Device for holding a microfluidic cardtridge
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-06-06
- Publication Date
- 2026-04-15
AI Technical Summary
Existing devices for holding microfluidic cartridges are limited in their ability to perform multiple biological analyses, leading to the frequent use of disposable cartridges and increased analysis time, with a need for a solution that allows for reusability and reduced environmental impact.
A device comprising a base and a cover with a pivot connection, featuring a rinsing system that connects to a reservoir to rinse the cartridge, enabling the reuse of microfluidic cartridges by selectively introducing a rinsing liquid through a female Luer-Lock type connector, and a locking mechanism to securely hold the cartridge in place.
The device allows for the reuse of microfluidic cartridges, reducing analysis time and environmental waste by enabling efficient rinsing and reutilization, while maintaining the stability and integrity of the biological analysis process.
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Figure FR2024050740_12122024_PF_FP_ABST
Abstract
Description
[0001] Description
[0002] Title: Device for holding a microfluidic cartridge
[0003] The field of the invention relates to the maintenance of a microfluidic cartridge, in particular for the purposes of analyzing a sample of biological liquid.
[0004] Microfluidics refers to the technology of systems whose operation is based on the flow of fluids - particularly liquids - within channels with dimensions of the order of a micrometer (pm). Such channels are commonly referred to as microchannels.
[0005] This order of magnitude has the particularity of making surface effects predominant in the behavior of a liquid, unlike a macroscopic object for which the volume component predominates over the surface component. In particular, microfluidics exploits certain physical phenomena, such as capillarity, laminarity or wettability, which occur when the liquid is in contact with a microchannel. At such a scale, the behavior of a liquid is also characterized by the speed of thermal exchanges and the exacerbation of electrokinetic effects.
[0006] Over the past few decades, microfluidics has contributed to the development of several innovations, such as the insertion of active substances into microdroplets encapsulated in an evanescent membrane for cosmetic purposes, the manufacture of inkjet print heads, and the design of micropumps for injecting drugs into the human body.
[0007] Furthermore, one of the most notable applications of microfluidics is the lab-on-a-chip (LOC), whose design is based on the miniaturization of components such as channels, valves, and pumps. Such labs-on-a-chip are used to perform biological analyses on small-volume samples and allow, among other things, the replacement of bulky devices, the implementation of a large number of analyses in parallel, and the reduction of the time required for experiments or tests.
[0008] A lab-on-a-chip typically takes the form of a microfluidic cartridge – also called a “microfluidic chip” in English literature.
[0009] In biological analysis, a microfluidic cartridge must be held stationary to accurately introduce the biological fluid sample to be analyzed, for example a blood or urine sample, and the reagents. Once the microfluidic cartridge is positioned and held, it is then possible to carry out the necessary mixtures - generally one or more dilutions - for the biological analysis. To do this, it is known to use a holding device, sometimes called a "chip holder".
[0010] Chinese utility model CN 208288057 U describes a device comprising a base on which a microfluidic cartridge can be arranged and a cover hinged to the base so as to be able to be folded down onto the microfluidic cartridge. A screw provided with a damping spring and surmounted by a locking nut is rotatably mounted on the base and is arranged to be received in a bayonet of the cover to lock the latter in the closed position.
[0011] US patent application US 2016 / 0367993 A1 relates to a holding apparatus comprising a lower part capable of receiving a microfluidic device and an upper part rotatably mounted on the lower part. The upper part comprises a coupler provided with flexible plugs, and a cover is interposed between the coupler and the lower part. The flexible plugs are arranged, when the holding apparatus is in the closed position, to bear on the cover and protrude from the upper part so as to form injection and sampling channels connected to the microfluidic device. European patent EP 2 694 214 B1 proposes a device for the sealed connection and disconnection of a microfluidic card. The device has a first surface intended to receive a microfluidic card and a second surface, parallel to the first surface, against which the microfluidic card is held in abutment.Such support is ensured by walls perpendicular to the first and second surfaces as well as by holding means such as a cylindrical spring-loaded ball bearing. The second surface has channels positioned so as to be connected to the fluidic channels of the microfluidic card.
[0012] However, such devices only allow a limited number of biological analyses to be carried out with the same microfluidic cartridge. It is therefore common to use disposable microfluidic cartridges. There is therefore a demand for a device that not only allows a microfluidic cartridge to be maintained but also allows it to be reused, which would reduce the time required for analyses and would be of environmental interest.
[0013] The present invention improves the situation.
[0014] In this respect, the invention relates to a device for holding a microfluidic cartridge, comprising:
[0015] - a base arranged to support a microfluidic cartridge, and
[0016] - a cover having an orifice and connected to the base by a pivot connection, which pivot connection allows the cover to pivot to reach a closed position in which, when a microfluidic cartridge is supported by the base, the orifice is opposite a fluid inlet of the microfluidic cartridge.
[0017] The device is characterized in that it further comprises a rinsing system arranged to selectively connect the orifice to a reservoir in order to rinse a microfluidic cartridge supported by the base.
[0018] In one or more embodiments, the flushing system includes an arm having a nozzle adapted to be connected to a reservoir and to deliver a liquid stored in the reservoir, and the arm is connected to the base by a pivot connection, which pivot connection allows the arm to pivot to reach a position in which the nozzle is received in the orifice.
[0019] Typically, the arm is further provided with a reservoir capable of containing a liquid and a conduit connecting the reservoir to the tip.
[0020] Advantageously, the cover has an opening and the arm has an elastic end capable of being fitted by deformation into the opening and of being held there by mechanical stress when the tip is received in the orifice.
[0021] Advantageously, the base has a shoulder capable of serving as a support for the arm when the latter pivots beyond a vertical position.
[0022] In one or more embodiments, the base is provided with stops together defining a location within which a microfluidic cartridge can be positioned.
[0023] In one or more embodiments, the port is a female Luer-Lock type fitting.
[0024] In one or more embodiments, the base comprises a fixed portion arranged to support a microfluidic cartridge and a portion movable in translation in a direction substantially orthogonal to the fixed portion, and the movable portion is provided with the pivot connection by which the cover is connected to the base.
[0025] In one or more embodiments, the device further comprises a locking mechanism arranged to lock the cover in a closed position on the base in a detachable manner.
[0026] The locking mechanism comprises for example at least one pair of a through hole and a complementary hole provided respectively in the cover and the base such that, when the cover is in the closed position, the through hole and the complementary hole are opposite each other to receive together a fixing screw.
[0027] Still by way of example, the locking mechanism may comprise a lever closure and a counter hook mounted respectively on the base and the cover, or vice versa. In one or more embodiments, the base is provided with a plurality of pneumatic fittings arranged to be coupled to a microfluidic cartridge supported by the base.
[0028] In one or more embodiments, the cover is provided with a plurality of fluidic connectors arranged to be coupled to a microfluidic cartridge supported by the base.
[0029] In one or more embodiments, the cover has a viewport.
[0030] The invention also relates to a method of using the device as described above comprising:
[0031] - place a microfluidic cartridge on the base,
[0032] - rotate the cover until it reaches the closed position,
[0033] - introduce a sample of biological fluid into the microfluidic cartridge via the orifice, and
[0034] - carry out at least one analysis of the biological fluid sample with the microfluidic cartridge.
[0035] The method is characterized in that it further comprises:
[0036] - connect the port to a tank storing a flushing liquid by means of the flushing system, and
[0037] - rinse the microfluidic cartridge by introducing the rinsing liquid through the orifice.
[0038] Other characteristics, details and advantages will appear on reading the detailed description below, and on analyzing the attached drawings in which:
[0039] [Fig. 1] illustrates a perspective view from above of a device for holding a microfluidic cartridge comprising a base, a cover and a rinsing system according to the invention in a configuration where the cover is in the open position,
[0040] [Fig. 2] illustrates an exploded view of a microfluidic cartridge,
[0041] [Fig. 3] illustrates a bottom perspective view of the device of [Fig. 1 ] in a configuration where the cover is in the open position, [Fig. 4] illustrates a sectional view of the device of [Fig. 1 ] in a configuration where the cover is in the closed position and where a liquid injection instrument is used,
[0042] [Fig. 5] illustrates a sectional view of the device of [Fig. 1] in a configuration where the cover is in the closed position,
[0043] [Fig. 6] illustrates a cross-sectional view of the device of [Fig. 1], and more particularly a problem related to the thickness of the microfluidic cartridge which may arise when closing the cover,
[0044] [Fig. 7] illustrates a top perspective view of the device of [Fig. 1] in a configuration where the cover is in the closed position,
[0045] [Fig. 8] illustrates a sectional view of the device of [Fig. 1] in a configuration where the cover is in the closed position and the rinsing system is in use,
[0046] [Fig. 9] illustrates a method of using the device of [Fig. 1] according to the invention,
[0047] [Fig. 10] illustrates a perspective view from above of a device for holding a microfluidic cartridge comprising a rinsing system other than that of the invention, and
[0048] [Fig. 11] illustrates a sectional view of the rinsing system of the device of [Fig. 10],
[0049] [Fig. 1] illustrates a device 1 for holding a microfluidic cartridge.
[0050] In the context of the invention, a microfluidic cartridge typically refers to a laboratory-on-a-chip - or LOC for "lab-on-a-chip" in the English literature - comprising a network of microchannels and reaction chambers.
[0051] A microfluidic cartridge can be used to perform analyses on a biological fluid sample, for example a blood or urine sample. The advantage of a microfluidic cartridge is that it can handle small volume samples, but also allows several analyses to be carried out in parallel and more quickly. As an example, [Fig. 2] illustrates the classic structure of a microfluidic cartridge 3.
[0052] The microfluidic cartridge 3 comprises a fluidic card 5, a pneumatic card 7, a membrane 9 and a lower card 11.
[0053] The fluidic card 5 has a fluidic inlet 13 for the introduction - for example by injection or aspiration - of a sample of biological liquid to be analyzed and inlet / outlet orifices 15 for the introduction of reagents or the evacuation of waste. Furthermore, the fluidic card 5 comprises a network of microchannels provided with valves to allow the sample of biological liquid and the reagents to circulate as well as reaction chambers within which mixtures can be made.
[0054] The pneumatic card 7 is arranged to control the circulation of liquids within the microfluidic cartridge 3, and more particularly to control the fluidic card 5. To do this, the pneumatic card 7 comprises pneumatic channels to actuate the opening and closing of the valves of the fluidic card 5 by targeted pressure variations.
[0055] The membrane 9 is intended to be interposed between the fluidic card 5 and the pneumatic card 7 so as to form a sandwich structure. The membrane 9 is elastic - or even hyperelastic - so that it can be deformed by the pressure induced by the pneumatic channels of the pneumatic card 7. Thus, any liquid present in the microfluidic cartridge 3 is caught between a fixed wall defined by the fluidic card 5 and a deformable wall defined by the membrane 9.
[0056] Finally, the lower card 11 is arranged to close the pneumatic channels of the pneumatic card 7 and thus provide external controls 17 to control the fluidic card 5.
[0057] In the perspective view of [Fig. 1], a microfluidic cartridge 3 is positioned on the device 1, for example for the purpose of analyzing a sample of biological fluid. The microfluidic cartridge 3 shown in this figure may be similar to or different from that illustrated in [Fig. 2]. As illustrated in [Fig. 1], the device 1 comprises a base 19, a cover 21, and a rinsing system 23.
[0058] The base 19 generally forms a support for the device 1. When in use, the device 1 can thus rest on the base 19.
[0059] The base 19 is arranged to support a microfluidic cartridge 3.
[0060] In order to facilitate the positioning of the microfluidic cartridge 3, the base 19 may be provided with stops 25 together delimiting a location intended for the microfluidic cartridge 3. In the example illustrated in [Fig. 1], the base 19 has the general shape of a plate having a rectangular upper surface on which the microfluidic cartridge 3 rests, and the stops 25 are arranged at the periphery of this upper surface.
[0061] Advantageously, at least one stop 25 has an elastic portion 26, which allows the device 1 to be able to adapt to microfluidic cartridges of different dimensions, but also to improve the holding of the microfluidic cartridge 3 by taking advantage of the restoring force exerted by the elastic portion 26. Of course, several stops 25 can have such an elastic portion 26. In the example of [Fig. 1], the base 19 is provided with three stops 25 and two of them have an elastic portion 26.
[0062] Furthermore, as illustrated in [Fig. 3] which shows a bottom view of the device 1, the base 19 can be provided with several pneumatic connectors 27 each arranged to be coupled to the microfluidic cartridge 3 supported by the base 19.
[0063] Such pneumatic connections 27 make it possible to induce targeted pressure variations within the microfluidic cartridge 3 to control the flow of liquids, in particular the biological liquid sample or the reagents.
[0064] In particular, when the microfluidic cartridge 3 has a structure similar to that illustrated in [Fig. 2], each pneumatic connector 27 is connected to an external control 17 to control the fluidic card 5 via the pneumatic channels of the pneumatic card 7. It should also be noted that the base 19 can be provided with a heating system (not shown here) which makes it possible to control the temperature of the microfluidic cartridge 3, which can be important for carrying out a biological analysis.
[0065] Again with reference to [Fig. 1], the cover 21 has an orifice 29 and is rotatably mounted on the base 19 by means of a pivot connection 31.
[0066] The pivot link 31 allows the cover 21 to pivot about a Y axis to move between an open position and a closed position.
[0067] The closed position is an equilibrium position of the cover 21 in which the latter is folded down onto the base 19 or, where appropriate, onto the microfluidic cartridge 3 arranged on the base 19. The cover 21 must be in the closed position to keep the microfluidic cartridge 3 stationary.
[0068] Conversely, the open position is a position of the cover 21 allowing the microfluidic cartridge 3 to be placed on the base 19 or removed. In the example of [Fig. 1], the cover 21 is in the open position and thus allows an operator to directly access the microfluidic cartridge 3, for example to remove it after a biological analysis.
[0069] The orifice 29 is a through hole and is positioned on the cover 21 such that, when the cover 21 is folded into the closed position on the microfluidic cartridge 3, the orifice 29 faces a fluid inlet 13 of the microfluidic cartridge 3.
[0070] In particular, when the microfluidic cartridge 3 has a structure similar to that illustrated in [Fig. 2], the orifice 29 is opposite the fluidic inlet 13 of the fluidic card 5.
[0071] Consequently, the orifice 29 allows, when the cover 21 is in the closed position, access to the fluidic inlet 13 of the microfluidic cartridge 3 and therefore to introduce a sample of biological liquid to be analyzed.
[0072] Advantageously, the orifice 29 is a female Luer-Lock type connector.
[0073] Luer-Lock connectors are commonly used to improve syringe assembly: the tip of the syringe barrel has a male connector, while the needle has a female connector. The male and female connectors each have a tapered shape, specifically a taper of approximately 6%. Furthermore, the male connector has an external thread, while the female connector has an internal thread. The male and female connectors can be screwed together to create a tight connection between the syringe barrel and needle.
[0074] In the medical field, there are also intravascular and hypodermic applications for Luer-Lock connectors. Such applications are regulated by the ISO 80369 standard.
[0075] In the embodiment in which the port 29 is a female Luer-Lock type connector, it is thus possible to easily couple a liquid injection instrument provided with a male Luer-Lock type connector and the fluid inlet 13 via the port 29.
[0076] More generally, the orifice 29 can take the form of any connector allowing a sealed connection between the device 1 and the injection instrument. For example, the orifice 29 can be a Simple Luer, quarter-turn, bayonet or even screw-on connector. Of course, in such cases, the injection instrument used is equipped with an additional connector.
[0077] [Fig. 4] shows a sectional view of the device 1 in which the cover 21 is in the closed position. The microfluidic cartridge 3 is thus held between the base 19 and the cover 21.
[0078] Furthermore, [Fig. 4] also shows an injection instrument assembled with the device 1 for injecting a sample of biological fluid into the fluid inlet 13 via the orifice 29. More particularly, the injection instrument comprises a sampling body 33 - of which only the lower part is shown here - terminated by an adapter 35 taking the form of a male Luer-Lock type connector within which a sleeve 37 is housed. It should be noted that, typically, a tube (not shown here) is present in the sampling body 33, which tube contains the sample of biological fluid to be analyzed. The adapter 35 and the orifice 29 have complementary shapes - a taper of approximately 6% - to obtain a sealed connection between the injection instrument and the fluid inlet 13.
[0079] As illustrated in [Fig. 4], the seal can be further improved with an O-ring 39 provided at the orifice 29, and more precisely at the outlet of the orifice 29 intended to be connected to the fluid inlet 13. Such an O-ring 39 makes it possible to prevent any leakage when introducing a sample of biological liquid into the microfluidic cartridge 3.
[0080] Again with reference to [Fig. 1], the cover 21 may be provided with several fluidic connections 41 each arranged to be coupled to the microfluidic cartridge 3 supported by the base 19.
[0081] The fluidic connections 41 are positioned on the cover 21 such that, when the cover 21 is folded into the closed position on the microfluidic cartridge 3, the fluidic connections 41 are each opposite an inlet / outlet orifice of the microfluidic cartridge 3.
[0082] Consequently, the fluidic connections 41 allow, when the cover 21 is in the closed position, access to the inlet / outlet orifices of the microfluidic cartridge 3 and therefore to introduce reagents therein or to evacuate waste therefrom.
[0083] In particular, when the microfluidic cartridge 3 has a structure similar to that illustrated in [Fig. 2], each fluidic connector 41 is connected to an inlet / outlet port 15 of the fluidic card 5.
[0084] [Fig. 5] shows a sectional view of the device 1 in which the cover 21 is in the closed position. The microfluidic cartridge 3 is thus held between the base 19 and the cover 21.
[0085] Furthermore, [Fig. 5] allows to see in more detail the fluidic connections 41 which take the form of cylindrical tubes each partially housed in a through hole. Such tubes are for example microtubes. In the example described here, the microfluidic cartridge 3 has a structure similar to that illustrated in [Fig. 2] and the fluidic connections 41 are each connected to an inlet / outlet orifice 15. [Fig. 5] also makes it possible to illustrate a particularly advantageous embodiment concerning the manner in which the base 19 and the cover 21 are articulated with each other. As mentioned previously, the cover 21 is connected to the base 19 by a Y-axis pivot connection 31. However, from one microfluidic cartridge 3 to another, the thickness can vary to the point that it may be impossible to completely fold the cover 21 onto the fluidic cartridge 3.In such a case, the contact surface between the cover 21 and the microfluidic cartridge 3 is greatly reduced. The orifice 29 cannot be connected in a satisfactory manner to the fluid inlet 13; the same applies to the fluid connectors 41 and the inlet / outlet orifices 15.
[0086] This problem is illustrated in [Fig. 6]. The only possible contact surface between the cover 21 and the microfluidic cartridge 3 is indicated by a circle C. It can be seen in this figure that the thickness of the microfluidic cartridge 3 is such that there remains a space between each fluid connection 41 and the corresponding inlet / outlet orifice 15.
[0087] To remedy this, it is proposed, in an embodiment illustrated in [Fig. 5], to form the base 19 from a fixed portion 43 and a movable portion 45. The fixed portion 43 is the part of the base 19 arranged to support the microfluidic cartridge 3 while the movable portion 45 is the part of the base 19 carrying the pivot connection 31 by which the cover 31 is connected to the base 19. The movable portion 45 is mounted in translation on the fixed portion 43 in a direction Z substantially orthogonal to the fixed portion 43.
[0088] Such an embodiment makes it possible to adjust the height of the pivot connection 31 relative to the base 19 and thus to adapt to the thickness of the microfluidic cartridge 3.
[0089] Again with reference to [Fig. 1], the cover 21 may also have a sight glass 47. Such a sight glass 47 allows an operator, when the cover 21 is in the closed position, to see the microfluidic cartridge 3. It is indeed common for the microfluidic cartridge 3 to be transparent to give visual feedback to the operator during the analysis of the biological liquid sample. Thus, the sight glass 47 is particularly useful for verifying that the operation of the microfluidic cartridge 3 is in accordance with the wishes of the operator who, for example by means of the pneumatic connectors 27, controls the flow of liquids - in particular the biological liquid sample and the reagents - within the microfluidic cartridge 3.
[0090] When the microfluidic cartridge 3 has a structure similar to that of [Fig. 2], the fluidic card 5 is thus generally transparent to be able to observe the network of microchannels and the reaction chambers. The operator can ensure that the actuation of the valves of the fluidic card 5, carried out via the pneumatic card 7, is as expected. The inspection window 47 makes such monitoring possible even when the microfluidic cartridge 3 is held by the device 1.
[0091] To improve the retention of the microfluidic cartridge 3, the device 1 may comprise a locking mechanism arranged to detachably lock the cover 21 in the closed position on the base 19.
[0092] For example, such a locking mechanism comprises at least one pair of a through hole and a complementary hole provided in the cover 21 and the base 19 respectively. The through hole and the complementary hole are positioned such that, when the cover 21 is in the closed position, the through hole and the complementary hole face each other to receive together a fixing screw. The complementary hole may be a through hole or a blind hole.
[0093] In the example of [Fig. 1], the locking mechanism comprises a first pair of a through hole 49 and a complementary hole 51 and a second pair of a through hole 53 and a complementary hole 55.
[0094] The locking of the cover 21 in the closed position is illustrated in [Fig. 7]. In this figure, the cover 21 is folded down onto the microfluidic cartridge 3 and is locked onto the base 19. More particularly, the cover 21 is screwed onto the base 19 by means of a first fixing screw 57 and a second fixing screw 59. Typically, the first fixing screw 57 has a threaded rod complementary to the respective internal threads - obtained by tapping - of the through hole 49 and the complementary hole 51, and the second fixing screw 59 has a threaded rod complementary to the respective internal threads - also obtained by tapping - of the through hole 53 and the complementary hole 55.
[0095] Those skilled in the art will understand that other locking mechanisms may be used to lock the cover 21 to the base 19 in the closed position.
[0096] For example, the locking mechanism may comprise a lever latch - also called a mechanical latch or industrial latch - and a counter-hook mounted respectively on the base 19 and the cover 21. Conversely, the lever latch may be mounted on the cover 21 while the counter-hook is mounted on the base 19. A lever latch is generally formed of a base which may be riveted, screwed or welded, a handle and a movable hook.
[0097] The locking mechanisms described above can be combined to strengthen the retention of the microfluidic cartridge 3.
[0098] [Fig. 7], in which the cover 21 is in the closed position, also shows the rinsing system 23 in detail.
[0099] The device 1 has the particularity of having the necessary means - namely an integrated rinsing system 23 - for rinsing a microfluidic cartridge 3, in particular after analyzing a sample of biological liquid. Consequently, it is not necessary to use a disposable microfluidic cartridge 3 and, moreover, the microfluidic cartridge 3 can be rinsed while remaining held between the base 19 and the cover 21, therefore without having to be removed from the device 1.
[0100] In particular, the rinsing system 23 is arranged to selectively connect the orifice 29 to a reservoir (not shown here) in order to rinse the microfluidic cartridge 3 supported by the base 19.
[0101] It is understood that the orifice 29 has a dual use when the cover 21 is folded down into the closed position on the microfluidic cartridge 3: it allows, on the one hand, to introduce a sample of biological liquid into the fluidic inlet 13 and, on the other hand, to rinse the microfluidic cartridge 3 by means of the rinsing system 23; these two operations can be carried out while maintaining the microfluidic cartridge 3.
[0102] As illustrated in [Fig. 7], the rinsing system 23 comprises for example an arm 61 provided with a nozzle 63.
[0103] The arm 61 is rotatably mounted on the base 19 by means of a pivot connection 65. The pivot connection 65 allows the arm 61 to pivot about an axis to reach a position in which the tip 63 is received in the orifice 29.
[0104] In the example of [Fig. 7], the axis of the pivot link 65 - that is to say the axis of rotation of the arm 61 - is the Y axis, that is to say the same axis as that of the pivot link 31. However, the axis of the pivot link 65 may be distinct from the Y axis. In other configurations, the axis of the pivot link 65 may thus be parallel or orthogonal to the Y axis.
[0105] The nozzle 63 is capable of being connected to a reservoir and of delivering a liquid stored therein.
[0106] In the context of the invention, it is understood that the reservoir is typically a storage reservoir for a rinsing liquid and that such a rinsing liquid is intended to be introduced into the microfluidic cartridge 3 to evacuate in the form of waste the liquids involved in the biological analysis carried out, whether it be the sample of biological liquid or the reagents.
[0107] Such a reservoir may be external to the device 1, in which case the operator must connect the reservoir to the end piece 63. Alternatively, the arm 61 may be provided with a reservoir, in which case the arm 61 also comprises a conduit connecting the reservoir to the end piece 63. In the latter case, the reservoir may be housed in the arm 61.
[0108] Advantageously, the base 19 has a shoulder (not shown here) capable of serving as a support for the arm 61 when the latter pivots beyond a vertical position.
[0109] Such a shoulder makes it possible to maintain the arm 61 in a stable position when the rinsing system 23 is not in use, in particular when introducing a sample of biological liquid into the microfluidic cartridge 3 via the orifice 29 or during biological analysis. The shoulder may take the form of a recess in the base 19 extending towards the outside of the device 1. An operator may tilt the arm 61 beyond the vertical position - that is to say a position in which the arm 61 and the base 19 form an angle substantially equal to 90° - to leave the arm 61 resting on the shoulder.
[0110] Furthermore, in the embodiment of [Fig. 7], the cover 21 has an opening 67 and the arm 61 has a resilient end 69. As explained below, the opening 67 and the resilient end 69 are involved in locking the arm 61.
[0111] Reference is now made to [Fig. 8] which illustrates a sectional view of the device 1 in which the cover 21 is in the closed position and in which the arm 61 is locked onto the cover 21. To do this, the elastic end 69 is fitted by deformation into the opening 67 and is held there by mechanical stress.
[0112] After fitting, the elastic end 69 is no longer subjected to compression and therefore returns to its resting shape. In particular, the elastic end 69 has a resting shape which prevents it from being removed from the opening 67. This fitting - sometimes also called "clipping" - is reversible: an operator can apply pressure to the elastic end 69 to deform it and then remove it from the opening 67.
[0113] A position sensor (not shown here) can be integrated into the device 1 to ensure that the arm 61 is locked onto the cover 21.
[0114] The elastic end 69 is for example made of plastic. However, those skilled in the art understand that any material capable of being deformed and of imparting elasticity to the end of the arm 61 can be used.
[0115] It should also be noted that [Fig. 8] shows a conduit 71 which, as mentioned previously, makes it possible to connect the tip 63 to the reservoir containing the rinsing liquid used to rinse the microfluidic cartridge 3.
[0116] A method of using the device 1 will now be described with reference to [Fig. 9]. Generally speaking, this method falls within the context of carrying out one or more analyses on a sample of biological liquid with a microfluidic cartridge 3.
[0117] First, during an operation 900, the microfluidic cartridge 3 is placed on the base 19.
[0118] To do this, the operator can pivot the cover 21 around the Y axis to keep it in the open position and thus have access to the base 19. Keeping the cover 21 in the open position is made easier when the base 19 has a shoulder as described previously; it is then possible to tilt the cover 21 beyond a vertical position and let it rest on the shoulder provided for this purpose.
[0119] Furthermore, the positioning of the microfluidic cartridge 3 can be facilitated by the presence of stops 25 which together delimit a location intended to accommodate the microfluidic cartridge 3. As mentioned previously, one or more of these stops 25 can have an elastic portion 26 to be able to adapt to different dimensions of the microfluidic cartridge 3. The elastic portion(s) 26 also make it easier to position the microfluidic cartridge 3 and improve its retention.
[0120] During an operation 910, the cover 21 is folded down onto the microfluidic cartridge 3.
[0121] To do this, the operator pivots the cover 21 around the Y axis to make it reach the closed position in which the orifice 29 is opposite the fluidic inlet 13 of the microfluidic cartridge 3.
[0122] Furthermore, when the base 19 is formed of a fixed portion 43 and a movable portion 45 as described previously with reference to [Fig. 5], reaching the closed position for the cover 21 can be facilitated by moving the movable portion 45 in translation along the Z axis to modify the height of the pivot connection 31 relative to the base 19 and thus adapt to the thickness of the microfluidic cartridge 3. Such an embodiment has the advantage that it makes it possible to avoid the problem illustrated in [Fig. 6], namely an insufficient contact surface between the cover 21 and the microfluidic cartridge 3 which results in too large a space between the orifice 29 and the fluid inlet 13, as well as between the fluid connectors 41 and the corresponding inlet / outlet orifices 15.
[0123] During an operation 920, the cover 21 can be locked onto the base 19 to improve the retention of the microfluidic cartridge 3.
[0124] As explained previously with reference to [Fig. 7], it is thus possible to screw the cover 21. More particularly, at least one fixing screw 57 (respectively 59) can be driven into a through hole 49 (respectively 53) and a complementary hole 51 (respectively 55) provided respectively in the cover 21 and the base 19 and which are opposite each other when the cover 21 is in the closed position. It is also possible to use a lever closure and a counter-hook mounted respectively on the base 19 and the cover 21, or vice versa.
[0125] During an operation 930, the sample of biological liquid to be analyzed is introduced into the microfluidic cartridge 3, and more precisely into the fluidic inlet 13, via the orifice 29.
[0126] For example, the biological fluid sample to be analyzed is a sample of blood, urine, cerebrospinal fluid, pleural fluid or even synovial fluid.
[0127] It should be noted that such an introduction is easier when the orifice 29 is a female Luer-Lock type connector since the liquid injection instruments are, for the most part, provided with a male Luer-Lock type connector. For example, in [Fig. 4], the injection instrument shown is provided with an adapter 35 in the form of a male Luer-Lock type connector. Another advantage is that such an orifice 29 makes it possible to improve the seal, which can be reinforced by the presence of an O-ring 39. As mentioned previously, the orifice 29 can take the form of a connector other than a female Luer-Lock type connector.
[0128] The introduction of the biological fluid sample is not necessarily carried out by injection, i.e. by jet or pressure using a suitable injection instrument. For example, it is possible to introduce the biological fluid sample into the microfluidic cartridge 3 by suction.
[0129] During an operation 940, one or more analyses of the biological fluid sample are carried out with the microfluidic cartridge 3.
[0130] Biological analyses are generally used in the field of medical biology to determine the pathophysiological origin of a disease. Biological analyses can also contribute to the prevention, screening, diagnosis or assessment of the risk of the occurrence of pathological conditions, as well as to the determination or monitoring of the physiological or pathophysiological state of a patient.
[0131] Furthermore, the biological analysis(s) to be carried out with the microfluidic cartridge 3 may involve mixing with reagents. In such a case, these reagents may be introduced into the microfluidic cartridge 3 via the fluidic connectors 41.
[0132] Reagents can be used, for example, to dilute the biological fluid sample. For example, in the field of hematology, dilution is used to perform a complete blood count (CBC). In the English literature, a complete blood count is also referred to as a CBC. Due to the concentration of blood cells in a blood sample, namely leukocytes (or white blood cells), erythrocytes (or red blood cells), and thrombocytes (or platelets), prior dilution is preferable to facilitate cell counting and differentiation.
[0133] To carry out a biological analysis, the operator can control the microfluidic cartridge 3 held by the device 1. Thus, as illustrated in particular in [Fig. 3], the underside of the base 19 gives the operator access to pneumatic connectors 27 which make it possible to control the circulation of liquids, in particular the biological liquid sample and the reagents, by targeted pressure variations. The sight glass 47 of the cover 21 also gives the operator visibility of the microfluidic cartridge 3. The operator can thus ensure that the biological analysis is taking place as planned and, if necessary, intervene using the pneumatic connectors 27.
[0134] When the microfluidic cartridge 3 has a structure similar to that of [Fig. 2], the biological fluid sample and the reagents circulate in a network of microchannels and reaction chambers of the fluidic card 5.
[0135] Once the biological analysis(s) have been carried out, the operator can rinse the microfluidic cartridge 3.
[0136] To do this, during an operation 950, the orifice 29 is connected to a reservoir storing a rinsing liquid by means of the rinsing system 23.
[0137] In the example illustrated in the figures, the rinsing system 23 takes the form of an arm 61 provided with a tip 63 and connected to the base 19 by a pivot connection 65. For rinsing the microfluidic cartridge 3, the arm 61 is folded onto the cover 21 - still in the closed position - to reach a position in which the tip 63 is received in the orifice 29.
[0138] Furthermore, as illustrated in [Fig. 8], the arm 61 can be locked onto the cover 61 to prevent any disconnection between the end piece 63 and the orifice 29. To do this, the operator simply has to exert pressure on the elastic end 69 of the arm 61 to deform it and fit it into the opening 67.
[0139] Finally, during an operation 960, the microfluidic cartridge 3 is rinsed by introducing the rinsing liquid via the orifice 29. The rinsing liquid is typically a diluent - or rinsing diluent.
[0140] As with the introduction of the biological fluid sample, the rinsing liquid can be introduced into the microfluidic cartridge 3 by injection or by aspiration.
[0141] In any event, the rinsing system 23 passes the rinsing liquid from the reservoir to the microfluidic cartridge 3.
[0142] In particular, in the example of the figures, the rinsing liquid is delivered by the end piece 63 of the arm 61. Furthermore, the reservoir may be external to the device 1, in which case the operator must connect the reservoir to the end piece 63, or be part of the arm 61, which then also comprises a conduit 71 connecting the reservoir to the end piece 63.
[0143] Once rinsed, the microfluidic cartridge 3 can be reused to carry out new analyses on another sample of biological liquid. It is not necessary to open the device 1 to replace the microfluidic cartridge 3; it can remain held between the base 19 and the cover 21.
[0144] A device 73 for holding a microfluidic cartridge will now be described with reference to [Fig. 10] and [Fig. 11],
[0145] Device 73 is not covered by the scope of the claims, although device 1 and device 73 share common elements.
[0146] In [Fig. 10] and [Fig. 11], several of these common elements are present and as such bear the same reference sign as in the drawings relating to the device 1, namely the cover 21, the orifice 29, the O-ring 39, the fluid connections 41, the inspection window 47, the through hole 49 and the through hole 53.
[0147] Other elements, although common to device 1 and device 73, are not shown in [Fig. 10] and [Fig. 1 1 ], such as the base 19, the stops 25 or the pivot connection 31 . The variants presented above and relating to the common elements also apply to device 73, for example the lever closure and the counter-hook to produce the locking mechanism.
[0148] Furthermore, the device 73 having the function of holding a microfluidic cartridge, such a microfluidic cartridge 3 is present in [Fig. 10] and typically has a structure similar to that illustrated in [Fig. 2],
[0149] However, the device 73 has the particularity of comprising a needle 75, which is integral with the cover 21 and passes through the orifice 29.
[0150] Typically, the needle 75 extends in a direction substantially orthogonal to the cover 21. In [Fig. 10] and [Fig. 11], the cover 21 is in the closed position and the needle 75 then extends substantially in the Z direction. When the cover 21 is folded into the closed position on the microfluidic cartridge 3, the needle 75 opens onto the fluid inlet 13 of the microfluidic cartridge 3.
[0151] Needle 75 is arranged to take a sample of biological fluid and guide it to the microfluidic cartridge 3.
[0152] Furthermore, as illustrated in [Fig. 1 1 ], the O-ring 39 provided at the orifice 29 also makes it possible to improve the seal and to prevent any leakage when introducing a sample of biological liquid into the microfluidic cartridge 3 by means of the needle 75.
[0153] The device 73 also has the particularity of comprising a rinsing system 77 different from the rinsing system 23.
[0154] The expression "rinsing system" used in the claims does not cover the rinsing system 77. First of all, the rinsing system 77 does not comprise an arm provided with a tip capable of being connected to a reservoir and of delivering a liquid stored in this reservoir. Furthermore, the rinsing system 77 is arranged to rinse the needle 75, and not the microfluidic cartridge 3.
[0155] The rinsing system 77 is formed by an elongated body 79 having a cavity 81, a conduit 83, a rinsing inlet 85 and a rinsing outlet 87.
[0156] The cavity 81 extends along only a portion of the elongated body 79 and is intended to partially or completely house a tube 89 closed by a plug 91. For this purpose, the elongated body 79 has an opening 93, which allows the tube 89 to be introduced into the cavity 81.
[0157] In the example of [Fig. 10] and [Fig. 11], the elongated body 79 has the shape of a cylinder of revolution and the opening 93 is circular.
[0158] The conduit 83 extends along the remaining part of the elongate body 79, and therefore in the extension of the cavity 81. The cavity 81 and the conduit 83 communicate via an orifice 95. The conduit 83 receives the needle 75. For this purpose, the elongate body 79 has an orifice 97 - opposite the opening 93 - through which the needle 75 penetrates the elongate body 79. The rinsing inlet 85 opens onto the outside of the elongate body 79 and communicates with the conduit 83. The rinsing inlet 85 is arranged to be connected to a storage tank for a rinsing liquid.
[0159] Likewise, the rinsing outlet 87 opens onto the outside of the elongated body 79 and communicates with the conduit 83. The rinsing outlet 87 is arranged to evacuate the rinsing liquid from the elongated body 79.
[0160] As illustrated in [Fig. 1 1 ], the flushing inlet 85 communicates with the flushing outlet 87 via the conduit 83 which connects them to each other in a fluidic manner.
[0161] The rinsing system 77, and more precisely the elongated body 79, is mounted in translation on the cover 21 by means of at least one axis 99, which extends from the cover 21 in a direction substantially parallel to the needle 75.
[0162] In the example of [Fig. 10] and [Fig. 11], two 99 axes are present.
[0163] The axes 99 are arranged to allow the rinsing system 77 to slide along the needle 75 received within the conduit 83.
[0164] Advantageously, and as illustrated in [Fig. 10], the axes 99 are each provided with a spring (not referenced) whose return force allows the rinsing system 77 to return to a rest position.
[0165] [Fig. 1 1 ] shows two different positions of the rinsing system 77. Diagram (a) shows the rinsing system 77 in the rest position, while diagram (b) shows the rinsing system 77 in a sampling position.
[0166] Diagram (a) and diagram (b) show how a sample of biological fluid, contained in the tube 89 closed by the stopper 91, can be taken by the needle 75 and introduced into the microfluidic cartridge 3 for analysis purposes.
[0167] First, in diagram (a), the rinsing system 77 is in the rest position and the tube 89 is partially housed in the cavity 81 so that the stopper 91 is in contact with the orifice 95. The operator can then press on the tube 89, which causes a translation of the rinsing system 77 along the axes 99. The rinsing system 77 thus slides along the needle 75, which passes through the conduit 83, passes through the orifice 95, pierces the stopper 91 and penetrates the tube 89 to come into contact with the sample of biological liquid.
[0168] In diagram (b), the rinsing system 77 is in the sampling position, which is reached when the rinsing system 77 comes into contact with the cover 21 and cannot slide further along the needle 75.
[0169] The biological fluid sample contained in the tube 89 can then be collected by the needle 75 by suction. The biological fluid sample is guided by the needle 75 along the conduit 83, passes through the orifice 97 then the orifice 29 and is finally introduced into the microfluidic cartridge 3 via the fluidic inlet 13.
[0170] Once the sample has been taken, the rinsing system 77 returns to the rest position, either thanks to the operator who can slide the rinsing system 77 in the opposite direction, or thanks to the return force of the springs with which the axes 99 are possibly provided. The operator can then remove the tube 89. The configuration of the device 73 is then that of [Fig. 10].
[0171] The 75 needle flush can then be implemented.
[0172] To do this, the rinsing inlet 85 is connected to the rinsing liquid storage tank. The rinsing liquid - which is typically a diluent - is drawn into the rinsing inlet 85, circulates along the conduit 83 where it comes into contact with the needle 75 received therein, and is finally discharged through the rinsing outlet 87. The circulation of the rinsing liquid from the rinsing inlet 85 to the rinsing outlet 87 is here facilitated by the fact that the rinsing inlet 85 is at a higher height than the rinsing outlet 87 relative to the cover 21. It is thus possible to rinse the outside, but also the inside, of the needle 75.
Claims
Claims
1. Device (1) for holding a microfluidic cartridge (3), comprising: - a base (19) arranged to support a microfluidic cartridge (3), - a cover (21) having an orifice (29) and connected to said base (19) by a pivot connection (31), which pivot connection (31) allows said cover (21) to pivot to reach a closed position in which, when a microfluidic cartridge (3) is supported by the base (19), the orifice (29) is opposite a fluidic inlet (13) of said microfluidic cartridge (3), and - a rinsing system (23) arranged to selectively connect the orifice (29) to a reservoir in order to rinse a microfluidic cartridge (3) supported by the base (19), said device (1) being characterized in that the rinsing system (23) comprises an arm (61) provided with a tip (63) capable of being connected to said reservoir and of delivering a liquid stored in said reservoir, and in that said arm (61) is connected to the base (19) by a pivot connection (65), which pivot connection (65) allows the arm (61) to pivot to reach a position in which the tip (63) is received in the orifice (29).
2. Device (1) according to claim 1, characterized in that the arm (61) is further provided with a reservoir capable of containing a liquid and a conduit connecting said reservoir to the end piece (63).
3. Device (1) according to claim 1 or 2, characterized in that the cover (21) has an opening (67) and in that the arm (61) has an elastic end (69) capable of being fitted by deformation into said opening (67) and of being held there by mechanical stress when the end piece (63) is received in the orifice (29).
4. Device (1) according to one of the preceding claims, characterized in that the base (19) has a shoulder capable of serving as a support for the arm (61) when the latter pivots beyond a vertical position.
5. Device (1) according to one of the preceding claims, characterized in that the base (19) is provided with stops (25) delimiting together a location within which a microfluidic cartridge (3) can be positioned.
6. Device (1) according to one of the preceding claims, characterized in that the orifice (29) is a female Luer-Lock type connector.
7. Device (1) according to one of the preceding claims, characterized in that the base (19) comprises a fixed portion (43) arranged to support a microfluidic cartridge (3) and a movable portion (45) in translation in a direction (Z) substantially orthogonal to said fixed portion (43), and in that the movable portion (45) is provided with the pivot connection (31) by which the cover (21) is connected to the base (19).
8. Device (1) according to one of the preceding claims, characterized in that it further comprises a locking mechanism arranged to lock the cover (21) in the closed position on the base (19) in a detachable manner.
9. Device (1) according to claim 8, characterized in that the locking mechanism comprises at least one pair of a through hole (49, 53) and a complementary hole (51, 55) provided respectively in the cover (21) and the base (19) such that, when the cover (21) is in the closed position, the through hole (49, 53) and the complementary hole (51, 55) are opposite each other to receive together a fixing screw (57, 59).
10. Device (1) according to claim 8 or 9, characterized in that the locking mechanism comprises a lever closure and a counter-hook mounted respectively on the base (19) and the cover (21), or vice versa.
11. Device (1) according to one of the preceding claims, characterized in that the base (19) is provided with a plurality of pneumatic connections (27) arranged to be coupled to a microfluidic cartridge (3) supported by the base (19).
12. Device (1) according to one of the preceding claims, characterized in that the cover (21) is provided with a plurality of fluidic connections (41) arranged to be coupled to a microfluidic cartridge (3) supported by the base (19).
13. Device (1) according to one of the preceding claims, characterized in that the cover (21) has a viewport (47).
14. Method of using the device (1) according to one of the preceding claims comprising: - placing (900) a microfluidic cartridge (3) on the base (19), - pivot (910) the cover (21) until it reaches the closed position, - introducing (930) a sample of biological liquid into the microfluidic cartridge (3) via the orifice (29), and - carrying out (940) at least one analysis of said biological liquid sample with the microfluidic cartridge (3), said method being characterized in that it further comprises: - connecting (950) the orifice (29) to a reservoir storing a rinsing liquid by means of the rinsing system (23) by pivoting the arm (61) to reach a position in which the tip (63) is received in the orifice (29), and - rinsing (960) the microfluidic cartridge (3) by introducing the rinsing liquid, delivered by the tip (63), via the orifice (29).