Fluidic device, method of making a fluidic device and its use
The fluidic device addresses the challenge of optical observation and mechanical support in microfluidic systems by using a transparent matrix with refractive index-matched support fibers, allowing for transparent and functional operation.
Patent Information
- Application Number
- PCT/EP2024/086981
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-19
- Filing Date
- 2024-12-17
- Publication Date
- 2025-06-26
AI Technical Summary
Existing microfluidic systems, particularly those used in organ-on-a-chip devices, face challenges in being transparent enough to allow optical observation of contents within embedded channels, while also requiring mechanical support and elasticity for functional operation.
A fluidic device comprising a transparent or translucent matrix with a network of support fibers embedded within, where the matrix and support fibers have refractive indices that differ by less than 0.05, allowing for the integration of channels that can be optically observed without compromising mechanical support.
The solution enables visual examination of the content within channels while maintaining the necessary mechanical properties, improving the functionality and applicability of microfluidic devices.
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Figure EP2024086981_26062025_PF_FP_ABST
Abstract
Description
[0001] FLUIDIC DEVICE, METHOD OF MAKING A FLUIDIC DEVICE AND ITS USE
[0002] TECHNICAL FIELD
[0003] The present disclosure relates to the domain of fluidic systems, and particularly to microfluidic systems. More specifically, it relates to fluidic and microfluidic systems comprising a matrix and supporting fibers, thus forming composite systems able to achieve fluidic and notably microfluidic functions. Among these functions, particularly useful applications are the technical fields of organ-on-a-chip, tissue-on-a-chip, culture of cells and organisms, wearables, point-of-need, point-of-care, biomedical and environmental analytical devices, windows in buildings, transportation devices, protection devices, instruments, notably scientific devices.
[0004] TECHNICAL BACKGROUND
[0005] Microfluidics has revolutionized the field of research in chemistry and biology through the development of increasingly efficient and precise platforms in numerous and various applications in medicine, health, energy, or environment. Some of them are now very prolific fields of interest in research such as organ-on-a-chip (OOC) devices, lab-on- a-chip (LOC) devices, analytical devices, production devices and the like. The combination of miniaturized technologies at the microscopic scale makes it possible to study new phenomena and develop new fields such as tissue-engineering by mimicking the body micro-environment with high fidelity. The field of organ-on-a-chip is an emerging area of biomedical research that aims at reproducing the structure and function of human organs using microfluidic platforms. It involves integrating various engineering principles, such as microfluidics, biomaterials, and cell biology, to create models of organ systems. The advantages of organ-on-a-chip systems lie in their ability to recreate the major features of organs, including their three-dimensional structure, tissue-tissue interfaces, and the ability to mimic physiological functions such as blood flow, mechanical forces, and biochemical gradients. This enables researchers to study organ responses, interactions between different cell types and the effects of drugs or toxins with greater precision and relevance than with traditional cell culture systems.
[0006] Current microfabrication techniques used to prepare organ-on-a-chip systems, or more generally microfluidic systems, however, involve microtechnology tools such as microlithography or micromachining. They are thus complex, expensive, and cannot be easily applied to large objects or high throughput production.
[0007] As a solution to this problem, Rahimi et al., investigated a possible microfluidic drug delivery platform by integrating highly flexible and stretchable channels into a textile substrate (R. Rahimi etal. “Directly embroidered microtubes for fluid transport in wearable applications", Lab Chip, 2017, 17, 1585-1593). In this document, surface functionalized micro-tubes by direct embroidery were integrated and coated with an Ecoflex™ elastomer layer for immobilization. The embroidered micro-tubes are ultra-thin, flexible and allow efficient drug perfusion. Safavieh et al., in Lab Chip, 2011 , 11 , 2618-2624, or Reches et al., in ACS Appl. Mater. Interfaces 2010, 2, 6, 1722-1728, proposed microfluidic systems, in which flow of fluid is driven by capillarity using threads or yarns. Such systems, however, cannot allow the flow of fluids containing colloids or cells, since they would get trapped by the fibers. In WO 2017 / 017002A1 , Viovy et al. proposed an approach aimed at building a hybrid microfluidic chip comprising a textile and an elastomer or hydrogel matrix. The textile plays several roles: sacrificial or removable fibers create channels in which cells can be cultured and perfused, and supporting fibers provide the mechanical properties required by the hydrogel, as well as the accurate positioning of sacrificial or removable fibers to define the future microchannels architecture.
[0008] The above systems, however, are not fully satisfactory for all applications. In particular, in many applications involving devices with embedded channels or tubes, it is useful to be able to optically observe what is contained inside said channels. Textile- reinforced matrices in general prevent such observation. This problem was partially addressed in WO 2017 / 017002 A1 , by providing windows devoid of textile fibers. This, however, is only a limited solution since the problem remains outside of the windows.
[0009] Besides, some systems exist, as disclosed e.g. in WO 2014 / 018378 A1 to Choiniere et al., which comprise a matrix reinforced by fibers and are nevertheless transparent, but they carry no channel, and cannot perform microfluidic functions. Besides, they are rigid, and do not either allow for the elasticity that is often needed in combination with said fluidic or microfluidic functions.
[0010] There is thus a need for devices with integrated channels, in particular microchannels, such devices being reinforced by fibers and making it possible to visually examine the content of said channels.
[0011] SUMMARY OF THE INVENTION
[0012] The invention relates to the following items.
[0013] Item 1 . A fluidic device comprising: a matrix having a first refractive index; a network of support fibers, at least some of the support fibers having a second refractive index, and the network being embedded at least partly in the matrix; and a channel embedded at least partly in the matrix and entangled at least partly in the network; wherein the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0014] The matrix is preferably transparent or translucent.
[0015] Item 2. The fluidic device of item 1 , wherein the support fibers are unsized, or sized by a sizing material with a third refractive index which differs from the second refractive index by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0016] Item 3. The fluidic device of item 2, wherein the third refractive index lies between the first and second refractive indices.
[0017] Item 4. The fluidic device of any one of items 1 to 3, wherein the network of support fibers comprises a textile, and the channel runs along the textile and / or within the textile.
[0018] Item 5. The fluidic device of item 4, wherein the channel has one or more underpasses and one or more overpasses with at least some of the support fibers of the textile, and a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of binding points between the channel and support fibers of the textile and y is the total number of the underpasses and the overpasses between the channel and the support fibers of the textile.
[0019] Item 6. A fluidic device comprising: a matrix; a textile component comprising support fibers, the textile component being embedded at least partly in the matrix; and a channel embedded at least partly in the matrix and running along the textile component, wherein the channel has one or more underpasses and one or more overpasses with at least some of the support fibers of the textile, and a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of binding points between the channel and support fibers of the textile and y is the total number of the underpasses and the overpasses between the channel and the support fibers of the textile.
[0020] The matrix is preferably transparent or translucent.
[0021] Item 7. The fluidic device of item 6, wherein the matrix has a first refractive index, at least some of the support fibers have a second refractive index, and the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0022] Item 8. The fluidic device of item 7, wherein the support fibers are unsized, or sized by a sizing material with a third refractive index which differs from the second refractive index by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0023] Item 9. The fluidic device of item 8, wherein the third refractive index lies between the first and second refractive indices.
[0024] Item 10. A method of making a fluidic device, comprising: providing a network of fibers comprising a plurality of support fibers and at least one removable fiber, at least some of the support fibers having a second refractive index; embedding the network at least partly within a matrix having a first refractive index; removing the removable fiber from the matrix to provide at least one channel embedded at least partly in the matrix and entangled at least partly in the network, wherein the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0025] The matrix is preferably transparent or translucent.
[0026] Item 11 . The method of item 10, wherein the support fibers are unsized, or sized by a sizing material with a third refractive index which differs from the second refractive index by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0027] Item 12. The method of item 11 , wherein the third refractive index lies between the first and second refractive indices.
[0028] Item 13. The method of any one of items 10 to 12, wherein the network comprises a textile, and the removable fiber runs along the textile.
[0029] Item 14. The method of item 13, wherein the removable fiber is tied by at least one of the support fibers on the textile at at least one binding point, the removable fiber floats over other support fibers at float points, and a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of the binding points and y is the total number of the binding points and the float points.
[0030] Item 15. A method of making a fluidic device, comprising: providing a textile component comprising a plurality of support fibers and at least one removable fiber; embedding the textile component at least partly within a matrix; removing the removable fiber from the matrix to provide at least one channel embedded at least partly in the matrix and running along the textile component, wherein the removable fiber is tied by at least one of the support fibers on the textile component at at least one binding point, the removable fiber floats over other support fibers at float points, and a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of the binding points and y is the total number of the binding points and the float points.
[0031] The matrix is preferably transparent or translucent.
[0032] Item 16. The method of item 15, wherein the matrix has a first refractive index, at least some of the support fibers have a second refractive index, and the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0033] Item 17. The method of item 16, wherein the support fibers are unsized, or sized by a sizing material with a third refractive index which differs from the second refractive index by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0034] Item 18. The method of item 17, wherein the third refractive index lies between the first and second refractive indices.
[0035] Item 19. The fluidic device of any one of items 5 to 9, or the method of any one of items 14 to 18, wherein at least one (possibly at least some, possibly all) of the support fibers which form the binding points has a diameter smaller than a diameter of at least some of the other support fibers of the textile.
[0036] Item 20. The fluidic device of any one of items 5 to 9 and 19, or the method of any one of items 14 to 19, wherein at least one (possibly at least some, possibly all) of the support fibers that form the binding points is a monofilament fiber, or a multifilament fiber having fewer filaments per fiber than other support fibers of the textile that are multifilament fibers.
[0037] Item 21 . The fluidic device of any one of item 5 to 9, 19 and 20, or the method of any one of items 14 to 20, wherein at least one (possibly at least some, possibly all) of the support fibers which form the binding points is made of the same material as the matrix.
[0038] Item 22. The fluidic device of any one of items 4 to 9 and 19 to 21 , or the method of any one of items 13 to 21 , wherein the textile is a non-woven textile, or a textile prepared by weaving, felting, knitting, sewing, warp knitting, weft knitting, knotting, braiding, plaiting, stitching, interlock, 3D weaving, filament winding, or multi-axes filament winding. Item 23. The fluidic device or the method of any one of items 1 to 22, wherein the support fibers comprise monofilament fibers, preferably having a diameter larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm.
[0039] Item 24. The fluidic device or the method of any one of items 1 to 23, wherein the support fibers comprise multifilament fibers, preferably having fewer than 10 filaments per fiber, preferably fewer than 5 filaments per fiber, at any given transverse cross-section of the fiber.
[0040] Item 25. The fluidic device or the method of item 24, wherein the diameter of the multifilament fibers is larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm.
[0041] Item 26. The fluidic device or the method of item 24 or 25, wherein the filaments of the multifilament fibers of the support fibers have a torsion of less than 1 turn per mm, or less than 1 turn per 5 mm, or less than 1 turn per cm.
[0042] Item 27. The fluidic device or the method of any one of items 1 to 26, wherein at least some of the support fibers, and / or the matrix, have an absorption coefficient smaller than 1 nrr1, or smaller than 0.3 nrr1, or smaller than 0, 1 nr1, or smaller than 0.03 nrr1, or smaller than 0.01 nr1in the wavelength range from 380 to 780 nm; or have an absorption coefficient smaller than 1 nrr1, or smaller than 0.3 nrr1, or smaller than 0,1 nrr1, or smaller than 0.03 nr1, or smaller than 0.01 nr1in the wavelength range from 450 to 700nm; or have an absorption coefficient smaller than 1 nrr1, or smaller than 0.3 nrr1, or smaller than 0,1 nrr1, or smaller than 0.03 nrr1, or smaller than 0.01 nr1in the wavelength range from 500 to 650 nm; or have an absorption coefficient smaller than 1 nr1, or smaller than 0.3 nrr1, or smaller than 0,1 nrr1, or smaller than 0.03 nrr1, or smaller than 0.01 nr1in the wavelength range from 380 to 780 nm at at least one predefined user-selected wavelength within the wavelength range of 380 to 780 nm.
[0043] Item 28. The fluidic device or the method of any one of items 1 to 27, wherein said device has, in at least some of its parts encompassing the channel, a transmittance along at least one direction of space, of more than 50%, preferably more than 75%, more preferably more than 80%, most preferably more than 90%, in the wavelength range from 380 to 780 nm; or a transmittance along at least one direction of space, of more than 50%, preferably more than 75%, more preferably more than 80%, most preferably more than 90%, in the wavelength range from 450 to 700 nm; or a transmittance along at least one direction of space, of more than 50%, preferably more than 75%, more preferably more than 80%, most preferably more than 90%, in the wavelength range from 500 to 650 nm; or a transmittance along at least one direction of space, of more than 50%, preferably more than 75%, more preferably more than 80%, most preferably more than 90%, in the wavelength range at at least one predefined user-selected wavelength within the wavelength range of 380 to 780 nm. Item 29. The fluidic device or the method of any one of items 1 to 28 which directly or indirectly refers to item 1 , 7, 10 or 16, wherein the first refractive index and / or the second refractive index range from 1.2 to 1.6, preferably from 1.3 to 1.5.
[0044] Item 30. The fluidic device or the method of any one of items 1 to 29, wherein the matrix comprises one or more of: an elastomer, preferably selected from the group consisting of: silicones, polydimethylsiloxanes (PDMS), polyurethanes, acrylic elastomers, fluoroelastomers, thermoplastic elastomers (TPEs), and polybutylene adipate terephthalates (PBAT); a thermoset, photopolymerizable or thermoplastic resin, preferably selected from epoxy, acrylic, polyurethane, polyester, fluoropolymers, polycarbonate, polystyrene, polyvinyl chloride, and polymethyl methacrylate (PMMA), norbornene-based polymers, polyolefins and notably cyclic olefin copolymers, or cyclic olefine polymers, polymethylpentene; and a hydrogel, preferably selected from the group consisting of: collagen, polyethylene glycol, extracellular matrix (ECM), gelatin, gelatin methacrylate (GelMA), polysaccharides, agarose, polylactic acid (PLA), and their derivatives.
[0045] Item 31. The fluidic device or the method of any one of items 1 to 30, wherein the matrix is biocompatible and / or bio-sourced.
[0046] Item 32. The fluidic device or the method of any one of items 1 to 31 , wherein at least some of the support fibers are made of PDMS.
[0047] Item 33. The fluidic device or the method of any one of items 1 to 32, wherein the matrix is made of PDMS, and the support fibers comprise, or consist of, fibers made of PDMS and / or fibers made of fluorocarbon and / or fibers made of polytetrafluoroethylene (PTFE).
[0048] Item 34. The fluidic device or the method of any one of items 1 to 32, wherein the matrix is made of hydrogel, preferably based on gelatin methacrylate (GelMA), or collagen, or extracellular matrix, or substitutes for extracellular matrix, or polyethylene glycol-derived hydrogel, and the support fibers comprise, or consist of, fibers made of fluoropolymers, preferably fluorinated ethylene propylene (FEP) or perfluoroalkoxy (PFA).
[0049] Item 35. The fluidic device or the method of any one of items 1 to 34, wherein the channel comprises at least one port, preferably at least two ports.
[0050] Item 36. The method of any one of items 10 to 35, wherein the step of removing the removable fiber comprises removing the removable fiber by mechanical action such as pulling, by physical action or chemical action such as dissolution, sublimation, melting, degradation with a chemical, or degradation with a radiation.
[0051] Item 37. The method of any one of items 10 to 36, wherein the removable fiber is made of PDMS.
[0052] Item 38. Use of the fluidic device of any one of items 1 to 9 and 19 to 35 for, or in, one or more of: cell culture; an organ-on-a-chip and / or a microfluidic chip; a wearable material, a garment and / or a part of a wearable material or a garment; an analytical device or part of an analytical device; a packaging or part of a packaging; an instrument with a temperature exchanger or part of an instrument with a temperature exchanger; a temperature control device or part of a temperature control device; an artificial skin; and a wound dressing.
[0053] Item 39. A method of imaging a compound comprising: providing the fluidic device of any one of items 1 to 9 and 19 to 35; introducing the compound into the channel of the fluidic device; and placing the fluidic device in an observation field of an imaging device to obtain an image of the compound.
[0054] Item 40. The method of item 39, wherein the imaging device is a microscope.
[0055] Item 41 . The method of item 39 or 40, wherein the compound comprises one or more cell and / or organism.
[0056] Item 42. A method of preparing a filament of a crosslinkable fluid material, comprising: a) providing the crosslinkable fluid material in a reservoir; b) extruding the crosslinkable fluid material from the reservoir through an orifice into a chamber without exposure to air, wherein physical and / or chemical conditions in the chamber are such that crosslinking of the crosslinkable fluid material is induced; and c) extracting the filament created by the crosslinking of the crosslinkable fluid material from the chamber.
[0057] Item 43. The method of item 42, wherein the steps a), b), c) are performed continuously. Item 44. The method of item 42 or 43, wherein the crosslinkable fluid material is extruded into the chamber at a flow rate of 1 mL / min or more, or 3 mL / min or more, or between 3 and 5 mL / min.
[0058] Item 45. The method of any one of items 42 to 44, wherein an inner diameter of the orifice is between 1.00 and 3.50 mm, or between 1.15 mm and 3.25 mm, or between 1.27 and 3.05 mm.
[0059] Item 46. The method of any one of items 42 to 45, wherein the extracting step is performed at a linear speed of between 8.0 and 14 m / min, preferably between 8.7 and 13.6 m / min.
[0060] Item 47. The method of any one of items 42 to 46, wherein the prepared filament has a diameter larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or lager than 100 pm.
[0061] Item 48. The method of any one of items 42 to 47, wherein the crosslinking is induced by temperature and the crosslinkable fluid material comprises a thermoset material.
[0062] Item 49. The method of item 48, wherein the chamber comprises a bath of a heated liquid, preferably an oil bath.
[0063] Item 50. The method of item 49, wherein the bath is maintained at a temperature between 200 and 215°C.
[0064] Item 51. The method of item 49 or 50, wherein the orifice is immersed at least partially in the bath.
[0065] Item 52. The method of any one of items 42 to 51 , further comprising: d) rinsing the extracted filament in a rinsing chamber.
[0066] Item 53. The method of any one of items 42 to 52, wherein the extracting step comprises passing the extracted filament through a cooling chamber or onto a cooling belt.
[0067] Item 54. The method of any one of items 42 to 53, wherein the crosslinkable fluid material comprises a mixture of a PDMS base polymer and a cross-linker.
[0068] Item 55. The method of item 54, wherein the weight ratio of the PDMS base polymer and the cross-linker is between 15:1 and 3:1, preferably between 12:1 and 5:1 , most preferably approximately 10:1.
[0069] Item 56. The method of any one of items 42 to 55, wherein the crosslinking is induced by light, and the crosslinkable fluid material comprises a photo-crosslinkable material.
[0070] Item 57. The method of any one of items 42 to 56, wherein the obtained filament is cylindrical, preferably having a substantially circular transverse cross-section. The invention thus defined addresses the need for devices with integrated channels, in particular microchannels, being reinforced by fibers and making it possible to visually examine the content of said channels.
[0071] BRIEF DESCRIPTION OF THE DRAWINGS
[0072] Figure 1 shows a variation of transparency along a fiber section for polyamide (•, circle dots), fluorocarbon (■, square dots), PTFE (♦ , diamond dots), FEP (A , triangle dots) and PFA ( — , bar dots), with pixels on the X-axis, normalized transparency on the Y-axis. See Example 1 below.
[0073] Figure 2 shows an example of a textile structure according to the invention prepared by weaving, and the textile while weaving on the weaving machine. A) shows the pattern of the weaving design, with the structural yarns (PFA) in light grey and the sacrificial or removable yarns (PTFE) crosshatched. B) shows a rear view of the loom, with the PFA and PTFE warp yarns. C) shows a final structure obtained after weaving, still stretched on the loom, with PFA and PTFE yarns in the warp direction and PFA yarns in the weft direction.
[0074] Figure 3 represents an exemplary scheme of a weaving pattern of the invention, showing from top, channels entangled with support fibers. A) illustrates a tie-up of the production. B) illustrates a drawing-in of the production. C) illustrates a peg plan of one of the woven production structures. D) illustrates a 2D simulation of the resulting production, seen from the fabric top. E) illustrates a code editor, one layer, eleven weft rows. The circles represent the PFA weft yarns, the light grey yarns represent the PTFE warp yarns and the dark grey one represents the PFA warp yarns. F) illustrates a 2D top view of the woven structure (angle with +Z: 0 deg; azimuth: 0 deg). G) illustrates a 2D cross section view of the resulting production (angle with +Z: 90 deg; azimuth: 0 deg). H) illustrates a 3D simulation of the resulting production (angle with +Z: 45 deg; azimuth: 45 deg).
[0075] Figure 4 shows woven structures for implementing the invention. A) shows a woven structure with simple monofilaments. B) shows a woven structure with multifilament yarns with three assembled sub-fibers. C) shows a woven structure with multifilament yarns with three assembled sub-fibers with twisting value of 50 twists / m in Z direction.
[0076] Figure 5 shows different textile structures usable for the invention, by changing a binding point parameter and a PTFE diameter. In A), one PTFE yarn with 500 pm diameter is above seven PFA yarns, then below one PFA yarn with a yarn density of 19 yarns / cm. In B), one PTFE yarn with 200 pm diameter is above one PFA yarn, then below one PFA yarn with a yarn density of 8-9 yarns / cm. In C), one PTFE yarn with 500 pm diameter is above one PFA yarn, then below one PFA yarn with a yarn density of 8-9 yarns / cm. D) is the same as A) with an angle allowing the visualization of undulation of the PTFE yarn. E) is the same as B) with visible undulation of the PTFE. F) is the same as C) without visible undulation.
[0077] Figure 6 illustrates an example of implementation of the invention, in a GelMA matrix, embedded in a capsule-like design for experimenting cell culture.
[0078] Figure 7 shows photographs of chips after manufacture. A) shows a photograph of a chip of prior art with a nontransparent yarn hiding channels. B) shows a photograph of a chip of the invention with a PFA yarn matching the refractive index of GelMA.
[0079] Figure 8 shows an observation image by confocal microscopy of HLIVEC cells in a chip of the invention after 7 days of perfusion. A) shows a bright field imaging of the top view of a channel. B) shows a channel cross-section view with confocal microscopy.
[0080] Figure 9 represents an example scheme of a system used in a method to prepare PDMS monofilament fibers.
[0081] Figure 10 schematically illustrates insertion of a removable or sacrificial fiber into a woven structure.
[0082] Figure 11 shows images of woven textiles for implementation of the invention, with a binding point in PDMS. A) shows a textile after weaving. B) shows a binding point in PDMS.
[0083] Figure 12 shows image of devices prepared with support fibers in PDMS vs polycarbonate. A) shows a binding point in PDMS. B) shows a binding point in polycarbonate.
[0084] Figure 13 represents an example of different types of weave diagrams with different numbers of binding points crossing the sacrificial or removable monofilament. The weave diagram is shown in A) with one binding point, B) with two binding points, C) with four binding points, D) with five binding points, E) with six binding points, and F) with eight binding points, respectively for 20 yarns in the warp direction.
[0085] Figure 14 shows different woven textile structures with a polycarbonate multifilament yarn and a PTFE sacrificial or removable yarn in the center. The structural yarns in a wavy shape cover the sacrificial or removable yarn after PDMS coating. A) shows a twill structure with ten floating warp yarns. B) shows a satin structure with ten floating warp yarns. C) shows a plain weave structure. D) shows a satin structure with five floating warp yarns.
[0086] Figure 15 shows a graph of % visibility of the channel depending on different numbers of binding points (the number of binding points on the sacrificial or removable monofilament on the X-axis, the visibility in % on the Y-axis).
[0087] DESCRIPTION OF EMBODIMENTS The invention will now be described in more detail, through the presentation of set of non-limiting examples of embodiments
[0088] Definitions
[0089] Fiber: by “fiber” or “wire” \s meant any linear solid object, with one dimension much larger than the two others. For the purpose of the present specification, fibers may be made of a single monolithic fiber, or of a plurality of smaller sub-fibers or filaments assembled together by any method, such as twisting, bundling, braiding, and the like. Objects called wires, cords, ropes, yarns, strings, strands, threads or filaments in the art of fibers, textile, or similar materials are also encompassed in the term “fiber”.
[0090] Monofilament Fiber: for the purpose of the present specification, by “monofilament fiber” is meant a monolithic elongated piece of material.
[0091] Multifilament Fiber: by "multifilament fiber" is meant a fiber composed of multiple sub-fibers or filaments. The sub-fibers or filaments may be bonded, bundled or twisted together to form a single multifilament fiber.
[0092] Support fiber: a support fiber is a fiber of a solid material, surrounded on at least part of its length by a matrix, and that will deform following deformations of the matrix. In some preferred embodiments, the support fibers have adhesion to the matrix and / or cohesion with the matrix. In some preferred embodiments, the support fibers contribute to the mechanical properties of a fluidic component or chip as a whole, imparting it, for instance, additional performances in areas such as better tear resistance or higher elongational modulus.
[0093] In some preferred embodiments, the support fibers are instrumental in defining a path of channel(s) or guiding duct(s) embedded in the fluidic component or chip, by retaining and / or positioning movable or removable fibers as defined below, at precise locations or along precise paths during the preparation of a device, thus avoiding the need for expensive microfabrication tools. The support fibers are not used to prepare a reserve for the future position of the channel in the matrix. The movable or removable fibers described below are used to prepare the channel in the matrix.
[0094] Network, reinforcement, backing: the support fibers form a structure which may be called a network, a reinforcement or a backing. The network, reinforcement or backing of the support fibers preferably comprises a textile. The definition of “textile” is described below. The network, reinforcement or backing is at least partly embedded in, contained in, covered by, or impregnated by the matrix.
[0095] Removable fiber: a removable fiber is a fiber that can be removed from the matrix, after the network of support fibers or the textile has been embedded in the matrix. The removal may be achieved by mechanical motion, in which case the removable fiber may also be called a movable fiber. Movable fiber: as opposed to the support fiber, a movable fiber is a fiber that is intended to be moved with respect to the matrix during the fabrication of the device. In contrast to threads or yarns used in microfluidic devices of prior art which adhere to the matrix when they are encompassed in such a matrix, the movable fiber in the present specification preferably does not adhere strongly to the matrix, and / or cannot be wicked by the matrix. Typically, the movable fibers can be made of a monolithic material, for instance plastic, glass, ceramic, metal or biopolymer. In some embodiments, the movable fibers can also keep some porosity, or be made of multiple sub-fibers, but in this case they present interfacial properties that prevent adhesion or absorption of the matrix. The movable fibers may also encompass fibers that have the property of being movable as defined above, on part of their length within the fluidic device, and may not have this property on another part of their length in the fluidic device.
[0096] Actionable fiber: by “actionable fiber” is meant a fiber that has at least one part that can be manipulated by external means so as to change its position or shape within the device. For instance, said manipulation may be any of pulling, pushing, twisting, rotation or combination thereof. The actionable fiber is in general a movable fiber.
[0097] Sacrificial fiber: in some embodiments, the removal of the removable fiber may be achieved by destroying said fiber, in which case the removable fiber may also be called a sacrificial fiber. The removal of the sacrificial fiber may be achieved e.g. by melting, sublimation, dissolution or ablation.
[0098] The removable fibers may encompass a set of sacrificial, movable and actionable fibers.
[0099] Sizing: in some embodiments, the fibers may be covered by a coating or sizing. Said sizing is common in the art of textile, and may be used for different functions, such as keeping together the sub-fibers or filaments composing the multifilament fiber, reducing friction, changing hydrophilicity or hydrophobicity, facilitating weaving and processing and / or reducing wear.
[0100] Textile: by “textile” is meant an object made of a multiplicity of threads or fibers, or made of a single fiber or thread with a multiplicity of bends or folds, so that said object involves multiple combinations of overcrosses (overpasses) and undercrosses (underpasses). Preferably, said combination of overcrosses and undercrosses contribute to give said object its shape and mechanical properties.
[0101] Objects designated as “fabric”, “cloth” or “felt” in the industry are also encompassed in the definition of “textile” for the purpose of the present specification, provided that they comprise a multiplicity of overcrosses (overpassses) and undercrosses (underpasses) between fibers, or a multiplicity of overcrosses (overpasses) and undercrosses (underpasses) of the same fiber. As a matter of example, the woven or non-woven fabrics or textiles used in clothing, as well as woven and non-woven technical textiles or geotextiles are encompassed in the definition of textile, and usable as such for the invention.
[0102] All kinds of textiles and textile preparation methods, such as described for example in WO 2017 / 017002 A1 can be used.
[0103] Interwoven or Entangled: a fiber is “interwoven" or “entangled" with a fiber, or with a textile or a fabric or a set of fibers, when it has a multiplicity of underpasses and overpasses with said fiber or with at least some fibers of said textile or fabric or set of fibers. This is used in a general sense, and is thus not necessarily restricted to devices prepared by a textile weaving method, although said textile weaving methods may advantageously be used in some embodiments. By analogy, the same definition applies to a channel, although it is a hollow structure, simply by considering a fiber occupying the same space. Thus a channel is “interwoven” or “entangled" with a fiber, or with a textile or a fabric or set of fibers, when it has a multiplicity of underpasses and overpasses with said fiber or with at least some fibers of said textile or fabric or set of fibers. For instance, a channel that travels within the thickness of a textile sheet while overpassing (overcrossing) and underpassing (undercrossing) the fibers of the textile sheet is considered as interwoven or entangled with said textile. However, a channel that is simply wrapped by a textile sheet, or a channel or a tube that is simply running between distinct layers constituting a textile sheet is not considered as interwoven or entangled.
[0104] Binding point (or tie point): when a channel is interwoven or entangled as defined above in the network of support fibers or with a textile, the channel thus has one or more underpasses and one or more overpasses with at least some of the support fibers of the network or the textile. Underpasses and overpasses between a channel and one or more fibers may be defined by considering the points P of minimal distance between the channel and the concerned fibers; and by drawing a plane or curved surface comprising all the centroids of the channel along the direction of elongation, such that the plane divides the space into two parts, some of the points P being in one part, and the other points P being in the other part. The underpasses then correspond to the points P in one part, while the overpasses correspond to the points P in the other part. If the number of overpasses is less than the number of underpasses, the binding points are the overpasses, and the underpasses can be designated as float points. If the number of underpasses is less than the number of overpasses, then the binding points are the underpasses, and the overpasses can be designated as float points. If there are the same number of overpasses and underpasses, then the binding points can be considered either as the overpasses or as the underpasses. The same applies analogously when considering a fiber, such as a removable fiber, instead of the channel. Since the channel can be formed in the network of support fibers by removing a removable fiber as defined above, a binding point may be considered as a point or position at which the original removable fiber was tied or bound by a support fiber.
[0105] Weave: The term “weave” generally refers to the way or pattern of interlacing warp and weft threads in a textile. As used herein, the weave refers to the way in which the binding points or binding points as defined above are distributed in the network of support fibers. The network of support fibers comprising the woven textile may be derived from three fundamental weaves: plain weave, twill and satin.
[0106] The weave of a textile or fabric describes the way in which the warp threads and weft threads will intersect and form a pattern. The geometric modeling of the weave of the textile consists of graphically representing all the points of connection between the warp threads and the weft threads, which amounts to specifying the types of intersection between the columns (warp threads) and the lines (weft threads) of the grid representing the weave of the textile. If a warp thread is “caught”, it is above a weft thread. It is represented by a black square (■) in the weave. Conversely, if a warp thread is “left”, it is below a weft thread, and is represented by a white square (□) in the weave. The phenomenon of warp or weft “floats” occurs when the same thread remains caught on several successive wefts or when the same weft passes over several successive threads. A weave may be defined by a weave ratio R, which corresponds to the number of warp threads and weft threads necessary to reproduce the pattern.
[0107] Float: in the field of textile or weaving, the term “float" refers to a length of yarn (fiber, filament or thread) on a surface of a woven fabric or textile between two consecutive intersections of the yarn with yarns woven at right angles to it, and notably between two binding points or tie points. The float is designated by the number of threads over or under which the floating yarn passes. The plain weave has no float since the warp and weft threads are interlaced in a basic crisscross pattern, with the weft thread passing over the warp thread in an ‘over and under’ sequence.
[0108] Matrix: a solid material in which the fibers and any of the guiding ducts or the channels of the invention are embedded at least in part.
[0109] Solid matrix: by “solid matrix" is meant a matrix constituted by a material that is able to keep a memory of its shape over long time periods, as opposed to a gas or a liquid. By “long time periods" is generally meant at least several hours, days, months or years. Solid matrices may have different viscoelastic properties, notably they can be rigid, elastic, viscoelastic, thermoplastic.
[0110] Embedded: by a fiber or channel “embedded” in a matrix is meant that said fiber or channel is surrounded by said matrix on all its perimeter on at least part of its length, notwithstanding the fact that there may be some local places at which said fiber or channel is not surrounded by the matrix, due to a local unwanted defect, or in contrast, to produce some specific functionality, such as an access port to the channel, or a window for observation, or a way to specifically manipulate one or a multiplicity of fibers.
[0111] Sheetlike: this term can designate an object such as a minifluidic device, a component, a chip, a matrix, a network or a structure of the support fibers. By “sheetlike’’ is meant that said object can be typically defined by two extended surfaces substantially parallel to each other, and separated by a given thickness. Usually, said thickness is small as compared to the surface’s length and width. This must be considered, though, in a broad sense. For instance, the thickness may not be the same everywhere, and the surfaces may have all kind of shapes. In preferred embodiments, said surfaces are developable.
[0112] In some preferred embodiments, the channel runs along a sheetlike object (e.g., textile) made of the support fibers, or within said sheetlike object. In that case, it is particularly suitable to have this channel running essentially parallel to the larger or main surface of this sheetlike object. Preferably, the device of the invention is sheetlike.
[0113] Channel: by “channel” is meant any elongated space, tube, duct, pipe or conduit along which a fluid substance can be transported. More specifically, the channels may be designated as microchannels if they are micrometric, i.e. if at least one dimension of their transversal cross-section is comprised between 1 pm and 1 mm. The channels may be designated as millichannels if they are millimetric, i.e. if at least one dimension of their transversal cross-section is comprised between 1 mm and 1 cm. The channels may be designated as nanochannels if they are nanometric, i.e. if at least one dimension of their transversal cross-section is comprised between 1 nm and 1 pm. The channels according to the invention may be delimited, at least along part of their length, by one or more walls that define an interior space. Further, channels in the devices according to the invention may be open along at least part of their length.
[0114] Minichannels: in many preferred embodiments, the invention is particularly interesting for microchannels. However, for the sake of conciseness and completeness, a channel comprising along its length at least a portion that is either millimetric, micrometric, or nanometric is generically called a minichannel in the present specification.
[0115] The channels may be "substantially enclosed" within a fluidic component or chip, or within a device, or within a matrix. Namely, the channels may represent a fluidic path substantially contained and circumscribed by one or more walls constituted by said fluidic component, chip, device or matrix, however a substantially enclosed channel can include inlets, outlets, exposed contact regions, and the like.
[0116] As used herein, "interconnected channels" refer to two or more channels within the structure that are able to communicate fluid between and through each other.
[0117] By “minifluidic chip” or “minifluidic component”, or more generally “chip” is meant an object comprising at least one channel, or at least one combination of channels, said channel or combination of channels being embedded at least partly in a matrix, and said channel being a minichannel as defined above. However, for the sake of simplicity, in the following, minifluidic chips, components or devices also encompass either microfluidic chips, components or devices, i.e. those comprising at least one microchannel; millifluidic chips, components or devices, i.e. those comprising at least one millichannel; nanofluidic chips, components or devices, i.e. those comprising at least one nanochannel; or any combination thereof.
[0118] By “instrument” is meant an integrated device that is able to perform at least one function without the addition of additional components other than components available in the operational environment, such as for instance an energy source or consumables. In the present specification, an instrument is thus a subcategory of an integrated device.
[0119] By “device” is meant any of a chip, a component, an instrument and a system.
[0120] By “system” is meant a combination of instruments associated to exert one or several tasks.
[0121] By “minifluidic device” (encompassing microfluidic, millifluidic or nanofluidic device as defined above) is meant a device comprising at least one minichannel (encompassing microchannel, millichannel or nanochannel as defined above) and optionally comprising other components which may not be necessarily fluidic or minifluidic in their nature or function. Minifluidic devices of the invention may involve different levels of integration. For instance, minifluidic devices may be a single minifluidic chip or component, integrating one or several functionalities. Minifluidic devices may also comprise all other kinds of elements and components, such as pumps, valves, sensors, actuators, detectors, and many others known in the art. In particular, minifluidic devices may also be full instruments, and integrate for instance any of holders, housings, power sources, control software and hardware, communication means, storage means, manipulation means, human-machine interfaces. In the present specification, when the word “component” is used without any specifying adjective such as “textile component”, or “additional component”, it is intended to designate the minifluidic component of the invention.
[0122] By “integrated (minifluidic) device” is meant a device comprising a (mini)fluidic chip of the invention and at least one additional component.
[0123] Refractive index: the “refractive index” or “index of refraction” is the ratio of the velocity of light in a vacuum to its velocity in the material of interest. It is expressed as a ratio of the sine of the angle of incidence to the sine of the angle of refraction. The refractive index may be measured by the standard method according to ASTM D542-22, which is technically equivalent to ISO 489:2022. There are several devices or instruments known for measuring the refraction index, such as an Abbe's refractometer, a Pulfrich refractometer and an immersion refractometer, for example commercially available devices such as the RC5 from Mettler Toledo or the Rudolph Research J457. For the refractive indices of polymers or other materials mentioned in the present specification, reference is to be made to Jan W. Gooch, Encyclopedic Dictionary of Polymers, Second Edition, DOI: 10.1007 / 978-1-4419-6247-8, page 615-620, and https: / / scipoly.com / technical-library / refractive-index-of-polymers-by-index /
[0124] Fluidic device
[0125] The fluidic device of the invention is a composite device which can be a microfluidic, nanofluidic, millifluidic or more generally a minifluidicdevice. It is desirably suitable for optical observation.
[0126] The fluidic device of the invention comprises a matrix, and a network of entangled fibers embedded at least in part in said matrix. Preferably, said network is a textile. In general, textiles are not transparent, at best translucent, and thus not suitable for see- through accurate visual observation. The invention, however, according to a preferred aspect, improves the possibility of visual observation or imaging by selecting fibers and matrices having specifically selected refractive indices. More specifically, a first refractive index of the matrix n1 and a second refractive index of at least some (in some cases, all) of the support fibers n2 differ by less than 0.05, or less than 0.03, or less then 0.015, or less than 0.01 , or less than 0.005.
[0127] The fluidic device of the invention also comprises at least one channel, embedded on at least part of its length inside the matrix. The channel can allow the transport of fluid by free flow under a difference of pressure. In some embodiments, said channel comprises at least one inlet port, and preferably one inlet port and one outlet port, and transport is induced by creating a difference of pressure between the inlet and outlet ports. In some embodiments, said difference of pressure is created by a pressure controller, for example an automated pressure controller or a flow controller. Preferably, said pressure or flow controller is automated and / or dynamic, i.e. can be changed in the course of time.
[0128] The number of channels in the device may not be limited to one channel, but the device may comprise a plurality of channels. The channels may also be connected, in part or in totality, creating one or several channel networks. The channels may have not only one or two ports, but also a multiplicity of ports to the outside of the device.
[0129] The channels may also have different types of shapes and dimensions, being minichannels, millichannels, microchannels, nanochannels as described in the above definitions, or others. Also, channels of different sizes and shapes may be combined, which makes the device of the invention particularly interesting as compared to microfluidic devices of prior art made by microlithography, in which channels are generally parallelepipedal, and making channels with different thicknesses is difficult. In some embodiments, the channels are advantageously entangled with at least some of the support fibers. This may be instrumental, in particular, in preserving the channels from damage from the outside, or in keeping in place the sacrificial or removable fibers that will give rise to the channel(s) during the fabrication process.
[0130] In most applications, the channels may contain a fluid and notably a liquid during at least part of their time of use. In some embodiments, said fluid is an aqueous fluid, or a biphasic combination of an aqueous fluid and an hydrophobic fluid. In some embodiments, said fluid is itself transparent or semi-transparent.
[0131] In addition, said fluid may contain various types of colloidal suspensions, such as, as an exemplary and non-limitative list, latex, living cells, blood cells, extracellular vesicles, vesicles, micro-organisms magnetic particles, droplets, and generally speaking all systems known in the art as capable of forming colloidal suspensions.
[0132] In some embodiments, the channels contain cells, and notably cells adhering to the walls of the channels.
[0133] In some embodiments, it may also be interesting to select the matrix and the fluid contained in the matrix such that the fluid has a fourth refractive index n4, that is close to the first refractive index n1 of the matrix, and notably differs by less than 0.1 , or less than 0.03, or less then 0.015, or less than 0.01 , or less than 0.005, from the first refractive index n1 of the matrix.
[0134] Preferably, the matrix is made of a transparent, or at least translucent material.
[0135] Preferably, some or all of the support fibers are made of a transparent, or at least translucent material.
[0136] Preferably, at least part, possibly all, of the device of the invention is transparent, or at least translucent.
[0137] For the purpose of the present specification, the term “transparency” means the physical property of allowing light to pass through an object or device without being scattered. The term “translucency” is a superset of transparency and allows light to pass through and also allows scattering. In other words, images can be seen without or with little blurring across a transparent medium, whereas light can pass through, but images are blurred or completely destroyed across a translucent material.
[0138] The transparency (or translucency) of an object or device may be measured by its total transmittance.
[0139] The transparency (or translucency) of a material may be characterized by its (light) absorption coefficient.
[0140] The total transmittance is a percentage of incident light transmitted through said object or device. Namely, T (%) = 100 x (l / lo), where T is the total transmittance, Io is the incident light intensity and I is the intensity of light transmitted by the material specimen. The total transmittance may depend on the type of light source and wavelength ranges of light. The total transmittance may be measured for example by the standard test method according to ISO 13468-1 :2019 and / or ISO 13468-2:2021. There are several transparency meters available on the market.
[0141] T ransmittance may also vary depending on the part of the device or object through which light is transmitted. In preferred embodiments, the transmittance to be considered refers to a zone of the device comprising at least one channel. Also, if the device is sheetlike, in some embodiments transmittance is preferably determined across its thickness, i.e. its smallest dimension. In other words, transmittance is preferably determined in a direction perpendicular to the main surface of the sheetlike object.
[0142] The transparency or translucency may also be expressed by the absorbance. The absorbance, also referred to as optical density is defined as the logarithm of the ratio of incident to transmitted radiant power through a sample. The absorbance is based on the Beer-Lambert law and can be obtained by a spectrometer. The absorbance (A) at a wavelength A can be expressed as AA = log (lo / l), = -log T = 2 - log T(%).
[0143] In some embodiments, the device of the invention has a transmittance, as defined above, which is more than 50%, preferably more than 75%, more preferably more than 80%, most preferably more than 90%, or even more than 92% or more than 95%. In some embodiments, these transmittance values are obtained across the entire visible wavelength range from 380 to 780 nm; in other embodiments, these transmittance values are obtained across the wavelength range from 450 to 700 nm; in other embodiments, these transmittance values are obtained across the wavelength range from 500 to 650 nm; in other embodiments, these transmittance values are obtained at at least one predefined user-selected wavelength within the wavelength range of 380 to 780 nm (such as: at approximately 550 nm). The predefined user-selected wavelength may be suitable for a given application.
[0144] In some embodiments, at least some of the support fibers, and / or the matrix, are made of a material have an absorption coefficient smaller than 1 nr1, or smaller than 0.3 nrr1, or smaller than 0,1 nrr1, or smaller than 0.03 nr1, or smaller than 0.01 nr1. Measuring absorption coefficients is a procedure well known for those skilled in the art. It can for instance be done by measuring the absorption of a sample of known thickness by a spectrophotometer, and calculating from that the absorption coefficient using the Beer- Lambert law. In some embodiments, these absorption coefficient values are obtained across the entire visible wavelength range from 380 to 780 nm; in other embodiments, these absorption coefficient values are obtained across the wavelength range from 450 to 700 nm; in other embodiments, these absorption coefficient values are obtained across the wavelength range from 500 to 650 nm; in other embodiments, these absorption coefficient values are obtained at at least one predefined user-selected wavelength within the wavelength range of 380 to 780 nm (such as: at approximately 550 nm). The predefined user-selected wavelength may be suitable for a given application.
[0145] The matrix may be an elastomer chosen among silicones, polydimethylsiloxanes (PDMS) such as of the Sylgard™ brand, polyurethanes, acrylic elastomers, fluoroelastomers such as of the Dyneon™ brand, thermoplastic elastomers (TPEs), polybutylene adipate terephthalates (PBAT) such as of the Ecoflex™ brand. Elastomers, notably PDMS, are widely used in microfluidics. They confer to the device various advantages, such as possibilities to adapt conformally to a substrate, to make easy and tight-proof connections, and to be transparent. The combination of these matrices with a textile may improve mechanical properties, without dramatically sacrificing transparency.
[0146] In other embodiments, notably when requiring a mechanically hard material, the matrix may also be a thermoset resin, a photopolymerizable resin or a thermoplastic resin. It can be chosen, as a matter of example and non-limitatively, among epoxy resins, acrylics, polyurethanes, polyesters, fluoropolymers, polycarbonate, polycaprolactone, polystyrene, polyvinyl chloride, polymethyl methacrylate (PMMA), or materials based on polysaccharides or cellulose, or more generally all derivatives and / or copolymers of the above.
[0147] The matrix may also be chosen among biocompatible polymers, notably for biology applications, and / or among bio-sourced materials.
[0148] Particularly suitable for cell culture, regenerative medicine, organ-on-a-chip or wound dressing, the matrix may be a hydrogel. A hydrogel is a biphasic material, a mixture of porous, permeable solids and at least 10% by weight of interstitial fluid predominantly or completely composed by water. In some embodiments, said hydrogel may be an artificial hydrogel, such as a hydrogel based on crosslinkable polyethylene glycol or polyethylene oxide, like polyethylene glycol diacrylate (PEG-DA), agarose and other hydrogels extracted from plants and / or algae. In some embodiments, the hydrogel contains cells such as fibroblasts, or cell aggregates such as cancer spheroids or organoids.
[0149] In other embodiments, also particularly suitable for cell culture, organ-on-a-chip or regenerative medicine, the hydrogel has the capacity to be remodeled by living cells. It can be, for example and non-limitatively, based on collagen, gelatin, gelatin methacrylate (GelMA), polysaccharides, agarose, polylactic acid (PLA), extracellular matrix (ECM) such as Matrigel™, chitosan, alginate, hyaluronic acid, and their equivalents and derivatives.
[0150] The combination of the hydrogel with the textile, or more generally the support fibers, is particularly advantageous. Hydrogels are known to be very soft and often fragile, so that the entanglement of fibers greatly increases their mechanical properties, and this is achieved without sacrificing other properties, such as capacity to drive fluids therein, to create complex fluidic networks, and to perform optical detection and imaging.
[0151] In some embodiments, the matrix (together with the embedded fibers and channel) may be partly or wholly encapsulated in another material so as to provide additional mechanical strength. For example, if the matrix is a hydrogel, partial or full encapsulation in an elastomeric material may be provided.
[0152] As examples and not limitatively, different materials and different structures may be used advantageously with the invention, to constitute support fibers. Typically, the support fibers may be yarn, threads, or other fibers, for example made of cotton, nylon, polyester, polyolefin (such as polypropylene), a fluoropolymer (such as polyvinylidene fluoride), nitrocellulose, cellulose, cellulose acetate, silicone polymer such as polydimethylsiloxane (PDMS), polyurethane or a glass microfiber structure.
[0153] In some embodiments, the support fibers are advantageously made of the same material as the matrix. This can provide optimal optical properties. In some particularly preferred embodiments, said common material for the support fibers and the matrix is an elastomer, a silicone, and in particular PDMS.
[0154] The internal structure of the support fibers or yarns can also affect the final properties of the device, and different structures may be preferred for different applications. The support fibers may be made of bundled sub-fibers or filaments, using various standard techniques known in the art, which may include twisting, braiding, holding multiple strands together tightly, and combinations thereof. Typically, structures with multiple filaments will increase mechanical properties and cohesion with the matrix, whereas minimizing the number of filaments will improve transparency. In some embodiments, the support fibers are monofilament support fibers. In some embodiments, the support fibers are multifilament support fibers preferably having fewer than 10 filaments or sub-fibers per fiber, and preferably fewer than 5 filaments or sub-fibers per fiber, at any given transverse cross-section of the fiber.
[0155] Multifilament fibers can consist of either continuous or discontinuous sub-fibers. However, the use of discontinuous sub-fibers may result in fluffiness, leading to random obscuration of the channel content and diminishing transparency. To mitigate this issue, continuous sub-fibers are preferable.
[0156] Preferably, the diameter of the support fibers is larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm; such as from 15 pm to 1 mm, or from 50 pm to 800 pm, or from 100 pm to 500 pm.
[0157] When the support fibers are multifilament fibers, the level of torsion is also instrumental in optimizing final properties. Typically, higher torsion will improve mechanical properties, and lower torsion will improve imaging and facilitate removal of the removable fibers. In devices optimized for imaging, the torsion of the filaments is low, such as no torsion ( / .e. “assembled” filaments), or less than 1 turn per mm, preferably less than 1 turn per 5 mm or less than 1 turn per cm. Low torsion also minimizes the deformation of the removable fibers, and thus facilitates their mechanical removal.
[0158] The fibers or sub-fibers (filaments) may comprise a sizing. This may alter the final optical properties of the device. In some embodiments, the support fibers have no sizing. Another option to mitigate possible adverse effects of sizing is to choose for the sizing a material that is transparent (as defined above), and / or has a third refractive index n3 that differs by less than 0.05, or less than 0.03, or less then 0.015, or less than 0.01 , or less than 0.005 from the second refractive index n2 of the support fiber.
[0159] Preferably, it may be advantageous that the third refractive index n3 of the sizing lies between the second refractive index n2 of the support fibers and the first refractive index n1 of the matrix.
[0160] In some applications, notably for those based on fluorescence, it may be advantageous that any of the support fibers, the matrix, and eventually the sizing if present, and preferably all of them, have low autofluorescence. Typically, said autofluorescence is at most equal to that of PDMS, or at most 2, 5, 10 times that of PDMS, in a range of excitation wavelengths comprised between 250 nm and 800 nm, or between 300 nm and 500 nm.
[0161] In some embodiments, all the support fibers in the network have a second refractive index n2 that differs by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005 from the first refractive index n1 of the matrix. For some applications, however, it may be interesting to combine, within the network of support fibers, said support fibers having the second refractive index n2 with other fibers having a different refractive index. This may be interesting, for instance to improve mechanical properties, or to make textile processing easier, if it is not possible to find or fabricate fibers combining an optimal refractive index with optimal mechanical properties.
[0162] The network of support fibers, which is a constitutive part of the device of the invention, may advantageously comprise a textile, or be prepared as a textile, allowing this way to benefit from the large know-how and potential of the textile industry. Said textile may be prepared by any methods known in this extensively developed industry, such as weaving, felting, knitting, sewing, warp knitting, weft knitting, knotting, braiding, plaiting, stitching, interlock, 3D weaving, filament winding, or multi-axes filament winding, and any combination of said techniques.
[0163] Also, depending on the final geometry of the device, said textile may preferably be a planar, 2D textile, for a planar chip, or a more complex 3D textile, for a chip with a more complex architecture. This would be the case, for instance, if the fluidic function of the device requires a 3D architecture of channels, or a multilayer architecture of channels. The network of support fibers may serve as a reinforcement or backing of a composite with the matrix, and may function to hold and position the removable fiber(s) for the subsequent matrix impregnation, so that one or more channels can be provided in a desired position by then removing the removable fiber(s).
[0164] The network of support fibers is desirably arranged so as not to hinder the visibility of the channel, nor prevent the removal of the removable fiber, nor cause fluid leakage when using the resulting fluidic device.
[0165] Preferably, the network of support fibers comprises or is a woven textile. Different weaves can be advantageously produced on the same weaving machine to provide the network of support fibers as the woven textile. The woven textile is then impregnated in a matrix (e.g. PDMS) to form the composite.
[0166] In some embodiments, the textile is made by weaving support fibers and one or more removable fibers as warp yarns, and support fibers only as weft yarns. In other embodiments, the textile is made by weaving support fibers only as warp yarns, and support fibers and one or more removable fibers as weft yarns.
[0167] In some embodiments, it may be advantageous that the removable fiber runs preferentially on one side of the textile, on which the removable fiber presents “floats”, said removable fiber being interlaced or entangled with the support fibers through binding points. In other words, the removable fiber forms a float between two adjacent binding points on one side of the textile. The length of the float is defined by the length between the two adjacent binding points. If there is only one binding point, the length of the float is defined by the length between the binding point and an end of the removable fiber. In some embodiments, there are a plurality of binding points regularly distributed along the removable fiber, that gives a plurality of floats of the same length. In some embodiments, there are a plurality of binding points randomly distributed along the removable fiber, that gives a plurality of floats each having a different length.
[0168] When the removable fiber is removed, this yields a channel that travels preferentially on one side of the textile, and visualization of said channel on that side of the device is improved due to the reduced number of binding points.
[0169] This is especially appropriate for the purpose of reflected light microscopy observation such as fluorescence imaging. These techniques do not require fully transparent material, as the light path does not need to traverse the entire material thickness. Rather, it only needs to penetrate from the observation side until reaching the sample in the fluidic channel. At this point, the reflected light emitted by the samples follows the same path until it reaches a sensor. Therefore, in order to enhance this type of observation, it may be appropriate to reduce the number of binding points by increasing the number of floating connections on the observation side. In some embodiments, it may also be advantageous to minimize the number of binding points, and / or to maximize the length of the float of the removable fiber.
[0170] In some embodiments, a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of binding points between the removable fiber (and thus the resulting channel) and the textile, and y is a sum of the number of points at which the floating removable fiber contacts the underlying support fibers and of the number of binding points (x).
[0171] In other words, on one side of the textile, the removable fiber has an underpass at the binding point, i.e. the removable fiber passes below the support fiber at the binding point, whereas in the float section, the floating removable fiber has an overpass, i.e. the removable fiber passes above the support fiber - or the opposite. The channel obtained by removing the removable fiber maintains the same arrangement of underpass and overpass with respect to the support fibers in the textile. Thus, in some embodiments, a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of binding points between the channel and the textile, and y is the total number of the underpasses and the overpasses between the channel and the support fibers of the textile.
[0172] In some embodiments, the support fibers with which the removable fiber (or the channel, after removal of the removable fiber) has underpasses and overpasses are substantially parallel. In some embodiments, there is no more than one underpass or overpass with each support fiber.
[0173] In some embodiment, it may be advantageous that the support fibers constituting the binding points have the second refractive index n2 with the properties described above with regards to the matrix. This improves the visibility of the channel.
[0174] In some embodiments, a, the or each support fiber constituting a, the or each binding point is a monofilament fiber.
[0175] In some embodiments, a, the or each support fiber constituting a, the or each binding point is a multifilament fiber having fewer filaments per fiber than other support fibers.
[0176] In some embodiments, a, the or each support fiber constituting a, the or each binding point has a diameter smaller than a diameter of at least some of the other support fibers.
[0177] In some embodiments, a, the or each support fiber constituting a, the or each binding point is made of the same material as the matrix.
[0178] Use The fluidic device of the invention may be useful for numerous applications that were not possible, or possible only with lower convenience or performance in prior art fluidic systems.
[0179] A first family of applications is analytical chemistry, or bioanalytical chemistry. It is thus also provided an analytical instrument comprising the fluidic device of the invention.
[0180] A second family of applications concerns the culture of living cells or living organisms. It is thus also provided a microfluidic device, or a microfluidic chip, or more generally a fluidic device for the culture of cells or tissue or organs or organisms, or organoids, or cell spheroids, comprising a fluidic chip according to the invention.
[0181] In some embodiments, said device is an organ-on-a-chip.
[0182] In some embodiments, said device is an implant for regenerative medicine. Regenerative medicine already uses a lot of textile-based implants, but it may be advantageous in some applications to pre-cellularize said implants, which is made particularly convenient with the invention. It is thus also provided an implant for regenerative medicine comprising the fluidic device of the invention, wherein the network of support fibers and at least one channel, preferably a network of channels are embedded on at least part of their lengths in a biocompatible matrix. Said matrix and / or said fibers may also be biodegradable or bioresorbable.
[0183] In some embodiments, said channels and / or said matrix contain cells. In some embodiments, said network of channels contain endothelial cells, and constitute a prevascularization. In some embodiments, said network of channels contain epithelial cells.
[0184] In some embodiments, the device of the invention may be configured as or comprised in an artificial skin or a sub-component of an artificial skin. Advantageously, the invention brings an optimal combination of fluid transport properties, substrate for cell development, mechanical properties, and possibility to observe during curing the behavior of the underlying tissue.
[0185] For similar reasons, in some embodiments, the device of the invention may be configured as or comprised in a wound dressing or a component of a wound dressing. In some embodiments, the device of the invention may be configured as or comprised in a wearable material, a garment, or a part of a wearable material or of a garment. In some embodiments, the device of the invention may be configured as or comprised in part of a packaging, combining transparence and improved mechanical strength.
[0186] As another possible application, the fluidic device of the invention may be used for heat exchange, while keeping the possibility to perform visual observation or more generally, perform optical functions. Thus, the device of the invention may be configured as or comprised in a heat exchanger, a temperature control device, or part of an instrument for heat exchange or temperature control. In some embodiments, the device of the invention may be configured as or comprised in a protection device or in a part of a protection device. In some embodiments, the device of the invention may be configured as or comprised in a portable protection device or in a part of a portable protection device. In some embodiments, the device of the invention may be configured as or comprised in part of a device for protecting living species, notably humans, or instruments, notably optical instruments, from heat. For instance, the device of the invention may be configured as or comprised in part, notably a window, of a cooled helmet, or window for a packaging for an instrument or a camera, said window comprising a channel which allows a flow of cooling fluid.
[0187] Imaging method
[0188] As mentioned previously, the device of the invention may be particularly interesting for imaging. It is thus also provided a method for imaging a compound, or for performing an optical operation on a compound within a channel, comprising the steps of: providing the fluidic device of the invention; introducing the compound into the channel of the fluidic device; and placing the fluidic device in an observation field or imaging field of an imaging device, or more generally along the optical path of an optical instrument, to obtain an image of the compound.
[0189] In some embodiments, said imaging device is a microscope.
[0190] In some embodiments, which can advantageously be combined with other embodiments, said compound comprises a cell, a group or set of cells, a tissue, an organism, part of a tissue or an organism, part of a body fluid, and / or an environmental fluid.
[0191] In some embodiments, imaging is carried out by transmitted light microscopy; in other embodiments, imaging is carried out by reflected light microscopy observation such as fluorescence imaging. This may be in particular appropriate with a fluidic device wherein the channel travels preferentially on one side of the textile, as mentioned above.
[0192] Manufacturing method
[0193] It is also provided a method of making a fluidic device, comprising: providing a network of fibers comprising a plurality of support fibers and at least one removable fiber, at least some of the support fibers having a second refractive index; embedding the network at least partly within a (preferably transparent or translucent) matrix having a first refractive index; removing the removable fiber from the matrix to provide at least one channel embedded at least partly in the matrix and entangled at least partly in the network, wherein the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
[0194] In some embodiments, the removable fiber may be removed by mechanical action such as pulling, by physical or chemical action such as dissolution, sublimation, melting, degradation with a chemical, or degradation with a radiation.
[0195] The embedding of the network within the matrix may be carried out by placing the network in a mold and casting the matrix, or a matrix precursor (such as a crosslinkable composition) into the mold.
[0196] The statements described above with regard to the fluidic device and its use according to the invention all apply to the method of making the fluidic device.
[0197] As mentioned above, a wide variety of fibers available in the prior art may be used as the support fibers for the fluidic device of the invention. For some applications, however, it may not be possible to achieve the best optical properties by combining matrices and fibers existing in the prior art. It is thus advantageous to provide a process able to prepare a fiber particularly well adapted for constituting the fluidic device of the invention.
[0198] It is thus also provided a method of preparing a filament of a crosslinkable fluid material, comprising: a) providing the crosslinkable fluid material in a reservoir; b) extruding the crosslinkable fluid material from the reservoir through an orifice into a chamber without exposure to air, wherein physical and / or chemical conditions in the chamber are such that crosslinking of the crosslinkable fluid material is induced; and c) extracting the filament created by the crosslinking of the crosslinkable fluid material from the chamber.
[0199] In some embodiments, the method is a continuous process and the steps a), b), c) are performed continuously.
[0200] Preferably, during said continuous process, the extrusion and / or the extraction are respectively performed at a constant speed, and / or regulated by a feedback loop to maintain the diameter of the extruded filament consistent with some predefined specifications.
[0201] In some embodiments, the extrusion is performed at a flow rate of 1 mL / min or more, or 3 mL / min or more, or between 3 and 5 mL / min.
[0202] In some embodiments, the extraction is performed at a linear speed of between 8.0 and 14 m / min, preferably between 8.7 and 13.6 m / min. In some embodiments, the crosslinking is induced by temperature, and the crosslinkable fluid material comprises a thermoset material. In such embodiments, the chamber is preferably a bath of a heated liquid, preferably an oil bath. The bath may be maintained at a suitable temperature to induce the crosslinking accordingly. For example, the bath may be maintained at a temperature between 200 and 215°C.
[0203] In the embodiments in which crosslinking is induced by temperature, step c) advantageously comprises or is followed by a cooling step in which the extracted filament is passed through a cooling chamber or onto a cooling belt. Said cooling belt may advantageously perform simultaneously two functions, of cooling the filament, and of pulling it by friction forces.
[0204] In the embodiments with the chamber being a bath of a heated liquid, step c) (including the cooling step if present) may advantageously be followed by a rinsing or cleaning step in which the extracted filament is rinsed or cleaned from residuals of said liquid. The rinsing or cleaning may be done by various methods known in the art, notably by plunging the filament in a bath of a solvent of said heated liquid.
[0205] In some embodiments, the crosslinking is induced by light, and the crosslinkable material comprises a photo-crosslinkable material. In such embodiments, the chamber is preferably an illumination chamber.
[0206] In some embodiments, the crosslinkable fluid material after crosslinking comprises: an elastomer, notably but not limitatively, a silicone polymer, including polydimethylsiloxane, a rubber, a polyurethane, a fluorinated elastomer, a vitrimer, a thermoplastic elastomer, a polyisobutadiene or more generally an elastomeric polyene.
[0207] In some embodiment, the crosslinkable fluid material comprises a thermoset resin, notably but not limitatively, an epoxy resin or a polyester.
[0208] In some embodiments, the crosslinkable fluid material comprises a mixture of a PDMS base polymer and a cross-linker.
[0209] In some embodiments, the weight ratio of the PDMS base polymer and the crosslinker is between 15:1 and 3:1 , preferably between 12:1 and 5:1 , most preferably approximately 10:1.
[0210] As such, the method may prepare a filament of an elastomer, preferably of PDMS, so that the prepared PDMS filament may be used for the support fibers of the fluidic device of the invention. Such support fibers may advantageously be made of the same material (PDMS) as the matrix, resulting in improved visibility of the fluidic device. In some embodiments, an inner diameter of the orifice is between 1.00 and 3.50 mm, or between 1.15 mm and 3.25 mm, or between 1.27 and 3.05 mm. The orifice may be a needle. Preferably, the orifice is immersed at least partially in the bath. In this way, the crosslinkable fluid material may be extruded from the reservoir through the orifice into the chamber without exposure to air. In some embodiments, the prepared filament has a diameter larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm, such as from 15 pm to 1 mm, or from 100 pm to 1 mm, or from 300 pm to 600 pm, or from 400 pm to 550 pm.
[0211] It has been found that the above method wherein the crosslinkable fluid material is extruded without exposure to air, such as in an oil bath, makes it possible to achieve a continuous production of long filaments having a substantially circular cross-section. This applies in particular to PDMS filaments. The filaments obtained owing to this method have desirable mechanical properties such as a desirable elasticity modulus (for example of at least 0.8 MPa or at least 1 MPa), a desirable elongation at break (for example of at least 300%, or at least 400%), and / or a desirable strain at break (for example of at least 5.5 MPa or at least 6 MPa).
[0212] A specific embodiment of the method is explained in Example 7 below with reference to Figure 9.
[0213] EXAMPLES
[0214] The following examples illustrate the present disclosure without limiting it.
[0215] Example 1 : Evaluation of the optical transmission of different fibers in a matrix, as a function of the refractive index difference.
[0216] A gelatin matrix was prepared by dissolving gelatine (G1890-100G from Merck) into Dulbecco Phosphate Buffer Saline (DPBS, Sigma-Aldrich D8537) to a final concentration of 10% weight / volume at approximately 50°C for 20 min.
[0217] A testing device was made of a 6 cm petri dish (Brand TPP) with the gelatine poured to completely cover at least one yarn previously trapped inside the dish. The evaluated yarns were made from a diverse range of materials: polyamide (NWIR bc0002 01 from Benecreat), fluorocarbon (2013064 from Caperlan), Fluorinated Ethylene Propylene Copolymer (FEP, FP34-MT-000125 from Goodfellow), perfluoroalkoxy (PFA, 809C027K160 from Polyfluor) and polytetrafluoroethylene (PTFE, 0000242310 - PTFE; Mono Special;*;.0197+ / -.002;*;Natural ;RPL-LLP-Spool;Z5; from Zeus).
[0218] The refractive index for polyamide, fluorocarbon, PTFE, FEP and PEA was respectively 1.539, 1.4, 1.356, 1.344 and 1.34.
[0219] In order to evaluate the light transmission through the fibers within the gelatin matrix, the device was placed under a microscope and illuminated with transmission light. The resulted image was captured by a CCD camera with 12 bits depth. The light intensity was fine adjusted to avoid over-exposure.
[0220] As seen in top of Figure 1 , an intensity profile was taken across the transverse cross section S of the fiber F, and then normalized with the average background light intensity passing through only the matrix. Figure 1 shows the obtained variation of transparency along a fiber section for polyamide (•, circle dots, curve No.1), fluorocarbon (■, square dots, curve No.2), PTFE (♦ , diamond dots, curve No.3), FEP ( ▲ , triangle dots, curve No.4) and PFA ( — , bar dots), with pixels on the X-axis, normalized transparency on the Y-axis.
[0221] The resulting profile reflects the transparency of fibers inside the matrix. As a thread is in a cylinder shape, the light intercepting the oblique interface at the edges is deviated due to a refractive index difference between the fiber material and the matrix. Thus, the deviated light is lost causing a decrease in a light intensity on the CCD camera and in the measured transparency profile.
[0222] As seen in Figure 1 , fibers with a refractive index close to 1.33 (PTFE, FEP and PFA) show less impact on the transparency profile than polyamide in the oblique region.
[0223] When light path is normal to the optical interface, at the fiber center, the absorbance property of the fiber material will only reduce the intensity of light. Although PTFE, FEP and PFA share a similar refractive index, the light going through PTFE never reaches the background light intensity and stays around 90 % while FEP and PFA reach approximately 100 % in the same region of the cylinder (Figure 1).
[0224] Due to the cylinder shape of fibers, the transparency of the composite will depends on the refractive index difference between the fiber material and the matrix, and on the material absorbance of the fiber. Thus, for a gelatin matrix, FEP and PFA both provide better transparency and visibility than other tested materials.
[0225] Example 2: Fabrication by weaving of textiles with different structures usable for the invention, and using fibers optimized according to Example 1.
[0226] Various textile structures were made from two types of material: perfluoroalkoxy (PFA) and polytetrafluoroethylene (PTFE). These materials were used to form structure yarns (support fibers) and removable yarns (removable fibers), respectively.
[0227] The structure yarns were 0.27 mm diameter PFA monofilaments, manufactured by Polyfluor (https: / / www.polyfluor.nl / en / products / wire-cables-and-fibre / fluoroplastic- wires-and-cables / ; article number: 809C027K160). This material had a refractive index of 1.34, a density of 2.15 g / m3and a natural color. To reduce a static charge, an aqueous spin finish was applied before winding the monofilament. This aqueous solution was made up of 18 parts water and 0.8 parts spin finish. This spin finish, whose sole function is to reduce a static charge, was washed off with warm water.
[0228] The removable yarns were 0.5 mm diameter polytetrafluoroethylene monofilaments, manufactured by Zeus (PTFE; Mono Special; *;.0197+ / -.002; *; Natural; RPL-LLP-Spool; Z5), obtained by extrusion. This material had a refractive index of 1.35, a density of 2.2 g / m3, and a natural color. The yarns were selected after evaluating the optical transmission of the materials in the matrix, as shown in Example 1.
[0229] The combination of perfluoroalkoxy (PFA) and polytetrafluoroethylene (PTFE) yarns made it possible to produce textile in a single step, using a weaving protocol in which the warp yarns were PFA and PTFE yarns, and the weft yarns were PFA yarns only. The production was carried out on a manual loom.
[0230] In Figure 2, A) shows the pattern of the weaving design, with the structural yarns (PFA) in light grey and the removable yarns (PTFE) crosshatched. B) shows a rear view of the loom, with the PFA and PTFE warp yarns. C) shows a final structure obtained after weaving, still stretched on the loom, with PFA and PTFE yarns in the warp direction and PFA yarns in the weft direction.
[0231] The weaving system made it possible to manage the distance between the PTFE yarns (cf. Figure 3), and therefore the distance between the channels, by placing them in the different reed’s tooth. The reed used for this production was a reed with 10 teeth per cm, and a yarn was inserted between two teeth. Thus, there were three PFA yarns between each PTFE yarn, around 0.3 cm.
[0232] Figure 3 represents an exemplary scheme of a weaving pattern of the invention, showing from top, channels entangled with support fibers. Specifically, Figures 3A to 3C show weaving drafts. A) illustrates a tie-up of the production. The “tie-up" refers to the connection point between the threading draft and the pedals (or levers) to operate while weaving. B) illustrates a drawing-in of the production. The “drawing -in" refers to a graph that represents how each warp end is drawn through its respective heddle and dent in the reed. C) illustrates a peg plan of one of the woven production structures. The “peg plan" refers to the graphical representation of how the loop will activate the harnesses during weaving. D) illustrates a 2D simulation of the resulting production, seen from the fabric top. The removable yarns 1 are seen in light gray. E) illustrates a code editor, one layer, eleven weft rows. The circles represent the PFA weft yarns, the light grey yarns represent the PTFE warp yarns and the dark grey one represents the PFA warp yarns.
[0233] F) illustrates a 2D top view of the woven structure (angle with +Z: 0 deg; azimuth: 0 deg).
[0234] G) illustrates a 2D cross section view of the resulting production (angle with +Z: 90 deg; azimuth: 0 deg). H) illustrates a 3D simulation of the resulting production (angle with +Z: 45 deg; azimuth: 45 deg).
[0235] Example 3: Comparison by imaging, of chips of the invention prepared from fibers with different number of sub-fibers and different levels of twist
[0236] The PFA fibers chosen in Example 1 were woven as described in Example 2 as simple monofilaments (Figure 4A) or as 3 sub-fibers assembled to form multifilament yarns (Figure 4B). Also, to reduce split of fibers in the assembled multifilament yarn, a twist of 50 twists / m was applied in the Z direction with a Twistec machine (TDM model) (Figure 4C).
[0237] The increase of number of sub-fibers or yarn twist created excessive friction leading to matrix damage when removing the removable yarn as described in Examples 4 and 5 below. Furthermore, the yarn twist introduced overlapping yarns, which subsequently reduced material transparency. Opting for simple monofilaments offered the best compromise by minimizing friction during the removal of the removable yarn and ensuring optimal transparency.
[0238] Example 4: Comparison by imaging of chips of the invention prepared from fibers with different structure and PTFE diameter
[0239] From Example 2, different structures were produced using the PFA fibers chosen in accordance with Example 1. The aim of these structures was to change the path of the PTFE yarn and adjust the stiffness of the PTFE yarn by changing the diameter. The following structures were produced: One PTFE yarn with a diameter of 500 pm was above seven PFA yarns, then below one PFA yarn with a density of 19 yarns / cm (Figure 5A); one PTFE yarn with a diameter of 200 pm was above one PFA yarn, then below one PFA yarn with a yarn density of 8-9 yarns / cm (Figure 5B); and one PTFE yarn with a diameter of 500 pm was above one PFA yarn, then below one PFA yarn with a yarn density of 8-9 yarns / cm (Figure 5C).
[0240] Binocular inspection enabled to check the PTFE yarn path along the woven fabric. An angle between the binocular and the textile revealed undulation in the textile plane when PTFE yarn was above seven PFA yarns then below one PFA yarn (Figure 5D). For a structure with symmetry in the textile plane, one PTFE yarn above one PFA yarn, then below one PFA yarn, undulation was reduced (Figure 5F). Despite having the same structure, undulations were visible for a lower diameter of PTFE yarn (200 pm) due to lower yarn rigidity (Figure 5E). PTFE with a diameter of at least 500 pm may be advantageous to obtain straight channels.
[0241] Example 5: Fabrication of a support suitable for implementation of devices of the invention, with a matrix made of GelMA hydrogel, and textile support prepared according to Example 2.
[0242] Figure 6 illustrates an example of implementation of the fluidic device of the invention, in a GelMA matrix, embedded in a capsule-like design for experimenting cell culture. The device of the invention was made of a 6 cm petri dish 7 (Brand TPP) with 2.1 mm diameter holes previously drilled, four holes for input and in opposite side four holes for output. The holes were located approximately at mid-height in the petri dish wall. A hole guide may be used to point with a pen the correct location for each fabrication batch. After drilling, the petri dish was cleaned with ethanol and dried with an air gun. Then 2.5 g of 1 :10 PDMS 2 (Sylgard™ 184) was dropped in the petri dish 7. A weighing scale may be used to precisely measure the deposited weight to prevent it from overflowing through petri dish holes. Next, the petri dish was put in an oven at 75°C for 1 hour to allow PDMS to cure. Eight pieces of 1 cm silicone tubing 3 (outer diameter (OD): 2.1 mm, inner diameter (ID): 0.5 mm) were put in every drilled hole to ensure a further connection with channels. A 1.5 x 2.5 cm (Length x Width) piece of textile 4 from Example 2 with four removable yarns 1 of 8-10 cm length was put on top of the cured PDMS layer 2 previously cut to fit the textile shape. The removable yarns 1 were threaded through the tubing pieces in the walls of the petri dish 7 and straightened. Then, 600 pL of the earlier prepared 10% w / v GelMA / DPBS with 5%w / w LAP solution 5 (900889-1 G from Merck) was added on top of the textile 4 dropwise with a pipette. The GelMA drop 5 did not exceed the textile area and only spread over the PDMS surface 2. After letting the solution become a gel 5 in around 1 hour at a room temperature, the capsule was exposed to a UV light (28 mW / cm2) for 2 minutes. Then, 15 g of Ecoflex™ Near Clear 00-45, 6 was carefully poured on top of the polymerized GelMA 5 in the capsule and let overnight at room temperature for polymerization.
[0243] The removable yarn 1 was manually removed delicately using tweezers, taking care to keep the pace slow, constant, and always in line with the axis of the chip. Alternatively, a manual linear stage combined with a clamping system holding four PTFE yarns may be used. The micrometric screw of the stage allows to remove four yarns at the same time at precise speed. After extraction, the 500 pm channel was formed inside the capsule textile chip, and microscopic or binocular inspection was performed to check integrity. Using a sterile 3 mL syringe and sterile DPBS (Sigma-Aldrich D8537), the chip channels were gently filled. Using 500 pm PTFE yarns cleaned in ethanol, the ends of the channels were plugged. In a larger-diameter petri dish filled halfway with DPBS, the chip was dipped and sealed with Parafilm® before placing in the fridge at 4°C. Under these storage conditions, the chip was kept for ten days. Before use, the chip was removed from its DPBS bath, dried and the DPBS contained in its channels was replaced with fresh DPBS. The chip was then placed in a large, new, sealed petri dish and subjected to UV light for 30 minutes.
[0244] Figure 7 shows photographs of chips after manufacture. A) shows a photograph of a chip of the prior art with a non-transparent yarn hiding channels. B) shows a photograph of a chip of the invention with a PFE yarn having a refractive index matching that of the GelMA matrix. In comparison to the prior art chip in Figure 7A, the chip of the invention in Figure 7B presents improved transparency and visibility of the channel. Example 6: Culture of endothelial cells and imaging by confocal microscopy, in orqan-on- a-chip devices of the invention, as prepared in Example 5
[0245] <Chip preparation>
[0246] Human Umbilical Vein Endothelial cells (HUVEC, C-12203 from Merck) were cultured and propagated. Initially, HUVEC cells were seeded in a cell culture dish or flask and covered with an appropriate volume of growth medium. The cells were then incubated at 37°C with 5% CO2. To ensure optimal growth conditions, the growth medium was replaced every 2-3 days. Upon reaching 70-80% confluence, the cells were detached from the dish or flask using a trypsin-EDTA solution. After centrifugation to pellet the cells and removal of the supernatant, the cells were resuspended in a fresh growth medium. Subsequently, cell counting was performed, and the cells were seeded into a new dish or flask at the desired cell density. This process was repeated, until the desired number of cells was obtained.
[0247] The day before starting the experiment, eight yarns of PTFE 500 pm were sterilized. In sterile conditions, the chip prepared in Example 5 was filled with DPBS to gently hydrate the hydrogel. It was then stored overnight at 4°C. A splitter chip (one input, four outputs) was prepared in PDMS following the classic manufacturing process. On the day of the experiment, the filling level of the channel was checked, and if needed, it was refilled as before. The chip was then stored for 15 minutes at 4°C. The capsule chip, three needles (0.6 mm OD), and the PTFE yarns were sterilized in an ethanol bath and then under a UV lamp (265 nm) for 40 minutes.
[0248] <Cell preparation>
[0249] First, 2 ml of medium was transferred into 2 x 2 ml Eppendorf tubes. The medium was gently injected into the channels of the capsule using a needle and syringe to remove air bubbles and fill the channels. This was repeated twice, and the capsule was left in the incubator for 15 minutes each time. The confluent cell culture flask was then aspirated, and 15 mL of PBS was added and agitated. After aspirating the PBS, 5 mL of dissociation reagent was added to the cell culture flask, which was then placed in the incubator for 5 minutes. The cells were checked under a microscope to ensure proper detachment, and if needed, the flask was gently shaken. Next, 20 mL of complete culture medium was added to deactivate the dissociation reagent. The cells were thoroughly resuspended, and the cell count in the flask was used to calculate the necessary volume to achieve a concentration of 20M cells / ml. The suspension was transferred to a 50 ml Falcon tube and centrifuged for 5 minutes at 500 G. The supernatant was then discarded.
[0250] <Seeding>
[0251] To start the seeding process, the necessary volume of medium was added to achieve a concentration of 20M cells / ml, and the cells were resuspended. The channels were rinsed once again with fresh medium. The cell suspension, which should be opaque due to the high cell concentration, was injected into the channels, ensuring they were filled with the cell suspension. The ends of the seeded channel were carefully sealed with a 500 pm PTFE thread. The dish was then turned by 90° every 10 minutes around the channel axis, to distribute the cells evenly in the channel, and it was placed in the cell incubator at 37°C, 5% CO2. This process was repeated three times for a total of four seedings and 160 minutes of seeding before the infusion. The capsule was placed in a larger petri dish for easier manipulation and better protection against contamination, and the channels were checked under a microscope. The chip was then connected with the circuit full of PBS or medium. A peristaltic pump with the splitter system was connected to the capsule to flush away unattached cells from the channels using the appropriate medium. After flushing, the exit tubing was transferred to the Falcon with the medium to create a full circuit in the system. The system was left to work, and the cells were allowed to grow for 24 hours or more.
[0252] <Chip imaging>
[0253] To monitor the progress of the experiment and address specific research questions, various imaging methods may be employed. Firstly, the fluidic tests were observed using an Olympus IX70 light inverted microscope equipped with an x4 objective and an Olympus ll-CMT video camera. The “Pylon Viewer” software was used to analyze the captured images, and food dye was employed for visualization of fluid transport in the channels. For the cell viability test, fluorescent microscopy, Nikon Ti Series was used, utilizing either the classic DAPI staining method or a commercial Live / Dead kit (INVITROGEN® LIVE / DEAD™ Cell Imaging Kit (488 / 570) R37601). To investigate the organization of cells within the chip, live labelling was performed, followed by confocal fluorescence imaging, LEICA confocal SP8, which was conducted at the IPGG imaging platform.
[0254] Figure 8 shows observation images of HUVEC cells covering the channels of the chip of the invention after 7 days of perfusion. A) shows bright field microscopy imaging of the top view of the channel. B) shows a cross-section view of the channel in confocal microscopy.
[0255] Confocal microscopy revealed noticeable results. In a double seeding experiment after 7 days of perfusion, endothelialization was apparent on both channel sides (Figure 8B). The average cell density of the upper channel section was 171.5 cell / mm2, and in the lower channel section was 146 cell / mm2.
[0256] Example 7: Preparation of monofilament fibers made of PDMS
[0257] Figure 9 represents an example scheme of a system used in a method to prepare PDMS monofilament fibers. A syringe pump 12 (NE-1000, New Era Pump Systems, USA) with a flow rate of 3 mL / min was used to flow PDMS 2 (Sylgard™ 184, 1 :10 ratio) stored inside a 20 mL syringe 11 . The pump 12 ensured a constant flow of the mixture across a connected tube 13 and a needle 14 previously soaked inside a chamber or bath 15. The steel needle 14 of 1.83 mm inner diameter (14G type) was partially immersed in the bath 15 to avoid any air contact and prevent PDMS 2 from floating at the liquid surface. The bath 15 was filled with canola oil and was heated between 200 and 215°C by a thermostat. At this temperature, PDMS 2 flowing out of the needle 14 started to reticulate and kept the cylinder shape of the needle. A conveyor belt 16 helped to extract at constant speed the produced PDMS monofilament 2’. The extraction speed was chosen to match the syringe pump flow rate. In this example, the linear speed of the conveyor belt 16 was between 8 and 13 m / min. At that time, some oil may remain on a surface of PDMS monofilament 2’. Thus, the monofilament was conveyed to a rinsing bath 17 filled with isopropanol.
[0258] Example 8: Weaving of textile from fibers prepared in Example 7, as the textile of support fibers for devices of the invention
[0259] Figure 10 schematically illustrates insertion of a removable or sacrificial fiber into a woven structure. The direction of the warp and weft threads is respectively indicated by “Wa” and “We”.
[0260] The removable or sacrificial fiber 1 is preferably woven in the weft direction We of the textile or woven structure 11 , which leaves a free length of fiber necessary for its extraction, with greater ease in terms of insertion into the woven structure 11 .
[0261] Optional selvedges may be added at one or both outer side edge(s) of the textile, parallel to the warp direction Wa. Such selvedges may be advantageous in stabilizing the textile once taken from the weaving machine, and ensuring that the removable fiber 1 is held across the entire width of the textile. The selvedges may be woven with the plain weave using the same fiber material as the support fibers.
[0262] In Figure 10, the inserted removable fiber 1 is tied or bound in the woven structure 11 at a binding point 8.
[0263] The woven reinforcements were produced on a 24-frames dobby weaving machine with manual weft insertion (ARM Touch, Handloom Holding, UK), with a warp thread density of 10 ends / cm. The weft yarns We were orthogonal to the warp yarns Wa and were inserted manually using a shuttle. Both weft and warp yarns (We, Wa) were using the same two assembled multifilament yarns made of 24 sub-fibers of 60 Tex each in polycarbonate (PC) material. The removal fiber 1 , in polyamide 6.6 (PA 6.6) or PTFE, was inserted in the weft direction. The fabrics produced were 200 mm long. To bind the removal fiber 1 into the woven fabric 11 , the PDMS filaments from Example 7 were installed on the weaving machine in the warp direction (cf. Figure 11). Figure 11 shows images of woven textiles for implementation of the invention, with a binding point 8 in PDMS. A) shows a textile after weaving, with warp direction Wa and weft direction We. B) shows an enlarged view of binding point 8 in PDMS and the removable fiber 1 in PA 6.6 with a diameter of 500 pm.
[0264] Example 9: Casting of PDMS around the textile prepared in Example 8 to form devices of the invention, and characterization of transparency by imaging
[0265] A vertical resin transfer mold was designed for the production of microfluidic textile chips. It consisted of two plastic plates facing each other, sealed by a gasket. Each plate was drilled to create an inlet and outlet for the PDMS mixture (1 :10 crosslinker). The mold was connected to a vacuum pump (EC4 Compact Composites Vacuum Pump, Easy Composites, UK). Once the mold was evacuated, the PDMS preparation was injected into the mold. The advantage of holding the mold vertically was that the resin interface was forced upwards through the entire woven reinforcement.
[0266] Before the dry woven reinforcement from Example 8 was placed into the mold, its component plates were cleaned with ethanol. The reinforcement was held in place by several pairs of 1 mm-thick magnets, enabling the constant thickness of the chips to be set at 2 mm. After impregnation, the mold was placed in an oven to cure the PDMS matrix (90 min, 75°C).
[0267] To assess the transparency of a PDMS binding point, an observation under a transmission microscope was performed between the PDMS binding point 8 (Figure 12A) and a polycarbonate (PC) binding point 8’ (Figure 12B). Figure 12 shows an observation image of a device impregnated with PDMS and prepared with PC support fibers. A) shows the binding point in PDMS 8 together with the removable monofilament 1 , the support yarn 9 and the dust 10. B) shows the binding point in PC 8’ together with the removable monofilament 1 and the support yarns 9. It revealed a noticeable increase of transparency for the PDMS binding point.
[0268] Example 10: Examples of devices of the invention prepared with continuous or discontinuous sub-fibers, different weave diagrams, different densities of binding points, and characterization of their transparency and visibility of sacrificial or removable yarn
[0269] Figure 13 represents examples of different types of weave diagrams with different numbers of binding points crossing a sacrificial or removable monofilament 1 . The weave diagram is shown in A) with one binding point, B) with two binding points, C) with four binding points, D) with five binding points, E) with six binding points, and F) with eight binding points, respectively for 20 yarns in the warp direction Wa. The width of the textile images corresponds to the weave ratio in the warp direction ( / .e. a total of 20 warp threads Wa). The textile structures were woven with a different number of binding points on the sacrificial or removable monofilament 1. To vary the number of binding points, these structures were designed with a maximized weave ratio on 20 warp threads. Since 200 warp threads were dedicated to weaving the structure, these weaves were repeated 10 times to form the textile. Thus, the woven structure e.g. in Figure 13A, which had one binding point in its weave ratio, ultimately formed 10 binding points (one binding point x ten weave repetitions) on the sacrificial or removable monofilament of the woven structure.
[0270] Depending on the structures, the sacrificial or removable monofilament was linked by 10 (Figure 13A), 20 (Figure 13B), 40 (Figure 13C), 50 (Figure 13D), 60 (Figure 13E), or 80 (Figure 13F) binding points. These structures were designed with binding points forming floats of warp thread of 3, namely the warp thread Wa floats at the binding point by passing over three weft threads We.
[0271] From Example 8, three different structures were explored: satin, twill, and plain weave. These structures utilized up to ten floating yarns between each binding point (cf. Figure 14).
[0272] Figure 14 shows different woven textile structures with a polycarbonate multifilament yarn and a PTFE removable yarn in the center. The structural yarns in a wavy shape cover the removable yarn after PDMS coating. A) shows a twill structure with ten floating warp yarns. B) shows a satin structure with ten floating warp yarns. C) shows a plain weave structure. The removable yarn moved to the side, close to the structural yarns. D) shows a satin structure with five floating warp yarns. The removable yarn did not move during the coating process.
[0273] However, when using a laboratory coating unit type SV for PDMS coating, the deformation of the textile can be observed, leading to a displacement of the removable yarn (Fig. 14C) or structural fibers getting a wavy shape (Fig. 14A-B). The resulting overlapping of structural yarn onto the removable yarn can be reduced by increasing the number of binding points. This helps keep the removable yarn straight in the chip (Fig. 14D). It is important to find the optimal number of binding points that balances the preservation of visualization and the cohesion of the textile structure.
[0274] The visibility corresponds to the surface area of removable monofilament which is not masked by the supporting fibers (warp or weft direction), and is expressed as a percentage. The visibility was measured with Imaged software on five samples of each woven structure designed as seen in Figures 13A) to 13F). The results obtained were averaged.
[0275] Figure 15 illustrates a graph of the visibility (%) of the channel on the Y-axis depending on the number of binding points which bind the removable monofilament in the textile structure on the X-axis. The obtained visibility was 93.2% for the structure with 10 binding points (Figure 13A), 87.4% for the structure with 20 binding points (Figure 13B), 74.9% for the structure with 40 binding points (Figure 13C), 65.7% for the structure with 50 binding points (Figure 13D), 59.3% for the structure with 60 binding points (Figure 13E), and 49.3% for the structure with 80 binding points (Figure 13F). As seen in Figure 15, the more binding points there were, the less visible the removable monofilament was. The decrease in visibility was proportional to the increase in the number of binding points of the textile structures. On the one hand, the slope of the equation obtained by linear regression showed that each binding point (made by the PC support fiber used) removed 0.65% of the visibility of the monofilament in the structure. On the other hand, a y-intercept was 99.8% which corresponds to the visibility of a structure without a binding point ( / .e. x = 0). Namely, the equation was obtained as y = - 0.65x + 99.8, with R2= 0.99.
[0276] The structure with the fewest binding points ( / .e. 10 binding points, Figure 13A) enabled the removable monofilament visible at 93.2%, thus may be considered as the most efficient structure in view of the visibility criterion.
Claims
CLAIMS1. A fluidic device comprising: a matrix with a first refractive index; a network of support fibers, at least some of the support fibers having a second refractive index, and the network being embedded at least partly in the matrix; and a channel embedded at least partly in the matrix and entangled at least partly in the network; wherein the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
2. A method of making a fluidic device, comprising: providing a network of fibers comprising a plurality of support fibers and at least one removable fiber, at least some of the support fibers having a second refractive index; embedding the network at least partly within a matrix having a first refractive index; removing the removable fiber from the matrix to provide at least one channel embedded at least partly in the matrix and entangled at least partly in the network, wherein the first and second refractive indices differ by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
3. The fluidic device of claim 1 or the method of claim 2, wherein the support fibers are unsized, or sized by a sizing material with a third refractive index which differs from the second refractive index by less than 0.05, or less than 0.03, or less than 0.015, or less than 0.01 , or less than 0.005.
4. The fluidic device or the method of claim 3, wherein the third refractive index lies between the first and second refractive indices.
5. The fluidic device or the method of any one of claims 1 to 4, wherein the network of support fibers comprises a textile, and the channel runs along and / or within the textile.
6. The fluidic device or the method of claim 5, wherein the channel has one or more underpasses and one or more overpasses with at least some of the support fibers of the textile, and a ratio x / y is less than 1 / 2, or less than 1 / 3, or less than 1 / 5, or less than 1 / 10, or less than 1 / 20, wherein x is the number of binding points between the channel and support fibers of the textile and y is the total number of the underpasses and the overpasses between the channel and the support fibers of the textile.
7. The fluidic device or the method of claim 6, wherein at least one (possibly at least some, possibly all) of the support fibers that form the binding points is a monofilament fiber, or a multifilament fiber having fewer filaments per fiber than other support fibers of the textile that are multifilament fibers.
8. The fluidic device or the method of claim 6 or 7, wherein at least one (possibly at least some, possibly all) of the support fibers which form the binding points is made of the same material as the matrix.
9. The fluidic device or the method of any one of claims 1 to 8, wherein the support fibers comprise monofilament fibers, preferably having a diameter larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm.
10. The fluidic device or the method of any one of claims 1 to 9, wherein the support fibers comprise multifilament fibers, preferably having fewer than 10 filaments per fiber, preferably fewer than 5 filaments per fiber, at any given transverse cross-section of the fiber.
11. The fluidic device or the method of claim 10, wherein the diameter of the multifilament fibers is larger than 15 pm, or larger than 20 pm, or larger than 50 pm, or larger than 100 pm.
12. The fluidic device or the method of claim 10 or 11 , wherein the filaments of the multifilament fibers of the support fibers have a torsion of less than 1 turn per mm, or less than 1 turn per 5 mm, or less than 1 turn per cm.
13. The fluidic device or the method of any one of claims 1 to 12, wherein at least some of the support fibers are made of PDMS.
14. Use of the fluidic device of any one of claims 1 , 3 to 13 for or in one or more of:cell culture; an organ-on-a-chip and / or a microfluidic chip; a wearable material, a garment and / or a part of a wearable material or a garment; an analytical device or part of an analytical device; a packaging or part of a packaging; an instrument with a temperature exchanger or part of an instrument with a temperature exchanger; a temperature control device or part of a temperature control device; a protection device or a part of a protection device, preferably a portable protection device or a part of a portable protection device; an artificial skin; and a wound dressing.
15. A method of imaging a compound comprising: providing the fluidic device of any one of claims 1 , 3 to 13; introducing the compound into the channel of the fluidic device; and placing the fluidic device in an observation field of an imaging device to obtain an image of the compound.
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