Patent Publication Number: US-11020775-B2

Title: Systems for cleaning test sample wells

Description:
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. 
     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. 
         FIG. 1  is an overall view showing a first variant embodiment of a cleaning head conforming to the invention. 
         FIG. 2  is a perspective view of the cleaning head illustrated in  FIG. 1 . 
         FIG. 3  is a section in elevation showing another embodiment of the variant of the cleaning head illustrated in  FIGS. 1 and 2 . 
         FIG. 4  illustrates another variant embodiment of a cleaning head conforming to the invention. 
         FIG. 5  illustrates a partial cutaway perspective view of the variant embodiment of the cleaning head illustrated in  FIG. 4 . 
         FIG. 6  is a sectional view of another variant embodiment of the cleaning head conforming to the invention. 
         FIG. 7  illustrates a variant embodiment of the suction tube forming part of a cleaning head conforming to the invention. 
         FIG. 8  illustrates another variant embodiment of the suction tube forming part of a cleaning head conforming to the invention. 
     
    
    
       FIG. 1  illustrates by way of an example a cleaning device  1  for at least one test sample well  2  provided in a diagnostic test card  3 . The device  1  according to the invention comprises at least one cleaning head  5  capable of cleaning a test sample well  2  in 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 in  FIG. 1 , the device  1  comprises a single cleaning head  5 . Of course it is clean that the cleaning device  1  can comprise a plurality of cleaning heads  5  arranged for example side by side in rows and columns, and in distributions identical or not to the test sample wells  2  to be cleaned, provided on the diagnostic test card  3 . For example, construction of a cleaning device  1  can be provided for comprising  8  or  12  cleaning heads  5 . 
     Each cleaning head  5  comprises a cleaning tube  7  having for example a circular cross-section. The cleaning tube  7  comprises an outer tubular wall  8  and an inner tubular wall  9 . The cleaning tube  7  exhibits a free end  7   1  delimited by an annular transverse face  10  providing the connection between the outer wall  8  and the inner wall  9 . By way of an example, the outer diameter of the cleaning tube  7  is comprised between 0.5 mm and 25 mm and preferably between 0.5 mm and 5 mm. 
     The free end  7   1  of the cleaning tube  7  can exhibit different shapes. This, in the example illustrated in  FIGS. 1 and 2 , the inner wall  9  of the cleaning tube  7  has a constant cross-section over its entire length, while the outer wall  8  of the cleaning  7  has a constant cross-section with the exception of its free end  7   1  which exhibits a cross-section decreasing up to its transverse face  10 .  FIG. 3  illustrates another variant embodiment according to which the cross-section of the inner wall  9  of the cleaning tube  7  is constant with the exception of its free end, which decreases up to the transverse face  10 . 
     The cleaning tube  7  exhibits an end  7   2  opposite to the free end  7   1  and communicating with a source of cleaning fluid  11 . 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 containd 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 head  5  also comprises a suction tube  14  mounted within the cleaning tube  7  and exhibiting a preferably circular cross-section. For example, the outer diameter of the suction tube  14  is comprised between 0.2 mm and 20 mm and preferably between 0.2 mm and 4 mm. The suction tube  14  comprises an outer tubular wall  15  and an inner tubular wall  16 . The suction tube  14  delimits, between its outer wall  15  and the inner wall  9  of the cleaning tube  7 , a tubular duct  18  for directing cleaning fluid to the free end  7   1  of the cleaning tube  7 . The suction tube  14  and cleaning tube  7  are preferably mounted coaxially. 
     The suction tube  14  comprises a free end  14   1  extending in proximity to the free end  7   1  of the cleaning tube  7 . The free end  14   1  of the suction tube  14  is delimited by the transverse face  19  connecting between the inner wall  16  and the outer wall  15  of the suction tube  14 . The suction tube  14  thus delimits by its inner wall  16  a duct  20  communicating from the end  14   2  opposite to the free end  14   1 , with a suction source  21  for the contaminated cleaning fluid, aspirated from its free end  14   1 . 
     By way of an example, the suction source  21  is embodied by a vacuum pump, a venture or the vacuum network. Generally, the flow of the suction source  21  is greater than the flow of the cleaning fluid source  11 . The difference between the flows of the cleaning fluid source  11  and the suction source  21  depends in particular on the operating conditions and on the geometry of the cleaning head  5  and of the test sample wells  2  to be cleaned. By way of an example, the ratio of the flow of the suction source to the flow of the cleaning fluid source  11  is comprised between 300 and 3000. 
     The cleaning device  1  according to the invention also comprises a system  25  for relative displacement between the cleaning head  5  and the diagnostic test card  3  so that the cleaning head  5  occupies at least one first position, called the rest position, wherein the cleaning head is separated from the diagnostic test card  3 , and a cleaning position for which the cleaning tube  7  provides delivery of cleaning fluid to the interior of the well and the suction tube  14  aspirates the contaminated cleaning fluid. The displacement system  25 , 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 system  25  is controlled so as to ensure, for the cleaning position, abutment of the cleaning tube  7  on the diagnostic test card  3  at its transverse face  10 , while the free end of the suction tube  14  is situated above the bottom  2   1  of the test sample well  2 . In this cleaning position, the cleaning tube partially or totally situated vertically above the test sample well  2 . In this cleaning position, the free end, and more precisely the transverse face  19  of the suction tube  14  is situated at a predetermined distance from the bottom of the well to be cleaned  2  so as to delimit, with the latter, a suction zone  27 . Advantageously, in the cleaning position, the transverse face  19  of the suction tube  14  is situated at a distance from the bottom of the well to be cleaned  2  which can range from 2 mm for micro-wells and up to 10 mm for micro-plates. 
     According to a preferred embodiment feature illustrated in  FIGS. 1 through 3 , the free end  14   1  of the suction tube  14  is set back with respect to the free end  7   1  of the cleaning tube  7 . In other words, the transverse face  19  of the suction tube  14  is set back relative to the transverse face  10  of the cleaning tube  7 . According to one advantageous embodiment feature, the transverse face  19  of the suction tube  14  is set back relative to the transverse face  10  of 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 tube  7  is equipped with an air intake  31  between the outer wall  8  and the inner wall  9 . In the example illustrated in  FIGS. 1 and 2 , the air intake  31  comprises a series of channels  32  provided on the transverse face  10  delimiting the free end of the cleaning tube  7 . These channels  32  extend radially between the outer wall  8  and the inner wall  9  of the cleaning tube, opening at the outer wall  8  and inner wall  9 . The channels  32  lead to or open at the tubular duct  18  for directing the cleaning fluid, which is delimited by the inner wall  9  of the cleaning tube  7 . According to a preferred variant embodiment, illustrated more particularly in  FIG. 2 , the channels  32  are distributed evenly over the transverse face  10  of the cleaning tube  7 . 
     According to another variant embodiment illustrated more particularly in  FIG. 3 , the cleaning tube  7  has a rough transverse face  10  delimiting the air intake  31  between the outer wall  8  and the inner wall  9  of the cleaning tube  7 . According to this variant embodiment, it must be understood that when the transverse face  10  is in abutment on a flat surface, the roughness of the transverse face  10  is such that the latter exhibits protruding portions delimiting between them passages forming together the air intake  31  between the outer wall  8  and the inner wall  9 . 
     According to another variant embodiment, not shown, it is to be noted that the air intake  31  can also be embodied by holes provided radially at the free end  7   1  of the cleaning tube  7  in proximity to the transverse face  10  and leading to the outer wall  8  and the inner wall  9 . 
     The implementation of the cleaning head  5  follows directly from the foregoing description. The process for cleaning a test sample well  2  thus consists of providing for relative displacement between the cleaning head  5  and the diagnostic test card  3  so as to place the cleaning head  5  in its cleaning position. In this position, illustrated in  FIG. 1 , the cleaning tube  7  is in abutment at its free end  7   1  on the test card. In this position, the transverse face  10  of the cleaning tube  7  is in abutment on at least a portion of the perimeter of the test sample well  2 . In these position, the cleaning tube  7  is able to inject cleaning fluid inside the well  2  while the suction tube  14  is situated vertically above the well  2  to aspirate the contaminated cleaning fluid. In this position, an air intake  31  appears between the outside and the inside of the cleaning tube  7 , through channels  32  for example which allow the air to be directed from the outside of the cleaning tube  7  to the inside of the test sample well  2  to be cleaned. 
     Injection of the cleaning fluid inside the tube  7  leads to its escape through the free end  7   1  of the cleaning tube  7 . Simultaneously, the suction source  21  aspirates, at the free end  14   1  of the suction tube  14 , the contaminated liquid. As a result of the air intake  31  formed between the outside and the inside of the cleaning tube  7 , there occurs within the test sample well  2 , a cleaning fluid vortex allowing effective and complete cleaning of the test sample well  2 . Inasmuch as the suction tube  14  is situated inside the cleaning tube  7 , good recovery of the contaminated cleaning fluid occurs. 
     It should be noted that the positioning of the free end  14   1  of the suction tube  14  relative to the free end  7   1  of the cleaning tube  7  depends in particular on the depth of the test sample well  2  to be cleaned. As indicated above, the free end  14   1  of the suction tube  14  is advantageously set back relative to the free end  7   1  of the cleaning tube  7 . 
     Consideration can, however, be given to implementing a cleaning head  5  wherein the free end  14   1  of the suction tube extends beyond the free end  71  of the cleaning tube  7  as seen more precisely in  FIGS. 4 and 5 . In other words, the transverse face  19  of the suction tube  14  protrudes with respect to the transverse face  10  of the cleaning tube  7 . Such an arrangement can thus be contemplated for test sample wells  2  exhibiting a relatively great depth, allowing the free end  14   1  of the suction tube  14  to be brought closer to the bottom  2   1  of the test sample well  2 . This variant embodiment makes it possible to maintain a suitable height for the suction zone  27  to ensure good aspiration of the contaminated cleaning fluid. Advantageously, as previously stated, in the cleaning position the transverse face  19  of the suction tube  14  is situated at a distance from the bottom of the well to be cleaned  2  which can range from 2 mm for micro-wells up to 10 mm for micro-plates. 
     In the foregoing examples, the air intake  31  between the outside and the inside of the free end  7   1  of the cleaning tube  7  is implemented by the geometry of the cleaning tube  7 . 
       FIG. 6  illustrates another exemplary embodiment wherein the air intake  31  is implemented by the geometry of the diagnostic test card  3 . According to this exemplary embodiment, the test sample well  2  communicates with at least one and, in the example illustrated in  FIG. 6 , two ducts  34  provided in the diagnostic test card  3  and forming the air intake  31 . These ducts  34  are provided such that in the position of the free end  7   1  of the cleaning tube  7  abutting on the diagnostic test card  3 , the ducts  34  extend to either side of the inner  9  and outer  8  walls to allow entry of air into the cleaning tube  7 . In this abutment position, the cleaning tube  7  surrounds or completely closes off the well  2 , with the exception of the ducts  34 . The cleaning tube  7  provides a seal between the cleaning head  5  and the diagnostic test card  3 . 
     According to one exemplary embodiment, the free end  7   1  of the cleaning tube  7  is designed to provide a seal with the diagnostic test card  3 . According to one variant embodiment, the cleaning tube  7  is provided, at its free end  7   1 , 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 tube  7  and the diagnostic test card  3 , and to compensate for tolerances in the displacement system  25  to provide for positioning the cleaning head  5  in its cleaning position. 
     Such a flexible tip can be added to the free end  7   1  of the cleaning tube, or be overmolded or co-injected at the free end  7   1  of the cleaning tube  7 . 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 intake  31  for example, by comprising channels  32 . 
     In the foregoing examples, the suction tube  14  comprises within it a duct  20  opening at the free end  14   1 , with a single suction section  20   a , corresponding to the full cross-section of the duct  20 .  FIGS. 7 and 8  illustrate another variant embodiment of the suction tube  14  allowing aspiration of the contaminated cleaning fluid at the free end  14   1 , at several suction sections  20   a  separated from one another by partitions  38 . These suction sections  20   a  are provided at the free end  14   1  of the suction tube  14  such that, in the cleaning position, these suction sections  20   a  are located vertically above spots placed in the test sample well  2 . Such an arrangement contributes toward reinforcing the cleaning of the well  2  and more particularly in the deposit areas of one or more products of interest, called spots. 
     In the example illustrated in  FIG. 7 , the duct  20  of the suction tube  14  is equipped at the free end  141  of the suction tube  14 , with partitions  38  which are arranged in any appropriate manner for forming a specific geometry or pattern. These partitions  38  delimit suction sections  20   a  which, in the example illustrated in  FIG. 7  have different shapes.  FIG. 8  illustrates another variant embodiment wherein the suction tube  14  comprises suction sections  20   a  having identical shapes, to with circular for example. According to this variant embodiment, the duct  20  of the suction tube  14  opens at the free end  14   1 , for example at four suction sections  20   a  separated from one another by partitions  38  made on a transverse face closing off the free end  14   1  of the suction tube  14 . 
     In the example illustrated in  FIG. 8 , each suction section  20   a  is equipped with a conical entry  39  converging toward the duct  20  of the suction tube  14  to facilitate the selective routing of the contaminated cleaning fluid through the suction sections  20   a.  Of course, it can be provided that the suction sections  20   a  of the example illustrated in  FIG. 8 , are made without the conical entries  39 . 
     In the foregoing examples, a relative displacement is carried out between the cleaning head  5  and the diagnostic test card  3  so as to place the cleaning head  5  in 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.