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CN110170343A - A kind of Water-In-Oil microlayer model manufacture system and manufacturing method - Google Patents

A kind of Water-In-Oil microlayer model manufacture system and manufacturing method Download PDF

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CN110170343A
CN110170343A CN201910447194.2A CN201910447194A CN110170343A CN 110170343 A CN110170343 A CN 110170343A CN 201910447194 A CN201910447194 A CN 201910447194A CN 110170343 A CN110170343 A CN 110170343A
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liquid
sample
bulk acoustic
film bulk
liquid column
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段学欣
周杨超
庞慰
何美杭
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Tianjin University
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip

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  • Health & Medical Sciences (AREA)
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Abstract

本发明提供了一种油包水微液滴制造系统及制造方法,包括样品存储容器,用于存储用于制造微液滴的液体样品,以及用于存储位于所述液体样品上表面的油层;所述样品存储容器上部开口设置;液柱产生装置,与所述样品存储容器连接,用于将所述样品存储容器中存储的液体样品向上推动以使得液体样品与油层相接的界面上形成一液柱;以及当所述液柱产生装置关闭,所述液柱回落时,界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。由上,本申请在制造微液滴时,不会影响微液滴中生物样品的活性,且不会出现装置堵塞的问题,不易损耗,且成本低。

The invention provides a water-in-oil microdroplet manufacturing system and a manufacturing method, comprising a sample storage container for storing a liquid sample for manufacturing microdroplets, and an oil layer on the upper surface of the liquid sample; The upper opening of the sample storage container is provided; the liquid column generating device is connected to the sample storage container and is used for pushing the liquid sample stored in the sample storage container upwards so that a liquid sample is formed on the interface where the oil layer is connected. a liquid column; and when the liquid column generating device is turned off and the liquid column falls back, the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface. From the above, when manufacturing microdroplets, the present application will not affect the activity of biological samples in the microdroplets, and will not cause the problem of device clogging, is not easy to lose, and has low cost.

Description

一种油包水微液滴制造系统及制造方法A kind of water-in-oil microdroplet manufacturing system and manufacturing method

技术领域technical field

本发明涉及微纳制造技术领域,尤其涉及一种油包水微液滴制造系统及制造方法。The invention relates to the technical field of micro-nano manufacturing, in particular to a water-in-oil micro-droplet manufacturing system and a manufacturing method.

背景技术Background technique

由于微液滴有体积小、反应条件稳定、可避免样品间的交叉污染等优点,已经被用在了化学和生命科学等领域下的众多反应及过程。如:化学分析及合成、蛋白结晶、细胞包埋、液滴PCR等。微液滴制造的关键在于:1)微液滴的均一性;2)微液滴的形貌(一般为规则的圆形);3)微液滴的尺寸。目前传统的微液滴制造技术具有如下缺点:1)造价高;2)生物兼容性差;3)对样品溶液耗损大;等等。又如现有技术中使用喷嘴生成微液滴的缺点如下:1)喷嘴在使用过程中容易堵塞。2)喷嘴使用结束后很难清洗,残留物在下次实验的时候会引起交叉污染。3)喷嘴的材质一般为金属,但金属易与某些材料(如蛋白质)相互作用而影响蛋白的生物活性。4)为了生成不同尺寸的液滴需要更换喷嘴,且制造微喷嘴价格比较高。Due to the advantages of small size, stable reaction conditions, and avoidance of cross-contamination between samples, microdroplets have been used in many reactions and processes in the fields of chemistry and life sciences. Such as: chemical analysis and synthesis, protein crystallization, cell embedding, droplet PCR, etc. The key to the manufacture of microdroplets is: 1) the uniformity of the microdroplets; 2) the morphology of the microdroplets (generally a regular circle); 3) the size of the microdroplets. The current traditional microdroplet manufacturing technology has the following disadvantages: 1) high cost; 2) poor biocompatibility; 3) large consumption of sample solution; and so on. In another example, the disadvantages of using a nozzle to generate micro droplets in the prior art are as follows: 1) The nozzle is easily blocked during use. 2) It is difficult to clean the nozzle after use, and the residue will cause cross-contamination in the next experiment. 3) The material of the nozzle is generally metal, but the metal easily interacts with certain materials (such as proteins) to affect the biological activity of the proteins. 4) In order to generate droplets of different sizes, nozzles need to be replaced, and the cost of manufacturing micro-nozzles is relatively high.

因此,目前亟需一种微液滴制造系统,以实现在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,且成本低。Therefore, there is an urgent need for a microdroplet manufacturing system, so as to achieve the production of microdroplets without affecting the biological activity of the sample, without the problem of instrument clogging, not easy to lose, and with low cost.

发明内容SUMMARY OF THE INVENTION

有鉴于此,本发明的主要目的在于提供了一种微液滴制造系统,以实现在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,且成本低。In view of this, the main purpose of the present invention is to provide a micro-droplet manufacturing system, so as to realize the production of micro-droplets without affecting the biological activity of the sample, without the problem of instrument clogging, not easy to lose, and with low cost.

本申请提供一种微液滴制造系统,包括:The present application provides a microdroplet manufacturing system, including:

样品存储容器,用于存储用于制造微液滴的液体样品,以及用于存储位于所述液体样品上表面的油层;所述样品存储容器上部开口设置;a sample storage container for storing a liquid sample for making microdroplets, and for storing an oil layer on the upper surface of the liquid sample; an upper opening of the sample storage container is provided;

液柱产生装置,与所述样品存储容器底部连接,用于将所述样品存储容器中存储的液体样品向上推动以使得液体样品与油层相接的界面上形成一液柱;以及当所述液柱产生装置关闭,所述液柱回落时,界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。a liquid column generating device, connected to the bottom of the sample storage container, for pushing the liquid sample stored in the sample storage container upwards so that a liquid column is formed on the interface where the liquid sample meets the oil layer; and when the liquid sample is in contact with the oil layer The column generating device is turned off, and when the liquid column falls back, the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface.

由上,本申请的微液滴制造系统通过液柱产生装置在液体样品-油层界面形成液柱,然后关闭器件,通过液柱受到表面张力而自由回落最终夹断液柱形成液滴。从而不需要喷嘴,因此避免了者喷嘴带来的问题。本申请通过上述技术特征实现了在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,效率高且成本低。其中,本申请中的油层可以使用其他的与液体样品不想溶解且密度比液体样品小的液体,凡属于通过产生液柱然后回落产生液滴的技术方案都在本申请的保护范围之内。From the above, the microdroplet manufacturing system of the present application forms a liquid column at the liquid sample-oil layer interface through a liquid column generating device, and then closes the device, and the liquid column is subjected to surface tension to fall back freely and finally pinch off the liquid column to form a droplet. There is thus no need for a nozzle, thus avoiding the problems associated with nozzles. Through the above technical features, the present application realizes that the biological activity of the sample is not affected, the problem of instrument clogging does not occur, the microdroplet is not easily lost, the efficiency is high, and the cost is low. Among them, the oil layer in this application can use other liquids that do not want to dissolve with the liquid sample and whose density is lower than that of the liquid sample, and all technical solutions that generate droplets by generating liquid columns and then falling back are within the protection scope of this application.

优选地,所述液柱产生装置,包括:Preferably, the liquid column generating device includes:

薄膜体声波谐振器,设置于所述样品存储容器内的底部;其中,所述薄膜体声波谐振器的数量至少为1;其中,所述薄膜体声波谐振器以阵列形式设置或者以其他指定排布形式设置。Thin-film bulk acoustic wave resonators, arranged at the bottom of the sample storage container; wherein, the number of thin-film bulk acoustic wave resonators is at least 1; wherein, the thin-film bulk acoustic wave resonators are arranged in an array form or in other specified rows cloth form set.

信号发生器,与所述薄膜体声波谐振器连接。A signal generator is connected to the thin film bulk acoustic wave resonator.

由上,通过所述信号发生器产生高频信号,驱动所述薄膜体声波谐振器谐振进而产生高频声波,该高频声波在所述样品存储容器中的液体样品内向上传播,产生强大的体积力推动液体向上运动。从而在液体样品-油层表面形成了一个液柱。由此,本申请的该技术特征避免现有技术的装置堵塞、易损耗,效率低,造价高生物兼容性差等问题。该薄膜体声波谐振器也可以是一些其它的可以产生液柱的声波器件。其中,当所述薄膜体声波谐振器以阵列形式设置或者以其他指定排布形式设置时,产生的油包水微液滴的大小均一且形貌规则。From the above, a high-frequency signal is generated by the signal generator, and the thin-film bulk acoustic wave resonator is driven to resonate to generate a high-frequency sound wave, and the high-frequency sound wave propagates upward in the liquid sample in the sample storage container to generate a strong The body force pushes the liquid upward. Thus, a liquid column is formed on the surface of the liquid sample-oil layer. Therefore, the technical feature of the present application avoids the problems of clogging, easy wear and tear, low efficiency, high cost and poor biocompatibility of the prior art device. The thin film bulk acoustic wave resonator can also be some other acoustic wave devices that can generate liquid columns. Wherein, when the thin-film bulk acoustic wave resonators are arranged in an array form or in other specified arrangement forms, the water-in-oil microdroplets produced are uniform in size and regular in morphology.

优选地,所述信号发生器与所述薄膜体声波谐振器之间还连接一功率放大器;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。Preferably, a power amplifier is further connected between the signal generator and the thin-film bulk acoustic resonator; wherein, the power amplifier is used to amplify the signal sent by the signal generator and then input it to the thin-film body Acoustic resonator.

由上,经过功率放大器可以将信号放大至所需的指定功率,以用于驱动所述薄膜体声波谐振器谐振进而产生高频声波。From the above, the signal can be amplified to the required specified power through the power amplifier, so as to drive the thin film bulk acoustic wave resonator to resonate and generate high-frequency acoustic waves.

优选地,所述系统,还包括:中央处理器,与所述信号发生器连接,用于控制信号的发射;以通过所述信号以控制薄膜体声波谐振器的工作时间和功率以控制产生油包水微液滴的大小。Preferably, the system further comprises: a central processing unit, connected with the signal generator, for controlling the emission of signals; to control the working time and power of the thin film bulk acoustic wave resonator through the signals to control the generation of oil The size of the water-containing microdroplets.

优选地,所述系统,还包括:高速摄像机,与所述中央处理器连接,设置于所述样品存储容器的侧面,用于实时采集微液滴形成的整个过程,并将其传输至中央处理器;其中,所述样品存储器的侧壁为透明材质。Preferably, the system further comprises: a high-speed camera connected to the central processing unit and disposed on the side of the sample storage container for real-time acquisition of the entire process of micro-droplet formation and transmission to the central processing unit wherein, the side wall of the sample storage is made of transparent material.

本申请还提供一种微液滴制造方法,包括步骤:The present application also provides a method for manufacturing microdroplets, comprising the steps of:

A、将液体样品和油样依次注入至样品存储容器中,以使得所述样品存储容器中由下至上依次形成液体样品层和油层;A. Inject the liquid sample and the oil sample into the sample storage container in turn, so that a liquid sample layer and an oil layer are formed in the sample storage container from bottom to top in sequence;

B、通过液柱产生装置将所述样品存储容器中存储的液体样品向上推动以使得液体样品与油层相接的界面上形成一液柱;B. The liquid sample stored in the sample storage container is pushed upward by the liquid column generating device so that a liquid column is formed on the interface where the liquid sample and the oil layer meet;

C、关闭所述液柱产生装置,所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。C. Turn off the liquid column generating device, the liquid column falls back, and the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface.

由上,本申请的微液滴制造系统不需要喷嘴,因此避免了喷嘴带来的问题。如喷嘴造价高且易堵塞等问题。本申请通过上述技术特征实现了在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,效率高且成本低。From the above, the microdroplet manufacturing system of the present application does not require nozzles, thus avoiding the problems caused by nozzles. Such as the high cost of the nozzle and easy to block and so on. Through the above technical features, the present application realizes that the biological activity of the sample is not affected, the problem of instrument clogging does not occur, the microdroplet is not easily lost, the efficiency is high, and the cost is low.

优选地,所述液柱产生装置包括:Preferably, the liquid column generating device comprises:

薄膜体声波谐振器,设置于所述样品存储容器内的底部;a thin-film bulk acoustic resonator, arranged at the bottom of the sample storage container;

信号发生器,与所述薄膜体声波谐振器连接;a signal generator, connected with the thin-film bulk acoustic resonator;

其中,所述信号发生器与所述薄膜体声波谐振器之间还连接一功率放大器;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。Wherein, a power amplifier is also connected between the signal generator and the thin-film bulk acoustic wave resonator; wherein, the power amplifier is used to amplify the signal sent by the signal generator and then input it to the thin-film bulk acoustic wave resonator.

由上,通过所述信号发生器产生高频信号,经过功率放大器放大后驱动所述薄膜体声波谐振器谐振进而产生高频声波,该高频声波在所述样品存储容器中的液体样品内向上传播,产生强大的体积力推动液体向上运动。从而在液体样品-油层表面形成了一个液柱。由此,本申请的该技术特征避免现有技术的装置堵塞、易损耗,效率低,造价高生物兼容性差等问题。该薄膜体声波谐振器也可以是一些其它的可以产生液柱的声波器件。From the above, a high-frequency signal is generated by the signal generator, and after being amplified by a power amplifier, the thin-film bulk acoustic wave resonator is driven to resonate to generate a high-frequency sound wave, and the high-frequency sound wave is upward in the liquid sample in the sample storage container. Propagation, creating a strong body force that pushes the liquid upwards. Thus, a liquid column is formed on the surface of the liquid sample-oil layer. Therefore, the technical feature of the present application avoids the problems of clogging, easy wear and tear, low efficiency, high cost and poor biocompatibility of the prior art device. The thin film bulk acoustic wave resonator can also be some other acoustic wave devices that can generate liquid columns.

优选地,所述步骤B,包括:Preferably, the step B includes:

B1、通过一中央处理器控制所述信号发生器产生高频信号;B1. Control the signal generator to generate a high-frequency signal through a central processing unit;

B2、所述高频信号经由功率放大器放大后驱动薄膜体声波谐振器谐振进而产生高频声波;所述高频声波作用于所述存储容器中的液体样品,产生强大的体积力推动液体向上运动,形成一液柱。B2. The high-frequency signal is amplified by the power amplifier and drives the thin-film bulk acoustic wave resonator to resonate to generate high-frequency sound waves; the high-frequency sound waves act on the liquid sample in the storage container to generate a strong body force to push the liquid upward. , forming a liquid column.

优选地,所述步骤C,包括:Preferably, the step C includes:

关闭所述功率放大器以停止所述信号发生器的信号输出,以使得所述薄膜体声波谐振器停止产生高频声波,以使所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。Turn off the power amplifier to stop the signal output of the signal generator, so that the thin film bulk acoustic wave resonator stops generating high-frequency sound waves, so that the liquid column falls back, and the surface tension of the interface reduces the liquid column. Pinch off and form water-in-oil microdroplets on the interface.

优选地,所述步骤A,还包括:Preferably, the step A further includes:

通过所述中央处理器控制所述信号发生器产生高频信号的时间以及强弱,以通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的大小,从而控制所述油包水微液滴的大小。The time and strength of the high-frequency signal generated by the signal generator are controlled by the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the operation of the thin film bulk acoustic wave resonator Time and power control the generation time of the liquid column and control the size of the liquid column, thereby controlling the size of the water-in-oil droplets.

优选地,所述步骤B,包括:Preferably, the step B includes:

B1、通过一中央处理器控制所述信号发生器产生高频信号;B1. Control the signal generator to generate a high-frequency signal through a central processing unit;

B2、所述高频信号经由功率放大器放大后驱动薄膜体声波谐振器谐振进而产生高频声波;所述高频声波作用于所述存储容器中的液体样品,产生强大的体积力推动液体向上运动,形成一液柱。B2. The high-frequency signal is amplified by the power amplifier and drives the thin-film bulk acoustic wave resonator to resonate to generate high-frequency sound waves; the high-frequency sound waves act on the liquid sample in the storage container to generate a strong body force to push the liquid upward. , forming a liquid column.

优选地,所述步骤C,包括:Preferably, the step C includes:

关闭所述功率放大器以停止所述信号发生器的信号输出,以使得所述薄膜体声波谐振器停止产生高频声波,以使所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。Turn off the power amplifier to stop the signal output of the signal generator, so that the thin film bulk acoustic wave resonator stops generating high-frequency sound waves, so that the liquid column falls back, and the surface tension of the interface reduces the liquid column. Pinch off and form water-in-oil microdroplets on the interface.

优选地,所述步骤A,还包括:Preferably, the step A further includes:

通过所述中央处理器控制所述信号发生器产生高频信号的时间以及强弱,以通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的大小,从而控制所述油包水微液滴的大小。The time and strength of the high-frequency signal generated by the signal generator are controlled by the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the operation of the thin film bulk acoustic wave resonator Time and power control the generation time of the liquid column and control the size of the liquid column, thereby controlling the size of the water-in-oil droplets.

综上所述,本申请的微液滴制造系统通过液柱产生装置在液体样品-油层界面形成液柱,然后关闭器件,通过液柱受到表面张力而自由回落最终夹断液柱形成液滴。本发明的微液滴制造系统不需要喷嘴,因此避免了喷嘴带来的问题。如现有技术中:喷嘴造价高且易堵塞等问题。本申请通过上述技术特征实现了在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,效率高且成本低。并且本申请可以通过中央处理器控制所述信号发生器产生高频信号的时间以及强弱,以通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的高度和直径,从而控制所述油包水微液滴的大小。其中,本申请中的油层可以使用其他的与液体样品不想溶解且密度比液体样品小的液体,凡属于通过产生液柱然后回落产生液滴的技术方案都在本申请的保护范围之内。To sum up, the micro-droplet manufacturing system of the present application forms a liquid column at the liquid sample-oil layer interface through a liquid column generating device, then closes the device, and the liquid column is subjected to surface tension to fall back freely and finally pinch off the liquid column to form droplets. The microdroplet manufacturing system of the present invention does not require nozzles, thus avoiding the problems associated with nozzles. As in the prior art, the nozzles are expensive and easy to block. Through the above technical features, the present application realizes that the biological activity of the sample is not affected, the problem of instrument clogging does not occur, the microdroplet is not easily lost, the efficiency is high, and the cost is low. And the present application can control the time and strength of the high-frequency signal generated by the signal generator through the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the thin film bulk acoustic wave resonator. The working time and power control the generation time of the liquid column and the height and diameter of the liquid column, thereby controlling the size of the water-in-oil droplet. Among them, the oil layer in this application can use other liquids that do not want to dissolve with the liquid sample and whose density is lower than that of the liquid sample, and all technical solutions that generate droplets by generating liquid columns and then falling back are within the protection scope of this application.

附图说明Description of drawings

图1是本申请的油包水微液滴制造系统的结构示意图;Fig. 1 is the structural representation of the water-in-oil microdroplet manufacturing system of the present application;

图2是本申请的油包水微液滴制造方法的流程示意图;Fig. 2 is the schematic flow sheet of the water-in-oil microdroplet manufacturing method of the present application;

图3所示,表示为薄膜体声波谐振器105的工作时间与产生的微液滴的尺寸的关系图;As shown in FIG. 3 , it is a graph showing the relationship between the working time of the thin film bulk acoustic wave resonator 105 and the size of the generated droplets;

图4所示,表示为薄膜体声波谐振器105的功率与产生的微液滴的尺寸的关系图。FIG. 4 is a graph showing the relationship between the power of the thin film bulk acoustic wave resonator 105 and the size of the generated droplets.

具体实施方式Detailed ways

本申请提供了一种油包水微液滴制造系统及方法,以实现在制造微液滴时,不影响样品生物活性,且不会出现仪器堵塞的问题,不易损耗,效率高。具体地,如下:The present application provides a water-in-oil micro-droplet manufacturing system and method, so as to realize that when micro-droplets are manufactured, the biological activity of the sample is not affected, the problem of instrument clogging will not occur, it is not easy to lose, and the efficiency is high. Specifically, as follows:

实施例一Example 1

如图1所示,本申请提供的一种油包水微液滴制造系统,包括:As shown in Figure 1, a water-in-oil microdroplet manufacturing system provided by this application includes:

样品存储容器101,用于存储用于制造微液滴的液体样品,以及用于存储位于所述液体样品103(例如去离子水)上表面的油层102(例如矿物油);其中,液体样品和油层的体积比小于1,即,油层的体积要大一些;其中,优选地,液体样品:油层的体积比为1:4。所述样品存储容器101上部开口设置;样品存储容器的底部以EVB板作为基底106,所述样品存储容器的侧壁为透明材质,例如,透明材质可以为PMMA有机玻璃,也可以是其他的透明材质。A sample storage container 101 for storing a liquid sample for making microdroplets, and for storing an oil layer 102 (eg, mineral oil) on the upper surface of the liquid sample 103 (eg, deionized water); wherein the liquid sample and The volume ratio of the oil layer is less than 1, that is, the volume of the oil layer is larger; wherein, preferably, the volume ratio of the liquid sample: the oil layer is 1:4. The upper part of the sample storage container 101 is provided with an opening; the bottom of the sample storage container is an EVB board as the base 106, and the side wall of the sample storage container is made of a transparent material. For example, the transparent material can be PMMA plexiglass, or other transparent materials. material.

液柱产生装置,与所述样品存储容器100底部基底106连接,用于将所述样品存储容器101中存储的液体样品103向上推动以使得液体样品103与油层102相接的界面上形成一液柱;以及当所述液柱产生装置关闭,所述液柱回落时,界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。The liquid column generating device is connected to the bottom substrate 106 of the sample storage container 100 and is used to push the liquid sample 103 stored in the sample storage container 101 upwards so that a liquid is formed on the interface where the liquid sample 103 meets the oil layer 102 and when the liquid column generating device is turned off and the liquid column falls back, the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface.

其中,所述液柱产生装置,包括:Wherein, the liquid column generating device includes:

薄膜体声波谐振器105,设置于所述样品存储容器内的底部;其中,所述薄膜体声波谐振器105的数量至少为1;其中,所述薄膜体声波谐振器105以阵列形式设置或者以其他指定的排布形式设置。其中,所述薄膜体声波谐振器105为利用标准的微电子机械系统(MEMS)工艺制造出薄膜体声波谐振器,生产效率高,成本低,且非常容易集成。并将其连接在样品存储容器底部的基底上以作用于所述液体样品。该薄膜体声波谐振器105也可以是一些其它的可以产生液柱的声波器件。Thin-film bulk acoustic resonators 105 are arranged at the bottom of the sample storage container; wherein the number of thin-film bulk acoustic resonators 105 is at least 1; wherein, the thin-film bulk acoustic resonators 105 are arranged in an array or in a Other specified layout settings. Wherein, the thin-film bulk acoustic resonator 105 is a thin-film bulk acoustic resonator manufactured by using a standard micro-electromechanical system (MEMS) process, which has high production efficiency, low cost, and is very easy to integrate. and attach it to the substrate at the bottom of the sample storage container to act on the liquid sample. The thin film bulk acoustic wave resonator 105 can also be some other acoustic wave devices that can generate liquid columns.

信号发生器110,与所述薄膜体声波谐振器105连接。The signal generator 110 is connected to the thin film bulk acoustic wave resonator 105 .

其中,所述信号发生器110与所述薄膜体声波谐振器105之间还连接一功率放大器109;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。Wherein, a power amplifier 109 is also connected between the signal generator 110 and the thin film bulk acoustic wave resonator 105; wherein, the power amplifier is used to amplify the signal sent by the signal generator and then input it to the Thin film bulk acoustic resonators.

通过所述信号发生器110产生高频信号,经过功率放大器109放大后驱动所述薄膜体声波谐振器105谐振进而产生高频声波104,该高频声波在所述样品存储容器中的液体样品内向上传播,耦合到去液体样品中的高频声波快速衰减,产生强大的体积力推动液体向上运动。从而在液体样品-油层表面形成了一液柱。之后通过计算机关闭信号发生器从而使薄膜体声波谐振器停止工作。由于此时液柱失去了体积力的推动,表面张力使液柱回落。由于Rayleigh–Plateau不稳定性(Plateau–Rayleigh instability是描述水柱流动过程中的扰动现象,Plateau首先对其进行测量,接着Rayleig提出数学模型进行解释),表面张力将液柱夹断并形成油包水液滴,停留在液体样品-油层界面。The high-frequency signal is generated by the signal generator 110, and amplified by the power amplifier 109, the thin-film bulk acoustic wave resonator 105 is driven to resonate to generate high-frequency acoustic waves 104, and the high-frequency acoustic waves are in the liquid sample in the sample storage container. Propagating upward, the high-frequency sound waves coupled into the de-liquid sample decay rapidly, creating a strong body force that pushes the liquid upward. Thus, a liquid column is formed on the surface of the liquid sample-oil layer. Afterwards, the signal generator is turned off by the computer, so that the thin film bulk acoustic wave resonator stops working. Since the liquid column loses the push of the body force at this time, the surface tension causes the liquid column to fall back. Due to the Rayleigh–Plateau instability (Plateau–Rayleigh instability is a disturbance phenomenon that describes the flow of the water column, Plateau first measured it, and then Rayleig proposed a mathematical model to explain it), the surface tension pinch off the liquid column and form water-in-oil Droplets stay at the liquid sample-oil layer interface.

其中,所述系统,还包括:中央处理器108,与所述信号发生器110连接,用于控制信号的发射;以通过所述信号以控制薄膜体声波谐振器105的工作时间和功率以控制产生油包水微液滴的大小,以是实现在数微米到数百微米之间自由控制液滴的尺寸。具体地,如图3所示,表示为薄膜体声波谐振器105的工作时间与产生的微液滴的尺寸的关系图;如图3所示,在功率稳定的前提下(此处对于功率得要求可以是400mw到2w之间任意一能够产生微液滴的功率),随着工作时间的增大,微液滴的尺寸呈现先增大后趋于稳定的趋势,如图3所示,1.5秒之前,随着工作时间的增大,微液滴的尺寸逐渐增大。1.5秒之后,随着工作时间的增大,微液滴的尺寸趋于稳定。如图4所示,表示为薄膜体声波谐振器105的功率与产生的微液滴的尺寸的关系图。在1.5秒之后(1.5秒之后时间对微液滴的大小不再产生影响),之后可以通过调整功率来调整生成的微液滴的尺寸,如图4所示,随着功率的增大,微液滴的尺寸逐渐增大。Wherein, the system further includes: a central processing unit 108, connected to the signal generator 110, for controlling the emission of signals; so as to control the working time and power of the thin film bulk acoustic wave resonator 105 through the signals to control the The size of the water-in-oil microdroplets is generated, so that the size of the droplets can be freely controlled from a few microns to hundreds of microns. Specifically, as shown in FIG. 3 , it is shown as the relationship between the working time of the thin film bulk acoustic wave resonator 105 and the size of the generated microdroplets; as shown in FIG. 3 , under the premise of stable power (here for the power The requirement can be any power between 400mw and 2w that can generate micro-droplets), with the increase of working time, the size of micro-droplets increases first and then tends to be stable, as shown in Figure 3, 1.5 Before seconds, the size of the microdroplets gradually increased with the increase of working time. After 1.5 seconds, the size of the microdroplets tends to stabilize with the increase of working time. As shown in FIG. 4 , it is shown as a graph of the power of the thin film bulk acoustic wave resonator 105 versus the size of the microdroplets produced. After 1.5 seconds (time no longer has an effect on the size of the microdroplets after 1.5 seconds), the size of the generated microdroplets can be adjusted by adjusting the power. The size of the droplets gradually increases.

其中,所述系统,还包括:高速摄像机107,与所述中央处理器108连接,设置于所述样品存储容器的侧面,用于实时采集所述油包水微液滴形成的整个过程;其中,所述样品存储器的侧壁为透明材质。Wherein, the system further includes: a high-speed camera 107 connected to the central processing unit 108 and disposed on the side of the sample storage container for real-time acquisition of the entire process of the formation of the water-in-oil microdroplets; wherein , the side wall of the sample storage is made of transparent material.

为了更清楚的说明本申请的技术方案,现将本申请的油包水微液滴制造系统的工作原理说明如下:In order to illustrate the technical solution of the present application more clearly, the working principle of the water-in-oil microdroplet manufacturing system of the present application is now described as follows:

通过中央处理器108控制信号发生器110产生GHz级的高频信号经由功率放大器109放大后驱动薄膜体声波谐振器105谐振进而产生高频声波。耦合到去液体样品103中的高频声波104快速衰减,并产生强大的体积力推动去液体样品103向上运动。在液体样品103-油层102界面,表面张力了液体向上的运动(满足动量守恒定律)。从而在水油界面形成了一液柱。之后通过计算机关闭信号发生器110从而使薄膜体声波谐振器105停止工作。由于此时液柱失去了体积力的推动,表面张力使液柱回落。由于Rayleigh–Plateau不稳定性,表面张力将液柱夹断并形成油包水液滴,停留在液体样品103-油层102界面。通过中央处理器108控制高速摄像机107可以实时地观察整个形成液滴地过程。The signal generator 110 is controlled by the central processing unit 108 to generate a high-frequency signal of GHz level, which is amplified by the power amplifier 109 and then drives the thin-film bulk acoustic wave resonator 105 to resonate to generate high-frequency acoustic waves. The high frequency sound waves 104 coupled into the de-liquid sample 103 decay rapidly and generate a strong body force to push the de-liquid sample 103 upward. At the liquid sample 103-oil layer 102 interface, the surface tension forces the upward movement of the liquid (which satisfies the law of conservation of momentum). Thus, a liquid column is formed at the water-oil interface. Then, the signal generator 110 is turned off by the computer to stop the thin film bulk acoustic resonator 105 from working. Since the liquid column loses the push of the body force at this time, the surface tension causes the liquid column to fall back. Due to the Rayleigh–Plateau instability, the surface tension pinch off the liquid column and form water-in-oil droplets that stay at the liquid sample 103-oil layer 102 interface. The whole process of forming droplets can be observed in real time by controlling the high-speed camera 107 by the central processing unit 108 .

实施例二Embodiment 2

基于实施例一中的本申请还提供一种油包水微液滴制造系统,本申请还提供一种微液滴制造方法,包括步骤:Based on the first embodiment, the present application also provides a water-in-oil microdroplet manufacturing system, and the present application also provides a microdroplet manufacturing method, comprising the steps of:

S201,将液体样品和油样依次注入至样品存储容器中,以使得所述样品存储容器中由下至上依次形成液体样品层和油层。S201, the liquid sample and the oil sample are sequentially injected into the sample storage container, so that a liquid sample layer and an oil layer are sequentially formed in the sample storage container from bottom to top.

S202,通过一中央处理器控制信号发生器产生高频信号。以及通过中央处理器控制信号发生器产生的高频信号的时间以及强弱。S202, a central processing unit controls a signal generator to generate a high-frequency signal. And the time and intensity of the high-frequency signal generated by the signal generator are controlled by the central processing unit.

S203,高频信号经由功率放大器放大后驱动薄膜体声波谐振器谐振进而产生高频声波;所述高频声波作用于所述存储容器中的液体样品,产生强大的体积力推动液体向上运动,使得液体样品与油层相接的界面上形成一液柱。S203, the high-frequency signal is amplified by the power amplifier and drives the thin-film bulk acoustic wave resonator to resonate to generate high-frequency sound waves; the high-frequency sound waves act on the liquid sample in the storage container to generate a strong body force to push the liquid upward, so that A liquid column is formed on the interface where the liquid sample meets the oil layer.

S204,停止所述信号发生器的信号输出,以使得所述薄膜体声波谐振器停止产生高频声波,以使所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。S204, stop the signal output of the signal generator, so that the thin-film bulk acoustic wave resonator stops generating high-frequency sound waves, so that the liquid column falls back, and the surface tension of the interface pinch off the liquid column and cause the Water-in-oil microdroplets are formed on the interface.

其中,通过所述中央处理器控制所述信号发生器产生高频信号的时间以及强弱,从而通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的大小,从而控制所述油包水微液滴的大小。Wherein, the time and strength of the high-frequency signal generated by the signal generator are controlled by the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the thin film bulk acoustic wave resonator. The working time and power control the generation time of the liquid column and the size of the liquid column, thereby controlling the size of the water-in-oil droplet.

薄膜体声波谐振器,设置于所述样品存储容器内的底部;a thin-film bulk acoustic resonator, arranged at the bottom of the sample storage container;

信号发生器,与所述薄膜体声波谐振器连接;a signal generator, connected with the thin-film bulk acoustic resonator;

其中,所述信号发生器与所述薄膜体声波谐振器之间还连接一功率放大器;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。Wherein, a power amplifier is also connected between the signal generator and the thin-film bulk acoustic wave resonator; wherein, the power amplifier is used to amplify the signal sent by the signal generator and then input it to the thin-film bulk acoustic wave resonator.

综上所述,本申请的油包水微液滴制造系统及方法通过在液体样品-油层界面形成液柱,然后关闭器件,通过液柱受到表面张力而自由回落最终夹断液柱形成液滴。本发的避免了喷嘴带来的问题。本申请通过上述技术特征实现了在制造微液滴时,不影响样品生物活性,不出现仪器堵塞的问题,不易损耗,效率高且成本低。并且本申请可以通过中央处理器控制所述信号发生器产生高频信号的时间以及强弱,以通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的高度和直径,从而控制所述油包水微液滴的大小。其中,本申请中的油层可以使用其他的与液体样品不想溶解且密度比液体样品小的液体,凡属于通过产生液柱然后回落产生液滴的技术方案都在本申请的保护范围之内。To sum up, the water-in-oil microdroplet manufacturing system and method of the present application forms a liquid column at the liquid sample-oil layer interface, then turns off the device, and the liquid column is subjected to surface tension to fall back freely, and finally pinch off the liquid column to form droplets. . The present invention avoids the problems caused by nozzles. Through the above technical features, the present application realizes that the biological activity of the sample is not affected, the problem of instrument clogging does not occur, the microdroplet is not easily lost, the efficiency is high, and the cost is low. And the present application can control the time and strength of the high-frequency signal generated by the signal generator through the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the thin film bulk acoustic wave resonator. The working time and power control the generation time of the liquid column and the height and diameter of the liquid column, thereby controlling the size of the water-in-oil droplet. Among them, the oil layer in this application can use other liquids that do not want to dissolve with the liquid sample and whose density is lower than that of the liquid sample, and all technical solutions that generate droplets by generating liquid columns and then falling back are within the protection scope of this application.

以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the scope of the present invention. within the scope of protection.

Claims (10)

1.一种油包水微液滴制造系统,其特征在于,包括:1. a water-in-oil microdroplet manufacturing system, is characterized in that, comprises: 样品存储容器,用于存储用于制造微液滴的液体样品,以及用于存储位于所述液体样品上表面的油层;所述样品存储容器上部开口设置;a sample storage container for storing a liquid sample for making microdroplets, and for storing an oil layer on the upper surface of the liquid sample; an upper opening of the sample storage container is provided; 液柱产生装置,与所述样品存储容器底部连接,用于将所述样品存储容器中存储的液体样品向上推动以使得液体样品与油层相接的界面上形成一液柱;以及当所述液柱产生装置关闭,所述液柱回落,界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。a liquid column generating device, connected to the bottom of the sample storage container, for pushing the liquid sample stored in the sample storage container upwards so that a liquid column is formed on the interface where the liquid sample meets the oil layer; and when the liquid sample is in contact with the oil layer The column generating device is turned off, the liquid column falls back, and the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface. 2.根据权利要求1所述的系统,其特征在于,所述液柱产生装置,包括:2. The system according to claim 1, wherein the liquid column generating device comprises: 薄膜体声波谐振器,设置于所述样品存储容器内的底部;其中,所述薄膜体声波谐振器的数量至少为1;其中,所述薄膜体声波谐振器以阵列形式设置或者以其他的指定的排布形式设置;Thin-film bulk acoustic resonators, arranged at the bottom of the sample storage container; wherein, the number of thin-film bulk acoustic resonators is at least 1; wherein, the thin-film bulk acoustic resonators are arranged in an array or specified by other Layout form settings; 信号发生器,与所述薄膜体声波谐振器连接。A signal generator is connected to the thin film bulk acoustic wave resonator. 3.根据权利要求2所述的系统,其特征在于,所述信号发生器与所述薄膜体声波谐振器之间还连接一功率放大器;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。3. The system according to claim 2, wherein a power amplifier is further connected between the signal generator and the thin film bulk acoustic resonator; wherein, the power amplifier is used to generate the signal The signal emitted by the tuner is amplified and then input to the thin film bulk acoustic wave resonator. 4.根据权利要求2所述的系统,其特征在于,还包括:4. The system of claim 2, further comprising: 中央处理器,与所述信号发生器连接,用于控制信号的发射;以通过所述信号以控制薄膜体声波谐振器的工作时间和功率以控制产生油包水微液滴的大小。The central processing unit, connected with the signal generator, is used to control the emission of the signal; to control the working time and power of the thin-film bulk acoustic wave resonator through the signal to control the size of the water-in-oil microdroplet. 5.根据权利要求2-4所述的系统,其特征在于,还包括:5. The system of claims 2-4, further comprising: 高速摄像机,与所述中央处理器连接,设置于所述样品存储容器的侧面,用于实时采集微液滴形成的整个过程,并将其传输至中央处理器;其中,所述样品存储器的侧壁为透明材质。A high-speed camera, connected with the central processing unit, is arranged on the side of the sample storage container, and is used for real-time acquisition of the entire process of the formation of microdroplets and transmits it to the central processing unit; wherein, the side of the sample storage container The walls are transparent. 6.一种油包水微液滴制造方法,其特征在于,包括步骤:6. a water-in-oil microdroplet manufacturing method, is characterized in that, comprises the steps: A、将液体样品和油样依次注入至样品存储容器中,以使得所述样品存储容器中由下至上依次形成液体样品层和油层;A. Inject the liquid sample and the oil sample into the sample storage container in turn, so that a liquid sample layer and an oil layer are formed in the sample storage container from bottom to top in sequence; B、通过液柱产生装置将所述样品存储容器中存储的液体样品向上推动以使得液体样品与油层相接的界面上形成一液柱;B. The liquid sample stored in the sample storage container is pushed upward by the liquid column generating device so that a liquid column is formed on the interface where the liquid sample and the oil layer meet; C、关闭所述液柱产生装置,所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。C. Turn off the liquid column generating device, the liquid column falls back, and the surface tension of the interface pinch off the liquid column and form water-in-oil microdroplets on the interface. 7.根据权利要求6所述的方法,其特征在于,所述液柱产生装置包括:7. The method according to claim 6, wherein the liquid column generating device comprises: 薄膜体声波谐振器,设置于所述样品存储容器内的底部;a thin-film bulk acoustic resonator, arranged at the bottom of the sample storage container; 信号发生器,与所述薄膜体声波谐振器连接;a signal generator, connected with the thin-film bulk acoustic resonator; 其中,所述信号发生器与所述薄膜体声波谐振器之间还连接一功率放大器;其中,所述功率放大器,用于将所述信号发生器发出的信号放大之后输入至所述薄膜体声波谐振器。Wherein, a power amplifier is also connected between the signal generator and the thin-film bulk acoustic wave resonator; wherein, the power amplifier is used to amplify the signal sent by the signal generator and then input it to the thin-film bulk acoustic wave resonator. 8.根据权利要求7所述的方法,其特征在于,所述步骤B,包括:8. The method according to claim 7, wherein the step B comprises: B1、通过一中央处理器控制所述信号发生器产生高频信号;B1. Control the signal generator to generate a high-frequency signal through a central processing unit; B2、所述高频信号经由功率放大器放大后驱动薄膜体声波谐振器谐振进而产生高频声波;所述高频声波作用于所述存储容器中的液体样品,产生强大的体积力推动液体向上运动,使得液体样品与油层相接的界面上形成一液柱。B2. The high-frequency signal is amplified by the power amplifier and drives the thin-film bulk acoustic wave resonator to resonate to generate high-frequency sound waves; the high-frequency sound waves act on the liquid sample in the storage container to generate a strong body force to push the liquid upward. , so that a liquid column is formed on the interface between the liquid sample and the oil layer. 9.根据权利要求8所述的方法,其特征在于,所述步骤C,包括:9. The method according to claim 8, wherein the step C comprises: 停止所述信号发生器的信号输出,以使得所述薄膜体声波谐振器停止产生高频声波,以使所述液柱回落,所述界面的表面张力将所述液柱夹断并在所述界面上形成油包水微液滴。Stop the signal output of the signal generator, so that the thin film bulk acoustic wave resonator stops generating high-frequency sound waves, so that the liquid column falls back, and the surface tension of the interface pinch off the liquid column and make Water-in-oil microdroplets are formed on the interface. 10.根据权利要求7所述的方法,其特征在于,所述步骤A,还包括:10. The method according to claim 7, wherein the step A further comprises: 通过中央处理器控制所述信号发生器产生高频信号的时间以及强弱,以通过所述信号控制薄膜体声波谐振器的工作时间和功率,以通过所述薄膜体声波谐振器的工作时间和功率控制所述液柱的产生时间以及控制所述液柱的高度和直径,从而控制所述油包水微液滴的大小。The time and strength of the high-frequency signal generated by the signal generator are controlled by the central processing unit, so as to control the working time and power of the thin film bulk acoustic wave resonator through the signal, so as to pass the working time and the power of the thin film bulk acoustic wave resonator. Power controls the generation time of the liquid column and controls the height and diameter of the liquid column, thereby controlling the size of the water-in-oil droplets.
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