Abstract:
The invention concerns an apparatus for preparing samples for analysis having at least a liquid-injecting needle ( 6 ), at least a column ( 32 ) for receiving the injecting needle, at least a tube ( 48 ), device ( 6, 26 ) for the tube and the column relative horizontal displacement between a position of coincidence in which the column bottom aperture ( 36 ) extends above the tube top aperture ( 50 ), and a relative lateral offset position of the two apertures ( 36, 50 ), and adapted device ( 6, 60 ) for the tube ( 48 ) and the column ( 32 ) relative vertical displacement such that in position of coincidence, the apertures ( 36, 50 ) interpenetrate, including vertical guide device for either the tube ( 48 ) or the column ( 32 ). The vertical guide device is adapted to operate the guiding under horizontal loading effect.

Description:
BACKGROUND OF THE INVENTION 
     The invention relates to apparatus for preparing samples for analysis, for example for analysis by chromatography. 
     1. Field of the Invention 
     Document EP-0 180 511-B1 discloses an apparatus of this type, comprising a baseplate, a set of columns running across the upper part of the baseplate and each receiving an agent in powder form, and a set of tubes spread out in a carriage, toward the lower part of the baseplate. The carriage can move in sliding between a position of coincidence in which an aperture at the bottom of the columns is opposite an aperture at the top of the tubes so that liquid can be transferred from the columns into the tubes, and a laterally offset position in which the columns are placed over a basin borne by the carriage and able to receive the content of the columns. The apparatus comprises a mobile injection needle designed to inject various liquids into the aperture at the top of the columns that they pass through the agent in powder form and are collected in the tubes. An apparatus of this kind makes it possible, starting from raw samples, to prepare in the tubes, in an automated fashion, a great many samples designed for subsequent analysis by chromatography, or any other kind of analysis, such as mass spectrography and radioimmunoassay. 
     2. Background of the Invention 
     However, a drawback of this apparatus is that when the columns and tubes are in the position of coincidence, there is a risk that the liquid transferred from each column will splash toward the tubes adjacent to the tube associated with the column in question. There is therefore a risk of these adjacent tubes becoming contaminated. Such a risk reduces the reliability of the subsequent analysis of the samples. This drawback is particularly keenly felt when the aperture at the bottom of the columns consists of a small nozzle and the liquid is driven through the nozzle under pressure. In such an instance, the risk of splashing toward the adjacent tubes is very high. 
     There is therefore a desire to have an apparatus which exhibits the same advantages but in which the risk of cross-contamination of samples is considerably reduced. 
     Document U.S. Pat. No. 5,260,028 discloses an apparatus for solid-phase extraction, comprising a motor for driving the horizontal movement of the tubes with respect to cassettes along horizontal slideways, and another motor for driving the tubes in a vertical movement with respect to the cassettes along vertical slideways with a view to coupling them so that liquid can be transferred from one to the other without splashing. However, this apparatus is of a complicated and bulky structure. 
     One purpose of the invention is to provide an apparatus of a different type, and which in particular is of simpler and less bulky design. 
     SUMMARY OF THE INVENTION 
     In order to achieve this aim, the invention provides an apparatus for preparing samples for analysis, comprising at least one liquid-injecting needle, at least one column designed to take the injection needle, at least one tube, means for the horizontal relative movement of the tube and of the column between a position of coincidence in which an aperture at the bottom of the column lies over an aperture at the top of the tube, and a position in which the two apertures are offset laterally relative to each other, and means for the relative vertical movement of the tube and of the column which are designed so that, in the position of coincidence, the apertures interpenetrate, these means comprising means for vertically guiding either the tube or the column, the vertical-guidance means being designed to provide guidance under the effect of a horizontal force. 
     Thus, in the penetration position, splashes are arrested by the walls of the tube and/or of the column, and do not contaminate the adjacent samples. The reliability of the subsequent analysis is therefore preserved. What is more, the drive means which produce the vertical movement may be the same as those which produce the horizontal movement. The apparatus can therefore have a simpler and less bulky structure. 
     Advantageously, the apparatus comprises means for horizontally forcing either the tube or the column, the guide means being independent of the forcing means and designed to provide vertical guidance under the effect of the horizontal force applied by the forcing means. 
     Thus, all that is required is for the vertical-guidance means to be located in the vicinity of the tube or of the column, it being possible for these means to be somewhat compact. 
     Advantageously, the forcing means comprise at least one arm designed to apply force to either the tube or the column, and secured to the other one, column or tube. 
     Thus, as the column and the tube move closer toward the position of coincidence, this initiates and automatically brings about the interpenetration of the apertures, without separate specific control means being needed to effect this. 
     Advantageously, the guide means comprise at least one ramp and a bearing piece designed to be moved with respect to the ramp, in contact with this ramp, in order to provide guidance. 
     Advantageously, the ramp and that zone of the bearing piece which is designed to be in contact with the ramp, are made of polyethylene terephthalate or polyoxymethylene. 
     Thus, the bearing piece slides well against the ramp. Furthermore, this material is chemically inert. 
     Advantageously, the apparatus comprises means for holding the column and the tube in the position of coincidence with the apertures interpenetrating. 
     Thus, any inadvertent change in the relative position of the tube and of the column in the position of coincidence is avoided, particularly when liquid is being transferred. If this were not the case, such a change could occur, for example, under the effect of vibrations and/or of gravity when the vertical movement involved raising the tube toward the column. 
     Advantageously, the holding means comprise magnetic means. 
     Advantageously, the apparatus comprises a film which covers the aperture of the tube. This film can be perforated by a nipple on the column so as to create an unsealed joint. The optional presence of such a film makes it possible to limit the ventilation of the zone in question and any possible resulting evaporation. 
     Advantageously, the apparatus comprises a baseplate, the column extending to a set horizontal level with respect to the baseplate, the vertical-movement means being designed to move the tube with respect to the column. 
     Advantageously, the column can move with horizontal sliding with respect to the baseplate. 
     The invention also provides for a carrier designed to form part, particularly such that it is removable, of an apparatus for preparing samples for analysis, the carrier comprising at least one column, at least one tube, means for the relative horizontal guidance of the tube and of the column between a position of coincidence in which an aperture at the bottom of the column lies over an aperture at the top of the tube, and a position in which the two apertures are laterally offset relative to each other, the carrier comprising means for the relative vertical guidance of the tube and of the column, which are designed so that, in the position of coincidence, the apertures interpenetrate, the guide means being designed to provide vertical guidance under the effect of a horizontal force applied to the tube or to the column. 
     A carrier of this kind may form part, for example in number, of an apparatus according to the invention. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     Other features and advantages of the invention will become clearly apparent from the following description of a preferred embodiment which is given by way of non limiting example. In the appended drawings: 
     FIG. 1 is a partial plan view of an apparatus according to the invention; 
     FIG. 2 is a side view of one of the carriers of the apparatus of FIG. 1, in the offset position; 
     FIG. 3 is a view similar to FIG. 2, showing the carrier in the position of coincidence; 
     FIG. 4 is a view in cross section on the plane IV—IV of the carrier of FIG. 3; 
     FIG. 5 is a part view in longitudinal section on a larger scale, of a detail of the carrier, showing the plate in the lowered position; 
     FIG. 6 is a view similar to FIG. 5 showing the plate in the raised position; 
     FIG. 7 is a plan view of the plate on the two slideways; 
     FIG. 8 is a part view in axial section in the region of the aperture at the bottom of a column and of the aperture at the top of a tube; 
     FIG. 9 is a part view in axial section of a stopper of a strip of stoppers; 
     FIG. 10 is a plan view of the strip of FIG. 9; and 
     FIG. 11 is a view in longitudinal section of the strip of FIG.  9 . 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     In the preferred embodiment which will now be described, the apparatus  2  for preparing samples for analysis is, in principle, of the type described in document EP-0 180 511-B1. In particular, its structure and operation are similar. 
     The apparatus comprises a fixed casing  4  containing, in particular, the control electronics. It comprises at least one vertical needle  6  (see FIG. 3) connected to means designed to cause the needle to draw in and inject fluids such as air or various liquids. The needle  6  is connected to the casing  4  with a known mechanism, not depicted, allowing the needle to move freely with respect to the casing in the three directions X, Y and Z, namely the longitudinal, transverse and vertical directions. 
     The apparatus comprises carriers  8 , in this particular instance  4  of these, with the overall shape of a rectangular parallelepiped and placed removably side by side with their longitudinal sides facing each other, on a plate  12  of the apparatus  2  so that they are contiguous with the baseplate  4  and within reach of the needle  6 . 
     The two carriers  8  furthest to the left in FIG. 1 carry vertical columns  14 ,  16  which may, for example, be tubes or cavities, respectively containing raw samples to be prepared and reagents used for this preparation. 
     One of the two right-hand carriers  8 , which are identical to each other, will now be described in detail with reference to FIGS. 2 to  4 . 
     The carrier  8  comprises a baseplate  17  with a horizontal flat bottom  18  and two vertical flat walls  20  at the front and  22  at the rear, which are mutually parallel and rise up from the longitudinal ends of the bottom  18 . The baseplate  17  comprises two mutually parallel horizontal profiled rails  26  which are parallel to the longitudinal direction X of the bottom  18  and extend from the front wall  20  to the rear wall  22 , at the upper ends thereof. The baseplate  17  also has two longitudinal rims  28 , parallel to the rails  26 , running vertically and projecting out from the longitudinal edges of the bottom  18 . The aforementioned elements of the carrier are, in this instance, made of a rustproof ferromagnetic metal, such as a stainless steel. 
     The carrier  8  comprises a carriage  30  supported by the two rails  26  in such a way that it can move with longitudinal sliding with respect to the baseplate  17 , along the rails, from the front wall  20  to the rear wall  22 . The carriage  30  has longitudinal slots collaborating with the profile of the rails  26  such that any relative vertical movement of the carriage  30  and of the rails  26  upward or downward is impossible. Thus, the carriage  30  is fixed permanently to the rails. At its center, the carriage has a vertical through-hole which houses a block  31  made of plastic in the shape of a rectangular parallelepiped, defining a rectangular array of 8×12 vertical columns  32  of circular cross section. Each column  32  has a circular aperture  34  at the top and a narrowed nozzle-shaped aperture  36  at the bottom, surrounded by a cylindrical surround  38  which does not extend down as far as does the nozzle  36 . 
     The carrier  8  comprises a drainage unit or basin  40 , also in the shape of a rectangular parallelepiped, fixed to the bottom  18  near the rear wall  22 . This unit defines a rectangular array of 8×12 vertical ducts  42  open at the upper face of the block, and connected within the block to a common discharge pipe communicating with an extension  44  passing through the rear wall  22  of the carrier. 
     The carrier  8  comprises a block  46  with tubes  48  made of plastic defining a rectangular array of 8×12 vertical tubes  48  of circular cross section the same size as the columns  32 . Each tube  48  has a circular aperture  50  at the top which is the same size as the surround  38  at the bottom of the columns and which are open at the upper face of the block  46 . The tubes  48  are plugged at their other end so that the tubes can be emptied only via the aperture  50  at the top. The tube block  46  is supported by a raising/lowering unit  60  which will now be described with reference to FIGS. 5 to  7 . 
     The raising/lowering unit  60  comprises a plate  62  of flat rectangular overall shape. This plate has a flat top face  64  equipped, at its four corners, with four respective blocks  66  and, at its longitudinal end edges, with a rim  68 , the blocks  66  and the rims  68  extending vertically upward and projecting from the face  64 . The blocks  66  and the rims  68  hold the tube block  46  housed on the upper face  64  of the plate  62  in place in the horizontal directions X and Y. The plate has two longitudinal end faces  70  and two side faces  72 , all four of which faces are flat and vertical. It has a flat underside  74  parallel to the top face  64 . 
     The plate  62  has two flat ramps  76  which are mutually parallel and inclined with respect to the longitudinal direction X and vertical direction Z. These inclined ramps  76  extend from the longitudinal end faces  70  of the plate. The plate is arranged in the carrier in such a way that the rear ramp  76  is contiguous with the underside  74 , and the front ramp  76  is connected to the underside  74  by a flat mating ramp  78 , which is also inclined with respect to the directions X and Z. 
     The raising/lowering unit  60  also comprises two mutually parallel elongate slideways  80  which are axially symmetrical with one another, fixed to the bottom  18  of the baseplate along its longitudinal edges, and distant from one another. 
     Each slideway  80  has a flat top face  82  parallel to the bottom  18  and the same length as the underside  74  of the plate. Each slideway has two flat ramps  84  which are mutually parallel and inclined with respect to the directions X and Z so as to be parallel to the ramps  76  of the plate. The spacing between the two ramps  84  of one same slideway  80  is equal to that of the two ramps  76  of the plate. Each slideway has a mating ramp  87  adjacent to the front ramp  84 , parallel to the mating ramp  78  of the plate and the same size as the latter ramp. 
     Each slideway  80  near its front end has a flat vertical stop face  86  oriented toward the rear of the carrier. Each slideway  80  has an outer longitudinal rim  88  extending upward at its outer edge, projecting from its top face  82 . The two rims  88  provide sliding guidance in the longitudinal direction X of the plate  62  with respect to the slideways  80 . 
     The plate  62  is housed and placed on the slideways  80 . It can move in sliding with respect to the slideways between a lowered position depicted in FIG. 5, where the underside  74  of the plate rests on the top face  82  of the slideways, and in which the mating ramp  78  of the plate rests on the mating ramps  87  of the slideways; and a raised position, in FIG. 6, in which the plate  62  is raised further relative to the slideways  80 , the aforementioned associated faces being parallel and distant from each other. The change from one of these positions into the other is brought about by sliding (translational movement) of the plate  62  with respect to the slideways  80  in a direction which is inclined with respect to the directions X and Z, by the sliding and the bearing of the ramps  76  of the plate against the ramps  84  of the slideways. The stop face  86  limits the forward sliding of the plate, thereby defining the raised position. The movement of the plate between the two positions is, in this instance, rectilinear, given the shape of the ramps. 
     The raising/lowering unit  60  is configured in such a way that, with the plate in the lowered position, when the carriage  30  is over the tube block  46 , the apertures  50  at the top of the tubes  48  are each opposite and some distance from the apertures  36  at the bottom of the columns  32 , in coincidence, coaxial therewith, without interpenetration of the apertures. Furthermore, in the raised position, the aperture  36  at the bottom of the columns, still coaxially in coincidence with the tubes, extends into the aperture  50  at the top of the respective tubes, the tubes being brought closer to the columns upward. The aperture  50  at the top of the tubes is then in contact with the surround  38  of the columns. As an option, it is possible to insert, between the apertures  50  at the top of the tubes and the surrounds  38  of the columns, a film which covers said apertures and can be perforated by the nipples of the columns to provide an unsealed connection to allow the liquid to drop from the column into the tube. This film may be pre-perforated, for example with a cross-shaped preform. 
     The carriage  30  has two vertical elongate arms  92  extending from a rear end of the carriage downward as far as the level of the plate  62 . These arms  92  are designed to come into contact with the rear end face  70  of the plate, so that when the carriage  30  is moved using one or more needles  6  toward the front wall  20  and comes close to this wall, the arms  92  come to bear against the rear face  70  of the plate which initially is in the lowered position. This bearing effect forces the plate  62  horizontally forward, and this causes it to slide from the lowered position (FIG. 5) into the raised position (FIG. 6) in the way mentioned earlier. When the carriage  30  is moved back toward the rear wall  22 , the action of gravity on the plate  62  causes the plate to slide the other way, downward, into the lowered position. 
     The carriage  30  comprises longitudinal permanent magnets  94  housed in the front and rear longitudinal end edges of the carriage. When the carriage is in contact via its front edge with the front wall  20  of the baseplate, the front magnet  94  magnetically cooperates with the metallic front wall  20  to hold the carriage  30  in this position, particularly against the action of gravity exerted on the plate  62  in the raised position. A similar cooperation occurs between the rear wall  22  of the baseplate and the magnet in the rear edge of the carriage  30  to hold the carriage over the basin. 
     The carriage  30 , the plate  62  and the slideways  80  have at least their outer faces made of polyethylene terephthalate and will advantageously be completely made of this material. 
     The apparatus operates as follows, with respect to these features. The carriage  30  at the start is, for example, in the position of FIG. 2 over the basin  40 . This position is the position of the fourth carriage in FIG. 1, counting from the left. In this position, the respective tubes  48  and columns  32  are laterally offset from one another. The needle  6  comes to bear against the rear edge of the carriage  30  and forces it horizontally toward the front wall  20 . The needle may just as well come to bear against the front edge or alternatively move the carriage by inserting itself in a well designed for this purpose. The rails  86  then guide the carriage horizontally as far as this wall. When the carriage comes close to this wall  20 , the arms  92  come to bear against the rear face  70  of the plate  62 , initially in the lowered position, and cause it to rise into the raised position in an inclined rectilinear path guided by the rims  98  and the ramps  76 ,  84 . The tubes  48  are thus raised as far as the columns  32  so that the nozzles  36  enter the tubes. The tubes  48  and the columns  32  find themselves respectively in a position of mutual axial coincidence as soon as the arms  92  come into contact with the plate, and remain thus throughout the travel of the plate between the raised position and the lowered position. 
     The front magnet  94  cooperating with the front wall  20  holds the assembly in this position after the needle  6  has stopped acting on the carriage. This position of the carriage  30  and of the plate  62  is visible in FIG.  6  and in the case of the fourth carrier  8  of FIG. 1, counting from the left. The needle  6  can therefore enter the aperture at the top of a column  32  sealed hermetically by a stopper  102 , for example to inject a fluid and raise the pressure in the column  32  so that liquid can be transferred from the column into the tube via the nozzle  36 . 
     To return the carriage  30  to the initial position, offset toward the rear of the carrier, the needle  6  forces the front edge of the carriage  30  horizontally backward against the magnetic retaining force of the magnet  94 , to cause the carriage and the plate to move in the opposite direction. The needle  6  may also come to bear against the front edge or alternatively move the carriage by inserting itself in a well designed for this purpose. 
     With reference to FIGS. 9 to  11 , the hermetic sealing of the aperture  34  at the top of the columns  32  may advantageously be achieved by means of a longitudinal strip  100  of several stoppers  102 , for example eight stoppers, connected together. The strips  100  are fixed parallel to each other on the block  31  to plug the apertures  34  at the top of the columns, as shown in FIG.  1 . Each stopper  102  has a circular internal lip  104  designed to press against the internal face of the column  32  and a peripheral groove  106  designed to hug the top aperture  34 . The internal lip  104  may also be square or of any other geometry that suits that of the column  32 . The upper face of the stopper is shaped into a funnel  108 , narrowing toward the bottom until it becomes a duct  110 , the diameter of which is smaller than that of the needle. The funnel  108  guides the needle  6  as far as the duct  110  which the needle enters so that, with the stopper  102 , it seals the column  32  closed. The needle  6  can then inject a liquid or pressurized air into the column so as to force all of the contents of the column to pass through an agent  112  in powder form deposited at the base of the column. Advantageously, this agent in powder form may be replaced by-a pellet cut from a film. 
     Of course, numerous modifications may be made to the invention without departing from its scope. The invention may be adapted so that the columns  32  are moved vertically with respect to the baseplate  17 . The path of the tubes  48  may be other than rectilinear, for example may be circular. This path may also be not inclined, but purely vertical. 
     The raising/lowering unit  60  may consist of a plate connected to the baseplate by link rods which define deformable parallelograms. The vertical-movement means may have their own drive means independent of the needle  6 . The holding means may be disengageable mechanical means. 
     The vertical-guidance means may comprise just one ramp in contact with a bearing piece. 
     The needle may be replaced by a raft of several mutually parallel needles which can enter columns simultaneously. 
     The ramp and that zone of the bearing piece which is designed to be in contact with the ramp may be made of polyoxymethylene.