WO2023138102A1 - 一种液体微流量控制系统及方法以及微流控检测装置 - Google Patents

一种液体微流量控制系统及方法以及微流控检测装置 Download PDF

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WO2023138102A1
WO2023138102A1 PCT/CN2022/123310 CN2022123310W WO2023138102A1 WO 2023138102 A1 WO2023138102 A1 WO 2023138102A1 CN 2022123310 W CN2022123310 W CN 2022123310W WO 2023138102 A1 WO2023138102 A1 WO 2023138102A1
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liquid
gas
liquid storage
delivery pipeline
air pressure
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PCT/CN2022/123310
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English (en)
French (fr)
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郑志伟
林钢
何建飞
张龙永
林斯武
陈涛
林柏均
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苏州莱博睿思生物科技有限公司
深圳莱博睿思生物科技有限公司
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Publication of WO2023138102A1 publication Critical patent/WO2023138102A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G05—CONTROLLING; REGULATING
    • G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
    • G05D16/00—Control of fluid pressure
    • G05D16/20—Control of fluid pressure characterised by the use of electric means
    • G05D16/2006—Control of fluid pressure characterised by the use of electric means with direct action of electric energy on controlling means
    • G05D16/2013—Control of fluid pressure characterised by the use of electric means with direct action of electric energy on controlling means using throttling means as controlling means
    • G05D16/2026—Control of fluid pressure characterised by the use of electric means with direct action of electric energy on controlling means using throttling means as controlling means with a plurality of throttling means
    • G05D16/204—Control of fluid pressure characterised by the use of electric means with direct action of electric energy on controlling means using throttling means as controlling means with a plurality of throttling means the plurality of throttling means being arranged in parallel
    • G—PHYSICS
    • G05—CONTROLLING; REGULATING
    • G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
    • G05D7/00—Control of flow
    • G05D7/06—Control of flow characterised by the use of electric means
    • G05D7/0617—Control of flow characterised by the use of electric means specially adapted for fluid materials
    • G05D7/0629—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means
    • G05D7/0635—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means by action on throttling means
    • G05D7/0641—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means by action on throttling means using a plurality of throttling means
    • G05D7/0652—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means by action on throttling means using a plurality of throttling means the plurality of throttling means being arranged in parallel
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1044—Using pneumatic means

Definitions

  • the invention relates to the technical field of biological fluid detection and analysis, in particular to a microfluidic flow rate control system and method and a microfluidic detection device.
  • Microfluidics refers to the science and technology involved in systems that use micropipes (tens to hundreds of microns in size) to process or manipulate tiny fluids (microliters in volume). It is an emerging interdisciplinary subject involving chemistry, fluid physics, microelectronics, new materials, biology and biomedical engineering.
  • Microfluidic technology has received great attention in the field of biological fluid biopsy in recent years, and high-precision microflow rate control technology is one of the difficulties.
  • due to the characteristics of body fluid biopsy it is necessary for the detection system to quickly and accurately detect body fluids in a non-contact manner.
  • the parts of the detection system that are in contact with body fluids generally appear in the form of consumables, and the one-time use requires higher cost.
  • the purpose of the present invention is to provide a system and method for precise control of liquid micro-flow and a micro-fluidic detection device through constant-flow air pressure control in a non-contact manner.
  • the present invention provides a liquid micro-flow control system, comprising: an air compressor, an air pressure controller, and a gas flow controller; the air compressor communicates with a liquid storage for storing the liquid to be processed through a first gas delivery pipeline; , the air pressure controller, the gas flow controller and the control valve are respectively connected to the control device for signals.
  • it also includes a pressure stabilizing container arranged on the second gas delivery pipeline and communicating with the air compressor and the air pressure controller respectively.
  • it also includes an air pressure sensor communicated with the liquid storage for detecting the air pressure in the liquid storage, and the air pressure sensor is connected with the control device in signal.
  • an alarm device is also included, and the alarm device is signal-connected with the control device.
  • the present invention also provides a liquid micro-flow control method, using the above-mentioned liquid micro-flow rate control system, comprising the following steps:
  • the container containing the liquid to be tested is sealed and communicated with the liquid storage through the liquid delivery pipe through the input end of the liquid storage; the air compressor is started by the control device, and the negative pressure is provided to the liquid storage through the first gas delivery pipeline, and the liquid to be tested is pumped into the liquid storage; then the air compressor is stopped;
  • step S3 start the air compressor to deliver gas to the pressure-stabilizing container, and then deliver gas to the air pressure controller through the pressure-stabilizing container.
  • step S4 when the air pressure sensor detects that the gas pressure in the liquid storage exceeds a set threshold, the alarm device issues an alarm through an audible and visual signal.
  • the present invention further provides a microfluidic detection device, comprising the above liquid microflow control system and a microfluidic detection package, the microfluidic detection package comprising: a liquid storage and a microfluidic chip connected to the outlet of the liquid storage.
  • the liquid micro-flow control system and method and the micro-fluidic detection device provided by the present invention can realize precise control of the liquid micro-flow in a non-contact manner through the air pressure controller and the gas flow controller.
  • the air pressure controller can quickly increase the liquid level pressure of the liquid to be measured in the liquid storage
  • the gas flow controller can fine-tune the liquid level pressure of the liquid to be tested in the liquid storage, and can accurately set the flow rate of the gas input to the liquid storage according to the needs, so as to accurately control the micro flow rate of the liquid to be tested in the microfluidic chip.
  • FIG. 1 is a schematic diagram of a liquid micro-flow control system in an embodiment of the present invention.
  • Fig. 2 is a flow chart of the liquid micro-flow control method in the embodiment of the present invention.
  • Air compressor 1. Air compressor, 2. Air pressure controller, 3. Gas flow controller, 4. Liquid storage, 5. Pressure stabilizing container, 6. Air pressure sensor, 7. Microfluidic chip, 10. First gas delivery pipeline, 20. Second gas delivery pipeline, 30. Third gas delivery pipeline, 40. Control valve.
  • an embodiment of the present invention provides a liquid micro-flow control system, including: an air compressor 1 , an air pressure controller 2 and a gas flow controller 3 .
  • the air compressor 1 communicates with the liquid storage 4 for storing the liquid to be treated through the first gas delivery pipeline 10 ;
  • the air compressor 1 is sequentially connected in series with the air pressure controller 2, the gas flow controller 3 and the liquid storage 4 through the second gas delivery pipeline 20;
  • the air pressure controller 2 also communicates with the liquid storage 4 through the third gas delivery pipeline 30 ; thus, there are two parallel gas delivery channels between the air pressure controller 2 and the liquid storage 4 .
  • a control valve 40 is also arranged on the third gas delivery pipeline 30 for controlling the gas transmission in the third gas delivery pipeline 30.
  • the air compressor 1, the air pressure controller 2, the gas flow controller 3, and the control valves 40 arranged on the first, second, and third gas delivery pipelines are respectively connected to the control device (not shown) in signal, so that the control device can control the start, operation and stop of the air compressor 1, the air pressure controller 2 and the gas flow controller 3 and the opening and closing of the control valve 40.
  • the air compressor 1 can not only provide positive pressure gas for the system, but also can form a negative pressure in the pipeline in the system;
  • the air pressure controller 2 can be a precision air pressure regulating valve, and a certain air pressure can be obtained by adjusting the air volume.
  • the gas flow controller 3 may be a constant-flow gas flow controller, which can realize continuous, high-precision, and trace gas flow control, for example, 10 ⁇ 0.01 ml/min.
  • the control valve 40 may be a solenoid valve.
  • the control device can be realized by a single-chip microcomputer, which can reach the control speed of millisecond level.
  • a pressure-stabilizing container 5 is provided between the air compressor 1 and the air pressure controller 2 , and the pressure-stabilizing container 5 communicates with the air compressor 1 and the air pressure controller 2 through the second gas delivery pipeline 20 .
  • the pressure-stabilizing container 5 can be used to store the gas delivered from the air compressor 1 .
  • an air pressure sensor 6 communicating with the liquid storage 4 is provided for detecting the air pressure in the liquid storage 4 .
  • the air pressure sensor 6 is signal-connected with the control device, so that the control device can read the air pressure data in the liquid storage 4 detected by the air pressure sensor 6 .
  • an alarm device is provided with a signal connection to the control device.
  • the control device makes the alarm device alarm by sound and light signals.
  • the embodiment of the present invention also provides a liquid micro-flow control method, which uses the above-mentioned liquid micro-flow rate control system, including the following steps:
  • the ends of the first gas delivery pipeline 10, the second gas delivery pipeline 20, and the third gas delivery pipeline 30 are respectively sealed and communicated with the liquid storage 4 through the input end of the liquid storage 4, and a set device can be used, such as a quick trachea joint, so that the ends of the first gas delivery pipeline 10, the second gas delivery pipeline 20, and the third gas delivery pipeline 30 can be conveniently and quickly sealed with the input end of the liquid storage 4.
  • a set device can be used, such as a quick trachea joint, so that the ends of the first gas delivery pipeline 10, the second gas delivery pipeline 20, and the third gas delivery pipeline 30 can be conveniently and quickly sealed with the input end of the liquid storage 4.
  • the container containing the liquid to be tested is sealed and communicated with the liquid storage 4 through the liquid delivery pipe through the input end of the liquid storage 4; the air compressor 1 is started by the control device, and the negative pressure is provided to the liquid storage 4 through the first gas delivery pipeline 10, and the liquid to be tested is pumped into the liquid storage 4; then the air compressor 1 is stopped.
  • the container containing the liquid to be tested may be a test tube containing the blood sample to be tested.
  • the liquid conveying pipe can also be sealedly connected with the input section of the liquid storage 4 through a quick air pipe connector. Start the air compression pump 1 to discharge the gas in the liquid storage 4 through the first gas delivery pipe 10 to form a negative pressure in the liquid storage 4 . Then, the liquid to be tested contained in the test tube is drawn into the liquid storage 4 by using the pressure difference. Afterwards, the air compressor 1 is stopped by the control device.
  • step S3 start the air compressor (1) to deliver gas to the pressure-stabilizing container (5), and then deliver gas to the air pressure controller (2) through the pressure-stabilizing container (5).
  • the gas communication between the air compressor 1 and the liquid storage 4 can be stopped by closing the control valve 40 provided on the first gas delivery pipeline 10 by the control device.
  • the air compressor 1 is activated by the control device to deliver gas to the pressure-stabilizing container 5.
  • the air compressor 1 can be turned off by the control device, and then only the gas in the pressure-stabilizing container 5 is used to control the flow rate of the liquid to be measured in the liquid storage 4. This can reduce the operating time of the air compressor 1 .
  • the air pressure controller 2 can adjust the air supply to the liquid storage 4 through the feedback of the air pressure value from the liquid storage 4, thereby adjusting the air pressure in the liquid storage 4 until it reaches the set value.
  • the liquid to be tested in the liquid storage 4 flows into the microfluidic chip under pressure. Since the internal resistance of the microfluidic chip is constant, controlling the liquid surface pressure of the liquid to be tested in the liquid storage 4 can control the flow rate of the liquid to be tested in the microfluidic chip.
  • the gas flow controller 3 can fine-tune the pressure of the liquid level of the liquid to be measured in the liquid storage 4, and make the pressure of the liquid surface reach a state of equilibrium, that is, the pressure of the liquid surface remains unchanged.
  • the volume of gas entering the liquid reservoir 4 is equal to the volume of liquid flowing out of the liquid reservoir 4 .
  • the gas is delivered to the liquid storage 4 at a set flow rate through the gas flow controller 3 , so that the liquid to be detected in the liquid storage 4 flows into the microfluidic chip at a set flow rate.
  • the control device can calculate the flow rate of the liquid to be measured according to the liquid level pressure in the liquid storage 4 detected by the air pressure sensor 6 and the flow rate of the gas output by the gas flow controller 3, or the flow rate of the liquid to be measured can be controlled by the flow rate of the gas output by the gas flow controller 3 to control the liquid level pressure of the liquid to be measured in an equilibrium state.
  • the control device sets the gas flow rate that the gas flow controller 3 inputs into the liquid storage 4 and measures the unit time variation of the liquid surface pressure in the liquid storage 4.
  • the compression coefficient Z is constant, it can be calculated according to this formula that in order to make the liquid to be measured entering the microfluidic chip reach the set flow rate, the required liquid level pressure of the liquid to be measured in the liquid storage 4 and the flow rate of the gas input by the gas flow controller 3 are required.
  • the control device can also quickly adjust the liquid level pressure of the liquid to be measured in the liquid storage 4 according to the detected flow rate to adjust to the set flow rate.
  • ⁇ n is the number of moles of gas added
  • n is the number of moles of gas before increasing the gas in the closed area in the liquid storage 4;
  • the liquid volume discharged from the closed area in the liquid storage 4 is V liquid , and after this second, the air pressure in the closed area in the liquid storage 4 becomes P 2 ,
  • V liquid P(V+V gas )/P 2 -V
  • the flow rate of the liquid to be tested in the microfluidic chip can be controlled by controlling the pressure of the liquid level of the liquid to be tested in the liquid storage 4 , and the pressure of the liquid level is positively correlated with the flow rate of the liquid.
  • the flow rate value can be observed in real time through the derivation of the ideal gas equation, and the flow rate control response speed depends on the adjustment speed of the liquid surface pressure. After reaching the final speed, maintain constant pressure, that is, to achieve the desired control flow rate.
  • the control device will increase the flow rate of the delivered gas through the gas flow controller 3, thereby increasing the pressure so that the flow rate of the liquid to be tested returns to the set flow rate. If the liquid surface pressure of the liquid to be measured in the liquid storage 4 continues to increase and exceeds the set threshold, the control device controls the alarm device (not shown in the figure) to give an alarm through sound and light signals. At the same time, the gas flow controller 3 is controlled to stop delivering gas to the liquid storage 4 .
  • an embodiment of the present invention further provides a microfluidic detection device, including the above-mentioned liquid microflow control system and a microfluidic detection package.
  • the microfluidic detection package includes: a liquid storage 4 and a microfluidic chip 7 connected to the outlet of the liquid storage 4 .
  • the microfluidic detection package can be an independent consumable package.
  • the liquid micro-flow control system and method and the micro-fluidic detection device provided by the present invention can realize precise control of the liquid micro-flow in a non-contact manner through the air pressure controller and the gas flow controller.
  • the air pressure controller can quickly increase the liquid level pressure of the liquid to be measured in the liquid storage
  • the gas flow controller can fine-tune the liquid level pressure of the liquid to be tested in the liquid storage, and can accurately set the flow rate of the gas input to the liquid storage according to the needs, so as to accurately control the micro flow rate of the liquid to be tested in the microfluidic chip.
  • the system is small in size and low in power consumption.
  • the microfluidic detection package can be mass-produced as an independent consumable package, which reduces the cost of detection.
  • connection should be understood in a broad sense, for example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection or a signal connection; it may be a direct connection or an indirect connection through an intermediate medium, or it may be an internal connection between two components.
  • connection should be understood in a broad sense, for example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection or a signal connection; it may be a direct connection or an indirect connection through an intermediate medium, or it may be an internal connection between two components.

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Abstract

本发明涉及生物体液检测分析技术领域，公开了一种液体微流量控制系统及方法以及一种微流控检测装置，该系统包括：空气压缩机、气压控制器和气体流量控制器；空气压缩机通过第一气体输送管道与用于存储待处理液体的液体存储器相连通，空气压缩机通过第二气体输送管道依次与气压控制器、气体流量控制器和液体存储器串联连通；气压控制器通过第三气体输送管道与液体存储器相连通；第一气体输送管道、第三气体输送管道以及位于气压控制器和气体流量控制器之间的第二气体输送管道段上设置有控制阀；空气压缩机、气压控制器、气体流量控制器以及控制阀分别与控制装置信号连接。本发明通过非接触的方式，实现了对液体微流量的精准控制。

Description

一种液体微流量控制系统及方法以及微流控检测装置 技术领域
本发明涉及生物体液检测分析技术领域，尤其涉及一种微量液体流速控制系统及方法以及一种微流控检测装置。
背景技术
微流控(Microfluidics)指的是使用微管道(尺寸为数十到数百微米)处理或操纵微小流体(体积为微升)的系统所涉及的科学和技术，是一门涉及化学、流体物理、微电子、新材料、生物学和生物医学工程的新兴交叉学科。
微流控技术近年来在生物体液活检领域受到极大关注，高精度的微流速控制技术是其中的难点之一。另外，由于体液活检的特点需要检测系统以非接触方式对体液进行快速、精准的检测。而且，检测系统中与体液相接触的部分一般以耗材形式出现，一次性的使用对成本的要求更高。
目前，业内实验室以半自动针筒泵的方式，通过手工设定方式来实现微流速控制，无法避免针筒泵重复使用。另外，靠步进电机以一定速度控制推进针筒方式不仅精准度低，而且，在过程中流速控制不稳定，影响实验检测效果。另外，电机推进针筒方式对后端阻力变化无法感知，后端发生部分堵塞无法监测。因此，这种方法一般以实验室内使用为主，检测过程需要大量人工操作，大规模商业化效果不理想。
发明内容
(一)要解决的技术问题
本发明的目的在于针对上述现有技术的不足，提供一种通过恒流气压控制，以非接触的方式，实现对液体微流量进行精准控制的系统和方法以及一种微流控检测装置。
(二)技术方案
为了解决上述问题，本发明提供了一种液体微流量控制系统，包括：空气压缩机、气压控制器和气体流量控制器；所述空气压缩机通过第一气体输送管道与用于存储待处理液体的液体存储器相连通，所述空气压缩机通过第二气体输送管道依次与所述气压控制器、气体流量控制器和所述液体存储器串联连通；所述气压控制器通过第三气体输送管道与所述液体存储器相连通；所述第一气体输送管道、第三气体输送管道以及位于所述气压控制器和气体流量控制器之间的第二气体输送管道段上设置有控制阀；所述空气压缩机、气压控制器、气体流量控制器以及所述控制阀分别与控制装置信号连接。
可选地，还包括设置在所述第二气体输送管道上分别与所述空气压缩机与所述气压控制器相连通的稳压容器。
可选地，还包括与所述液体存储器相连通的气压传感器，用于检测所述液体存储器内的气压，所述气压传感器与所述控制装置信号连接。
可选地，还包括报警装置，所述报警装置与所述控制装置信号连接。
本发明还提供了一种液体微流量控制方法，使用上述的液体微量流速控制系统，包括以下步骤：
S1、通过控制装置关闭设置在第二气体输送管道和第三气体输送管道上的控制阀；
S2、将盛待测液体的容器通过液体输送管经由液体存储器的输入端与所述液体存储器密封连通；通过所述控制装置启动空气压缩机，经由第一气体输送管道向液体存储器提供负压，将待测液体抽到所述 液体存储器内；然后使所述空气压缩机停止运行；
S3、通过所述控制装置关闭设置在所述第一气体输送管道上的控制阀，打开设置在所述第三气体输送管道上的控制阀，启动所述空气压缩机；调节气压控制器向液体存储器内输送气体，使液体存储器内的气压达到设定值；
S4、通过所述控制装置关闭设置在所述第三气体输送管道上的控制阀，打开设置在所述第二气体输送管道上的控制阀，通过气体流量控制器以设定的流量向所述液体存储器内输送气体，将所述液体存储器的待检测液体以设定的流速排出。
可选地，在步骤S3中，启动所述空气压缩机向稳压容器输送气体，再通过所述稳压容器向所述气压控制器输送气体。
可选地，在步骤S4中，当气压传感器检测到所述液体存储器内的气体压力超过设定的阈值时，报警装置通过声光信号报警。
本发明又提供了一种微流控检测装置，包括上述的液体微流量控制系统和微流控检测包，所述微流控检测包包括：液体存储器和与所述液体存储器的出口端相连通的微流控芯片。
(三)有益效果
本发明提供的液体微流量控制系统及方法以及微流控检测装置，通过气压控制器和气体流量控制器，能够通过非接触方式实现对液体微流量的精准控制。通过气压控制器能够快速的提升液体存储器中待测液体的液面气压，通过气体流量控制器能够对液体存储器中待测液体的液面气压进行微调，并且能够根据需要精确地设定输入到液体存储器的气体的流量，从而精准地控制待测液体在微流控芯片中的微流量。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面 将对实施例或现有技术描述中所需要使用的附图作简单地介绍。显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本发明实施例中的液体微流量控制系统的示意图；
图2为本发明实施例中的液体微流量控制方法的过程流程图。
附图中的附图标记依次为：
1、空气压缩机，2、气压控制器，3、气体流量控制器，4、液体存储器，5、稳压容器，6、气压传感器，7、微流控芯片，10、第一气体输送管道，20、第二气体输送管道，30、第三气体输送管道，40、控制阀。
具体实施方式
下面结合实施例和附图，对本发明的具体实施方式做进一步详细说明。在此，本发明的以下实施例用于说明本发明，但不用来限定本发明的范围。
如图1所示，本发明的实施例提供一种液体微流量控制系统，包括：空气压缩机1、气压控制器2和气体流量控制器3。
空气压缩机1通过第一气体输送管道10与用于存储待处理液体的液体存储器4相连通；并且在第一气体输送管道10设置有控制阀40，用于控制第一气体输送管道10中的气体传输。空气压缩机1通过第二气体输送管道20依次与气压控制器2、气体流量控制器3和液体存储器4串联连通；并且在位于气压控制器2和气体流量控制器3之间的第二气体输送管道20段上设置有控制阀40，用于控制第二气体输送管道20中气压控制器2和气体流量控制器3之间的气体传输。气压控制器2还通过第三气体输送管道30与液体存储器4相连通；从而使得在气压控制器2和液体存储器4有两个并行的气体输送通道。在第三气体输送管 道30上也设置有控制阀40，用于控制第三气体输送管道30中的气体传输。
空气压缩机1、气压控制器2、气体流量控制器3以及设置在第一、二、三气体输送管道上的控制阀40分别与控制装置(图中未示出)信号连接，使得控制装置能够控制空气压缩机1、气压控制器2和气体流量控制器3的启动、运行和停止以及控制阀40的开启和关闭。本实施例中，空气压缩机1既能够为系统提供正压的气体，也能够使在系统中的管道中形成负压；气压控制器2可以是精密气压调节阀，通过调节气量获得一定的气压。气体流量控制器3可以是恒流式气体流量控制器，能够实现持续的，高精度的，微量的气体流量控制，例如，10±0.01毫升/分钟。控制阀40可以是电磁阀。控制装置可以由单片机实现，能够达到毫秒级的控制速度。
在一个实施例中，在空气压缩机1与气压控制器2之间设置有稳压容器5，稳压容器5通过第二气体输送管道20分别与空气压缩机1和气压控制器2相连通。稳压容器5可用于存储从空气压缩机1输送过来的气体。
在一个实施例中，设置有与液体存储器4相连通的气压传感器6，用于检测液体存储器4内的气压。气压传感器6与控制装置信号连接，使得控制装置能够读取气压传感器6检测到的液体存储器4内的气压数据。
在一个实施例中，设置有控制装置信号连接的报警装置，当控制装置读取到的液体存储器4内的气压值超过设定阈值时，控制装置使得报警装置通过声光信号报警。
如图2所示，本发明的实施例还提供一种液体微流量控制方法，该方法使用上述的液体微量流速控制系统，包括以下步骤：
S1、通过控制装置关闭设置在第二气体输送管道20和第三气体输送管道30上的控制阀40。
在步骤S1之前，将第一气体输送管道10、第二气体输送管道20和第三气体输送管道30的末端分别通过液体存储器4的输入端与液体存储器4密封连通，可以利用设定的装置，例如，快速气管接头，使得第一气体输送管道10、第二气体输送管道20和第三气体输送管道30的末端能够方便、快捷地与液体存储器4的输入端密封连接。
S2、将盛装待测液体的容器通过液体输送管经由液体存储器4的输入端与液体存储器4密封连通；通过控制装置启动空气压缩机1，经由第一气体输送管道10向液体存储器4提供负压，将待测液体抽到液体存储器4内；然后使空气压缩机1停止运行。
盛装待测液体的容器可以是装有待检测的血液样本的试管。液体输送管也可以通过快速气管接头与液体存储器4的输入段密封连接。启动空气压缩泵1，通过第一气体输送管道10排出液体存储器4内的气体，在液体存储器4内形成负压。然后利用压力差，将盛装在试管中的待测液体抽入液体存储器4内。之后，通过控制装置使得空气压缩机1停止运行。
S3、通过控制装置关闭设置在第一气体输送管道10上的控制阀40，打开设置在第三气体输送管道30上的控制阀40；启动空气压缩机1；调节气压控制器2向液体存储器4内输送气体，使液体存储器4内的气压达到设定值。
在步骤S3中，启动所述空气压缩机(1)向稳压容器(5)输送气体，再通过所述稳压容器(5)向所述气压控制器(2)输送气体。
可以通过控制装置关闭设置在第一气体输送管道10上的控制阀40，停止空气压缩机1与液体存储器4之间的气体连通。通过控制装置启动空气压缩机1向稳压容器5输送气体，当稳压容器5存储的气体气压达到期望值时，可以通过控制装置关闭空气压缩机1，后续只利用稳压容器5的气体来控制液体存储器4中待测液体的流量。这样可以减少空气压缩机1的运转时间。
通过控制装置打开设置在第三气体输送管道30上的控制阀40，调节气压控制器2，使得稳压容器5中气体通过气压控制器2和第三气体输送管道30进入到液体存储器4中。气压控制器2可以通过从液体存储器4中反馈回来的气压值，调节向液体存储器4的供气量，从而调节液体存储器4内的气压，直至达到设定值。
S4、通过控制装置关闭设置在第三气体输送管道30上的控制阀40，打开设置在第二气体输送管道20上的控制阀40，通过气体流量控制器3以设定的流量向液体存储器4内输送气体，将液体存储器4的待检测液体以设定的流速排出。
关闭设置在第三气体输送管道30上的控制阀40，使得停止从气压控制器2直接向液体存储器4供气。打开设置在第二气体输送管道20上的控制阀40，使得从稳压容器5输出气体经过气压控制器2和气体流量控制器3输入到液体存储器4中。
当液体存储器4的出口端与进行相关检测的检测装置相连接时，例如，与微流控芯片相连接，液体存储器4中的待测液体在压力作用下流入微流控芯片。由于微流控芯片内部的阻力是一定的，因此控制液体存储器4中待测液体的液面气压就可以控制待测液体在微流控芯片内的流速。在待测液体的液面与气体流量控制器3的输出口之间形成的封闭空间内，通过气体流量控制器3可以对液体存储器4中待测液体的液面气压进行微调，并使得液面气压会达到一种平衡状态，即液面气压保持不变。在这种状态下，进入液体存储器4的气体体积与流出液体存储器4的液体体积相等。通过气体流量控制器3以设定的流量向液体存储器4内输送气体，使得液体存储器4的待检测液体以设定的流速流入微流控芯片。
控制装置可以根据气压传感器6检测到的液体存储器4中的液面气压和气体流量控制器3输出气体的流速算出待测液体的流速，也可以通过气体流量控制器3输出气体的流量来控制平衡态的待测液体的 液面气压来控制待测液体的流速。
控制装置通过设置气体流量控制器3输入到液体存储器4中的气体流量和测量液体存储器4中液面气压单位时间变化量，根据理想气体状态方程，PV＝nRT，其中，P为液体存储器4中待测液体的液面气压；V为单位时间内流入液体存储器4中的气体体积；n为气体摩尔数，R为摩尔气体常数，T是热力学温度。实际空气气体状态方程在常温高压下存在压缩系数Z，使PV/nRT＝Z，在压缩系数Z一定的情况下，可以根据该公式推算出为了使进入微流控芯片中的待测液体要达到设定的流速，而所需的液体存储器4中待测液体的液面气压和气体流量控制器3输入气体的流速。控制装置还可以根据检测到的流速迅速调整液体存储器4中待测液体的液面气压的大小以调整到我们所设定的流速。
假设当前通过气体流量控制器3流入液体存储器4中的封闭区域内的每秒气体等效体积为V 气，可以通过控制装置来设置该参数；液体存储器4中的当前的气体体积为V，气压为P，在气压差异很小时，假设压缩系数Z相等，则
PV 气＝ΔnRTZ
其中，Δn为增加的气体摩尔数；
P(V+V 气)＝(n+Δn)RTZ
其中，n为液体存储器4中的封闭区域中在增加气体前的气体摩尔数；
液体存储器4中的封闭区域排出的液体体积为V 液，经过这一秒的时间，液体存储器4中的封闭区域内的气压变为P 2，
P 2(V+V 液)＝(n+Δn)RTZ
P 2(V+V 液)＝P(V+V 气)
V 液＝P(V+V 气)/P 2-V
当液体存储器4中的封闭区域处于平衡状态时，P 2＝P，由此得出，
V 液＝V 气
综上所述，通过控制液体存储器4中待测液体的液面气压就可以控制待测液体在微流控芯片中的流速，液面气压和液体流速正相关。通过理想气体方程推导可实时观测流速值，流速控制反应速度取决于液面气压调整速度。达到最终速度后保持恒压，即达到所要的控制流速。当微流控芯片中出现气泡、灰尘或其他颗粒堵塞导致阻力增大，从而导致待测液体在微流控芯片中的流速下降，液体存储器4中待测液体的液面气压升高；气压传感器6会将检测到的压力值发送至控制装置。控制装置会通过气体流量控制器3提高输送气体的流量，从而增加压力使得待测液体的流速恢复至设定的流速。如果液体存储器4中待测液体的液面压力持续增加，超过设定的阈值时，控制装置控制报警装置(图中未示出)通过声光信号报警。同时，控制气体流量控制器3停止向液体存储器4中输送气体。
如图1所示，本发明的实施例又提供了一种微流控检测装置，包括上述的液体微流量控制系统和微流控检测包。微流控检测包包括：液体存储器4和与液体存储器4的出口端相连通的微流控芯片7。在检测过程中，微流控检测包可以是独立的耗材包，通过与液体微流量控制系统快速连接和分离，在检测过程中现实非接触式的，对液体微流量的精准控制，并且由于独立的耗材包可以大批量的生产，降低了检测了的成本。
本发明提供的液体微流量控制系统及方法以及微流控检测装置，通过气压控制器和气体流量控制器，能够通过非接触方式实现对液体微流量的精准控制。通过气压控制器能够快速的提升液体存储器中待测液体的液面气压，通过气体流量控制器能够对液体存储器中待测液体的液面气压进行微调，并且能够根据需要精确地设定输入到液体存储器的气体的流量，从而精准地控制待测液体在微流控芯片中的微流量。并且，该系统体积小，功耗低。微流控检测包可以作为独立的耗 材包大批量的生产，降低了检测了的成本。
在本发明中，术语如“上”、“下”、“左”、“右”、“前”、“后”、“竖直”、“水平”、“侧”、“底”等指示的方位或位置关系为基于附图所示的方位或位置关系，只是为了便于叙述本发明各部件或元件结构关系而确定的关系词，并非特指本发明中任一部件或元件，不能理解为对本发明的限制。
在本发明的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是信号连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本发明中的具体含义，不能理解为对本发明的限制。
需要注意的是，这里所使用的术语仅是为了描述具体实施方式，而非意图限制根据本申请的示例性实施方式。如在这里所使用的，除非上下文另外明确指出，否则单数形式也意图包括复数形式，此外，还应当理解的是，当在本说明书中使用术语“包含”和/或“包括”时，其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
以上实施方式仅用于说明本发明，而非对本发明的限制。尽管参照实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，对本发明的技术方案进行各种组合、修改或者等同替换，都不脱离本发明技术方案的精神和范围，均应涵盖在本发明的权利要求范围当中。

Claims (8)

  1. 一种液体微流量控制系统，其特征在于，包括：空气压缩机(1)、气压控制器(2)和气体流量控制器(3)；
    所述空气压缩机(1)通过第一气体输送管道(10)与用于存储待处理液体的液体存储器(4)相连通；
    所述空气压缩机(1)通过第二气体输送管道(20)依次与所述气压控制器(2)、气体流量控制器(3)和所述液体存储器(4)串联连通；
    所述气压控制器(2)通过第三气体输送管道(30)与所述液体存储器(4)相连通；
    所述第一气体输送管道(10)、第三气体输送管道(30)以及位于所述气压控制器(2)和气体流量控制器(3)之间的第二气体输送管道(20)段上设置有控制阀(40)；
    所述空气压缩机(1)、气压控制器(2)、气体流量控制器(3)以及所述控制阀(40)分别与控制装置信号连接。
  2. 根据权利要求1所述的液体微流量控制系统，其特征在于，还包括设置在所述第二气体输送管道(20)上分别与所述空气压缩机(1)与所述气压控制器(2)相连通的稳压容器(5)。
  3. 根据权利要求2所述的液体微流量控制系统，其特征在于，还包括与所述液体存储器(4)相连通的气压传感器(6)，用于检测所述液体存储器(4)内的气压，所述气压传感器(6)与所述控制装置信号连接。
  4. 根据权利要求3所述的液体微流量控制系统，其特征在于，还包括报警装置，所述报警装置与所述控制装置信号连接。
  5. 一种液体微流量控制方法，其特征在于，使用权利要求1至4中任一项所述的液体微量流速控制系统，包括以下步骤：
    S1、通过控制装置关闭设置在第二气体输送管道(20)和第三气 体输送管道(30)上的控制阀(40)；
    S2、将盛待测液体的容器通过液体输送管经由液体存储器(4)的输入端与所述液体存储器(4)密封连通；通过所述控制装置启动空气压缩机(1)，经由第一气体输送管道(10)向所述液体存储器(4)提供负压，将待测液体抽到所述液体存储器(4)内；然后使所述空气压缩机(1)停止运行；
    S3、通过所述控制装置关闭设置在所述第一气体输送管道(10)上的控制阀(40)，打开设置在所述第三气体输送管道(30)上的控制阀(40)，启动所述空气压缩机(1)；调节气压控制器(2)向所述液体存储器(4)内输送气体，使所述液体存储器(4)内的气压达到设定值；
    S4、通过所述控制装置关闭设置在所述第三气体输送管道(30)上的控制阀(40)，打开设置在所述第二气体输送管道(20)上的控制阀(40)，通过气体流量控制器(3)以设定的流量向所述液体存储器(4)内输送气体，将所述液体存储器(4)的待检测液体以设定的流速排出。
  6. 根据权利要求5所述的液体微流量控制方法，其特征在于，在步骤S3中，启动所述空气压缩机(1)向稳压容器(5)输送气体，再通过所述稳压容器(5)向所述气压控制器(2)输送气体。
  7. 根据权利要求5所述的液体微流量控制方法，其特征在于，在步骤S4中，当气压传感器(6)检测到所述液体存储器(4)内的气体压力超过设定的阈值时，报警装置通过声光信号报警。
  8. 一种微流控检测装置，其特征在于，包括权利要求1-4中任一项所述的液体微流量控制系统和微流控检测包，
    所述微流控检测包包括：液体存储器(4)和与所述液体存储器(4)的出口端相连通的微流控芯片(7)。
PCT/CN2022/123310 2022-01-21 2022-09-30 一种液体微流量控制系统及方法以及微流控检测装置 WO2023138102A1 (zh)

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