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WO2025078603A1 - Puces microfluidiques et leurs procédés de fabrication - Google Patents

Puces microfluidiques et leurs procédés de fabrication Download PDF

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Publication number
WO2025078603A1
WO2025078603A1 PCT/EP2024/078687 EP2024078687W WO2025078603A1 WO 2025078603 A1 WO2025078603 A1 WO 2025078603A1 EP 2024078687 W EP2024078687 W EP 2024078687W WO 2025078603 A1 WO2025078603 A1 WO 2025078603A1
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WO
WIPO (PCT)
Prior art keywords
micrometres
laser
wafer
modified material
regions
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.)
Pending
Application number
PCT/EP2024/078687
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English (en)
Inventor
Bruce Scott
Svilen SAVOV
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TTP PLC
Original Assignee
TTP PLC
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Filing date
Publication date
Application filed by TTP PLC filed Critical TTP PLC
Publication of WO2025078603A1 publication Critical patent/WO2025078603A1/fr
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Anticipated expiration legal-status Critical

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
    • B05B1/26—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectors; Breaking-up the discharged liquid or other fluent material by impinging jets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/001—Particle size control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00—Working by laser beam, e.g. welding, cutting or boring
    • B23K26/02—Positioning or observing the workpiece, e.g. with respect to the point of impact; Aligning, aiming or focusing the laser beam
    • B23K26/06—Shaping the laser beam, e.g. by masks or multi-focusing
    • B23K26/062—Shaping the laser beam, e.g. by masks or multi-focusing by direct control of the laser beam
    • B23K26/0622—Shaping the laser beam, e.g. by masks or multi-focusing by direct control of the laser beam by shaping pulses
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00—Working by laser beam, e.g. welding, cutting or boring
    • B23K26/50—Working by transmitting the laser beam through or within the workpiece
    • B23K26/53—Working by transmitting the laser beam through or within the workpiece for modifying or reforming the material inside the workpiece, e.g. for producing break initiation cracks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00119—Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K2101/00—Articles made by soldering, welding or cutting
    • B23K2101/36—Electric or electronic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K2103/00—Materials to be soldered, welded or cut
    • B23K2103/50—Inorganic material, e.g. metals, not provided for in B23K2103/02 – B23K2103/26
    • B23K2103/54—Glass
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K2103/00—Materials to be soldered, welded or cut
    • B23K2103/50—Inorganic material, e.g. metals, not provided for in B23K2103/02 – B23K2103/26
    • B23K2103/56—Inorganic material, e.g. metals, not provided for in B23K2103/02 – B23K2103/26 semiconducting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/05—Microfluidics
    • B81B2201/058—Microfluidics not provided for in B81B2201/051 - B81B2201/054

Definitions

  • Microfluidic chips are commonly manufactured by etching fluid channels into the surface of a silicon layer.
  • a glass layer is subsequently bonded to the silicon wafer using anodic bonding such that the fluid channels are sealed, being sandwiched between the layers.
  • the microfluidic chip is cut from the combined wafer using an abrasive blade or disc.
  • the blade and wafer are cooled by a flow of water or other liquid.
  • the cutting creates a surface in the side of the chip in which one or more nozzles from the fluid channels are positioned. During use, jets of liquid which can be used to produce aerosol are expressed from the nozzles.
  • the present invention seeks to address at least some of the above problems.
  • the present invention provides methods for manufacturing microfluidic chips which use a laser to create internal regions of laser modified material within a wafer.
  • the internal regions of laser modified material form regions of weakness within the wafer. Consequently, when the wafer is exposed to mechanical stress (e.g. a tensile stress, a bending stress or a shear stress), cracks tend to propagate from the laser modified material, fracturing the wafer.
  • mechanical stress e.g. a tensile stress, a bending stress or a shear stress
  • cracks tend to propagate from the laser modified material, fracturing the wafer.
  • the methods offer a clean and dry approach for manufacturing microfluidic chips.
  • a method of manufacturing a microfluidic chip for generating aerosols from liquids comprising forming one or more fluid channels in a surface of a first substrate layer, providing a second substrate layer in contact with said surface of the first substrate layer, and bonding the first substrate layer and second substrate layer together to form a wafer that comprises the one or more fluid channels extending therethrough, dividing the wafer to form the microfluidic chip, wherein the fluid channels in the microfluidic chip define at least one nozzle in an outlet surface of the microfluidic chip, and wherein dividing the wafer to form the microfluidic chip comprises irradiating the wafer with a laser, wherein the laser is focused inside the wafer to create one or more internal regions of laser modified material within the wafer, wherein the one or more internal regions of laser modified material extend in an intended fracture plane defining a desired arrangement of the outlet surface of the microfluidic chip, and applying mechanical stress to the wafer to fracture the wafer along the
  • the method uses a laser to modify material within a wafer, to as to accurately control where the wafer splits under mechanical stress (e.g. tensile stress, bending stress or shear stress).
  • mechanical stress e.g. tensile stress, bending stress or shear stress.
  • the laser energy Near the focal point of the laser, where the laser energy is high, large amounts of energy from the laser will be absorbed by the material of the wafer thereby melting, charring, forming a crack or otherwise modifying the material within the wafer local to the focal point. Away from the focal point, the wafer material will be unchanged.
  • the internal regions of laser modified material are regions in which the material properties of the substrates forming the wafer are permanently changed.
  • the regions of laser modified material are formed integrally within or inside the wafer, rather than being at an outside surface of the wafer.
  • the one or more nozzles (i.e. outlets) formed in the outlet surface are also accurately positioned.
  • the nozzles have consistent shapes and are formed in smooth surfaces. Therefore, liquid jets directed from the nozzles during use are typically directed as intended, and the microfluidic chips can reliably form aerosols.
  • the microfluidic chips may be configured such that two or more jets of liquid from two or more respective nozzles are directed into each other such that they collide, breaking the jets into an aerosol. Equally a jet of liquid from one nozzle may be directed to collide with a wall or feature to generate an aerosol.
  • the method allows the microfluidic chips to be consistently manufactured so that the jets of liquid collide with each other and/or a wall in an intended manner.
  • microfluidic chips In microfluidic chips the efficiency of the aerosolisation depends on (among other factors): how much overlap there is between the impinging jets, or in the case of a single jet, the jet hitting the intended target; how far away from the nozzle collision happens; and the velocity of the jets.
  • the microfluidic chips manufactured with the methods discussed herein avoid errors or surface defects which might otherwise cause the jets to only partially impinge or miss their intended target, change the location of collision or impingement, or affect the velocity of the jets.
  • the outlet surface may be positioned further from the inlets in the microfluidic chip than is desirable, meaning the channels within the chip will be longer than expected, have a larger pressure drop through them and eject liquid at lower velocities.
  • the channels will be shorter than expected and the liquid in the jets may be ejected at particularly high velocities.
  • dividing it will be understood that the wafer may be diced, being divided or separated from other portions of the wafer. In particularly preferred examples a wafer may be diced to form a plurality of microfluidic chips. Such processes of making multiple microfluidic chips from the same wafer are discussed further below.
  • the microfluidic chips produced using this method may be configured to receive liquid at a pressure in the range from 50 to 600 bar, or preferably 100 to 400 bar, more preferably 150 to 350 bar, and more preferably still 200 to 300 bar.
  • the first and second substrate layers are preferably planar pieces of material which have one direction which has a relatively small dimension in comparison to their other two dimensions.
  • the fluid channels formed into the first substrate layer are preferably open recesses or grooves formed in the surface of the first substrate layer. These open recesses or grooves are enclosed by providing and bonding an overlaying second substrate layer.
  • the distance between each nozzle and the respective nearest portion of laser modified material is at least 15 micrometres, preferably at least 20 micrometres, more preferably at least 25 micrometres, more preferably still at least 30 micrometres. Providing an appropriate spacing between the laser modified material and the desired position of the nozzles in the intended fracture plane is important to ensure high yields of microfluidic chips that can reliably produce an aerosol.
  • the channels from which the nozzles are formed are microfluidic channels, and the chip is a microfluidic chip.
  • the outlet channel from which the nozzle is formed, which is arranged at an angle to the outlet plane may have a depth of approximately 5 micrometres (e.g. 3 to 7 micrometres) and a width of approximately 7 micrometres (e.g. 5 to 10 micrometre).
  • the fluid channels define two nozzles in the outlet surface of the microfluidic chip, the two nozzles configured to direct respective jets of liquid towards one another. This collision produces a fine aerosol of liquid particles with consistent particle sizes.
  • the distance between the two nozzles is at least 20 micrometres.
  • the distance between the two nozzles is preferably in the range from 20 to 100 micrometres. More preferably the distance between the two nozzles is in in the range from 25 to 60 micrometres and more preferably still in the range from 30 to 50 micrometres.
  • other distances may also be suitable.
  • the one or more internal regions of laser modified material comprise a plurality of linear regions of laser modified material that extend in a direction parallel to the fluid channel plane.
  • a linear region it is understood that the region has an elongate shape in the intended fracture plane, having one dimension that is significantly longer than the other.
  • the focal point of the laser may be moved or traversed linearly inside the wafer to create a continuous region of laser modified material embedded within the wafer.
  • the focal point of the laser may be moved across the intended fracture plane continuously or intermittently. Equally, the laser may be applied continuously whilst it is moved or intermittently as its focal point moved across the intended fracture plane. It is not essential that the laser modified material is formed in linear regions.
  • the regions of laser modified material may be curved or formed in circular or square shapes. Equally, the regions of laser modified material need not be parallel to the fluid channel plane. Having said this, linear regions of laser modified materials that are parallel to the fluid channel plane and/or parallel to the surface of the wafer are particularly easy to produce since the laser may be applied at consistent depths within the wafer relative to the fluid channel and/or the exterior of the wafer.
  • At least some linear regions of laser modified material are arranged in groups of colinear regions of laser modified material, wherein each group of colinear regions of laser modified material comprises at least two linear regions of laser modified material separated by unmodified material.
  • the laser may be applied along multiple separate sections of a line constant depth within the intended fracture plane.
  • the nozzles are positioned within the region of unmodified material. More preferably still, the region of unmodified material extends from the nozzles to at least one edge of the intended fracture plane in a direction perpendicular to the fluid channel plane. Therefore, the region of unmodified material may extend to an upper or lower edge of the intended fracture plane and the ultimate outlet surface.
  • These arrangements offer particularly consistent positioning of nozzles within microfluidic chips, and therefore the methods offer particular high yields. Equally, this approach leads to nozzles with consistent geometry and dimensions - i.e. nozzles can be reliably be produced with straight sides and regular shapes.
  • the nozzles are positioned between two adjacent linear regions of laser modified material in a direction perpendicular to the fluid channel plane; or between two colinear regions of laser modified material in a direction parallel to the fluid channel plane.
  • irradiating the wafer with a laser comprises irradiating the wafer with a laser from a single side of the wafer.
  • This provides benefits over arrangements where the wafer is irradiated from both sides, since it can be difficult to align or register regions of laser modified material formed from laser beams incident from different sides of the wafer.
  • laser modified material is not aligned in a single intended fracture plane, the wafer will not fracture in a smooth and consistent manner and may produce microfluidic chips with notches or steps in their outlet surfaces. These notches or steps can affect the performance of the microfluidic chips if they affect the position and orientation of the nozzles in the outlet surface.
  • irradiating the wafer from a single side avoids the need to use multiple lasers positioned on different sides of the wafer and/or the need to flip ior rotate the wafer relative to a laser source.
  • the methods discussed above may be used to produce large numbers of microfluidic chips from the same wafer.
  • the process of forming regions of laser modified material within the wafer and applying mechanical force may be used to singulate a wafer, dividing it into multiple separate chips. This offers an efficient way to produce large numbers of microfluidic chips.
  • a microfluidic chip for generating aerosol from liquid, the microfluidic chip comprising one or more inlets for receiving liquids, the inlets being formed in an inlet surface of the microfluidic chip, one or more nozzles configured to emit a jet of liquid, the nozzles being formed in an outlet surface of the microfluidic chip, one or more fluidic channels connecting the one or more inlets to the one or more nozzles, wherein the outlet surface of the microfluidic chip comprises one or more regions of laser modified material.
  • the microfluidic chips may be manufactured using any of the methods discussed above, including any preferable or optional features.
  • the microfluidic chips may offer any of the benefits and advantages discussed above. In particular, higher yields means that microfluidic chips are on average more economic to produce.
  • the microfluidic chip may be configured receive a liquid at its inlet or inlets with a pressure in the range from 50 to 600 bar, or preferably 100 to 400 bar, more preferably 150 to 350 bar, and more preferably still 200 to 300 bar. Additionally or alternatively, the microfluidic chip may be configured to dispense droplets with an average diameter in the range of 1 to 10 microns, preferably from 2 to 6 microns, and more preferably from 3 to 5 microns.
  • an inhaler system comprising a microfluidic chip as discussed in relation to the previous aspects of the invention.
  • These systems may include any or the preferable or optional features discussed above with reference to the preceding aspects of the invention and offer corresponding benefits.
  • the inhaler system is a soft mist inhaler system.
  • a soft mist inhaler is an inhaler which produces an aerosol (mist) that spreads out relatively slowly.
  • the inhaler system may be configured to dispense an aerosol at 2 m/s or less when measured at a distance of 10 cm from a mouthpiece or nozzle, preferably 1.6 m/s or less and more preferably less than 1m/s and/or wherein the dispensing or nebulization of a dose takes longer than 0.7 seconds, and preferably at least 1 second.
  • the inhaler system is configured to dispense fluid in puffs with a volume of medicament in the range of 0.5 microlitres to 50 microlitres, more preferably 0.5 microlitres to 30 microlitres, more preferably still from 10 to 20 microliters.
  • An intended dose of the medicament from the inhaler may comprise a single puff, or a plurality of puffs (e.g. two puffs).
  • the inhaler system may be configured to provide a liquid to the inlets of the microfluidic chip at a pressure in the range from 50 to 600 bar, or preferably 100 to 400 bar, more preferably 150 to 350 bar, and more preferably still 200 to 300 bar. Such pressures produce fine aerosols of high quality.
  • the inhaler system is configured to dispense droplets with an average diameter in the range of 1 to 10 microns, preferably from 2 to 6 microns, and more preferably from 3 to 5 microns.
  • the inhaler system is a multidose inhaler system, wherein the collapsible bag of the cartridge is configured to store a plurality of doses of liquid medicament.
  • the collapsible bag has a capacity or internal volume in the range of 0.5 to 10 millilitres, preferably in the range of 1 to 5 millilitres.
  • Figure 1 shows schematically in perspective view a microfluidic chip according to an embodiment of the invention
  • Figures 2a to 2f show schematically in perspective view a series of a steps of a method of manufacturing the microfluidic chip of Figure 1 according to an embodiment of the invention
  • Figure 3a shows a pattern of lines across which a laser can be applied in an intended fracture plane within a wafer during the manufacturing of microfluidic chips in accordance with the invention
  • Figures 3b and 3c show images image obtained by microscope of an outlet face of a microfluidic chip according to an embodiment of the invention manufactured using the pattern for laser modified material shown in Figure 3a
  • Figure 4a shows a pattern of lines across which a laser can be applied in an intended fracture plane within a wafer during the manufacturing of microfluidic chips in accordance with the invention
  • Figures 4b and 4c show images image obtained by microscope of an outlet face of a microfluidic chip according to an embodiment of the invention manufactured using the pattern for laser modified material shown in Figure 4a;
  • Figure 5a shows a pattern of lines across which a laser can be applied in an intended fracture plane within a wafer during the manufacturing of microfluidic chips in accordance with the invention
  • Figures 5b and 5c show images obtained by microscope of an outlet face of a microfluidic chip according to an embodiment of the invention manufactured using the pattern for laser modified material shown in Figure 5a;
  • Figures 6a and 6b shows an images obtained by microscope of an outlet face of a further microfluidic chip according to an embodiment of the invention manufactured using the pattern for laser modified material shown in Figure 5a;
  • Figure 5c shows the nozzles of the microfluidic chip of Figure 5b;
  • Figure 7 shows schematically a series of steps of a method of manufacturing a microfluidic chip according to an embodiment of the invention
  • Figure 8a, 8b and 8c show images obtained by microscope of the outlet faces of further microfluidic chips according to embodiments of the invention.
  • Figure 10 shows a pattern of lines across which a laser can be applied in an intended fracture plane within a wafer during the manufacturing of microfluidic chips in accordance with the invention
  • Figures 11a to 11 e show schematically a series of steps of a method of manufacturing a plurality of microfluidic chips according to an embodiment of the invention
  • Figure 12 shows an etch pattern for an individual fluid channel unit which may be used to manufacture microfluidic chips in accordance with an embodiment of the invention
  • Figure 13 shows an inhaler system comprising microfluidic chips in accordance with the invention.
  • FIG. 1 shows a microfluidic chip 50 according to the invention.
  • the microfluidic chip 50 is configured to generate an aerosol from a liquid such as a medicine or medicament.
  • the microfluidic chip 50 is well suited for use in an inhaler.
  • the inhaler may push a liquid medicament through the microfluidic chip 50 to form an aerosol, at which point the aerosol may be dispensed to a user so that the user may breathe the aerosol in.
  • the microfluidic chip 50 is cuboidal, and has an inlet face 52 and an outlet face 54.
  • the inlet face 52 and outlet face 54 are opposed on opposite sides of the fluidic chip, the outlet face 54 being shown in Figure 1 with the inlet face 52 being to the rear of the microfluidic chip as shown.
  • FIGs 2a to 2g schematically show sequential steps in a method of manufacturing the microfluidic chip 50 of Figure 1. These figures show the creation of a single microfluidic chip 50 from a cuboidal wafer 30 for understanding. However, in preferred implementations large numbers of microfluidic chips (e.g. over 100 chips) may be created from each wafer. These approaches of forming multiple microfluidic chips from a single wafer are discussed below in relation to Figures 11 and 12.
  • the fluid channels 14 extend in a plane that is parallel or substantially parallel to the upper surface of the first substrate layer which is parallel with the x-y plane as shown.
  • the fluid channels 14 define a fluid channel plane, that is the plane in which the fluid channels 14 extend in.
  • This fluid channel plane can be defined by the centreline of the depth of the fluid channels 14 and, because the fluid channels 14 have substantially constant depth, is a plane parallel to the upper surface 12 of the first substrate layer and located a below the the upper surface 12 of the first substrate layer 10 by a distance is equal to half of the depth of the fluid channels 14.
  • a dotted line L illustrates the position of the original interface between the first and second layers 10, 20 before they are bonded.
  • This dotted line L is provided for understanding only and may not be visible in practice, especially where the first and substrate layers 10, 20 are formed of the same material.
  • the laser beam 42 is focused through a light-converging lens with: a magnification of 50 times; a numerical aperture of 0.55; and a transmittance at the wavelength of the laser light of at least 60%.
  • the focal point 44 of the laser beam 42 is also traversed through the wafer 30 at a speed of 100 mm/s.
  • This movement of the laser beam 42 relative to the wafer 30 may be achieved by moving the wafer 30 (e.g. where the wafer 30 is mounted on a moveable mounting table), adjusting the arrangement of a lens, mirror or other optical element, or by moving the laser and lens together relative to the wafer 30.
  • the size of the regions of laser modified material have been formed that are approximately 100 micrometres in depth in the direction perpendicular to the fluid channel plane (i.e. in the z direction as shown).
  • the laser beam 42 is focused through a light-converging lens with: a magnification of 50 times and a numerical aperture of 0.55 or a magnification of 100 and a numerical aperture of 0.80; and a transmittance at the wavelength of the laser light of at least 60%.
  • the focal point 44 of the laser beam 42 is also traversed through the wafer 30 at a speed of 100 mm/s.
  • This movement of the laser beam 42 relative to the wafer 30 may be achieved by moving the wafer 30 (e.g. where the wafer 30 is mounted on a moveable mounting table), adjusting the arrangement of a lens, mirror or other optical element, or by moving the laser and lens together relative to the wafer 30.
  • the size of the regions of laser modified material have been found to be approximately 100 micrometres in depth in the direction perpendicular to the fluid channel plane (i.e. in the z direction as shown).
  • the focal point 44 is traversed through the wafer 30 to form a series of linear regions 32a, 32b, 32c, 32d of laser modified material 32 at different depths within the wafer 30 (i.e. at different distances from the plane in which the fluid channels 14 extend).
  • the linear regions 32a, 32b, 32c, 32d extend in a direction that is substantially parallel to the x-y plane and the plane along which the fluid channels 14 extend.
  • this is not essential and in further examples the regions of laser modified material 32 may be formed in a variety of patterns across the intended fracture plane O'.
  • Figure 2d shows an arrangement of the wafer 30 and laser beam source 40 part-way through the irradiation process, where two linear regions 32a, 32b of laser modified material 32 are complete, and the focal point 44 of the laser beam 42 is being traversed to form a third linear region 32c of laser modified material 32.
  • four linear regions 32a, 32b, 32c, 32d of laser modified material 32 are formed within the intended fracture plane O', with two linear regions of laser modified material 32 on either side of the fluid channel plane and on either side of the original interface L between the first and second substrate layers 10, 20.
  • the final visual appearance of the microfluidic chip 50 shown in Figures 1 is particularly striking.
  • the regions of laser modified material 32 are easily observed on the outlet face 54 of the microfluidic chip 50 - e.g. under a microscope.
  • the regions of laser modified material 32 appears as regions of darkened or blackened material.
  • the microfluidic chips produced using these cutting methods have outlet faces with a consistent appearance - i.e. exhibit material that of consistent colour similar to the remainder of the material and that is of a consistent texture and roughness.
  • the striking appearance microfluidic chips formed by methods discussed above can be seen in Figures 3b, 4b, 5b and 6, which will be discussed further below.
  • Figures 3a, 4a and 5a show schematic illustrations of three patterns in which a laser may be focused within an intended fracture plane O' within a wafer, to form internal regions of laser modified material 62, 72, 82.
  • Figures 3c, 4c and 5c show microscope images of the nozzles 66, 76, 86 formed in the respective microfluidic chip 60, 70, 80 obtained using a Tescan (RTM) VEGA3 SEM microscope at increased magnifications of 3560x, 3380x, and 3470x respectively.
  • RTM Tescan
  • microfluidic chips 60, 70, 80 shown in Figures 3b & 3c, 4b & 4c and 5b & 5c each have total thickness or depth in the z-direction of approximately 1 .4 mm (e.g. from 1000 to 2000 micrometres) and a width in the y-direction of approximately 2.5 mm (e.g. from 2000 micrometres to 3000 micrometres).
  • the pattern of laser modified material 62 shown in Figures 3a, 3b and 3c is broadly similar to the example shown in Figure 1 and 2.
  • a plurality of linear regions of laser modified material 62 are formed in the intended fracture plane O'.
  • the linear regions each extend parallel or substantially parallel to the fluid channel plane (illustrated by the intended position of the nozzles N'), and parallel or substantially parallel to the original interface L between the first and second substrate layers from which the microfluidic chip 60 is formed (i.e. parallel to the y-axis as shown).
  • Each linear region of laser modified material 62 extends across the full width of the intended fracture plane O' and the microfluidic chip 70 in the y-direction (although this is not essential).
  • the plurality of linear regions of laser modified material 62 may be grouped into a first plurality of linear regions 62a located above the plane in which the fluid channels extend (i.e. on a first side of fluid channel plane) formed and a second plurality of linear regions 62b located below the plane in which the fluid channels extend (i.e. on an opposing second side of the fluid channel plane).
  • the first plurality of linear regions 62a are formed by applying a laser along a first plurality of lines 62a' in the intended fracture plane O'
  • the second plurality of linear regions 62b are formed by applying a laser along a first plurality of lines 62b' in the intended fracture plane O'
  • the gaps between the nearest parts of adjacent linear regions of laser modified material 62 in a direction perpendicular to the fluid channel plane is typically in the region of 40 to 100 micrometres, and more preferably 50 to 90 micrometres.
  • the distance between the centrelines of adjacent linear regions of laser modified material 62 is typically in the range from 50 to 150 micrometres, and preferably in the range from 60 to 140 micron.
  • the linear regions of laser modified material 62 typically have an average thickness in the range from 10 to 75 micrometres, preferably in the range from 20 to 50 micrometres.
  • the nozzles 66 have a height perpendicular to the fluid channel plane (the plane in which the fluid channels extend) of approximately 5 micrometres and a width parallel to the plane in which the fluid channels extend (i.e. a dimension in the y- direction) of approximately 10 to 13 micrometres. These figures are not essential, and in further examples each nozzle 66 may have a height and a width that is in the range from 1 micrometres to 50 micrometres, and preferably 3 to 25 micrometres. The distance between the pair of nozzles 66 is typically in the range from 30 to 75 micrometres and is preferably in the range from 30 to 60 micrometres.
  • the nozzles 66 are preferably positioned centrally between two linear regions of laser modified material 62 in the direction perpendicular to the fluid channel plane. As such, the nozzles 66 may be positioned at a location that in the range from 25 to 75% of the distance between the two closest linear regions of modified 62 material above and below the nozzles 66.
  • Figure 4a shows a further pattern of lines 72' for the formation of laser modified material 72 across an intended fracture plane O' of a wafer. Again, marked on the figure in dotted lines are the intended positions of a pair of nozzles N' and initial interface L between first and second substrate layers used to form the wafer. The nozzles N' also indicate the position of the fluid channel plane extending through the wafer parallel to the y-axis.
  • a laser may be focused along the pattern of lines 72' in the figure to generate a corresponding pattern of regions of laser modified material 72.
  • Figures 4b and 4c show a microfluidic chip 70 manufactured using this pattern of laser modified material 72.
  • the pattern of laser modified material 72 shown in Figures 4a, 4b and 4c comprises a plurality of linear regions of laser modified material 72 formed in the intended fracture plane O'.
  • the linear regions each extend parallel or substantially parallel to a fluid channel plane defined by the fluid channels extending through the microfluidic chip 70, and parallel or substantially parallel to the original interface L between the first and second substrate layers from which the microfluidic chip 70 is formed (i.e. parallel to the y-axis as shown).
  • the plurality of linear regions of laser modified material 72 may again be grouped into a first plurality of linear regions 72a located above the plane in which the fluid channels extend (i.e.
  • a region of unmodified material 78 extends perpendicular to the plane in which the fluid channels are formed across the outlet surface 74 of the microfluidic chip 70.
  • the nozzles 76 are positioned within this region of unmodified material 78, being positioned between the pairs of collinear regions of laser modified material 72 in the y-direction.
  • the pair of nozzles 76 is positioned centrally within the region of unmodified material 78 (i.e. centrally between the pairs of collinear regions of laser modified material 72 in the y- direction).
  • the centre of the pair of nozzles may be positioned at a location that in the range from 20 to 80% of the distance across the region of unmodified material 78, more preferably in the range from 25 to 75% of said distance.
  • the region of unmodified material 78 extends through the full height of the microfluidic chip 70 (although this is not essential and in some cases a region of unmodified material may extend across at least 75% of the height of the chip or at least 50% of the height of the chip).
  • the region of unmodified material 78 typically has a width in the range from 100 to 300 micrometres.
  • the nozzles 76 are preferably positioned centrally between two adjacent pairs of linear regions of laser modified material 72 in the z direction, perpendicular to the fluid channel plane.
  • the nozzles 76 may positioned at a location that in the range from 25 to 75% of the distance between the two closest pairs of colinear regions of laser modified material 72 above and below the nozzles 76 in a direction perpendicular to the fluid channel plane.
  • the gaps between adjacent linear regions of laser modified material 72 in the z direction, the distances between the centrelines of adjacent linear regions of laser modified material 72 in the z direction and the thicknesses of the linear regions of laser modified material 72 are similar to the corresponding dimensions discussed above in relation to Figure 3.
  • the nozzles 76 have similar dimensions and spacing as in the corresponding figures discussed above in relation to Figure 3.
  • Figure 5a shows a further pattern of lines 82' for the formation of laser modified material 82 across an intended fracture plane O' of a wafer. Again, marked on the figure in dotted lines are the intended positions of a pair of nozzles N' and the initial interface L between first and second substrate layers used to form the wafer. A laser may be focused along the pattern of lines 82' in this figure to generate a corresponding pattern of regions of laser modified material 82.
  • Figures 5b and 5c show a microfluidic chip 80 manufactured using this pattern for laser modified material 82.
  • the pattern of laser modified material 82 shown in Figure 5b comprises a plurality of linear regions of laser modified material 82 formed in the intended fracture plane O'.
  • the linear regions each extend parallel or substantially parallel to the plane in which the fluid channels extend through the microfluidic chip 80 (i.e. the fluid channel plane).
  • the linear regions also extend parallel or substantially parallel to the original interface L between the first and second substrate layers from which the microfluidic chip 80 is formed (i.e. parallel to the y-axis as shown).
  • the plurality of linear regions of laser modified material 82 may again be grouped into a first plurality of linear regions 82a located above the plane in which the fluid channels extend (i.e. on a first side of the fluid channel plane) and a second plurality of linear regions 82b located below the plane in which the fluid channels extend (i.e. on an opposing second side of the fluid channel plane).
  • the first plurality of linear regions 82a are formed by applying a laser along a first plurality of lines 82a' in the intended fracture plane O'
  • the second plurality of linear regions 82b are formed by applying a laser along a first plurality of lines 82b' in the intended fracture plane O'
  • the nozzles 86 are positioned in the y-direction between the pairs of collinear regions 82b of laser modified material 82 within the second plurality.
  • the region of unmodified material 88 extends across the outlet surface 84 of the microfluidic chip 80 from the nozzles 86 to a bottom edge 84b of the microfluidic chip 80.
  • the pair of nozzles 86 is positioned centrally within the region of unmodified material 88 (i.e. centrally between the pairs of collinear regions of laser modified material 82 in the y-direction).
  • the centre of the pair of nozzles may be positioned at a location that in the range from 25 to 75% of the distance across the region of unmodified material 88.
  • the nozzles 86 are positioned between the closest linear region of the first plurality and the closest pair of colinear regions of the second plurality.
  • the nozzles 86 are preferably centrally between the two closest linear regions of laser modified material 82 above and below the nozzle 86 in the direction perpendicular to the fluid channel plane.
  • the nozzles 66 may be positioned at a location that in the range from 25 to 75% of the distance between the two closest linear regions of modified 62 material above and below the nozzles 66 the direction perpendicular to the fluid channel plane.
  • FIGs 6a and 6b show further images obtained using a Keyence (RTM) VHX-700 microscope at magnifications of 400x and 1000x respectively of the outlet surface of a microfluidic chip 80 manufactured using the pattern of lines 82' shown in Figure 5a.
  • regions of laser modified material 82 are formed across the outlet surface.
  • the regions are linear and are arranged parallel to the direction in which fluidic channels extend through the microfluidic chip 80, the position of which can be observed from the location of the nozzles 86.
  • the linear regions 82a of laser modified material 82 above the nozzles 86 and above the fluid channel plane extend across the full width of the outlet surface.
  • the linear regions 82b of laser modified material 82 below the nozzles 86 i.e.
  • the nozzles 86 are aligned to and positioned within the unmodified region 88 which as shown extends from the nozzles 86 to the bottom edge of the outlet surface.
  • Figures 1 to 6 provide specific examples of microfluidic chips and arrangements of laser modified material on their outlet surfaces, it will be appreciated that a wide variety of arrangements of laser modified material may be formed across the intended fracture plane O' of a wafer.
  • the laser modified material need not be formed in linear regions. Equally regions of laser modified material need not be provided parallel to the fluid channel plane in which the fluid channels extend.
  • Laser modified material is provided across the intended fracture plane O' to ensure that cracks propagate through the intended fracture plane O' and the wafer splits as intended under mechanical stress.
  • Laser modified material may be formed over at least 5% of the intended fracture plane O', preferably at least 10%, more preferably at least 15%, more preferably still at least 20%.
  • the laser is preferably applied in swathes across substantially the full width of the intended fracture plane O' to ensure that the wafer splits smoothly across its full width.
  • the swathes may be formed by a single linear region or set of colinear regions.
  • the regions of laser modified material extend across at least 75% of the width of the outlet face of a microfluidic chip, more preferably at least 80%, more preferably still at least 90%.
  • Figures 9a and 9b Two examples of pairs of nozzles 90, 95 which do not exhibit the intended, rectangular shape are shown in Figures 9a and 9b.
  • the image of Figure 9a was obtained using a Tescan (RTM) VEGA3 SEM microscope at a magnification of 311 Ox.
  • the image of Figure 9b was obtained using a Keyence (RTM) VHX- 700 microscope at a magnification of 10OOx.
  • a microfluidic chip was manufactured in accordance with the pattern of laser modified material discussed above in reference to Figure 3. However, in each case the distance between the nozzles 90, 95 and the nearest region of laser modified material 91 , 96 is very low.
  • nozzles are not rectangular and even, as seen in the examples shown in Figures 3c, 4c and 5c.
  • a series of “teeth marks” or recesses 92 are formed in the openings to the nozzles 90. These recesses 92 are seen above the nozzles 90 in Figure 9a.
  • the nozzles 95 shown in Figure 9b exhibit both these “teeth marks” or recesses 92 and a chip 97 is formed in the outlet face below each nozzle 95.
  • Microfluidic chips with nozzles that include the deformations shown in Figures 9a and 9b do not consistently generate impinging jets of liquid or consistently produce aerosols. As such, the yields of manufacturing processes for obtaining functioning microfluidic chips are reduced.
  • the distance between each nozzle and the respective nearest portion of laser modified material in a direction parallel to the plane of the fluid channels is at least 15 micrometres, or more preferably 20 micrometres, 25 micrometres, or 30 micrometres, and/or the distance between each nozzle of the microfluidic chip and the respective nearest portion of laser modified material in a direction perpendicular to the plane of the fluid channels is at least 15 micrometres, or more preferably 20 micrometres, 25 micrometres, or 30 micrometres.
  • microfluidic chips manufactured using laser patterns according to the examples shown in Figures 4, 5 and 6 tend to offer a higher yield than the patterns of Figure 3 since the unmodified regions 78, 88 in which their nozzles 76, 86 are positioned provide greater margin for the location in which material is modified. Errors in the positioning of the focal point of the laser are less likely to impact the performance of the microfluidic chip.
  • the ridge 79 is sufficiently small and sufficiently centrally positioned between the nozzles that it does not affect the performance of the microfluidic chip shown in Figure 4, the margin for error in the position of their nozzles 76 is reduced.
  • microfluidic chips manufactured in accordance with the patterns shown in Figures 5 and 6 tend to offer improve yields in comparison to Figure 4 (and Figure 3, as discussed above). Therefore, the distance between each nozzle of the microfluidic chip and the respective nearest portion of laser modified material is at most 250 micrometres, preferably at most 200 micrometres, more preferably at most 150 micrometres, more preferably still at most 125 micrometres, and more preferably still at most 100 micrometres.
  • the distance between each nozzle of the microfluidic chip and the respective nearest portion of laser modified material in a direction perpendicular to the plane of the fluid channels is preferably at most 100 micrometres, preferably at most 75 micrometres and more preferably still at most 50 micrometres.
  • the distance between each nozzle of the microfluidic chip and the respective nearest portion of laser modified material in a direction parallel to the plane of the fluid channels is preferably at most 150 micrometres, preferably at most 100 micrometres, and more preferably still at most 75 micrometres.
  • microfluidic chips 50, 60, 70, 80 comprise a pair of nozzles
  • alternative microfluidic chips may comprise a group of three or more nozzles that are configured to direct respective jets of liquids such that they impinge on one another to form an aerosol.
  • microfluidic chips may comprise a single nozzle configured to direct a jet of liquid into a wall or other permanent structure. As the jet of liquid collides with the wall the liquid may be aerosolised.
  • the wall or other permanent structure may part of a device such as an inhaler in which the microfluidic chip is placed.
  • a microfluidic chip may comprise multiple pairs or groups of nozzles, wherein each pair or group is configured to cause respective jets of liquid to impinge on one another.
  • a laser source 110 applies a laser beam 111 to a first side 101 of the wafer 100 to form a first plurality of regions of laser modified material on a first side of the fluid channel plane (e.g. the first pluralities of regions of laser modified material discussed above with reference to Figures 3 to 5).
  • the wafer is then rotated or flipped by 180 degrees.
  • the laser source 110 applies a laser beam 111 to the opposing second side 102 of the wafer 100 to form a second plurality of regions of laser modified material on a second side of the fluid channel plane (e.g. the second pluralities of regions of laser modified material discussed above with reference to Figures 3 to 5).
  • FIG. 8a, 8b and 8c A comparison of microfluidic chips manufactured using single sided and double sided approaches is shown in Figures 8a, 8b and 8c.
  • the images in Figures 8a, 8b and 8c were obtained using Keyence (RTM) VHX-700 microscope at magnifications of 100x, 100x and 700x respectively.
  • RTM Keyence
  • Figure 8b shows a microfluidic chip 130 formed using a double-sided approach.
  • the edges 131 of the microfluidic chip 130 are not straight as a result of misalignment between the positioning of laser modified material formed by laser beams incident from different sides of a wafer during manufacture.
  • the microfluidic chip 130 shown in Figure 8b comprises a significant notch 132 in its outlet surface.
  • This notch 132 can be seen in greater magnification in Figure 8c, with the area of the microfluidic chip 130 shown in Figure 8c being shown approximate by the dashed box on Figure 8b. Whilst the notch 132 is most easily seen at the edge 131 of the microfluidic chip 130, it extends across the full width of the outlet surface of the microfluidic chip 130.
  • Notches can affect the relative positions of the nozzles within the outlet surface of the microfluidic chips and the directions in which liquid jets are directed from the microfluidic chips.
  • single-sided methods of manufacturing microfluidic chips tend to offer improved yields as the jets of liquid ejected from their chips are more likely to collide in the intended manner and form an effective aerosol.
  • the method involves irradiating the wafer with a laser to form a plurality of linear regions of laser modified material wherein the linear regions of laser modified material extend in a direction that is substantially parallel to the fluid channel plane in which the fluid channels extend and wherein two or more linear regions of laser modified material are provided on either side of the fluid channel plane at different distances relative to the fluid channel plane, as shown in Figures 2, 3, 4 and 5, and wherein at least the linear regions of laser modified material that are nearest the fluid channel plane on each side of the fluid channel plane are formed using a laser beam from a laser source on a single side of the wafer relative to the fluid channel plane.
  • Figure 10 shows a modified version of the line pattern shown in Figure 3a where the different hatching of the line pattern corresponds to regions of laser modified material which should be formed using a laser from opposing sides of the wafer 30.
  • the pattern of lines 132' shown in Figure 10 may be used to produce microfluidic chips with outlet surfaces and nozzles similar to those shown in Figures 3b and 3c
  • all of the lines 132a' above the fluid channel plane and the two nearest lines 132b' below the fluid channel plane are to be irradiated using a laser beam emitted by a source on the same side of the wafer (as shown by the thick down-ward hatching).
  • all of the remaining lines 132c' (shown by the thin up-ward hatching) that are further from the fluid channel plane extend are irradiated using a laser source on the opposite side of the wafer - e.g. a second laser source positioned on the opposing side of the wafer or the same laser source after the wafer is flipped relative to said source.
  • the processes for dividing a wafer described above with reference to Figures 1 to 10 can also be used within methods where multiple microfluidic chips are formed from a single wafer. Such processes are discussed below in reference to Figure 11a to 11 e. According to these examples of the invention the method steps, multiple microfluidic chips are formed simultaneously from the same wafer. Fluid channels for multiple microfluidic chips can be formed internally within a large wafer and the wafer subsequently divided using the laser irradiation process discussed above to form individual microfluidic chips. This process of singulation is particularly efficient. Moreover, the process and microfluidic chips offer corresponding benefits to the examples discussed above.
  • Figure 11a shows steps of providing a first substrate layer 210 and forming array of fluid channels 214 in a surface 211 of the substrate layer 210.
  • the fluid channels 214 correspond to a plurality of microfluidic chips and comprise a repeated array of identical individual fluid channel units 215. Each of the individual fluid channel units corresponds to a single microfluidic chip and comprises the fluid channels for said microfluidic chip.
  • the fluid channels 214 may be etched into the surface of the first substrate layer 210 as discussed above with reference to Figure 2b.
  • a second substrate layer 220 is provided over the first substrate layer 210 and the first and second substrate layers 220, 210 are bonded together to form a single wafer 230 as shown in Figure 11 b.
  • This bonding step is equivalent to the step discussed above in relation to Figure 2c and encloses the fluid channels 214 within the wafer 230.
  • the first and second substrate layers 210, 220 and the wafer 230 are circular, although this is not essential.
  • the laser modified material 232 is weaker than the surrounding material of the wafer 230, and cracks will propagate from the laser modified material 232 under stress
  • the position of the laser modified material 232 formed inside the wafer 230 corresponds to the boundaries between the repeated fluid channels units 215 within the wafer 230, such that dividing the wafer along the laser modified material 232 divides the wafer 230 into individual microfluidic chips.
  • the process of forming laser modified material 232 corresponds to the methods discussed previously, especially in relation to Figure 2d.
  • the laser modified material 232 preferably arranged to cut through the fluid channels to form nozzles and inlets in respective inlet and outlet faces of the microfluidic chips.
  • a preferred process for applying mechanical stress and dividing the wafer 230 in this manner is shown in schematic cross sections in Figures 11 d and 11 e.
  • the wafer 230 is first applied to an expandable dicing tape 240 secured by a clamp 250 around its edge, as shown in Figure 11 d.
  • a piston 260 is raised from below the dicing tape 240, contacting the opposing side of the dicing tape 240 from the side on which the wafer 230 is applied.
  • the movement of the piston is shown by arrow P in Figure 11 e.
  • the piston 260 deflects the dicing tape 240 relative the clamp 250.
  • the tensile stress applied to the wafer 230 causes cracks to propagate from the laser modified material 232, separating the wafer 230 into individual microfluidic chips 270 which each include a respective set of fluid channels, inlets and nozzles, and configured to generate an aerosol from liquid received at their inlets.
  • the inhaler system 300 comprises a main body 310 into which a replaceable cartridge 320 containing may be inserted.
  • the cartridge 320 comprises an internal volume 321 in which liquid such as liquid medicament may be stored.
  • the inhaler system 300 further comprises a cartridge cover 330 that is configured to attach to the main body 310 and encloses and protects the cartridge 320 that is inserted into the main body 310.
  • the inhaler system 300 further comprises a hollow tube 340 through which the contents of the cartridge 320 can be dispensed. Inserting the cartridge 320 into the inhaler system 300 involves pushing a proximal end 341 of the tube 340 into the cartridge 320.
  • the cartridge 320 may be inserted manually into the inhaler system 300, but this is not essential.
  • a one-way valve 343 (also sometimes termed a non-return valve).
  • the one-way valve 343 is positioned within the tube 340 and is configured to allow liquid to flow in a direction from the proximal end 341 of the tube 340 to the distal end 342 but to prevent flow of liquid in the opposite direction.
  • the one-way valve 343 may be positioned elsewhere within the liquid path of the contents of the cartridge 310 out of the inhaler system 300.
  • the inhaler system 300 further comprises a filter 350 configured to receive liquid that has passed through the tube 340.
  • the filter 350 is configured to allow liquid to pass therethrough but to prevent the passage of solid particles within the liquid.
  • the microfluidic chip 400 according to the invention is configured to receive liquid that has passed through the filter 350 and to convert the liquid passing therethrough into an aerosol.
  • the aerosol may then be dispensed to a user by a mouthpiece 360 which the user may insert into their mouth.
  • the mouthpiece 360 is protected by a mouthpiece cover 361.
  • the mouthpiece cover 361 is mounted on a hinge 362 and may rotate about the hinge 362 between open and closed positions.
  • the mouthpiece cover 361 is shown in a closed position in Figure 5.
  • the tensioner body 370, tube 340 and cartridge 310 are moved away from the mouthpiece 360 to prime the system. This movement increases the size of a priming volume 390 between the distal end 342 of the tube 340 and the filter 350. As this volume increases in size its pressure decreases, drawing liquid from the cartridge 320, through the tube 340 and past the non-return valve 343. The inhaler system 300 is then fired by releasing the tensioner body 370, tube 340 and cartridge 310.
  • the inhaler system is configured to dispense fluid in puffs with a volume of medicament in the range of 0.5 microlitres to 50 microlitres, more preferably 0.5 microlitres to 30 microlitres, more preferably still from 10 to 20 microliters.
  • An intended dose of the medicament from the inhaler may comprise a single puff, or a plurality of puffs (e.g. two puffs).
  • the inhaler system 300 and the microfluidic chip 400 are configured to dispense droplets with an average diameter in the range of 1 to 10 microns, preferably from 2 to 6 microns, and more preferably from 3 to 5 microns.
  • the inhaler system 300 is a multidose inhaler system, wherein the cartridge 320 is configured to store a plurality of doses of liquid medicament.
  • the cartridge 320 has a capacity or internal volume in the range of 0.5 to 10 millilitres, preferably in the range of 1 to 5 millilitres.

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Abstract

L'invention concerne des procédés de fabrication de puces microfluidiques, les procédés comprenant la formation d'un ou de plusieurs canaux de fluide dans une première couche de substrat, la fourniture d'une seconde couche de substrat en contact avec la première couche de substrat, et la liaison de la première couche de substrat et de la seconde couche de substrat ensemble pour former une tranche, et la division de la tranche pour former la puce microfluidique, la division de la tranche pour former la puce microfluidique comprenant l'irradiation de la tranche avec un laser, le laser étant focalisé à l'intérieur de la tranche pour créer une ou plusieurs régions internes de matériau modifié par laser à l'intérieur de la tranche, l'une ou les plusieurs régions internes de matériau modifié par laser s'étendant dans un plan de fracture prévu définissant un agencement souhaité de la surface de sortie de la puce microfluidique et l'application d'une contrainte mécanique à la tranche pour fracturer la tranche le long du plan de fracture prévu.
PCT/EP2024/078687 2023-10-11 2024-10-11 Puces microfluidiques et leurs procédés de fabrication Pending WO2025078603A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030075623A1 (en) * 1992-09-29 2003-04-24 Frank Bartels Atomising nozzel and filter and spray generating device
US20100148315A1 (en) * 2008-10-31 2010-06-17 Panasonic Corporation Semiconductor wafer and a method of separating the same
US20130126573A1 (en) * 2010-07-12 2013-05-23 Filaser Inc. Method of material processing by laser filamentation
US20160243833A1 (en) * 2015-02-25 2016-08-25 Canon Kabushiki Kaisha Method for manufacturing semiconductor chip
WO2020253647A1 (fr) * 2019-06-17 2020-12-24 Suzhou Skywell Healthcare Information Co., Ltd. Dispositif microfluidique et procédé de fabrication associé
US20210093802A1 (en) * 2018-03-21 2021-04-01 Softhale Nv Spray nozzle for an inhalation device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030075623A1 (en) * 1992-09-29 2003-04-24 Frank Bartels Atomising nozzel and filter and spray generating device
US20100148315A1 (en) * 2008-10-31 2010-06-17 Panasonic Corporation Semiconductor wafer and a method of separating the same
US20130126573A1 (en) * 2010-07-12 2013-05-23 Filaser Inc. Method of material processing by laser filamentation
US20160243833A1 (en) * 2015-02-25 2016-08-25 Canon Kabushiki Kaisha Method for manufacturing semiconductor chip
US20210093802A1 (en) * 2018-03-21 2021-04-01 Softhale Nv Spray nozzle for an inhalation device
WO2020253647A1 (fr) * 2019-06-17 2020-12-24 Suzhou Skywell Healthcare Information Co., Ltd. Dispositif microfluidique et procédé de fabrication associé

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