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WO2012004423A1 - Método de fabricación de dispositivos microfluidicos. - Google Patents

Método de fabricación de dispositivos microfluidicos. Download PDF

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Publication number
WO2012004423A1
WO2012004423A1 PCT/ES2010/070468 ES2010070468W WO2012004423A1 WO 2012004423 A1 WO2012004423 A1 WO 2012004423A1 ES 2010070468 W ES2010070468 W ES 2010070468W WO 2012004423 A1 WO2012004423 A1 WO 2012004423A1
Authority
WO
WIPO (PCT)
Prior art keywords
sheet
rigid
piece
stage
thermoplastic
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/ES2010/070468
Other languages
English (en)
French (fr)
Inventor
Luis J. FERNÁNDEZ
Florian Laouenan
Iñigo ARAMBURU
María AGIRREGABIRIA
Jorge Elizalde
Javier Berganzo
Jesús RUANO
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.)
Ikerlan S Coop
Original Assignee
Ikerlan S Coop
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 Ikerlan S Coop filed Critical Ikerlan S Coop
Priority to PCT/ES2010/070468 priority Critical patent/WO2012004423A1/es
Priority to US13/808,853 priority patent/US9409167B2/en
Priority to PCT/ES2011/070291 priority patent/WO2012004432A1/es
Priority to EP11729126.0A priority patent/EP2592044B1/en
Priority to ES11729126.0T priority patent/ES2493929T3/es
Publication of WO2012004423A1 publication Critical patent/WO2012004423A1/es
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C65/00Joining or sealing of preformed parts, e.g. welding of plastics materials; Apparatus therefor
    • B29C65/76Making non-permanent or releasable joints
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/01General aspects dealing with the joint area or with the area to be joined
    • B29C66/02Preparation of the material, in the area to be joined, prior to joining or welding
    • B29C66/028Non-mechanical surface pre-treatments, i.e. by flame treatment, electric discharge treatment, plasma treatment, wave energy or particle radiation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/01General aspects dealing with the joint area or with the area to be joined
    • B29C66/05Particular design of joint configurations
    • B29C66/10Particular design of joint configurations particular design of the joint cross-sections
    • B29C66/11Joint cross-sections comprising a single joint-segment, i.e. one of the parts to be joined comprising a single joint-segment in the joint cross-section
    • B29C66/112Single lapped joints
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/01General aspects dealing with the joint area or with the area to be joined
    • B29C66/05Particular design of joint configurations
    • B29C66/10Particular design of joint configurations particular design of the joint cross-sections
    • B29C66/11Joint cross-sections comprising a single joint-segment, i.e. one of the parts to be joined comprising a single joint-segment in the joint cross-section
    • B29C66/114Single butt joints
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/50General aspects of joining tubular articles; General aspects of joining long products, i.e. bars or profiled elements; General aspects of joining single elements to tubular articles, hollow articles or bars; General aspects of joining several hollow-preforms to form hollow or tubular articles
    • B29C66/51Joining tubular articles, profiled elements or bars; Joining single elements to tubular articles, hollow articles or bars; Joining several hollow-preforms to form hollow or tubular articles
    • B29C66/53Joining single elements to tubular articles, hollow articles or bars
    • B29C66/534Joining single elements to open ends of tubular or hollow articles or to the ends of bars
    • B29C66/5346Joining single elements to open ends of tubular or hollow articles or to the ends of bars said single elements being substantially flat
    • B29C66/53461Joining single elements to open ends of tubular or hollow articles or to the ends of bars said single elements being substantially flat joining substantially flat covers and/or substantially flat bottoms to open ends of container bodies
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/70General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/73General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset
    • B29C66/739General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the material of the parts to be joined being a thermoplastic or a thermoset
    • B29C66/7392General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the material of at least one of the parts being a thermoplastic
    • B29C66/73921General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the material of at least one of the parts being a thermoplastic characterised by the materials of both parts being thermoplastics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81CPROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C3/00Assembling of devices or systems from individually processed components
    • B81C3/001Bonding of two components
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K99/0001Microvalves
    • F16K99/0003Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0015Diaphragm or membrane valves
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/70General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/71General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the composition of the plastics material of the parts to be joined
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/70General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/73General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset
    • B29C66/731General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the intensive physical properties of the material of the parts to be joined
    • B29C66/7311Thermal properties
    • B29C66/73117Tg, i.e. glass transition temperature
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29CSHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C66/00General aspects of processes or apparatus for joining preformed parts
    • B29C66/70General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material
    • B29C66/73General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset
    • B29C66/735General aspects of processes or apparatus for joining preformed parts characterised by the composition, physical properties or the structure of the material of the parts to be joined; Joining with non-plastics material characterised by the intensive physical properties of the material of the parts to be joined, by the optical properties of the material of the parts to be joined, by the extensive physical properties of the parts to be joined, by the state of the material of the parts to be joined or by the material of the parts to be joined being a thermoplastic or a thermoset characterised by the extensive physical properties of the parts to be joined
    • B29C66/7352Thickness, e.g. very thin
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B29WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29LINDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00Other particular articles
    • B29L2031/756Microarticles, nanoarticles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00Specific applications of microelectromechanical systems
    • B81B2201/05Microfluidics
    • B81B2201/054Microvalves
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81CPROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2203/00Forming microstructural systems
    • B81C2203/03Bonding two components
    • B81C2203/032Gluing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81CPROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2203/00Forming microstructural systems
    • B81C2203/03Bonding two components
    • B81C2203/033Thermal bonding
    • B81C2203/036Fusion bonding
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0073Fabrication methods specifically adapted for microvalves
    • F16K2099/008Multi-layer fabrications
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0082Microvalves adapted for a particular use
    • F16K2099/0084Chemistry or biology, e.g. "lab-on-a-chip" technology
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16KVALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00Subject matter not provided for in other groups of this subclass
    • F16K2099/0082Microvalves adapted for a particular use
    • F16K2099/0094Micropumps

Definitions

  • the present invention relates to a method of joint manufacturing in a single step and without the need for alignment of microfluidic devices through a process of thermal compression between a sheet of equal or equal thickness. less than 200 micrometers and a rigid piece of thermoplastic materials so that the sheet is completely flat
  • thermoplastic piece to be glued has a thickness of less than 200 microns (sheet)
  • sheet the process of thermal bonding causes permanent deformation of the sheet, making it impossible to manufacture the device with a flat finish surface.
  • the temperatures required for permanent bonding between the sheet and the thermoplastic part cause said deformation.
  • the deformation of said membrane is counterproductive for many applications (lack of dimensional reproducibility, poor heat transmission due to poor contact with the heating element, creation of bubbles if used for the manufacture of microfluidic chips, inadequate transmission of an optical signal due to the curvature of the membrane that seals a possible reaction chamber, etc.).
  • the method of manufacturing the present invention solves the aforementioned problems and is based on the thermal compression of a flexible sheet with a rigid piece, so that the sheet is not curved, forming chambers, microvalves and micropumps without adhesive and without need for alignment. It involves the manufacture of microfluidic devices without the use of adhesives where the layer that seals the existing channels and chambers (cover) is of a thickness equal to or less than 200 micrometers with a deformation that may be less than 1 micrometer with respect to the horizontal plane.
  • the sheet maintains a completely flat surface (deformations below the micrometer) it is possible to contact a heating element without the presence of trapped air, which would make it difficult to transmit heat to the device.
  • lid as a mobile element for use in fluid control devices such as valves and pumps.
  • the manufacture of the final piece using a sheet without any structuring means that the sheet can be placed on the piece without any need to align the sheet with the piece to obtain the final system, something very common in the construction of This type of structure, where both pieces are structured and need micrometric alignment to work properly.
  • the process of the invention comprises permanent bonding by thermal compression of a thin sheet of less than 200 micrometers, to a piece of the same or similar material where the necessary microchannels, microchambers and through holes have been previously molded.
  • the sheet is used to seal the channels, as a mobile membrane to be used as a shut-off valve, as a mobile membrane to be used to displace fluids, and as a thin closing element of a microcamera that allows the possibility of applying cycles of temperature of a fast form.
  • This flat and reproducible seal allows an optical signal that crosses the sheet not to be affected by the curvature or this signal changes when introducing different chips.
  • the manufacturing method presented in this patent also allows the thin sheet to be completely flat. This is especially complicated when bonding is done by thermocompression, since when the sheet is subjected to high temperature, it tends to deform in a natural way.
  • the molded rigid part is a piece of a thermoplastic polymeric material (COC, COP, P MA, PC etc.) which has been microstructured to form microchannels, microchambers, microvalves or micropumps. This structuring can be done through processes such as “hot-embossing”, “injection molding”, “fine machining” or others.
  • the thin sheet refers to a sheet of the same material as the molded part (for example, COC, COP, PMMA, PC etc.), with a thickness less than . 200 micrometers, thickness being understood as the thickness of the sheet.
  • the process of gluing molded part-sheet includes:
  • thermoplastic polymer sheet and a rigid auxiliary part, for example glass, degassed in the first stage, selected from temporary bonding by thermal compression, temporary bonding assisted by ozone and / or temporary bonding assisted by electrostatic charges, giving rise to a rigid auxiliary sheet-piece assembly.
  • Rigid part is understood as the one that does not deform during the mechanical and thermal stress to which it must be subjected during the rest of the process.
  • thermoplastic polymeric sheet is brought into contact with the rigid auxiliary part and is subjected to a thermocompression process.
  • This process consists in subjecting both materials at a temperature close to the glass transition of the thermoplastic sheet and at a pressure between 0.1 and 10 bar.
  • the sheet is temporarily crushed to the auxiliary part, being able to be removed manually without problem, but with sufficient adhesion force to Do not allow the sheet to deform during the next process of bonding to the rigid thermoplastic part.
  • thermoplastic polymeric sheet When the thermoplastic polymeric sheet is capable of being activated by contact with ozone (COP, COC, etc.) and / or ultraviolet light, temporary bonding can be made to a rigid substrate activated by ozone and / or ultraviolet light.
  • the power of the ultraviolet light must be adapted to the size of the pieces to be activated and the specific material being used. Excessive power (more than 3J / cm 2 ) produces an irreversible bond between polymeric sheet and rigid piece, while a poor ultraviolet light power leads to deformation of the sheet during the next process of bonding with the rigid piece.
  • the dose should be between 0.7 J / cm2 and 0.9 J / cm2.
  • a smaller dose does not allow the process of bonding the sheet without deformation of the sheet; while a higher dose makes the bond between the lamina and the pyrex so strong that it is impossible to detach without breaking sheet, pyrex or both.
  • ionized gas to electrostatically charge the sheet and a rigid substrate so that they are temporarily adhered. Again, sheet and substrate are temporarily glued so as to avoid deformation of the sheet during the process of bonding with the rigid thermoplastic part.
  • thermoplastic polymeric rigid piece resulting from the temporary bonding ajar in the second stage, to give rise to a sheet of thickness equal to or greater than 200 microns fixed to a thermoplastic polymeric rigid piece, without loss of piano. In this way there is a completely polymeric final piece.
  • the correct use of the first stage allows the manufacture of the thermoplastic device without the creation of bubbling in the pieces.
  • the sheet of thermoplastic polymeric material does not deform during the bonding process with ⁇ a second polymeric rigid part (third stage).
  • This is a key process, since it prevents deformation of the sheet during the bonding process between it and the rigid piece.
  • a temporary sealing process is carried out on a rigid substrate, so that the deformation of the sheet is not allowed.
  • no type of adhesive material capable of containing air or expanding through temperature can be used, since this would cause deformation of the membrane during the application of the necessary temperature during the thermocompression process for bonding with the rigid piece.
  • thermoplastic polymer sheet and thermoplastic polymer rigid part are melted in a single device without damaging or modifying the structure previously made in the thermoplastic polymer rigid part or the thickness of the sheet
  • the glass transition temperature (Tg) is defined as the temperature at which the polymer ceases to be rigid and begins to be soft, in the case of thermoplastic polymeric materials the glass transition temperature will have a range of ⁇ 5 ° C.
  • FIG. 1 Microfluidic device with an open external microvalve
  • FIG. 1a Microfluidic device with the external microvalve of Figure 1a closed
  • FIG. 3a Microfluidic device with an open inner microvalve
  • FIG. 1 Microfluidic device with the interioir microvalve of Figure 2a closed
  • Figure 4a Microfluidic device with an open micropump and two microvalves, a first closed and a second open Figure 4b.-Microfluidic device of Figure 3a with the Micropump closed
  • Figure 4c Microfluidic device of Figure 3a with the micropump open and the first microvalve open and the second closed.
  • thermoplastic material 100 microns thick and a rigid auxiliary piece (2) of 1 mm thick glass, both degassed in a first stage, together with a polymer rigid piece of thermoplastic material ( 3), by introduction in a vacuum chamber at 10 mbar and heating at 60 ° C for 8 hours.
  • thermoplastic polymer sheet (1) to the rigid auxiliary part (2) of 1 mm thickness.
  • This temporary bonding is achieved by subjecting the thermoplastic polymer sheet (1) for 2 minutes to the presence of ozone and ultraviolet light and putting it in contact with the rigid auxiliary part (2), so that both are temporarily attached.
  • both materials are temporarily bonded tightly enough to prevent deformation of the sheet during the thermo-compression process to the rigid thermoplastic part, but at the same time it is easily detachable from the pyrex substrate manually, resulting in to a sheet-piece assembly auxiliary part (4),
  • a third stage (B) the bonding between the sheet-auxiliary part assembly (4) obtained in the second stage and the thermoplastic polymeric rigid part (3) degassed in the first stage is performed, by thermal compression, subjecting them to a pressure and temperature such that they allow permanent sealing between the sheet and the piece without damaging the structure of the rigid piece or varying the thickness of the sheet, that is, subject to a temperature equal to the glass transition of the sheet ( ⁇ 5 °).
  • the detachment (D) of the rigid auxiliary part (2) of the thermoplastic polymer sheet (1) resulting from the temporary bonding between the two in the second stage is carried out, to give rise to a final piece completely polymeric (5).
  • the membrane When the membrane is not pressed against the conduit, the flow can pass through the device, or vice versa, without problems. Instead, when the membrane is pressed it blocks the passage of fluid through the inlet conduit and the flow stops.
  • micro valve that blocks the passage of fluid at a different point to an inlet or outlet conduit, that is, blocks the passage in an internal channel of the device.
  • the proposed solution is based on a glue of two sheets on both sides of the piece. Said bonding is done at once through a thermocompression process (see figures 3a and 3b) J
  • the manufacturing method also allows the integration of micropumps based on the creation of a fixed fluid chamber to be displaced, and two valves, one on each side, that define the direction towards which the fluid moves through its synchronization as and as seen in figures 4a, 4b and 4c.

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  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Plasma & Fusion (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Lining Or Joining Of Plastics Or The Like (AREA)
  • Micromachines (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

Método de fabricación de dispositivos microfluidicos compuestos por una lamina (1) de espesor igual o inferior a 200 micrometros y una pieza rígida (3) ambos de material polimérico termoplástico que comprende: - Una primera etapa de desgasificado de: - una lámina polimérica de material termoplástico (1) - una pieza auxiliar rígida (2) - una pieza rígida polimérica de material termoplástico (3) - Una segunda etapa de pegado temporal entre la lámina polimérica termoplástica (1 ) a una pieza auxiliar rígida (2), - Una tercera etapa de pegado entre el conjunto lámina-pieza auxiliar (4) obtenido en la segunda etapa y la pieza rígida polimérica termoplástica (3) desgasificada en la primera etapa, por termocompresión - Una cuarta etapa de despegado de la pieza auxiliar rígida (2) de la lámina polimérica termoplástica (1 ) resultante del pegado temporal entre ambas en la segunda etapa, para dar lugar a una pieza final totalmente polimérica (5).

Description

MÉTODO DE FABRICACIÓN DE DISPOSITIVOS MICROFLUIDICOS
Campo de la invención
La presente invención se refiere a un método de fabricación conjunta en un solo paso y sin necesidad de alineamiento de dispositivos microfluidicos a través de un proceso de pegado por termocompresión entre una lamina de espesor igual o. inferior a 200 micrometros y una pieza rígida de materiales termoplásticos de forma que la lamina quede completamente plana
Antecedentes de la invención
El pegado de dos piezas rígidas de materiales termoplásticos por termocompresión esta publicado en Soo Hyun Lee et al "A polymer lab-on-a-chip for reverse transcription (RT)-PCR based point-of-care cíinicai diagnostics", The Royal Society of Chemistry 2008, Lab Chip, 2008, 8, 2121-2127. Al utilizar dos piezas rígidas y gruesas (del orden de! milímetro), en el caso de requerir el calentamiento de líquidos o gases presentes dentro del dispositivo, desde un elemento situado fuera de la estructura fluídica, éste se ve dificultado al tener que atravesar un material plástico, de baja conductividad térmica y de espesor considerable (varias centenas de micrometros). Además, no se disponen de partes susceptibles de ser móviles para su uso como elementos de control fluídico (válvulas, bombas...) por la misma razón.
Cuando una de las dos piezas termoplásticas a pegar tiene un espesor menor de 200 mieras (lamina) el proceso de pegado por termocompresion provoca la deformación permanente de la lamina, imposibilitando la fabricación del dispositivo con una superficie de acabado plano. Las temperaturas requeridas para el pegado permanente entre la lámina y la pieza termoplásticas provocan dicha deformación. La deformación de dicha membrana es contraproducente para muchas aplicaciones (falta de reproducibilidad dimensional, pobre transmisión de calor por un mal contacto con el elemento calentador, creación de burbujas en caso de ser utilizada para la fabricación de chips microfluidicos, inadecuada transmisión de una señal óptica debido a la curvatura de la membrana que sella una posible cámara de reacción, etc.).
Descripción de la invención
El método de fabricación de la presente invénción resuelve los problemas antes mencionados y se basa, en el pegado por termocompresión de una lámina flexible con una pieza rígida, de forma que la lámina no quede curvada, formándose cámaras, microválvulas y microbombas sin adhesivo y sin necesidad de alineamiento. Se trata de la fabricación de dispositivos microfluidicos sin uso de adhesivos donde la capa que sella los canales y cámaras existentes (tapa) es de un espesor igual o inferior a 200 micrometros con una deformación que puede llegar a ser inferior a 1 micrometro con respecto al plano horizontal.
De esta forma, es posible:
Calentar los líquidos presentes en el dispositivo a través de la tapa, ya que su bajo espesor permite una transmisión de calor eficiente.
Dado que la lamina mantiene una superficie totalmente plana (deformaciones por debajo del micrometro) es posible el contacto con un elemento calentador sin la presencia de aire atrapado, lo cual dificultaría la transmisión de calor al dispositivo.
Utilizar la tapa como elemento móvil para su uso en dispositivos de control fluidico tales como válvulas y bombas.
Obtener una tapa ópticamente plana para ensayos ópticos realizados dentro de la cámaras del chip.
Obtener una reproducibilidad dimensional de chip a chip facilitando cualquier tipo de transducción: mecánica, óptica, térmica, etc. Esta característica es muy importante dado que los chips son generalmente desechables y una vez usados necesitan ser reemplazados por nuevos.
Al no utilizar adhesivo no se introduce ningún compuesto extraño en el circuito fluidico que pueda interaccionar con la muestra^ sino que el fluido solamente esta en contacto con el material estructural del dispositivo.
Por otro lado, la fabricación de la pieza final usando una lamina sin ningún tipo de estructuración hace que ia lamina pueda colocarse sobre la pieza sin ninguna necesidad de alinear la lamina con la pieza para obtener el sistema final, algo muy común en la construcción de este tipo de estructuras, donde ambas piezas están estructuradas y necesitan de alineación micrométrica para que funcionen correctamente.
El procedimiento de la invención comprende el pegado permanente por termocompresion de una lámina delgada de menos de 200 micrometros, a una pieza del mismo o similar material donde se han moldeado previamente los microcanales, microcamaras y agujeros pasantes necesarios. De esta manera, la lámina es utilizada para sellar los canales, como membrana móvil para ser utilizada como válvula de cierre, como membrana móvil para ser utilizada para desplazar fluidos, y como elemento fino de cierre de una microcámara que permite la posibilidad de aplicar ciclos de temperatura de una forma rápida. Este sellado plano y reproducible permite que una señal óptica que atraviese la lámina no sea afectada por la curvatura o ésta señal cambie al introducir diferentes chips. El método de fabricación presentado en esta patente permite además que la lámina delgada esté totalmente plana. Esto es especialmente complicado cuando el pegado se realiza por termocompresión, ya que al someter la lámina a alta températura, ésta tiende de manera natural a deformarse.
La pieza rígida moldeada es una pieza de un material polimerico termoplástico (COC, COP, P MA, PC etc.) la cual se ha microestructurado para formar microcanales, microcámaras, microválvulas o microbombas. Esta estructuración se puede hacer por medio de procesos como "hot-embossing", "injection moulding", "fine machining" u otros.
La lámina delgada se refiere a una lámina del mismo material que la pieza moldeada (por ejemplo, COC, COP, PMMA, PC etc.), con un espesor inferior a .200 micrometros, entendiéndose por espesor el grosor de la lámina.
El proceso de pegado pieza moldeada-lámina comprende:
- Una primera etapa de desgasificado de:
- una lámina polimérica de material termoplástico
- una pieza auxiliar rígida
- una pieza rígida polimérica de material termoplástico
a través de su introducción en una cámara de vacío a una presión por debajo del 500 mbar y/o calentamiento a una temperatura seleccionada entre la temperatura ambiente y la temperatura de transición vitrea de cada pieza dependiendo de la presión de vacio utilizada, durante un tiempo dependiente del grosor de las piezas (de 1 a 24 horas), para evitar la aparición de burbujas en la superficie de las piezas
- Una segunda etapa de pegado temporal entre la lámina polimérica termoplástica y una pieza auxiliar rígida, por ejemplo vidrio, desgasificados en la primera etapa, seleccionado entre pegado temporal por termocompresión, pegado temporal asistido por ozono y/o pegado temporal asistido por cargas electrostáticas, dando lugar a un conjunto lámina-pieza auxiliar rígida. Entendiéndose por pieza rígida a aquella que no se deforme durante el stress mecánico y térmico al que se le debe someter durante el resto del proceso.
a) Termocompresión no permanente:
La lámina polimérica termoplástica se pone en contacto con la pieza auxiliar rígida y se somete a un proceso de termocompresión. Dicho proceso consiste en someter ambos materiales a una temperatura cercana a la transición vitrea de la lamina termoplástica y a una presión entre 0.1 y 10 bar. Como resultado, la lámina queda aplastada de forma temporal a la pieza auxiliar, pudiéndose retirar manualmente sin problema, pero con una fuerza de adherencia suficiente como para no permitir que la lámina se deforme durante el proceso siguiente de pegado a la pieza termopíástica rígida.
b) Pegado temporal asistido por ozono y/o luz ultravioleta:
Cuando la lámina polimérica termopíástica es susceptible de activarse por contacto con el ozono (COP, COC, etc) y/o luz ultravioleta, se puede realizar ei pegado temporal a un substrato rígido activable por ozono y/o luz ultravioleta. En este caso, la potencia de la luz ultravioleta debe adecuarse al tamaño de las piezas a activar y el material especifico que se está usando. Una potencia excesiva (mas de 3J/cm2) produce un pegado irreversible entre lamina polimérica y pieza rígida, mientras que una potencia de luz ultravioleta deficiente desemboca en la deformación de la lamina durante el siguiente proceso de pegado con la pieza rígida. En el caso de un pegado temporal entre material COP y Pyrex (pyrex es el nombre comercial de un vidrio que se usaría como substrato rígido) la dosis debe ser entre 0.7 J/cm2 y 0.9 J/cm2. Una dosis menor no permite hacer el proceso de pegado de la lamina sin la deformación de ésta; mientras que una dosis mayor hace que el pegado entre ía lamina y.el pyrex sea tan fuerte que resulta imposible el despegado sin romper lámina, pyrex o ambos.
c) Pegado temporal asistido por cargas electrostáticas:
Otra opción es la utilización de gas ionizado para cargar electrostáticamente la lámina y un substrato rígido de forma que queden adheridos temporalmente. De nuevo, lámina y substrato son temporalmente pegados de forma que evitan la deformación de la lámina durante el proceso de pegado con la pieza rígida termopíástica.
- Una tercera etapa de pegado entre el conjunto lámina-pieza obtenido en la segunda etapa anterior y una pieza rígida polimérica desgasificado en la primera etapa, aplicando una temperatura igual a la temperatura de transición vitrea del termoplástico (± 5°C) utilizado (tanto para la lámina como para la pieza rígida) y aplicando una de presión (de 0.1 a 10 bar) que permita la fusión entre lámina y pieza rígida sin la deformación de las estructuras ya definidas en la pieza (por ejemplo, en el caso de piezas y lamina de COC 5013 la temperatura es de 130 C y la presión es de 1 bar).
- Una cuarta etapa de despegado de la pieza auxiliar rígida de la lámina polimérica termopíástica resultante del pegado temporal entreambas en la segunda etapa, para dar lugar a una lámina de espesor igual o mayor a 200 mieras fijada a una pieza rígida polimérico termopíástica, sin pérdida de pianitud. De esta forma queda una pieza final totalmente polimérica. La utilización correcta de la primera etapa permite la fabricación del dispositivo termoplástico sin ia creación de burbujeo en las piezas.
A través de ia pieza auxiliar rígida de la segunda etapa, se consigue que la lámina de material polimérico termoplástico no se deforme durante el proceso de pegado con <\a segunda pieza rígida polimérica (etapa tercera). Este es un proceso clave, ya que impide la deformación de la lamina durante el proceso de pegado entre esta y la pieza rígida. Hay que aclarar que al tratarse de un proceso por termocompresión, una lámina delgada de 200 micrometros o inferior tiende a deformarse y curvarse cuando se le somete a las, temperaturas y presiones necesarias para su pegado a la pieza rígida. Por tanto, para conseguir que la lámina se quede completamente plana, se realiza un proceso de sellado temporal a un substrato rígido, de forma que no se permita ia deformación de la lámina. Para dicho sellado temporal no se puede utilizar ningún tipo de material adhesivo susceptible de contener aire o expandirse a través de temperatura, ya que esto provocaría la deformación de la membrana durante la aplicación de la temperatura necesaria durante el proceso de termocompresión para el pegado con la pieza rígida.
A través de la etapa tercera citada arriba, se consigue que ambos, lámina polimérica termoplástica y pieza rígida polimérica termoplástica, se fundan en un único dispositivo sin dañar o modificar la estructuración realizada con anterioridad en la pieza rígida polimérica termoplástica o el espesor de la lámina
La temperatura de transición vitrea (Tg) se define como la temperatura a la que el polímero deja de ser rígido y comienza a ser blando, en el caso de materiales poliméricos termoplásticos la temperatura de transición vitrea tendrán un intervalo de ± 5°C.
Breve descripción de los dibujos
A continuación se pasa a describir de manera muy breve una serie de dibujos que ayudan a comprender mejor la invención y que se relacionan expresamente con una realización de dicha invención que se presenta como un ejemplo no limitativo de ésta.
Figura 1.- Esquema de las etapas del método de la invención hasta la obtención del conjunto lámina-pieza
Figura 2a.- Dispositivo microfluidico con una microválvula exterior abierta
Figura 2b.- Dispositivo microfluidico con la microválvula exterior de la figura 1a cerrada
Figura 3a.- Dispositivo microfluidico con una Microválvula interior abierta
Figura 3.a.- Dispositivo microfluidico con la microválvula interioir de la figura 2a cerrada
Figura 4a - Dispositivo microfluidico con una microbomba abierta y dos microválvulas, una primera cerrada y otra segunda abierta Figura 4b.-Dispositivo microfluidico de la figura 3a con la Microbomba cerrada
Figura 4c- Dispositivo microfluidico de la figura 3a con la microbomba abierta y la primera microválvula abierta y la segunda cerrada.
Las referencias numéricas representadas en las figuras corresponden a los siguientes elementos sin que ello suponga carácter limitativo alguno:
1. - Lámina polimérica termoplástica
2. - Pieza auxiliar rígida
3. - Pieza rígida polimérica termoplástica
4. - conjunto lámina-pieza pieza auxiliar
5. - pieza final totalmente polimérica
Descripción de una realización preferida de la invención
A continuación se procede a describir un ejemplo de fabricación de un dispositivo microfluidico mediante el método descrito en la presente invención tal y como se muestra en la figura 1:
Se parte de una lámina polimérica de material termoplástico (1) de 100 mieras de espesor y una pieza auxiliar rígida (2) de vidrio de 1 mm de espesor, ambas desgasificadas en una primera etapa, junto con una pieza rígida polimérica de material termoplástico (3), por introducción en una cámara de vacío a 10 mbar y calentamiento a 60 °C durante 8 horas.
Posteriormente, en una segunda etapa (A), se realiza un pegado temporal entre la lámina polimérica termoplástica (1 ) a la pieza auxiliar rígida (2) de 1 mm de espesor. Este pegado temporal se consigue sometiendo a la lámina polimérica termoplástica (1 ) durante 2 minutos a la presencia de ozono y luz ultravioleta y poniéndola en contacto con la pieza auxiliar rígida (2), de forma que ambos quedan temporalmente adheridos.
Como resultado ambos materiales quedan adheridos de forma temporal lo suficientemente fuerte como para evitar la deformación de la lámina durante el proceso de pegado por termocompresion a la pieza rígida termoplástica, pero a la vez es fácilmente separable del substrato de pyrex de forma manual, dando lugar a un conjunto lámina-pieza pieza auxiliar (4),
En una tercera etapa (B) se realiza el pegado entre el conjunto lámina-pieza auxiliar (4) obtenido en la segunda etapa y la pieza rígida polimérica termoplástica (3) desgasificada en la primera etapa, por termocompresion, sometiéndolos á una presión y temperatura tales que permitan el sellado permanente entre ía lamina y la pieza sin dañar la estructuración de la pieza rígida ni variar el espesor de la lamina, es decir, sometidos a una temperatura igual a la transición vitrea de la lamina (±5°). Y finalmente, en una cuarta etapa, se realiza el despegado (D) de la pieza auxiliar rígida (2) de la lámina polimérica termopiástica (1 ) resultante del pegado temporal entre ambas en la segunda etapa, para dar lugar a una pieza final totalmente polimérica (5). 1
Dos tipos de microválvula se pueden obtener por medio de este método de fabricación de dispositivos:
a) Microválvula exterior (out-line microvalve):
Es una microválvula basada en la actuación de Una membrana que se encuentra en el lado contrario y directamente opuesta al punto de inserción o extracción del fluido (ver figuras 2a y 2b).
Cuando la membrana no esta presionada contra el conducto el flujo puede pasar a través del dispositivo, o viceversa, sin problemas. En cambio, cuando la membrana esta presionada bloquea el paso del fluido a través del conducto de entrada y el flujo se detiene.
b) Microválvula interior (ln-line Microválvula)
Se refiere a aquella microválvula que bloquea el paso del fluido en un punto diferente a un conducto de entrada o salida, esto es, bloquea el paso en un canal interno del dispositivo. La solución propuesta se basa en un pegado de dos láminas a ambos lados de la pieza. Dicho pegado se realiza de una sola vez a través de un proceso de termocompresion (ver figuras 3a y 3b) J
El método de fabricación también permite la integración de microbombas basadas en la creación de una cámara de fluido fijo a desplazar, y dos válvulas, una a cada lado, que definen la dirección hacia la que el fluido se desplaza por medio de su sincronización tal y como se observa en las figuras 4a, 4b y 4c.

Claims

REIVINDICACIONES
1. - Método de fabricación de dispositivos microfluidicos compuestos por una lamina (1) de espesor igual o inferior a 200 micrometros y una pieza rígida (3) ambos de material polimérico termoplástico caracterizado por comprender:
- Una primera etapa de desgasificado de: ·
- una lámina polimérica de material termoplástico (1)
- una pieza auxiliar rígida (2)
- una pieza rígida polimérica de material termoplástico (3) a través de su introducción en una cámara de vacío y/o calentamiento a una temperatura seleccionada entre la temperatura ambiente y la temperatura de transición vitrea de cada pieza,
- Una segunda etapa de pegado temporal entre la lámina polimérica termoplástica (1 ) a una pieza auxiliar rígida (2) dando luga'r a un conjunto lámina-pieza pieza auxiliar (4),
- Una tercera etapa de pegado entre el conjunto lámina-pieza auxiliar (4) obtenido en la segunda etapa y la pieza rígida polimérica termoplástica (3) desgasificada en la primera etapa, por termocompresión
- Una cuarta etapa de despegado de la pieza auxiliar rígida (2) de la lámina polimérica termoplástica (1 ) resultante del pegado temporal entre ambas en la segunda etapa, para dar lugar a una pieza final totalmente polimérica (5).
2. - Método de fabricación según la reivindicación 1 caracterizado por que la segunda etapa se lleva a cabo por termocompresión no permanente consistente a lámina polimérica termoplástica (1) y la pieza auxiliar rígida (2), a una temperatura cercana a la transición vitrea de la lamina termoplástica (1 ) y a una presión entre 0.1 y 10 bar.
3. - Método de fabricación según la reivindicación 1 caracterizado por que la segunda etapa se lleva a cabo por pegado temporal asistido por ozono.
4. - Método de fabricación según la reivindicación 3 caracterizado por que la lámina polimérica termoplástica es COP o COC.
5. - Método de fabricación según la reivindicación 1 caracterizado por que la segunda etapa se lleva a cabo por pegado temporal asistido por cargas electrostáticas.
PCT/ES2010/070468 2010-07-07 2010-07-07 Método de fabricación de dispositivos microfluidicos. Ceased WO2012004423A1 (es)

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US20140102636A1 (en) 2014-04-17
US9409167B2 (en) 2016-08-09

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