EP3838409A1 - Mikrofluidische vorrichtung, hergestellt durch prägedruck eines papierbasierten substrats - Google Patents

Mikrofluidische vorrichtung, hergestellt durch prägedruck eines papierbasierten substrats Download PDF

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Publication number
EP3838409A1
EP3838409A1 EP20213730.3A EP20213730A EP3838409A1 EP 3838409 A1 EP3838409 A1 EP 3838409A1 EP 20213730 A EP20213730 A EP 20213730A EP 3838409 A1 EP3838409 A1 EP 3838409A1
Authority
EP
European Patent Office
Prior art keywords
layer
substrate
embossing
paper
electrode
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.)
Withdrawn
Application number
EP20213730.3A
Other languages
English (en)
French (fr)
Inventor
Pierre-Alexandre Setier
Raphaël TROUILLON
Gaël DEPRES
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Arjowiggins France
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Original Assignee
Arjowiggins France
Commissariat a lEnergie Atomique CEA
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Arjowiggins France, Commissariat a lEnergie Atomique CEA, Commissariat a lEnergie Atomique et aux Energies Alternatives CEA filed Critical Arjowiggins France
Publication of EP3838409A1 publication Critical patent/EP3838409A1/de
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/126—Paper
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements

Definitions

  • the invention relates to a method for producing a microfluidic device as well as to the microfluidic device which can be produced by said method.
  • the method consists in particular in carrying out an embossing of a substrate which is based on paper.
  • Microfluidics makes it possible to perform manipulations and analyzes on small samples of liquid, of the order of a few tens of microliters to a few milliliters.
  • microfluidic devices are produced by casting crosslinking materials of the PDMS (poly-dimethyl siloxane) type on previously machined molds. The manufacture of these microfluidic devices requires clean room type equipment involving significant means and manufacturing time.
  • a less expensive technology currently exists which consists in fabricating microfluidic circuits in a paper-based substrate having a hydrophobic surface treatment.
  • the microfluidic circuit produced by embossing can be closed from above with a transparent adhesive film using mainly materials based on poly (ethylene terephthalate) (PET) or ethylene vinyl acetate. (EVA).
  • PET poly (ethylene terephthalate)
  • EVA ethylene vinyl acetate.
  • a method for producing a microfluidic device comprising a step of embossing a substrate composed of at least two superimposed layers, a first layer made of paper and a second layer deposited on it. the first layer and made of a material based on vinylidene polymer and having a so-called upper face to be embossed, said embossing step being performed on said upper face of the second layer of the substrate to form a pattern thereon, said pattern comprising at least at least one cavity delimited by at least one bottom wall and one side wall, said method also comprising a step of producing conductive electrodes by screen printing at the bottom of said cavity.
  • the electrodes comprise at least one reference electrode and one or more working electrodes.
  • each electrode is screen printed with silver ink on the substrate.
  • the reference electrode is then covered with an Ag / AgCl ink and each working electrode with a carbon ink.
  • an insulator is deposited around each electrode.
  • the invention also relates to a microfluidic device, the device comprising a substrate composed of at least two superimposed layers, a first layer made of paper and a second layer deposited on the first layer, made of a material based on a polymer of vinylidene and having a so-called upper face to be embossed, said substrate being embossed on at least part of the upper face of its second layer to form a pattern thereon, said pattern comprising at least one cavity delimited by at least one bottom wall and one side wall, said device also comprising conductive electrodes produced by screen printing at the bottom of said cavity.
  • the electrodes comprise at least one reference electrode and one or more working electrodes.
  • each electrode is screen printed with silver ink on the substrate.
  • the reference electrode is then covered with an Ag / AgCl ink and each working electrode with a carbon ink.
  • the device comprises an insulator deposited around each electrode.
  • the object of the present invention is to provide an easily achievable and multifunctional layer on paper in the field of biological diagnosis.
  • the microfluidic device comprises a substrate 2 formed of at least two layers 20, 21, advantageously only two layers.
  • the paper used is sold under the trademark “Powercoat” (registered trademark) having a basis weight of 219 g / m 2 .
  • the second layer 21 of the substrate 2 is deposited on the first layer of “Powercoat”.
  • the second layer 21 is advantageously a vinylidene polymer, advantageously “polyvinylidene chloride” (hereinafter PVDC) or polyvinylidene fluoride (PVDF), advantageously polyvinylidene chloride PVDC.
  • PVDC polyvinylidene chloride
  • PVDF polyvinylidene fluoride
  • the figure 2 shows an example of the process for manufacturing substrate 2.
  • the layer 21 of PVDC is deposited on the first layer 20 of paper by coating.
  • the PVDC layer is deposited at a thickness between 5 and 20 ⁇ m, which corresponds to basis weights between 15 and 25 g / m 2 .
  • This technique makes it possible to deposit a preparation based on PVDC on the paper then to scrape the excess to keep only a thin functional layer. Drying is then carried out to evaporate the excess water. Drying can be carried out at room temperature; it is possible to carry it out at temperatures up to 70 ° C or even 90 ° C to speed up the process.
  • the PVDC used can be a commercial aqueous emulsion named Diofan A050 (Solvay-registered trademark).
  • the figure 3A shows a first variant of the method for producing a microfluidic device according to the invention, by embossing the substrate 2 with two layers 20, 21.
  • This step consists in carrying out an embossing of the substrate 2 obtained in order to functionalize the latter with microfluidic channels.
  • the embossing is carried out on the upper face of the second layer.
  • the embossing can consist in placing the substrate between two dies of a press, a lower die M1 in hollow and an upper die M2 in relief. During the press, the reliefs are duplicated on said upper face of the substrate so as to form an imprint. Other techniques can of course be considered.
  • E21 A hollow is made by embossing said substrate 2, forming a cavity 22.
  • a substrate 2 is thus obtained provided with the cavity 22 obtained by embossing.
  • the embossing can thus make it possible to produce a pattern on the upper face of the second layer of the substrate.
  • the embossing can thus make it possible to produce a pattern forming a concavity on the upper face of the second layer of the substrate.
  • This concavity can be in any possible form.
  • Several patterns can be made juxtaposed on the same substrate in order to obtain several juxtaposed elements
  • it may be a microfluidic imprint in the form of one or more cavities and one or more channels.
  • the cavity may have a hollow shape of constant section over its entire height, with a circular contour. It can also have a hollow shape in the form of a truncated cone. Any other form can be considered.
  • this rough bearing surface 23 may also be a rough bearing surface 23 allowing lysis of the biological species contained in a biological sample.
  • This rough bearing surface is thus produced by embossing using a sandpaper (grit 18 to 800, preferably 400 to 600), for example using a vice coupled to a torque wrench (applied moment 10 Nm ).
  • the pressure of the sandpaper against the surface is exerted at a force between 0.5 and 20 MPa and between 3 and 10 MPa in nominal.
  • the microfluidic device can be as shown in the figure. figure 4 and comprising a body having a bottom wall 10, a side wall 11 and a top wall 12.
  • the device 1 comprises a chamber 13 formed in the body. This chamber represents the location in which both purification / concentration, mechanical lysis, separation and optionally detection in biological species can be performed.
  • the chamber 13 is closed at the bottom by the lower wall.
  • the device comprises a first channel 14 for injecting fluids into the chamber or for discharging fluids outside the chamber.
  • the first channel 14 has a first end comprising an opening formed for example at through the upper wall 12 of the body and a second end which opens into said chamber 13.
  • the first end of the first channel 14 is for example arranged vertically and its second end opens for example horizontally into the chamber 13.
  • the first end of the first channel is for example for example flared to apply the cone of a pipette thereto or will be adapted to the type of device used to inject the fluid into the device.
  • the device comprises a second channel 15.
  • This second channel 15 also comprises a first end which communicates with the outside, forming an opening made for example through the upper wall and a second end which communicates with the space formed by the chamber 13.
  • This second channel 15 it is also possible to inject fluids into said chamber or to evacuate fluids outside said chamber.
  • Its first end is for example arranged vertically and its second end horizontally.
  • the chamber 13 is placed between the first channel 14 and the second channel 15.
  • the first end of this second channel is for example flared to apply the cone of a pipette thereto or will be adapted to the type of device used for injecting. the fluid in the device.
  • the chamber 13 can be closed by a flexible and stretchable membrane 18, preferably transparent.
  • the upper wall 12 of the device housing thus comprises an opening which is hermetically covered by said membrane 18.
  • This membrane 18 will for example be composed of a film, for example of the MicroAmp, 3M (registered trademarks) type, of thickness. , of dimensions and constitution adapted to deform elastically, with respect to its anchoring points, in particular to the bottom of the chamber 13.
  • transparent is understood to mean that the material used is at least partially transparent to visible light, so as to allow at least 80% of this light to pass. It should thus be understood that it will be sufficiently transparent to see the interior of the chamber 13, at least the second space located above the filter.
  • the device comprises a filter 16 arranged in said chamber 13 and separating said chamber 13 into two spaces.
  • the two spaces are for example superimposed and thus designated lower space 130 located under the filter and upper space 131 located above the filter.
  • This filter 16 is preferably produced in whole or in part in the form of a flexible and thin film, drawn in the space formed by the chamber so as to allow passage from one space to another only through the pores of the chamber. filter 16.
  • the film has an elastic deformability allowing it to stretch during the exercise of a support force in a substantially vertical direction, this elastic deformability having a sufficient level to reach the lower surface of the chamber 13.
  • Filter 16 has a average pore diameter as defined above. The diameter of the pores is of course adapted to ensure separation between different biological species present in the sample.
  • the filter 16 will for example be composed of a film of thickness, dimensions and constitution adapted to deform to the bottom of the chamber 13 relative to its anchoring points. According to a particular embodiment, the filter could also be made of a transparent material, for example with the same transparency characteristics as the membrane.
  • the device can advantageously comprise a rough bearing surface 17 arranged on the bottom of the chamber 13.
  • This rough bearing surface 17 extends over a majority part of the bottom of the chamber. It includes an average surface roughness parameter between 0.1 ⁇ m and 10 ⁇ m, preferably between 0.2 ⁇ m and 3 ⁇ m.
  • This rough bearing surface 17 is intended to allow mechanical lysis of the biological species present in a biological sample placed in the device.
  • the mechanical lysis is carried out by grinding said biological species, by abrasion on said rough bearing surface.
  • the grinding operation is carried out by a friction movement of the biological species against the rough bearing surface, using a suitable grinding member.
  • This member will for example be a spatula or a rod, for example made of plastic or metallic material.
  • This member is applied from the outside of the chamber 13 and its end is applied against the outer surface of the membrane 18 so as to stretch the membrane 18 and the filter towards the bottom of the chamber and thus rub the biological species present in a sample against the rough bearing surface.
  • the device can integrate means for heating the internal space of the chamber, for example composed of at least one heating resistor or of a Peltier element.
  • the resistance is for example fixed under the bottom wall.
  • a power source will for example be provided to power the resistance.
  • the power source will for example include one or more electric cells, providing enough energy to heat the chamber to a temperature within the range defined above, that is to say from 20 ° C to 100 ° C. .
  • other heating means could be used, comprising for example a conductive ink deposited by printing or screen printing under the lower wall of the housing.
  • the membrane 18 is for example composed of a film made of a hyper-elastic two-component polymer material, for example a silicone or polysiloxane polymer. It may in particular be an elastomer of PDMS type (for Polydimethylsiloxane) or ECOFLEX (trademark registered by the company "Smooth-On" - for example Ecoflex 00-50). Its thickness can be between 20 and 500 ⁇ m.
  • such a device can be produced in several superimposed layers.
  • first lower layer C1 which consists of a substrate in accordance with the invention, that is to say comprising two layers, a layer of paper and a layer of PVDC.
  • a rough bearing surface 30 is produced on the upper face of the substrate 2 formed by its layer of PVDC, on at least part of this face.
  • This rough bearing surface can be produced by embossing using a sandpaper (grit 18 to 800, preferably 400 to 600) at a pressure between 0.5 and 20 MPa, according to the principle detailed below. above.
  • the channel forms said first channel of the device.
  • microfluidic imprint formed of one or more cavities and / or one or more channels.
  • This microfluidic impression will be made by embossing, using a matrix with the relief suited to the impression to be created.
  • the device can then include a second layer C2 formed of an adhesive cut according to the desired structure and bonded to the upper face of the substrate.
  • This adhesive comprises in particular a wide opening 31 delimiting the side walls of the lower space 130 of the chamber 13.
  • the device may include a third layer C3 forming the filter 16 affixed on the upper face of the second layer to cover the opening.
  • the filter is made of a film.
  • the device can have a fourth layer C4 formed of an adhesive cut according to the desired structure and bonded to the second layer while maintaining the filter between the two layers.
  • This fourth layer comprises a wide opening 32 forming the upper space 131 of the chamber 13 and a second cutout forming the first channel 14.
  • the device may comprise a fifth layer C5 comprising the deformable membrane 18 described above and also comprising two orifices.
  • the device may include a sixth layer C6 formed of an adhesive cut to the desired shape and bonded to the layer C5 formed by the membrane, comprising two orifices each forming the inlet / outlet, respectively of the first channel 14 and of the second channel 15. .
  • lysis is achieved mechanically by compressing the chamber. This stress induces the rupture of biological membranes on the rough surface and the DNA can then be harvested by rinsing.
  • the PVDC layer minimizes the impact of warping on the printed tracks during embossing. No drop in conductivity is observed after the embossing of conductive lines deposited on a layer of PVDC whose surface density is> 15 gm -2 . At lower densities (10 gm -2 ), an increase in resistance is measured.
  • Electrodes can be integrated into the chamber of the device or at the bottom of a cavity produced by embossing the substrate.
  • the first layer of the device formed from the substrate according to the invention, it is possible to integrate any type of microfluidic circuit therein by embossing the upper face of the substrate. It is thus possible to hollow out other cavities and / or microfluidic channels.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
EP20213730.3A 2019-12-20 2020-12-14 Mikrofluidische vorrichtung, hergestellt durch prägedruck eines papierbasierten substrats Withdrawn EP3838409A1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR1915051A FR3105025A1 (fr) 2019-12-20 2019-12-20 Dispositif micro-fluidique réalisé par embossage d’un substrat à base de papier

Publications (1)

Publication Number Publication Date
EP3838409A1 true EP3838409A1 (de) 2021-06-23

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EP20213730.3A Withdrawn EP3838409A1 (de) 2019-12-20 2020-12-14 Mikrofluidische vorrichtung, hergestellt durch prägedruck eines papierbasierten substrats

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EP (1) EP3838409A1 (de)
FR (1) FR3105025A1 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116020582B (zh) * 2022-12-15 2023-11-17 西交利物浦大学 一种纳米纤维素基微流控分析平台及其制备方法和用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013181656A1 (en) 2012-06-01 2013-12-05 President And Fellows Of Harvard College Microfluidic devices formed from hydrophobic paper
EP3053652A1 (de) 2015-02-03 2016-08-10 Commissariat à l'Énergie Atomique et aux Énergies Alternatives Mikrofluidik-vorrichtung und verfahren zur realisierung einer mikrofluidik-vorrichtung
WO2018053108A1 (en) * 2016-09-16 2018-03-22 Uenal Baris Microplates and open-channel microfluidics devices including coated and uncoated cellophane
WO2018197814A1 (fr) 2017-04-27 2018-11-01 bioMérieux Plaque d'analyse maldi-tof a support papier et son utilisation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102791468B (zh) * 2009-12-09 2015-06-10 弗莱米迪克斯公司 制造包含纳米结构的结构的方法
GB2551122A (en) * 2016-06-02 2017-12-13 Univ Southampton Fluid flow device and method for making the same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013181656A1 (en) 2012-06-01 2013-12-05 President And Fellows Of Harvard College Microfluidic devices formed from hydrophobic paper
EP3053652A1 (de) 2015-02-03 2016-08-10 Commissariat à l'Énergie Atomique et aux Énergies Alternatives Mikrofluidik-vorrichtung und verfahren zur realisierung einer mikrofluidik-vorrichtung
WO2018053108A1 (en) * 2016-09-16 2018-03-22 Uenal Baris Microplates and open-channel microfluidics devices including coated and uncoated cellophane
WO2018197814A1 (fr) 2017-04-27 2018-11-01 bioMérieux Plaque d'analyse maldi-tof a support papier et son utilisation

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Publication number Publication date
FR3105025A1 (fr) 2021-06-25

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