WO2021237397A1 - Fluid control device and fluid control method - Google Patents

Fluid control device and fluid control method Download PDF

Info

Publication number
WO2021237397A1
WO2021237397A1 PCT/CN2020/092010 CN2020092010W WO2021237397A1 WO 2021237397 A1 WO2021237397 A1 WO 2021237397A1 CN 2020092010 W CN2020092010 W CN 2020092010W WO 2021237397 A1 WO2021237397 A1 WO 2021237397A1
Authority
WO
WIPO (PCT)
Prior art keywords
chamber
reagent
fluid
way valve
valve structure
Prior art date
Application number
PCT/CN2020/092010
Other languages
French (fr)
Chinese (zh)
Inventor
刘鹏
耿智
林宝宝
Original Assignee
杭州梓晶生物有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 杭州梓晶生物有限公司 filed Critical 杭州梓晶生物有限公司
Priority to PCT/CN2020/092010 priority Critical patent/WO2021237397A1/en
Publication of WO2021237397A1 publication Critical patent/WO2021237397A1/en

Links

Images

Classifications

    • 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00Apparatus for enzymology or microbiology
    • C12M1/34Measuring or testing with condition measuring or sensing means, e.g. colony counters

Definitions

  • the invention relates to a fluid control device, in particular to a fluid control device and a fluid control method that can realize simple and stable micro-fluid control.
  • Microfluidic chips can realize precise control of trace fluids by processing micro-pumps, micro-valves, micro-pipes, micro-electrodes and other structures on micro-scale chips, which can convert biochemical products that could only be operated by professionals in the laboratory.
  • the analysis reaction is transferred to the chip for automation.
  • the specially designed microfluidic chip can be used for cell screening and capture, cell culture, protein detection, nucleic acid extraction, nucleic acid amplification, capillary electrophoresis, etc., in medical treatment, environmental protection, scientific research, criminal investigation, etc.
  • the field has huge application prospects.
  • microfluidic chips Compared with the traditional use of pipettes and centrifuge tubes for experimental operations, microfluidic chips have advantages in integration and automation, but due to the limitations of fluid control methods, microfluidic chips also face the following problems: (1) The fluid control method is complicated. The fluid control on the microfluidic chip often requires external air pressure sources such as syringe pumps and air pumps, or the use of centrifuges to provide fluid driving force, which greatly increases the volume and cost of the entire system; or the use of surface modification, Using capillary force to achieve fluid self-driving, but at the same time, it will also cause insufficient stability, which limits the application scenarios of microfluidic systems; (2) It is difficult to quantify trace fluids, and many steps in biochemical analysis experiments require precise pipetting.
  • the purpose of the present invention is to provide a fluid control device and a fluid control method that can simply and stably realize microfluid control, which relies on a microfluidic chip to realize simple and stable fluid control, microfluid quantification and one-step method
  • the liquid is mixed and transferred, and the system can be completely enclosed.
  • a fluid manipulation device for realizing the function of quantifying a trace fluid
  • the fluid manipulation device includes: a cartridge on which a control chamber, a reagent chamber, and a recovery chamber are formed , And the bottom of the control chamber, the reagent chamber and the recovery chamber are all formed with an opening; a lower layer chip on which a quantitative cell is formed; an elastic membrane for bonding the lower layer chip to the cartridge
  • the elastic membrane is provided with the same number of through holes as the openings at the bottom of the cartridge, wherein the opening of the control chamber coincides with the through hole on the elastic membrane, so that the control chamber and The quantitative cell is connected; the openings of the reagent chamber and the recovery chamber do not overlap with the through holes on the elastic membrane, so that the opening of the reagent chamber and the quantitative cell can only be formed
  • the first one-way valve structure that cannot enter, the second one-way valve structure that can only enter and cannot exit is formed between the opening of the recovery chamber and the dosing
  • the elastic film is made of a double-sided tape base material and undergoes partial de-tackification treatment.
  • the control chamber adopts a push rod piston structure, an external air pump or a syringe pump to achieve control; a liquid reaction reagent is pre-stored in the reagent chamber, and a detection device is pre-stored in the recovery chamber Chromogenic reagent or test strip; the volume of the quantitative cell is 20-100 ⁇ L, and a dry powder reaction reagent is pre-stored inside.
  • a fluid control method based on the above-mentioned fluid control device includes the following steps:
  • a fluid manipulation device is used to realize a one-step fluid mixing and transferring function.
  • the fluid manipulation device includes a cartridge on which a reagent chamber, a mixing chamber, and a recovery chamber are formed, and the reagent chamber and An opening is formed at the bottom of the recovery chamber, the mixing chamber is a closed chamber and an inlet and an outlet are formed at the bottom; the lower chip has at least two disconnected fluid pipes formed thereon; the elastic membrane is used When the lower layer chip is bonded to the bottom of the cartridge, the elastic membrane is provided with the same number of through holes as the bottom openings of the cartridge, and the reagent chamber, the mixing chamber, and the recovery chamber The through holes on the chamber and the elastic membrane do not overlap, so that the opening of the reagent chamber and one of the fluid pipes and the outlet of the mixing chamber and the other fluid pipe A first one-way valve structure that can only exit and cannot enter is formed. Between the inlet of the mixing chamber and one of the fluid pipes, and between the opening of the recovery chamber and the other fluid pipe, only The second one
  • an airbag structure is provided on the top of the cartridge for fully enclosing the top of the cartridge, and except for the mixing chamber, the reagent chamber and The recovery chambers are all communicated with the airbag structure through the air guiding structure.
  • the airbag structure includes but is not limited to a sealing tube, a sealing film and an elastic airbag;
  • the air guiding structure includes but is not limited to an air guiding hole, an air guiding groove and an air guiding pipe.
  • the elastic film is made of a double-sided tape base material and undergoes partial de-tackification treatment.
  • a liquid reaction reagent is pre-stored in the reagent chamber and the mixing chamber, a color developer or test strip for detection is pre-stored in the recovery chamber, and the fluid pipe is pre-stored There are dry powder reaction reagents.
  • a fluid control method based on the above-mentioned fluid control device includes the following steps:
  • the present invention has the following advantages due to the above technical scheme: 1.
  • the fluid manipulation device provided by the present invention does not rely on the control and operation of any external instrument, and only a few simple pressure actions can complete reagent quantification and mixing. And the reagent transfer operation.
  • the present invention uses the hydrophobic membrane to realize the fluid limit during the pressing action, and realizes the accurate quantification of the micro-level liquid through the hydrophobic membrane and the quantification pool on the lower chip, which solves the problem of difficult quantification on the microfluidic chip. 3.
  • the present invention realizes the one-step fluid mixing and transfer, the liquid and gas are successively introduced into the closed reagent chamber, the different reagents are mixed when the liquid is introduced, and the gas is compressed and the liquid is pumped out when the gas is introduced.
  • the two steps of reagent mixing and transfer can be realized by applying positive pressure in one step, which simplifies the operation of fluid control of the microfluidic chip. 4.
  • the fluid control device provided by the present invention realizes the communication and sealing of the reaction chamber through the air guide hole and the sealing film, and can realize the complete sealing of the entire reaction system, thereby effectively avoiding problems such as pollutant leakage and aerosol pollution.
  • Fig. 1 is a schematic structural diagram of a fluid manipulation device in the first embodiment of the present invention
  • Figures 2(a) and 1(b) are schematic diagrams of the principle of realizing micro-fluid quantification in the first embodiment of the present invention
  • FIG. 3 is a schematic diagram of the structure of the fluid manipulation device in the second embodiment of the present invention.
  • Figures 4(a) to 2(d) are schematic diagrams of the principle of implementing one-step fluid mixing and transfer in the second embodiment of the present invention.
  • Figure 5 is a schematic structural diagram of a fully enclosed fluid manipulation device of the present invention.
  • Fig. 6 is a schematic diagram of the principle of a fully enclosed fluid manipulation device of the present invention.
  • Figures 1 and 2 show a fluid manipulation device capable of realizing the quantitative function of microfluid provided by the first embodiment of the present invention.
  • the fluid manipulation device includes: a cartridge 1 on which a control chamber 6, a reagent chamber 8 and a recovery chamber are formed.
  • An opening is formed at the bottom of the chamber 10, the control chamber 6, the reagent chamber 8 and the recovery chamber 10; the lower chip 2 has a quantitative cell 11 formed thereon; the elastic membrane 3 is used to bond the lower chip 2 At the bottom of the card box 1, and the elastic membrane 3 is provided with the same number of through holes as the bottom openings of the card box 1, wherein the opening of the control chamber 6 coincides with the through hole on the elastic membrane 3, so that the control chamber 6 and The quantitative cell 11 is connected; the openings of the reagent chamber 8 and the recovery chamber 10 are not overlapped with the through holes on the elastic membrane 3, so that the opening of the reagent chamber 8 and the quantitative cell 11 can only exit and cannot enter.
  • the first one-way valve structure 15 forms a second one-way valve structure 18 between the opening of the recovery chamber 10 and the dosing tank 11, which can only enter and cannot go out; the hydrophobic membrane 4 is arranged in the control chamber 6 and the dosing tank 11. At the through hole of the elastic membrane 3 in between, the hydrophobic membrane 4 can allow air to pass through, but block liquid from passing through.
  • control chamber 6 can be controlled by a push rod piston structure, an external air pump or a syringe pump and other air pressure sources; the reagent chamber 8 is pre-stored with liquid reaction reagents, and the recovery chamber 10 is pre-stored with detection Chromogenic reagent or test strip used; the volume of the quantitative cell 11 is 20-100 ⁇ L, and the dry powder reaction reagent can be pre-stored inside.
  • the elastic film 3 can be a double-sided adhesive substrate, and after partial detackification treatment, it can not only realize the one-way valve function, but also realize the bonding of the cartridge 1 and the lower chip 2.
  • the present invention also provides a fluid control method based on the fluid manipulation device, which includes the following steps:
  • Figures 3 and 4 show a fluid manipulation device that can realize the function of one-step fluid mixing and transfer according to the second embodiment of the present invention.
  • the fluid manipulation device includes: a cartridge 1 on which a reagent chamber 8 and a mixing chamber are formed The bottom of the chamber 9 and the recovery chamber 10, and the reagent chamber 8 and the recovery chamber 10 are both formed with an opening.
  • the mixing chamber 9 is a closed chamber with an inlet and an outlet formed at the bottom; the lower chip 2 has an opening on it.
  • At least two disconnected fluid pipes 19 are formed; an elastic membrane 3 is used to bond the lower chip 2 to the bottom of the card box 1, and the elastic membrane 3 is provided with the same number of through holes as the bottom openings of the card box 1, and
  • the reagent chamber 8, the mixing chamber 9, and the recovery chamber 10 do not overlap with the through holes on the elastic membrane 3, so that the opening of the reagent chamber 8 and one of the fluid pipes 19 and the mixing chamber 9
  • the first one-way valve structure 15 is formed between the outlet and the other fluid pipe 19, which can only go out and cannot enter, between the inlet of the mixing chamber 9 and one of the fluid pipes 19, and the opening of the recovery chamber 10 and the other fluid.
  • a second one-way valve structure 18 that can only enter and cannot exit is formed between the pipes 19.
  • an airbag structure 20 is provided on the top of the cartridge 1 for fully enclosing the top of the cartridge 1, except for the mixing chamber 9. , Both the reagent chamber 8 and the recovery chamber 10 are connected to the airbag structure 20 through the air guiding structure 14.
  • the airbag structure 20 includes, but is not limited to, a sealing tube, a sealing film, an elastic airbag, and the like.
  • the air guiding structure 14 includes but not limited to air guiding holes, air guiding grooves, air guiding pipes, and the like.
  • the reagent chamber 8 and the mixing chamber 9 are pre-stored with liquid reaction reagents, and the recovery chamber 10 is pre-stored with a color developer or test strip for detection; the fluid pipe 19 can be pre-stored Dry powder reaction reagent.
  • the elastic film 3 can be a double-sided adhesive substrate, and after partial detackification treatment, it can not only realize the one-way valve function, but also realize the bonding of the cartridge 1 and the lower chip 2.
  • the present invention also provides a fluid control method of the fluid manipulation device, which includes the following steps:
  • Reagent A is pre-stored in the reagent chamber 8 and reagent B is pre-stored in the mixing chamber 9 (as shown in Figure 4(a)).
  • the fluid manipulation device adopts a shape similar to a tape cartridge, but without departing from the essence of the invention, the fluid manipulation device can also be modified for specific practical applications, for example, in terms of structure.
  • the following variants are possible: 1The shape of the cartridge 1 can be adjusted according to the processing method and functional requirements, and it can be a combination of rectangular, cylindrical, and truncated cone shapes; 2The order of the chambers on the cartridge 1 can be adjusted according to the function Corresponding adjustments are required; 3For the order of the chambers on the cartridge 1, the arrangement of the dosing cell 11 or the fluid channel 19 on the lower chip 2 can also be adjusted accordingly; 4The control chamber 6 or the control chamber on the cartridge 1 The number of mixing chambers 9 can be adjusted according to requirements, and the number of quantitative cells 11 or fluid channels 19 on the lower chip 2 can be adjusted according to requirements.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

A fluid control device and a fluid control method, which are used for achieving the function of micro-fluid quantification, or liquid mixing and transferring by means of a one-step method. The fluid control device comprises: a card box (1), on which a control chamber (6)/mixing chamber (9), a reagent chamber (8) and a recovery chamber (10) are formed; a lower-layer chip (2), on which a quantitative pool (11) or a fluid passage (19) is formed; and an elastic membrane (3), which is used for bonding the lower-layer chip (2) at the bottom of the card box (1). A first one-way valve structure (15) which only allows for exiting and not entering or a second one-way valve structure (18) which only allows for entering and not exiting is formed among the control chamber (6)/mixing chamber (9), the reagent chamber (8) and the recovery chamber (10), and the quantitative pool (11) or the fluid passage (19) by means of the elastic membrane (3). The fluid control device need not to depend on the control and operation of any external instrument, and can complete fluid control, micro-fluid quantification, and liquid mixing and transferring operations by means of a one-step method with only several simple pressure applying actions, and can implement full sealing of the system, thereby effectively avoiding problems such as pollutant leakage and aerosol pollution.

Description

一种流体操控装置及流体控制方法Fluid control device and fluid control method 技术领域Technical field
本发明涉及一种流体操控装置,具体是关于一种可以简单、稳定地实现微量流体操控的流体操控装置及流体控制方法。The invention relates to a fluid control device, in particular to a fluid control device and a fluid control method that can realize simple and stable micro-fluid control.
背景技术Background technique
微流控芯片通过在微小尺度的芯片上加工出微泵、微阀、微管道、微电极等结构,实现对微量流体的精密操控,可以将原本只能在实验室中由专业人员操作的生化分析反应转移至芯片上自动化实现,经过专门设计的微流控芯片可用于细胞筛选与捕获、细胞培养、蛋白检测、核酸提取、核酸扩增、毛细管电泳等,在医疗、环保、科研、刑侦等领域有着巨大的应用前景。Microfluidic chips can realize precise control of trace fluids by processing micro-pumps, micro-valves, micro-pipes, micro-electrodes and other structures on micro-scale chips, which can convert biochemical products that could only be operated by professionals in the laboratory. The analysis reaction is transferred to the chip for automation. The specially designed microfluidic chip can be used for cell screening and capture, cell culture, protein detection, nucleic acid extraction, nucleic acid amplification, capillary electrophoresis, etc., in medical treatment, environmental protection, scientific research, criminal investigation, etc. The field has huge application prospects.
相比于传统的使用移液枪、离心管进行实验操作,微流控芯片在集成化、自动化方面具有优势,但受到流体控制方式的限制,微流控芯片还面临着如下问题:(1)流体控制方式复杂,微流控芯片上的流体控制往往需要外接注射泵、气泵等气压源,或使用离心机,提供流体驱动力,这大大增加了整个***的体积和成本;或者使用表面修饰、借助毛细力等实现流体自驱动,但同时也会导致稳定性不够,限制了微流控***的应用场景;(2)微量流体定量困难,生化分析实验中许多步骤需要用移液枪精确的吸取微升级别的液体,用作反应体系配置等,但该步骤在微流控芯片上实现较为困难,往往需要设计复杂的阀结构,或牺牲整个***的精度;(3)流体混匀问题,生化反应过程中涉及多步液体混合步骤,这为微流控芯片的设计造成更多困难;(4)***封闭性问题,生化反应过程需要在离心管内密闭进行,以核酸扩增为例,由于核酸在扩增过程中需要加热,并以指数倍放大,容易产生气溶胶污染,并可能导致假阳性;因此需要微流控芯片内部流体空间做到全封闭,同时兼顾芯片与外界实现流体控制的接口。Compared with the traditional use of pipettes and centrifuge tubes for experimental operations, microfluidic chips have advantages in integration and automation, but due to the limitations of fluid control methods, microfluidic chips also face the following problems: (1) The fluid control method is complicated. The fluid control on the microfluidic chip often requires external air pressure sources such as syringe pumps and air pumps, or the use of centrifuges to provide fluid driving force, which greatly increases the volume and cost of the entire system; or the use of surface modification, Using capillary force to achieve fluid self-driving, but at the same time, it will also cause insufficient stability, which limits the application scenarios of microfluidic systems; (2) It is difficult to quantify trace fluids, and many steps in biochemical analysis experiments require precise pipetting. Micro-upgrading other liquids for reaction system configuration, etc., but this step is difficult to implement on microfluidic chips, often requiring the design of complex valve structures, or sacrificing the accuracy of the entire system; (3) fluid mixing problems, biochemical The reaction process involves multiple liquid mixing steps, which causes more difficulties for the design of the microfluidic chip; (4) The system is closed. The biochemical reaction process needs to be carried out in a closed centrifuge tube. Take nucleic acid amplification as an example. In the amplification process, heating is required and exponentially magnified, which is prone to aerosol pollution and may lead to false positives; therefore, the internal fluid space of the microfluidic chip is required to be fully enclosed, while taking into account the interface between the chip and the outside world to achieve fluid control .
发明内容Summary of the invention
针对上述问题,本发明的目的是提供一种可以简单、稳定地实现微量流体控制的流体操控装置及流体控制方法,其依靠微流控芯片实现了简单稳定的流体控制、微量流体定量及一步法液体混匀转移,并可以实现***的全封闭。In view of the above-mentioned problems, the purpose of the present invention is to provide a fluid control device and a fluid control method that can simply and stably realize microfluid control, which relies on a microfluidic chip to realize simple and stable fluid control, microfluid quantification and one-step method The liquid is mixed and transferred, and the system can be completely enclosed.
为实现上述目的,本发明采取以下技术方案:一种流体操控装置,用于实现微量流体定量功能,该流体操控装置包括:卡盒,其上形成有控制腔室、试剂腔室和回收腔室,且所述控制腔室、试剂腔室和回收腔室的底部均形成有一开口;下层芯 片,其上形成有定量池;弹性膜,用于将所述下层芯片键合在所述卡盒的底部,且所述弹性膜上开设有与所述卡盒底部开口数目相同的通孔,其中所述控制腔室的开口与所述弹性膜上的通孔重合,以使所述控制腔室与所述定量池相连通;所述试剂腔室和回收腔室的开口均与所述弹性膜上的通孔不重合,以使所述试剂腔室的开口与所述定量池之间形成只能出不能进的第一单向阀结构,所述回收腔室的开口与所述定量池之间形成只能进不能出的第二单向阀结构;疏水膜,设置在位于所述控制腔室与所述定量池之间的所述弹性膜通孔处。In order to achieve the above objective, the present invention adopts the following technical solutions: a fluid manipulation device for realizing the function of quantifying a trace fluid, the fluid manipulation device includes: a cartridge on which a control chamber, a reagent chamber, and a recovery chamber are formed , And the bottom of the control chamber, the reagent chamber and the recovery chamber are all formed with an opening; a lower layer chip on which a quantitative cell is formed; an elastic membrane for bonding the lower layer chip to the cartridge The elastic membrane is provided with the same number of through holes as the openings at the bottom of the cartridge, wherein the opening of the control chamber coincides with the through hole on the elastic membrane, so that the control chamber and The quantitative cell is connected; the openings of the reagent chamber and the recovery chamber do not overlap with the through holes on the elastic membrane, so that the opening of the reagent chamber and the quantitative cell can only be formed The first one-way valve structure that cannot enter, the second one-way valve structure that can only enter and cannot exit is formed between the opening of the recovery chamber and the dosing tank; the hydrophobic membrane is arranged between the control chamber and the At the through holes of the elastic membrane between the quantitative cells.
所述的流体操控装置,优选地,所述弹性膜选用双面胶基材,经过局部去粘性处理。In the fluid manipulation device, preferably, the elastic film is made of a double-sided tape base material and undergoes partial de-tackification treatment.
所述的流体操控装置,优选地,所述控制腔室采用推杆活塞结构、外接气泵或注射泵实现控制;所述试剂腔室内预存有液状反应试剂,所述回收腔室内预存有检测用的显色剂或试纸条;所述定量池的容积为20-100μL,内部预存有干粉状反应试剂。In the fluid control device, preferably, the control chamber adopts a push rod piston structure, an external air pump or a syringe pump to achieve control; a liquid reaction reagent is pre-stored in the reagent chamber, and a detection device is pre-stored in the recovery chamber Chromogenic reagent or test strip; the volume of the quantitative cell is 20-100 μL, and a dry powder reaction reagent is pre-stored inside.
一种基于上述流体操控装置的流体控制方法,包括以下步骤:A fluid control method based on the above-mentioned fluid control device includes the following steps:
1)对控制腔室施加负压,试剂腔室与定量池之间的第一单向阀结构在负压作用下打开,试剂腔室的液体流入定量池中,但无法穿过疏水膜进入控制腔室;同时回收腔室与定量池之间的第二单向阀结构在负压作用下保持关闭;1) Apply negative pressure to the control chamber, the first one-way valve structure between the reagent chamber and the dosing cell is opened under the action of negative pressure, and the liquid in the reagent chamber flows into the dosing cell, but cannot enter the control chamber through the hydrophobic membrane Chamber; At the same time, the second one-way valve structure between the recovery chamber and the dosing tank is kept closed under the action of negative pressure;
2)对控制腔室施加正压,试剂腔室与定量池之间的第一单向阀结构在正压作用下关闭,而回收腔室与定量池之间的第二单向阀结构在正压作用下打开,此时定量池内的液体流入回收腔室中,且流入回收腔室内的液体体积与定量池的容积相等。2) Positive pressure is applied to the control chamber, the first one-way valve structure between the reagent chamber and the dosing cell is closed under the positive pressure, and the second one-way valve structure between the recovery chamber and the dosing cell is under the positive pressure When the bottom is opened, the liquid in the dosing tank flows into the recovery chamber, and the volume of the liquid flowing into the recovery chamber is equal to the volume of the dosing tank.
一种流体操控装置,用于实现一步法流体混匀转移功能,该流体操控装置包括:卡盒,其上形成有试剂腔室、混匀腔室和回收腔室,且所述试剂腔室和回收腔室的底部均形成有一开口,所述混匀腔室为密闭腔室且其底部形成有一进口和一出口;下层芯片,其上形成有至少两个不连通的流体管道;弹性膜,用于将所述下层芯片键合在所述卡盒的底部,所述弹性膜上开设有与所述卡盒底部开口数目相同的通孔,且所述试剂腔室、混匀腔室和回收腔室与所述弹性膜上的通孔均不重合,以使所述试剂腔室的开口与其中一所述流体管道之间以及所述混匀腔室的出口与另一所述流体管道之间形成只能出不能进的第一单向阀结构,所述混匀腔室的进口与其中一所述流体管道之间以及所述回收腔室的开口与另一所述流体管道之间形成只能进不能出的第二单向阀结构。A fluid manipulation device is used to realize a one-step fluid mixing and transferring function. The fluid manipulation device includes a cartridge on which a reagent chamber, a mixing chamber, and a recovery chamber are formed, and the reagent chamber and An opening is formed at the bottom of the recovery chamber, the mixing chamber is a closed chamber and an inlet and an outlet are formed at the bottom; the lower chip has at least two disconnected fluid pipes formed thereon; the elastic membrane is used When the lower layer chip is bonded to the bottom of the cartridge, the elastic membrane is provided with the same number of through holes as the bottom openings of the cartridge, and the reagent chamber, the mixing chamber, and the recovery chamber The through holes on the chamber and the elastic membrane do not overlap, so that the opening of the reagent chamber and one of the fluid pipes and the outlet of the mixing chamber and the other fluid pipe A first one-way valve structure that can only exit and cannot enter is formed. Between the inlet of the mixing chamber and one of the fluid pipes, and between the opening of the recovery chamber and the other fluid pipe, only The second one-way valve structure that can enter but not exit.
所述的流体操控装置,优选地,在所述卡盒的顶部设置有气囊结构,用于对所 述卡盒的顶部进行全封闭,且除所述混匀腔室外,所述试剂腔室和回收腔室均通过导气结构与所述气囊结构相连通。In the fluid manipulation device, preferably, an airbag structure is provided on the top of the cartridge for fully enclosing the top of the cartridge, and except for the mixing chamber, the reagent chamber and The recovery chambers are all communicated with the airbag structure through the air guiding structure.
所述的流体操控装置,优选地,所述气囊结构包含但不限于密封管、密封膜和弹性气囊;所述导气结构包含但不限于导气孔、导气槽和导气管道。In the fluid manipulation device, preferably, the airbag structure includes but is not limited to a sealing tube, a sealing film and an elastic airbag; the air guiding structure includes but is not limited to an air guiding hole, an air guiding groove and an air guiding pipe.
所述的流体操控装置,优选地,所述弹性膜选用双面胶基材,经过局部去粘性处理。In the fluid manipulation device, preferably, the elastic film is made of a double-sided tape base material and undergoes partial de-tackification treatment.
所述的流体操控装置,优选地,所述试剂腔室和混匀腔室内预存有液状反应试剂,所述回收腔室内预存有检测用的显色剂或试纸条,所述流体管道内预存有干粉状反应试剂。In the fluid manipulation device, preferably, a liquid reaction reagent is pre-stored in the reagent chamber and the mixing chamber, a color developer or test strip for detection is pre-stored in the recovery chamber, and the fluid pipe is pre-stored There are dry powder reaction reagents.
一种基于上述流体操控装置的流体控制方法,包括以下步骤:A fluid control method based on the above-mentioned fluid control device includes the following steps:
1)在试剂腔室内预置试剂,在混匀腔室内预置试剂;1) Preset reagents in the reagent chamber, and preset reagents in the mixing chamber;
2)对试剂腔室施加正压,试剂腔室的开口和混匀腔室的进口之间的第一单向阀结构和第二单向阀结构在正压作用下均打开,试剂经其中一流体管道进入混匀腔室,与混匀腔室内的试剂接触;由于混匀腔室内空气具有压缩性,混匀腔室的出口与另一流体管道之间的第一单向阀未被打开;2) Apply positive pressure to the reagent chamber, the first check valve structure and the second check valve structure between the opening of the reagent chamber and the inlet of the mixing chamber are both opened under the action of positive pressure, and the reagent passes through one of them. The fluid pipeline enters the mixing chamber and contacts the reagent in the mixing chamber; due to the compressibility of the air in the mixing chamber, the first one-way valve between the outlet of the mixing chamber and the other fluid pipeline is not opened;
3)继续对试剂腔室施加正压,空气进入混匀腔室,试剂与试剂在气泡振荡的作用下迅速混匀;3) Continue to apply positive pressure to the reagent chamber, air enters the mixing chamber, and the reagent and reagent are quickly mixed under the action of bubble oscillation;
4)当混匀腔室内部气压达到临界值时,混匀腔室的出口与回收腔室的开口之间的第一单向阀结构和第二单向阀结构在正压作用下均打开,混匀后的试剂经另一流体管道进入回收腔室。4) When the air pressure inside the mixing chamber reaches a critical value, the first check valve structure and the second check valve structure between the outlet of the mixing chamber and the opening of the recovery chamber are both opened under the action of positive pressure, The mixed reagent enters the recovery chamber through another fluid pipe.
本发明由于采取以上技术方案,其具有以下优点:1、本发明提供的流体操控装置不依赖于外部任何仪器的控制与操作,只需若干次简单的施压动作即可完成试剂定量、混匀以及试剂转移操作。2、本发明使用疏水膜实现施压动作过程中的流体限位,通过疏水膜与下层芯片上的定量池实现微升级别液体的准确定量,解决了微流控芯片上定量困难的问题。3、本发明在实现一步法流体混匀转移时,向密闭的试剂腔室内先后通入液体和气体,通入液体时实现不同试剂的混匀,通入气体时实现气体压缩及液体泵出,可以通过一步的施加正压实现试剂混匀和转移两个步骤,简化了微流控芯片流体控制的操作。4、本发明提供的流体操控装置通过导气孔和密封膜实现反应腔室的连通和封闭,可以实现整个反应体系的全封闭,从而可以有效避免污染物泄漏、气溶胶污染等问题。The present invention has the following advantages due to the above technical scheme: 1. The fluid manipulation device provided by the present invention does not rely on the control and operation of any external instrument, and only a few simple pressure actions can complete reagent quantification and mixing. And the reagent transfer operation. 2. The present invention uses the hydrophobic membrane to realize the fluid limit during the pressing action, and realizes the accurate quantification of the micro-level liquid through the hydrophobic membrane and the quantification pool on the lower chip, which solves the problem of difficult quantification on the microfluidic chip. 3. When the present invention realizes the one-step fluid mixing and transfer, the liquid and gas are successively introduced into the closed reagent chamber, the different reagents are mixed when the liquid is introduced, and the gas is compressed and the liquid is pumped out when the gas is introduced. The two steps of reagent mixing and transfer can be realized by applying positive pressure in one step, which simplifies the operation of fluid control of the microfluidic chip. 4. The fluid control device provided by the present invention realizes the communication and sealing of the reaction chamber through the air guide hole and the sealing film, and can realize the complete sealing of the entire reaction system, thereby effectively avoiding problems such as pollutant leakage and aerosol pollution.
附图说明Description of the drawings
图1是本发明实施例一中流体操控装置的结构示意图;Fig. 1 is a schematic structural diagram of a fluid manipulation device in the first embodiment of the present invention;
图2(a)和图1(b)是本发明实施例一实现微量流体定量的原理示意图;Figures 2(a) and 1(b) are schematic diagrams of the principle of realizing micro-fluid quantification in the first embodiment of the present invention;
图3是本发明实施例二中流体操控装置的结构示意图;3 is a schematic diagram of the structure of the fluid manipulation device in the second embodiment of the present invention;
图4(a)至图2(d)是本发明实施例二实现一步法流体混匀转移的原理示意图;Figures 4(a) to 2(d) are schematic diagrams of the principle of implementing one-step fluid mixing and transfer in the second embodiment of the present invention;
图5是本发明一种全封闭流体操控装置的结构示意图;Figure 5 is a schematic structural diagram of a fully enclosed fluid manipulation device of the present invention;
图6是本发明一种全封闭流体操控装置的原理示意图。Fig. 6 is a schematic diagram of the principle of a fully enclosed fluid manipulation device of the present invention.
具体实施方式Detailed ways
以下将结合附图对本发明的较佳实施例进行详细说明,以便更清楚理解本发明的目的、特点和优点。应理解的是,附图所示的实施例并不是对本发明范围的限制,而只是为了说明本发明技术方案的实质精神。Hereinafter, the preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings in order to understand the purpose, features and advantages of the present invention more clearly. It should be understood that the embodiments shown in the drawings do not limit the scope of the present invention, but merely illustrate the essential spirit of the technical solution of the present invention.
实施例一:Example one:
图1、图2展示根据本发明实施例一提供的可以实现微量流体定量功能的流体操控装置,该流体操控装置包括:卡盒1,其上形成有控制腔室6、试剂腔室8和回收腔室10,且控制腔室6、试剂腔室8和回收腔室10的底部均形成有一开口;下层芯片2,其上形成有定量池11;弹性膜3,用于将下层芯片2键合在卡盒1的底部,且弹性膜3上开设有与卡盒1底部开口数目相同的通孔,其中控制腔室6的开口与弹性膜3上的通孔重合,以使控制腔室6与定量池11相连通;试剂腔室8和回收腔室10的开口均与弹性膜3上的通孔不重合,以使试剂腔室8的开口与定量池11之间形成只能出不能进的第一单向阀结构15,回收腔室10的开口与定量池11之间形成只能进不能出的第二单向阀结构18;疏水膜4,设置在位于控制腔室6与定量池11之间的弹性膜3通孔处,该疏水膜4可供空气通过,但阻挡液体通过。Figures 1 and 2 show a fluid manipulation device capable of realizing the quantitative function of microfluid provided by the first embodiment of the present invention. The fluid manipulation device includes: a cartridge 1 on which a control chamber 6, a reagent chamber 8 and a recovery chamber are formed. An opening is formed at the bottom of the chamber 10, the control chamber 6, the reagent chamber 8 and the recovery chamber 10; the lower chip 2 has a quantitative cell 11 formed thereon; the elastic membrane 3 is used to bond the lower chip 2 At the bottom of the card box 1, and the elastic membrane 3 is provided with the same number of through holes as the bottom openings of the card box 1, wherein the opening of the control chamber 6 coincides with the through hole on the elastic membrane 3, so that the control chamber 6 and The quantitative cell 11 is connected; the openings of the reagent chamber 8 and the recovery chamber 10 are not overlapped with the through holes on the elastic membrane 3, so that the opening of the reagent chamber 8 and the quantitative cell 11 can only exit and cannot enter. The first one-way valve structure 15 forms a second one-way valve structure 18 between the opening of the recovery chamber 10 and the dosing tank 11, which can only enter and cannot go out; the hydrophobic membrane 4 is arranged in the control chamber 6 and the dosing tank 11. At the through hole of the elastic membrane 3 in between, the hydrophobic membrane 4 can allow air to pass through, but block liquid from passing through.
在上述实施例中,优选地,控制腔室6可以采用推杆活塞结构、外接气泵或注射泵等气压源实现控制;试剂腔室8内预存有液状反应试剂,回收腔室10内预存有检测用的显色剂或试纸条;定量池11的容积为20-100μL,内部可以预存干粉状反应试剂。In the above-mentioned embodiment, preferably, the control chamber 6 can be controlled by a push rod piston structure, an external air pump or a syringe pump and other air pressure sources; the reagent chamber 8 is pre-stored with liquid reaction reagents, and the recovery chamber 10 is pre-stored with detection Chromogenic reagent or test strip used; the volume of the quantitative cell 11 is 20-100 μL, and the dry powder reaction reagent can be pre-stored inside.
在上述实施例中,优选地,弹性膜3可选用双面胶基材,经过局部去粘性处理,既可实现单向阀功能,又能实现卡盒1和下层芯片2的键合。In the above-mentioned embodiment, preferably, the elastic film 3 can be a double-sided adhesive substrate, and after partial detackification treatment, it can not only realize the one-way valve function, but also realize the bonding of the cartridge 1 and the lower chip 2.
基于上述实施例提供的流体操控装置,本发明还提出了一种基于该流体操控装置的流体控制方法,包括以下步骤:Based on the fluid manipulation device provided in the above embodiments, the present invention also provides a fluid control method based on the fluid manipulation device, which includes the following steps:
1)对控制腔室6施加负压,试剂腔室8与定量池11之间的第一单向阀结构15在负压作用下打开,试剂腔室8的液体流入定量池11中,但无法穿过疏水膜4进 入控制腔室6;同时回收腔室10与定量池11之间的第二单向阀结构18在负压作用下保持关闭(如图2(a)所示)。1) A negative pressure is applied to the control chamber 6, the first one-way valve structure 15 between the reagent chamber 8 and the dosing cell 11 is opened under the action of the negative pressure, and the liquid in the reagent chamber 8 flows into the dosing cell 11, but cannot Pass through the hydrophobic membrane 4 and enter the control chamber 6; meanwhile, the second one-way valve structure 18 between the recovery chamber 10 and the dosing cell 11 is kept closed under the action of negative pressure (as shown in Fig. 2(a)).
2)对控制腔室6施加正压,试剂腔室8与定量池11之间的第一单向阀结构15在正压作用下关闭,而回收腔室10与定量池11之间的第二单向阀结构18在正压作用下打开,此时定量池11内的液体流入回收腔室10中,且流入回收腔室10内的液体体积与定量池11的容积相等(如图2(b)所示)。2) A positive pressure is applied to the control chamber 6, the first one-way valve structure 15 between the reagent chamber 8 and the dosing cell 11 is closed under the positive pressure, and the second one between the recovery chamber 10 and the dosing cell 11 is closed. The one-way valve structure 18 is opened under positive pressure. At this time, the liquid in the dosing tank 11 flows into the recovery chamber 10, and the volume of the liquid flowing into the recovery chamber 10 is equal to the volume of the dosing tank 11 (Figure 2(b) ) Shown).
实施例二:Embodiment two:
图3、图4展示根据本发明实施例二提供的可以实现一步法流体混匀转移功能的流体操控装置,该流体操控装置包括:卡盒1,其上形成有试剂腔室8、混匀腔室9和回收腔室10,且试剂腔室8和回收腔室10的底部均形成有一开口,混匀腔室9为密闭腔室且其底部形成有一进口和一出口;下层芯片2,其上形成有至少两个不连通的流体管道19;弹性膜3,用于将下层芯片2键合在卡盒1的底部,弹性膜3上开设有与卡盒1底部开口数目相同的通孔,且试剂腔室8、混匀腔室9和回收腔室10与弹性膜3上的通孔均不重合,以使试剂腔室8的开口与其中一流体管道19之间以及混匀腔室9的出口与另一流体管道19之间形成只能出不能进的第一单向阀结构15,混匀腔室9的进口与其中一流体管道19之间以及回收腔室10的开口与另一流体管道19之间形成只能进不能出的第二单向阀结构18。Figures 3 and 4 show a fluid manipulation device that can realize the function of one-step fluid mixing and transfer according to the second embodiment of the present invention. The fluid manipulation device includes: a cartridge 1 on which a reagent chamber 8 and a mixing chamber are formed The bottom of the chamber 9 and the recovery chamber 10, and the reagent chamber 8 and the recovery chamber 10 are both formed with an opening. The mixing chamber 9 is a closed chamber with an inlet and an outlet formed at the bottom; the lower chip 2 has an opening on it. At least two disconnected fluid pipes 19 are formed; an elastic membrane 3 is used to bond the lower chip 2 to the bottom of the card box 1, and the elastic membrane 3 is provided with the same number of through holes as the bottom openings of the card box 1, and The reagent chamber 8, the mixing chamber 9, and the recovery chamber 10 do not overlap with the through holes on the elastic membrane 3, so that the opening of the reagent chamber 8 and one of the fluid pipes 19 and the mixing chamber 9 The first one-way valve structure 15 is formed between the outlet and the other fluid pipe 19, which can only go out and cannot enter, between the inlet of the mixing chamber 9 and one of the fluid pipes 19, and the opening of the recovery chamber 10 and the other fluid. A second one-way valve structure 18 that can only enter and cannot exit is formed between the pipes 19.
在上述实施例中,优选地,如图5、图6所示,在卡盒1的顶部设置有气囊结构20,用于对卡盒1的顶部进行全封闭,且除混匀腔室9外,试剂腔室8和回收腔室10均通过导气结构14与气囊结构20相连通。In the above-mentioned embodiment, preferably, as shown in Figures 5 and 6, an airbag structure 20 is provided on the top of the cartridge 1 for fully enclosing the top of the cartridge 1, except for the mixing chamber 9. , Both the reagent chamber 8 and the recovery chamber 10 are connected to the airbag structure 20 through the air guiding structure 14.
在上述实施例中,优选地,气囊结构20包含但不限于密封管、密封膜和弹性气囊等。In the above-mentioned embodiment, preferably, the airbag structure 20 includes, but is not limited to, a sealing tube, a sealing film, an elastic airbag, and the like.
在上述实施例中,优选地,导气结构14包含但不限于导气孔、导气槽和导气管道等。In the above embodiment, preferably, the air guiding structure 14 includes but not limited to air guiding holes, air guiding grooves, air guiding pipes, and the like.
在上述实施例中,优选地,试剂腔室8和混匀腔室9内预存有液状反应试剂,回收腔室10内预存有检测用的显色剂或试纸条;流体管道19内可以预存干粉状反应试剂。In the above embodiment, preferably, the reagent chamber 8 and the mixing chamber 9 are pre-stored with liquid reaction reagents, and the recovery chamber 10 is pre-stored with a color developer or test strip for detection; the fluid pipe 19 can be pre-stored Dry powder reaction reagent.
在上述实施例中,优选地,弹性膜3可选用双面胶基材,经过局部去粘性处理,既可实现单向阀功能,又能实现卡盒1和下层芯片2的键合。In the above-mentioned embodiment, preferably, the elastic film 3 can be a double-sided adhesive substrate, and after partial detackification treatment, it can not only realize the one-way valve function, but also realize the bonding of the cartridge 1 and the lower chip 2.
基于上述实施例提供的流体操控装置,本发明还提出了一种该流体操控装置的流体控制方法,包括以下步骤:Based on the fluid manipulation device provided in the foregoing embodiment, the present invention also provides a fluid control method of the fluid manipulation device, which includes the following steps:
1)在试剂腔室8内预存试剂A,在混匀腔室9内预存试剂B(如图4(a)所示)。1) Reagent A is pre-stored in the reagent chamber 8 and reagent B is pre-stored in the mixing chamber 9 (as shown in Figure 4(a)).
2)对试剂腔室8施加正压,试剂腔室8的开口和混匀腔室9的进口之间的第一单向阀结构15和第二单向阀结构18在正压作用下均打开,试剂A经其中一流体管道19进入混匀腔室9,与混匀腔室9内的试剂B接触;由于混匀腔室9内空气具有压缩性,混匀腔室9的出口与另一流体管道19之间的第一单向阀15未被打开(如图4(b)所示)。2) A positive pressure is applied to the reagent chamber 8, and the first check valve structure 15 and the second check valve structure 18 between the opening of the reagent chamber 8 and the inlet of the mixing chamber 9 are both opened under the positive pressure , Reagent A enters the mixing chamber 9 through one of the fluid pipes 19, and contacts the reagent B in the mixing chamber 9; because the air in the mixing chamber 9 is compressible, the outlet of the mixing chamber 9 is The first one-way valve 15 between the fluid pipes 19 is not opened (as shown in Fig. 4(b)).
3)继续对试剂腔室8施加正压,空气进入混匀腔室9,试剂A与试剂B在气泡振荡的作用下迅速混匀(如图4(c)所示)。3) Continue to apply positive pressure to the reagent chamber 8, air enters the mixing chamber 9, and reagent A and reagent B are quickly mixed under the action of bubble oscillation (as shown in Figure 4(c)).
4)当混匀腔室9内部气压达到临界值时,混匀腔室9的出口与回收腔室10的开口之间的第一单向阀结构15和第二单向阀结构18在正压作用下均打开,混匀后的试剂经另一流体管道19进入回收腔室10(如图4(d)所示)。4) When the internal pressure of the mixing chamber 9 reaches a critical value, the first one-way valve structure 15 and the second one-way valve structure 18 between the outlet of the mixing chamber 9 and the opening of the recovery chamber 10 are at a positive pressure Both are opened under the action, and the mixed reagent enters the recovery chamber 10 through another fluid pipe 19 (as shown in Fig. 4(d)).
需要指出的是,在上述实施例中,流体操控装置采用类似磁带卡盒形状,但在不脱离本发明创造本质的情况下,流体操控装置也可以针对特定实际应用进行变体,例如在结构上可以有以下几种变体:①卡盒1的形状可因加工方式、功能需求进行调整,具体可为长方体、圆柱体、圆台等形状组合;②卡盒1上各腔室排列顺序可因功能需求进行相应的调整;③针对卡盒1上各腔室排列顺序,下层芯片2上的定量池11或流体通道19排布也可进行相应的调整;④卡盒1上的控制腔室6或混匀腔室9的数目可以根据需求进行调整,而下层芯片2上的定量池11或流体通道19的数目可以根据需求进行调整。It should be pointed out that in the above embodiments, the fluid manipulation device adopts a shape similar to a tape cartridge, but without departing from the essence of the invention, the fluid manipulation device can also be modified for specific practical applications, for example, in terms of structure. The following variants are possible: ①The shape of the cartridge 1 can be adjusted according to the processing method and functional requirements, and it can be a combination of rectangular, cylindrical, and truncated cone shapes; ②The order of the chambers on the cartridge 1 can be adjusted according to the function Corresponding adjustments are required; ③For the order of the chambers on the cartridge 1, the arrangement of the dosing cell 11 or the fluid channel 19 on the lower chip 2 can also be adjusted accordingly; ④The control chamber 6 or the control chamber on the cartridge 1 The number of mixing chambers 9 can be adjusted according to requirements, and the number of quantitative cells 11 or fluid channels 19 on the lower chip 2 can be adjusted according to requirements.
最后应说明的是:以上实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: The technical solutions recorded in the foregoing embodiments are modified, or some of the technical features thereof are equivalently replaced; these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

  1. 一种流体操控装置,用于实现微量流体定量功能,其特征在于,该流体操控装置包括:A fluid manipulation device for realizing the quantitative function of trace fluid, characterized in that the fluid manipulation device includes:
    卡盒(1),其上形成有控制腔室(6)、试剂腔室(8)和回收腔室(10),且所述控制腔室(6)、试剂腔室(8)和回收腔室(10)的底部均形成有一开口;The cartridge (1) has a control chamber (6), a reagent chamber (8) and a recovery chamber (10) formed thereon, and the control chamber (6), the reagent chamber (8) and the recovery chamber An opening is formed at the bottom of the chamber (10);
    下层芯片(2),其上形成有定量池(11);The lower chip (2), on which is formed a dosing cell (11);
    弹性膜(3),用于将所述下层芯片(2)键合在所述卡盒(1)的底部,且所述弹性膜(3)上开设有与所述卡盒(1)底部开口数目相同的通孔,其中所述控制腔室(6)的开口与所述弹性膜(3)上的通孔重合,以使所述控制腔室(6)与所述定量池(11)相连通;所述试剂腔室(8)和回收腔室(10)的开口均与所述弹性膜(3)上的通孔不重合,以使所述试剂腔室(8)的开口与所述定量池(11)之间形成只能出不能进的第一单向阀结构(15),所述回收腔室(10)的开口与所述定量池(11)之间形成只能进不能出的第二单向阀结构(18);The elastic film (3) is used to bond the lower chip (2) to the bottom of the card box (1), and the elastic film (3) is provided with an opening at the bottom of the card box (1) The same number of through holes, wherein the opening of the control chamber (6) coincides with the through hole on the elastic membrane (3), so that the control chamber (6) is connected with the quantitative cell (11) The openings of the reagent chamber (8) and the recovery chamber (10) are not overlapped with the through holes on the elastic membrane (3), so that the opening of the reagent chamber (8) and the The first one-way valve structure (15) is formed between the dosing tank (11), which can only enter and cannot enter. The opening of the recovery chamber (10) and the dosing tank (11) are formed with only access but not exit. The second one-way valve structure (18);
    疏水膜(4),设置在位于所述控制腔室(6)与所述定量池(11)之间的所述弹性膜(3)通孔处。The hydrophobic membrane (4) is arranged at the through hole of the elastic membrane (3) located between the control chamber (6) and the dosing cell (11).
  2. 根据权利要求1所述的流体操控装置,其特征在于,所述弹性膜(3)选用双面胶基材,经过局部去粘性处理。The fluid manipulation device according to claim 1, wherein the elastic film (3) is a double-sided adhesive base material, which has undergone a partial detackification treatment.
  3. 根据权利要求1所述的流体操控装置,其特征在于,所述控制腔室(6)采用推杆活塞结构、外接气泵或注射泵实现控制;所述试剂腔室(8)内预存有液状反应试剂,所述回收腔室(10)内预存有检测用的显色剂或试纸条;所述定量池(11)的容积为20-100μL,内部预存有干粉状反应试剂。The fluid control device according to claim 1, wherein the control chamber (6) adopts a push rod piston structure, an external air pump or a syringe pump to achieve control; a liquid reaction is pre-stored in the reagent chamber (8) Reagents, the recovery chamber (10) is pre-stored with a developer or test strip for detection; the volume of the quantitative cell (11) is 20-100 μL, and a dry powder reaction reagent is pre-stored inside.
  4. 一种基于权利要求1到3任一项所述流体操控装置的流体控制方法,其特征在于,包括以下步骤:A fluid control method based on the fluid control device according to any one of claims 1 to 3, characterized in that it comprises the following steps:
    1)对控制腔室(6)施加负压,试剂腔室(8)与定量池(11)之间的第一单向阀结构(15)在负压作用下打开,试剂腔室(8)的液体流入定量池(11)中,但无法穿过疏水膜(4)进入控制腔室(6);同时回收腔室(10)与定量池(11)之间的第二单向阀结构(18)在负压作用下保持关闭;1) Apply negative pressure to the control chamber (6), the first one-way valve structure (15) between the reagent chamber (8) and the dosing cell (11) is opened under the action of the negative pressure, and the reagent chamber (8) The liquid flows into the dosing tank (11), but cannot pass through the hydrophobic membrane (4) into the control chamber (6); at the same time, the second one-way valve structure between the recovery chamber (10) and the dosing tank (11) ( 18) Keep closed under negative pressure;
    2)对控制腔室(6)施加正压,试剂腔室(8)与定量池(11)之间的第一单向阀结构(15)在正压作用下关闭,而回收腔室(10)与定量池(11)之间的第二单向阀结构(18)在正压作用下打开,此时定量池(11)内的液体流入回收腔室(10)中,且流入回收腔室(10)内的液体体积与定量池(11)的容积相等。2) Positive pressure is applied to the control chamber (6), the first one-way valve structure (15) between the reagent chamber (8) and the dosing cell (11) is closed under the positive pressure, and the recovery chamber (10) The second one-way valve structure (18) between) and the dosing tank (11) is opened under positive pressure. At this time, the liquid in the dosing tank (11) flows into the recovery chamber (10) and flows into the recovery chamber The volume of the liquid in (10) is equal to the volume of the dosing cell (11).
  5. 一种流体操控装置,用于实现一步法流体混匀转移功能,其特征在于,该 流体操控装置包括:A fluid manipulation device for realizing the function of one-step fluid mixing and transfer, characterized in that the fluid manipulation device includes:
    卡盒(1),其上形成有试剂腔室(8)、混匀腔室(9)和回收腔室(10),且所述试剂腔室(8)和回收腔室(10)的底部均形成有一开口,所述混匀腔室(9)为密闭腔室且其底部形成有一进口和一出口;The cartridge (1) has a reagent chamber (8), a mixing chamber (9) and a recovery chamber (10) formed thereon, and the bottom of the reagent chamber (8) and the recovery chamber (10) Each is formed with an opening, the mixing chamber (9) is a closed chamber, and an inlet and an outlet are formed at the bottom of the mixing chamber (9);
    下层芯片(2),其上形成有至少两个不连通的流体管道(19);The lower chip (2), on which at least two disconnected fluid pipes (19) are formed;
    弹性膜(3),用于将所述下层芯片(2)键合在所述卡盒(1)的底部,所述弹性膜(3)上开设有与所述卡盒(1)底部开口数目相同的通孔,且所述试剂腔室(8)、混匀腔室(9)和回收腔室(10)与所述弹性膜(3)上的通孔均不重合,以使所述试剂腔室(8)的开口与其中一所述流体管道(19)之间以及所述混匀腔室(9)的出口与另一所述流体管道(19)之间形成只能出不能进的第一单向阀结构(15),所述混匀腔室(9)的进口与其中一所述流体管道(19)之间以及所述回收腔室(10)的开口与另一所述流体管道(19)之间形成只能进不能出的第二单向阀结构(18)。The elastic film (3) is used to bond the lower chip (2) to the bottom of the card box (1), and the elastic film (3) is provided with a number of openings at the bottom of the card box (1) The same through holes, and the reagent chamber (8), mixing chamber (9), and recovery chamber (10) do not overlap with the through holes on the elastic membrane (3), so that the reagent Between the opening of the chamber (8) and one of the fluid pipes (19) and between the outlet of the mixing chamber (9) and the other fluid pipe (19), there are only outgoing and inaccessible The first one-way valve structure (15), between the inlet of the mixing chamber (9) and one of the fluid pipes (19), and the opening of the recovery chamber (10) and the other fluid A second one-way valve structure (18) that can only enter but not exit is formed between the pipes (19).
  6. 根据权利要求5所述的流体操控装置,其特征在于,在所述卡盒(1)的顶部设置有气囊结构(20),用于对所述卡盒(1)的顶部进行全封闭,且除所述混匀腔室(9)外,所述试剂腔室(8)和回收腔室(10)均通过导气结构(14)与所述气囊结构(20)相连通。The fluid manipulation device according to claim 5, characterized in that an airbag structure (20) is provided on the top of the card box (1) for fully enclosing the top of the card box (1), and Except for the mixing chamber (9), the reagent chamber (8) and the recovery chamber (10) are all connected with the air bag structure (20) through a gas guiding structure (14).
  7. 根据权利要求6所述的流体操控装置,其特征在于,所述气囊结构(20)包含但不限于密封管、密封膜和弹性气囊;所述导气结构(14)包含但不限于导气孔、导气槽和导气管道。The fluid manipulation device according to claim 6, characterized in that the airbag structure (20) includes but is not limited to a sealing tube, a sealing film and an elastic airbag; the air guiding structure (14) includes but is not limited to air guiding holes, Air duct and air duct.
  8. 根据权利要求5所述的流体操控装置,其特征在于,所述弹性膜(3)选用双面胶基材,经过局部去粘性处理。The fluid manipulation device according to claim 5, characterized in that the elastic film (3) is a double-sided adhesive base material, which has been partially detackified.
  9. 根据权利要求5所述的流体操控装置,其特征在于,所述试剂腔室(8)和混匀腔室(9)内预存有液状反应试剂,所述回收腔室(10)内预存有检测用的显色剂或试纸条,所述流体管道(19)内预存有干粉状反应试剂。The fluid manipulation device according to claim 5, wherein the reagent chamber (8) and the mixing chamber (9) are pre-stored with liquid reaction reagents, and the recovery chamber (10) is pre-stored with detection reagents. For the developer or test strip used, the fluid pipe (19) is pre-stored with a dry powdered reaction reagent.
  10. 一种基于权利要求5到9任一项所述流体操控装置的流体控制方法,其特征在于,包括以下步骤:A fluid control method based on the fluid control device according to any one of claims 5 to 9, characterized in that it comprises the following steps:
    1)在试剂腔室(8)内预置试剂(A),在混匀腔室(9)内预置试剂(B);1) Preset reagent (A) in the reagent chamber (8), and preset reagent (B) in the mixing chamber (9);
    2)对试剂腔室(8)施加正压,试剂腔室(8)的开口和混匀腔室(9)的进口之间的第一单向阀结构(15)和第二单向阀结构(18)在正压作用下均打开,试剂(A)经其中一流体管道(19)进入混匀腔室(9),与混匀腔室(9)内的试剂(B)接触;由于混匀腔室(9)内空气具有压缩性,混匀腔室(9)的出口与另一流体管 道(19)之间的第一单向阀(15)未被打开;2) Apply positive pressure to the reagent chamber (8), the first one-way valve structure (15) and the second one-way valve structure between the opening of the reagent chamber (8) and the inlet of the mixing chamber (9) (18) When both are opened under positive pressure, the reagent (A) enters the mixing chamber (9) through one of the fluid pipes (19), and contacts the reagent (B) in the mixing chamber (9); The air in the homogenization chamber (9) is compressible, and the first one-way valve (15) between the outlet of the homogenization chamber (9) and the other fluid pipe (19) is not opened;
    3)继续对试剂腔室(8)施加正压,空气进入混匀腔室(9),试剂(A)与试剂(B)在气泡振荡的作用下迅速混匀;3) Continue to apply positive pressure to the reagent chamber (8), air enters the mixing chamber (9), and the reagent (A) and the reagent (B) are quickly mixed under the action of bubble oscillation;
    4)当混匀腔室(9)内部气压达到临界值时,混匀腔室(9)的出口与回收腔室(10)的开口之间的第一单向阀结构(15)和第二单向阀结构(18)在正压作用下均打开,混匀后的试剂经另一流体管道(19)进入回收腔室(10)。4) When the internal pressure of the mixing chamber (9) reaches a critical value, the first check valve structure (15) and the second one-way valve structure (15) and the second one between the outlet of the mixing chamber (9) and the opening of the recovery chamber (10) The one-way valve structure (18) is all opened under the action of positive pressure, and the mixed reagent enters the recovery chamber (10) through another fluid pipe (19).
PCT/CN2020/092010 2020-05-25 2020-05-25 Fluid control device and fluid control method WO2021237397A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2020/092010 WO2021237397A1 (en) 2020-05-25 2020-05-25 Fluid control device and fluid control method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2020/092010 WO2021237397A1 (en) 2020-05-25 2020-05-25 Fluid control device and fluid control method

Publications (1)

Publication Number Publication Date
WO2021237397A1 true WO2021237397A1 (en) 2021-12-02

Family

ID=78745134

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/092010 WO2021237397A1 (en) 2020-05-25 2020-05-25 Fluid control device and fluid control method

Country Status (1)

Country Link
WO (1) WO2021237397A1 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114324753A (en) * 2021-12-21 2022-04-12 广州万孚生物技术股份有限公司 Reagent card
CN114570449A (en) * 2022-04-26 2022-06-03 广州国家实验室 Liquid transfer device and multi-path parallel liquid transfer device
CN114574324A (en) * 2022-04-26 2022-06-03 广州国家实验室 Sample extraction device
CN115181655A (en) * 2022-07-07 2022-10-14 四川华汉三创生物科技有限公司 Microfluidic card box for PCR amplification and hybridization reaction and use method thereof
CN115970781A (en) * 2023-03-21 2023-04-18 杭州霆科生物科技有限公司 Quantitative sample adding structure, concentration gradient micro-fluidic chip thereof and control method
WO2023206093A1 (en) * 2022-04-26 2023-11-02 广州国家实验室 Sample extraction device

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100641832B1 (en) * 2005-05-11 2006-11-02 한국생명공학연구원 A micro-well chip for bioreactor
CN107502544A (en) * 2017-09-20 2017-12-22 北京丰特云基科技发展有限公司 A kind of micro-fluidic chip detecting and controlling system
CN107541452A (en) * 2017-09-20 2018-01-05 清华大学 A kind of micro-fluidic chip and chip assembly
CN207552287U (en) * 2017-09-20 2018-06-29 清华大学 A kind of micro-fluidic chip and chip assembly
CN108728327A (en) * 2018-05-23 2018-11-02 博奥生物集团有限公司 A kind of full-automatic sample preparation microfluidic system and preparation method thereof and application method
CN110038655A (en) * 2019-05-20 2019-07-23 徐州昊洋生物科技有限公司 A kind of microfluidic control chip and system
CN110551681A (en) * 2019-09-12 2019-12-10 清华大学 micro-fluidic chip for simulating embryo implantation angiogenesis and preparation method and application thereof
CN110841730A (en) * 2019-10-21 2020-02-28 清华大学 Micro-fluidic chip and tumor DNA detection chip
CN111644213A (en) * 2020-05-25 2020-09-11 清华大学 Fluid control device and fluid control method

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100641832B1 (en) * 2005-05-11 2006-11-02 한국생명공학연구원 A micro-well chip for bioreactor
CN107502544A (en) * 2017-09-20 2017-12-22 北京丰特云基科技发展有限公司 A kind of micro-fluidic chip detecting and controlling system
CN107541452A (en) * 2017-09-20 2018-01-05 清华大学 A kind of micro-fluidic chip and chip assembly
CN207552287U (en) * 2017-09-20 2018-06-29 清华大学 A kind of micro-fluidic chip and chip assembly
CN108728327A (en) * 2018-05-23 2018-11-02 博奥生物集团有限公司 A kind of full-automatic sample preparation microfluidic system and preparation method thereof and application method
CN110038655A (en) * 2019-05-20 2019-07-23 徐州昊洋生物科技有限公司 A kind of microfluidic control chip and system
CN110551681A (en) * 2019-09-12 2019-12-10 清华大学 micro-fluidic chip for simulating embryo implantation angiogenesis and preparation method and application thereof
CN110841730A (en) * 2019-10-21 2020-02-28 清华大学 Micro-fluidic chip and tumor DNA detection chip
CN111644213A (en) * 2020-05-25 2020-09-11 清华大学 Fluid control device and fluid control method

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114324753A (en) * 2021-12-21 2022-04-12 广州万孚生物技术股份有限公司 Reagent card
CN114570449A (en) * 2022-04-26 2022-06-03 广州国家实验室 Liquid transfer device and multi-path parallel liquid transfer device
CN114574324A (en) * 2022-04-26 2022-06-03 广州国家实验室 Sample extraction device
WO2023206093A1 (en) * 2022-04-26 2023-11-02 广州国家实验室 Sample extraction device
CN115181655A (en) * 2022-07-07 2022-10-14 四川华汉三创生物科技有限公司 Microfluidic card box for PCR amplification and hybridization reaction and use method thereof
CN115970781A (en) * 2023-03-21 2023-04-18 杭州霆科生物科技有限公司 Quantitative sample adding structure, concentration gradient micro-fluidic chip thereof and control method
CN115970781B (en) * 2023-03-21 2024-01-12 杭州霆科生物科技有限公司 Quantitative sample adding structure, concentration gradient micro-fluidic chip and control method thereof

Similar Documents

Publication Publication Date Title
WO2021237397A1 (en) Fluid control device and fluid control method
CN111644213B (en) Fluid control device and fluid control method
US6536477B1 (en) Fluidic couplers and modular microfluidic systems
EP3698872B1 (en) Microfluidic detection chip for multi-channel quick detecting
US7666687B2 (en) Miniaturized fluid delivery and analysis system
US20200094252A1 (en) Microfluidic chip for separating and detecting whole blood sample and detection method thereof
US20110146390A1 (en) Process for Continuous On-Chip Flow Injection Analysis
US8309039B2 (en) Valve structure for consistent valve operation of a miniaturized fluid delivery and analysis system
US9248448B2 (en) Multisample bionanochip platform
WO2006123578A1 (en) Testing chip for analyzing target substance contained in analyte, and microscopic comprehensive analytical system
US10246675B2 (en) Biochemical cartridge, and biochemical cartridge and cartridge holder set
JP2011506939A (en) Microfluidic cartridge with solution reservoir-pump chamber
CN111804352A (en) Integrated exosome separation and detection microfluidic chip and application
US20220226813A1 (en) Microfluidic chip and manufacturing method therefor
KR20070121464A (en) Device for passive microfluidic washing using capillary force
CN113441194A (en) Micro-fluidic detection chip
CN111804351A (en) Integrated exosome separation and detection microfluidic chip and preparation method thereof
CN111468197B (en) Hydraulic-driven elastic diaphragm micro valve for centrifugal microfluidic system and preparation method thereof
CN103055984B (en) Driving device in micro-flow pipeline
Silverio et al. Lab-on-a-chip: Systems integration at the microscale
JP2006284451A (en) Micro total analysis system for analyzing target material in specimen
CN111500425B (en) Fluid control and processing cartridge
CN211800909U (en) Micro-fluidic detection chip
CN211999644U (en) Through hole type sealing cover for separating single cell microparticles in high flux
WO2023231158A1 (en) Handheld nucleic acid testing device having micro-fluidic chip, and use method therefor

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20938486

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20938486

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 20938486

Country of ref document: EP

Kind code of ref document: A1

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC

122 Ep: pct application non-entry in european phase

Ref document number: 20938486

Country of ref document: EP

Kind code of ref document: A1