Method for cleaning test sample wells, and cleaning head using said method

A method for cleaning a test sample well, provided in a diagnostic test card, using a cleaning head having a cleaning tube delivering, at its free end, a cleaning fluid, and a suction tube mounted inside the cleaning tube for aspirating the contaminated cleaning fluid from its free end located in proximity to the free end of the cleaning tube. The method provides for relative displacement between the test card and the cleaning head, so that the test card occupies a cleaning position wherein the cleaning tube delivers, at its free end, the cleaning fluid to the inside of the well to be cleaned and the suction tube aspirates the contaminated cleaning fluid.

This application is a 371 of PCT/FR2013/050847, filed on Apr. 17, 2013, which claims priority to French Application No. 1253607, filed Apr. 19, 2012.

SUMMARY OF THE INVENTION

The present invention relates to the technology of micro-fluidic systems generally, and it relates more particularly to the field of diagnostic test cards wherein are formed channels for supplying fluid, leading to wells designed to accommodate a reagent and a test or fluid sample containing analytes to be detected, representing an illness or the presence of microorganisms.

BACKGROUND OF THE INVENTION

The object of the invention relates more precisely to technical means suitable for cleaning the wells of such test cards.

The prior art has proposed various devices for cleaning the wells of a test card. For example, U.S. Pat. No. 4,635,665 describes a cleaning device comprising at least one washing head with two coaxial tubes designed to be inserted into the interior of the well to be cleaned to extend in proximity to the bottom of the well. The cleaning head comprises a cleaning tube delivering, at its free end, a cleaning fluid, and a suction tube mounted concentrically within the cleaning tube and designed to aspirate the contaminated cleaning fluid. The adjoining ends of the suction tube and the cleaning tube are situated in one and the same plane to ensure effective aspiration. Injection of the cleaning liquid at the center of the head and the aspiration of the contaminated liquid at the periphery of the head does not make it possible to ensure total recovery of the contaminated liquid.

U.S. Pat. No. 5,882,597 describes a cleaning device comprising a series of cleaning heads each comprising a cleaning tube communicating with a cleaning fluid storage chamber and delivering, at its free end, a cleaning fluid. Each cleaning head also comprises a suction tube for aspirating the contaminated cleaning fluid from its free end, which extends beyond the free end of the cleaning tube. The terminal portion of the cleaning tube is flared to ensure that the liquid leaves in an annular pattern so as to ensure fluid-tightness preventing air from rising into the storage chamber. The cleaning head is displaced so as to enter the interior of the well to be cleaned.

It appears difficult in practice to ensure coaxial mounting of the two tubes, so the proper functioning of such a cleaning head cannot be ensured. Moreover, it has been observed that such a cleaning head does not give satisfaction, inasmuch as it does not allow effective cleaning of the well to be obtained with certainty.

The present invention therefore aims to correct the disadvantages of the prior art by proposing a new technique for cleaning the wells of a diagnostic test card, designed to completely and reproducibly clean the test sample wells of a diagnostic test card.

To attain such a goal, the object of the invention aims to propose a method for cleaning at least one test sample well, provided in a diagnostic test card, using at least one cleaning head comprising at least one cleaning tube delivering, at its free end, a cleaning fluid, and suction tube mounted within the cleaning tube, for aspirating the contaminated cleaning fluid from its free end located in proximity to the free end of the cleaning tube, the method consisting of providing for relative displacement between the test card and the cleaning head so that the test card occupies a cleaning position wherein the cleaning tube delivers the cleaning fluid, at its free end, into the well to be cleaned, and the suction tube aspirates the contaminated cleaning fluid.

According to the invention, the method consists, in the cleaning position, of providing for intake of air between the exterior and the interior of the free end of the cleaning tube so as to create a vortex in the cleaning fluid within the well to be cleaned.

In addition, the method according to the invention can also exhibit, in combination, at least one and/or another of the following additional features:

providing for relative displacement between the test card and the cleaning head so as to ensure abutment of the free end of the cleaning tube on the test card for the purpose of creating the air intake.

equipping the free end of the cleaning tube so that the free end of the cleaning tube creates the air intake when it is in abutment on the test card,

equipping the test card so that said test card creates the air intake when the free end of the cleaning tube is in abutment on the test card,

equipping the free end of the cleaning tube with a flexible tip, which either delimits the air intake or ensures fluid-tightness with the card when said tip is in abutment on the test card,

ensuring abutment of the free end of the cleaning tube on the card for the purpose of creating a suction zone of predetermined height between the free end of the suction tube and the bottom of the well,

creating the suction zone of predetermined height between the free end of the suction tube and the bottom of the well, with the free end of the suction tube extending beyond the free end of the cleaning tube,

creating the suction zone of predetermined height between the free end of the suction tube and the bottom of the well, with the free end of the suction tube extending short of the free end of the cleaning tube,

aspirating the contaminated cleaning fluid at the free end of the suction tube, at several separate suction sections located, in the cleaning position, vertically above spots placed in the test sample well,

providing for relative displacement between the test card and the cleaning head so as to laterally displace the suction zone with a predetermined height between the free end of the suction tube and the bottom of the well when the suction zone does not allow cleaning the bottom of the well in a single position.

Another object of the invention is to propose a cleaning head for at least one test sample well provided in a diagnostic test card, comprising at least one cleaning tube connected to a cleaning fluid source and delivering, at its free end the cleaning fluid, and a suction tube mounted inside the cleaning tube and connected to a suction source and aspirating, at its free end, located in proximity to the free end of the cleaning tube, the contaminated cleaning fluid.

According to the invention, the cleaning tube is provided with an air inlet between the outside and the inside of its free end, in proximity to or on its transverse face.

In addition, the cleaning head according to the invention can also exhibit, in combination, at least one and/or another of the following additional features:

the air intake comprises a series of channels provided on the transverse face delimiting the free end of the cleaning tube, said channels extending radially between the outside wall and the inside wall of the cleaning tube,

the channels are distributed evenly over the transverse face of the cleaning tube,

the cleaning tube has a rough transverse face delimiting the air intake between the outer wall and the inner wall of the cleaning tube,

the free end of the suction tube is located short of the free end of the cleaning tube,

the free end of the suction tube is located short of the free end of the cleaning tube by a value comprised between 10 and 300 μm,

the cleaning tube is provided with a flexible tip forming the free end of said cleaning tube,

the suction tube comprises within it a duct communicating with the suction source and equipped at its free end with partitions delimiting separate suction sections.

Another object of the invention is to propose a cleaning device comprising a cleaning fluid source, a suction source for the contaminated cleaning fluid, at least one cleaning had and a system for relative displacement between the cleaning head and the diagnostic test card wherein is provided at least one test sample well, the displacement system being controlled to occupy at least one well cleaning position.

According to the invention, the device comprises at least one cleaning head, the tube whereof is capable, in the cleaning position, of coming into abutment at its free end on the test card to create an air intake between the outside and the inside of the free end of said cleaning tube.

Various other features are revealed by the description given below with reference to the appended drawings which show, by way of non-limiting examples, embodiments of the object of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

LaFIG. 1illustrates by way of an example a cleaning device1for at least one test sample well2provided in a diagnostic test card3. The device1according to the invention comprises at least one cleaning head5capable of cleaning a test sample well2in one or more positions depending on the shape of the well, for example in the case of a well with an oblong shape. In the example illustrated inFIG. 1, the device1comprises a single cleaning head5. Of course it is clean that the cleaning device1can comprise a plurality of cleaning heads5arranged for example side by side in rows and columns, and in distributions identical or not to the test sample wells2to be cleaned, provided on the diagnostic test card3. For example, construction of a cleaning device1can be provided for comprising8or12cleaning heads5.

Each cleaning head5comprises a cleaning tube7having for example a circular cross-section. The cleaning tube7comprises an outer tubular wall8and an inner tubular wall9. The cleaning tube7exhibits a free end71delimited by an annular transverse face10providing the connection between the outer wall8and the inner wall9. By way of an example, the outer diameter of the cleaning tube7is comprised between 0.5 mm and 25 mm and preferably between 0.5 mm and 5 mm.

The free end71of the cleaning tube7can exhibit different shapes. This, in the example illustrated inFIGS. 1 and 2, the inner wall9of the cleaning tube7has a constant cross-section over its entire length, while the outer wall8of the cleaning7has a constant cross-section with the exception of its free end71which exhibits a cross-section decreasing up to its transverse face10.FIG. 3illustrates another variant embodiment according to which the cross-section of the inner wall9of the cleaning tube7is constant with the exception of its free end, which decreases up to the transverse face10.

The cleaning tube7exhibits an end72opposite to the free end71and communicating with a source of cleaning fluid11. For example, the cleaning fluid used is water with or without added adjuvants, an aqueous and/or organic solvent, a solvent containing proteins, a cleaning buffer which can contained HEPES, sodium chloride, BSA (bovine serum albumin), casein, PEG (polyethylene glycol), sodium nitride, surfactants such as Tween-20, sugar, etc. The cleaning fluid can also include fillers such as talc, particles, corundum, alumina, glass, so as to add mechanical action to the cleaning process.

The cleaning head5also comprises a suction tube14mounted within the cleaning tube7and exhibiting a preferably circular cross-section. For example, the outer diameter of the suction tube14is comprised between 0.2 mm and 20 mm and preferably between 0.2 mm and 4 mm. The suction tube14comprises an outer tubular wall15and an inner tubular wall16. The suction tube14delimits, between its outer wall15and the inner wall9of the cleaning tube7, a tubular duct18for directing cleaning fluid to the free end71of the cleaning tube7. The suction tube14and cleaning tube7are preferably mounted coaxially.

The suction tube14comprises a free end141extending in proximity to the free end71of the cleaning tube7. The free end141of the suction tube14is delimited by the transverse face19connecting between the inner wall16and the outer wall15of the suction tube14. The suction tube14thus delimits by its inner wall16a duct20communicating from the end142opposite to the free end141, with a suction source21for the contaminated cleaning fluid, aspirated from its free end141.

By way of an example, the suction source21is embodied by a vacuum pump, a venture or the vacuum network. Generally, the flow of the suction source21is greater than the flow of the cleaning fluid source11. The difference between the flows of the cleaning fluid source11and the suction source21depends in particular on the operating conditions and on the geometry of the cleaning head5and of the test sample wells2to be cleaned. By way of an example, the ratio of the flow of the suction source to the flow of the cleaning fluid source11is comprised between 300 and 3000.

The cleaning device1according to the invention also comprises a system25for relative displacement between the cleaning head5and the diagnostic test card3so that the cleaning head5occupies at least one first position, called the rest position, wherein the cleaning head is separated from the diagnostic test card3, and a cleaning position for which the cleaning tube7provides delivery of cleaning fluid to the interior of the well and the suction tube14aspirates the contaminated cleaning fluid. The displacement system25, which can be of any inherently known type, is not described more precisely because it is known to those skilled in the art and is not itself a part of the invention.

According to one advantageous embodiment feature, the displacement system25is controlled so as to ensure, for the cleaning position, abutment of the cleaning tube7on the diagnostic test card3at its transverse face10, while the free end of the suction tube14is situated above the bottom21of the test sample well2. In this cleaning position, the cleaning tube partially or totally situated vertically above the test sample well2. In this cleaning position, the free end, and more precisely the transverse face19of the suction tube14is situated at a predetermined distance from the bottom of the well to be cleaned2so as to delimit, with the latter, a suction zone27. Advantageously, in the cleaning position, the transverse face19of the suction tube14is situated at a distance from the bottom of the well to be cleaned2which can range from 2 mm for micro-wells and up to 10 mm for micro-plates.

According to a preferred embodiment feature illustrated inFIGS. 1 through 3, the free end141of the suction tube14is set back with respect to the free end71of the cleaning tube7. In other words, the transverse face19of the suction tube14is set back relative to the transverse face10of the cleaning tube7. According to one advantageous embodiment feature, the transverse face19of the suction tube14is set back relative to the transverse face10of the cleaning tube by a value comprised between 10 μm and 3 mm and preferably, for a micro-plate washing application for example, between 1 mm and 3 mm and again preferably, for a micro-well washing application, between 10 μm and 300 μm.

In conformity with the invention, the cleaning tube7is equipped with an air intake31between the outer wall8and the inner wall9. In the example illustrated inFIGS. 1 and 2, the air intake31comprises a series of channels32provided on the transverse face10delimiting the free end of the cleaning tube7. These channels32extend radially between the outer wall8and the inner wall9of the cleaning tube, opening at the outer wall8and inner wall9. The channels32lead to or open at the tubular duct18for directing the cleaning fluid, which is delimited by the inner wall9of the cleaning tube7. According to a preferred variant embodiment, illustrated more particularly inFIG. 2, the channels32are distributed evenly over the transverse face10of the cleaning tube7.

According to another variant embodiment illustrated more particularly inFIG. 3, the cleaning tube7has a rough transverse face10delimiting the air intake31between the outer wall8and the inner wall9of the cleaning tube7. According to this variant embodiment, it must be understood that when the transverse face10is in abutment on a flat surface, the roughness of the transverse face10is such that the latter exhibits protruding portions delimiting between them passages forming together the air intake31between the outer wall8and the inner wall9.

According to another variant embodiment, not shown, it is to be noted that the air intake31can also be embodied by holes provided radially at the free end71of the cleaning tube7in proximity to the transverse face10and leading to the outer wall8and the inner wall9.

The implementation of the cleaning head5follows directly from the foregoing description. The process for cleaning a test sample well2thus consists of providing for relative displacement between the cleaning head5and the diagnostic test card3so as to place the cleaning head5in its cleaning position. In this position, illustrated inFIG. 1, the cleaning tube7is in abutment at its free end71on the test card. In this position, the transverse face10of the cleaning tube7is in abutment on at least a portion of the perimeter of the test sample well2. In this position, the cleaning tube7is able to inject cleaning fluid inside the well2while the suction tube14is situated vertically above the well2to aspirate the contaminated cleaning fluid. In this position, an air intake31appears between the outside and the inside of the cleaning tube7, through channels32for example which allow the air to be directed from the outside of the cleaning tube7to the inside of the test sample well2to be cleaned.

Injection of the cleaning fluid inside the tube7leads to its escape through the free end71of the cleaning tube7. Simultaneously, the suction source21aspirates, at the free end141of the suction tube14, the contaminated liquid. As a result of the air intake31formed between the outside and the inside of the cleaning tube7, there occurs within the test sample well2, a cleaning fluid vortex allowing effective and complete cleaning of the test sample well2. Inasmuch as the suction tube14is situated inside the cleaning tube7, good recovery of the contaminated cleaning fluid occurs.

It should be noted that the positioning of the free end141of the suction tube14relative to the free end71of the cleaning tube7depends in particular on the depth of the test sample well2to be cleaned. As indicated above, the free end141of the suction tube14is advantageously set back relative to the free end71of the cleaning tube7.

Consideration can, however, be given to implementing a cleaning head5wherein the free end141of the suction tube extends beyond the free end71of the cleaning tube7as seen more precisely inFIGS. 4 and 5. In other words, the transverse face19of the suction tube14protrudes with respect to the transverse face10of the cleaning tube7. Such an arrangement can thus be contemplated for test sample wells2exhibiting a relatively great depth, allowing the free end141of the suction tube14to be brought closer to the bottom21of the test sample well2. This variant embodiment makes it possible to maintain a suitable height for the suction zone27to ensure good aspiration of the contaminated cleaning fluid. Advantageously, as previously stated, in the cleaning position the transverse face19of the suction tube14is situated at a distance from the bottom of the well to be cleaned2which can range from 2 mm for micro-wells up to 10 mm for micro-plates.

In the foregoing examples, the air intake31between the outside and the inside of the free end71of the cleaning tube7is implemented by the geometry of the cleaning tube7.

FIG. 6illustrates another exemplary embodiment wherein the air intake31is implemented by the geometry of the diagnostic test card3. According to this exemplary embodiment, the test sample well2communicates with at least one and, in the example illustrated inFIG. 6, two ducts34provided in the diagnostic test card3and forming the air intake31. These ducts34are provided such that in the position of the free end71of the cleaning tube7abutting on the diagnostic test card3, the ducts34extend to either side of the inner9and outer8walls to allow entry of air into the cleaning tube7. In this abutment position, the cleaning tube7surrounds or completely closes off the well2, with the exception of the ducts34. The cleaning tube7provides a seal between the cleaning head5and the diagnostic test card3.

According to one exemplary embodiment, the free end71of the cleaning tube7is designed to provide a seal with the diagnostic test card3. According to one variant embodiment, the cleaning tube7is provided, at its free end71, with a flexible tip providing a seal with the test card. Such a flexible tip also makes it possible to achieve soft contact between the cleaning tube7and the diagnostic test card3, and to compensate for tolerances in the displacement system25to provide for positioning the cleaning head5in its cleaning position.

Such a flexible tip can be added to the free end71of the cleaning tube, or be overmolded or co-injected at the free end71of the cleaning tube7. For example, the flexible tip can exhibit a Shore A hardness comprised between 20 and 80. Such a tip can be made of silicone, of elastomers such as EPDMs (Ethylene Propylene Diene Monomer), SBR (Styrene Butadiene Rubber) . . . or others, or of thermoplastic elastomers such as Arnitel, Pebax . . . or others.

Of course, consideration can also be given to having such a flexible tip able to also delimit the air intake31for example, by comprising channels32.

In the foregoing examples, the suction tube14comprises within it a duct20opening at the free end141, with a single suction section20a, corresponding to the full cross-section of the duct20.FIGS. 7 and 8illustrate another variant embodiment of the suction tube14allowing aspiration of the contaminated cleaning fluid at the free end141, at several suction sections20aseparated from one another by partitions38. These suction sections20aare provided at the free end141of the suction tube14such that, in the cleaning position, these suction sections20aare located vertically above spots placed in the test sample well2. Such an arrangement contributes toward reinforcing the cleaning of the well2and more particularly in the deposit areas of one or more products of interest, called spots.

In the example illustrated inFIG. 7, the duct20of the suction tube14is equipped at the free end141of the suction tube14, with partitions38which are arranged in any appropriate manner for forming a specific geometry or pattern. These partitions38delimit suction sections20awhich, in the example illustrated inFIG. 7have different shapes.FIG. 8illustrates another variant embodiment wherein the suction tube14comprises suction sections20ahaving identical shapes, to with circular for example. According to this variant embodiment, the duct20of the suction tube14opens at the free end141, for example at four suction sections20aseparated from one another by partitions38made on a transverse face closing off the free end141of the suction tube14.

In the example illustrated inFIG. 8, each suction section20ais equipped with a conical entry39converging toward the duct20of the suction tube14to facilitate the selective routing of the contaminated cleaning fluid through the suction sections20a. Of course, it can be provided that the suction sections20aof the example illustrated inFIG. 8, are made without the conical entries39.

In the foregoing examples, a relative displacement is carried out between the cleaning head5and the diagnostic test card3so as to place the cleaning head5in a cleaning position. It should be noted that provision can also be made for providing the relative displacement between the test card and the cleaning head so as to laterally displace the suction zone at a predetermined height between the free end of the suction tube and the bottom of the well when the suction zone does not allow cleaning the bottom of the well in a single cleaning position.

The invention is not limited to the examples described and shown, because various modifications can be applied to it without departing from its scope.