Collector collecting liquid samples on paper for microfluidic systems, and microfluidic system thereof

Abstract

The invention relates to an effluent collector (5, 5') for recovering effluents in the form of a suspension or solution at the outlet of a microfluidic device (3), comprising: - at least one absorbent paper (8, 8') for receiving the effluents, the absorbent paper being configured such that the received effluents migrate by capillarity into the absorbent paper and then dry, depositing solid objects or the dissolved molecules contained in the effluents on the fibres of the absorbent paper, - a rotating support (7, 7') extending along a longitudinal axis (X, X') and on which the absorbent paper is deposited, the rotating support being configured to move the absorbent paper relative to the discharge duct.

Description

[0001] Description

[0002] Title: Paper-based liquid sample collector for microfluidic systems, Associated microfluidic system.

[0003] Technical field

[0004] The present invention relates to the field of microfluidic systems. In particular, the present invention relates to effluent collectors for microfluidic systems.

[0005] Prior art

[0006] A microfluidic system is a system suitable for manipulating geometrically constrained fluids at submillimeter, particularly micrometer, length scales.

[0007] Figure 1 illustrates a standard microfluidic system 1. The system 1 comprises an injection device 2 connected upstream to a microfluidic device 3 by a tributary conduit 4 in order to supply said microfluidic device 3 with a fluid of interest.

[0008] The system 1 also comprises an effluent collector 5 connected downstream to the microfluidic device 3 by an effluent conduit 6 in order to recover the effluents leaving the microfluidic device 3.

[0009] The effluents recovered by the collector 5 may form samples intended to be analyzed, for example to study their nature and / or their composition. These samples may be synthesis products of a chemical or biological reaction or suspensions comprising microbiological objects.

[0010] However, the continuous recovery of liquid samples by conventional effluent collectors 5 is tedious and complex. In addition, the space occupied by samples recovered by conventional effluent collectors 5 is voluminous.

[0011] Furthermore, conventional effluent collectors 5 are not necessarily suitable for the storage and preservation of samples in the form of microbiological suspension without degradation over time. This is particularly problematic when the analysis of the recovered samples must be postponed, for example because the systems necessary for said analysis are not immediately accessible. Generally, the recovered samples are frozen in order to preserve them, however this freezing entails a significant additional energy cost. Recently, the democratization of open source electronic prototyping and the rise of 3D printing have enabled the development of new low-cost effluent collectors allowing automated and continuous recovery of samples from microfluidic devices [1], [2], [3] and [4].Samples are collected in liquid state in containers, for example microtubes or test tubes.

[0012] However, the containers in which these new effluent collectors collect samples quickly become bulky and difficult to handle when accumulated in large quantities. They are also not suitable for storing samples in suspension form including microbiological objects, as storage is over long periods and without degradation of the samples.

[0013] There is therefore a need for an effluent collector suitable for recovering, particularly continuously, samples in suspension form by storing them in a space-saving, easily handled manner and allowing preservation without degradation of the samples over time.

[0014] The aim of the invention is to respond, at least in part, to this(these) need(s).

[0015] Statement of the invention

[0016] To do this, the invention relates to an effluent collector for recovering effluents in the form of suspension at the outlet of a microfluidic device, comprising:

[0017] - at least one absorbent paper for receiving the effluents, the absorbent paper being configured so that the effluents received migrate by capillarity into the absorbent paper and then dry by depositing solid objects or dissolved molecules contained by the effluents on the fibers of the absorbent paper,

[0018] - a rotating support extending along a longitudinal axis and on which the absorbent paper is mounted, the rotating support being configured to set the absorbent paper in motion relative to the discharge duct.

[0019] By "absorbent paper" is meant here and within the scope of the invention, an assembly of natural or synthetic fibers shaped into a sheet which is capable of absorbing by capillarity and retaining liquids. According to an advantageous embodiment, the collector comprises at least one discharge conduit comprising one end opening onto the absorbent paper and another end intended to be connected downstream to the microfluidic device.

[0020] Preferably, the rotating support is configured to move the absorbent paper between a first position, in which the discharge conduit comprises an end opening onto a first portion of the absorbent paper, and at least a second position, in which the discharge conduit comprises an end opening onto a second portion of the absorbent paper different from the first portion.

[0021] Preferably, the absorbent paper comprises at least one portion wound around a winding axis, the rotating support being configured to rotate said wound portion of the absorbent paper around the winding axis.

[0022] According to an advantageous embodiment variant, the absorbent paper comprises a plurality of sampling zones delimited from one another by a marking, preferably the marking being a hydrophobic ink drawing or a relief, preferably the sampling zones being aligned along the length, or respectively the width, of the absorbent paper extending transversely, respectively parallel, to the longitudinal axis of the absorbent paper.

[0023] Preferably, the absorbent paper is porous, for example a filter paper or a cellulose-based or nitrocellulose-based paper.

[0024] According to another advantageous embodiment variant, the absorbent paper comprises functionalized portions for selecting, concentrating and detecting molecules of interest among the solid objects contained by the effluents so that only said molecules of interest are deposited and preserved on the fibers of said portions during drying of the effluents, preferably the molecules of interest being chosen from DNA, RNA, peptides, proteins and / or antibodies.

[0025] Preferably, the absorbent paper is sterile.

[0026] More preferably, the rotating support is made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS).

[0027] Advantageously, the surface of the rotating support on which the absorbent paper is deposited is hydrophobic. According to an advantageous configuration, the rotating support is cylindrical in shape with a longitudinal axis (X) and the absorbent paper is wound on the lateral surface of the rotating support so as to be rotated by a rotation of the rotating support around said longitudinal axis (X).

[0028] According to an advantageous embodiment, the rotating support comprises:

[0029] - a rolling shaft which is movable in rotation about its longitudinal axis and around which the absorbent paper is wound, the inner end of the roll formed by the absorbent paper being fixed to the rolling shaft so that the rotation of said rolling shaft causes the roll to unwind,

[0030] - a rewinding shaft movable in rotation around its longitudinal axis and to which the external end of the roll formed by the absorbent paper is fixed so that the rotation of said rewinding shaft causes the rewinding of the absorbent paper 8' around said rewinding shaft, the unwinding shaft and the rewinding shaft being mechanically linked together so that their rotations are synchronous, at the same speed and in the same direction.

[0031] According to an advantageous variant, the rotating support comprises a guide shaft movable in rotation around its longitudinal axis and on which the unrolled portion of the absorbent paper between the unrolling and rewinding shafts is supported, the guide shaft being mechanically linked to the unrolling and rewinding shafts so that their rotations are synchronous, at the same speed and in the same direction.

[0032] According to an advantageous variant, the collector comprises a motor for rotating the rotating support, preferably the motor being a stepping motor, preferably the effluent collector comprising a control unit for controlling the rotation of the rotating support by the motor.

[0033] According to an advantageous variant, the collector comprises a housing on or in which the rotating support is mounted.

[0034] According to an advantageous variant, the collector comprises a holding bar fixed relative to the longitudinal axis (X, X') of the rotating support and comprising at least one through opening into which the evacuation conduit is inserted.

[0035] The invention also relates to a microfluidic system comprising:

[0036] - a microfluidic device, - an injection device connected upstream to the microfluidic device, in order to supply said microfluidic device with a fluid of interest,

[0037] - an effluent collector as described above, the effluent collector being connected downstream to the microfluidic device in order to recover the effluents leaving the microfluidic device.

[0038] The invention also relates to a method for manufacturing an effluent collector as described above, comprising a step of manufacturing the rotating support by 3D printing, preferably by 3D filament printing, preferably the filament being made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS).

[0039] The invention also relates to the use of a collector as described above for recovering effluents in the form of a suspension or solution at the outlet of a microfluidic device.

[0040] The invention therefore essentially consists of an effluent collector recovering, on absorbent paper, the effluents in the form of suspension at the outlet of a microfluidic device. The invention is thus based on the migration of the liquid phase of the suspensions by capillarity to collect the objects contained in said suspensions in the absorbent paper.

[0041] Unlike other storage media described in the prior art, paper is compact, easy to handle, and allows objects placed within it to be stored for a long period without the need for freezing.

[0042] The effluent collector according to the present invention allows the movement of the absorbent paper relative to the recovery conduit from which the effluent arrives at the outlet of one or more microfluidic devices. Thus, the effluent collector according to the present invention is suitable for continuous, even automated, collection, or even over long periods, of said effluents.

[0043] Furthermore, the effluent collector according to the present invention is simple to manufacture, inexpensive, and can be adapted to various microfluidic systems.

[0044] Other advantages and characteristics will become more apparent upon reading the detailed description, given for illustrative and non-limiting purposes, with reference to the following figures.

[0045] Brief Description of the Drawings [Fig 1] Figure 1 is a schematic perspective view of a microfluidic system comprising an injection device, a microfluidic device and an effluent collector.

[0046] [Fig 2] Figure 2 is a perspective view of an effluent collector according to the present invention.

[0047] [Fig 3] Figure 3 is a perspective view of a rotating support of an effluent collector according to Figure 2.

[0048] [Fig 4] Figure 4 is a perspective view of a gable of an effluent collector according to Figure 2.

[0049] [Fig 5] Figure 5 is a perspective view of a housing of an effluent collector according to Figure 2.

[0050] [Fig 6] Figure 6 is a perspective view of a holding bar of an effluent collector according to Figure 2.

[0051] [Fig 7] Figure 7 is a perspective view of another embodiment of an effluent collector according to the present invention.

[0052] [Fig 8] Figure 8 is a perspective view of a master shaft of the rotating support of an effluent collector according to Figure 7.

[0053] [Fig 9] Figure 9 is a perspective view of a slave shaft of the rotating support of an effluent collector according to Figure 7.

[0054] [Fig 10] Figure 10 is a perspective view of a housing of an effluent collector according to Figure 7.

[0055] [Fig 11] Figure 11 is a perspective view of a holding bar of an effluent collector according to Figure 7.

[0056] [Fig 12] Figure 12 is a schematic perspective view of cutting a strip of paper to obtain absorbent paper for an effluent collector according to the present invention.

[0057] [Fig 13] Figure 13 is a schematic perspective view of a felt-tip pen marking of a paper strip to obtain absorbent paper for an effluent collector according to the present invention. [Fig 14] Figure 14 is a schematic perspective view of a laser marking of a paper strip to obtain absorbent paper for an effluent collector according to the present invention.

[0058] [Fig 15] Figure 15 is a schematic perspective view of a paper strip comprising sampling areas delimited from each other by markings.

[0059] [Fig 16] Figure 16 is a schematic perspective view of sterilization of a paper strip to obtain absorbent paper for an effluent collector according to the present invention.

[0060] [Fig 17] Figure 17 is a schematic perspective view of the storage of sterilized absorbent paper for the manufacture of an effluent collector according to the present invention.

[0061] [Fig 18] Figure 18 is a schematic perspective view of an absorbent paper for an effluent collector according to the present invention, the absorbent paper comprising functionalized portions to select molecules of interest.

[0062] Detailed description

[0063] For the sake of clarity, the same references designating the same elements according to the state of the art and according to the invention are used for all figures 1 to 18.

[0064] Figure 1 has already been described previously and will not be further described in what follows.

[0065] Figure 2 illustrates an effluent collector 5 according to the present invention. The effluent collector 5 comprises a rotating support 7 on which absorbent papers 8 are arranged.

[0066] The rotating support 7 is illustrated in Figure 3. The rotating support 7 is a hollow cylinder extending along a longitudinal axis X. The rotating support 7 has a height of between 5 and 50 cm, for example equal to 20 cm, and / or an outer diameter of between 5 and 50 cm, for example equal to 10 cm, and / or a wall thickness of between 0.5 and 10 mm, for example equal to 2.5 mm. The wall thickness of the rotating support 7 is equal to the difference between its outer diameter and its inner diameter. The cylinder did not need to be hollow, this is simply to save material. The absorbent papers 8 are in the form of strips of length greater than or equal to the outer circumference of the rotating support 7, for example between 16 and 160 cm, and / or of width of between 5 and 50 cm, for example 5 cm.

[0067] Each absorbent paper 8 is divided into a plurality of sampling zones 9 aligned along the length of the absorbent paper 8 extending transversely to the longitudinal axis of the absorbent paper 8. Preferably, each sampling zone 9 is in the form of a strip extending over the entire width of the absorbent paper 8. Preferably, each sampling zone 9 has a width of between 0.1 and 3 cm, for example equal to 1 cm.

[0068] The sampling areas 9 are delimited from each other by markings 10. The markings 10 may be reliefs or drawings made in a hydrophobic ink.

[0069] The absorbent papers 8 are wound around the rotating support 7 by being removably fixed, preferably taped, on its outer lateral surface. The longitudinal axis X is thus also the winding axis of the absorbent papers 8.

[0070] The outer lateral surface of the rotating support 7 is hydrophobic.

[0071] The rotating support 7 is intended to be rotated around its longitudinal axis X. Thus, the rotating support 7 drives the absorbent papers 8 in rotation around the longitudinal axis X when it is itself rotated.

[0072] The effluent collector 5 also comprises recovery conduits 11, each comprising one end opening onto one of the absorbent papers 8, the other end being intended to be fluidically connected downstream to a microfluidic device 3. Thus, each recovery conduit 11 is configured to bring effluents in the form of a suspension or solution to the outlet of the corresponding microfluidic device 3 and deposit them on the corresponding absorbent paper 8.

[0073] By comprising a plurality of recovery conduits 11, the effluent collector 5 allows the simultaneous recovery of effluents at the outlet of several different microfluidic devices 3.

[0074] The effluents deposited on the absorbent paper 8 then migrate by capillarity into the pores of the absorbent paper 8 and then dry by depositing the solid objects, dispersed in the liquid phase of the effluents, on the fibers of the absorbent paper 8. For each recovery conduit 11, the deposition of effluents is carried out on a single sampling zone 9 at a time. Then, when a predetermined quantity of effluents has been deposited on a sampling zone 9 of the absorbent paper 8, the rotating support 7 rotates on itself so as to place a new sampling zone 9 opposite the emerging end of the recovery conduit 11. Each sampling zone 9 on which effluents have been deposited defines a sample.

[0075] After evaporation of the liquid phase of the effluent, each sample can be stored, the solid objects and dissolved molecules, previously dispersed in the liquid phase of the effluent, being preserved without degradation over time.

[0076] In order to carry out analyses on the sample, an extraction solution can be brought into contact with the sample, which will hydrate the absorbent paper 8 and allow the recovery of solid objects from the effluents in the form of a new suspension. The contacting of the extraction solution with the sample can be carried out by immersing the sample in the extraction solution or by flowing the extraction solution over the sample.

[0077] The effluent collector 5 comprises a motor 12 for rotating the rotating support 7, as symbolized by the arrow R. Preferably, the motor 12 is a stepping motor, but it can also be a clockwork mechanism, or a manual movement.

[0078] The hollow interior of the rotating support 7 has a toothed portion 13 and the motor 12 can rotate the rotating support 7 by means of a pinion 14 meshed in said toothed portion 13. For the sake of visibility and clarity, the pinion 14 is not shown in FIG. 2.

[0079] Figure 4 illustrates the pinion 14. The pinion 14 may have a diameter of between 5 and 50 cm, for example equal to 10 cm, and / or a thickness of between 1 and 3 cm, for example equal to 2 cm. The pinion 14 comprises a central hole 15 in which the rotation rod 16 is fixed at the output of the motor 12. The central hole 15 may have a diameter of between 0.5 and 1.5 cm, for example equal to 1 cm.

[0080] The motor 12 is housed in a housing 17 serving as a base for the entire effluent collector 5. The housing 17 is illustrated in FIG. 5. The housing 17 has the shape of a cylinder or a rectangular parallelepiped with a length of between 10 and 60 cm, for example equal to 15 cm, and / or a width of between 10 and 60 cm, for example equal to 13 cm, and / or a height of between 7 and 10 cm, for example equal to 7 cm. The wall of the housing 17 has a thickness of between 0.5 and 1 cm, for example equal to 0.5 cm.

[0081] The housing 17 comprises a fixing zone 18, in which the motor 12 is fixed, and an opening 19, superimposed on the fixing zone 18 and through which the pinion 14 movable in rotation is arranged so as to drive the rotating support 7 in rotation around the longitudinal axis X.

[0082] The effluent collector 5 may comprise a control unit for controlling the rotation of the rotating support 7 by the motor 12. In particular, the control unit controls the motor 12 to rotate the rotating support 7 regularly according to a predetermined time interval, for example every ten minutes.

[0083] Preferably, the control unit is configured so that the angle of rotation traveled by the rotating support 7 is the same for each rotation of the rotating support 7. In particular, the motor 12 may be a stepper motor and the control unit may cause the motor 12 to perform a predefined number of steps.

[0084] The rotation angle is such that the sampling zone 9 facing the discharge duct 11 is different after each rotation of the rotating support 7. Preferably, the rotation angle is such that after each rotation of the rotating support 7, the new sampling zone 9 facing the discharge duct 11 is adjacent to the sampling zone 9 previously facing the discharge duct 11.

[0085] The control unit may be a microcontroller, for example an Arduino microcontroller. Preferably, the control unit is housed in a predefined location of the housing 17. A touch display may be present on the housing 17 to indicate the progress of the collection, and to control movements of the motor.

[0086] The effluent collector 5 also comprises a holding bar 20 fixed to the housing 17 and comprising through openings 21, each opening opposite one of the absorbent papers 8. Each evacuation conduit 11 is threaded into one of the openings 21 while being held fixed by the holding bar 20. Thus, the holding bar 20 ensures the correct positioning and fixed holding of each of the evacuation conduits 11 with their end opening opposite one of the absorbent papers 8. Figure 6 illustrates the holding bar 20. The latter 20 has a cylindrical shape with a rectangular base, preferably square, with a height of between 5 and 50 cm, for example equal to 20 cm, and / or a width and / or length of between 0.5 and 5 cm, for example equal to 1 cm.

[0087] Each through opening 21 has an opening diameter of between 0.5 and 3 mm, for example equal to 1 mm.

[0088] Screws can hold pipes in place inside these through screws.

[0089] The housing 17 includes a housing 22 for receiving and holding the retaining bar 20 fixed with the housing 17.

[0090] The rotating support 7 and / or the pinion 14 and / or the housing 17 and / or the holding bar 20 are preferably made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS). PLA has the advantage of being light, inexpensive and biodegradable. ABS has the advantage of being more robust than PLA and of having better resistance to humidity.

[0091] Preferably, the rotating support 7 and / or the pinion 14 and / or the housing 17 and / or the holding bar 20 are manufactured by additive manufacturing, in particular by 3D filament printing.

[0092] Advantageously, this makes it possible to manufacture the effluent collector 5 quickly and at low cost. It is thus possible to easily adapt the shape and dimensions of the effluent collector 5 according to the microfluidic system 1 in which it is intended to be used. In particular, the dimensions of the rotating support 7 can be adapted according to the desired use for the effluent collector 5, for example the external diameter of the rotating support 7 can be chosen according to the desired length for the absorbent papers 8 and the height of the rotating support 7 can be chosen according to the desired number of absorbent papers.

[0093] In addition, the rotating support 7 and / or the pinion 14 and / or the housing 17 and / or the holding bar 20 can be used directly after their additive manufacturing without requiring post-processing.

[0094] The manufacture of the rotating support 7 and / or the pinion 14 and / or the housing 17 and / or the holding bar 20 may comprise their 3D modeling, in particular using computer-aided design software, the 3D model resulting from this modeling then being transmitted to a 3D filament printer for printing. Prior to transfer to the 3D printer, the 3D modeling may be followed by a step of converting the data format of the 3D model into a format readable by the 3D filament printer, in particular using 3D cutting software, for example the “UltiMaker Cura” software.

[0095] Obtaining the effluent collector 5 according to figure 2 comprises the assembly together of the rotating support 7, the pinion 14, the motor 12, the housing 17, the holding bar 20, the recovery conduits 11 and the absorbent papers 8.

[0096] The rotating support 7 and / or the pinion 14 and / or the housing 17 and / or the holding bar 20 may have been previously manufactured by 3D printing according to the above. The absorbent paper 8 may be obtained according to the production method described later. The motor 12 may be commercially available. The recovery conduits 11 may be similar to those usually used at the outlet of a microfluidic device.

[0097] The assembly of the effluent collector 5 may include a step of fixing, preferably by taping, the absorbent papers 8 around the rotating support 7.

[0098] The assembly of the effluent collector 5 may also comprise the following steps: i) placing the motor 12 in the fixing zone 18 of the housing 17, the rotation rod 16 of the motor 12 being opposite the opening 19 of the housing 17; ii) inserting the pinion 14 through the opening 19 to fix it to the rotation rod 16; iii) mounting the rotating support 7 on the pinion 14 with the notched portion 13 of the rotating support 7 meshing with the pinion 14.

[0099] The assembly of the effluent collector 5 may also comprise a step of fixing, by gluing or screwing, the retaining bar 20 in the housing 22 of the casing 17, followed by a step of inserting the recovery conduits 11 into the through openings 21 of the retaining bar 20.

[0100] The assembly and / or use of the effluent collector 5 can be carried out in a confined and sterile atmosphere. This avoids potential contamination of the absorbent papers 8.

[0101] Illustrated in Figure 7 is an effluent collector 5' according to another embodiment of the present invention. The effluent collector 5' comprises a rotating support 7' on which an absorbent paper 8' is disposed. The absorbent paper may have a back side covered with a plastic film or other support material, to prevent transfer or contamination during rewinding. The speed must be adapted to allow the deposited liquid to dry before the paper is wound.

[0102] The rotating support 7' comprises an unwinding shaft 23, a guide shaft 24 and a rewinding shaft 25, said shafts 23, 24 and 25 extending parallel to the longitudinal axis X' of the rotating support 7' while being movable in rotation around their longitudinal axis.

[0103] When viewed lengthwise, the unwinding shafts 23, guide shafts 24 and rewinding shafts 25 form the vertices of a triangle, preferably a right triangle. Preferably, the rewinding shaft 25 is located on the right-angled vertex of the triangle formed by the shafts 23, 24 and 25.

[0104] The rotating support 7' also comprises belts 26 for transmitting the rotation of the guide shaft 24 about its longitudinal axis into a rotation of each of the unwinding shafts 23 and rewinding shafts 25 about their longitudinal axis. The rotations of the shafts 23, 24 and 25 are thus synchronous, at the same speed and in the same direction. Preferably, the belts 26 are made of rubber.

[0105] Figures 8 and 9 illustrate the guide shaft 24 and, respectively, the unwinding shaft 23. The rewinding shaft 25 may be identical to the unwinding shaft 23. The guide shaft 24 and / or the unwinding shafts 23 and rewinding shafts 25 have a cylindrical shape with a height of between 5 and 50 cm, for example equal to 15 cm, and / or a diameter of between 1 and 5 cm, for example equal to 1.5 cm.

[0106] The absorbent paper 8' is in the form of a roll, the inner end of which is fixed to the unwinding shaft 23 so that rotation of said unwinding shaft 23 causes the roll to unwind. The outer end of the roll is fixed to the rewinding shaft 25 so that rotation of said rewinding shaft 25 causes the absorbent paper 8' to be rewound around said rewinding shaft 25.

[0107] The unrolled portion of the absorbent paper 8' between the unrolling shaft 23 and rewinding shaft 25 is pressed against the guide shaft 24. The guide shaft 24 thus accompanies and guides the unrolling and rewinding of the absorbent paper 8'. The unrolling shaft 23 and rewinding shaft 25 each have two notches hollowed out along their length in order to fix the ends of the roll formed by the absorbent paper 8'.

[0108] The 8' absorbent paper has an unrolled length of between 50 and 500 cm, and / or a width of between 5 and 50 cm, for example equal to 13 cm.

[0109] The absorbent paper 8' is divided into a plurality of sampling zones 9' aligned along the width of the absorbent paper 8' extending longitudinally in the unrolling direction of the absorbent paper 8'. Preferably, each sampling zone 9' is in the form of a strip extending along the entire length of the absorbent paper 8' when unrolled. Preferably, each sampling zone 9' has a width of between 0.5 and 5 cm, for example equal to 1 cm.

[0110] The 9' sampling areas are delimited from each other by 10' markings. The 10' markings can be reliefs or drawings made in a hydrophobic ink.

[0111] The effluent collector 5' also comprises recovery conduits 11' each comprising one end opening onto one of the sampling zones 9' at the level of the unrolled portion of the absorbent paper 8' between the unrolling shaft 23 and guide shaft 24, the other end being intended to be fluidically connected downstream to a microfluidic device 3. Thus, each recovery conduit 11' is configured to bring the effluents in the form of a suspension to the outlet of the microfluidic device 3 and deposit them on the absorbent paper 8', at the corresponding sampling zone 9'.

[0112] The operation of effluent storage on 8' absorbent paper is similar to that for the 8 absorbent papers illustrated in Figure 2.

[0113] The effluent collector 5' comprises a motor 12' for rotating the guide shaft 24, as symbolized by the arrow R'. The rotation of the guide shaft 24 drives, by the belts 26, the unwinding shaft 23 and rewinding shaft 25 in rotation as symbolized by the arrow R”. Preferably, the motor 12' is a stepping motor.

[0114] The guide shaft 24 comprises a blind hole dug in one of its bases and in which the rotation rod 16' is fixed at the output of the motor 12'. The blind hole may have a diameter between 1 and 5 cm, for example equal to 1 cm. The motor 12' may be controlled by a control unit. The control unit may be a microcontroller, for example an Arduino microcontroller.

[0115] The rotating support 7' and the absorbent paper 8' are housed in a housing 17'. The housing 17' is illustrated in Figure 10. The housing 17' has the shape of a rectangular parallelepiped with a length of between 5 and 50 cm, for example equal to 15 cm, and / or a width of between 5 and 50 cm, for example equal to 15 cm, and / or a height of between 5 and 50 cm, for example equal to 15 cm. The wall of the housing 17 has a thickness of between 0.5 and 1 cm, for example equal to 0.5 cm.

[0116] One of the faces of the housing 17', called the front face 27, is open and another of the faces of the housing 17', called the top face 28, is semi-open. The open part 29 of the top face 28 is in contact with the front face 27. The closed part 30 of the top face 28 extends over the entire length of the top face 28, covering between 50 and 70% of its width, for example the width of the closed part 30 is equal to 7 cm. It is thus easy to access the interior of the housing 17' to put in place the rotating support 7' and the absorbent paper 8'.

[0117] The unwinding shaft 23 is mounted adjacent to the top face 28, the guide shaft 24 is mounted adjacent to the front face 27 and the rewinding shaft 25 is mounted spaced from the front faces 27 and the top 28.

[0118] The effluent collector 5' may comprise a window for hermetically sealing the front face 27 and the top face 28 of the housing 17', the window comprising openings for the passage of the evacuation conduits 11'. The window is advantageously transparent in the visible range, thus allowing observation of the deposition of the effluents on the absorbent paper 8'.

[0119] Preferably, the glass is made of plexiglass. It can be obtained by cutting plexiglass sheets. Preferably, the glass has a thickness of between 0.5 and 1 cm, for example equal to 0.5 cm.

[0120] One of the side faces of the housing 17' comprises insertion openings 31 and the other of the side faces comprises tenons 32. The insertion openings 31 form passages for inserting the unwinding shafts 23, guide shafts 24 and rewinding shafts 25 into the housing 17'. They 31 have a diameter of between 1 and 2 cm, for example equal to 1.7 cm. The tenons 32 cooperate with mortises 33 complementary to the unwinding shafts 23, guide shafts 24 and rewinding shafts 25 in order to fix them removably in the housing 17' while leaving them free to rotate about their longitudinal axis. Of course, it is possible to interchange each of the tenons 32 by mortises and complementary mortises 33 by tenons.

[0121] Each of the unwinding shafts 23 and rewinding shafts 25 comprises a rod 34 projecting through the corresponding insertion opening 31 and on which a nut 35 is mounted in order to ensure the mechanical retention of the unwinding shafts 23 and rewinding shafts 25.

[0122] The 17' housing also includes a 36' side housing to accommodate the 12' motor.

[0123] The effluent collector 5' also comprises a holding bar 20' fixed protruding from the top face 28 of the housing 17' and comprising through openings 21', each opening towards the open part 29 of the top face 28 while being aligned with one of the sampling zones 9' of the absorbent paper 8'.

[0124] Each evacuation conduit 11' is inserted into one of the openings 21' while being held fixed by the holding bar 20'. Thus, the holding bar 20' ensures the correct positioning and fixed holding of each of the evacuation conduits 11' with their opening end facing the absorbent paper 8'.

[0125] Figure 11 illustrates the support bar 20'. This 20' has a cylindrical shape with a rectangular base, preferably square, with a height of between 5 and 50 cm, for example equal to 13 cm, and / or a width and / or length of between 0.5 and 1 cm, for example equal to 1 cm.

[0126] Each through opening 21' has an opening diameter of between 1 and 5 mm, for example equal to 3 mm.

[0127] The unwinding shaft 23 and / or the guide shaft 24 and / or the rewinding shaft 25 and / or the housing 17' and / or the holding bar 20' are preferably made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS).

[0128] Preferably, the unwinding shaft 23 and / or the guide shaft 24 and / or the rewinding shaft 25 and / or the housing 17' and / or the holding bar 20' are manufactured by additive manufacturing, in particular by 3D filament printing. Their manufacturing method may be similar to that described previously for the elements of the effluent collector 5 illustrated in FIG. 2.

[0129] Advantageously, this allows the effluent collector 5' to be manufactured quickly and at low cost. It is thus possible to easily adapt the shape and dimensions of the effluent collector 5' according to the microfluidic system 1 in which it is intended to be used. In particular, the dimensions of the rotating support 7' can be adapted according to the desired use for the effluent collector 5', for example the length of the shafts 23, 24 and 25 can be chosen according to the desired width for the absorbent paper 8'. It is also possible to carry out rapid prototyping of the effluent collector 5'.

[0130] Obtaining the effluent collector 5' according to figure 7 includes the assembly together of the rotating support 7', the motor 12', the housing 17', the holding bar 20', the recovery conduits 11' and the absorbent paper 8'.

[0131] The unwinding shaft 23 and / or the guide shaft 24 and / or the rewinding shaft 25 and / or the housing 17' and / or the holding bar 20' may have been previously manufactured by 3D printing according to the above. The absorbent paper 8' may be obtained according to the production method described later. The belts 26 and the motor 12' may be commercially available. The recovery conduits 11' may be similar to those usually used at the outlet of a microfluidic device.

[0132] The assembly of the effluent collector 5' may comprise the following steps: i') assembly of the absorbent paper 8' wound around the guide shaft 24, said assembly comprising the fixing of the guide shaft 24 with the internal end of the roll formed by the absorbent paper 8'; ii') fixing the external end of the roll formed by the absorbent paper 8' on the rewinding shaft 25, by passing the absorbent paper 8' around the guide shaft 24 so that the unwound portion of the absorbent paper 8' between the unwinding shaft 23 and rewinding shaft 25 is pressed against the guide shaft 24.

[0133] Step ii') may be preceded by a step of placing the unwinding shafts 23, guide shafts 24 and rewinding shafts 25 in the housing 17', preferably by insertion through the insertion openings 31 of the housing 17'; The assembly of the effluent collector 5' may also comprise a step of fixing, preferably by gluing, the retaining bar 20' on the top face 28 of the housing 17', followed by a step of threading the recovery conduits 11' into the through openings 21' of the retaining bar 20'.

[0134] The assembly of the effluent collector 5' may also include a step of placing the motor 12' in the lateral housing 36 of the housing 17' and fixing the rotation rod 16' in the blind hole of the guide shaft 24.

[0135] The 5' effluent collector can be installed in a confined and sterile atmosphere. This avoids potential contamination of the 8' absorbent papers.

[0136] Figures 12 to 18 illustrate the different steps of a method for obtaining an absorbent paper 8 for an effluent collector 5 according to the present invention. The same method can be carried out to obtain the absorbent paper 8' for the effluent collector 5'.

[0137] Said obtaining method comprises a step a) of cutting a strip 37 of paper from a sheet of paper, the strip 37 being of the desired dimensions for the absorbent paper 8. Step a) is illustrated by figure 12.

[0138] The paper sheet is chosen according to the type of sample to be deposited and stored. For example, the material of the paper sheet will be different if the sample is a bacterial suspension or a physiological sample. Preferably, the paper sheet is made of a porous paper, for example a filter paper, in particular a Whatman grade 42 paper or a quartz-based filter paper, or a cellulose-based or nitrocellulose-based paper, or one loaded with silica particles.

[0139] Step a) is followed by a step b) of marking the strip 37 in order to delimit the sampling zones 9 of the absorbent paper 8. The marked strip 37 is illustrated in Figure 15. The marks 10 obtained by this step b) constrain and confine the flow of effluents in each of the sampling zones 9 during their deposition.

[0140] The marking can also be carried out around the entire perimeter of the strip 37 in order to prevent the effluents from flowing out of the absorbent paper 8 when they are deposited.

[0141] The marking can be carried out by drawing using a felt-tip pen 38 with hydrophobic ink, as illustrated in Figure 13. The felt-tip pen 38 can be a PAP PEN marker for immunostaining. Alternatively, the marking can be carried out by laser marking, as illustrated in Figure 14. For this, a laser cutter 39 can scan the surface of the paper strip 37 so as to form the marks 10 in the form of grooves. The power of the laser cutter 39 is chosen so as not to cut the entire paper strip 37. The laser cutter 39 can be computer-controlled, in particular the scanning path can be carried out by computer-aided design software. A sheet of plastic or aluminum support material can be adhered to the back of the paper to ensure the stability of the paper during cutting.

[0142] Step b) is followed by a step c) of sterilizing the paper strip 37, as illustrated in Figure 16. The sterilization comprises sandwiching the paper strip 37 with aluminum sheets 40 followed by heating in an oven 41 the assembly comprising the paper strip 37 and the aluminum sheets 40. The heating is carried out at a temperature above 80°C for at least 10 h.

[0143] Advantageously, in the case where the marking is carried out by drawing with a felt-tip pen, the sterilization of the paper strip 37 also ensures the drying of the ink.

[0144] Step c) is followed by a step d) of storing the sterilized paper strip 37, forming the absorbent paper 8, as illustrated in Figure 17. During said storage, the paper strip 37 is kept sandwiched by the aluminum sheets 40 in a hermetically sealed container 42 whose confined atmosphere is sterile.

[0145] The method for obtaining the absorbent paper 8 may also comprise a step e) of functionalizing portions of the paper strip 37, the functionalized portions being configured to select molecules of interest from among the solid objects contained by the effluents so that only said molecules of interest are deposited and retained on the fibers of said portions during the drying of the effluents. Step e) may be carried out after step d).

[0146] Figure 18 illustrates an absorbent paper comprising functionalized portions 43. Every other sampling area 9 comprises two functionalized portions 43 for selecting a molecule of interest. For each sampling area 9, a first of the functionalized portions 43 is intended to receive the effluents and the second of the functionalized portions 43 is intended to control the proper reception of the effluents by the first of the functionalized portions 43. The functionalization step e) may be similar to a protocol for functionalizing diagnostic strips for immunochromatography tests. The functionalization step e) may comprise the deposition on the portions 43 to be functionalized of a conjugated detection reagent comprising an antibody, adapted to react by forming an immune complex with the molecule of interest.Preferably, the conjugated reagent also comprises a detection reagent for changing visual appearance upon formation of the immune complex. Preferably, the detection reagent is colloidal gold.

[0147] Other variations and improvements may be envisaged without departing from the scope of the invention. List of cited references

[0148] [1] David Dfaz et al.: “D1Y Universal Fraction Collector”, Analytical Chemistry, 2021, 93, 27, 9314-9318.

[0149] [2] John P. Efromson et al.: “BioSamplr: An open source, low cost automated sampling system for bioreactors”, HardwareX, vol. 9, 2021, e00177. [3] Scott A. Longwell et al.: ''micrIO: an open-source autosampler and fraction collector for automated microfluidic input-output”, Lab Chip, 2020, 20, 93-106.

[0150] [4] A. Sina Booeshaghi et al.: “Low -cost, scalable, and automated fluid sampling for fluidics applications” , HardwareX, vol. 10, 2021, e00201.

Claims

Claims 1. Effluent collector (5, 5') for recovering effluents in the form of suspension or solution at the outlet of a microfluidic device (3), comprising: - at least one absorbent paper (8, 8') for receiving the effluents, the absorbent paper being configured so that the effluents received migrate by capillarity in the absorbent paper then dry by depositing solid objects or the dissolved molecules contained by the effluents on the fibers of the absorbent paper, - a rotating support (7, 7') extending along a longitudinal axis (X, X') and on which the absorbent paper is placed, the rotating support being configured to set the absorbent paper in motion relative to the evacuation duct, - at least one evacuation conduit (11, 11') comprising one end opening onto the absorbent paper and another end intended to be connected downstream to the microfluidic device.

2. Effluent collector according to claim 1, the absorbent paper comprising a plurality of sampling areas (9, 9') delimited from each other by a marking (10, 10'), preferably the marking being a hydrophobic ink drawing or a relief, preferably the sampling areas being aligned along the length, or respectively the width, of the absorbent paper extending transversely, respectively parallel, to the longitudinal axis of the absorbent paper.

3. Effluent collector according to one of the preceding claims, the absorbent paper being porous, for example a filter paper or a cellulose-based or nitrocellulose-based paper.

4. Effluent collector according to one of the preceding claims, the absorbent paper comprising functionalized portions (43) for selecting, concentrating and detecting molecules of interest among the solid objects contained by the effluents so that only said molecules of interest are deposited and preserved on the fibers of said portions during drying of the effluents, preferably the molecules of interest being chosen from DNA, RNA, peptides, proteins and / or antibodies.

5. Effluent collector according to one of the preceding claims, the absorbent paper being sterile.

6. Effluent collector according to one of the preceding claims, the rotating support being made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS).

7. Effluent collector according to one of the preceding claims, the surface of the rotating support on which the absorbent paper is deposited being hydrophobic.

8. Effluent collector according to one of the preceding claims, the rotating support (7) being cylindrical in shape with a longitudinal axis (X) and the absorbent paper being wound on the lateral surface of the rotating support so as to be rotated by a rotation of the rotating support around said longitudinal axis (X).

9. Effluent collector according to one of claims 1 to 7, the rotating support (7') comprising: - an unwinding shaft (23) rotatable about its longitudinal axis and around which the absorbent paper (8') is wound, the internal end of the roll formed by the absorbent paper being fixed to the unwinding shaft so that the rotation of said unwinding shaft causes the roll to unwind, - a rewinding shaft (25) movable in rotation around its longitudinal axis and to which the external end of the roll formed by the absorbent paper is fixed so that the rotation of said rewinding shaft causes the rewinding of the absorbent paper 8' around said rewinding shaft, the unwinding shaft and the rewinding shaft being mechanically linked together so that their rotations are synchronous, at the same speed and in the same direction.

10. Effluent collector according to the preceding claim, the rotating support comprising a guide shaft (24) movable in rotation around its longitudinal axis and on which the unrolled portion of the absorbent paper between the unrolling and rewinding shafts is supported, the guide shaft being mechanically linked to the unrolling and rewinding shafts so that their rotations are synchronous, at the same speed and in the same direction.

11. Effluent collector according to one of the preceding claims, comprising a motor (12, 12') for rotating the rotating support, preferably the motor being a stepping motor, preferably the effluent collector comprising a control unit for controlling the rotation of the rotating support by the motor.

12. Effluent collector according to one of the preceding claims, comprising a housing (17, 17') on or in which the rotating support is mounted.

13. Effluent collector according to one of the preceding claims, comprising a holding bar (20, 20') fixed relative to the longitudinal axis (X, X') of the rotating support and comprising at least one through opening (21, 21') into which the evacuation conduit is inserted.

14. Microfluidic system (1) comprising: - a microfluidic device (3), - an injection device (2) connected upstream to the microfluidic device in order to supply said microfluidic device with a fluid of interest, - an effluent collector (5, 5') according to one of the preceding claims, the effluent collector being connected downstream to the microfluidic device in order to recover the effluents leaving the microfluidic device.

15. Method of manufacturing an effluent collector according to one of claims 1 to 13, comprising a step of manufacturing the rotating support (7, 7') by 3D printing, preferably by filament 3D printing, preferably the filament being made of polylactic acid (PLA) or acrylonitrile butadiene styrene (ABS).

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