EP3488929B1 - Vorrichtung zur injektion eines fluidischen probenstroms - Google Patents

Vorrichtung zur injektion eines fluidischen probenstroms Download PDF

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Publication number
EP3488929B1
EP3488929B1 EP18203778.8A EP18203778A EP3488929B1 EP 3488929 B1 EP3488929 B1 EP 3488929B1 EP 18203778 A EP18203778 A EP 18203778A EP 3488929 B1 EP3488929 B1 EP 3488929B1
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EP
European Patent Office
Prior art keywords
pneumatic
fluidic
inlet
injection device
network
Prior art date
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Application number
EP18203778.8A
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English (en)
French (fr)
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EP3488929A1 (de
Inventor
Charlotte PARENT
François BOIZOT
Yves Fouillet
Eloise PARISET
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Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Original Assignee
Commissariat a lEnergie Atomique CEA
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/56—Labware specially adapted for transferring fluids
    • B01L3/563—Joints or fittings ; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors

Definitions

  • the present invention relates to a device for injecting a fluid sample.
  • the invention also relates to a microfluidic system comprising a microfluidic device and an injection device used to inject a fluidic sample into said microfluidic device.
  • the invention relates to a method for injecting a fluidic sample, implemented using said injection device adapted to the microfluidic device.
  • a fluid sample into a microfluidic device there are many devices for injecting a fluid sample into a microfluidic device.
  • a plunger device such as a syringe, for example equipped with a Luer type connector to connect to a fluid inlet of the microfluidic device.
  • It can also be a device already integrated into the card such as that described in the patent application.
  • EP2679307A1 This solution consists in placing the fluid sample in a pocket glued to a microfluidic card and closed by a film interposed between said pocket and a fluid inlet of the card. After removing the film, mechanical pressure on the top of the pocket allows the liquid sample to be injected into the card.
  • the patent application WO 2015/181170 A1 describes a fluidic card comprising a reservoir for storing at least one fluid and an associated hyper-elastic membrane, as well as a method for storing and delivering at least one fluid by means of such a fluidic card.
  • the patent application US 2014/261868 A1 describes a container assembly for use with a high pressure liquid chromatography (HPLC) apparatus, the container assembly, when coupled to a source of pressurized gas, providing the HPLC apparatus with a positive pressure fluid medium.
  • HPLC high pressure liquid chromatography
  • the object of the invention is therefore to propose an injection device which overcomes the drawbacks of the previous solutions. This can in particular be independent of the micro-fluidic device and allows precise adjustment of the injected volume, even in the event of low volume.
  • said device comprises at least a first face on which opens said pneumatic inlet and a second face on which opens said fluid outlet and said first face and said second face are parallel.
  • the membrane is made of a deformable material such as an elastomer of the family of silicones.
  • the device comprises at least one film arranged on said housing to close off said fluid outlet and said pneumatic inlet.
  • said pneumatic network comprises a channel connected to said pneumatic inlet and opening into said tank.
  • said fluid network comprises a channel connecting said reservoir to said fluid outlet.
  • the invention also relates to a microfluidic system comprising a microfluidic device which comprises a fluidic network comprising a fluidic inlet for receiving a fluidic sample and a pneumatic network comprising at least one auxiliary pneumatic inlet intended to be connected to a source of pneumatic supply and an auxiliary pneumatic outlet communicating with said auxiliary pneumatic inlet, characterized in that it comprises a fluid injection device as defined above, said pneumatic inlet of the injection device being configured to connect to said auxiliary pneumatic outlet of the microfluidic device and said fluid outlet of the injection device being configured to connect to the fluid inlet of the microfluidic device.
  • the pneumatic network of the microfluidic device comprises a pneumatic control input intended to be connected to a pneumatic power source.
  • the fluidic network of the card comprises several fluidic valves actuable by said pneumatic network, via said pneumatic control input by which a pneumatic force is generated.
  • each fluid valve comprises a microfluidic capsule actuable between a first closed state blocking the flow of a fluid and a second open state authorizing the flow of said fluid.
  • the microfluidic device comprises at least one deformable membrane arranged in each capsule and actuable between two states by said pneumatic force.
  • the invention relates to a device 2 for injecting a fluid sample into a microfluidic device 1.
  • the two devices are initially independent.
  • the injection device can be adapted on the microfluidic device for injecting the fluid sample.
  • the two devices form a complete microfluidic system which can be used during an analysis of a fluid sample.
  • the injection device can be of the single-use type, that is to say disposable.
  • fluid sample it should be understood that it can be a liquid or even a gas. Preferably, it will be a liquid type sample.
  • microfluidic device compatible with the injection device of the invention can be of all types, that is to say that it can take any possible structure, whether for its external shape or for its fluid architecture. internal.
  • the microfluidic device can be produced in the form of a card, known as a microfluidic card.
  • This card can have a rectangular format.
  • fluidic network By fluidic network is meant fluidic elements such as one or more fluidic inlets, one or more fluidic outlets, one or more reservoirs, connecting channels, chambers, fluidic valves or any other element of this type.
  • pneumatic network pneumatic elements such as one or more pneumatic inlets, one or more pneumatic outlets, connecting channels, chambers or other elements of this type.
  • the microfluidic device 1 has a fluid inlet IN1 through which the fluid sample is injected into the fluid network of the microfluidic device 1.
  • This fluid inlet IN1 can be formed in a fluid connector.
  • This connector can be of the male type and is arranged to cooperate with a corresponding suitable connector.
  • the figure 1 shows an example of a micro-fluidic device 1 of card type, as it could be used within the framework of the invention.
  • this device is to be considered in a nonlimiting manner for the description of the invention.
  • microfluidic device is notably described in the application EP3085444A1 .
  • this microfluidic device 1 can comprise two substrates 10, 11 and a deformable membrane 12 disposed between the two substrates.
  • Each substrate 10, 11 has two surfaces, a so-called upper surface and a so-called lower surface.
  • the lower surface of the first substrate 10 faces the upper surface of the second substrate 11 and both form the microfluidic surfaces of the device, since it supports its fluid network.
  • the two substrates can have a rectangular, circular or any other shape.
  • Each of the first 10 and second 11 substrates has a thickness, for example between approximately 200 ⁇ m and 10 mm and an area of the order of several square centimeters, typically an area equivalent to that of a microscope slide, a well plate (called “96 well plate” ) or a credit card.
  • the deformable membrane has a thickness of the order of a hundred microns (10 ⁇ m to 1 mm), for example of 300 ⁇ m.
  • the material of the first substrate 10 and / or of the second substrate 11 is selected from the following materials: polycarbonate polymer, PMMA, COC, silicon, and paper.
  • the membrane 12 is formed from a very elastically deformable material, allowing it to return to its initial shape after deformation.
  • the material is chosen with a percentage of elastic deformation at least equal to 200% (an elongation of twice its initial size before deformation) and up to 1000%.
  • the material and its deformability characteristic can be adapted to the intended application.
  • the membrane 12 can be made from an elastomeric material of the family of silicones such as MQ (Methyl-Polysiloxanes), VMQ (Vinyl-Methyl-Polysiloxanes, PVMQ (Phenyl-Vynil-Methyl-Polysiloxanes) or elastomer of thermoplastic type (TPE), for example TPE-S, TPS, TPE-E, TPC.
  • MQ Metal-Polysiloxanes
  • VMQ Vinyl-Methyl-Polysiloxanes
  • PVMQ Phenyl-Vynil-Methyl-Polysiloxanes
  • TPE thermoplastic type
  • the fluid network of the device 1 shown in the Figures 1 and 2 may include a series of microfluidic capsules 13.
  • Each microfluidic capsule 13 of a microfluidic device comprises a chamber 130 formed by a cavity into which an inlet channel opens and from which an outlet channel emerges.
  • the membrane 12 is deformable inside the chamber of each capsule allowing, depending on its position, to confer at least two distinct states on the microfluidic capsule.
  • Each capsule can be controlled individually by action of the part of the membrane associated with the capsule. Depending on the position of the membrane, the volume of the chamber 130 varies, between an almost zero volume and a maximum volume.
  • the capsule when its membrane 12 is at rest, the capsule may be in the first state or in the second state.
  • the capsule when its membrane 12 is at rest, the capsule may be in the first state or in the second state.
  • we can thus speak of a "normally closed” or "normally open” configuration.
  • the membrane 12 is adapted to open or block the passage of the fluid as well as to pump the fluid from a reservoir or a chamber to at least one other chamber.
  • the capsules can thus have different shapes and configurations:
  • the capsules have a semi-spherical cap shape.
  • the capsule 13 is in a closed state.
  • the membrane 12 is put in a deployed shape and is pressed to perfectly match the shape of the cavity.
  • the volume between the membrane 12 and the cavity is almost zero, thus blocking the flow of the fluid through the chamber 130.
  • the figure 3B illustrates a view of the same microfluidic chamber 130 in an open state.
  • the corresponding part of the deformable membrane 12 is in the rest state and allows the fluid to flow through the chamber.
  • Each cavity is represented in the form of a semi-spherical cap.
  • the capsule On the figure 4A , the capsule is in a closed state, the membrane 12 is however not deployed.
  • the membrane 12 is deployed and allows the flow of fluid through the chamber, from the inlet channel to the outlet channel.
  • FIGS. 5A and 5B represent an operating architecture equivalent to that of Figures 4A and 4B , the difference residing in the fact that the microfluidic capsule is of cylindrical shape and not in the shape of a hemispherical cap.
  • the microfluidic device 1 is associated with an actuation system adapted to act on the membrane 12 at the level of each capsule in order to switch the selected capsule between its two states.
  • the actuation system includes a pneumatic supply source 3.
  • the device comprises microfluidic communication channels 14 forming the inlet and outlet channels described above. According to the embodiment chosen, they are formed on one or the other of the two microfluidic surfaces of each substrate 10, 11.
  • each communication channel 14 has a length of between approximately 0.5 mm and 5 mm and a section of between approximately 50 ⁇ m and 500 ⁇ m on the side.
  • the volume of a microfluidic channel 14 is at least ten times smaller than the volume of a microfluidic chamber 2.
  • the fluid input IN1 is produced through the upper substrate 10 of the card and may have its connector on the upper surface of the card.
  • the micro-fluidic device 1 comprises a pneumatic network.
  • This pneumatic network may include one or more pneumatic control inputs 15 each opening at a microfluidic chamber 2 of a capsule. These control inputs 15 are used to actuate the deformable membrane 12 by applying a pneumatic force generated by a pneumatic power source.
  • the displacement of the membrane 12 between its two positions can be achieved by applying a positive pressure or a negative pressure on its pneumatic control input.
  • the actuation system may include a control unit configured to control each control input 15 in a suitable manner, for example according to a given sequence.
  • the command can be global, all the inputs 15 being connected to the same pneumatic source 3, or selective, each input can be activated individually. Pneumatic valves are then controlled by the control unit to select each control input 15.
  • the fluidic network and the pneumatic network of the device 1 can be machined according to methods known by the plastics industries such as mechanical machining with a numerically controlled machine, by 3D printing, or preferably by injection.
  • the first substrate 10, the membrane 12 and the second substrate 11 are assembled so as to ensure sealed contact between the membrane 12 and the two microfluidic surfaces of the first and second substrates, while providing a flow space at the level of the capsules 13 and microfluidic channels 14.
  • the assembly can be carried out by gluing, by plasma, or by mechanical plating.
  • the pneumatic network of the microfluidic device also includes an auxiliary pneumatic inlet IN_aux and an auxiliary pneumatic outlet OUT_aux connected together by a connecting channel.
  • the auxiliary pneumatic input IN_aux is arranged in a pneumatic connector intended to be connected to a pneumatic supply source, this supply source can be identical to the pneumatic source 3 used for the actuation of each fluidic valve described above .
  • the auxiliary pneumatic output OUT_aux is also arranged in a pneumatic connector suitable for establishing a connection with an external device.
  • the auxiliary pneumatic output OUT_aux is thus available directly on the microfluidic device 1 for an external device.
  • the connector in which the auxiliary pneumatic output OUT_aux is formed may be of the male type.
  • auxiliary pneumatic input IN_aux, the auxiliary pneumatic output OUT_aux and their connecting channel are advantageously produced by a channel traversing the card over its entire thickness, opening onto the lower surface to form the auxiliary pneumatic input and onto the upper surface to form the auxiliary pneumatic outlet.
  • the connector of the auxiliary output can be male. Any other arrangement could be envisaged.
  • the invention relates in particular to an injection device 2 arranged to connect in particular to the auxiliary pneumatic outlet OUT_aux of the microfluidic device 1 in order to be able to benefit from a pneumatic force for injecting a fluidic sample into the microfluidic device 1.
  • the injection device 2 thus comprises a pneumatic network and a fluidic network. Two embodiments are proposed, a first mode on the Figures 6A to 6C and a second mode on Figures 7A to 7C .
  • the injection device 2 comprises a housing 20 in which its fluid network and its pneumatic network are produced.
  • the housing can be of rectangular shape.
  • Its fluid network includes a reservoir 21 produced in an internal space of the housing and intended to receive a fluid sample 22 to be injected. It also includes a fluid outlet OUT2 through which the fluid sample is injected. A fluid outlet channel can connect the fluid outlet OUT2 to the reservoir 21.
  • the fluid output OUT2 can be arranged in a fluid connector arranged to cooperate with a corresponding connector in order to ensure a reliable and tight fluid connection.
  • the connector in which the OUT2 fluid outlet is formed can be of the female type.
  • Its pneumatic network includes an IN2 pneumatic input.
  • the pneumatic input IN2 is arranged in a pneumatic connector, suitable for connecting to the auxiliary pneumatic output OUT_aux available on the microfluidic device 1.
  • the connector in which the pneumatic input IN2 is formed may be of the female type.
  • the distance between the pneumatic inlet IN2 and the fluid outlet OUT2 of the injection device 2 and their respective positions are of course configured to be identical to those existing between the auxiliary pneumatic outlet OUT_aux and the fluid inlet IN1 of the microfluidic device 1.
  • Its pneumatic network may include a pneumatic inlet channel 23 connected to its pneumatic inlet IN2 and intended to connect said pneumatic inlet to its fluid network so as to convey the pneumatic force to the fluid network.
  • This pneumatic inlet channel 23 opens into the reservoir 21, advantageously opposite the fluid outlet channel joining the fluid outlet OUT2.
  • the injection device 2 can also include a deformable membrane 24, forming a sealed interface between its pneumatic network and its fluidic network.
  • This membrane 24 is for example arranged in the reservoir 21 and extends transversely relative to the direction of the pneumatic force generated at the interface between the pneumatic network and the fluid network of the injection device.
  • This membrane 24 is configured to deform during the exercise of a pneumatic force of sufficient intensity. By deforming under the action of said force, the membrane 24 pushes the liquid out of the reservoir 21 in the direction of the fluid outlet OUT2 of the injection device 2.
  • this membrane 24 can be made of an elastomeric material of the family of silicones such as MQ (Methyl-Polysiloxanes), VMQ (Vinyl-Methyl -Polysiloxanes, PVMQ (Phenyl-Vynil-Methyl-Polysiloxanes) or elastomer of the thermoplastic type (TPE), for example TPE-S, TPS, TPE-E, TPC.
  • MQ Metal-Polysiloxanes
  • VMQ Vinyl-Methyl -Polysiloxanes
  • PVMQ Phenyl-Vynil-Methyl-Polysiloxanes
  • TPE thermoplastic type
  • the injection device 2 also includes one or more perforable or tear-off covers. It may be an adhesive film 25 deposited on the housing 20 of the device and arranged to seal the pneumatic inlet IN2 and the fluid outlet OUT2 of the injection device, thereby forming a barrier layer.
  • the pneumatic inlet IN2 and the fluid outlet OUT2 of the injection device 2 are arranged in parallel and their opening sections, traversed by a gaseous flow (of air) for the pneumatic inlet and by a liquid flow for the fluid outlet, are produced in two parallel planes.
  • the two planes are combined.
  • the two planes will be arranged perpendicular to the axis (X).
  • the pneumatic network and the fluidic network of the device are thus arranged so as to form an inverted U, the first branch of the U ending in the pneumatic inlet IN2 and the second branch of the U ending in the fluid outlet OUT2.
  • the pneumatic inlet IN2 and the fluid outlet OUT2 thus open on the same face of the device or at least on two parallel faces.
  • the pneumatic network and the fluidic network of the device are then arranged in the device to ensure the operation of the device, in particular the guiding of a pneumatic force towards the reservoir 21.
  • the injection device when the injection device is filled with the fluid sample, it is injected by the fluid outlet OUT2 which then acts as an inlet.
  • the pneumatic input IN2 of the device can be used to evacuate the air.
  • the pneumatic inlet IN2 can be used to aspirate the fluid sample inside the device by being connected to a pumping system having a connection adapted to that of the pneumatic inlet IN2 of the injection device.
  • the film 25 for closing the entrance pneumatic and the fluid outlet is then bonded to the housing 20 of the device to finalize its preparation.
  • the injection device 2 can also have an architecture in which the opening sections of the pneumatic inlet and of the fluid outlet are no longer produced in two parallel planes, but in two inclined planes, one relative to the other, forming a single cavity, for example of conical shape, into which the pneumatic inlet and the fluid outlet open.
  • This cavity is intended to cooperate with a corresponding protuberance of the microfluidic device on the blank of which opens its auxiliary pneumatic outlet and its fluid inlet.
  • the male type connector located for example on the microfluidic card side
  • the male type connector has a central protrusion making it possible to promote the piercing of the film 25, at the level of the pneumatic inlet IN2 and the outlet fluid flow OUT2 of the injection device.
  • FIGS. 6A to 6C represent the injection device without membrane and the Figures 7A to 7C show the injection device with a membrane 24.
  • the injection device 2 can be produced by assembling several superimposed layers.
  • It may include a first substrate 40 in which the fluid network and the pneumatic network of the injection device are made in part.
  • the first substrate 40 has an initially planar upper face 400 (that is to say before machining of the fluidic network and the pneumatic network) and a planar lower face 401, perpendicular to the axis (X). It comprises a first cavity 402 produced on its upper face, for example of cylindrical shape of revolution, at the bottom of which a first channel 403 is produced in the direction of the axis (X) opening at its end in a second cavity 404 forming a flare opening on its underside 401.
  • the first substrate 40 also comprises a second channel 405 produced axially, from its upper face towards its lower face and opening into a third cavity 406 produced on its lower face 401.
  • a transverse channel 407 is also machined to provide the junction between the second channel 405 and said first cavity 402.
  • the injection device 2 comprises a second substrate 41 having a planar lower face 411 and a planar upper face 410.
  • the first substrate 40 and the second substrate 41 advantageously have a cross section of identical dimensions.
  • the second substrate 41 is fixed on the first substrate so that its lower face 411 comes to bear on the upper face 400 of the first card 40, covering the first cavity 402 to form the reservoir 21 of the device and the channels 405, 407 for form the pneumatic network.
  • the film 25 can be affixed to obtain a ready-to-use pre-filled injection device ( figure 6C ).
  • the injection device comprises a membrane 24 as described above.
  • the device comprises a first substrate 50.
  • the first substrate 50 comprises an upper face 500 initially planar (that is to say before machining of the fluidic network and the pneumatic network) and a lower face 501 planar, perpendicular to the axis (X). It comprises a first cavity 502 produced on its upper face 500, for example of cylindrical shape of revolution, at the bottom of which a first channel 503 is produced in the direction of the axis (X) opening at its end in a second cavity 504 forming a flare opening onto its underside 501.
  • the first substrate 50 also comprises a second channel 505 produced axially from its upper face in the direction of its lower face and opening into a third cavity 506 produced on its lower face 501.
  • the membrane 24 is then fixed directly over the entire upper face 500 of the first substrate 50, closing off the first cavity 502.
  • the membrane 24 is cut in the section of the second channel 505 to leave an opening.
  • the injection device 2 can then comprise a second substrate 51 comprising a planar upper face 510 and a planar lower face 511, and intended to be fixed by its lower face on the surface of the available membrane.
  • This second substrate 51 has two through openings, a first opening 512 facing the opening formed through the membrane 24 and a second opening 513 opening onto the closed part of the first cavity 502 by the membrane 24.
  • This substrate 51 also has on its upper face 510, a channel 514 arranged to provide the junction between the two openings 512, 513.
  • the device may finally comprise a third substrate 52 having an upper face 520 and a lower face 521.
  • the third substrate 52 is fixed by its lower face 521 to the upper face 511 of the second substrate 51. It can be a simple adhesive membrane covering the substrate 51 and closing its channel 514.
  • the fluidic network and the pneumatic network of the injection device 2 can be machined according to methods known by the plastics industries such as mechanical machining with a numerically controlled machine, by 3D printing, or preferably by injection.
  • each substrate 40, 41, 50, 51, 52 can be selected from the following materials: polycarbonate polymer, PMMA, COC, silicon, and paper.
  • FIGS. 8A and 8B illustrate the operating principle of the injection device, respectively in its first embodiment and in its second embodiment described above.
  • the injection device forms a complete microfluidic system.
  • the microfluidic device is chosen with the configuration of the figure 1 .
  • the principle will be identical whatever the micro-fluidic device to which the injection device 2 is connected.
  • the injection device 2 can be filled with the liquid sample during a filling step as described above. This step can be carried out during the manufacture of the device. Once the injection device is partially or completely emptied, it can be discarded.
  • this step it involves connecting the injection device 2 to the microfluidic device 1.
  • the pneumatic inlet IN2 of the injection device 2 and the fluid outlet OUT2 of the injection device 2 are thus connected respectively on the auxiliary pneumatic output OUT_aux of the micro-fluidic device and on the fluidic input IN1 of the micro-fluidic device.
  • the protective film 25 is pierced to allow the fluidic and pneumatic connections to be established between the two devices.
  • the auxiliary pneumatic input IN_aux of the microfluidic device 1 being connected to a pneumatic supply source 3, for example an air source, an air pressure (P) is applied through the auxiliary pneumatic input IN_aux and the auxiliary output OUT_aux of the microfluidic device.
  • a pneumatic supply source 3 for example an air source
  • the air is brought into the injection device 2 via its pneumatic inlet IN2.
  • the air pressure pushes the liquid present in the reservoir 21, through the fluid outlet OUT2 of the device.
  • the liquid crosses the fluid outlet OUT2 and enters the microfluidic device 1 via the fluid inlet IN1 thereof.
  • the injection continues until the desired volume is injected into the microfluidic device 1.
  • the source 3 thus remains active as long as the desired volume has not been injected.
  • the liquid injected into the microfluidic device can then continue its movement in the fluidic network of the microfluidic device 1, according to the state of the microfluidic capsules of the device.
  • the auxiliary pneumatic input IN_aux of the microfluidic device 1 being connected to a pneumatic supply source 3, for example an air source, an air pressure (P) is applied through the auxiliary pneumatic input IN_aux and the auxiliary output OUT_aux of the microfluidic device.
  • a pneumatic supply source 3 for example an air source
  • the air is brought into the injection device 2 via its pneumatic inlet IN2.
  • the air pressure pushes the liquid present in the reservoir 21, through the fluid outlet OUT2 of the device.
  • the pressure is applied to the membrane 24 of the injection device. Under the effect of the pressure, the membrane 24 deforms and pushes the liquid outside of the injection device 2 via its fluid outlet OUT2.
  • the liquid crosses the fluid outlet OUT2 and enters the microfluidic device 1 via the fluid inlet IN1 thereof.
  • the injection continues until the desired volume is injected into the microfluidic device 1.
  • the source 3 thus remains active as long as the desired volume has not been injected.
  • the membrane continues to deform as long as the pressure in the tank increases.
  • the liquid injected into the microfluidic device can then continue its movement in the fluidic network of the microfluidic device 1, according to the state of the microfluidic capsules of the device.

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Claims (12)

  1. Injektionsvorrichtung (2) für ein Fluid, die dazu bestimmt ist, an eine mikrofluidische Vorrichtung (1) angepasst zu werden, wobei die Injektionsvorrichtung umfasst:
    - ein Gehäuse (20),
    - ein Fluidnetz, das in dem Gehäuse (20) angeordnet ist und das eine Vorratskammer (21) aufweist, die in einem Innenraum des Gehäuses angeordnet ist, und einen Fluidausgang (OUT2), der mit der Vorratskammer (21) verbunden ist und in einem Fluidanschluss angeordnet ist,
    - ein pneumatisches Netz, das in dem Gehäuse (20) angeordnet ist und einen pneumatischen Eingang (IN2) umfasst,
    - dadurch gekennzeichnet, dass:
    - der pneumatische Eingang (IN2) in einem pneumatischen Anschluss angeordnet ist, der geeignet ist, dicht an einen pneumatischen Hilfsausgang (OUT-aux) der mikrofluidischen Vorrichtung angeschlossen zu werden,
    - eine elastisch verformbare Membran (24) in der Vorratskammer (21) angeordnet ist und eine dichte Grenzfläche bildet, um das Fluidnetz vom pneumatischen Netz zu trennen,
    - die Vorrichtung aus einer Anordnung mehrerer übereinanderliegender Substrate besteht, wobei die Membran eines der Substrate bildet.
  2. Injektionsvorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass die Vorrichtung mindestens eine erste Fläche aufweist, an welcher der pneumatische Eingang (IN2) mündet, und eine zweite Fläche, an welcher der Fluidausgang (OUT2) mündet, und dadurch, dass die erste Fläche und die zweite Fläche parallel sind.
  3. Injektionsvorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass die Membran (24) aus einem verformbaren Material wie einem Elastomer aus der Familie der Silikone hergestellt ist.
  4. Injektionsvorrichtung nach Anspruch 1, dadurch gekennzeichnet, dass sie mindestens eine Folie (25) aufweist, die an dem Gehäuse (20) angeordnet ist, um den Fluidausgang (OUT2) und den pneumatischen Eingang (IN2) abzudichten.
  5. Injektionsvorrichtung nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass das pneumatische Netz einen Kanal (23) aufweist, der an den pneumatischen Eingang (IN2) angeschlossen ist und in die Vorratskammer (21) mündet.
  6. Injektionsvorrichtung nach einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass das Fluidnetz einen Kanal aufweist, der die Vorratskammer mit dem Fluidausgang (OUT2) verbindet.
  7. Mikrofluidisches System, das eine mikrofluidische Vorrichtung (1) umfasst, die ein Fluidnetz aufweist, das einen Fluideingang (IN1) umfasst, um eine Fluidprobe aufzunehmen, und ein pneumatisches Netz, das mindestens einen pneumatischen Hilfseingang (IN-aux) umfasst, der dazu bestimmt ist, an eine pneumatische Versorgungsquelle (3) angeschlossen zu werden, und einen pneumatischen Hilfsausgang (OUT-aux), der mit dem pneumatischen Hilfseingang kommuniziert, dadurch gekennzeichnet, dass es eine Injektionsvorrichtung (2) für ein Fluid mit den Merkmalen eines der Ansprüche 1 bis 8 aufweist, wobei der pneumatische Eingang (IN2) der Injektionsvorrichtung (2) dazu ausgestaltet ist, an den pneumatischen Hilfsausgang (OUT-aux) der mikrofluidischen Vorrichtung (1) angeschlossen zu werden, und der Fluidausgang (OUT2) der Injektionsvorrichtung (2) dazu ausgestaltet ist, an den Fluideingang (IN1) der mikrofluidischen Vorrichtung (1) angeschlossen zu werden.
  8. System nach Anspruch 7, dadurch gekennzeichnet, dass das pneumatische Netz der mikrofluidischen Vorrichtung (1) einen pneumatischen Steuereingang (15) aufweist, der dazu bestimmt ist, an eine pneumatische Versorgungsquelle (3) angeschlossen zu werden.
  9. System nach Anspruch 8, dadurch gekennzeichnet, dass das Fluidnetz der mikrofluidischen Vorrichtung mehrere Fluidventile aufweist, die dank des pneumatischen Netzes über den pneumatischen Steuereingang betätigbar sind, durch den eine pneumatische Kraft erzeugt wird.
  10. System nach Anspruch 9, dadurch gekennzeichnet, dass jedes Fluidventil eine mikrofluidische Kapsel (13) aufweist, die zwischen einem ersten geschlossenen Zustand, der das Fließen eines Fluids sperrt, und einem zweiten geöffneten Zustand, der das Fließen des Fluids zulässt, betätigbar ist.
  11. System nach Anspruch 10, dadurch gekennzeichnet, dass die mikrofluidische Vorrichtung mindestens eine verformbare Membran (12) aufweist, die in jeder Kapsel (13) angeordnet ist und durch die pneumatische Kraft zwischen zwei Zuständen betätigbar ist.
  12. Verfahren zur Injektion einer Fluidprobe in eine mikrofluidische Vorrichtung (1), die ein Fluidnetz aufweist, das einen Fluideingang (IN1) umfasst, um eine Fluidprobe aufzunehmen, und ein pneumatisches Netz, das mindestens einen pneumatischen Hilfseingang (IN-aux) umfasst, der dazu bestimmt ist, an eine pneumatische Versorgungsquelle (3) angeschlossen zu werden, und einen pneumatischen Hilfsausgang (OUT-aux), der mit dem pneumatischen Hilfseingang kommuniziert, wobei das Verfahren dadurch gekennzeichnet ist, dass es mithilfe einer Injektionsvorrichtung (2) mit den Merkmalen eines der Ansprüche 1 bis 6 ausgeführt wird, wobei die Vorratskammer (21) der Injektionsvorrichtung (2) die Fluidprobe (22) umfasst, und dadurch, dass es die folgenden Schritte umfasst:
    - Anschließen der Injektionsvorrichtung (2) an die mikrofluidische Vorrichtung, indem der Fluidausgang (OUT2) der Injektionsvorrichtung (2) an den Fluideingang (IN1) der mikrofluidischen Vorrichtung (1) und der pneumatische Eingang (IN2) der Injektionsvorrichtung (2) an den pneumatischen Hilfsausgang (OUT-aux) der mikrofluidischen Vorrichtung (1) angeschlossen wird,
    - Anschließen des pneumatischen Hilfseingangs (IN-aux) der mikrofluidischen Vorrichtung an eine pneumatische Versorgungsquelle (3),
    - Aufbringen einer pneumatischen Kraft durch den pneumatischen Hilfseingang (IN-aux) der mikrofluidischen Vorrichtung (1) und das pneumatische Netz der Injektionsvorrichtung (2) hindurch derart, dass die Fluidprobe (22) in das Fluidnetz der mikrofluidischen Vorrichtung (1) über den Fluidausgang (OUT2) der Injektionsvorrichtung (2) und den Fluideingang (IN1) der mikrofluidischen Vorrichtung (1) injiziert wird.
EP18203778.8A 2017-11-28 2018-10-31 Vorrichtung zur injektion eines fluidischen probenstroms Active EP3488929B1 (de)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102019215030A1 (de) * 2019-09-30 2021-04-01 Robert Bosch Gmbh Einrichtung und Verfahren zur Handhabung eines Fluidvolumens und Überführung in ein mikrofluidisches System

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR3105024B1 (fr) * 2019-12-20 2022-04-15 Commissariat Energie Atomique Dispositif à actionnement pneumatique à substrats à base de papier
DE102022202860A1 (de) 2022-03-24 2023-09-28 Robert Bosch Gesellschaft mit beschränkter Haftung Mikrofluidische Vorrichtung mit einer Membran zur Aufnahme einer Probe

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102009045685A1 (de) * 2009-10-14 2011-04-21 Robert Bosch Gmbh Mikrofluidischer Chip
EP2969096B1 (de) * 2013-03-14 2022-11-16 Bio-Rad Laboratories, Inc. Flaschendruckbeaufschlagungssystem
FR3021559B1 (fr) * 2014-05-27 2017-09-15 Commissariat Energie Atomique Carte fluidique comportant un reservoir de stockage d'un fluide et une membrane hyper-elastique
FR3035009B1 (fr) * 2015-04-20 2020-02-07 Commissariat A L'energie Atomique Et Aux Energies Alternatives Dispositif microfluidique de controle d'ecoulement d'un fluide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102019215030A1 (de) * 2019-09-30 2021-04-01 Robert Bosch Gmbh Einrichtung und Verfahren zur Handhabung eines Fluidvolumens und Überführung in ein mikrofluidisches System

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