Method for manufacturing a fluidic device comprising a substrate carrying at least one porous or hollow solid element

Abstract

The present invention relates to a method for manufacturing a device (10) for fluid flow along at least one fluid flow path through hollow or porous solid elements (30) fluidly connected to one another and at least a portion of a fluid circuit (50), the method comprising the steps of: e) printing a path (62) of the fluid circuit (50) with ink on a support and placing the solid elements (30) on the support, the ink being adjacent to the solid elements (30) in the fluid flow path; f) coating the solidified ink and the solid elements (30) with a crosslinkable polymer (25), the polymer (25) being immiscible with the solidified ink; g) crosslinking the polymer (25) to solidify it; and h) extracting the solidified ink to form the fluid flow path.

Description

[Technical Field]

[0001] The present invention relates to a method for manufacturing a device for fluid flow in at least one fluid flow path through a porous or hollow solid element and at least part of a fluid circuit. [Background technology]

[0002] The integration of hollow or porous elements in fluidic devices, particularly microfluidic devices, is challenging due to the need to precisely position the hollow or porous elements in the device to ensure (i) connection with the fluid circuit, (ii) fluid flow in the hollow or porous elements, and (iii) maintaining the properties of the hollow or porous elements, particularly the integrity of the pores or hollows and / or permeability of the hollow or porous elements, as well as their separation or catalytic function.

[0003] Most methods for fabricating fluidic devices employ at least one step involving the use of a liquid precursor to allow the generation of open regions, particularly passageways, in a solid material, which, after solidification, forms an impermeable wall between the open regions and the solid material. The liquid precursor is solidified, in particular, by polymerization, such as in fabrication of PDMS chips, or by heating above the glass transition of the polymer followed by cooling, as in chips made from molded thermoplastics.

[0004] The first of these methods, referred to as the ex situ technique, involves positioning hollow or porous elements before fabricating the chip. However, this technique naturally allows the liquid precursor to enter open spaces and become unable to be extracted when solidified, which impedes the flow of liquid in the hollow or porous element after solidification. This problem is particularly acute for small-sized elements compatible with miniaturized systems, but it can also be encountered for large-sized hollow or porous elements that may be intended to be encapsulated by the solidifying liquid to provide better impermeability than that achieved by the use and application of heat-shrink sheaths, for example, for shapes with complex shapes or sharp protruding edges. This penetration of liquid into open spaces not only interferes with the porous or hollow material, but also limits the connection of these elements to the fluid flow. Specifically, this requires having a fluid circuit whose cross section is perfectly adapted to the porous element and the porous element being fixed to ensure that the liquid flowing through the circuit necessarily traverses the circuit. It is also necessary that the hollow or porous element not be degraded when incorporated, and more specifically that it retain its integrity, its porosity, and / or its hollow or porous volume.

[0005] Conventional solutions for integrating porous or hollow solid elements into fluid passages involve forcibly inserting the solid element into the passage or using a sheath that conforms to the shape of the material, specifically a heat-shrink sheath, as described in articles by Namera et al., Trends in Analytical Chemistry, vol. 45, 2013, and Nakanishi, Wiley, Synthesis Concepts and Preparation of Silica Monoliths, 2011-10.1002 / 9783527633241.ch2. These techniques are limited by the mechanical stresses the elements are subjected to, particularly when the elements are small in size. For example, cylindrical monoliths with hierarchical porosity and diameters greater than 3 mm can be placed in a heat-shrink sheath, but for diameters less than 3 mm, problems are observed, such as material degradation following sheath shrinkage.

[0006] Han et al., Microsystems & Nanoengineering 2019, 5:30, describe porous elements encapsulated in a sheath, which is then encased in polymethylmethacrylate (PMMA), for very simple architectures, such as a single passageway. The solid sheath integration solution is technically very limiting for fabricating fluidic devices, particularly when one or more functions need to be integrated into a complex fluidic architecture. This is even more true for functions that require complex architectures, such as the integration of moving elements or optical constraints.

[0007] Patent applications U.S. Pat. No. 7,651,762 B2 and WO 2004 / 039495 disclose the production of sheaths via solidifying liquids. This is an alternative that allows for a perfect conformance to the shape of hollow or porous elements. This type of technique is used, in particular, to manufacture certain chromatographic columns with diameters exceeding 1 mm. However, as the diameter of the material becomes smaller, techniques based on solidifying liquids become more difficult to implement, in particular due to the penetration of the liquid into some of the open spaces or pores. This is a major disadvantage for miniaturization, and is particularly detrimental for elements with small diameters or thicknesses, such as tubes with diameters typically less than 2 mm. Furthermore, such materials completely encapsulate the solid elements, preventing them from being integrated into fluid circuits.

[0008] The second technique, called the in-situ technique, involves the integration of various elements into the fluidic device after its fabrication and solidification, specifically the pores. For this purpose, hollow or porous elements are directly fabricated in the device. Patent application EP 3017866B1 and an article by Wu et al., Anal. Chem. 2006, 78 (16), 5704-5710, describe such in-situ fabrication. Nevertheless, apart from the fact that it can be difficult to control the size of the generated hollow or porous elements and that it can be difficult to reproduce the porosity and structural properties of the hollow or porous elements, there can be a loss of impermeability between the hollow or porous elements and the fluidic device. This problem of maintaining the impermeable properties, and more generally of reproducibility, is also encountered in the literature on in situ integration of porous materials, especially in the case of monoliths obtained by sol-gel processes, which are already difficult to integrate into a single glass capillary, as demonstrated by the article by Ishizuka et al., Journal of Chromatography A (2002), 960(1-2), 85-96.

[0009] For the manufacture of fluidic devices, WO 2019 / 077144 discloses the use of sacrificial inks to trace fluidic circuits on a substrate before coating the ink with a crosslinkable polymer, and after solidification of the polymer, removing the ink to form the fluidic circuits within the structure of the crosslinked polymer.

[0010] In view of the difficulties presented above, it is understood that it is difficult to fabricate fluidic devices that integrate hollow or porous elements with complex designs that combine two or more functions in a small space, for example. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] U.S. Patent No. 7,651,762 [Patent Document 2] International Publication No. 2004 / 039495 [Patent Document 3] European Patent No. 3017866 [Patent Document 4] International Publication No. 2019 / 077144 [Non-patent literature]

[0012] [Non-Patent Document 1] Namera et al., Trends in Analytical Chemistry, vol. 45, 2013 [Non-patent document 2] Nakanishi, Wiley, Synthesis Concepts and Preparation of Silica Monoliths, 2011-10.1002 / 9783527633241.ch2 [Non-patent document 3] Han et al., Microsystems & Nanoengineering 2019, 5:30 [Non-patent document 4] Wu et al., Anal. Chem. 2006, 78 (16), 5704-5710 [Non-patent document 5] Ishizuka et al., Journal of Chromatography A (2002), 960(1-2), 85-96 Summary of the Invention [Problem to be solved by the invention]

[0013] Therefore, there is a need for a method for manufacturing fluidic devices that can integrate porous or hollow solid elements without making the fluidic device more complex, in a way that is simple, universal, or at least compatible with the majority of methods for manufacturing fluidic devices, and that is reproducible and robust in terms of fluid flow and functionality. This is particularly needed to be able to create columns, extraction supports, catalysts, and microsystems without having to redeploy expertise and research to readapt the necessary experimental parameters due to changes in the format and / or size of the hollow or porous elements. [Means for solving the problem]

[0014] The present invention addresses this need by providing a method for manufacturing a device for fluid flow in at least one fluid flow path through a porous or hollow solid element and at least a part of a fluid circuit, the solid element and the part of the fluid circuit being fluidly connected to each other, comprising: a) printing a fluid circuit path with ink on a support and placing solid elements on the support, the ink being adjacent to the solid elements in the fluid flow path; b) coating the solidified ink and solid elements with a crosslinkable polymer, the polymer being immiscible with the solidified ink; c) cross-linking the polymer to solidify it; d) extracting the solidified ink to form a fluid flow path; The method includes:

[0015] Fluidly connected to each other means that a fluid can pass from one to the other by means of a fluid flow area extending between the two. The fluid connection between the solid element and the fluid circuit is preferably achieved directly by having at least one pore, preferably two or more pores, or at least one hollow portion of the solid element in a portion of the fluid circuit unobstructed.

[0016] Printing the path of a fluid circuit with ink on a support means that ink is placed on the support so that the accumulation areas formed by the ink represent the path of the recessed areas of the fluid circuit, reproducing the path of the fluid circuit on the support.

[0017] The fluid flow in the fluid flow path through the porous or hollow solid element and at least part of the fluid circuit means that after extraction of the ink in step d), there is a continuous path through the solid element and at least part of the fluid circuit through which the fluid can flow. This means that the solid element, after fabrication of the device, retains within itself transverse paths through which the fluid can flow, and the connection between the solid element and the fluid circuit allows the fluid to flow from one to the other, the ink and the solid element being joined at a surface of the solid element from which the pores open or at least one hollow part of the solid element opens.

[0018] Immiscible means that the solidified ink is not miscible with the polymer.

[0019] This type of method allows hollow or porous solid elements to be easily integrated into a fluid circuit while allowing fluid to flow through the solid elements in the fluid circuit. The ink forms one or more microcavities and / or one or more microchannels in the polymer that form the fluid circuit. When the ink contacts the solid element in the fluid flow path, the solid element is protected from contact with the polymer at its junction with the ink, thereby preventing the polymer from penetrating into the hollow or pore at this junction during the polymer coating step b). Therefore, after the ink extraction step, at least one of the microcavities or one of the microchannels is directly fluidically connected to the hollow or free pore in the fluid flow surface of the solid element.

[0020] Extraction of the ink in step d) after solidification of the polymer causes recessed areas of the fluid circuit to form, which partially define the fluid path in the solidified polymer. The junction between the ink and the porous element in the fluid flow path in step a) allows an area at this junction to remain for the passage of fluid from the solid element to the circuit formed by extraction of the ink, and the fluid flow is not impeded by the polymer at this junction due to the presence of ink.

[0021] The solid element may be disposed on the support in a predetermined area of ​​the support, the predetermined area being determined such that the solid element is in the fluid flow path and such that the solid element is adjacent to at least a portion of the fluid circuit.

[0022] method Maintaining fluid flow paths The method preferably includes a step of protecting at least some of the pores or one or more hollows of the solid element along the fluid flow path. The protecting step may include filling at least some of the solid element, in particular the center of the solid element, more preferably the whole solid element, with a protective agent that prevents penetration of the polymer into the solid element in the covering step b) before the covering step b), and extracting the protective agent after the polymer cross-linking step c) to allow fluid flow in the solid element. The protective agent is preferably liquid when introduced into the solid element and solidifies before covering the solid element with the polymer. The solid element may be cooled to a temperature below the solidification temperature of the protective agent.

[0023] The solidified protectant is preferably immiscible with the polymer. The solidified protectant may be extracted before, simultaneously with, or after the extraction of the ink. The protectant is preferably extracted simultaneously with the extraction of the ink by the same extraction technique.

[0024] Filling of at least a part of the solid element, in particular the centre of the solid element, more preferably the whole of the solid element with the protective agent may be performed before step a) of printing the ink and placing the solid element.

[0025] The protective agent is preferably miscible with the ink for printing the fluidic circuit, which facilitates bonding of the solid elements with the ink in step b).

[0026] The protective agent may be the same as the ink for printing the paths of the fluid circuit, in which case the filling of at least a part of the solid elements, in particular the centres of the solid elements, more preferably the whole of the solid elements, with the protective agent may precede the printing of the ink, or, as a variant, step a) may comprise placing the solid elements on a support and then printing the ink on the support so that the ink fills at least a part of the solid elements, in particular the centres of the solid elements, more preferably the whole of the solid elements.

[0027] As a variant, in the case of a porous solid element, the polymer is crosslinked before it is able to fill the pores of at least one flow crossing area of ​​the fluid flow channels of the solid element.

[0028] The method may be configured such that the polymer outside the surface area of ​​the solid element in contact with the ink penetrates into the pores of the solid element during the coating step b) and the bridging step c) over a skin depth of the solid element of not more than 40%, more preferably not more than 30%, even more preferably not more than 20%, preferentially not more than 10% of the smallest dimension of the solid element at each flow intersection area of ​​the fluid flow paths in the solid element. The flow intersection area of ​​the fluid flow paths in the solid element means a cross section across the fluid flow paths in the solid element. This allows for a region within the solid element at each flow intersection area within the solid element for the flow of fluid along the fluid paths.

[0029] Step a) The substrate is preferably cooled to a temperature below the solidification temperature of the ink.

[0030] The ink can be printed before the hollow or porous elements are placed on the substrate, or conversely, after the hollow or porous elements are placed on the substrate.

[0031] The path may be continuous or discontinuous. The path may comprise a number of successive portions of printing that are discontinuous from one another, in particular connected to one another by solid and / or auxiliary solid elements.

[0032] The method may involve pre-treatment of the substrate to enhance the strength of adhesion with the ink to be deposited and / or the polymer intended to form the shell.

[0033] The ink is supplied to the printing nozzle and -1The ink may be printed by inkjet printing using a liquid ink having the following viscosity: The distance between the print nozzle on the one hand and the substrate on the other hand may be between 0.5 mm and 20 mm; The size of the ink droplets ejected by the print nozzle may be between 10 μm and 100 μm; The frequency at which ink droplets are ejected from the nozzle may be between 50 Hz and 5 kHz; The substrate on the one hand and the print nozzle on the other hand may be adapted to allow a relative displacement of one with respect to the other at a controlled relative displacement speed of between 1 mm / s and 100 mm / s.

[0034] In a variant, the ink is printed using a syringe containing the ink. The distance between the end of the syringe, through which the ink is dispensed, on the one hand, and the support, on the other hand, can be between 0.1 mm and 1 mm. The flow rate of the ink dispensed by the end of the syringe can be between 0.01 nl / s and 10 nl / s. The support, on the one hand, and the syringe end, on the other hand, can be adapted to allow a relative displacement of one with respect to the other at a controlled relative displacement speed between 0.1 mm / s and 10 mm / s.

[0035] Printing can be carried out by printing on a preferably flat printing surface of the support. As a variant, the printing surface can be curved, in particular concave or convex.

[0036] The method may involve localized printing of multiple successive layers of ink one on top of the other, followed by solidification of the ink between each layer, to provide a predetermined thickness of ink printed on a substrate, thereby providing a predetermined localized depth of fluidic circuitry. This provides access to many device architectures interfacing with a wide variety of solid state elements, making the method versatile.

[0037] The steps of printing paths and disposing solid elements can include a first printing of ink to form the paths of the fluid circuit and disposing of the fixed elements on the support, followed by a second printing of ink to form a bond between the solid elements and the ink of the first printing, particularly at the bond between the solid elements and the ink of the first printing. Through this technique, it is possible to have a bond between the solid elements and the ink that prevents the polymer from penetrating between them. Furthermore, this technique allows for an effective bond despite manufacturing imperfections, thereby increasing the reproducibility of the method. Finally, this technique can lock the porous elements in place, particularly during the addition of the polymer, which further enhances the effective formation of the fluid flow paths.

[0038] The thickness of the ink at the junction with the solid element is preferably substantially equal to the thickness of the solid element at the same junction. The cross section of the ink placed at the junction is preferably substantially equal to the cross section of the solid element at the junction. As a variant, the cross sections are different.

[0039] As a variant, the method may comprise printing at least two separate, consecutive sections to form the path of the fluid circuit, and arranging a solid element at least partially between the two consecutive structures, which allows, after extraction of the ink, to form a junction by the solid element between the two consecutive sections that forms the conduit, so that the fluid flow path necessarily proceeds through a pore or hollow in the solid element between the two sections.

[0040] The solid element may be positioned across two continuous portions. In this embodiment, each end of the solid element may extend over one of the two continuous portions. The two continuous portions may include a notch for receiving the end of the solid element. This specifically allows the solid element to be lifted relative to the support, with the two continuous portions forming a lifting block during manufacturing. Thus, during coating with polymer, part of the polymer extends underneath the solid element between the two continuous portions, but not on the surface of the solid element, in such a way that the solid element is encapsulated by the polymer. As a result, specifically, the solid element can be held during ink extraction to form fluid channels, as will be seen later. This allows for the solid element to be held in part at its ends and at the fluid junction, enhancing contact between the ink and the solid element.

[0041] Furthermore, in this case, as explained above, it is preferable to provide for printing twice, once before and once after the placement of the solid elements, in order to improve the retention of the solid elements when the polymer is inserted and also to improve the retention of the bond between the solid elements and the ink.

[0042] The method may comprise a step of solidifying the ink and / or protective agent before coating with the polymer in step b), which may be spontaneous, taking into account the properties of the ink and / or protective agent, in particular by waiting for a solidification time, in particular the time for evaporation of the solvent, or may be controlled, in particular by heating.

[0043] Between steps a) and b), the method may include an annealing step at a temperature below the extraction temperature of the ink and, if appropriate, the extraction temperature of the protective agent. Such an annealing step can reduce the roughness of the surface of the deposited pathways. Indeed, it can be noted that when the ink solidifies, even taking into account the deposition conditions, the surface of the ink in solid form exhibits a considerable roughness. This roughness can consequently be transferred to the polymer walls of the fluidic circuit. The roughness can have a non-trivial effect on the flow conditions in the device, resulting in head losses and / or undesirable heat exchange, or can alter the analytical conditions.

[0044] The method may include arranging a plurality of hollow and / or porous solid elements in step a), each adjacent to the printed ink along the fluid flow path. The solid elements may be fluidly connected to one another in series or parallel along the fluid flow path by one or more continuous portions of a fluid circuit. The solid elements may have substantially the same dimensions, structure, and / or porosity, or, as a variant, may differ in their dimensions, structure, and / or porosity. The continuous portion of the fluid circuit may form a junction, particularly between two or more solid elements of different nature, more specifically between a hollow solid element forming a passageway and a porous solid element.

[0045] The method may include adding one or more solid auxiliary elements in step a), wherein the one or more auxiliary elements are: - interconnection elements that allow fluid flow in a fluid circuit, in particular for connecting a fluid circuit to a fluid inlet or outlet or for connecting a device to another identical or different device; and / or - elements for the arrangement of the solid elements on the support, in particular blocks each arranged at least partially under at least one part of the solid elements, in particular under each of the edges of the solid elements; may be selected from:

[0046] Covering The step of coating the solid elements and solidified ink with a polymer can be performed by pouring the polymer onto the support, the solid elements, and the printed and solidified ink.

[0047] The polymer introduced in step b) may include polydimethylsiloxane (PDMS), polyimide, agarose gel, adhesives such as acrylic, or mixtures thereof.

[0048] The polymer may include a cross-linking additive, which may be a cross-linking agent, such as methylhydrosiloxane, a photoinitiator, such as 1-hydroxycyclohexylphenyl ketone, benzophenone, or quinone, or a solvent, such as formaldehyde.

[0049] If the additive is a crosslinking agent, depending on the nature of this crosslinking agent and / or the polymer, crosslinking can be carried out at ambient temperature, optionally assisted by slow heating to accelerate crosslinking. Also, if the nature of the crosslinking agent and / or the polymer does not allow crosslinking at ambient temperature, crosslinking can be carried out by heating, in particular at a temperature below the extraction temperature of the ink and, where appropriate, the extraction temperature of the protective liquid, at equivalent pressure.

[0050] If the additive is a photoinitiator, crosslinking can be achieved by exposing the polymer to ultraviolet radiation. Photoinitiators may be specifically considered for certain adhesives that are crosslinkable by ultraviolet radiation.

[0051] Finally, if the additive is a solvent, crosslinking, which generally occurs at ambient temperature, involves evaporation of the solvent, which causes the polymer to crosslink.

[0052] The cross-linking of the polymer is preferably controlled so that the cross-linking time is shorter than the time for filling of the porous solid element with the polymer. The cross-linking time can be controlled by controlling the temperature and / or pressure at which the polymer is cross-linked.

[0053] extraction Extraction of the ink and, where appropriate, the protective agent may be accomplished by any technique that maintains the integrity of the solid elements and the crosslinked polymer. Preferably, extraction of the ink and, where appropriate, the protective agent is accomplished by evaporating the ink and, where appropriate, the protective agent, and venting the vapors.

[0054] Extraction of the ink and / or protective agent may be accomplished by sublimation, depending on the properties of the ink and, if appropriate, the protective agent, or by liquefaction of the ink and, if appropriate, the solidified protective agent, followed by evaporation, depending on the properties of the ink and / or protective agent. Other extraction solutions are possible if they can extract the ink to form fluid channels. Depending on the properties of the ink and crosslinkable polymer, consideration may be given to, for example, thermal decomposition by heat treatment at an ink decomposition temperature lower than the melting temperature of the crosslinkable polymer, dilution by circulation of the ink diluted product with or without prior liquefaction of the ink, or suction / excess pressure with prior liquefaction of the ink. Preferably, the extraction temperature of the ink and, if appropriate, the solidified protective agent is lower than the melting temperature of the polymer at the same pressure.

[0055] Therefore, in order to sublimate the ink and, if appropriate, the protective agent, the extraction step can be carried out by heating and by applying a pressure difference between the inside and outside of the assembly formed at the end of step c). This makes it possible to position the system at a pressure / temperature combination that directly allows the transition from the solid state to the vapor state in the phase diagram of the ink and, if appropriate, the protective agent. This is particularly advantageous, when conceivable, since it limits the level of heating of the assembly formed in step c) and therefore the ink and, if appropriate, the protective agent, to evaporate, thereby limiting the energy consumed to remove the ink and, if appropriate, the protective agent so as to form the fluid flow channels.

[0056] As a variant, the extraction step d) is carried out by heating, so as to ensure the liquefaction and subsequent evaporation of the ink and, where appropriate, the protective agent.

[0057] The method may include circulating a cleaning liquid along the fluid flow paths in the device to clean the device after extraction of the ink and / or protectant. The method may include drying the device after cleaning.

[0058] Before or after coating with the polymer, and before or after extraction, the method may include adding additional structures in the polymer, specifically adding perforation structures in the polymer to connect the fluid circuit in the polymer to the outside.

[0059] In a variant, when the ink is deposited in at least partial contact with the support, the extraction of the ink can be - separation of the initial support of the assembly formed at least from the crosslinked polymer, the ink and the solid element forming a single block; - extraction of the ink from the assembly, in particular by dissolution in alcohol and / or evaporation or sublimation of the ink, as previously described; - installation of the assembly from which the ink has been extracted to form a fluid circuit on the same or a different support as the initial support; The fastening on the support can be performed by adhesion of the polymer on the support, with or without adhesive, or by any other known technique that allows an impermeable adhesion on the support.

[0060] This variant is more particularly applicable when the solid element is at least partially encapsulated in the polymer, and the solid element is raised relative to the support, because, with the solid element held in the polymer, it is not in contact with the support, making it easier to remove and re-fix the assembly of the support. In the case of solid elements that are flush with the support, this variant is also applicable, but is not preferred.

[0061] support The support may comprise a substrate made of a hydrophobic material selected from the following: polyimide (PI), silicones including polydimethylsiloxane (PDMS), polypropylene (PP), polytetrafluoroethylene (PTFE), and cyclic olefin copolymer (COC), or a hydrophilic material selected from silicon, glass, cellulose, and glass fiber.

[0062] The substrate may be rigid. The substrate may be multi-layered.

[0063] The printing surface may be the surface of a substrate. The printing surface may be flat. In a variant, the printing surface is not flat, but in particular is curved, more in particular is concave or convex, or comprises surface relief.

[0064] The method may comprise withdrawing at least a portion of the support, in particular at least a portion of the substrate.

[0065] In a variant, the support comprises a substrate as described above and one or more support elements arranged on the substrate. The support elements may, if appropriate, have the same thickness taken across the plane of extension of the substrate. The printing surface may comprise the outer surface of each support element. The outer surface or surface may be flat. The outer surfaces of the printing surface may be coplanar. The method may comprise the step of forming the support by adding one or more support elements to the substrate.

[0066] The support may comprise at least two support elements in the substrate, in particular made from the same cross-linked polymer as in step b), the at least two support elements being spaced apart by a non-zero distance, the device being configured such that a solid element is placed in step a) across the two support elements and the ink is printed on one or both support elements, this being particularly useful when the substrate is pulled out after steps c) or d), as described later, since the encapsulation of the solid elements and fluidic circuitry in the polymer enhances the rigidity of the device.

[0067] The contact surface between the solid element and the support may be positioned flush with the surface for printing of the ink.

[0068] In a variant, the support has a cavity for receiving the solid element on its surface configured for receiving the solid element, and the solid element is placed in the cavity in step a). This type of cavity allows the porous element to be easily and accurately positioned on the support. It also allows the porous element to be held on the support during the ink printing and polymer coating steps. The cavity for receiving the solid element preferably has a depth that is equal to or less than the size of the solid element taken perpendicular to the support, in particular equal to or less than the thickness of the solid element, so as to allow a fluid circuit to be formed at the junction between the ink and the solid element. The depth of the cavity for receiving the solid element may be equal to or less than 80%, more preferably equal to 50%, of the size of the solid element taken perpendicular to the support. The cavity for receiving the solid element may be formed by a recess or groove in the crosslinked polymer layer of the substrate or the support, which may or may not be adjusted to the shape of the solid element in which the solid element is placed in step a). As a variant, the cavity for receiving the solid element is defined by a plurality of surface elements, in particular made from the same crosslinked polymer as in step b), which surface elements are arranged on the substrate to form the cavity for receiving the solid element, in which case the solid element is arranged on the substrate in the cavity and is bordered contiguously on at least one of its sides, more preferably on at least two of its sides and even more preferably on its two longitudinal ends, by the surface elements forming the surface for printing of the ink in step a).

[0069] fluid circuit The fluid circuit may comprise passages and / or chambers, the passages or chambers being adjacent to solid elements along the fluid flow path.

[0070] The fluid circuit may be a microfluidic circuit. The fluid circuit may include at least one microchannel and / or at least one microfluidic chamber. The solid element is preferably adjacent to the microchannel in the fluid flow path. The presence of a microfluidic circuit allows for the processing of small volumes, thereby reducing analysis time, liquid consumption, and ultimately costs.

[0071] The fluid circuit may comprise two passages that fluidly connect one end of the solid element with a fluid flow path defined from one micropassage to the other micropassage and passing through the solid element.

[0072] The fluid surface may extend in a plane of extension substantially parallel to the printing surface.

[0073] At the junction with the solid element, the fluid circuit can have a cross section substantially equal to the cross section of the solid element to which it is attached. As a variant, at the junction with the solid element, the fluid circuit can have a cross section larger than the cross section of the solid element to which it is attached. For example, the fluid circuit can have a passage extending along the plane of extension in the support and having a vertical extension for attaching the end of the solid element encapsulated in a cross-linked polymer at the junction with the solid element. In this case, the height of the passage at the level of the end of the solid element can be equal to or greater than the sum of the height of the end of the fixing element to which the passage is attached and the lift height of the fixing element relative to the support.

[0074] solid elements The solid elements may be arranged above the support with or without contact with the support, in blocks arranged on the substrate with contact with the support, or in one or more successive print portions without contact with the substrate.

[0075] The solid element may extend in a fluid flow path such that the fluid flow path traverses the solid element from an entry point to an exit point, the entry and exit points being separated by a distance of 0.5 mm or more, more preferably 1 mm or more, even more preferably 2 mm or more. The entry and exit points are preferably separated by a distance of 10% or more, more preferably 50% or more of the largest dimension of the solid element, even more preferably the entire distance. The entry and exit points may be on opposite faces of the solid element, particularly at opposite ends of the solid element.

[0076] The straight line between the entry and exit points of the fluid flow path preferably extends parallel to the printing surface of the support.

[0077] The solid element may be positioned in the fluid flow path such that a line connecting the entry point and exit point of the fluid flow path in the solid element extends along the median axis of the solid element.

[0078] The solid element may have a maximum dimension, taken across a line connecting the inlet and outlet points of the fluid flow paths in the solid element, in particular a thickness taken perpendicular to the plane of extension of the support, of 10 mm or less, more preferably 5 mm or less, even more preferably 2 mm or less, even more preferably 1.5 mm or less, and even more preferably 1 mm or less. The solid element may have a maximum dimension, taken across a line connecting the inlet and outlet points of the fluid flow paths in the solid element, in particular a thickness taken perpendicular to the plane of extension of the support, of 20 μm (microns) or more, more preferably 50 μm or more, even more preferably 100 μm or more, and preferably 200 μm or more.

[0079] The solid element is preferably cylindrical with a polygonal, elliptical, triangular or circular base, in particular a cylinder of revolution.

[0080] The solid element may be elongated along an elongated linear or non-linear axis and may have a length of 0.5 mm or more, more preferably 1 mm or more, even more preferably 2 mm or more, and / or 10 cm or less, more preferably 5 cm or less. The elongated axis may extend in a plane.

[0081] The fluid flow path preferably intersects the solid element over its entire length.

[0082] The solid element is preferably cylindrical with a diameter of 10 mm or less, more preferably 6 mm or less, and / or a diameter of 0.02 mm or more, and / or a length of 0.5 mm or more, more preferably 1 mm or more, even more preferably 2 mm or more.

[0083] The solid element may have an aspect ratio, defined as the ratio of its length to its largest transverse dimension, of 0.2 or more, more preferably 0.4 or more, more preferably 1 or more, and / or 1000 or less, more preferably 500 or less, even more preferably 100 or less, even more preferably 50 or less, even more preferably 20 or less.

[0084] The solid elements may be arranged on the support such that the fluid flow path intersects the solid elements over a length greater than the thickness of the solid elements taken perpendicular to the printing surface.

[0085] hollow element The solid element can be hollow, with the two open ends of the hollow element located in the fluid flow path and the central axis of the hollow element extending along the fluid flow path. The central axis of the hollow element can be straight or curved. In the case of a hollow solid element, the fluid flow path can be maintained in the hollow element by plugging the two ends with a protective agent before addition to the support, or by a fluid circuit ink applied to the hollow ends of the solid element during step a).

[0086] The solid element may be a tube or capillary made of silica, glass, or any other material compatible with the ink and polymer used in cross-linking. As a variant, the solid element is a hollow element other than a tube or capillary. The solid element may in particular be a fluid junction, such as a Y-, T-, or X-junction, a valve, a gate, a sheath, or any other form of hollow element.

[0087] The capillary may have a diameter of 2 mm or less.

[0088] Porous Elements The solid element is preferably porous.

[0089] The solid element preferably comprises a porous monolith with graded porosity, meaning at least two orders of magnitude of pore size, preferably including macropores (as described above) formed during the sol-gel matrix formation step and mesopores (as described above) formed during the controlled mesopore generation step. This type of porous monolith provides efficient surface area exchange between the fluid traversing the porous monolith and the porous monolith's bulk, minimizing the distance that must be covered by diffusion. Furthermore, this can provide flexibility to the porous monolith, reducing the risk of fracture.

[0090] The solid element preferably comprises a self-supporting porous monolith, meaning that the porous monolith is stable due to its own rigidity and is stable enough to be handled and therefore does not require any support.

[0091] The porous monolith may be disposed bare on the support, meaning that the porous monolith is not provided with an additional outer shell before being disposed on the support, specifically, it is not provided with a heat shrink sheath or received in a conduit, or conduit, as previously described. Alternatively, the porous monolith may be impregnated with a protective agent.

[0092] In a variant, the solid element comprises a porous monolith and a protective outer sheath for the porous monolith, which is open at the entry and exit points of the fluid flow paths, the ink being adjacent to at least one open end of the tube or capillary in step a) of the method. The porous monolith and outer sheath are preferably configured such that the fluid flow paths intersect the porous monolith over a distance of at least 10%, more preferably at least 50%, and even more preferably the entire distance of a straight line between the entry and exit points at the porous monolith in the fluid flow paths.

[0093] The protective outer sheath may be a heat shrink sheath. The method may include inserting the porous monolith into the heat shrink sheath and heating the sheath to shrink it around the porous monolith. This causes the porous monolith to wear the shrunken sheath which adjusts to said monolith and ensures that the fluid flow path actually traverses the porous monolith.

[0094] Alternatively, the outer sheath may be rigid. The outer sheath may take the form of a tube or capillary. In this case, the porous monolith is preferably formed directly on the outer sheath, in particular by the sol-gel method described below. In the case of a capillary, the diameter of the capillary is preferably 2 mm or less.

[0095] The porous monolith may comprise macropores, in particular macropores with a size of 50 nm or more. The macropores may have a size of 30 μm or less.

[0096] The porous monolith may comprise mesopores, in particular mesopores with a size of 50 nm or less, more preferably between 2 nm and 50 nm. The pores are preferably interconnected in the porous monolith.

[0097] The porous monolith may have a substantially constant structure throughout its volume.

[0098] Porous monoliths can exhibit pore surface functionalization. The pore surfaces of porous monoliths can be coated with compounds such as hydrophobic hydrocarbon ligands (e.g., octadecyl ligands) or hydrophilic ligands such as 2,3-dihydroxypropyl derivatives. The ligands of such modified porous monoliths can be further modified using known procedures. Porous catalyst or enzyme supports can be prepared by adding enzymes such as glucose isomerase or catalytic metal elements such as platinum and palladium.

[0099] Method for forming a porous monolith The porous monolith is preferably formed by a sol-gel process, which comprises forming a porous monolith with the chemical formula M(OR) n Or R'-M(OR) n-1 This refers to a process carried out using precursors containing alkoxides of or other sodium silicate or titanium colloids, where M is a metal, transition metal, or metal alloy, specifically silicon; R or R' is an alkyl group; and n is the oxidation state of the metal. In the presence of water, the alkoxy groups (OR) hydrolyze to form small particles, typically with sizes less than 1 nanometer. These particles aggregate to form clusters that remain in suspension without settling, forming a sol. The growth of the clusters and their condensation increases the concentration of the medium, forming what is called a gel. Thus, the gel can continue to grow during an aging process, which involves densification of the polymer network present in the gel. Subsequently, the gel shrinks, expelling the solvent from the formed polymer network in a step called syneresis. Next, the solvent evaporates in a so-called drying step, resulting in a porous, glassy solid material, providing a porous monolith. The syneresis and drying steps can occur simultaneously. This type of process specifically produces porous monoliths with controlled porosity and pore size distribution. This type of method also produces a wide variety of configurations.

[0100] The method is: - forming a sol comprising a sol-gel precursor in an aqueous solution, preferably comprising a pore-forming agent; - at least partially filling the enclosure and at least one mold contained in the enclosure with a preformed sol, the mold having at least one opening that opens into the sol after filling with the sol; - forming a sol-gel matrix from the sol in the enclosure; - Extraction of the mold together with the sol-gel matrix contained therein from the enclosure; - Formation of porous monoliths from sol-gel matrices and Preferably, the method comprises forming a porous monolith by a manufacturing method comprising: The sol, sol-gel matrix, and porous monolith are formed by the sol-gel method.

[0101] The method may include extracting the sol-gel matrix from the mold before or after formation of the porous monolith.

[0102] The presence of at least one opening in the mold below the sol level after filling allows the mold to be filled with sol during the filling step and allows fluid flow of the sol between the sol contained in the mold and the sol contained in the enclosure during the remainder of the method. Creating a large sol-gel matrix in the enclosure and extracting a portion of this matrix contained in the mold during matrix formation allows for the avoidance of edge effects present in previously described methods, which always create sol-gel matrices in containers of the same size. This type of method allows for the production of self-supporting porous monoliths, particularly those with similar textural properties over a wide range of diameters, without the need to reoptimize or even modify the initial mixture formulation. This type of method allows for the use of a wide variety of monolith morphologies and aspect ratios, but also the use of reproducibly controlled internal structures, particularly porosity and pore size distribution. The resulting structure is particularly uniform, ensuring uniform resistance to mechanical stress. This may prove useful, for example, to prevent fracture when pressure is exerted on the monolith when it is integrated into a fluid conduit, particularly when enclosed in a heat-shrink fluid conduit.

[0103] The sol can be formed by stirring a solution containing sol-gel precursors, preferably containing the sol-gel precursors and the pore-forming agent, for a period of time of at least 5 minutes, more preferably at least 10 minutes, and even more preferably at least 15 minutes. The stirring time can be at most 3 hours, more preferably at most 2 hours. During stirring, the temperature can be controlled at a substantially constant predetermined value, specifically between 0°C and 90°C, more preferably between 0°C and 50°C.

[0104] Filling can be accomplished without the presence of solvent bubbles in the enclosure and mold and / or gradients in chemical composition and / or temperature.

[0105] Forming the sol-gel matrix can include condensation to form a gel and can optionally include at least partial aging to densify the gel.

[0106] The sol-gel matrix is ​​preferably formed into the enclosure without drying the sol-gel matrix.

[0107] Formation of the sol-gel matrix can be accomplished in the same manner in the surround and the mold. The overall porosity and pore size is preferably substantially uniform in the surround and the mold.

[0108] Extraction of the matrix-containing molds from their surroundings can involve extracting a block of sol-gel matrix containing the molds from the surroundings and extracting the molds and the sol-gel matrix they contain from the previously extracted block. Extraction of each mold from the block can be accomplished by cutting the sol-gel matrix flush with the corresponding mold or by breaking the sol-gel matrix surrounding the mold. As a variant, extraction of the molds or each mold containing matrix can be accomplished by extracting the corresponding mold from the sol-gel matrix surrounding it after extraction of the block as described above, or by extracting it directly in the surroundings without prior extraction of the block, particularly when the corresponding mold is only partially immersed in the sol-gel matrix.

[0109] The extraction of the sol-gel matrix contained in each mold can be carried out using a controlled pressure on said sol-gel matrix, for example by direct pressure with a solid whose size is smaller than that of the mold, by the pressure of a gas at a controlled flow rate, or by opening each mold, in particular by cutting each mold, or by separating the two parts of each mold from each other. The molds can be in the form of two parts that can be moved relative to each other, in particular two parts that are separable or that can be moved relative to each other thanks to a hinge.

[0110] The mold containing the sol-gel matrix may be immersed in a liquid during the step of extracting the sol-gel matrix contained in the mold, which facilitates the extraction of the sol-gel matrix.

[0111] Formation of the porous monolith can include controlled generation of mesoporosity in the sol-gel matrix to form a graded porosity sol-gel matrix after extraction of the mold from the surroundings and prior to formation of the porous monolith from the mold's sol-gel matrix. Controlled generation of mesoporosity can be accomplished by immersing each extracted or unextracted sol-gel matrix from the mold in an aqueous mesoporosity-generating solution containing a dissolving agent for the sol-gel matrix and / or a precursor to the dissolving agent for the sol-gel matrix. The dissolving agent can be ammonium hydroxide, sodium hydroxide, hydrofluoric acid, or a mixture thereof, such as at a 1 M concentration. The precursor to the dissolving agent for the sol-gel matrix can be urea or a compound with an amide function, specifically formamide, acetamide, N-methylformamide (NMF), and a mixture thereof. The concentration of the dissolving agent and / or the concentration of the precursor of the dissolving agent is preferably such that it allows localized dissolution of the sol-gel matrix to form mesopores in the sol-gel matrix without dissolving the sol-gel matrix entirely.

[0112] Formation of the porous monolith may include at least partial aging to densify the sol-gel matrix, particularly when no aging has occurred beforehand.

[0113] The formation of the porous monolith may, where appropriate, include drying the sol-gel matrix, which may or may not be extracted from the mold after the development of mesopores, to form a dry sol-gel matrix. The drying step may be carried out in a stream of air or an inert gas, in particular dinitrogen, argon or carbon dioxide, helium, or even dioxygen or dihydrogen.

[0114] Formation of the porous monolith may involve heat treatment of the sol-gel matrix, which may or may not be extracted from each mold, particularly after drying. Heat treatment may be carried out in a closed container in a stream of air or an inert gas, particularly dinitrogen, argon, or carbon dioxide, helium, or even dioxygen or dihydrogen, by gradual heating followed by holding at the final temperature for a predetermined time. The gradual heating may be in increments of 0.5°C / min until a temperature of 300°C or higher, more preferably 340°C or higher, such as substantially equal to 350°C, is reached to provide the porous monolith. The final temperature may be held for more than one hour. This may stabilize the structure of the monolith and remove organic residues resulting from the synthesis.

[0115] As a variant, the porous monolith is formed directly in a mould into which the sol is inserted and then extracted from the mould, in particular by the techniques mentioned above.

[0116] The method may include post-fabrication modification of the porous monolith, particularly after extraction of the ink and / or protective agent, particularly before or after disposing the porous monolith on a support, particularly functionalizing the surface of the porous monolith, which may be coated with molecules as previously described.

[0117] ink The ink and / or protectant may be one of the following: - General molecular formula C 2n H 4n+2linear glycols having O2, where n is a positive integer greater than or equal to 1, such that n=3, 4, or 5; cyclohexanediol, - biphenyl, - tri(cyclohexyl)methane, - Molecular formula C n H 2n+2 O, where n is a positive integer greater than or equal to 1, such that n=10, 11, or 12, and mixtures thereof may be selected from:

[0118] The ink and / or protective agent, specifically for inkjet printing, must be at a pressure of 1013.25 hPa, a temperature of 22°C, and 1 s -1 The viscosity may be measured using a cone and plate viscometer, specifically an Anton Paar rheometer, Physica MCR 30 model, or a similar device.

[0119] The protective agent preferably has the characteristic of wetting the material of the solid element, which allows the porous solid element to fill spontaneously upon contact by simple capillary action. Wetting means that a drop placed on the material of the solid element has a contact angle of less than 90°, more preferably 45° or less.

[0120] In a variant, the protective agent is characterized as non-wetting with respect to the material of the solid element, meaning that a drop placed on the material of the solid element has a contact angle of greater than 90°. In this case, the method may comprise the step of applying an overpressure during application of the protective agent to the porous solid element, in particular to balance the Laplace pressure between 1 mbar and 1 bar, in particular to balance the overpressure depending on the pore size and the surface tension.

[0121] device The device comprises a fluid inlet and / or a fluid outlet, and a fluid flow path extends from the fluid inlet to the fluid outlet in the device. The fluid inlet and the fluid outlet are preferably separate. The fluid inlet and / or the fluid outlet may comprise perforations in the thickness of the polymer that are fluidly connected to the fluid circuit. As a variant, the fluid inlet and / or the fluid outlet are formed by a fluid circuit and / or a solid element, in particular by a fluid circuit and / or a solid element that opens to the outside of the polymer.

[0122] The device may be porous or may comprise a plurality of solid elements fluidly connected to one another in series or parallel by one or more portions of a fluid circuit, preferably in series. The solid elements may have substantially the same dimensions, structure, and / or porosity, or, alternatively, may differ in one of their properties, specifically their dimensions, structure, and / or porosity.

[0123] The device may form functional modules and functional units comprising the fluid inlets and outlets of the device. A functional unit is configured to be connected in series via its fluid inlets and / or fluid outlets to one or more adjacent fluidic units to form complex fluid flow structures. The one or more adjacent fluidic units may be identical or, preferably, may differ at least in their functionality. [Brief explanation of the drawings]

[0124] [Figure 1] 1A-1D are diagrams of the various steps of a manufacturing method according to the invention; [Figure 2] 1A-1D are schematic diagrams of various fluid flow devices. [Figure 3] 1A-1D are schematic diagrams of various fluid flow devices. [Figure 4] 1A-1D are schematic diagrams of various fluid flow devices. [Figure 5] 1 is a schematic diagram in cross section of various details showing solid elements of a fluid flow device; [Figure 6]1 is a schematic diagram in cross section of various details showing solid elements of a fluid flow device; [Figure 7] 1 is a schematic diagram in cross section of various details showing solid elements of a fluid flow device; [Figure 8] 1 is a schematic diagram in cross section of various details showing solid elements of a fluid flow device; [Figure 9] FIG. 1 is a schematic diagram of a method for producing a porous monolith. [Figure 10] 1A-1D are schematic diagrams of various methods for fabricating fluid flow devices in a fluid flow path. DETAILED DESCRIPTION OF THE INVENTION

[0125] FIG. 1 illustrates a method for manufacturing a fluid flow device 10 in a fluid flow path.

[0126] The resulting device, shown in step d of FIG. 1, comprises a rigid substrate 20, made for example from glass or plastic, on which extends a layer 25 made from a cross-linked polymer.

[0127] Within layer 25 is a hollow or porous solid element 30 connected by a fluid circuit 50 to two inlets / outlets 40 and 42. The solid element 30 is preferably cylindrical and is connected by its two opposite ends 31 and 32 to the inlets / outlets, forming the entry and exit points for a fluid flow path such that fluid flowing through the device traverses completely through the solid element 30 over its entire length.

[0128] The two inlets / outlets 40 and 42 may form vertical fluid conduits, made from PDMS or the like, through the polymer layer 25, particularly at the junction between the substrate 20 and the polymer layer 25, for fluidly connecting the exterior of the device to a fluidic circuit 50 extending within the polymer layer 25. The fluidic circuit 50 comprises two chambers 52 and 54 into which the two outlets / inlets 40 and 42 open, and two passages 56 and 58 connecting the chambers 52 and 54 to the solid element 30. Various open elements of the device allow fluid to flow between the two inlets / outlets 40 and 42 through the fluidic circuit 50 and the solid element 30.

[0129] However, this may be different and at least one of the two inlets / outlets 40 and 42, more preferably the two inlets / outlets, may extend laterally from the polymer layer 25 and may be formed by ends 53 and 55 of a fluid circuit 50 opening in a lateral face of the polymer layer 25, as shown in Figure 2, or by a part of a solid element 30 extending through the surface of the polymer layer 25, as shown in Figure 3, or by a part of a solid element 30 extending flush with the surface of the polymer layer 25, as shown in Figure 4. As a variant (not shown), the device may have only one inlet and no outlet fluidically connected to the fluid circuit 50. The fluid circuit may form a loop.

[0130] In the example shown in FIG. 1, the fluidic circuit 50 and the solid element 30 are located at the interface between the substrate 20 and the polymer layer 25 .

[0131] However, this may vary and the fluidic circuitry 50 and / or solid state elements 30 may be disposed within the polymer layer 25 with or without the device comprising a rigid substrate 20 .

[0132] The device may comprise a plurality of hollow or porous solid elements integrated within the polymer layer 25 .

[0133] The fluid flow paths in the device are preferably planar, in a plane parallel to the surface of the substrate 20. As a variant, the fluid circuit may have a three-dimensional structure, so that the fluid flow paths in the polymer are also three-dimensional.

[0134] The solid element can be a tube or a hollow capillary. Alternatively, the solid element can be a porous monolith with a simple or graded porosity. In this case, the solid element is preferably produced by a sol-gel method, as will be explained later.

[0135] The device may in particular form a functional unit that can be connected to a larger scale system with other different or identical functional units, with or without hollow or porous solid elements.

[0136] It is important to have solid elements integrated into a device that are configured so that the solid elements retain their integrity and properties, particularly their porosity in the case of porous elements with fluid flow within the element, and so that fluid flows along fluid flow paths through the solid element rather than around it in the device. It is also important that the connection between the solid element 30 and the fluid circuitry allows for effective fluid flow between the two. The issue is whether the solid element is substantially porous or hollow, since the solid element may be plugged with polymer during fabrication, reside in the polymer layer at the fluid junction between the solid element and the fluid circuitry, and / or reside in the polymer layer at the interface between the polymer layer and at least a partially open surface of the solid element, which may allow the polymer to penetrate the porous element during fabrication and thus impede fluid flow in the solid element. This issue is exacerbated in the case of self-supporting porous solid elements integrated into a device without a protective sheath due to the presence of pores that are open across the entire surface and allow the polymer to penetrate as the polymer layer is formed.

[0137] To form the described device, the method involves, in step a shown in FIG. 1, placing a hollow or porous solid element 30 in a predetermined position on the upper planar surface of a support consisting of a substrate 20, and then printing fluid circuit paths 62, including fluid chambers 52 and 54, onto the support with ink, the ink having the general molecular formula C 2n H 4n+2 O2, where n is a positive integer greater than or equal to 1, preferably n=3, 4, or 5, linear glycols, cyclohexanediol, biphenyl, tri(cyclohexyl)methane, molecular formula C n H 2n+2 0 alcohols, where n is a positive integer greater than or equal to 1, preferably n=10, 11, or 12. As a variant, the paths 62 in the fluidic circuit are printed before the positioning of the solid element 30 on the support. The paths 62 are printed, and the solid element 30 is positioned so that at the junction between the solid element 30 and the ink, the ink and the solid element 30 are in contact, here at the two ends 31 and 32 of the solid element 30. The ink can penetrate the solid element 30 to fill it if it is not previously filled with a protective liquid, or it can penetrate the solid element 30 over a certain distance at the surface, at the junction. Such contact / penetration can be used to prevent polymer interference at the junction between the two, which would hinder the subsequent fluid flow. As a further variant, the paths 62 in the fluidic circuit are printed in several steps, with a first printing being performed before the positioning of the solid element 30 on the support, and a second printing being performed afterwards, as shown in FIG. 10. This may make it possible to have an effective joint between the path and the solid element, and to position the solid element in one or more layers of ink before the second print.

[0138] Printing is performed with a printing nozzle and a pressure of 30 mPa.s -1This can be accomplished by inkjet printing using a liquid ink having the following viscosity: The distance between the printing nozzle on the one hand and the substrate on the other hand can be between 0.5 mm and 20 mm. The size of the ink droplets ejected by the printing nozzle can be between 10 μm and 100 μm. The speed of ink droplet ejection by the nozzle can be between 50 Hz and 5 kHz. The substrate on the one hand and the printing nozzle on the other hand can be adapted to allow a relative displacement of one relative to the other at a controlled relative displacement speed between 1 mm / s and 100 mm / s. In a variant, the ink is printed using a syringe. The distance between the end of the syringe through which the ink is dispensed on the one hand and the substrate on the other hand can be between 0.1 mm and 1 mm. The flow rate of the ink dispensed by the end of the syringe can be between 0.01 nl / s and 10 nl / s. The support on the one hand and the end of the syringe on the other hand may be adapted to allow relative displacement of one relative to the other at a controlled relative displacement speed between 0.1 mm / s and 10 mm / s.

[0139] Depending on the thickness of the fluid circuit pathway 62 and / or the structure of the fluid circuit in the polymer, it may be necessary to overlap multiple layers of ink, at least in certain places, after each layer has dried or solidified. This may particularly allow for the fabrication of three-dimensional structures of the pathway 62.

[0140] The ink is then allowed to dry or solidify, either spontaneously given its nature, or by heating or cooling.

[0141] The ink can optionally be annealed at a temperature below the extraction temperature of the ink at an equivalent pressure. Such annealing can reduce the roughness of the deposited paths. Indeed, it can be noted that when the ink solidifies, even taking into account the deposition conditions, the surface of the ink in solid form can exhibit significant roughness. This roughness can consequently be transferred to the polymer walls of the fluidic circuit. The roughness can have a non-trivial effect on the flow conditions in the device, resulting in head loss and / or undesirable heat exchange, or can alter the analytical conditions depending on the device architecture.

[0142] After drying or solidifying the ink, and optionally after annealing, the method includes positioning a mold 64 on the substrate to mold the polymer into the fluidic circuit 50 and solid element 30, as shown in step b of Figure 1. The method may also include positioning additional elements, in this case tubes 66 and 67, to form two inlets / outlets 40, 42 in the thickness of the polymer.

[0143] As shown in step c of Fig. 1, a polymer 25 in liquid state is then poured into the mold to cover the ink forming the paths 50 of the fluid circuit and the solid elements 30. The polymer is then solidified by cross-linking. Cross-linking can be facilitated by cross-linking agents or photoinitiators present in the polymer. As a variant, the polymer may contain a solvent, which cross-links after evaporation of the solvent. Cross-linking can be performed by heating to a temperature below the extraction temperature of the ink at equal pressure. The polymer 25 is made incompatible with the ink.

[0144] 1, the ink is extracted from the polymer 25 by evaporation, in particular by sublimation or by liquefaction and subsequent evaporation, by heating the device, and / or by subjecting the device to a pressure differential. Optional removable additional elements, in particular the inlet / outlet tubes 40 and 42, are withdrawn before or after extraction of the ink.

[0145] The device is then washed by passing a liquid from an inlet to an outlet in the device.

[0146] However, the invention is not limited to this type of extraction technique: other techniques can be considered, in particular pulling out the substrate to expose the ink in the polymer, dissolving the ink with a solvent, in particular alcohol, and / or evaporating or subliming the ink residue before replacing it with the same or a different substrate.

[0147] Extraction of the ink after cross-linking can cause fluid circuits 50 to form in the polymer 25 .

[0148] The mold 64 can be retained or withdrawn after solidification.

[0149] In the case of hollow solid elements 30, the hollow ends of the solid element can be covered with ink so that the polymer 25 cannot penetrate into the hollow solid element 30. In this case, the thickness of the ink is greater than or substantially equal to the height of the solid element 30. As a variant, the hollows of the solid element can be plugged or filled at the inlets and / or outlets, in particular with a protective agent identical or different from the printing ink, before the hollow element is placed on the support. Said agent can be extracted simultaneously with the ink by the same techniques. In that case, the thickness of the ink is relatively unimportant and can, for example, be less than the height of the solid element, since the hollows are protected from penetration by the polymer.

[0150] In the case of a porous solid element 30, the solid element 30 can be coated over its entire surface, or at least filled in the fluid channels, before being placed on the support, with a protective agent, in particular the same or different from the printing ink, to prevent the polymer from entering the element. Said agent can be extracted simultaneously with the ink, by the same techniques. As a variant, the polymer 25 is crosslinked quickly enough to prevent it from blocking the solid element at all cross sections along which the fluid channels extend, in order to ensure the possibility of fluid flow within the solid element 30.

[0151] As a variant, the support may comprise one or more support or receiving elements 28 arranged on the substrate 20. The elements may be made of a cross-linked polymer with a flat outer surface, in particular from the same polymer as the polymer layer 25. The support may comprise a support element 28 forming a support layer for printing and depositing the solid elements 30, as shown in detail in cross section in FIGS. 5 and 7. A support of this type may be arranged on the substrate 20 or may be formed directly on the substrate by pouring it into a mold on the substrate and cross-linking it. The support layer 28 may form a flat surface, as shown in FIG. 5, or may have one or more surface irregularities, in particular cavities 31 for receiving the solid elements 30, as shown in FIG. 7. In the case of a surface irregularity, the cavities 31 for receiving the solid elements 30 have a depth p in the direction of the depth of the cavity that is less than 50% of the dimension e of the solid elements 30. 6 and 8, the support comprises a plurality of support or receiving elements 28a and 28b arranged on the substrate 20 and spaced apart by a non-zero distance to form a cavity 29. As shown in FIG. 6, a solid element 30 may be arranged across two support elements 28a and 28b, spaced apart by a distance d less than the length L of the solid element 30, with the fluid circuit paths 62 printed on the support elements 28a and 28b. In this embodiment, the polymer 25, when poured, surrounds the solid element 30 in the free cavity 29 between the two support elements 28a and 28b. In this way, the solid element 30 is encapsulated in a monolithic polymer layer, thereby reducing the risk of fracture at the joint with the substrate 20 when the substrate 20 is pulled out, particularly if the solid element has a large cross-sectional dimension. 8, the solid element 30 is received in a cavity formed between the receiving elements 28a and 28b, the cavity having a depth p that is smaller than the dimension of the solid element in the direction of the depth of the cavity. The solid element 30 preferably contacts the receiving elements 28a and 28b in the cavity 29 via its two longitudinal ends so that ink deposited on the receiving element comes into contact with the solid element 30.

[0152] The substrate 20 can be withdrawn after extraction of the ink, more particularly when the fluid circuit 50 and the solid elements 30 are not in contact with the substrate 20, especially due to the presence of one or more support elements 28.

[0153] In the illustrated example, the fluid circuit is primarily composed of channels. It goes without saying that the circuit can have any structure compatible with a manufacturing method involving ink printing. The circuit may, in particular, comprise one or more fluid chambers, or may integrate solid auxiliary elements other than the solid elements, in particular interconnection elements for flowing fluids through the fluid circuit, in particular interconnection elements for connecting the fluid circuit to a fluid inlet or outlet, or interconnection elements for connecting the device to other identical or different devices, and / or elements for positioning the solid elements on the support, in particular blocks arranged below the solid elements, and / or elements for the functionality of the fluid circuit, in particular functional or non-functional beads extending in a portion of the fluid circuit. These auxiliary elements may remain in the final fluid circuit, or may serve only to form the channels, for example during manufacturing.

[0154] In the example shown, filling with polymer and cross-linking of the polymer is performed in one operation, although this step may also be performed in multiple successive steps of partial filling and cross-linking.

[0155] FIG. 7 illustrates the various steps of an example method for producing a porous monolith.

[0156] The method includes a first step, not shown, of forming an aqueous solution of the pore-forming agent and sol-gel precursor, and optional additives such as acids and / or chemicals to dissolve the matrix.

[0157] The pore-forming agent may be selected from water-soluble polymers, in particular polyethylene glycol (PEG), polyacrylic acid, sodium polystyrene sulfonate, and polyethyleneimine.

[0158] The water-soluble polymer(s) may have a molecular weight between 1,000 and 100,000 daltons, preferably between 5,000 and 50,000 daltons, and even more preferably between 5,000 and 30,000 daltons.

[0159] The concentration of the pore former, specifically the PEG, can be between 0.015 g and 0.35 g per ml of sol, preferably between 0.002 g and 0.2 g per ml of sol. These values ​​are related to the concentration of the sol-gel precursor, specifically the concentration of tetramethoxysilane (TMOS), by a value of 0.03 g to 1 g of pore former, specifically PEG, per ml of sol-gel precursor, specifically tetramethoxysilane (TMOS), preferably by a value of 0.06 g to 0.6 g of pore former, specifically PEG, per ml of sol-gel precursor, specifically tetramethoxysilane (TMOS). The value is selected depending on the desired macropore size in the final porous monolith.

[0160] The sol-gel precursors may be selected from alkoxides, in particular hydrolyzable and condensable organometallic compounds, such as zirconium alkoxides, in particular zirconium butoxide (TBOZ) and zirconium propoxide (TPOZ), titanium alkoxides, niobium alkoxides, vanadium alkoxides, yttrium alkoxides, cerium alkoxides, aluminum alkoxides, or silicon alkoxides, in particular tetramethoxysilane (TMOS), tetraethoxysilane (TEOS), tetrapropoxysilane (TPOS), tetrabutoxysilane (TBOS), trimethoxysilanes, in particular methyltrimethoxysilane (MTMOS), propyltrimethoxysilane (PTMOS), ethyltrimethoxysilane (ETMOS), triethoxysilanes, in particular methyltriethoxysilane (MTEOS), ethyltriethoxysilane (ETEOS), propyltriethoxysilane (PTEOS), aminopropyltriethoxysilane (APTES), and mixtures thereof, such as TMOS. It is also possible to use precursors such as sodium silicate, or titanium colloid, especially if the purity requirements allow this, ie if the purity requirements are not too high.

[0161] The proportion of pore former in the sol and the proportion of sol-gel precursor in the sol are predetermined depending on the properties of a sample of the known sol-gel matrix taken immediately after gelation, in particular depending on the overall porosity and the average size of the macropores.

[0162] The solution is then stirred for a predetermined time period of between 5 minutes and 3 hours, and even more preferably between 15 minutes and 2 hours, at a substantially constant and controlled temperature between 0° C. and 90° C., and more preferably between 0° C. and 50° C. This stirring step initiates the sol-gel process to form sol 5 prior to phase separation.

[0163] The sol 5 is then added in step 2 to the container 12 to at least partially fill the container 12 and at least one mold 15 contained within the enclosure 12 .

[0164] The mold 15 can be positioned in the enclosure, and the enclosure is gradually filled with the sol 5 in such a way that the mold 15 is gradually filled without bubbles or gradients in chemical composition. Filling can be carried out until the mold 15 is completely immersed. Partial immersion is also possible. Addition of the mold to the sol 5 contained in the enclosure 12 is also possible.

[0165] The enclosure 12 may be configured to include multiple identical or non-identical molds 15. The enclosure 12 may be cylindrical as shown, or may have any other shape. The enclosure 12 may be made from plastic, specifically PTFE, PP, PE, PC, PET, PVC, glass, or stainless steel.

[0166] The mold 15 comprises two openings 17 and 18 on opposite surfaces of the mold 15, at least one of the two openings 17 extending downward from the level of the sol after filling. Such openings allow the mold 15 to be filled by filling the enclosure 12 containing the mold 15, or by at least partial immersion of the mold 15 in the sol 5 contained in the enclosure 12 and flow of the sol 5 between the inside and outside of the mold before complete condensation of the sol. In the example shown, the mold 15 is in the form of a tube that is open at two ends and extends vertically in the enclosure 12, but it may be entirely different, the tube may be oriented differently in the enclosure, and / or the mold may have a different shape.

[0167] The mold 15 may be entirely contained in the enclosure 12, as shown, or may protrude from said enclosure. If entirely contained, the mold 15 may or may not be entirely immersed in the sol 5 after filling.

[0168] The mold 15 may be made from plastic, in particular PTFE, PEEK, PEP, PE, PP, or polylactic acid, glass, or stainless steel, in particular fused quartz or borosilicate.

[0169] The mold may be made from a porous material.

[0170] The mold may be formed by 3D printing or molding.

[0171] The maximum transverse dimension of the cavity of the mould 15, specifically the diameter d of this cavity, may be between 13 mm and 0.025 mm.

[0172] When the sol 5 is introduced into the enclosure 12 and the mold 15, condensation takes place in the assembly of the enclosure and the mold in step 3. This sol-gel transition can be followed by at least partial aging of the assembly. Through this step, it is possible to ensure the formation of uniform macropores of the same type in the formed sol-gel matrix 22, regardless of the shape and size of said matrix.

[0173] During condensation, the temperature may be kept substantially constant, specifically between 15° C. and 90° C., preferably between 25° C. and 70° C., for a time period between 10 minutes and 4 hours. The condensation time and the predetermined temperature depend on the desired internal structure of the sol-gel matrix and the stirring time for the initial solution in the sol formation step.

[0174] The at least partial aging may last for between 30 minutes and 2 weeks, particularly less than 72 hours at ambient temperature. The aging time is preferably short enough to prevent the formation of mesopores and / or micropores.

[0175] The block of sol-gel matrix 22 containing the mold 15 is then extracted from the enclosure 12 in step 4. In this case where the mold 15 is only partially immersed, this step may be optional, as will be seen later.

[0176] The mold 15 containing the sol-gel matrix 19 is then extracted from the porous solid in step 5, for example, by cutting the sol-gel matrix from the block 22 flush with the mold and then extracting the mold 15 containing the sol-gel matrix 19, or by breaking the sol-gel matrix from the block 22 around the mold 15. If the immersion was partial, it is possible to extract the mold 15 containing the sol-gel matrix 19 from the block from which it was previously extracted, or directly from the enclosure 12.

[0177] Optionally, the sol-gel matrix 19 is extracted from the mold 15 in step 6 to provide a self-supporting monolith. This is done using controlled pressure exerted on the sol-gel matrix 19 while holding the mold 15. The pressure can be obtained either with a solid, such as a fused silica capillary tube made from plastic or glass, or any other material that is sufficiently rigid and smaller than the size of the mold 15, or with a gas at a controlled flow rate. The extraction operation can be more easily achieved by immersing the assembly of the mold 15 and sol-gel matrix 19 in a liquid. Optionally, a slight pressure difference can be generated by gently tapping the assembly of the mold 15 and sol-gel matrix 19 to extract the sol-gel matrix 19.

[0178] Next, the method may include a step of controlled mesoporosity generation. This step can be accomplished by immersing the sol-gel matrix 19 or the mold / sol-gel matrix assembly in a basic solution, such as a 1M solution of ammonium hydroxide, or by heating the material in water in the presence of a precursor, such as urea, to generate ammonia in situ. It should be noted that the technique of heating the material allows for the addition of ammonium hydroxide. This operation can last for between 0.5 and 50 hours at a substantially constant, predetermined temperature of the sol-gel matrix, between 30°C and 150°C. This step can be performed simultaneously on multiple sol-gel matrices, whether obtained from a single block or not, i.e., in a single bath.

[0179] The resulting pore size is preferably less than 50 nm, more preferably between 2 and 50 nm.

[0180] The resulting sol-gel matrix is ​​then dried. To do this, it is placed in a closed container, in particular an autoclave, to dry under critical or supercritical conditions, in particular in a stream of air or inert gas, in particular nitrogen (N), for a period of between 10 and 20 hours. It is then subjected to a ramp of 0.5°C / min up to 350°C, followed by a stabilization period at this temperature for several hours in a stream of inert gas (other gases may also be used).

[0181] The result is a monolith that is self-supporting or integrated into a mold, specifically a capillary, and is ready for use.

[0182] The resulting porous monolith preferably comprises macropores, i.e. pores with a selected size of 50 nm or greater, and mesopores, i.e. pores with a selected size between 2 nm and 50 nm.

[0183] The monolith preferably has a substantially uniform structure throughout its volume.

[0184] The porous monolith or monoliths may have an aspect ratio, defined as their height relative to their largest transverse dimension, of between 0.2 and 100.

[0185] The method may include post-fabrication modification of the porous monolith, specifically functionalization of the interior surface of the porous monolith, which may be performed by liquid or gas phase methods using organosilanes, specifically chlorosilanes (e.g., octadecyltrichlorosilane) and alkoxysilanes (octadecyltriethoxysilane, aminopropyltriethoxysilane, propyltrimethoxysilane), or else hexadimethylsilazane.

[0186] As a variant, the mould may have only one opening, which opens into the sol after filling, to allow the sol to flow between the mould and the enclosure.

[0187] As a variant, the initial solution can be an emulsion or solution of a "template" containing sol-gel precursors. [Example]

[0188] In this example, a self-supporting porous monolith, cylindrical in shape with a diameter of about 700 μm and a length of about 15 mm, and having macropores of about 2 μm and mesopores of about 15 nm, is integrated into a microfluidic device at the center of a straight fluid flow passage with a diameter of several hundred microns, as shown in FIG.

[0189] The porous monoliths were fabricated by a sol-gel method described below.

[0190] A solution was prepared by mixing 0.33 g of PEG with 2 mL of TMOS in 4 mL of 0.01 M acetic acid. The solution was stirred for 30 minutes at 0 °C to form a sol, then transferred to a polypropylene (PP) container, into which a PTFE tube with a diameter of approximately 1 mm was previously positioned vertically. Using a micropipette, the sol was gradually added to the enclosure, starting from the lowest point. The amount of solution added was such that the mold was completely immersed.

[0191] The enclosure is placed at a temperature of 40°C, and gelation is carried out for 45 to 50 minutes after transfer to the enclosure. When gelation has taken place, the gel is left to age at 40°C for 24 hours. The sol-gel matrix resulting from gelation and aging is then extracted from the enclosure and broken with metal tongs to recover the mold embedded in it. The monolithic sol-gel matrix enclosed in the mold is then extracted using manual pressure exerted by a tube with a diameter of less than 1 mm. For this procedure, this pressure through a rigid tube is sufficient to extract the monolith and not weaken the gel.

[0192] The resulting sol-gel matrix is ​​quickly immersed in a 1 M NH4OH solution, and a ratio of about 5 is observed between the volume of the base solution and the volume occupied by the sol-gel matrix.

[0193] The resulting matrix is ​​then placed in an autoclave, which is placed in an oven and connected by a tube that allows gas flow. The gel is then dried under N2 for 12 hours. Finally, a heat treatment is performed with a ramp of 0.5°C / min up to 350°C and a 2-hour plateau at this temperature.

[0194] The self-supporting porous monolith thus obtained is subsequently protected by immersion for about 1 minute in 1,8-octanediol, which forms an impregnation ink, at 80° C. The impregnated cylindrical monolith is preferably contacted with absorbent paper to remove excess liquid before being placed in a glass dish until the protection liquid present in the porous material solidifies.

[0195] A rectangular polydimethylsiloxane (PDMS) substrate is fabricated and placed on a glass slide.

[0196] The impregnated porous monolith is then placed on a PDMS substrate. On either side of the edge of the porous monolith, 1,8-octanediol is printed in the form of two straight passageways with a diameter of less than 0.7 mm, the passageways connecting the monolith at each end, allowing the ink to contact the edge of the impregnated porous monolith and mix with the impregnated ink. Printing is performed using a low-volume micropipette or a printer.

[0197] At the free end of each channel, a cylindrical hole is formed through the PDMS substrate using a dedicated 0.5 mm PDMS punch. These holes will constitute the inlets and outlets of the future device. The holes are then coated with the ink and connected to the ends of the channels. It is also possible that these holes could be generated during or after coating using means other than protective ink (e.g., adding elements made from PDMS).

[0198] A rectangular PDMS mold, open on the top and bottom and with dimensions equal to or smaller than those of the substrate, is then placed on the substrate to prevent the liquid polymer coating from spreading while allowing for the addition of the liquid polymer coating.

[0199] Next, liquid PDMS containing a cross-linking agent is added to the mold so that it completely covers the monolith and the ink, and the PDMS is then cross-linked at 100°C for 2 hours.

[0200] The formed device is then placed under vacuum and heated to 100°C to allow the ink present in the material and forming channels on either side of the porous monolith to undergo sublimation and / or evaporation. To complete, the device is washed with a water / ethanol mixture (50 / 50) and then with pure ethanol before being dried in an oven at 40°C for 24 hours.

[0201] The resulting fluidic device allows fluid flow from an inlet to an outlet through the porous monolith. [Example]

[0202] In this example, the substrate is made of glass, the covering layer is made of PDMS, and a porous monolith with a diameter of 5 mm, obtained by the same sol-gel method as described in Example 1, except for the size of the tube, is placed on two elements made of PDMS that form support elements, which are themselves placed on a glass substrate as shown in Figure 6. The addition of liquid PDMS therefore allows the formation of a polymer layer around the porous monolith, ensuring effective impermeability.

[0203] The method is carried out as follows:

[0204] A porous monolith with a diameter of 5 mm and having macropores of about 2 μm and mesopores of about 15 nm is protected by immersion for about 1 minute in the protection liquid 1,8-octanediol heated to 80° C. The impregnated cylindrical monolith is preferably placed and rolled in absorbent paper to remove excess liquid before being placed in a glass dish until the protection liquid present in the porous material solidifies.

[0205] A glass slide is used. Two squares of PDMS are placed on the glass slide so that the distance between them is less than the length of the impregnated porous monolith. The porous monolith is placed across the PDMS squares. 1,8-octanediol is placed on either side of the material edges of the two PDMS support elements to form straight passages with a diameter of less than 0.7 mm that connect to the impregnated porous monoliths by contact at their edges. Placement is performed using a small-volume micropipette or a printing machine.

[0206] A rectangular mold based on PDMS, open on the top and bottom, with dimensions equal to or smaller than those of the substrate, is placed on the substrate to prevent the liquid polymer coating from spreading while allowing the liquid polymer coating to form. Liquid PDMS containing a cross-linking agent is then added to the mold to completely cover the channels and the porous monolith. The PDMS is then cross-linked at 100°C for 2 hours.

[0207] The device, still containing the ink, is then placed under vacuum and heated to 100°C so that the ink present in the material and forming the channels can undergo sublimation and / or evaporation. To complete, the device is washed with a water / ethanol mixture (50 / 50), then with pure ethanol, and then dried in an oven at 40°C for 24 hours.

[0208] The glass slide is withdrawn, and then a 0.5 mm PDMS punch is used to form cylindrical holes through the PDMS shell at each end of the linear channel. The glass slide can be withdrawn either before or after ink extraction. [Example]

[0209] This example is described with reference to FIG. 10, which illustrates the various steps described below.

[0210] In this example, the substrate is made of glass.

[0211] A porous monolith with a diameter of 800 μm is formed by the same sol-gel method as described in Example 1, except for the size of the tube. The porous monolith has macropores of about 2 μm and mesopores of about 15 nm and is protected by immersion in the protection liquid 1,8-octanediol heated to 80° C. for about 1 minute. The impregnated cylindrical monolith is preferably placed and rolled in absorbent paper to remove excess liquid before being placed in a glass dish until the protection liquid present in the porous material solidifies.

[0212] In step a), illustrated by the device in cross-section on the left and plan view on the right, a first print of 1,8-octanediol is performed on the initial support 20a to form two continuous ink portions 70a and 70b separated from each other. The printing is performed using a small volume micropipette or a printer at one or more thicknesses. When the ink in the two continuous portions 70a and 70b dries, the impregnated porous monolith 30 is placed in the ink of the continuous portions 70a and 70b, with each edge of the porous monolith 30 extending over one of the two continuous portions 70a and 70b to form a bridge between the two continuous portions 70a and 70b.

[0213] In step b), illustrated by the device in cross section on the left and plan view on the right, a second print of 1,8-octanediol is made at the junction between the porous monolith 30 and the ink of portions 70a and 70b to form vertical portions 72a and 72b, respectively, covering the edges of the porous monolith 30.

[0214] Thus, porous monolith 30 is held by the ink, with its edges encapsulated in the ink of portions 70a and 70b and portions 72a and 72b, respectively. Porous monolith 30 is elevated relative to initial support 20a by a height k ranging from a few microns to a few millimeters. Height k may be substantially equal to the thickness of the ink in portions 70a and 70b. Height k may be 200 μm.

[0215] In step c), illustrated by the device in cross section, a rectangular mold based on PDMS, open on top and bottom, and having dimensions equal to or smaller than those of the substrate, is placed on the substrate to prevent the liquid polymer coating from spreading while allowing the liquid polymer coating to form. Liquid PDMS containing a cross-linking agent is then added to the mold so as to entirely cover the ink-formed channels 62 and the porous monolith. The PDMS is then cross-linked, for example, by heating at 100°C for 2 hours, or at ambient temperature for 24 hours, or by heating at 40°C for 2 hours and then at 100°C for 1 hour. The PDMS passes under the porous monolith 30 between sections 70a and 70b.

[0216] In step d), illustrated by the device in cross section, the initial support 20a is pulled out and the ink of the passages 62 of the assembly formed from the ink, monolith, and cross-linked polymer is dissolved in alcohol. The assembly is then placed under vacuum and heated to 100°C so that any residual ink present in the material can undergo sublimation and / or evaporation. To complete, the device is washed with a water / ethanol mixture (50 / 50), then with pure ethanol, and then dried in an oven at 40°C for 24 hours. This allows the formation of the microchannels 56a and 56b of the fluid circuit 50 in the cross-linked polymer 25.

[0217] In step e), shown with the device in cross section, the assembly formed from the monolith, cross-linked polymer, and channels 56a and 56b is fastened to a new support 20b, which may be the same as or different from the initial support 20a, so as to imperviously close channels 56a and 56b. Using a 0.5 mm punch for PDMS, cylindrical holes through the PDMS shell are formed at each end of microchannels 56a and 56b to form inlets 40 and outlets 42.

[0218] The resulting device is used to perform chromatography, specifically adsorption chromatography. In this case, the porous monolith as the stationary phase allows for the separation of molecules from a mixture, such as the food dyes E133 and E129, using a gradient of a water / acetonitrile mixture as the mobile phase. Two dyes, E133 (blue) and E129 (red), are mixed. 200 μl of the mixture is introduced into the fluid circuit via the inlet 40 at a flow rate of 100 μl / min. The device is observed from above with a camera. The inlet channel 56a shows the color of the mixture as it passes through it, and the monolith 30 shows a dark brown color that turns toward blue at the end of the flow. The outlet channel 56b shows the red color characteristic of only E129.

[0219] Next, 100 μl of water is admitted to the fluid circuit via inlet 40 at a flow rate of 100 μl / min. Inlet passage 56a shows the color of the water as it passes through it, and monolith 30 shows an increasing blue color as E129 passes to outlet passage 56b. Only E133 is retained by the monolith, so E129 is completely eluted.

[0220] Next, 400 μl of acetonitrile is admitted to the fluidic circuit via inlet 40 at a flow rate of 100 μl / min, thereby eluting E133 and driving its migration along the monolith towards outlet 56b, which eventually turns white indicating the complete elution of E133.

[0221] It is therefore possible to perform chromatography with this type of device.

[0222] Alternatively, the portions 70a and 70b of the channel 62 for forming the microchannels 56a and 56b may be formed through the use of a hollow element with an opening in its sidewall at the junction with the monolith. The junction between the hollow element and the monolith may then be created by printing at the junction. In this case, the method for extracting the ink may be similar to that described in connection with Example 2. [Explanation of symbols]

[0223] 5 Zoll 10 Fluid Flow Device 12 Containers, enclosures 15-inch 17, 18 Openings 19 Sol-gel matrix 20 PCB 20a Early support 20b New Support 22 Sol-gel matrix, block 25 Polymer layer, cross-linked polymer 28, 28a, 28b Support element, receiving element, support layer 29 Cavity 30 Solid elements, porous monoliths 31 end, hollow 32 ends 40, 42 inlet / outlet 50 Fluid circuits, paths 52, 54 Fluid chamber Aisles 56 and 58 56a Micro passageway, entrance passageway 56b Micro passageway, exit passageway 62 routes 64-inch 66, 67 tube 70a, 70b continuous part 72a, 72b vertical section d Separation distance e Dimensions of solid element 30 k height L length of solid element 30 p Depth of cavity 31

Claims

1. A method for manufacturing a device (10) for fluid flow in at least one fluid flow path through a porous or hollow solid element (30) and at least a part of a fluid circuit (50), wherein said solid element and said part of the fluid circuit are fluidly connected to each other, a) printing a path (62) of the fluid circuit (50) with ink on a support and placing the solid element (30) on the support, the ink being adjacent to the solid element (30) in the fluid flow path; b) coating the solidified ink and the solid elements (30) with a crosslinkable polymer (25), the polymer (25) being immiscible with the solidified ink; c) cross-linking said polymer (25) to solidify said polymer (25); d) extracting the solidified ink to form the fluid flow paths; A method comprising:

2. 2. The method according to claim 1, comprising the steps of: protecting at least some of the pores or one or more hollows of the solid element (30) along the fluid flow path by previously filling at least a part of the solid element (30), in particular the center of the solid element (30), more preferably the whole of the solid element (30), with a protective agent, in particular the same as the ink, which agent prevents penetration of the polymer (25) into the solid element (30) in the covering step b); and extracting the protective agent after a step c) of cross-linking the polymer to allow fluid flow in the solid element.

3. 2. The method of claim 1, wherein the solid element (30) is porous and the polymer (25) is crosslinked before allowing the polymer (25) to fill the pores of at least one flow intersection area of ​​the fluid flow paths of the solid element.

4. 4. The method according to claim 1, wherein the polymer (25) outside the surface area of ​​the solid element (30) in contact with the ink is configured to penetrate into the pores of the solid element (30) between the coating step b) and the cross-linking step c) over a skin depth of the solid element (30) of not more than 40%, more preferably not more than 30%, even more preferably not more than 20%, preferentially not more than 10% of the smallest dimension of the solid element (30) in the flow cross-section area of ​​each of the fluid flow paths in the solid element (30).

5. 5. The method according to claim 1, wherein the support comprises a substrate (20) made of a hydrophobic material, for example selected from the following: polyimide (PI), silicone including polydimethylsiloxane (PDMS), polypropylene (PP), polytetrafluoroethylene (PTFE), and cyclic olefin copolymer (COC), or a hydrophilic material selected from silicon, glass, cellulose, and glass fiber, and optionally one or more support elements (28; 28a, 28b) arranged on the substrate (20), the support comprising at least two support elements (28a, 28b) made from the same crosslinked polymer as in step b), the at least two support elements (28a, 28b) being spaced apart by a non-zero distance, the device being configured such that the solid element (30) is arranged in step a) straddling the two support elements (28a, 28b).

6. 6. The method according to any one of claims 1 to 5, wherein the support comprises a cavity (29) at its surface for receiving the solid element (30), the solid element (30) being placed in the cavity in step a).

7. The method of any one of claims 1 to 6, wherein the solid element (30) is adjacent to a micropassage (56, 58) in the fluid flow path.

8. 8. The method of any one of claims 1 to 7, wherein the solid element (30) extends in the fluid flow path such that the fluid flow path traverses the solid element (30) from an entry point (31, 32) to an exit point (31, 32), the entry point (31, 32) and the exit point (31, 32) being spaced apart by a distance of at least 10%, more preferably 50%, and even more preferably the entire distance of the largest dimension of the solid element (30).

9. 9. The method according to claim 1, wherein the solid element (30) is hollow, the open ends at the two ends (31, 32) of the hollow part of the solid element are in the fluid flow path, the central axis of the hollow part extends along the fluid flow path, and the fluid flow path is maintained in the hollow part by plugging the two ends with a protective agent before addition to the support or by the ink of the fluid circuit being applied to the hollow ends of the solid element during step a).

10. 10. The method according to any one of claims 1 to 9, wherein the solid element (30) comprises a porous monolith with graded porosity, in particular a self-supporting monolith, more particularly the porous monolith arranged bare on the support (20) or the porous monolith (30) and a protective outer sheath for the porous monolith, which is open at the inlet (40) and the outlet (42) points of the fluid flow paths, and wherein the ink adjoins at least one open end of a tube or capillary in step a) of the method.

11. 11. The method according to any one of claims 1 to 10, wherein the step of printing the path (62) and arranging the solid element (30) can include a first printing (70a, 70b) of ink and the arranging of the solid element (30) on the support (20), and then a second printing (72a, 72b) of ink to form a joint between the solid element (30) and the ink of the first printing, in particular at the joint between the solid element (30) and the first printing (70a, 70b) of ink.

12. 12. The method according to claim 1, comprising printing at least two consecutive portions (70a, 70b) separate from one another to form the path (62) of the fluid circuit, and disposing the solid element (30) across the two portions (70a, 70b).

13. - formation of a sol (5) comprising a sol-gel precursor in an aqueous solution, preferably comprising a pore-forming agent; - at least partial filling of the enclosure (12) and of at least one mould (15) contained in said enclosure (12) with a preformed sol (5), said mould (15) having at least one opening (17) opening into said sol (5) after filling with the sol; - formation of a sol-gel matrix (22) from said sol (5) in said enclosure (12); - extraction of said mould (15) together with said sol-gel matrix (19) contained in said mould from said enclosure; - forming a porous monolith from said sol-gel matrix; forming the porous monolith by a manufacturing method comprising:

13. The method of claim 1, wherein the sol, the sol-gel matrix, and the porous monolith are formed by a sol-gel method.

14. The ink and / or the protective agent may be: - General molecular formula C ２ｎ H ４ｎ ＋２ O ２ wherein n is a positive integer greater than or equal to 1, such that n=3, 4, or 5; - cyclohexanediol, - biphenyl, - tri(cyclohexyl)methane, - Molecular formula C ｎ H ２ｎ ＋２ O, wherein n is a positive integer greater than or equal to 1, such that n=10, 11, or 12; and mixtures thereof 14. The method of any one of claims 1 to 13, wherein the compound is selected from the group consisting of:

15. 15. The method according to any one of the preceding claims, comprising withdrawing at least a part of the support, in particular at least a part of the substrate (20).

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