EP1159070B1 - Apparatus enabling liquid transfer by capillary action therein - Google Patents

Abstract

An apparatus ( 1 ) which includes at least one planar surface ( 2 ) having compartments ( 3 ) which are defined by a partition ( 4 ), the compartments creating a space which makes it possible to displace at least one liquid sample ( 5 and/or 15 ) and, when there are at least two liquid samples ( 5 and 15 ), makes it possible to displace them both in an independent way and bring them together so that they can react with one another. The compartments ( 3 ) include at least two different types of groove: a deep groove ( 6 ), capable of partitioning the sample(s) ( 5 and/or 15 ), and a shallow groove capable of receiving the sample (s) ( 5 and/or 15 ), the two types of groove ( 6 and 16 ) making it possible to direct sample movements ( 5 and/or 15 ) by altering the orientation of the apparatus ( 1 ). The invention is particularly applicable for the micromanipulation of fluids in biological applications.

Description

The present invention relates to an apparatus which includes within it compartments delimited by a partition, creating a space for oriented movement and independently of at least one liquid sample. When there is at least two different liquid samples, it is possible to move them, to make them converge and make them react together.

Numerous prior art documents involve capillarity in micro-fluidics. Document GB-A -2,261,284 therefore proposes a transfer device fluids to perform diagnostic tests. This device uses channels made of porous material.

In this embodiment, the capillary function is used due to the use of a porous material. This requires the insertion of this porous material and also to provide an impermeable material between two channels of porous material containing different liquids. This technique is therefore quite expensive to implement. artwork.

The patent US-A-5,842,787 relates to microfluidic systems which incorporate channels of variable dimensions. These channels have essentially depths which may vary. However, these variations are also associated with the width of these channels. Thus the greater the depth of a channel, the more its width is small, and vice versa.

These channels are unfortunately not open, in other words the liquids, to be transferred within them, normally occupy the entire section of these channels. There are therefore many retention forces that hinder movement of these liquids, which requires more sophisticated means of transfer (pumps more powerful, creation of larger voids, etc.).

In US-A-5,660,993, capillarity is used to form a valve, by crossing two capillary channels.

In addition to this new function for closing and opening a liquid flow, the problems encountered are identical to those raised by the previous document, since these channels are closed and therefore there are retention phenomena.

According to documents EP-A-0.075.605 and WO-A-99 / 55852, superficial and deep grooves are associated for guiding liquids.

However, the use of physical characteristics (capillarity or not) associated with deep and shallow grooves are absolutely not described and are not no longer obvious to those skilled in the art.

In accordance with the present invention, the proposed apparatus solves all of the problems raised by proposing a structure which uses capillarity to allow moving liquids while minimizing retention phenomena. This allows perfectly efficient guidance even in the presence of a free space, which does not provide delimitation of the transferred liquid.

• un premier type de rainure(s) dite(s) profonde(s), faisant office de moyen de cloisonnement du ou des échantillons, la ou les rainures profondes sont à une distance de la cloison qui ne fait pas intervenir la capillarité, et
• un second type de rainure(s) dite(s) superficielle(s), faisant office de moyens de réception dudit ou desdits échantillons, la ou les rainures superficielles sont à une distance de ladite cloison qui fait intervenir la capillarité,

les deux types de rainures permettant de guider les déplacements du ou des échantillons en fonction de l'orientation donnée à l'appareil.To this end, the present invention relates to an apparatus comprising at least one flat surface at the level of which compartments are present and delimited by a partition, the compartments creating a space which allows the displacement of at least one liquid sample independently and , when there are at least two liquid samples, their independent displacement and their bringing together to react them together, characterized in that the compartments are made up of at least two different types of grooves:

• a first type of groove (s) called (s) deep (s), acting as partitioning means of the sample (s), the deep groove (s) are at a distance from the partition which does not involve capillarity, and
• a second type of groove (s) known as surface (s), acting as means for receiving said sample (s), the surface groove (s) are at a distance from said partition which involves capillarity,

the two types of grooves used to guide the movements of the sample or samples as a function of the orientation given to the device.

According to a preferred embodiment, the width of each groove deep has a dimension that does not involve capillarity.

According to another variant or another embodiment, at least one groove superficial is adjacent to a deep groove.

According to another embodiment, which can be complementary to the previous one, at least one deep groove is adjacent to a surface groove.

Preferably, and whatever the embodiment, a deep groove is positioned between two surface grooves.

In this case, the deep groove has one end, and the two grooves surface meet at this end to create a reaction zone.

According to a first embodiment, the reaction zone is at a distance from the bulkhead or bulkhead film that involves capillary action.

According to a second embodiment, the reaction zone is at a distance from the partition or partitioning film which does not involve capillary action.

The attached figures are given as an explanatory example and have no limiting character. They will allow a better understanding of the invention.

Figure 1 shows an elevational view of the face of the apparatus having the compartment according to the invention.

FIG. 2 represents a partial cross-sectional view along A-A of the figure 1.

FIG. 3 represents a view identical to FIG. 2 in which a sample liquid is present.

FIG. 4 represents a view identical to FIGS. 2 and 3 in which two different liquid samples are present.

Figure 5 shows a sectional view identical to Figure 2, but from a second embodiment containing a liquid sample.

Finally, Figure 6 shows a sectional view identical to Figure 2, but of a third embodiment of the present invention, wherein a liquid sample is present.

The present invention relates to an apparatus 1 well represented on all of the Figures 2 to 6 in partial sectional view according to three different embodiments.

The present invention relates to an apparatus 1 well represented on all of the Figures 2 to 6 in partial sectional view according to three different embodiments.

Such an apparatus 1 can be used for the analysis of one or more samples different liquids in which one seeks to identify one or more analytes, according to all simple or complex analysis processes involving one or more different reagents depending on the chemical, physical or biological nature of the analyte (s) research. The technical principles defined below are not limited to an analyte particular, the only requirement being that the analyte is distributed in the sample to be analyzed in suspension or in solution. In particular, the analysis process implemented work can be done, in homogeneous or heterogeneous or mixed form.

One particular, non-limiting mode of such an apparatus relates to the analysis biological, of one or more ligands, requiring for their detection and / or their quantification the use of one or more anti-ligands. By ligand is meant any biological species such as, for example, an antigen, an antigen fragment, a peptide, antibody, antibody fragment, hapten, nucleic acid, fragment of nucleic acid, a hormone, a vitamin. An example of application of analysis techniques concern immunoassays, whatever their format, by analysis direct or by competition. Another example of application relates to the detection and / or quantification of nucleic acids including all the necessary operations to this detection and / or quantification from any sample containing target nucleic acids. Among these different operations, we can cite the lysis, fluidification, concentration, steps of enzymatic amplification of nucleic acids, the detection steps incorporating a hybridization step using for example a DNA chip or a labeled probe. Patent application WO-A-97/02357 explains the different steps required in the case of acid analysis Nucleic.

In a particularly interesting embodiment represented on the Figures 1 to 4, we note that the device 1 is in fact made up of a card whose two upper and lower faces are parallel to each other. Well

In the figures, the two faces are flat but the upper face is the most interesting for the present invention. So the upper flat surface 2 of the device 1 has cavities which create compartments 3. The compartments are partitioned from the flush surfaces of surface 2 by means of a partition or partitioning film 4. This compartment 3, thus isolated, is in fact made up of different shapes. First there are two lateral surface grooves 16 and then a deep central groove 6. This figure 2 corresponds to the sectional view partial according to A-A of Figure 1. In this figure 1, we notice that the two grooves surface 16 are parallel to each other along the groove deep 6. However, the deep groove 6 has one end 7 where the two surface grooves 16 meet to create a reaction zone 8.

It is possible to isolate a first liquid sample 5 at one of the surface grooves 16. This is the case in FIG. 3. It is also possible to isolate by plus a second liquid sample 15 at the other surface groove 16. This is the case of FIG. 4. In fact, so that the liquids 5 and 15 remain in position at the level surface grooves 16 and do not mix, it is necessary that the distance separating the bottom of the surface groove 16 relative to the partitioning film 4 or low enough to involve the capillary force. The right distance between the film 4 and the groove 16 to have an optimal capillary force is included between 50 and 800 micrometers (µm), and preferably between 300 and 500 µm. In the case of a device consisting of a card machined from impact polystyrene and a BOPP film and the transfer of an aqueous solution containing for example 9g / l of NaCl, 1g / l of NaN3, 1ml / l of Tween 20 (registered trademark) or Triton X100 (registered trademark), the distance between the film 4 and the groove 16 is chosen at 400 μm. This dimension is actually characteristic of liquids 5 and / or 15 which are used in the apparatus 1 in connection with the nature of the materials used in the device. Depending on the viscosity of the density, the wettability or surface tension of liquids and depending on the nature hydrophilic or hydrophobic of the materials used, such as for example the film of partitioning or the map, it will be necessary to vary this distance if necessary.

Conversely, the distance separating the film 4 from the bottom of the deep groove 6 is very important so that no capillary force allows the retention of like for example the partitioning film or the card, it will be necessary to make possibly vary this distance.

Conversely, the distance separating the film 4 from the bottom of the deep groove 6 is very important so that no capillary force allows the retention of liquid 5 or 15 at this level. It is of course obvious that it is necessary, that level of the width of this deep groove, there is no possibility of making intervene capillary action.

The nature of the flexible film may vary depending on the nature of the card analysis and fluids tested in particular for compatibility reasons. Through example, a polymer film TPX (polymethylpentene) or BOPP (bi-oriented polypropylene) allows for biological tests. The fixation of these films can be produced by gluing (coating of glue such as silicone glues on the film) or by welding. An example of adhesive BOPP is provided by the company BioMérieux Inc (St Louis, MO, USA) under the reference 022004-2184.

In terms of implementation, the analysis card is obtained by machining a material technical plastic such as impact polystyrene reference R540E from the GOODFELLOW company, compatible with treated liquids. In a mode of industrial realization, the card could be obtained by precision molding, but all other manufacturing methods and in particular those used in the techniques of semiconductor like those described in patent application WO-A-97/02357 can be used to manufacture the analysis card.

Of course, it is possible to imagine a number of other modes of embodiments which are represented in FIGS. 5 and 6.

In Figure 5; it is essentially a reverse construction to the first embodiment of Figures 1 to 4. Thus, in Figure 5, the surface groove 16 is located in the center and is surrounded by two deep grooves 6. The liquid sample 5 is then only in contact with the bottom of the surface groove 16.

In another embodiment, it is possible according to FIG. 6 not to have only one surface groove 16 and only one deep groove 6.

• « Dispositif et procédé de positionnement d'un liquide », pour le premier document,
• « Dispositif de pompage permettant de transférer au moins un fluide dans un consommable », pour le deuxième document, et enfm
• « Carte d'analyse à remplissage amélioré », pour le troisième document.

Of course, all cases are possible and conceivable. Thus, there can be a multitude of successions of deep grooves 6 or superficial 16. The only necessity lies in the fact that the deep grooves 6 are interposed between the superficial grooves 16 and vice versa. The introduction of liquids 5 and / or 15 can be carried out via valve systems, pumps and / or channels as described in the patent applications filed today by the applicant under the following titles:

• "Device and method for positioning a liquid", for the first document,
• "Pumping device for transferring at least one fluid into a consumable", for the second document, and finally
• "Analysis card with improved filling", for the third document.

The movement of liquids 5 and 15 is carried out in different ways. Through example, we can generate vibrations; we can position the card 1 in a substantially vertical position, in which liquids have their movement which is eased by gravity; you can use centrifugal force. Pumping systems can be incorporated inside or outside the device, for example diaphragm pumps (US-A-5,277,556), piezoelectric peristaltic pumps (US-A-5,126,022), ferrofluid transport systems, pumps electrical and hydrodynamic (Richter et al., Sensors and Actuators, 29, p159-165, 1991). It is also possible to use the combination of at least two of these techniques.

REFERENCES

1. Device

2. Flat surface of the device 1

3. Compartments

4. Partition or partitioning film

5. First liquid sample

6. First type of so-called deep groove

7. End of groove 6

8. Reaction area

15. Second liquid sample

16. Second type of surface groove

Claims (8)

1. An apparatus (1) comprising at least one plane surface (2) whereat compartments (3) are found and are defined by a partition (4), the compartments creating a space which allows for the displacement of a liquid sample (5 or 15) or the independent movement of at least two liquid samples (5 and 15), compartments (3) made up of at least two different types of grooves:

   a first type of so-called deep groove(s) (6), serving as a means for partitioning sample(s) (5 and/or 15), deep groove(s) (6) being at a distance from partition (4) that does not enable capillary action, and

   a second type of so-called shallow groove(s) (16), serving as means for receiving said sample(s) (5 and/or 15), shallow groove(s) (16) being at a distance from said partition (4) that enables capillary action,

   both types of grooves (6 and 16) allowing the displacements of sample(s) (5 and/or 15) to be guided according to the orientation of device (1).
2. The apparatus according to claim 1, characterised in that the width of each deep groove (6) is of a size that does not enable capillary action.
3. The apparatus according to any one of claims 1 or 2, characterised in that at least one shallow groove (16) is adjacent to a deep groove (6).
4. The apparatus according to any one of claims 1 to 3, characterised in that at least one deep groove (6) is adjacent to a shallow groove (16).
5. The apparatus according to any one of claims 1 to 4, characterised in that a deep groove (6) is positioned between two shallow grooves (16).
6. The apparatus according to claim 5, characterised in that deep groove (6) comprises a free end (7), and that both shallow grooves (16) meet at this free end to create a reaction zone (8), where at least two liquid samples (5 and 15) are brought together (5) (15) and possibly react.
7. The apparatus according to claim 6, characterised in that reaction zone (8) is at a distance from partition (4) that enables capillary action.
8. The apparatus according to claim 6, characterised in that the reaction zone is at a distance from partition (4) that does not enable capillary action.

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