器官芯片,组合形成的设备可以很好地模拟人体血管微环境,完成培养液的流动更换,提供类似人体心脏的流体系统。设备包括培养器官腔室101、第一流管102、第二流管103、转换中心104、连接管及微泵。转换中心104可以将新鲜的特殊培养液通过一定的流速转运至器官培养腔室,同时可以将经过器官组织利用的培养液进行回收,将回收的培养液中的代谢产物进行分析检测将进一步了解器官组织的功能及生理生化状态,同时摆脱常规静态器官培养导致的代谢产物残留时间长,对器官组织产生影响,保证最终分析结果的可靠性。Specifically, the audio-driven microfluidic control system can be connected to an adapter chip, and the combined device can well simulate the human vascular microenvironment, complete the flow replacement of the culture medium, and provide a fluid system similar to the human heart. The equipment includes a culture organ chamber 101, a first flow tube 102, a second flow tube 103, a conversion center 104, connecting tubes and a micropump. The conversion center 104 can transport fresh special culture medium to the organ culture chamber at a certain flow rate. At the same time, it can recover the culture medium that has been used by organ tissues. The metabolites in the recovered culture medium can be analyzed and detected to further understand the organs. The function and physiological and biochemical status of the tissue, while getting rid of the long residual time of metabolites caused by conventional static organ culture, which has an impact on the organ tissue, ensuring the reliability of the final analysis results.
以上所述的具体实施方式,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施方式而已,并不用于限定本发明的保护范围,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。The above-described specific embodiments further describe the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above-mentioned are only specific embodiments of the present invention and are not intended to limit the scope of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention.
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| US20140011291A1 (en) * | 2011-09-13 | 2014-01-09 | The Regents Of The University Of California | Lateral cavity acoustic transducer based microfluidic switch |
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