CN111468197B - Hydraulic-driven elastic diaphragm micro valve for centrifugal microfluidic system and preparation method thereof - Google Patents

Hydraulic-driven elastic diaphragm micro valve for centrifugal microfluidic system and preparation method thereof Download PDF

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CN111468197B
CN111468197B CN202010286143.9A CN202010286143A CN111468197B CN 111468197 B CN111468197 B CN 111468197B CN 202010286143 A CN202010286143 A CN 202010286143A CN 111468197 B CN111468197 B CN 111468197B
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layer
control
pmma
chamber
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CN111468197A (en
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杜新
王松
王金龙
王海宇
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Changchun University of Science and Technology
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0638—Valves, specific forms thereof with moving parts membrane valves, flap valves

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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Abstract

The invention provides a hydraulic-driven elastic diaphragm micro valve for a centrifugal micro-fluid system and a preparation method thereof. The invention has the beneficial effects that: when the micro valve is not opened, the inner channel of the sample layer is closed, so that the sample cannot leak; the hydraulic pressure on the two sides of the micro valve is used for controlling the opening and closing of the micro valve, the rotary table and the capillary force of the liquid are used for driving the whole device, and extra power is not required; the control liquid in the control layer is completely separated from the sample liquid in the sample layer, the control liquid uses common deionized water, the flow is controlled by using a capillary passive valve, the manufacturing difficulty is low, the control layer can be repeatedly used, and the manufacturing and using cost is reduced; the method solves the flow control problem of the strong hydrophilic liquid, and is suitable for detecting hydrophilic and hydrophobic sample liquids.

Description

Hydraulic-driven elastic diaphragm micro valve for centrifugal microfluidic system and preparation method thereof
Technical Field
The invention belongs to the technical field of biochemical detection equipment, relates to a micro valve for controlling fluid flow in biochemical detection equipment by using a microfluidic system, and particularly relates to a water pressure driven elastic diaphragm micro valve for a centrifugal microfluidic system and a preparation method thereof.
Background
The centrifugal microfluidic system belongs to medical consumables, is widely applied to biochemical detection, can realize instant diagnosis, and can conveniently and quickly output a reaction result. The method is characterized in that the microfluidic structure is integrated on a wafer-shaped chip, and the flow of microfluid is driven by centrifugal force, so that the detection and analysis of a sample are realized. The centrifugal system can complete sample pretreatment, mixing, separation and detection of accurate volume and the like. In recent years, centrifugal microfluidic systems have been rapidly developed with the advantages of high throughput, high integration, multiple parallel analysis, portability, low cost, automation, small consumption of samples and reagents, and the like, and have been widely used in the fields of biochemical detection, immunoassay, nucleic acid amplification, environmental monitoring, cell sorting, food safety, and the like.
The centrifugal microfluidic system uses centrifugal force generated by rotation as driving force to complete sample preparation, detection and other functions on a disc-shaped turntable.
Corresponding microvalves are required to control fluid flow during operation of the microfluidic system. The micro valve is divided into two types, namely, an active valve which needs an external power source to drive a diaphragm to move so as to switch on and off the micro valve; the other is a passive valve which has no moving part and uses the liquid surface bending when the channel size suddenly expands to stop the liquid flow by the generated capillary force.
Centrifugal microfluidic systems are commonly used in the prior art to control fluid flow using capillary passive valves. This is mainly because: the capillary passive valve has no movable part, and is convenient to manufacture and integrate; external power sources are difficult to integrate on a rotating platform.
However, in biochemical detection, many biological samples and reagents have strong hydrophilicity, so that the liquid level cannot stop at the expansion section of the pipeline, and further the passive valve fails.
The current solutions to this problem mainly include the following:
the first scheme is as follows: and sealing the pipeline by using paraffin, melting the paraffin by using an external light source, and opening the micro valve.
Scheme II: and sealing the pipeline by using paraffin, melting the paraffin by using an external heat source, and opening the micro valve.
The third scheme is as follows: diaphragm valves are used, using pneumatic or piezoelectric effects to actuate diaphragm switches.
However, the schemes have certain limitations, for example, the schemes one and two require an external power source, which is not favorable for system integration; the need to precisely locate and control the exotherm is not applicable to heat sensitive biological samples and reagents. In the third scheme, a great deal of difficulty exists in the process of integrating an external air source and a circuit on the rotary table.
Therefore, there is an urgent need to develop a new centrifugal microfluidic platform to solve the flow control problem of such strongly hydrophilic liquid.
Disclosure of Invention
In order to make up the defects of the prior art, the invention provides a hydraulic-driven elastic diaphragm micro valve for a centrifugal micro-fluid system and a preparation method thereof.
The invention provides a hydraulic-driven elastic diaphragm micro valve for a centrifugal micro-fluidic system, which is a diaphragm micro valve with a sample layer and a control layer separated from each other; the liquid in the control layer is deionized water, and is driven by capillary and centrifugal force, and the micro valve is switched on and off by hydraulic pressure on two sides of the control layer;
the elastic diaphragm micro valve comprises two parts, namely a sample layer and a control layer, wherein the sample layer sequentially comprises a first PDMS diaphragm sample layer, a first PMMA sample layer, a second PMMA sample layer and a second PDMS diaphragm sample layer from top to bottom; the control layers are a PDMS membrane control layer, a first PMMA control layer, a second PMMA control layer and a glass control layer from top to bottom respectively; the first PDMS membrane sample layer, the second PDMS membrane sample layer, the PDMS membrane control layer and the glass control layer have no internal structure, the first PMMA sample layer and the second PMMA sample layer are provided with sample layer internal through hole structures, and the first PMMA control layer and the second PMMA control layer are also provided with control layer internal through hole structures;
the sample layer and the control layer are arranged in an up-and-down overlapping mode, positioned through the positioning holes and bound on the rotary table through the adhesive tape.
The through hole structure in the control layer comprises a positioning hole, a first injection chamber, a first inflow channel, a control chamber, a first capillary valve, a first siphon, a second capillary valve, a first waste liquid pool, an overflow valve and a second waste liquid pool;
the positioning hole is an independent structure and is used for aligning and positioning the control layer and the sample layer during installation; the first injection hole is arranged right above the first injection chamber and used for injecting deionized water; the first injection chamber is connected with an inlet of the control chamber through the first inflow channel, an outlet of the control chamber is connected with an inlet of the first siphon through the first capillary valve, an outlet of the first siphon is connected with the first waste liquid pool through the second capillary valve, and the overflow valve is arranged at a connection position between the first injection chamber and the second waste liquid pool.
The sample layer comprises a positioning hole, a second injection chamber, a sample chamber, a detection chamber, a second siphon, a third capillary valve and a third waste liquid pool;
the positioning hole is an independent structure and is used for aligning and positioning the control layer and the sample layer during installation; the second injection hole is arranged right above the second injection chamber and is used for injecting a sample; the second injection chamber is connected with the sample chamber, the outlet of the sample chamber is connected with the inlet of the second siphon, and the outlet of the second siphon is connected with the third waste liquid tank through the third capillary valve; the detection chamber is arranged below the sample chamber and is separated by the PDMS membrane and the PMMA rib structure.
Further, the working process of the control layer is as follows: deionized water is used as a control liquid and is dripped from the first injection chamber, and the control liquid flows into the control chamber along the first inflow channel and stops at the first capillary valve due to the hydrophilicity of the glass control layer; meanwhile, the control liquid is stopped after reaching the inlet of the second waste liquid pool from the injection chamber through the overflow valve; then, the rotary table rotates, in the rotating process, the first capillary valve is opened, the control liquid flows into the first siphon, but the height of the top end of the first siphon is higher than the height of the inlet of the first inflow channel, the control liquid cannot flow out of the control chamber, and the micro valve is in a closed state; the rotary table stops rotating, and the control liquid stops after advancing to a second capillary valve at the outlet of the first siphon along the first siphon; the rotary table rotates again, due to siphoning, the control liquid flows out of the control chamber through the first siphon, meanwhile, a sample in the sample chamber above the control layer presses open the control layer diaphragm due to centrifugal force, the micro valve is opened, and the sample layer liquid flows out of the micro valve.
Further, the working process of the sample layer is as follows: initially, puncturing the first PDMS membrane sample layer above the second injection chamber with a pipette, and injecting a sample liquid, wherein if the sample liquid is hydrophobic, the sample liquid stays in the second injection chamber, and if the sample liquid is hydrophilic, the sample liquid flows into the sample chamber above the membrane; the rotary table rotates, and under the action of centrifugal force, sample liquid flows into the sample chamber above the micro valve; at the position of the micro valve, the pressure generated by the liquid below is greater than the pressure generated by the sample liquid in the sample layer, so that the micro valve is closed, and the sample liquid in the sample layer can complete the functions of quantification, separation and mixing in the sample chamber, but the micro valve cannot be opened actively; the rotary table stops rotating, and because of no centrifugal force, the pressures on the two sides of the micro valve are the same, and the micro valve cannot be opened; and the turntable rotates again, the control liquid flows out of the control chamber through the first siphon, when the turntable reaches a sufficient rotating speed, the pressure of the upper liquid enables the PDMS membrane between the control chamber and the sample chamber to bend downwards, the micro valve is opened, and the sample liquid in the sample chamber flows into the detection chamber through the micro valve.
Furthermore, the first siphon is an inverted U-shaped siphon.
Further, the sample liquid is a biological sample or reagent.
Further, the pressure generated by the lower liquid and the pressure generated by the sample liquid of the sample layer are both centrifugal forces.
The invention also provides a preparation method of the hydraulic-driven elastic diaphragm micro valve for the centrifugal micro-fluidic system, which comprises the following steps:
preparing a PMMA layer: firstly, the method comprises the following steps of 1: 1, drawing a contour diagram of a required structure in proportion, and then cutting the required structure on a PMMA plate by laser according to the contour diagram; preparing a first PMMA sample layer, a second PMMA sample layer, a first PMMA control layer and a second PMMA control layer according to the method;
preparing a PDMS membrane: adsorbing a disc-shaped PC (polycarbonate) plate on a spin coater to serve as a bottom plate, and spin-coating a PDMS (polydimethylsiloxane) liquid film added with a curing agent on the bottom plate, wherein the thickness of the liquid film is related to the rotating speed and the rotating time; then heating to cure the PDMS liquid film to obtain a PDMS membrane; preparing a first PDMS membrane sample layer, a second PDMS membrane sample layer and a PDMS membrane control layer according to the method;
bonding of the first PDMS membrane sample layer and the first PMMA sample layer: carrying out plasma treatment on the plane of the first PDMS membrane sample layer to be bonded, and then attaching the plane of the first PDMS membrane sample layer to the corresponding plane of the first PMMA sample layer to realize bonding;
bonding the second PMMA sample layer and the second PDMS membrane sample layer: the second PMMA sample layer and the second PDMS membrane sample layer are separable at the membrane microvalve, without being bonded together; for other locations, the second PMMA sample layer and the second PDMS membrane sample layer remain bonded; in order to realize the functions, before bonding, firstly, an oil marking pen is used for smearing a layer of printing ink at the position of a membrane micro valve on a second PDMS membrane sample layer, then, a plane of the second PDMS membrane sample layer needing bonding is subjected to plasma treatment, and then, the plane is attached to the corresponding plane of the second PMMA sample layer to realize bonding;
bonding the first PMMA sample layer and the second PMMA sample layer: before preparing the second PMMA sample layer, adhering a double-sided adhesive tape on a required plane in advance, then carrying out laser processing, tearing off a double-sided adhesive tape protective film after the bonding of the third step and the fourth step is finished, and carrying out bonding between the first PMMA sample layer and the second PMMA sample layer through alignment of positioning holes; after the bonding is finished, preparing the sample layer;
bonding of the PDMS membrane control layer and the first PMMA control layer: carrying out plasma treatment on the plane of the PDMS membrane control layer to be bonded, and then attaching the plane to the corresponding plane of the first PMMA control layer to realize bonding;
bonding the second PMMA control layer with the first PMMA control layer and the glass control layer: before preparing the second PMMA control layer, adhering double-sided adhesive tapes on both sides of the second PMMA control layer in advance, then carrying out laser processing, tearing off the protective film of the double-sided adhesive tapes after the bonding of the step (c), and carrying out adhesion between the first PMMA control layer and the second PMMA control layer and between the second PMMA control layer and the glass control layer through alignment of the positioning holes; after the bonding is finished, the control layer is prepared;
aligning and installing a sample layer and a control layer: and (3) vertically stacking the sample layer and the control layer, namely, enabling the second PDMS membrane sample layer to be in contact with the PDMS membrane control layer, positioning through the positioning hole, and binding the sample layer and the control layer on the turntable through an adhesive tape to finish alignment and installation.
The elastic diaphragm micro valve for the hydraulic drive of the centrifugal micro-fluid system and the preparation method thereof have the following advantages:
firstly, when the elastic diaphragm micro valve is not opened, the channel in the sample layer is completely sealed, so that the leakage of a biological sample and a reagent can not be caused;
secondly, the hydraulic pressure on the two sides of the elastic diaphragm micro valve is used for controlling the opening and closing of the elastic diaphragm micro valve, the rotary table and the liquid capillary force are used for driving the whole device, and the hydraulic pressure on the two sides of the elastic diaphragm micro valve is controlled to open and close the micro valve without extra power;
thirdly, the control liquid in the control layer is completely separated from the sample liquid in the sample layer, the control liquid uses common deionized water, and the capillary passive valve is used for controlling the flow, so that the manufacturing difficulty is low;
fourthly, the control layer and the sample layer are manufactured respectively, the control layer can be used and cleaned repeatedly, and the manufacturing and using cost is greatly reduced;
fifthly, the flow control problem of the strong hydrophilic liquid is solved by adopting a unique sample layer and control layer structure, and the method is suitable for detecting hydrophilic and hydrophobic sample liquids.
Drawings
FIG. 1 is a schematic diagram of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 1 of the present invention;
FIG. 2 is a schematic diagram showing the structure of a first PMMA control layer in a hydraulically actuated elastic diaphragm microvalve for use in a centrifugal microfluidic system in example 1 of the present invention;
FIG. 3 is a schematic diagram showing the structure of a second PMMA control layer in a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 1 of the present invention;
FIG. 4 is a schematic diagram showing the structure of a first PMMA sample layer in a hydraulically actuated elastic diaphragm microvalve for use in a centrifugal microfluidic system in example 1 of the present invention;
FIG. 5 is a schematic diagram showing the structure of a second PMMA sample layer in a hydraulically actuated elastic diaphragm microvalve used in a centrifugal microfluidic system in example 1 of the present invention;
FIG. 6 is a schematic diagram showing the operation of a hydraulically actuated elastic diaphragm microvalve for use in a centrifugal microfluidic system in example 1 of the present invention;
FIG. 7 is a side view of a closed state of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 1 of the present invention;
FIG. 8 is a side view of an open state of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 1 of the present invention;
FIG. 9 is a schematic representation of a first step in the operation of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 2 of the present invention;
FIG. 10 is a schematic diagram of a second step in the operation of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 2 of the present invention;
FIG. 11 is a schematic diagram showing a third step in the operation of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 2 of the present invention;
FIG. 12 is a schematic diagram of the fourth step of the operation of a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system in accordance with example 2 of the present invention.
The reference numerals in the figures have the meaning: 1-sample layer, 2-control layer, 3-locating hole, 4-first filling hole, 5-first filling chamber, 6-first inflow channel, 7-control chamber, 8-first capillary valve, 9-first siphon, 10-second capillary valve, 11-first waste liquid pool, 12-overflow valve, 13-second waste liquid pool, 14-second filling hole, 15-second filling chamber, 16-sample chamber, 17-detection chamber, 18-second siphon, 19-third capillary valve and 20-third waste liquid pool.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are clearly and completely described, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A kind of elastic diaphragm microvalve used for water pressure drive of the centrifugal microfluid system, the said elastic diaphragm microvalve is the diaphragm microvalve that the sample layer 1 and control layer 2 separate; the liquid in the control layer 2 is deionized water, and the micro valve is switched on and off by utilizing capillary and centrifugal force driving and hydraulic pressure on two sides of the control layer 2.
The elastic diaphragm micro valve comprises two parts, namely a sample layer 1 and a control layer 2, wherein the sample layer 1 sequentially comprises a first PDMS diaphragm sample layer, a first PMMA sample layer, a second PMMA sample layer and a second PDMS diaphragm sample layer from top to bottom; the control layer 2 is a PDMS membrane control layer, a first PMMA control layer, a second PMMA control layer and a glass control layer from top to bottom; the first PDMS membrane sample layer, the second PDMS membrane sample layer, the PDMS membrane control layer and the glass control layer have no internal structure, the first PMMA sample layer and the second PMMA sample layer are provided with sample layer internal through hole structures, and the first PMMA control layer and the second PMMA control layer are also provided with control layer internal through hole structures; the sample layer 1 and the control layer 2 are placed in an up-and-down overlapping mode, positioned through the positioning holes 3 and bound on the rotary table through an adhesive tape, as shown in fig. 1.
The internal through hole structure shown in the control layer (as shown in fig. 2 and 3) comprises a positioning hole 3, a first injection hole 4, a first injection chamber 5, a first inflow channel 6, a control chamber 7, a first capillary valve 8, a first siphon 9, a second capillary valve 10, a first waste liquid pool 11, an overflow valve 12 and a second waste liquid pool 13;
the positioning hole 3 is an independent structure and is used for aligning and positioning the control layer 2 and the sample layer 1 during installation; the first injection hole 4 is arranged right above the first injection chamber 5 and is used for injecting deionized water; the first injection chamber 5 is connected with an inlet of the control chamber 7 through the first inflow channel 6, an outlet of the control chamber 7 is connected with an inlet of the first siphon 9 through the first capillary valve 8, an outlet of the first siphon 9 is connected with the first waste liquid pool 11 through the second capillary valve 10, and the overflow valve 12 is arranged at a connecting position between the first injection chamber 5 and the second waste liquid pool 13.
The through hole structure in the sample layer (as shown in fig. 4 and 5) comprises a positioning hole 3, a second injection hole 14, a second injection chamber 15, a sample chamber 16, a detection chamber 17, a second siphon 18, a third capillary valve 19 and a third waste liquid pool 20;
the positioning hole 3 is an independent structure and is used for aligning and positioning the control layer 2 and the sample layer 1 during installation; the second injection hole 14 is arranged right above the second injection chamber 15 and is used for injecting a sample; the second injection chamber 15 is connected with the sample chamber 16, the outlet of the sample chamber 16 is connected with the inlet of the second siphon 18, and the outlet of the second siphon 18 is connected with the third waste liquid pool 20 through the third capillary valve 19; the detection chamber 17 is below the sample chamber 16, and is separated by the seal of the PDMS membrane and the PMMA rib structure.
As shown in fig. 6, the operation process of the control layer 2 is as follows: deionized water is dripped from the injection chamber No. one 5 as a control liquid, and the control liquid flows into the control chamber No. 7 along the inflow channel No. one 6 due to the hydrophilicity of the glass control layer and stops at the capillary valve No. one 8; meanwhile, the control liquid is stopped after reaching the inlet of the second waste liquid pool 13 from the injection chamber 5 through the overflow valve 12; then, the turntable rotates, during the rotation, the first capillary valve 8 is opened, the control liquid flows into the first siphon 9, but because the height of the top end of the first siphon 9 is higher than the inlet height of the first inflow channel 6, the control liquid cannot flow out of the control chamber 7, and the micro valve is in a closed state as shown in fig. 7; the rotary table stops rotating, and the control liquid stops after advancing to a second capillary valve 10 at the outlet of the first siphon 9 along the first siphon 9; the turntable is rotated again, the control liquid flows out of the control chamber 7 through the first siphon 9 due to siphon, and simultaneously, the sample in the sample chamber 16 above the control layer 2 presses open the membrane of the control layer 2 due to centrifugal force, the micro valve is opened as shown in fig. 8, and the sample layer liquid flows out of the micro valve.
The working process of the sample layer 1 is as follows: initially, a pipettor is used to pierce the first PDMS membrane sample layer above the second injection chamber 15 and inject a sample fluid, which stays in the second injection chamber 15 if the sample fluid is hydrophobic, and flows into the sample chamber 16 above the membrane if the sample fluid is hydrophilic; the turntable is rotated, and under the action of centrifugal force, sample liquid flows into the sample chamber 16 above the micro valve; but at the microvalve, since the pressure generated by the liquid below is greater than the pressure generated by the sample liquid in the sample layer 1, the microvalve is closed as shown in fig. 7, and the sample liquid in the sample layer 1 can perform the functions of quantification, separation and mixing in the sample chamber 16, but the microvalve is not actively opened; the rotary table stops rotating, and because of no centrifugal force, the pressures on the two sides of the micro valve are the same, and the micro valve cannot be opened; when the turntable rotates again, the control liquid flows out of the control chamber 7 through the first siphon 9, when the turntable reaches a sufficient rotating speed, the upper liquid pressure bends the PDMS membrane between the control chamber 7 and the sample chamber 16 downwards, the micro valve is opened (as shown in fig. 8), and the sample liquid in the sample chamber 16 flows into the detection chamber 17 through the micro valve.
Example 2
As shown in fig. 9-12, a specific operation of a hydraulically actuated elastic diaphragm microvalve for a centrifugal microfluidic system is that, in a first step, a sample layer is filled with deionized water (hatched portion of the bar) (as shown in fig. 9), and it can be seen that, because the microvalve is closed, the channel communicating with the sample chamber 16 is closed, a portion of the gas cannot be discharged, and deionized water (hatched portion of the bar) does not enter the control chamber 7; secondly, the control chamber 7 is filled with deionized water (hatched part of vertical bar) (as shown in fig. 10), and the liquid (hatched part of horizontal bar) fills the control chamber 7 and stops at the first capillary valve 8; thirdly, the turntable is stopped after rotating for a period of time (as shown in fig. 11), and it can be seen that the liquid (cross hatched portion) discharges bubbles but does not flow out of the micro valve, and the control layer liquid (vertical hatched portion) flows through the siphon pipe 9I and stops at the capillary valve II 10; fourthly, the turret is again rotated for a period of time and then stopped (as shown in figure 12), the majority of the liquid in the control chamber 7 (hatched in the horizontal lines) flows out, the microvalve is opened and the liquid in the sample chamber 16 (hatched in the horizontal lines) flows into the detection chamber 17 below the microvalve.
It should be understood that the above-described specific embodiments are merely illustrative of the present invention and are not intended to limit the present invention. Obvious variations or modifications which are within the spirit of the invention are possible within the scope of the invention.

Claims (7)

1. A hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system, said elastomeric diaphragm microvalve being a diaphragm microvalve having a sample layer (1) and a control layer (2) separated; the liquid in the control layer (2) is deionized water, and the micro valve is switched on and off by utilizing capillary and centrifugal force drive through hydraulic pressure on two sides of the control layer (2);
the elastic diaphragm micro valve comprises two parts, namely a sample layer (1) and a control layer (2), wherein the sample layer (1) sequentially comprises a first PDMS diaphragm sample layer, a first PMMA sample layer, a second PMMA sample layer and a second PDMS diaphragm sample layer from top to bottom; the control layer (2) is a PDMS membrane control layer, a first PMMA control layer, a second PMMA control layer and a glass control layer from top to bottom respectively; the first PDMS membrane sample layer, the second PDMS membrane sample layer, the PDMS membrane control layer and the glass control layer have no internal structure, the first PMMA sample layer and the second PMMA sample layer are provided with sample layer internal through hole structures, and the first PMMA control layer and the second PMMA control layer are also provided with control layer internal through hole structures;
the sample layer (1) and the control layer (2) are vertically stacked, positioned through the positioning hole (3) and bound on the rotary table through an adhesive tape;
the through hole structure in the control layer comprises a positioning hole (3), a first injection hole (4), a first injection chamber (5), a first inflow channel (6), a control chamber (7), a first capillary valve (8), a first siphon (9), a second capillary valve (10), a first waste liquid pool (11), an overflow valve (12) and a second waste liquid pool (13);
the positioning hole (3) is an independent structure and is used for aligning and positioning the control layer (2) and the sample layer (1) during installation; the first injection hole (4) is arranged right above the first injection chamber (5) and is used for injecting deionized water; the first injection chamber (5) is connected with an inlet of the control chamber (7) through the first inflow channel (6), an outlet of the control chamber (7) is connected with an inlet of the first siphon (9) through the first capillary valve (8), an outlet of the first siphon (9) is connected with the first waste liquid pool (11) through the second capillary valve (10), and the overflow valve (12) is arranged at a connection position between the first injection chamber (5) and the second waste liquid pool (13);
the through hole structure in the sample layer comprises a positioning hole (3), a second injection hole (14), a second injection chamber (15), a sample chamber (16), a detection chamber (17), a second siphon (18), a third capillary valve (19) and a third waste liquid pool (20);
the positioning hole (3) is an independent structure and is used for aligning and positioning the control layer (2) and the sample layer (1) during installation; the second injection hole (14) is arranged right above the second injection chamber (15) and is used for injecting a sample; the second injection chamber (15) is connected with the sample chamber (16), the outlet of the sample chamber (16) is connected with the inlet of the second siphon (18), and the outlet of the second siphon (18) is connected with the third waste liquid pool (20) through the third capillary valve (19); the detection chamber (17) is arranged below the sample chamber (16) and is separated by the PDMS membrane and the PMMA rib structure.
2. A hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system as claimed in claim 1, wherein said control layer (2) operates by: deionized water is dripped from the injection chamber I (5) as a control liquid, and the control liquid flows into the control chamber I (7) along the inflow channel I (6) due to the hydrophilicity of the glass control layer and stops at the capillary valve I (8); meanwhile, the control liquid is stopped after reaching the inlet of the second waste liquid pool (13) from the first injection chamber (5) through the overflow valve (12); then, the rotary table rotates, in the rotating process, the first capillary valve (8) is opened, the control liquid flows into the first siphon (9), but the control liquid cannot flow out of the control chamber (7) because the height of the top end of the first siphon (9) is higher than the height of the inlet of the first inflow channel (6), and the micro valve is in a closed state; the rotary table stops rotating, and the control liquid stops after advancing to a second capillary valve (10) at the outlet of the first siphon (9) along the first siphon (9); the rotary table rotates again, due to siphoning, the control liquid flows out of the control chamber (7) through the first siphon (9), meanwhile, a sample in a sample chamber (16) above the control layer (2) presses open a diaphragm of the control layer (2) due to centrifugal force, the micro valve is opened, and the sample layer liquid flows out of the micro valve.
3. A hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system according to claim 2, characterized in that the sample layer (1) operates by: initially, puncturing the first PDMS membrane sample layer above the second injection chamber (15) with a pipette, injecting a sample liquid, which stays in the second injection chamber (15) if the sample liquid is hydrophobic, and flows into the sample chamber (16) above the membrane if the sample liquid is hydrophilic; the turntable is rotated, and under the action of centrifugal force, sample liquid flows into the sample chamber (16) above the micro valve; but at the micro valve, because the pressure generated by the liquid below is larger than the pressure generated by the sample liquid in the sample layer (1), the micro valve is closed, and the sample liquid in the sample layer (1) can complete the functions of quantification, separation and mixing in the sample chamber (16), but the micro valve is not opened actively; the rotary table stops rotating, and because of no centrifugal force, the pressures on the two sides of the micro valve are the same, and the micro valve cannot be opened; the turntable rotates again, the control liquid flows out of the control chamber through the first siphon (9), when the turntable reaches a sufficient rotating speed, the pressure of the upper liquid bends a PDMS membrane between the control chamber (7) and the sample chamber (16) downwards, a micro valve is opened, and the sample liquid in the sample chamber (16) flows into the detection chamber (17) through the micro valve.
4. A hydraulically actuated elastomeric diaphragm microvalve for use in centrifugal microfluidic systems as claimed in claim 2, wherein said first siphon (9) is an inverted U-shaped tube.
5. A hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system as claimed in claim 3, wherein said sample liquid is a biological sample or reagent.
6. A hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system according to claim 3, wherein the pressure generated by said underlying liquid and the pressure generated by the sample liquid in said sample layer (1) are both centrifugal forces.
7. A method of manufacturing a hydraulically actuated elastomeric diaphragm microvalve for use in a centrifugal microfluidic system as claimed in any one of claims 1 to 6, wherein said method of manufacturing comprises the steps of:
preparing a PMMA layer: firstly, the method comprises the following steps of 1: 1, drawing a contour diagram of a required structure in proportion, and then cutting the required structure on a PMMA plate by laser according to the contour diagram; preparing a first PMMA sample layer, a second PMMA sample layer, a first PMMA control layer and a second PMMA control layer according to the method;
preparing a PDMS membrane: adsorbing a disc-shaped PC (polycarbonate) plate on a spin coater to serve as a bottom plate, and spin-coating a PDMS (polydimethylsiloxane) liquid film added with a curing agent on the bottom plate, wherein the thickness of the liquid film is related to the rotating speed and the rotating time; then heating to cure the PDMS liquid film to obtain a PDMS membrane; preparing a first PDMS membrane sample layer, a second PDMS membrane sample layer and a PDMS membrane control layer according to the method;
bonding of the first PDMS membrane sample layer and the first PMMA sample layer: carrying out plasma treatment on the plane of the first PDMS membrane sample layer to be bonded, and then attaching the plane of the first PDMS membrane sample layer to the corresponding plane of the first PMMA sample layer to realize bonding;
bonding the second PMMA sample layer and the second PDMS membrane sample layer: the second PMMA sample layer and the second PDMS membrane sample layer are separable at the membrane microvalve, without being bonded together; for other locations, the second PMMA sample layer and the second PDMS membrane sample layer remain bonded; in order to realize the functions, before bonding, firstly, an oil marking pen is used for smearing a layer of printing ink at the position of a membrane micro valve on a second PDMS membrane sample layer, then, a plane of the second PDMS membrane sample layer needing bonding is subjected to plasma treatment, and then, the plane is attached to the corresponding plane of the second PMMA sample layer to realize bonding;
bonding the first PMMA sample layer and the second PMMA sample layer: before preparing the second PMMA sample layer, adhering a double-sided adhesive tape on a required plane in advance, then carrying out laser processing, tearing off a double-sided adhesive tape protective film after the bonding of the third step and the fourth step is finished, and carrying out bonding between the first PMMA sample layer and the second PMMA sample layer through alignment of positioning holes; after the bonding is finished, preparing the sample layer;
bonding of the PDMS membrane control layer and the first PMMA control layer: carrying out plasma treatment on the plane of the PDMS membrane control layer to be bonded, and then attaching the plane to the corresponding plane of the first PMMA control layer to realize bonding;
bonding the second PMMA control layer with the first PMMA control layer and the glass control layer: before preparing the second PMMA control layer, adhering double-sided adhesive tapes on both sides of the second PMMA control layer in advance, then carrying out laser processing, tearing off the protective film of the double-sided adhesive tapes after the bonding of the step (c), and carrying out adhesion between the first PMMA control layer and the second PMMA control layer and between the second PMMA control layer and the glass control layer through alignment of the positioning holes; after the bonding is finished, the control layer is prepared;
aligning and installing a sample layer and a control layer: and (3) vertically stacking the sample layer and the control layer, namely, enabling the second PDMS membrane sample layer to be in contact with the PDMS membrane control layer, positioning through the positioning hole, and binding the sample layer and the control layer on the turntable through an adhesive tape to finish alignment and installation.
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