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WO2018104516A1 - Soupape microfluidique - Google Patents

Soupape microfluidique Download PDF

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Publication number
WO2018104516A1
WO2018104516A1 PCT/EP2017/082010 EP2017082010W WO2018104516A1 WO 2018104516 A1 WO2018104516 A1 WO 2018104516A1 EP 2017082010 W EP2017082010 W EP 2017082010W WO 2018104516 A1 WO2018104516 A1 WO 2018104516A1
Authority
WO
WIPO (PCT)
Prior art keywords
channel
pressure
flexible layer
microfluidic
microfluidic valve
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2017/082010
Other languages
English (en)
Inventor
Seetal POTLURI
Paul POP
Jan Madsen
Alexander Rüdiger SCHNEIDER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Danmarks Tekniske Universitet
Original Assignee
Danmarks Tekniske Universitet
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 Danmarks Tekniske Universitet filed Critical Danmarks Tekniske Universitet
Publication of WO2018104516A1 publication Critical patent/WO2018104516A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0015—Diaphragm or membrane valves
    • 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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0055—Operating means specially adapted for microvalves actuated by fluids
    • F16K99/0057—Operating means specially adapted for microvalves actuated by fluids the fluid being the circulating fluid itself, e.g. check valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0055—Operating means specially adapted for microvalves actuated by fluids
    • F16K99/0059—Operating means specially adapted for microvalves actuated by fluids actuated by a pilot fluid
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/14—Means for pressure control
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0073—Fabrication methods specifically adapted for microvalves
    • F16K2099/008—Multi-layer fabrications
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology

Definitions

  • the present disclosure relates to a membrane valve, e.g. for microfluidics, such as a monolithic membrane valve, such as a three layer monolithic membrane valve.
  • a membrane valve e.g. for microfluidics
  • a monolithic membrane valve such as a three layer monolithic membrane valve.
  • the disclosure furthermore relates to complementary pneumatic digital logic, such as a complementary pneumatic NOT gate.
  • Microfluidics-based biochips integrate different biochemical analysis functionalities on- chip, miniaturizing the macroscopic biochemical processes to a sub-millimeter scale. These microsystems offer several advantages over the conventional biochemical analyzers, e.g., reduced sample and reagent volumes, faster biochemical reactions, ultra-sensitive detection and higher system throughput, with several assays being integrated on the same chip.
  • Biochips are used in many application areas like in vitro diagnostics, drug discovery, biotechnology and ecology. There are several types of biochip platforms, each having advantages and limitations.
  • on-chip pneumatic control logic gates are constructed with valves and pull-up resistors.
  • the pull-up resistors are much larger than the valves themselves, thereby making these gates very huge in area.
  • the large size of on-chip control gates is a major bottleneck in the practical scaling of flow based microfluidic biochips.
  • these gates have poor noise margin due to the large pull-up pneumatic resistor inside each of them, which make dimensioning and optimization very difficult.
  • a microfluidic valve comprising: a first rigid layer, a second rigid layer, a flexible layer being arranged between a first side of the first rigid layer and a second side of the second rigid layer, and a first control gate channel.
  • the first rigid layer has the first side comprising a first primary recess and a first secondary recess.
  • the first primary recess forms a first input channel.
  • the first secondary recess forms a first output channel.
  • the first primary recess and the first secondary recess are separated by a first bridge of material of the first rigid layer.
  • the second rigid layer has a second side facing the first side of the first rigid layer.
  • the second side comprises a first indentation overlaying a part of the first primary recess and a part of the first secondary recess and the first bridge.
  • the flexible layer is arranged between the first side of the first rigid layer and the second side of the second rigid layer. In a first state the flexible layer prevents fluid connection between the first input channel and the first output channel. In a second state the flexible layer protrudes into the first indentation providing fluid connection between the first input channel and the first output channel.
  • the first control gate channel is not forming part of the first primary recces and the first secondary recess, and the first control gate channel is configured to receive a first fluidic control pressure.
  • first fluidic control pressure is lower than a pressure threshold the flexible layer is in the first state.
  • first fluidic control pressure is higher than the pressure threshold the flexible layer is in the second state.
  • microfluidic inverter comprising a first microfluidic valve, such as the microfluidic valve as disclosed above, and a second microfluidic valve.
  • the second microfluidic valve comprises a first rigid layer, a second rigid layer, a flexible layer being arranged between a first side of the first rigid layer and a second side of the second rigid layer, and a second control gate channel.
  • the first rigid layer of the second microfluidic valve has the first side comprising a second primary recess and a second secondary recess.
  • the second primary recess forms a second input channel and the second secondary recess forms a second output channel.
  • the second primary recess and the second secondary recess are separated by a second bridge of material of the first rigid layer.
  • the second rigid layer of the second microfluidic valve has the second side facing the first side of the first rigid layer, the second side comprises a second indentation overlaying a part of the second primary recess and a part of the second secondary recess and the second bridge.
  • the flexible layer of the second microfluidic valve is arranged between the first side of the first rigid layer and the second side of the second rigid layer. In a first state the flexible layer protrudes into the second indentation providing a fluid connection between the second input channel and the second output channel. In a second state the flexible layer prevents fluid connection between the second input channel and the second output channel.
  • the second control gate channel is not forming part of the second primary recces and the second secondary recess, and the second control gate channel is configured to receive a second fluidic control pressure.
  • the second fluidic control pressure is lower than the pressure threshold the flexible layer is in the first state.
  • the second fluidic control pressure is higher than the pressure threshold the flexible layer is in the second state.
  • the first output channel is in fluid connection with the second output channel forming a common output channel.
  • a microfluidic valve and a microfluidic inverter are provided that increases accuracy, e.g. in eliminating or at least reducing the need for pull-up resistors.
  • microfluidic valve and a microfluidic inverter are provided that decreases the area needed for certain parts of the microfluidic chips.
  • the first control gate channel may be in fluid connection with the second control gate channel.
  • the first control gate channel and the second control gate channel being in fluid connection may form a common control gate channel.
  • Pressure threshold for the flexible layer of the first microfluidic valve to be in the first state and/or second state, and pressure threshold for the flexible layer of the second microfluidic valve to be in the first state and/or second may be the same.
  • the first microfluidic valve and the second microfluidic valve may be integrally formed, and/or one or more parts of the first microfluidic valve and the second microfluidic valve may be integrally formed.
  • the first rigid layer of the first microfluidic valve may be integrally formed with the first rigid layer of the second microfluidic valve.
  • the second rigid layer of the first microfluidic valve may be integrally formed with the second rigid layer of the second microfluidic valve.
  • the flexible layer of the first microfluidic valve may be integrally formed with the flexible layer of the second microfluidic valve.
  • first rigid layer the second rigid layer, and/or the flexible layer may refer to the first rigid layer, the second rigid layer, and/or the flexible layer of either or both of the first microfluidic valve and/or the second microfluidic valve.
  • control gate channels may be comprised in the rigid layers.
  • the first control gate channel may be comprised in the first rigid layer.
  • the second control gate channel may be comprised in the second rigid layer.
  • the first control gate channel may also be comprised in the second rigid layer, and alternatively or additionally, the second control gate channel may be comprised in the first rigid layer.
  • the first control gate channel and/or the second control gate channel may comprise a bend, such as a 90 deg. bend.
  • the first control gate channel and/or the second control gate channel may have an L-shaped form. Such shape may provide that the control gate channel, such as the first control gate channel and/or the second control gate channel, terminates on a side of the microfluidic chip rather than on the top/bottom.
  • the control gate channel, such as the first control gate channel and/or the second control gate channel may terminate parallel to the first input port and/or the second input port and/or the first output port and/or the second output port and/or the common output port.
  • the first control gate channel may be in fluid connection with the first input channel and/or the first output channel, e.g. when the flexible layer is in a state, such as the second state, providing fluid connection between the first input channel and the first output channel.
  • the first control gate channel may comprise a structure.
  • the structure may be configured to mechanically manipulate the flexible layer. For example, when the first fluidic control pressure is higher than the pressure threshold the structure is extending and the flexible layer is manipulated by the structure to the second state. Additionally or alternatively, when the first fluidic control pressure is lower than the pressure threshold the structure is retracting and the flexible layer may be manipulated by the structure to the first state.
  • the structure may be attached to the flexible layer, such as fastened to the flexible layer.
  • the structure may be glued to the structure.
  • the structure may be loosely positioned in the first control gate channel, and abut the flexible layer at least when the first fluidic control pressure is higher than the pressure threshold.
  • the structure may be integrally formed with the flexible layer.
  • the flexible layer may be manufactured with the structure for fitting with the first control gate channel.
  • the first rigid layer and/or the second rigid layer may be made of acrylic glass, such as polymethyl methacrylate (PMMA), or glass.
  • PMMA polymethyl methacrylate
  • the flexible layer may be made of Polydimethylsiloxane (PDMS).
  • PDMS Polydimethylsiloxane
  • the structure may be made of Polydimethylsiloxane (PDMS).
  • PDMS Polydimethylsiloxane
  • the structure and the flexible layer may be made of the same material.
  • the input channels may receive respective fluidic input pressures.
  • the first input channel may be configured to receive a first fluidic input pressure.
  • the second input channel may be configured to receive a second fluidic input pressure.
  • the first fluidic input pressure may be lower than the second fluidic input pressure.
  • the second fluidic input pressure may be between 0 kPa and 20 kPa, such as 5 kPa and/or 10 kPa and/or 15 kPa.
  • the first fluidic input pressure may be between -20 kPa and 0 kPa, such as -5 kPa and/or -10 kPa and/or -15 kPa.
  • the second fluidic input pressure may be between 0 kPa and 50 kPa, such as 5 kPa and/or 10 kPa and/or 15 kPa and/or 20 kPa and/or 25 kPa and/or 30 kPa and/or 35 kPa and/or 40 kPa and/or 45 kPa and/or 50 kPa.
  • the first fluidic input pressure may be between -80 kPa and 0 kPa, such as -10 kPa and/or -20 kPa and/or -30 kPa and/or -40 kPa and/or -50 kPa and/or -60 kPa and/or -70 kPa and/or -80 kPa.
  • the first input channel may alternatively be configured to receive the second fluidic input pressure and vice versa.
  • the pressure threshold may be between the first fluidic input pressure and the second fluidic input pressure.
  • the pressure threshold may be 0 kPa.
  • the flexible layer may be in the first state when the first fluidic control pressure and/or the second fluidic control pressure and/or the common fluidic control pressure is lower than the pressure threshold, e.g. lower than 0 kPa.
  • the flexible layer may be in the first state when the first fluidic control pressure and/or the second fluidic control pressure and/or the common fluidic control pressure is equal to the second fluidic input pressure.
  • the flexible layer may be in the second state when the first fluidic control pressure and/or the second fluidic control pressure and/or the common fluidic control pressure is higher than the pressure threshold, e.g. higher than 0 kPa.
  • the flexible layer may be in the second state when the first fluidic control pressure and/or the second fluidic control pressure and/or the common fluidic control pressure is equal to the first fluidic input pressure.
  • Fig. 1 schematically llustrates a side view of an exemplary first microfluidic valve
  • Fig. 2 schematically llustrates a side view of an exemplary first microfluidic valve
  • Fig. 3 schematically llustrates a side view of an exemplary second microfluidic valve
  • Fig. 4 schematically llustrates a side view of an exemplary microfluidic inverter
  • Fig. 5 schematically llustrates a side view of an exemplary first microfluidic valve
  • Fig. 6 schematically llustrates a side view of an exemplary second microfluidic valve
  • Fig. 7 schematically llustrates a side view of an exemplary microfluidic inverter
  • Fig. 8 schematically llustrates a top view of an exemplary first or second microfluidic valve
  • Fig. 9 schematically illustrates a top view of an exemplary microfluidic inverter
  • Fig. 10 schematically illustrates a top view of an exemplary microfluidic inverter wherein the first control gate channel is in fluid connect with the second control gate channel forming a common control gate channel.
  • Fig. 1 schematically illustrates a side view of an exemplary first microfluidic valve 2.
  • the first microfluidic valve 2 comprises a first rigid layer 4, a second rigid layer 18, and a flexible layer 24.
  • the first rigid layer 4 has a first side 6.
  • the first side 6 comprises a first primary recess 8 and a first secondary recess 10.
  • the first primary recess 8 forms a first input channel 12.
  • the first secondary recess 10 forms a first output channel 14.
  • the first primary recess 8 and the first secondary recess 10 are separated by a first bridge of material 16 of the first rigid layer 4.
  • the second rigid layer 18 has a second side 20 facing the first side 6 of the first rigid layer 4.
  • the second side 20 comprises a first indentation 22.
  • the first indentation 22 overlays a part of the first primary recess 8 and a part of the first secondary 10 recess and the first bridge 16.
  • the flexible layer 24 is arranged between the first side 6 of the first rigid layer 4 and the second side 20 of the second rigid layer 18. In a first state (Fig. 1 a) the flexible layer 24 prevents fluid connection between the first input channel 12 and the first output channel 14. In a second state (Fig. 1 b) the flexible layer 24 protrudes into the first indentation 22 providing fluid connection between the first input channel 12 and the first output channel 14.
  • the first microfluidic valve 2 comprises a first control gate channel 26.
  • the first control gate channel 26 is configured to receive a first fluidic control pressure. When the first fluidic control pressure is lower than a pressure threshold the flexible layer 24 is in the first state (Fig. 1 a). When the first fluidic control pressure is higher than the pressure threshold the flexible layer 24 is in the second state (Fig. 1 b).
  • the first control gate channel 26 is comprised in the first rigid layer 4, and has an L-shape providing that the first control gate channel 26 terminates parallel to the first input channel 12 and the first output channel 14.
  • the first control gate channel 26 may be a straight channel, such as a straight channel terminating in the top of the first rigid layer 4.
  • Fig. 2 schematically illustrates a side view of an exemplary first microfluidic valve 2'.
  • the first microfluidic valve 2' comprises a first rigid layer 4, a second rigid layer 18, and a flexible layer 24.
  • the first rigid layer 4, the second rigid layer 18, and the flexible layer 24 is as described in relation to Fig. 1 .
  • the first microfluidic valve 2' comprises a first control gate channel 26'.
  • the first control gate channel 26' is configured to receive a first fluidic control pressure. When the first fluidic control pressure is lower than a pressure threshold the flexible layer 24 is in the first state (Fig. 2a). When the first fluidic control pressure is higher than the pressure threshold the flexible layer 24 is in the second state (Fig. 2b).
  • the first control gate channel 26' is comprised in the first rigid layer 4, and has an L-shape providing that the first control gate channel 26' terminates parallel to the first input channel 12 and the first output channel 14.
  • the first control gate channel 26' may be a straight channel, such as a straight channel terminating in the top of the first rigid layer 4.
  • the first control gate channel 26' comprises a structure 28.
  • the structure 28 is configured to mechanically manipulate the flexible layer 24.
  • the structure When the first fluidic control pressure is higher than the pressure threshold the structure is extending and the flexible layer is manipulated by the structure to the second state (Fig. 2b).
  • the structure When the first fluidic control pressure is lower than the pressure threshold the structure is retracted (Fig. 2a).
  • the structure When the structure retracts, the flexible layer 24 is able to return to the first state, thereby preventing fluid connection between the first input channel 12 and the first output channel 14 (Fig. 2a).
  • the structure 28 provides for fluidic flow around it, i.e. it does not block the fluidic connection between the input channel 12 and the output channel 14.
  • the structure 28 may be attached to the flexible layer 24, such as fastened to the flexible layer 24.
  • the structure 28 may be integrally formed with the flexible layer 24.
  • the structure 28 being attached to the flexible layer 24 and/or the structure 28 being integrally formed with the flexible layer 24 may provide that the flexible layer 24 can be manipulated by the structure 28 to the first state (Fig. 2a).
  • the structure 28 may be positioned in the first control gate channel 26' without fastening to the flexible layer 24.
  • the length of the structure 28 may be adapted such that at least a part of the structure 28 remains in the first control gate channel 26' when the flexible layer 24 is in the second state (Fig. 2b).
  • Fig. 3 schematically illustrates a side view of an exemplary second microfluidic valve 32.
  • the second microfluidic valve 32 comprises a first rigid layer 4', a second rigid layer 18', and a flexible layer 24'.
  • the first rigid layer 4' has a first side 6'.
  • the first side 6' comprises a second primary recess 34 and a second secondary recess 36.
  • the second primary recess 34 forms a second input channel 38.
  • the second secondary recess 36 forms a second output channel 40.
  • the secondary primary recess 36 and the second secondary recess 38 are separated by a second bridge of material 42 of the first rigid layer 4'.
  • the second rigid layer 18' has a second side 20' facing the first side 6' of the first rigid layer 4'.
  • the second side 20' comprises a second indentation 44.
  • the second indentation 44 overlays a part of the second primary recess 34 and a part of the second secondary 36 recess and the second bridge 42.
  • the flexible layer 24' is arranged between the first side 6' of the first rigid layer 4' and the second side 20' of the second rigid layer 18'.
  • a first state Fig. 3a
  • the flexible layer 24' protrudes into the second indentation 44 providing a fluid connection between the second input channel 38 and the second output channel 40.
  • a second state Fig. 3b
  • the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • the second microfluidic valve 32 comprises a second control gate channel 46.
  • the second control gate channel 46 is configured to receive a second fluidic control pressure. When the second fluidic control pressure is lower than a pressure threshold the flexible layer 24' is in the first state (Fig. 3a). When the second fluidic control pressure is higher than the pressure threshold the flexible layer 24' is in the second state (Fig. 3b).
  • the second control gate channel 46 is comprised in the second rigid layer 18', and has an L-shape providing that the second control gate channel 46 terminates parallel to the second input channel 38 and the second output channel 40.
  • the second control gate channel 46 may be a straight channel, such as a straight channel terminating in the bottom of the second rigid layer 18'.
  • Fig. 4 schematically illustrates a side view of an exemplary first microfluidic inverter 30.
  • the first microfluidic inverter 30 comprises a first microfluidic valve 2, as explained in relation to Fig. 1 , and a second microfluidic valve 32, as explained in relation to Fig. 3.
  • the first microfluidic inverter 30 comprises a first microfluidic valve 2', as explained in relation to Fig. 2, and a second microfluidic valve 32, as explained in relation to Fig. 3.
  • the first output channel 14 is in fluid connection with the second output channel 40.
  • the first output channel 14 and the second output channel 40 forms a common output channel 48.
  • the first microfluidic valve 2 and the second microfluidic valve 32 may be separate valves. However, as also illustrated, they may be formed from the same elements.
  • the first rigid layer 4 of the first microfluidic valve 2 is integrally formed with the first rigid layer 4' of the second microfluidic valve 32.
  • the first rigid layer 4 of the first microfluidic valve 2 may be the first rigid layer 4' of the second microfluidic valve 32, and vice versa.
  • the second rigid layer 18 of the first microfluidic valve 2 is integrally formed with the second rigid layer 18' of the second microfluidic valve 32.
  • the second rigid layer 18 of the first microfluidic valve 2 may be the second rigid layer 18' of the second microfluidic valve 32, and vice versa.
  • the flexible layer 24 of the first microfluidic valve 2 is integrally formed with the flexible layer 24' of the second microfluidic valve 32.
  • the flexible layer 24 of the first microfluidic valve 2 may be the flexible layer 24' of the second microfluidic valve 32, and vice versa.
  • Fig. 4a shows the flexible layer 24 of the first microfluidic valve 2 being in the first state, wherein the flexible layer 24 prevents fluid connection between the first input channel 12 and the first output channel 14, and the flexible layer 24' of the second microfluidic valve 32 being in the second state, wherein the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • Fig. 4b shows the flexible layer 24 of the first microfluidic valve 2 being in the first state, wherein the flexible layer 24 prevents fluid connection between the first input channel 12 and the first output channel 14, and the flexible layer 24' of the second microfluidic valve 32 being in the first state, wherein the flexible layer 24' provides fluid connection between the second input channel 38 and the second output channel 40.
  • Fig. 4c shows the flexible layer 24 of the first microfluidic valve 2 being in the second state, wherein the flexible layer 24 provides fluid connection between the first input channel 12 and the first output channel 14, and the flexible layer 24' of the second microfluidic valve 32 being in the second state, wherein the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • first control gate channel 26 may be in fluid connection with the second control gate channel 46.
  • the first control gate channel 26 and the second control gate channel 46 may form a common control gate channel. This may be advantageous as it reduces the complexity.
  • Pressure threshold for the flexible layer of the first microfluidic valve to be in the first state and/or second state, and pressure threshold for the flexible layer of the second microfluidic valve to be in the first state and/or second may be the same.
  • the first microfluidic inverter 30 may be configured to receive a first fluidic input pressure on the first input channel 12 and a second fluidic input pressure on the second channel 38.
  • the output pressure in the common output channel 48 is determined by the state of the flexible layer 24, 24'.
  • the first fluidic input pressure may be a negative pressure, such as -20 kPa
  • the second fluidic input pressure may be a positive pressure, such as 20 kPa
  • the pressure threshold of the flexible layer 24, 24' of the first microfluidic valve 2 and the second microfluidic valve 32 may be between the first fluidic input pressure and the second fluidic input pressure, such as 0 kPa.
  • the control gate channels 26, 46 may be coupled to pressure of the first fluidic pressure and/or the second fluidic pressure. If the control gate channels 26, 46 receive the first fluidic pressure, e.g. -20 kPa, the situation as illustrated in Fig. 4b will arise and the output pressure in the common output channel 48 will be the pressure in the second input channel 38, e.g. the second fluidic pressure, e.g. 20 kPa. If the control gate channels 26, 46 receive the second fluidic pressure, e.g. 20 kPa, the situation as illustrated in Fig. 4c will arise and the output pressure in the common output channel 48 will be the pressure in the first input channel 12, e.g. the first fluidic pressure, e.g. -20 kPa.
  • Fig. 5 schematically illustrates a side view of an exemplary first microfluidic valve 2".
  • the first microfluidic valve 2" comprises a first rigid layer 4", a second rigid layer 18, and a flexible layer 24.
  • the first rigid layer 4" has a first side 6".
  • the first side 6" comprises a first primary recess 8' and a first secondary recess 10'.
  • the first primary recess 8' forms a first input channel 12'.
  • the first secondary recess 10' forms a first output channel 14'.
  • the first primary recess 8' and the first secondary recess 10' are separated by a first bridge of material 16' of the first rigid layer 4".
  • the second rigid layer 18 has a second side 20 facing the first side 6" of the first rigid layer 4".
  • the second side 20 comprises a first indentation 22.
  • the first indentation 22 overlays a part of the first primary recess 8' and a part of the first secondary 10' recess and the first bridge 16'.
  • the flexible layer 24 is arranged between the first side 6" of the first rigid layer 4" and the second side 20 of the second rigid layer 18. In a first state (Fig. 5a) the flexible layer 24 prevents fluid connection between the first input channel 12' and the first output channel 14'. In a second state (Fig. 5b) the flexible layer 24 protrudes into the first indentation 22 providing fluid connection between the first input channel 12' and the first output channel 14'.
  • the first microfluidic valve 2" comprises a first control gate channel 26".
  • the first control gate channel 26" is configured to receive a first fluidic control pressure. When the first fluidic control pressure is lower than a pressure threshold the flexible layer 24 is in the first state (Fig. 5a). When the first fluidic control pressure is higher than the pressure threshold the flexible layer 24 is in the second state (Fig. 5b).
  • the first control gate channel 26" is comprised in the first rigid layer 4", and the first control gate channel 26" is directed towards another side than the first input channel 12' and the first output channel 14', such as e.g. the first control gate channel 26" is perpendicular to the first input channel 12' and the first output channel 14'.
  • the first control gate channel 26" may be a straight channel, such as a straight channel terminating in the top of the first rigid layer 4".
  • Fig. 6 schematically illustrates a side view of an exemplary second microfluidic valve 32'.
  • the second microfluidic valve 32' comprises a first rigid layer 4', a second rigid layer 18", and a flexible layer 24'.
  • the first rigid layer 4' has a first side 6'.
  • the first side 6' comprises a second primary recess 34 and a second secondary recess 36.
  • the second primary recess 34 forms a second input channel 38.
  • the second secondary recess 36 forms a second output channel 40.
  • the secondary primary recess 36 and the second secondary recess 38 are separated by a second bridge of material 42 of the first rigid layer 4'.
  • the second rigid layer 18" has a second side 20" facing the first side 6' of the first rigid layer 4'.
  • the second side 20" comprises a second indentation 44'.
  • the second indentation 44' overlays a part of the second primary recess 34 and a part of the second secondary 36 recess and the second bridge 42.
  • the flexible layer 24' is arranged between the first side 6' of the first rigid layer 4' and the second side 20" of the second rigid layer 18".
  • a first state Fig. 6a
  • the flexible layer 24' protrudes into the second indentation 44' providing a fluid connection between the second input channel 38 and the second output channel 40.
  • a second state Fig. 6b
  • the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • the second microfluidic valve 32' comprises a second control gate channel 46'.
  • the second control gate channel 46' is configured to receive a second fluidic control pressure. When the second fluidic control pressure is lower than a pressure threshold the flexible layer 24' is in the first state (Fig. 6a). When the second fluidic control pressure is higher than the pressure threshold the flexible layer 24' is in the second state (Fig. 6b).
  • the second control gate channel 46' is comprised in the second rigid layer 18", and the second control gate channel 46' is directed towards another side than the second input channel 38 and the second output channel 40 such as e.g. the second control gate channel 46' is perpendicular to the second input channel 38 and the second output channel 40.
  • the second control gate channel 46' may be a straight channel, such as a straight channel terminating in the bottom of the second rigid layer 18".
  • Fig. 7 schematically illustrates a side view of an exemplary microfluidic inverter 30'.
  • the microfluidic inverter 30' comprises a first microfluidic valve 2", as explained in relation to Fig. 5, and a second microfluidic valve 32', as explained in relation to Fig. 6.
  • the microfluidic inverter 30' comprises a first microfluidic valve 2', as explained in relation to Fig. 2, and a second microfluidic valve 32', as explained in relation to Fig. 6.
  • the first output channel 14' is in fluid connection with the second output channel 40.
  • the first output channel 14' and the second output channel 40 forms a common output channel 48'.
  • the first microfluidic valve 2" and the second microfluidic valve 32' may be separate valves. However, as also illustrated, they may be formed from the same elements.
  • the first rigid layer 4" of the first microfluidic valve 2" is integrally formed with the first rigid layer 4' of the second microfluidic valve 32'.
  • the first rigid layer 4" of the first microfluidic valve 2" may be the first rigid layer 4' of the forth microfluidic valve 32', and vice versa.
  • the second rigid layer 18 of the first microfluidic valve 2" is integrally formed with the second rigid layer 18" of the second microfluidic valve 32'.
  • the second rigid layer 18 of the first microfluidic valve 2" may be the second rigid layer 18" of the second microfluidic valve 32', and vice versa.
  • the flexible layer 24 of the first microfluidic valve 2" is integrally formed with the flexible layer 24' of the second microfluidic valve 32'.
  • the flexible layer 24 of the first microfluidic valve 2" may be the flexible layer 24' of the second microfluidic valve 32', and vice versa.
  • Fig. 7a shows the flexible layer 24 of the first microfluidic valve 2" being in the first state, wherein the flexible layer 24 prevents fluid connection between the first input channel 12' and the first output channel 14', and the flexible layer 24' of the second microfluidic valve 32' being in the second state, wherein the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • Fig. 7b shows the flexible layer 24 of the first microfluidic valve 2" being in the first state, wherein the flexible layer 24 prevents fluid connection between the first input channel 12' and the first output channel 14', and the flexible layer 24' of the second microfluidic valve 32' being in the first state, wherein the flexible layer 24' provides fluid connection between the second input channel 38 and the second output channel 40.
  • Fig. 7c shows the flexible layer 24 of the first microfluidic valve 2" being in the second state, wherein the flexible layer 24 provides fluid connection between the first input channel 12' and the first output channel 14', and the flexible layer 24' of the second microfluidic valve 32' being in the second state, wherein the flexible layer 24' prevents fluid connection between the second input channel 38 and the second output channel 40.
  • first control gate channel 26" may be in fluid connection with the second control gate channel 46'.
  • the first control gate channel 26" and the second control gate channel 46' may form a common control gate channel.
  • Pressure threshold for the flexible layer of the first microfluidic valve to be in the first state and/or second state, and pressure threshold for the flexible layer of the second microfluidic valve to be in the first state and/or second may be the same.
  • the microfluidic inverter 30' may be configured to receive a first fluidic input pressure on the first input channel 12' and a second fluidic input pressure on the second channel 38.
  • the output pressure in the common output channel 48' is determined by the state of the flexible layer 24, 24'.
  • the first fluidic input pressure may be a negative pressure, such as -20 kPa
  • the second fluidic input pressure may be a positive pressure, such as 20 kPa
  • the pressure threshold of the flexible layer 24, 24' of the first microfluidic valve 2" and the second microfluidic valve 32' may be between the first fluidic input pressure and the second fluidic input pressure, such as 0 kPa.
  • the control gate channels 26", 46' may be coupled to pressure of the first fluidic pressure and/or the second fluidic pressure. If the control gate channels 26", 46' receive the first fluidic pressure, e.g. -20 kPa, the situation as illustrated in Fig. 7b will arise and the output pressure in the common output channel 48' will be the pressure in the second input channel 38, e.g. the second fluidic pressure, e.g. 20 kPa. If the control gate channels 26", 46' receive the second fluidic pressure, e.g. 20 kPa, the situation as illustrated in Fig. 7c will arise and the output pressure in the common output channel 48' will be the pressure in the first input channel 12', e.g. the first fluidic pressure, e.g. -20 kPa.
  • Fig. 8 schematically illustrates a top view of an exemplary first microfluidic system comprising one microfluidic valve 2", as explained in relation to Fig. 1. For a more clear view the shading has been removed from Fig. 8. The schematically illustration is viewed from the top, and part of the microfluidic system is see-through to get an easy overview of the microfluidic channels.
  • the microfluidic system comprises a first input channel 12', 38 formed by a first primary recess as shown in e.g. Fig. 1 , and a first output channel 14' formed by a first secondary recess as shown in e.g. Fig 1 .
  • the microfluidic system further comprises a first control gate channel 26", 46', as illustrated in e.g. Fig 5 or 6.
  • the first control gate channel 26", 46' is configured to receive a first fluidic control pressure. When the first fluidic control pressure is lower than a pressure threshold a flexible layer in the microfluidic valve is in the first state. When the first fluidic control pressure is higher than the pressure threshold the flexible layer is in the second state.
  • first control gate channel 26", 46' is perpendicular to the first input channel 12' and the first output channel 14'.
  • the first control gate channel 26", 46' may have other angels in relation to the first input channel 12' and the first output channel 14', such as 45 degree angle or 60 degree angle.
  • Fig. 9 schematically illustrates a top view of an exemplary third microfluidic system comprising two microfluidic valves 2" and 32' creating a microfluidic inverter 30'.
  • the microfluidic inverter 30' is only an inverter when it is configured to receive a first fluidic input pressure on the first input channel 12' and a second fluidic input pressure on the second channel and the first input pressure is equal to the second input pressure.
  • the shading has been removed from Fig. 9.
  • the schematically illustration is viewed from the top, and part of the microfluidic system is see-through to get an easy overview of the microfluidic channels.
  • the microfluidic system comprises a first input channel 12' formed by a first primary recess as shown in e.g. Fig. 7, and a first output channel 14' formed by a first secondary recess as shown in e.g. Fig 7.
  • the microfluidic system further comprises a second input channel 38 formed by a secondary primary recess as shown in e.g. Fig. 7, and a second output channel 40 formed by a second secondary recess as shown in e.g. Fig 7.
  • the first output channel 14' is in fluid connection with the second output channel 40.
  • the first output channel 14' and the second output channel 40 forms a common output channel 48'.
  • the microfluidic system further comprises a first control gate channel 26", as illustrated in Fig 7, and a second control gate channel 46', as illustrated in Fig 7.
  • the first control gate channel 26" is configured to receive a first fluidic control pressure.
  • the first fluidic control pressure is lower than a pressure threshold a flexible layer in the first microfluid valve 2"
  • the flexible layer is in the first state (see e.g. Fig. 5a).
  • the first fluidic control pressure is higher than the pressure threshold the flexible layer is in the second state (see e.g. Fig. 5b).
  • the second control gate channel 46' is configured to receive a second fluidic control pressure.
  • the flexible layer When the second fluidic control pressure is lower than a pressure threshold of the flexible layer in the second microfluidic valve 32', the flexible layer is in the first state (see e.g. Fig. 6a). When the second fluidic control pressure is higher than the pressure threshold, the flexible layer is in the second state (see e.g. Fig. 6b).
  • Pressure threshold for the flexible layer of the first microfluidic valve 2" to be in the first state and/or second state, and pressure threshold for the flexible layer of the second microfluidic valve 32' to be in the first state and/or second may be the same.
  • the microfluidic inverter 30' may be configured to receive a first fluidic input pressure on the first input channel 12' and a second fluidic input pressure on the second channel 38.
  • the output pressure in the common output channel 48' is determined by the state of the flexible layers in the microfluidic valves 2" and 32'.
  • first control gate channel 26" and the second control gate channel 46' are perpendicular to the input channels and the output channels.
  • the control gate channels 26" and 46' may have other angels in relation to the input channels and the output channels, such as 45 degree angle or 60 degree angle.
  • Fig. 10 schematically illustrates a top view of an exemplary second microfluidic system comprising two microfluidic valves 2" and 32' creating a microfluidic inverter 30', as explained in relation to Fig. 7.
  • Fig. 10 schematically illustrates a top view of an exemplary second microfluidic system comprising two microfluidic valves 2" and 32' creating a microfluidic inverter 30', as explained in relation to Fig. 7.
  • the schematically illustration is viewed from the top, and part of the microfluidic system is see-through to get an easy overview of the microfluidic channels.
  • the microfluidic system comprises a first input channel 12' formed by a first primary recess as shown in e.g. Fig. 7, and a first output channel 14' formed by a first secondary recess as shown in e.g. Fig 7.
  • the microfluidic system further comprises a second input channel 38 formed by a secondary primary recess as shown in e.g. Fig. 7, and a second output channel 40 formed by a second secondary recess as shown in e.g. Fig 7.
  • the first output channel 14' is in fluid connection with the second output channel 40.
  • the first output channel 14' and the second output channel 40 forms a common output channel 48'.
  • the microfluidic system further comprises a first control gate channel 26", as illustrated in Fig 7, and a second control gate channel 46', as illustrated in Fig 7.
  • the first control gate channel 26" is configured to receive a first fluidic control pressure.
  • the first fluidic control pressure is lower than a pressure threshold a flexible layer in the first microfluid valve 2"
  • the flexible layer is in the first state (see e.g. Fig. 5a).
  • the first fluidic control pressure is higher than the pressure threshold the flexible layer is in the second state (see e.g. Fig. 5b).
  • the second control gate channel 46' is configured to receive a second fluidic control pressure.
  • the flexible layer When the second fluidic control pressure is lower than a pressure threshold of the flexible layer in the second microfluidic valve 32', the flexible layer is in the first state (see e.g. Fig. 6a). When the second fluidic control pressure is higher than the pressure threshold, the flexible layer is in the second state (see e.g. Fig. 6b).
  • the first control gate channel 26" is in fluid connection with the second control gate channel 46'.
  • the first control gate channel 26" and the second control gate channel 46' hereby form a common control gate channel.
  • Pressure threshold for the flexible layer of the first microfluidic valve to be in the first state and/or second state, and pressure threshold for the flexible layer of the second microfluidic valve to be in the first state and/or second may be the same.
  • the microfluidic inverter 30' may be configured to receive a first fluidic input pressure on the first input channel 12' and a second fluidic input pressure on the second channel 38.
  • the output pressure in the common output channel 48' is determined by the state of the flexible layers in the microfluidic valves 2" and 32'.
  • the first fluidic input pressure may be a negative pressure, such as -20 kPa
  • the second fluidic input pressure may be a positive pressure, such as 20 kPa
  • the pressure threshold of the flexible layer of the first microfluidic valve 2" and the second microfluidic valve 32' may be between the first fluidic input pressure and the second fluidic input pressure, such as 0 kPa.
  • the common control gate channel created by the first control gate channel 26" beeing in fluid connection with the second control gate channel 46', may be coupled to pressure of the first fluidic pressure and/or the second fluidic pressure. If the common control gate channel receives the first fluidic pressure, e.g. -20 kPa, the situation as illustrated in Fig. 7b will arise and the output pressure in the common output channel 48' will be the pressure in the second input channel 38, e.g. the second fluidic pressure, e.g. 20 kPa. If the common control gate channel receives the second fluidic pressure, e.g. 20 kPa, the situation as illustrated in Fig. 7c will arise and the output pressure in the common output channel 48' will be the pressure in the first input channel 12', e.g. the first fluidic pressure, e.g. -20 kPa.
  • first control gate channel 26" and the second control gate channel 46' are perpendicular to the input channels and the output channels.
  • the control gate channels 26" and 46' may have other angels in relation to the input channels and the output channels, such as 45 degree angle or 60 degree angle.

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Abstract

L'invention concerne une soupape microfluidique et un onduleur microfluidique comprenant la soupape. La soupape microfluidique comprend une première couche rigide ayant un premier côté ; une seconde couche rigide ayant un second côté faisant face au premier côté de la première couche rigide ; une couche souple disposée entre le premier côté de la première couche rigide et le second côté de la seconde couche rigide, la couche flexible, dans un premier état, empêchant une connexion fluidique entre un premier canal d'entrée et un premier canal de sortie, et la couche flexible, dans un second état, faisant saillie dans une première indentation assurant une connexion fluidique entre le premier canal d'entrée et le premier canal de sortie ; et un premier canal de grille de commande conçu pour recevoir une première pression de commande fluidique.
PCT/EP2017/082010 2016-12-08 2017-12-08 Soupape microfluidique Ceased WO2018104516A1 (fr)

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CN110257249A (zh) * 2019-07-19 2019-09-20 东北大学 一种用于肿瘤细胞三维培养的微流控芯片及给药培养方法
WO2021144396A1 (fr) 2020-01-17 2021-07-22 F. Hoffmann-La Roche Ag Dispositif microfluidique et procédé de synthèse automatisée par division de groupe
WO2021148488A2 (fr) 2020-01-22 2021-07-29 F. Hoffmann-La Roche Ag Dispositifs microfluidiques de piégeage de billes et procédés de préparation de banque de séquences de nouvelle génération
WO2022008641A1 (fr) 2020-07-08 2022-01-13 Roche Sequencing Solutions, Inc. Appareil de synthèse split-pool et procédés de réalisation d'une synthèse split-pool
WO2022081741A1 (fr) 2020-10-15 2022-04-21 Roche Sequencing Solutions, Inc. Dispositifs électrophorétiques et procédés de préparation de bibliothèque de séquençage de nouvelle génération
CN114534802A (zh) * 2022-01-06 2022-05-27 北京大学 一种微流控芯片及其制备方法

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CN110257249A (zh) * 2019-07-19 2019-09-20 东北大学 一种用于肿瘤细胞三维培养的微流控芯片及给药培养方法
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WO2021148488A2 (fr) 2020-01-22 2021-07-29 F. Hoffmann-La Roche Ag Dispositifs microfluidiques de piégeage de billes et procédés de préparation de banque de séquences de nouvelle génération
WO2022008641A1 (fr) 2020-07-08 2022-01-13 Roche Sequencing Solutions, Inc. Appareil de synthèse split-pool et procédés de réalisation d'une synthèse split-pool
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CN114534802A (zh) * 2022-01-06 2022-05-27 北京大学 一种微流控芯片及其制备方法

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