Device for filling a cavity of a test card

Abstract

The invention relates to a device (1) for filling a cavity (60) of a test card (6) with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument, the device (1) comprising: - a main needle (2) which allows the cavity (60) to be filled with a reagent up to a first reagent level (N1); - a secondary needle (4) which is coaxial with the main needle (2) and is suitable for suctioning an amount of reagent from the cavity (60) such that the cavity (60) contains reagent up to a second reagent level (N2) which is lower than the first reagent level (N1).

Description

[0001] Title: Device for filling a cavity in an analysis card

[0002] Technical field of the invention

[0003] The present invention relates to the field of analysis cards for the analysis of a biological sample using an in vitro diagnostic instrument, more specifically to a device for filling a cavity of such an analysis card.

[0004] Technological background of the invention

[0005] Analysis cards for the analysis of a biological sample using an in vitro diagnostic instrument may include different cavities containing reagents that are released to react with the biological sample.

[0006] These cavities typically take the form of blisters, that is, thermoformed blisters in a polymer envelope.

[0007] When manufacturing an analysis card, it is necessary to fill these cavities with reagents, which are usually liquids. Filling these cavities raises several problems.

[0008] In practice, the cavity is filled with excess reagent to ensure that, after sealing, it is completely filled without air bubbles. However, this excess reagent is wasted and represents an additional cost. Furthermore, the excess reagent can contaminate the analysis card production line.

[0009] Object of the invention

[0010] One object of the invention is to provide a solution to enable the filling of a cavity of an analysis card for the analysis of a biological sample by means of an in vitro diagnostic instrument that is more economical.

[0011] Another objective of the invention is to provide a solution for filling a cavity in an analysis card without contaminating the analysis card production line. To this end, the invention relates to a device for filling a cavity in an analysis card with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument, the device comprising:

[0012] - a main needle adapted to allow filling of the cavity with a reagent according to a first reagent level,

[0013] - a secondary needle coaxial with the main needle, adapted to aspirate a quantity of reagent into the cavity so that the cavity contains reagent at a second level of reagent lower than the first level of reagent.

[0014] Advantageously, the coaxiality of the needles allows for filling and aspiration centered on the shape of the cavity. This avoids any asymmetry that could induce non-uniform edge effects.

[0015] According to one feature of the invention, the secondary needle includes a pumping orifice adapted to be disposed in the cavity and a suction orifice adapted to be connected to a suction system.

[0016] According to one feature of the invention, the main needle comprises a first main end including a filling orifice, the secondary needle comprises a first secondary end including a pumping orifice, the first main end and the first secondary end being adapted to be disposed in the cavity when filling the cavity or aspirating the quantity of reagent, the first main end being flush with the first secondary end.

[0017] Advantageously, the fact that the orifices are flush allows the suction to define a precise filling level and volume without any liquid retention effects from the main needle. If the main needle protrudes, the suction would not be able to aspirate any residual liquid present on that part.

[0018] According to one feature of the invention, the secondary needle is arranged around the main needle.

[0019] The invention also relates to a system for filling a cavity of an analysis card with a reagent for the analysis of a biological sample by means of an in vitro diagnostic instrument comprising a device according to the invention, an aspiration system connected to the secondary needle and a reagent dispensing system connected to the main needle.

[0020] According to one feature of the invention, the suction system and / or the reagent dispensing system is a pump.

[0021] According to one feature of the invention, the reagent dispensing system is adapted to be connected to a reagent reservoir and the suction system (8) is adapted to be connected to the reagent reservoir.

[0022] The invention also relates to a method of filling a cavity of an analysis card with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument from a system according to the invention, comprising the steps of: a) disposition of the filling device with respect to the cavity, b) filling of the cavity with the reagent via the main needle according to the first level of reagent, c) aspiration of a quantity of reagent via the secondary needle into the cavity so that the cavity contains reagent according to the second level of reagent.

[0023] According to one feature of the invention, the secondary needle comprises a first secondary end including a pumping orifice and adapted to be disposed in the cavity when aspirating the quantity of reagent and in which, prior to step c), the filling device is disposed so that the first secondary end is disposed at the second level of reagent.

[0024] According to one feature of the invention, in step c), the quantity of reagent aspirated flows to the reagent reservoir.

[0025] According to one feature of the invention, step c) of aspiration is carried out during the implementation of step b) of filling.

[0026] The invention also relates to a method of manufacturing an analysis card for the analysis of a biological sample using an in vitro diagnostic instrument comprising the steps of: i) filling a cavity of the analysis card with a reagent according to the filling method according to the invention, ii) sealing the cavity at the second level of reagent.

[0027] Brief description of the figures

[0028] The invention will be better understood from the following description, which relates to an embodiment of the present invention, given by way of non-limiting example and explained with reference to the accompanying schematic figures. The accompanying schematic figures are listed below:

[0029] Fig. 1 illustrates a system for filling a cavity of an analysis card with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument;

[0030] Fig. 2 illustrates an analysis card and a device for filling a cavity of the analysis card with a reagent;

[0031] Fig. 3 illustrates a filling device and a cavity during a cavity filling step;

[0032] Fig. 4 illustrates a filling device and a cavity at the end of a filling step;

[0033] Fig. 5 illustrates a filling device and a cavity during a step of aspirating reagent out of the cavity;

[0034] Fig. 6 illustrates a filling device and a cavity at the end of an aspiration step;

[0035] Fig. 7 represents the steps in a manufacturing process for an analysis card.

[0036] Detailed description

[0037] With reference to Figures 1 and 2, a device 1 is proposed for filling a cavity 60 of an analysis card 6 with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument. The in vitro diagnostic instrument could, for example, be an imager.

[0038] The analysis card 6 is a microfluidic system for performing analyses on a biological sample. The analysis card 6 typically includes one or more cavities 60 adapted to hold reagents. The cavities 60 may be blister-shaped. The analysis card 6 also includes a microplate 61 comprising one or more wells connected by microfluidic conduits to the cavities 60. The conduits 62 include, for example, weak valves adapted to rupture when the cavities 60, i.e., blisters, are squeezed until the pressure applied to the weak valves reaches a certain pressure threshold necessary for their rupture, thus allowing reagent to flow from a cavity to the wells of the microplate. The analysis card 6 further includes a sample introduction port 63 connected to the microplate by microfluidic conduits and adapted to allow sample introduction into the microplate.

[0039] During the manufacture of the analysis card 6, it is necessary to fill the cavities 60 before they are sealed. Device 1 is provided for this purpose.

[0040] With reference to Figure 4, the device 1 includes a main needle 2 adapted to allow filling of cavity 60 with a reagent according to a first level NI of reagent.

[0041] The main needle 2 has an internal channel adapted to allow the passage of liquid reagent. Advantageously, the internal channel of the main needle 2 has a diameter less than or equal to 0.9 mm, and preferably less than or equal to 0.6 mm. The upper diameter of the internal channel of the main needle 2 is proportional to and smaller than the lower diameter of the main needle 2.

[0042] The main needle 2 preferably has a length greater than or equal to 60mm, more preferably greater than or equal to 50mm.

[0043] The main needle 2 is advantageously made of stainless steel.

[0044] With reference to Figure 1, the main needle 2 comprises a first main end 22 and a second main end 26. The main needle 2 extends from the first main end 22 to the second main end 26. The first main end 22 includes a filling port 24. The second main end 26 includes a reagent dispensing port 28.

[0045] The first main end 22 and therefore the filling orifice 24 are adapted to be disposed in the cavity 60 when filling the cavity 60.

[0046] The main needle 2 is adapted for connection to a reagent dispensing system 9. More specifically, the second main end 26 and the reagent dispensing port 28 are adapted for connection to the dispensing system 9. The dispensing system 9 can typically be a pump such as a peristaltic pump. The dispensing system 9 is adapted for connection to a reagent reservoir 92.

[0047] The main needle 2 is adapted to fill cavity 60 to a first level NI of reagent. By level, we mean the height reached by the reagent in cavity 60 when the analysis card 6 is positioned according to a cavity 60 filling orientation. It is understood that the filling orientation of a cavity 60 is an orientation according to which the analysis card 6 can be positioned to fill the cavity 60. The filling orientation is associated with a cavity 60. The filling orientation of one cavity 60 according to which the analysis card 6 can be positioned may be different from the filling orientation of another cavity 60. The filling orientation of cavity 60 advantageously corresponds to an orientation in which the bottom of the cavity 60 is positioned below the cavity opening 60, allowing the cavity 60 to be filled, the axis extending between the bottom and the opening being a vertical axis.The filling orientation of cavity 60 advantageously corresponds to an orientation in which, when reagent is contained within cavity 60, the free surface of the reagent at rest is parallel to a horizontal plane. The free surface corresponds to the surface of the reagent at the interface between the reagent in the cavity and the air or other fluid other than the reagent that is above the reagent. By "at rest," it is understood that the analysis plate 6 is not subjected to any disturbances, for example, any movement, so that the free surface of the reagent is flat. By horizontal plane, it is understood that a plane perpendicular to a direction, to an axis that conventionally represents the vertical. The vertical direction corresponds to the direction of gravity.

[0048] Thus, the level can also be understood as a virtual graduation of the cavity. If the tip of a needle is positioned at a first level NI, it means that the tip is at a level of the cavity corresponding to the free surface area of ​​a reagent that would fill cavity 60 according to the first level NI if cavity 60 contained reagent. The first level NI corresponds to a reagent level higher than the desired final level of reagent in cavity 60. In other words, the amount of reagent present in cavity 60 when cavity 60 is filled to a first level NI is greater than the desired amount of reagent in cavity 60. The desired amount of reagent corresponds to the amount of reagent identified as necessary to perform the analysis of a biological sample.

[0049] Device 1 further includes a secondary needle 4. The secondary needle 4 is adapted to aspirate a quantity of reagent into cavity 60. The secondary needle 4 has an internal channel adapted to allow the passage of liquid reagent. Advantageously, the internal channel of the secondary needle 4 has a diameter less than or equal to 1.4 mm, and preferably less than or equal to 1.2 mm. The upper diameter of the internal channel of the secondary needle 4 is proportional to and smaller than the lower diameter of the internal channel of the secondary needle 4.

[0050] Secondary needle 4 preferably has a length greater than or equal to 50mm, more preferably greater than or equal to 40mm.

[0051] Secondary needle 4 is advantageously made of stainless steel.

[0052] The secondary needle comprises a first secondary end 42 and a second secondary end 46. The first secondary end 42 comprises a pumping port 44. The second secondary end 46 comprises a suction port 48.

[0053] The first secondary end 42 and therefore the pumping orifice 44 are adapted to be disposed in the cavity 60 during aspirating of reagent into the cavity 60.

[0054] The secondary needle 4 is adapted for connection to a reagent aspiration system 8. More specifically, the second secondary end 46 and the aspiration port 48 are adapted for connection to the aspiration system 8. The aspiration system 8 can typically be a pump such as a peristaltic pump. The dispensing system 8 is advantageously adapted for connection to the reagent reservoir 92. The secondary needle 4 is coaxial with the primary needle 2. In this way, the positioning of the device 1 relative to the cavity 60 is facilitated. Furthermore, the device 1 is less bulky, and both needles 2 and 4 can be inserted into the cavity 60. Filling and aspiration can be performed without requiring multiple steps of inserting, positioning, and removing needles from the cavity 60.

[0055] Advantageously, the secondary needle 4 is arranged around the main needle 2. In other words, as illustrated in Figure 1, at least a part of the main needle 2 is arranged inside the secondary needle 4.

[0056] The main needle 2 is preferably centered to ensure homogeneous filling of cavity 60. The filling fluid jet is located at the center of cavity 60. The fluid level rises evenly during filling, distributed across the surface of cavity 60. The fluid meniscus is thus horizontal, allowing for subsequent sealing of cavity 60 without trapped air bubbles. Advantageously, the first main end 22 is flush with the first secondary end 42. In other words, the filling port 24 and the pumping port 44 are aligned and at the same level.

[0057] As illustrated in Figure 6, the secondary needle 4 is adapted to aspirate a quantity of reagent into cavity 60 such that cavity 60 contains reagent at a second level N2 that is lower than the first level NI. It is therefore understood that when the analysis card 6 is positioned in the cavity 60 filling orientation, the second level N2 is lower than the first level NI. In other words, when cavity 60 is filled to a second level N2 of reagent, the amount of reagent in cavity 60 is less than the amount of reagent in cavity 60 when it is filled to the first level NI.

[0058] With reference to Figure 1, a system 10 is proposed for filling a cavity 60 of an analysis card 6 with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument.

[0059] System 10 includes device 1 presented previously.

[0060] The system 10 further includes an aspiration system 8 connected to the secondary needle 4 and a reagent dispensing system 9 connected to the main needle 2.

[0061] The suction system 8 and / or the dispensing system 9 are advantageously pumps, for example peristaltic pumps.

[0062] The reagent dispensing system 9 is designed to be connected to a reagent reservoir 92. The dispensing system 9 is designed to circulate reagent from the reservoir 92 to the main needle 2.

[0063] Advantageously, the suction system 8 is also suitable for connection to the reagent reservoir 92. Therefore, the system 10 is suitable for returning a quantity of reagent withdrawn from a cavity 60 to the reagent reservoir 92, this quantity being able to be reused to fill another cavity 60.

[0064] With reference to Figure 7, a method is proposed for filling a cavity 60 of an analysis card 6 with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument.

[0065] The process is implemented using the system 10 presented previously. The process includes a step a) of arranging the filling device 1 relative to the cavity 60.

[0066] More specifically, the first main end 22 and the first secondary end 42 are inserted into the cavity 60.

[0067] The first secondary end 42 is advantageously inserted into the cavity 60 at a position that corresponds to the desired reagent level in the cavity 60 when the analysis card 6 is oriented according to the cavity 60 filling orientation. The first secondary end 42 is inserted into the cavity 60 such that the pumping orifice 44 is at this level. In other words, the first secondary end 42 is inserted into the cavity 60 such that the pumping orifice 44 is at the same level as the reagent-free surface if the cavity 60 were filled to a second level N2 of reagent.

[0068] According to another embodiment, the first main end 22 and the first secondary end 42 are inserted into the cavity 60 at a random position. The arrangement of the first secondary end 42 in the cavity 60 such that the pumping orifice 44 is at the second level N2 will be carried out no later than before the implementation of a suction step c) which is detailed later.

[0069] In step b), as illustrated in Figure 3, cavity 60 is filled with reagent R to the first NI level. More specifically, the dispensing system 9 dispenses reagent from reservoir 92 to the main needle 2 via the reagent dispensing port 28. The reagent flows through the main needle 2 from the second main end 26 to the first main end 22 and then falls into cavity 60. An amount of reagent necessary to reach the first NI level is thus injected into cavity 60. Recall that this amount is greater than the amount required in cavity 60 when the analysis card 6 is finalized and cavity 60 is sealed. In other words, there is more reagent in cavity 60 than is needed for the sample analysis when the analysis card 6 is used.

[0070] At the end of step b), cavity 60 is filled with reagent R according to the first NI level as illustrated in figure 4.

[0071] Advantageously, prior to step c) of aspiration, the filling device 1 is arranged so that the first secondary end 42 is positioned at the second level N2 of the reagent. In other words, the first secondary end 42 is inserted into the cavity 60 so that the pumping orifice 44 is at the second level N2.

[0072] In step c), as illustrated in figure 5, a quantity of reagent is aspirated out of cavity 60. More specifically, the aspiration system 8 causes the reagent to be pumped from cavity 60. The reagent enters the secondary needle 4 through the pumping port 44 and flows in the secondary needle 4 from the first secondary end 42 to the second secondary end 46.

[0073] Step c) can be implemented after or during the filling step b). Aspirating reagent out of the cavity directly after, or during, the filling step b) prevents any migration of reagent out of cavity 60 by capillary action which could lead to contamination of other cavities 60 of the analysis card 6 which are intended to receive other types of reagents.

[0074] It is understood that the aspiration system 8 can be activated simultaneously with the reagent dispensing system 9. Since the first secondary end 42, and therefore the pumping port 44 of the secondary needle 4, is specifically positioned at the second N2 level, reagent will only be aspirated from cavity 60 if cavity 60 is filled beyond the second N2 level. This prevents any risk of reagent overflowing from cavity 60.

[0075] Advantageously, the reagent exits the secondary needle 4 via the aspiration port 48 and flows to the reservoir 92.

[0076] At the end of step c), cavity 60 is filled to the second level N2 of reagent R as illustrated in Figure 6. The second level N2 of reagent is lower than the first level NI of reagent. At the end of step c), cavity 60 is filled with reagent as desired. There is no excess reagent unnecessary for the analysis of a biological sample.

[0077] It is therefore clear that it is not necessary to precisely control the quantity of reagent injected into cavity 60 via the main needle 2. Consequently, a dispensing system 8 capable of delivering very precise quantities of reagent is unnecessary and would be costly. In fact, it is only necessary that this quantity be greater than the quantity of reagent in cavity 60 when the cavity is filled according to the second level N2. The secondary needle 4, by virtue of its specific positioning relative to cavity 60, and the aspiration system 8 then ensure that cavity 60 is filled with the desired amount of reagent. Thus, the fill level of cavity 60 at the end of the filling process does not depend on the precision of the dispensing system 9 but solely on the positioning of the secondary needle 4 relative to cavity 60.The system 10 can therefore be easily used to fill cavities 60 of different capacities, it is enough to adapt the positioning of the secondary needle 4 according to the desired level of filling.

[0078] With reference to Figure 7, a method is proposed for manufacturing an analysis card 6 for the analysis of a biological sample using an in vitro diagnostic instrument.

[0079] The manufacturing process includes step i) filling at least one cavity of the analysis card 6 with a reagent according to the filling process described previously. Then, in step ii), the cavity 60 is sealed at the second reagent level N2. In other words, the cavity 60 is sealed, for example by heat-sealing two films forming the cavity 60, at the reagent-free surface when the analysis card 6 is positioned in a cavity-filling orientation. Since the cavity 60 has been filled with exactly the amount required for the sample analysis, no excess reagent escapes from the sealed cavity 60 and could contaminate the production line of the analysis cards 6. Furthermore, there is no reagent deficiency in the cavity 60, so the cavity does not contain air bubbles that could interfere with the reaction between the reagent and the sample.Also, since there is no shortage of reagent, the desired reaction will take place correctly when using analysis card 6.

[0080] Of course, the invention is not limited to the embodiment described and shown in the accompanying figures. Modifications remain possible, particularly with regard to the composition of the various elements or by substitution of technical equivalents, without departing from the scope of protection of the invention.

Claims

DEMANDS 1. Device (1) for filling a cavity (60) of an analysis card (6) with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument, the device (1) comprising: - a main needle (2) adapted to allow filling of the cavity (60) with a reagent according to a first level (NI) of reagent, - a secondary needle (4) coaxial to the main needle (2), adapted to aspirate a quantity of reagent into the cavity (60) so that the cavity (60) includes reagent at a second level (N2) of reagent lower than the first level (NI) of reagent.

2. Device (1) according to claim 1, wherein the secondary needle (4) comprises a pumping orifice (44) adapted to be disposed in the cavity (60) and an aspiration orifice (48) adapted to be connected to an aspiration system (8).

3. Device (1) according to any one of claims 1 and 2, wherein the main needle (2) comprises a first main end (22) comprising a filling orifice (24), the secondary needle (4) comprises a first secondary end (42) comprising a pumping orifice (44), the first main end (22) and the first secondary end (42) being adapted to be disposed in the cavity (60) during filling of the cavity (60) or aspiration of the quantity of reagent, the first main end (22) being flush with the first secondary end (42).

4. Device (1) according to any one of claims 1 to 3, wherein the secondary needle (4) is arranged around the main needle (2).

5. System (10) for filling with a reagent a cavity (60) of an analysis card (6) for the analysis of a biological sample by means of an in vitro diagnostic instrument comprising a device (1) according to any one of claims 1 to 4, an aspiration system (8) connected to the secondary needle (4) and a reagent dispensing system (9) connected to the main needle (2).

6. System (10) according to claim 5, wherein the reagent suction system (8) and / or dispensing system (9) is a pump.

7. System according to any one of claims 5 and 6, wherein the reagent dispensing system (9) is adapted to be connected to a reagent reservoir (92) and the suction system (8) is adapted to be connected to the reagent reservoir (92).

8. Method of filling a cavity (60) of an analysis card (6) with a reagent for the analysis of a biological sample using an in vitro diagnostic instrument from a system according to any one of claims 5 to 7, comprising the steps of: a) arranging the filling device (1) relative to the cavity (60), b) filling the cavity (60) with the reagent via the main needle (2) according to the first level (NI) of reagent, c) aspirating a quantity of reagent via the secondary needle (4) into the cavity (60) so that the cavity (60) contains reagent according to the second level (N2) of reagent.

9. Method according to claim 8, wherein the secondary needle (4) comprises a first secondary end (42) comprising a pumping orifice (44) and adapted to be disposed in the cavity (60) during aspiration of the quantity of reagent and wherein, prior to step c), the filling device (1) is disposed so that the first secondary end (42) is disposed at the second level (N2) of reagent.

10. A method according to any one of claims 8 and 9 from the system according to claim 7, wherein, in step c), the aspirated quantity of reagent flows to the reagent reservoir (92).

11. A method according to any one of claims 8 to 10, wherein step c) of aspiration is carried out during the implementation of step b) of filling.

12. A method for manufacturing an analysis card (6) for the analysis of a biological sample using an in vitro diagnostic instrument comprising the steps of: i) filling a cavity (60) of the analysis card (6) with a reagent according to the filling method according to any one of claims 8 to 11, ii) sealing of cavity (60) at the second level (N2) of reagent.

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