EP3225309B1 - Herstellungsverfahren von analysemembranen für mikrofluidgeräte - Google Patents

Herstellungsverfahren von analysemembranen für mikrofluidgeräte Download PDF

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Publication number
EP3225309B1
EP3225309B1 EP16163217.9A EP16163217A EP3225309B1 EP 3225309 B1 EP3225309 B1 EP 3225309B1 EP 16163217 A EP16163217 A EP 16163217A EP 3225309 B1 EP3225309 B1 EP 3225309B1
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Prior art keywords
substrate sheet
wax
thickness
mechanical
faces
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English (en)
French (fr)
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EP3225309A1 (de
Inventor
Frédèric Bedin
Frédèric Foucault
Agnès RUBENS
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Biomerieux SA
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Biomerieux SA
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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
    • B01L3/502707—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
    • 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
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • 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
    • B01L2200/12—Specific details about manufacturing 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces

Definitions

  • microfluidic sensors these devices not only make it possible to analyze small volumes of liquid samples, they also make it possible to undertake, on a single platform, a plurality of detection or even quantification tests, targeted analytes and / or pathogens by simple and fast manipulation.
  • the present invention is more specifically concerned with disposable microfluidic devices, of the type of those which comprise an analysis membrane made of a porous material and operating according to a so-called fluid lateral movement principle, in this case liquids.
  • said analysis membrane has long been made from a sheet of cellulose fiber or nitrocellulose, the designation " ⁇ PAD" (for "microfluidic paper-based analytical devices", in English) has been widely adopted to refer to this technology.
  • ⁇ PAD for "microfluidic paper-based analytical devices", in English
  • Other porous, hydrophilic and absorbent materials as long as they can allow lateral movement of the liquids by capillarity, have also been envisaged and then improved in order to be able to act as analysis membranes for the fabrication of these microfluidic devices. These are for example materials made from nitrocellulose fibers, cellulose acetate, fabrics, porous films of polymers.
  • the general principle of operation of this type of microfluidic device is essentially based on an analysis membrane made up / fabricated from a sheet of porous, hydrophilic and absorbent material, on which and in the bulk of which is formed a hydrophilic network formed areas of interest and channels.
  • a liquid to be analyzed for example a liquid biological sample
  • a series of qualitative and / or quantitative analyzes of its constituents can progress by simple capillarity and be submitted an analysis or a series of qualitative and / or quantitative analyzes of its constituents (immunodetection, molecular detection, affinity test, ligand-receptor coupling test, pH evaluation ).
  • a porous substrate sheet is first impregnated with a negative photoresist (for example, the photolithographic resin SU-8 2010), by immersion in a solubilized resin solution in a solvent. After removal of the excess resin, on one of its faces, the substrate sheet is coated with a mask material opaque to light waves.
  • This mask is provided with perforated parts (or simply transparent to ultraviolet) and ultraviolet opaque parts which respectively produce the hydrophobic parts and the hydrophilic parts to be transferred onto the substrate.
  • the assembly is then subjected to ultraviolet irradiation, at wavelengths capable of causing photopolymerization of the negative resin at the exposed areas.
  • UV irradiation at wavelengths capable of causing photopolymerization of the negative resin at the exposed areas.
  • hydrophilic zones delimited by impermeable borders are then drawn.
  • An optional additional heat treatment makes it possible to completely evaporate the initial solvent and perfect the crosslinking.
  • a substrate sheet is first impregnated with a conventional resin by immersion in a solution of resin solubilized with volatile solvent. The substrate sheet is then placed in a heated and ventilated chamber in order to evaporate the solvent and cause the resin to crosslink.
  • the substrate sheet thus made entirely hydrophobic, is coated on its upper face with an etching mask.
  • This mask has perforated parts and non-perforated parts, which respectively reproduce the hydrophilic parts and impermeable edges to be transferred to the substrate.
  • a plasma or corona treatment is applied to the assembly and makes it possible to remove the resin present on the surface of the substrate, at the level of the exposed zones. At these exposed areas, the upper layers of the substrate find wettability and hydrophilic qualities.
  • US 2008/0241953 discloses a method of contacting a wax-coated surface with a porous substrate prior to applying pressure thereto using a heated pad having a predetermined pattern on its surface. This makes it possible to transfer a wax layer having said pattern onto the porous substrate.
  • the wax is previously melted on a hot plate and is maintained in the liquid state throughout the process.
  • a porous substrate sheet is laid on a glass slide and its free face is surmounted by a plane iron mask. The openwork portions of this mask define the hydrophobic portions to be transferred to and through the thickness of the substrate sheet.
  • the desired pattern is thus first designed by computer. Then, using a solid ink printer, it is printed with the desired image resolution on one side of a porous substrate sheet. With the printed side facing up, the substrate sheet is coated on a hot plate heated to a temperature of the order of 150 ° C, for about 2 minutes. Under the effect of heat, the wax contained in the printed ink melts and, by gravity, penetrates and impregnates the substrate in its thickness. By cooling, the wax resolidifies and forms, in the thickness of the substrate, impermeable edges defining hydrophilic zones, like the pattern initially designed by computer.
  • the solid ink printers currently available commercially are unfortunately suitable only for printing on printing media (paper, transparent, cardboard) of standard sizes, well defined dimensions and whose thicknesses hardly exceed 250 microns.
  • the thickness of the print medium is a limiting parameter which is however not only related to the computer hardware currently available, it is also related to the method itself.
  • image resolution and impermeability of the borders formed the quality of the result decreases progressively with the increase of the thickness of the substrate.
  • the thicker and more porous a printing substrate the more quantity / density of wax needed to form the impermeable edges will be important.
  • the greater the quantity / density of wax required the more the lateral diffusion of the melted wax will be marked and deleterious for the fineness of the borders of the pattern initially designed in computer science.
  • the way in which the printer is used in this method induces another limiting parameter, that of the constituent material of the porous substrate sheet to be printed. Indeed, it must be able to give the substrate sheet mechanical strength and tensile strength (or tear resistance) sufficient to allow it to be conveyed through the printer, and to be able to withstand all the constraints mechanical and thermal forces inflicted during the printing process.
  • the porous substrate sheets made of flexible material, such as a fabric or a wadding, or a material of high friability, for example a fiberglass filter paper, can not be transformed / reworked by this method.
  • US 2015/0767342 discloses a method in which a pattern is printed with wax on a first side of a porous substrate, before being pressed between two rollers: The roll on the side of the second unprinted side being heated, the solidified wax can thus be melt and penetrate the substrate.
  • the object of the present invention is to propose a process for manufacturing microfluidic devices, more specifically a process for making the analysis membrane part, which does not suffer from the abovementioned disadvantages. More specifically, it aims to improve the method described in WO 2010/102294 .
  • An object of the present invention is therefore to provide a method of manufacturing analysis membranes for microfluidic devices whose implementation is not limited to the processing of sheets of cellulose fiber or nitrocellulose, but also to made sheets. in other porous materials, as well as substrate sheets of relatively large thickness, that is to say with a thickness of at least 200 ⁇ m, in particular between 200 ⁇ m and 1000 ⁇ m. .mu.m.
  • Another objective of the present invention is also to be able to propose a method that is compatible with the constraints of an industrial operation of a single-use diagnostic device, particularly in terms of production cost and profitability.
  • the present invention aims at providing a method of manufacturing analysis membranes, the originality of which is not only at the level of their design but also at the level of their structure and / or the nature of the substrates used, as well as the level of analytical performance that can be provided.
  • the present invention therefore relates, firstly, to a method of manufacturing a microfluidic device analysis membrane; said microfluidic membrane being formed from a porous substrate sheet, in the thickness of which solid wax forms impermeable edges defining hydrophilic zones. These impermeable edges thus describe, through said substrate sheet, a pattern drawn with wax.
  • said substrate sheet thus transformed is re-cut to the final dimensions of the desired analysis membrane.
  • the lower face is covered with a sealing layer, for example, by spraying or by applying a resin composition or a wax, or by laminating an impermeable plastic film, for example of the poly (ethylene terephthalate) or PET type.
  • this sealing layer may also have the advantage of stiffening and strengthening the structure of said analysis membrane.
  • the term "sheet” is used in a very general and broad sense to designate a part, a piece of substrate whose thickness corresponds to an insignificant value with respect to its surface. In this context, this term is used here to designate a sheet in the strict sense, a ribbon or a disc.
  • the term “film” will be used hereinafter to denote a piece, a piece of material whose thickness is significantly less than that of a sheet taken in the sense of the present invention.
  • the term "waxes” denotes lipophilic substances, solid at room temperature (25 ° C.) and having a melting point of between 45 ° C. and 120 ° C. Just above the melting point, the waxes are liquid and have a particularly low viscosity. They can be of animal origin (for example, beeswax, Chinese wax, lanolin ...), vegetable (for example, rice wax, mimosa, candellila wax, carnauba, the wax of Japan, the vegetaline %), mineral (for example, paraffin, ozokerite %) or synthetic (for example, stearin, ethylene polymers, fatty amines, polyethylene glycol or PEG, ).
  • the wax deposited on the underside of the substrate sheet gradually permeates the substrate in all directions, including upwards.
  • the vertical path of the wax is reduced. In doing so, the deep impregnation is favored and the migration time is shortened. Less freedom is left to the wax to be able to diffuse in one direction radial / lateral; the smoothness of the initial wax pattern is affected less significantly.
  • these mechanical means may consist of one or more plates, having a certain mass, which is applied to the substrate sheet. It may also be a vise device adapted to maintain, between its jaws, the substrate sheet in a horizontal position, and to compress the thickness.
  • thermo-controlled compression device a layer of flexible and elastic material, plane, is interposed between each of the faces of said substrate sheet and the heating compression plates. Said layer of flexible and elastic material then serves as a thermal and mechanical buffer; On the one hand, it makes it possible to slow the transmission of heat substrate and, on the other hand, more evenly distribute the heat and pressure over the entire substrate sheet.
  • a thermal and mechanical buffer element one can for example use a piece of rubber or any other similar polymeric material, a piece of tissue, a piece of cork.
  • Cooling can be done passively, stopping heating and / or removing and moving the substrate sheet away from any heat source.
  • mechanical expansion can be achieved simply by quickly removing the mechanical stresses applied or by gradually reducing their intensity.
  • the chronological order in which thermal expansion and mechanical expansion are triggered is not very important.
  • the two detents are triggered simultaneously or one after the other.
  • any suitable techniques known to those skilled in the art can be used.
  • 3D printing can be used.
  • the intermediate patterns are traced directly on the substrate sheet by deposition of wax.
  • the intermediate pattern reproduces identically the desired final pattern.
  • the intermediate pattern appears as an inverted image of the desired final pattern.
  • the two intermediate units are positioned opposite one another.
  • the waxed intermediate units are affixed to each of the faces of the porous substrate sheet with a wax transfer technique.
  • the intermediate patterns are first printed on a transfer film.
  • the intermediate pattern intended to coat the underside of the substrate sheet appears identical to the final pattern to be produced, whereas the intermediate pattern intended to coat the upper face of the substrate sheet appears as an image. inverted of the first intermediate pattern.
  • a solid ink printer can advantageously be used to print the intermediate patterns.
  • the amount (per unit area) of wax deposited on the transfer film depends on the print quality chosen, the inks used - more precisely the wax concentration present in these compositions. ink-, and the intensity of the coloring of the patterns to be printed.
  • transfer film usable for the implementation of the method according to the invention various materials are possible, since they are printable. This may include a printable plastic sheet (transparent or opaque), a sheet of printing paper, a sheet of parchment paper.
  • the two intermediate units intended to coat the upper and lower faces of the substrate sheet are printed on two separate transfer films.
  • the substrate sheet is then placed between the two transfer films, the wax patterns being pressed against the faces of the substrate sheet.
  • the assembly is held together and is subjected to heat and mechanical treatments according to the invention.
  • the two intermediate units intended to coat the upper and lower faces of the substrate sheet are printed on one and the same transfer film.
  • the two intermediate units are arranged side by side, symmetrically with respect to an axis.
  • the transfer film is folded in half along said axis of symmetry with the printed side turned inward.
  • the two intermediate patterns are thus superimposed.
  • the substrate sheet is inserted inside the folded transfer film between the two printed intermediate patterns. The assembly is held together and is subjected to said thermal and mechanical treatments according to the invention.
  • the transfer film is a paper sheet of cellulose fiber. Slightly absorbent, this film makes it possible, during the thermal and mechanical treatments according to the invention, to capture at least a portion of the molten wax remaining on the surface of the substrate before it slinks / flows on the sides.
  • the method according to the invention can be implemented from a wide range of porous substrate sheets, in particular from a fibrous composition chosen from: cellulose, nitrocellulose, cotton, linter, glass, silk fiber , viscose, polypropylene, polyester, polyamide (Nylon®), poly (lactic acid) or PLA.
  • Said fibers may optionally be functionalized and / or loaded and / or doped with additives (for example, talc, diatomite, etc.).
  • the process according to the invention is carried out starting from a porous substrate sheet of the same composition as a filtering medium made of cellulose fiber, nitrocellulose, cotton, linter, silk, viscose, polypropylene, polyester, preferably fiberglass.
  • the analysis membranes are conventionally made of cellulose fiber or nitrocellulose. These analysis membranes alone are incapable of separating the plasma fraction from the cell fraction. Whole blood deposited on such analysis membranes coagulates rapidly; after the deposition of the blood sample on these supports, the cells block the plasma and prevent its lateral diffusion through the hydrophilic channels.
  • the ⁇ PADs heretofore proposed comprise an assembly of an analysis membrane with a filtration system (for example, a fiberglass filtering medium) capable of implementing a fractionation of the blood. ; once separated from the cells that remain blocked at the level of the filtration system, the plasma diffuses through the analysis membrane where its components are then analyzed.
  • said analysis membrane may also comprise, in its thickness, wax encrustations, present at the level of at least one hydrophilic zone. These wax encrustations do not form impermeable barriers to passage of liquids. Positioned at various hydrophilic zones, they are intended to disrupt and / or slow down the flow of liquid locally and / or to create well-defined reservoir and / or reaction zones. They can also define the contours of wax-free zones, thus very hydrophilic, which can make use of reservoirs or well-defined reaction zones.
  • an image 12'a corresponding to the pattern to be integrated in the thickness of the substrate sheet 11 is created by computer and by means of a drawing software. This first image 12'a is duplicated in FIG. a symmetrical image 12'b.
  • the two images 12'a and 12'b are printed on a transfer film 20, so as to form two intermediate units 12a and 12b arranged symmetrically with respect to an axis.
  • This axis of symmetry S is also printed on the transfer film 20, as a visual cue.
  • the printing is carried out with a XEROX® ColorQube TM type printer, supplied with solid inks of reference XEROX® 108R00931 (cyan color), 108R00932 (magenta color), 108R00933 (yellow color) and 108R00934 / 108R00935 ( black color).
  • the transfer film 20 is an ordinary office paper sheet. The contours of the pattern are printed in quality / photo resolution in black ink.
  • the transfer film 20 is folded in two along the axis of symmetry S, the intermediate units 12a and 12b turned inwards. The latter are thus superimposed on one another.
  • a substrate sheet 11 is slid inside the folded transfer film 20, interposed between the two intermediate units 12a and 12b.
  • the substrate sheet 11, sandwiched between the two flaps of the transfer film 20, is then pressed between two horizontal heating plates and two rubber parts 15 forming a thermal and mechanical buffer.
  • the assembly is subjected to a pressure of the order of 1 kg / cm 2 and at a temperature of 120 ° C for about 3 minutes. During this process, the wax previously printed on the transfer film 20 is transferred onto both sides of the substrate sheet 11 and then impregnates the thickness.
  • FIG. 2 is a photograph of a WHATMAN TM MF1 membrane after an unsuccessful direct print attempt. This membrane, previously taped on a sheet of standard size paper to facilitate its passage through the printer and to consolidate somewhat the structure, comes out of the printer completely deteriorated.
  • the intermediate units 12a and 12b of generally rectilinear shape, have a flared upper part and a narrow lower part with an open end. Their contours are printed in black ink (reference XEROX® 108R00934), in photo quality. This solid ink contains a wax concentration which has been found to be sufficient to achieve and obtain impermeable edges in the thickness of relatively thick substrate sheets, including WHATMAN TM VF2 membranes of 785 ⁇ m in thickness.
  • the Figure 4 discloses the photograph of two analysis membranes made from a WHATMAN TM MF1 membrane-type substrate sheet (367 ⁇ m thick) and using a transfer film 20, as set forth in FIG. Figure 3 and as described in the previous example.
  • the tightness of the patterns is checked by means of a deposit of a colored solution in the flared portion of the pattern (deposition zone).
  • the analysis membrane 10 has been functionalized for the detection of hepatitis B, by immunodetection of the HBs antigen contained in the blood.
  • the zone 13d is functionalized by means of monoclonal antibodies anti-HBs, specific for the reaction; zone 13d forms the "spot test".
  • the 13th zone is functionalized by means of anti-alkaline phosphatase monoclonal antibodies, specific for the detection conjugate; the 13th zone forms the "positive control spot”.
  • the zone 13c is functionalized by means of non-specific antibodies of the reaction (for example, anti-rat antibodies); zone 13c forms the "negative control spot".
  • the functionalization of these different zones by the antibodies is carried out by passive adsorption of the antibodies on the constituent fibers of the substrate.
  • zone 13b is dedicated to storage of the second part of the conjugate complex (monoclonal antibodies anti-HBs labeled with biotin); zone 13b forms the "anti-HBs-biot Ac spot".
  • the deposition zone 13a can also be used for storing the conjugate of the enzyme-linked immunosorbent reaction (streptavidin-alkaline phosphatase or STRE-PAL) in dried form.
  • This conjugate will be resolubilized by the liquid phase of the sample to be analyzed.
  • the analysis membrane 10 According to a second mode of application of the analysis membrane 10 previously described, it has been functionalized for the detection, in blood and plasma, of two proteins of the dengue virus: the NS1 protein and the domain III of the envelope protein of the virus (DomIII).

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Laminated Bodies (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Claims (10)

  1. Verfahren zur Herstellung einer Analysemembran (10) eines Mikrofluidgeräts; wobei die Analysemembran (10) aus einer Folie eines porösen Substrats (11) gebildet ist, in deren Dicke festes Wachs undurchlässige Ränder (12) bildet, die hydrophile Zonen (13) begrenzen; wobei die undurchlässigen Ränder (12) durch die Substratfolie (11) ein in das Wachs gezeichnetes Motiv beschreiben;
    dadurch gekennzeichnet, dass es die folgenden Schritte umfasst:
    - ein Zwischenmotiv (12a, 12b), das mit dem Wachs nach dem Abbild des in das Wachs gezeichneten Motivs, das die undurchlässigen Ränder der Analysemembran (10) bilden, geformt ist, wird auf jede der Seiten einer Folie eines porösen Substrats (11) aufgebracht, so dass beiderseits der Dicke der Substratfolie (11) die Zwischenmotive (12a, 12b), die wechselseitig symmetrisch sind, einander gegenüber angeordnet sind;
    - horizontal gehalten, wird die Substratfolie (11) einer thermischen Behandlung, die geeignet ist, ein zumindest teilweises Schmelzen des Wachses hervorzurufen, aus dem die Zwischenmotive (12a, 12b) bestehen, die auf die Seiten der Substratfolie (11) aufgebracht sind, und einer mechanischen Behandlung unterzogen, die geeignet ist, die Dicke der Gesamtheit oder eines Teils der Substratfolie (11) zusammenzudrücken;
    - die Substratfolie (11) wird einer mechanischen und thermischen Entspannungsphase unterzogen, die geeignet ist, es der Substratfolie (11) zu ermöglichen, zumindest teilweise wieder ihre ursprüngliche Dicke anzunehmen, und es dem Wachs zu ermöglichen, sich innerhalb der Dicke der Substratfolie (11) wieder zu verfestigen; und
    dass die Dicke der Substratfolie (11) zwischen 200 µm und 1000 µm beträgt.
  2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass das Verfahren auf Basis einer Substratfolie (11) mit faseriger Zusammensetzung eingesetzt wird, ausgewählt unter: Zellulosefaser, Nitrozellulose, Baumwolle, Linter, Glas, Seide, Viskose, Polypropylen, Polyester, Polyamid, Poly(milchsäure).
  3. Verfahren nach Anspruch 1 oder 2, dadurch gekennzeichnet, dass es auf Basis einer Substratfolie (11) eingesetzt wird, die die Zusammensetzung eines Filtermediums aus Glasfaser übernimmt.
  4. Verfahren nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass die thermische Behandlung innerhalb eines thermisch kontrollierten Heizraums eingesetzt wird, und die mechanische Behandlung durch mechanische Mittel eingesetzt wird, die innerhalb des thermisch kontrollierten Raums installiert und geeignet sind, einen Druck oder eine Kompressionskraft auszuüben, die ausreichend sind, um die Dicke der Substratfolie (11) zumindest im Bereich der Zwischenmotive zusammenzudrücken.
  5. Verfahren nach einem der Ansprüche 1 bis 4, dadurch gekennzeichnet, dass die thermische Behandlung und die mechanische Behandlung gleichzeitig mit Hilfe einer thermisch kontrollierten Heiz-Kompressions-Vorrichtung erfolgen, die mit zwei horizontalen Heiz-Kompressions-Platen versehen ist.
  6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, dass für den Einsatz der thermischen Behandlung und mechanischen Behandlung eine weiche und elastische, flache Materialschicht zwischen jede der Seiten der Substratfolie (11) und die Heiz-Kompressions-Platten zwischengefügt wird; wobei die weiche Materialschicht als thermischer und mechanischer Puffer (15) dient.
  7. Verfahren nach Anspruch 6, dadurch gekennzeichnet, dass eine absorbierende Materialschicht zwischen jedes Zwischenmotiv (12a, 12b), das auf eine der Seiten der Substratfolie (11) aufgebracht ist, und den thermischen und mechanischen Puffer zwischengefügt ist.
  8. Verfahren nach einem der Ansprüche 1 bis 7, dadurch gekennzeichnet, dass die Zwischenmotive (12a; 12b) auf jede der Seiten der Substratfolie (11) mit einer Wachstransfertechnik aufgebracht sind.
  9. Verfahren nach Anspruch 8, dadurch gekennzeichnet, dass die Zwischenmotive (12a, 12b) zuerst auf eine Transferfolie (20) gedruckt werden, und dann auf jede der Seiten der Substratfolie (11), dann in ihre Dicke transferiert werden, wobei die thermischen und mechanischen Behandlungen durchgeführt werden.
  10. Verfahren nach Anspruch 9, dadurch gekennzeichnet, dass die Transferfolie (20) eine Folie aus Zellulosefaserpapier ist.
EP16163217.9A 2016-03-31 2016-03-31 Herstellungsverfahren von analysemembranen für mikrofluidgeräte Active EP3225309B1 (de)

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