Fluidic devices with at least one actionnable fiber

Abstract

Disclosed is a minifluidic device including a matrix, an elongated guiding duct embedded at least in part in the matrix, with at least one port to the outside of the matrix, a movable fiber at least partly contained in the guiding duct, and able to undergo within the guiding duct, and at least along some part of the fiber, at least one action selected among a sliding, or a deformation, or a rotation and at least one of the movable fiber or the guiding duct is elastic or is non linear along at least part of its length, or at least part of the matrix is elastic.

Claims

1. A minifluidic device, comprising: actuation means; a matrix; an elongated guiding duct embedded at least in part in said matrix with at least one port to the outside of the matrix, all of a perimeter of said guiding duct, on at least part of a length of said guiding duct, being surrounded by said matrix; a movable fiber at least partly contained in said guiding duct, said movable fiber being slidable so as to undergo a sliding with respect to the matrix within said guiding duct, at least a portion of a length of the movable fiber being elastic or non-linear, or at least part of the matrix being elastic such as to be one of: a hard elastic material having an elastic modulus comprised between 100 kPa and 100 MPa, a moderately hard elastic material having an elastic modulus comprised between 20 and 500 kPa, and a soft elastic material having an elastic modulus comprised between 50 Pa and 100 kPa, wherein said actuation means induces onto said movable fiber at least one of a pulling or a pushing, at least along a part of said fiber.

2. The minifluidic device according to claim 1, further comprising: at least one zone in fluidic connection with said guiding duct, said zone being selected from: a fluid drop area, a reservoir, and a chamber.

3. The minifluidic device according to claim 1, wherein the means for actuation are mechanical means that induce onto said movable fibers at least one of a pulling or a pushing.

4. The minifluidic device according to claim 1, wherein a multiplicity of said movable fibers are at least partly contained in a multiplicity of said guiding ducts and are slidable so as to undergo a sliding within said guiding ducts and along said fibers.

5. The minifluidic device according to claim 4, wherein at least some of said movable fibers re mechanically related, and actuatable together by a single manipulation means.

6. The minifluidic device according to claim 1, wherein the movable fiber comprises at least one zone presenting fluid flow properties different from fluid flow properties in a part of the fiber different from said at least one zone.

7. The minifluidic device according to claim 1, wherein at least one of the guiding duct, the matrix, and the movable fiber is flexible or semi-flexible.

8. The minifluidic device according to claim 1, further comprising: at least one channel intersecting with the guiding duct, or at least one channel network in fluidic communication with the guiding duct.

9. The minifluidic device according to claim 1, wherein the actuation of said movable fiber within the guiding duct modifies a fluidic connectivity, or at least one fluidic resistance, within a channel or within a channel network of the device.

10. The minifluidic device according to claim 1, further comprising: a textile component embedded in said matrix, wherein the guiding duct is entangled with said textile component.

11. The minifluidic device according to claim 1, wherein the path of the guiding duct is non-linear or is three-dimensional, or the guiding duct is in fluidic connection with a non-linear or three dimensional channel or with a non-linear or three-dimensional channel network.

12. An instrument comprising a device according to claim 1, said instrument being any of, or any combination of, an analytical instrument, a medical instrument, a functional clothing, a wearable instrument, an implantable instrument, a monitoring instrument, a processing instrument.

13. A kit for preparing, connecting or using a minifluidic device or instrument, comprising: a minifluidic device according to claim 1; and at least one component selected among: a fluid, a chemical product or a biological product, and an additional physical component.

14. A method of initiating, or modifying, or controlling, or stopping fluid flow in a fluidic device according to claim 1, wherein said method comprises at least one of a pulling along the movable fiber or a pushing along the movable fiber.

15. A method for analyzing any of a biological, a physical or a chemical agent, or for monitoring a process, an environment, a living species, a condition of a patient or for producing a product, or for discovering or testing a drug or an active product, wherein said analysis, monitoring, production, discovery, or test, is performed using a device according to claim 1.

16. The device of claim 2, wherein said fluid drop area or reservoir or chamber is enclosed at least in part within said matrix or supported by said matrix.

17. The device of claim 6, wherein the zone is selected from a group consisting of: a hole, a via, a lumen, an indentation, a change in cross-section, a porous zone, a zone of material permeable to fluids, and a gel.

18. The minifluidic device according to claim 2, wherein a multiplicity of said movable fibers are at least partly contained in a multiplicity of said guiding ducts and are slidable so as to undergo a sliding within said guiding ducts and along said fibers.

Description

FIGURES

(1) It will be convenient to further describe the invention with respect to the accompanying figures which illustrate preferred embodiments of the three dimensional microfluidic system according to the present invention. Other embodiments of the invention are possible, and consequently, the particularity of the accompanying figures is not to be understood as superseding the generality of the preceding description of the invention.

(2) FIG. 1 shows a schematic fabrication protocol for a microfluidic chip with a single straight microchannel, taking advantage of support fibers embedded in the matrix.

(3) FIG. 2 shows a schematic illustration of the use of a chip of the invention as an integrated pump.

(4) FIG. 3 shows a schematic illustration of a chip of the invention with a nonlinear guiding duct, and a method to prepare it.

(5) FIG. 4 shows four time-lapse pictures of the same microfluidic chips made with a matrix made of a hydrogel and naturally sourced material: agarose.

(6) FIG. 5 shows another schematic fabrication protocol for a microfluidic device of the invention with non-linear guiding duct.

(7) FIG. 6 shows a schematics of the fabrication of a microfluidic chip of the invention using a hybrid structure comprising microchannels partly open and partly filled with a wicking material.

(8) FIG. 7 is a picture that shows a particular realization of an embodiment structure comprising microchannels partly open and partly filled with a wicking material.

(9) FIG. 8 shows a schematic fabrication protocol for the microchip with one movable fiber combined with a microchannel prepared by microlithography.

(10) FIG. 9 shows a picture of a microchip resulting from the protocol schematized in the FIG. 8.

(11) FIG. 10 shows two pictures of a first application of this microchip.

(12) FIG. 11 shows a picture of a movable fiber prepared by 3-D printing.

(13) FIG. 12 shows four pictures illustrating an example for operation of a device of the invention, with a movable fiber as described in FIG. 10.

(14) FIG. 13 shows a picture of an embodiment comprising two movable fibers connected together, prepared by 3D printing

(15) FIG. 14 provides two pictures illustrating examples of movable fibers connected together by interweaving in a textile.

(16) FIG. 15 provides a schematic illustration of an example of a multiple valve for sequential filling of a channel, constituted using 4 movable fibers of the invention, connected together.

(17) FIG. 16 shows the use of a movable fiber with a flattened part, as a valve allowing opening and closing of transport of species and fluids between two parts of a chamber.

(18) FIG. 17 provides examples of via usable along movable fibers of the invention with two via in the shape of through-holes, and their use to connect two parts of a channel

(19) FIG. 18 presents example of another movable fiber with via, prepared by micromilling

(20) FIG. 19 presents a few exemplary embodiments of movable fibers, with via of different shapes.

(21) FIG. 20 presents the schematic operation of a device of the invention comprising an integrated pump based on three movable fibers, two of which are connected together, and the third actuated synchronously with the first two.

(22) FIG. 21 presents embodiments of movable fibers used to operate the device presented in FIG. 20, prepared by 3D printing

(23) FIG. 22 presents a schematics of a microfluidic network or instrument according to the invention and the schematic operation this device.

(24) In the figures, a same object is designated with a same reference on distinct figures.

EXPERIMENTAL PART

Example 1

(25) The first example, shown in FIG. 1, illustrates one of the fabrication methods employed to create a component or chip of the invention, using a textile support [1], and containing one single straight guiding duct [4] comprising a movable fiber [2], and the motion of said movable fiber. First, a fabric [1], made with support fibers [1.1] is halfway woven with a loom (Ashford, NZ). Apart from the looming, a movable fiber [2] is inserted into two short silicone tubings [3], which serve as external ports in the resulting chip. Together with the tubings [3], the movable fiber [2] is then added at the end of the half woven fabric along the weft support fiber [1.2] by replacing one passage of the weft fiber, and the other half of the fabric is continued to be woven as shown in FIG. 1a.

(26) After completion of the weaving the fabric [1] is detached from the loom and immerged into a matrix precursor material [5]. The matrix precursor material wicks the support fibers [1.1, 1.2] prior to be hardened and its spatial extension is limited to the fabric [1], as shown in FIG. 1b.

(27) The movable fiber [2] can then be moved within the matrix [5] and the embedded fabric [1], as shown in the FIG. 1c. In FIG. 1c, the guiding duct [6] defined after removal of the movable fiber [2] remains empty.

Example 2: Use of the Invention as an Integrated Pump

(28) The device of FIG. 2 is prepared the same way as for example 1, except for two features:

(29) First, only one end of the movable fiber [2] is inserted into a silicone tubing [21]. The other end is partially inserted into the shed during the picking, and is thus protruding from the surface of the textile [1]. After the matrix [5] hardening, the movable fiber [2] protrudes from the matrix [5]. A drop of colored water [22a] is put on the fabric, at the place [22] where the movable fiber [2] exits the fabric, and this place defines a fluid drop area [22]. Then, the movable fiber [2] is pulled and partly removed, which makes the liquid enter into the guiding duct [23], i.e. a space created by the fiber [2], like a microsyringe would (see FIG. 2b).

(30) For this example, the support fibers of the textile [1] are white cotton threads (n 7, Phildar, FR). The movable fiber [2] is a fluorocarbon monofilament fishing line (Varivas Super Tippet, 3X, Morris Co, JP) with a 200 m diameter. The matrix [5] used is a 10:1 (weight par weight) mix of polydimethylsiloxane (PDMS) base and its curing agent (Sylgard 184, Dow Corning, USA). The fabric [1] is immerged into a fresh mix of the base and the curing agent, then put under a vacuum belt for 1 hour, and then suspended in an oven at 65 C. for 5 h.

Example 3

(31) The third example of the invention illustrates the possibility to create a guiding duct with a tortuous design, as shown in FIG. 3. The fabrication process remains identical to the one described in the first example, except that entangling of the movable fiber [2] with the support fibers [1.1] and [1.2] is performed in two steps. During the picking, the movable fiber [2] doesn't go through the entire shed as shown in FIG. 3a. FIG. 3b shows that the movable [2] fiber is partially reintroduced into the next sheds [8], until it reaches one extremity of the fabric [9]. Of course this process can be performed manually, or in an automated manner, using machines of the textile industry such as Jacquard loom. After impregnation with a matrix precursor material [5], matrix solidification and retrieval of the movable fiber [2], the guiding duct [10] has a path that folds back by 180, as shown in FIG. 3c. Two ports [3] are located at the extremities of the guiding duct [10], parallel to an axis of the fabric [1]. The ports [3] are constituted of silicon tubings coaxial with the extremities of the guiding duct [10].

Example 4

(32) Example 4 illustrates the ability to use a hydrogel as matrix. For this example, the matrix is made of a 4% agarose gel, as shown in FIG. 4a. A mix of 2 g of agarose (UltraPure Agarose, Invitrogen) and 50 ml of water is heated until the agarose is dissolved. The fabric [1] described in Example 1, with a movable fiber [2] interwoven in it, is immerged rapidly into the agarose solution until the solution wicks through the fabric [1], and left at room temperature for 20 minutes to gelify the agarose. The movable fiber [2] is then removed, in order to create a guiding duct [10].

(33) When a drop of colored water [7] is introduced in the microchannel by a micropipette tip connected to a micropipette, the solution follows first the microchannel [29] as shown in FIG. 4b. After some time, the solution diffuses slowly into the hydrogel matrix as shown in FIG. 4b-d. These three pictures are taken with an interval of 5 minutes between each other.

Example 5

Example 5Part a

(34) First, movable fibers [30] are sewn into the central part [31] of a fabric [1] made with support fibers [32]. Holes [33] are punched in an adjacent part [34] of the fabric [1], as seen in FIG. 5 a. This part is then folded above the central part [31] of the fabric [1] and the ends of the movable fibers [30] are passed through the holes [33]. The last third of the fabric [35] is folded under the central part [31] as shown in the FIGS. 5 b and 5 c.

(35) The fabric is then immersed into a matrix precursor material [36]. The matrix precursor material [36] wicks the support fibers [32] and its spatial extension is limited to the fabric [1]. The matrix precursor material [36] is hardened to a solid in a known manner.

(36) To obtain a microchannel network [37] inside the matrix-impregnated fabric, the movable fibers [30] are retrieved from the fabric [1] as shown in FIGS. 5 d and 5 e.

(37) An embodiment of the microfluidic chip was made with this protocol. For this example, the fabric used [1] is a microfiber sheet. The movable fiber [30] is a fluorocarbon monofilament fishing line (Varivas Super Tippet, 3X, Morris Co, JP) with a 200 m diameter. The matrix precursor material used [36] is a 10:1 mix of polydimethylsiloxane (PDMS) base and curing reagent (Sylgard 184, Dow Corning, USA). The fabric [1] is immersed into a fresh mix of base and curing reagent, then put under a vacuum belt for 1 hour, and then suspended in an oven at 65 C. for 5 h. The microchannels created [37] are easily filled with a fluid by following the protocol of example 5 and the two crossing microchannel [37] and [38] which can acting as guiding ducts are connected together.

Example 5Part B

(38) This example, depicted in FIG. 6, illustrates embodiments of the invention comprising partly open flow paths, comprising microchannel arrays in part fluidically open, and in part filled with a porous material, defining a wicking flow path. This also illustrates the possibility to use capillary wicking as a driving force within devices of the invention. For this example, we use a sewn chip described in Example 5A. This microfluidic chip contains a first movable fiber [39], here a nylon fishing line with a diameter of 200 m, and four movable fibers [40], here nylon fishing lines with a diameter of 100 m. Each of the latter movable fibers [40] is embedded twice in the microfiber sheet [41] making a loop [42] on one side of the chip, as shown in FIG. 6a.

(39) After embedment of the microfluidic chip with a matrix precursor material, here a PDMS matrix, and hardening of the matrix, the first movable fiber [39] is removed from the microfluidic chip, and colored water is introduced in the created channel [43], for instance by following the protocol presented in example 5, or thanks to an external pumping means. Four polyester threads [44] (Gtermann, 110 yds/vgs), which have wicking properties for water and aqueous solutions, are then passed in the loops of the 4 nylon fishing lines [42]. Pulling on these nylon fishing lines [42] allow the polyester thread to enter inside the channels [45] created by the removal of the 100 m nylon fishing lines. These channels [45] thus play the role of guiding ducts for the fishing lines [42] and the polyester threads [44] (FIG. 6).

(40) FIG. 7 shows the operation of an embodiment prepared by this method. The PDMS embedded textile [41] supports the device. Colored water [48] is introduced in channel [43], thanks to the pumping effect previously explained in example 5. When the liquid contacts the polyester threads [44], it is wicked by capillary effect, and is transported by wicking along said threads [44], until it can be seen as a darker zone on the threads protruding from the chip, at location [46] on FIG. 17.

Example 6

(41) This example describes a microfluidic chip of the invention prepared without support fibers or textile. The first embodiment of the invention is shown in FIGS. 8 and 9 in which a movable fiber is used in order to separate a microchamber into two compartments.

(42) FIG. 8 shows the fabrication process employed to create such a microfluidic chip. Firstly, a pattern comprising a 2 mm-wide microchamber [51], two loading channels [52] connecting said chamber with loading ports [55], and two 70 m-wide guiding ducts [59] is micromachined with a height of 80 m on a brass plate [50] by micromilling, and used as a mold [50]. A mixture of PDMS and its curing agent at the ratio of 10:1 (w/w) [53] is degassed, poured on the brass mold [50], and reticulated at 65 C. for 4 hours (FIG. 8a). After being hardened, the PDMS block [60] is demolded and four inlets [54] are punched in it (FIG. 8b).

(43) A movable fiber [56] made of fluorocarbon with a diameter of 86 m is inserted in the middle of the microchamber [51] along the two guiding ducts [59] on the obtained PDMS block, and further embedded in the block by using a needle [62], with its extremities piercing out from the block [57] (FIG. 8c). The PDMS block [60] is then bonded to a substrate [58], either a bare glass slide or a PDMS-coated glass slide, with the microchannel side down, by using oxygen plasma (FIG. 8d). FIG. 8e schematizes the top view of the final microfluidic chip [61], whereas FIG. 9 shows a picture of a real microfluidic chip.

Example 7

(44) This example shows an application of the embodiment described in example 6. Here, the microfluidic chip is used to position neuronal cell bodies [13] on one side of the microchamber [11], and to guide axons into the other side, by using a micro-patterned substrate.

(45) After completing a microfluidic chip as described in Example 6 (FIG. 9), one side [14] of the whole microchamber [11] divided into two by the movable fiber [12], is filled with a culture medium containing neuronal cells [13], whereas the other side [16] is filled with a medium without cells (FIG. 10a). This filling is performed thanks to the inlet (reference [57] on FIG. 9) on each side. As shown in FIG. 10a, the neuronal cells are positioned and attached on one side of the guiding duct. The movable fiber [12] is then removed from the guiding duct by pulling from one of its extremities. After 6 days of cell culture at 37 C. with 5% CO.sub.2, axons [15] are successfully guided toward the other side of the channel [16] by a micro-pattern on the bottom substrate. FIG. 10b shows the immunofluorescence image of tau protein, which is abundant in axons. Note that all the cell bodies remain in the original side of the microchamber [14] (FIG. 10b).

Example 8

(46) This example shows another technical solution to compartmentalize a microchannel, using another type of moving fiber.

(47) Instead of using a conventional fiber, the movable fiber here is a thin bar of plastic [17], as shown in FIG. 11. In this embodiment, the fiber [17] was prepared by 3D printing, but any other fabrication means known in the art could be suitable, such as molding, casting, micromachining, lithography, and the like. FIG. 12 a, b, c, d show the top view of a microchamber [18] with the 3D-printed bar [17] inserted in the channel along a guiding duct [17a] made of PolyDiMethyl Siloxane, an elastomeric elastic material. On FIG. 12a, the movable fiber compartmentalizes the microchamber. One side [19] is filled with water, whereas the other side [20] is filled with orange ink. FIG. 12 b, c and d illustrate the removal of the movable fiber and the diffusion of the ink into the upper part [19]. For visibility, on FIG. 12, the end of the movable fiber [17] is indicated by white arrows.

Example 9

(48) Movable fibers can be linked together in order to allow the opening or closing of several compartments with a single move. This example shows two technical solutions to this linking. On FIG. 13, two 3D-printed movable fiber [71] are attached to a support structure [72]. On FIG. 14, four nylon movable fibers [73] are loomed in a fabric structure [74]. FIG. 14b shows the possibility to use several movable fibers [73] with different lengths, linked to the same support structure [74]. The schematic on FIG. 15 illustrates the use of such movable comb [75] for a sequential filling of a microchannel [76]. As the movable comb is pulled out of the chip, as shown on the FIG. 15 b, c, d, movable fibers [73a] are removed from the microchannel [76], by sliding along the guiding ducts [73b], the liquid [77], initially in the chamber [78] fills sequentially the whole microchannel.

Example 10

(49) This example shows another functionality of the chip described in Example 6, using a movable fiber with non-uniform thickness along its length. The system can be used as a valve that can be opened and closed repeatedly. The movable fiber blocks or lets fluid pass from one side of a microchannel to the other, depending on the thickness of the fiber that separates the microchannel into two, by moving the fiber along its length.

(50) A fluorocarbon movable fiber [80] used in this example has originally a homogenous diameter of 86 m, which is 6 m larger than the microchannel height. Some part [81] of its length are flattened to have a smaller thickness than the microchannel height by pinching with tweezers. First, the movable fiber [80] is positioned in the guiding duct [82] with its flattened parts [81] away from the intersection [83] with the microchamber. In this configuration, which corresponds to a closed state of the valve, the microchamber is initially separated into two compartments. One compartment [84] is filled with colored water and the other compartment [85] is filled with non-colored water. As shown in FIG. 16a, there is no leakage between the two compartments in this configuration. Next, the fiber [80] is moved along the guiding duct [82] so that the flattened parts [81] are brought inside the guiding duct [82]. This configuration corresponds to an open configuration of the valve. As shown in FIGS. 16b and 16c, colored water [84a] crosses the movable fiber [80] through the flattened parts [81] of the movable fiber. This valve can be closed again by moving the flattened parts outside the guiding duct [82], as shown in FIG. 16d.

Example 11

(51) This example shows another technical solution to create a valve in a microchannel, using a movable fiber [86] with via [87], in the same configuration as Example 9.

(52) The movable fiber here is a thin bar of plastic [86] with via [87], as shown in FIG. 17a. In this embodiment, the fiber was prepared by 3D printing, but any other fabrication means known in the art could be suitable, such as molding, casting, micromachining, lithography, and the like. FIGS. 17b and c show the top view of a microchannel [88] with a 3D-printed movable fiber [86] inserted into a guiding duct [85]. FIG. 17b illustrates a closed-position of the valve. All the vias [87] are located outside the microchamber [89] in the guiding duct [85], and the microchamber [89] is hermetically separated into two compartments. FIG. 17c shows an open-position of the valve. Sliding the 3D-printed element allows the via [87] to be displaced to the channel or guiding duct [88] joining the chambers, and create a fluidic connection between the right side [88a], and the left side [88b]. In this position, the two compartments communicate through the via [87] and the ink can diffuse on the previously inaccessible part of the microchannel.

Example 12

(53) This example shows different movable fibers with a via. FIG. 18 illustrates a technical solution to create a rectangular movable fiber [86] by micromilling. A planar copper sheet of 250 m is taped to a metallic support and milled by a tool with a diameter of 1 mm. Two vias [87] are then created with a tool with a diameter of 200 m.

Example 13

(54) FIG. 19 illustrates different exemplary embodiments of via in a movable fiber, with various shapes and positions: a circular fiber [90] with a indentation [91] (FIG. 19a), a rectangular and transversal via [92] in a circular fiber [93] (FIG. 19b), a via [94] between two adjacent planes [95] of a square fiber [95a] (FIG. 19c) and a via with one inlet [96] and two outlets [97] in a square fiber [98] (FIG. 19d).

Example 14

(55) This example describes an exemplary embodiment of an integrated pump, operating thanks to three movable fibers [100a, 100b, 100c] of the invention, two of which [100a, 100b] are connected together, and a third one [100c] being actuated synchronously with the first two. The two linked movable fibers [100a, 100b] present via [101a, 101b], and the third movable fiber [100c] does not present a via. The pump operates as shown on FIG. 20. On FIG. 20b, the movable fiber [100c] is pulled out of the microchannel [102] and sucks the liquid from the inlet [103] through the upstream via [101a], like a microsyringe. The linked movable fibers [100a, 100b] are then displaced (FIG. 20c) by pulling the support structure [104], the downstream via [101b] is now in the microchannel [102]. The movable fiber [100c] is then pushed in the microchannel [102], pulling the liquid through the downstream via [101a] (FIG. 20d). The linked movable fibers [100a, 100b] are then pulled out in order to place the upstream via [101b] in the microchannel [102] (FIG. 20e). The cycle can be repeated to induce a pumping from the inlet to the outlet. FIG. 21 shows a 3D-printed embodiment of this movable fiber pump, with the central movable fiber [100c] mobile with respect of the two linked fibers with vias [100a, 100b].

Example 15

(56) This example shows an application of the invention. A microfluidic network including a multiplicity of microchannels [108] and a multiplicity of microchambers [107] is represented on FIGS. 22a and 22b. A movable fiber [104] with indentation [105], capable of sliding along a guiding duct [109], closes or opens microchannels [106] connected to microchambers [107]. FIG. 22a shows an open state of the system, enabling the loading of the microchambers [107] from the loading microchannels [108]. After loading, the microchambers [107] are isolated by sliding the movable fiber [104] to the close state of the system, as shown on the FIG. 22b. Then, each chamber [107] is insulated, and can be used for instance to perform digital PCR and single cell experiments.