Patent Publication Number: US-2005129579-A1

Title: System and method for analysing laboratory samples

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
      This application claims the benefit of Australian Provisional Patent Application No. 2003906081 filed Nov. 5, 2003, which application is herein incorporated by reference in its entirety. 
    
    
     BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      This invention relates to a system and method for analysing laboratory samples. The invention has particular but not exclusive application to punching out for testing purposes samples from a filter paper on which liquid biological samples have been dried.  
      2. Discussion of the Background Art  
      It is known for laboratory samples that are normally in a liquid state to be dried on filter paper for ease of transport and storage. One such application involves a filter paper card format where the card has the same footprint as an SBS laboratory-standard plate having 96 sample sites.  
      The present applicant&#39;s earlier International Patent Publication No. WO 99/65625 describes a punching apparatus having a punch and a die for punching out portions of samples retained on paper media. It has been found that, in the case of paper and other fine grade materials to be punched, the clearances required between the outside diameter of the punch and the inside diameter of the hole in the die are very tight, being in the order of 10 microns.  
      Frames or similar peripheral support arrangements for paper cards or other media for retaining samples are presently under development. Typically these support arrangements result in the medium being suspended at its periphery. These arrangements present further difficulties in punching portions of samples cleanly and effectively from a sample medium, due to difficulties in effectively accessing or supporting the medium at the desired sample sites.  
     SUMMARY OF THE INVENTION  
      Object of the Invention  
      The present invention aims to provide an alternative to known systems and methods of the above type, which addresses these and other problems.  
      Disclosure of the Invention  
      This invention in one aspect resides broadly in a system for analysing laboratory samples wherein samples to be tested are impregnated in designated areas on a sheet such as a filter card or like medium, the system comprising: 
      a frame supporting the filter card for the manipulation and transport thereof;     a sampling assembly for removing a portion of the sample impregnated in the designated areas on the filter card, wherein said sampling assembly includes: 
        a punch and die mechanism having a punch movable into a hole provided in the die;     locating means for positioning the punch and die mechanism relative to the designated area; and     wherein said die is arranged to directly support the medium during removal of said portion of the sample from the filter card.    
       

      Suitably, the die includes a raised section to directly support the medium adjacent to said portion of the sample in a designated area.  
      In another aspect, the invention resides in a sampling assembly for removing a portion of a sample impregnated in designated areas of a medium, suitably filter card, supported in a frame; said assembly comprising: 
          a punch and die mechanism having a punch movable into a hole provided in the die;     locating means for positioning the punch and die mechanism relative to the designated area of the filter card; and     a raised section provided on said die and arranged to directly support the medium adjacent to the portion of the sample during removal of said portion from the filter card.        

      Preferably, the raised section of the die is arranged such that the sampling assembly conveniently provides clearance for the frame supporting the filter card.  
      A periphery of the raised section of the die may include surfaces sloping outwardly and downwardly from the hole in the die.  
      Suitably, the sampling assembly includes a guide member having a bore for the punch and an opposing die member incorporating the hole, which guide member and die member are either fixed together or integrally formed. Most suitably, the guide member and opposing die member define a mouth or slot for insertion of the frame.  
      If required, first and second inert layers juxtaposing opposite surfaces of the filter card are provided for the protection thereof.  
      Apertures may be provided in at least one inert layer positioned to substantially overlay the designated areas when the inert layers and the filter card juxtapose.  
      It is preferred that the apertures are substantially square.  
      It is also preferred that the corners of the substantially square apertures are rounded and the designated areas on the filter card are substantially circular, the length of the side of the square substantially corresponding with the diameter of the substantially circular designated areas.  
      It is preferred that there are apertures in each inert layer and that the sampling assembly includes a punch and die assembly, locating means positioning the punch and die assembly relative to the designated area.  
      It is also preferred that the punch is positioned adjacent one of the inert layers and the die is positioned adjacent the other inert layer, the locating means being the apertures in the respective inert layers.  
      It is also preferred that the punch is adapted to remove a portion of the sample which is substantially smaller than the designated area such that a plurality of samples can be removed from a designated area.  
      It is also preferred that the die has a single recess for cooperating with the punch to receive the removed portion, the die and the punch both moving relative to the filter card and being positioned prior to punching by engagement with the respective apertures in both inert layers.  
      It is to be understood that references to movement of the punch and die relative to the filter card include movement of the filter card relative to a stationary punch and die assembly.  
      Alternatively, the die can have a plurality of recesses for cooperating with the punch to receive the removed portion, the punch moving relative to the filter card and the die, and being positioned prior to punching by engagement with an aperture in the one inert layer, the die being in engagement with an aperture in the other inert layer.  
      It is also preferred that the apertures in the other inert layer which locate the die are substantially frustro-conical, the portion of the die adapted to engage these apertures being correspondingly frustro-conical.  
      Alternatively, the apertures in the other inert layer which locate the die can be slightly larger than the apertures in the one inert layer which locate the punch.  
      In another embodiment the sampling assembly can include a corer for removing the portion of the sample by coring. In this embodiment it is preferred that there are apertures in only one layer, the other layer constituting a backing.  
      The corer can optionally include a rotating hollow coring tool.  
      In another aspect this invention resides broadly in a method of analysing laboratory samples wherein samples to be tested are impregnated in designated areas on a filter card or the like supported in a frame, the method comprising: 
      providing a sampling assembly having a punch and die mechanism having a punch movable into a hole provided in the die;     positioning the punch and die mechanism relative to a selected designated area with a locating means of the sampling assembly;     directly supporting the medium with a raised section provided on said die; and     removing from the filter card a portion of the sample impregnated in the designated areas thereon, said portion of the sample being removed by punching the portion into the die.    

      If required, the method may include the steps of juxtaposing first and second inert layers adjacent opposite surfaces of the filter card for the protection thereof; 
      forming apertures in at least one inert layer, the apertures being positioned to substantially overlay the designated areas when the inert layers and the filter card juxtapose.    

      It is preferred that the apertures are substantially square.  
      It is also preferred that the method includes positioning a punch adjacent one of the inert layers and positioning a die adjacent the other inert layer by locating the punch and die in the apertures in the respective inert layers.  
      In a further aspect this invention resides broadly in a filter card assembly for analysing laboratory samples, the assembly comprising: 
      a filter card or the like whereon samples to be tested can be impregnated in designated areas,     first and second inert layers juxtaposing opposite surfaces of the filter card for the protection thereof, and     apertures in at least one inert layer positioned to substantially overlay the designated areas when the inert layers and the filter card juxtapose.    

      It is preferred that the apertures are substantially square.  
      It is also preferred that there are apertures in each inert layer respectively adapted to locate a punch positioned adjacent one of the inert layers and a die positioned adjacent the other inert layer.  
      In an alternative embodiment there are apertures in only one layer adapted to locate a cover positioned adjacent the one inert layer, the other layer constituting a backing. 
    
    
     BRIEF DETAILS OF THE DRAWINGS  
      In order that this invention may be more easily understood and put into practical effect, reference will now be made to the accompanying drawings which illustrate a preferred embodiment of the invention, wherein:  
       FIG. 1  is a partial plan view of a filter plate assembly in accordance with a preferred embodiment of present invention showing four substantially square cut-outs in the upper protective layer;  
       FIG. 2  is a cross sectional elevation of the filter plate assembly of  FIG. 1  showing the filter paper sandwiched between the upper and lower protective layers;  
       FIG. 3  is a cross sectional view corresponding to that shown in  FIG. 2  and schematically illustrating a representative arrangement of a punch and die assembly for removing samples from the filter paper in accordance with a preferred embodiment of the present invention;  
       FIG. 4  is a partial plan view of a filter plate assembly showing four substantially circular cut-outs in the upper protective layer;  
       FIG. 5  is a cross sectional elevation of the filter plate assembly of  FIG. 4  showing the filter paper sandwiched between the upper and lower protective layers;  
       FIG. 6  is a cross-sectional elevation showing another preferred embodiment of a filter plate assembly in which the filter paper is sandwiched between an upper protective layer having cut-outs or apertures therein and a lower hard base protective layer, together with a coring device for removing samples from the filter paper;  
       FIG. 7  is a cross-sectional elevation showing a further preferred embodiment of a sampling apparatus including a punch and die mechanism;  
       FIG. 8  is a top plan view of the sampling apparatus of  FIG. 7 ;  
       FIG. 9  is an enlarged side elevation of the die member of the sampling apparatus of  FIG. 7 ;  
       FIG. 10  is a side elevation of a still further preferred embodiment of a sampling apparatus, adapted for use with relatively bulky supporting frames; and  
       FIG. 11  is a partial plan view of the die member of the sampling apparatus of  FIG. 10 . 
    
    
     DESCRIPTION OF EMBODIMENTS OF THE INVENTION  
      In order to minimise the risk of cross-contamination and to aid automated handling in a system and method as described above, an inert medium  11 ,  12  is placed on either side of a sheet medium such as a filter card  13  and touching the card, either in a frame, or attached directly to the card.  
      To enable small parts of the dried biological sample (such as blood, urine or saliva) in the 96 sample sites to be punched out for testing purposes, the inert medium  11 ,  12  on each side of the card includes holes  14 ,  15  respectively to allow a punch and die mechanism  17 ,  18  (as seen schematically in  FIG. 3  or in  FIG. 7 ) to access the cards and sample sites.  
      In some applications it may be desired to punch out and remove disks of sample material with smaller diameter than the diameter of the sample site disc itself. Such sample site discs are typically 13 mm diameter and the smaller sample discs (as seen at  16  in  FIG. 1 ) could be for example, 2 mm diameter.  
      It has been found that a particular shape of holes  14 ,  15  in the inert medium on each side of the card is most suitable for this automated punching purpose, given the nature of a typical punch and die operation. This particular shape is seen in  FIG. 1  as being substantially square. The corners of the square can be slightly rounded and in the example shown the radius of curvature of the corners is 2.5 mm.  
      To facilitate the small disks being cut cleanly from the card, the punch  17  and the die  18  is positioned immediately adjacent to the card  13  at the time of punching. Support members for the punch and the die are fixed relative to one another, such as by mounting to a common C-shaped guide block  31  of a sampling assembly  30  of the embodiment depicted in  FIG. 7 . This embodiment is discussed in more detail below.  
      In view of the clearance within which the punch  17  and die  18  are normally required to operate, for example in the order of 10 microns, separate support members for punch and die that are independently movable in the x-y plane are considered uneconomic. Accordingly, a locating means (not shown) is provided for the C-shaped guide block  31 , as desired, under program control.  
      While the particular shaped hole  14  in the upper medium  11  assists in allowing the punch to access the sample, a complementary die can also be used, such that the die incorporates a special raised section  19  that fits into the shaped hole  15  in medium  12  beneath the card  13 .  
      In some applications, the raised section  19  of the die plate  18  could incorporate four punching holes  21 , corresponding to the maximum number of 2 mm disks to be cut from the sample. In this case, the punch  17  would move in an x y direction, relative to the card  13  and die plate  18 .  
      In some other applications, the raised section  19  of the die plate  18  could be smaller and incorporate one punching hole  20  only, in which case, the raised section  19  of the die plate  18  and the punch  17  could move in an x-y direction, relative to the card  13 .  
      In both of the above cases, the card  13  and die plate  18  would move in a z axis relative to the other, to allow for the re-positioning of the card  13  on the raised die section  19 .  
      The shaped hole  15  in the medium  12  beneath the card can, in some applications, have a sloping or chamfered inner face as seen in  FIG. 2 .  
      It will be appreciated that the shape of the opening  14  in the upper medium  11  as seen in  FIG. 1 , in comparison with the circular shaped opening  21  as illustrated in  FIGS. 4 and 5 , provides a greater integrity to the sample in that whereas in the  FIG. 4  arrangement, 2 mm diameter discs centred 2.5 mm apart are only 0.48 mm from the periphery of a 13 mm circular cut-out, in the arrangement illustrated in  FIG. 1  similarly located 2 mm discs are 1.25 mm from the periphery of the substantially square cut-out with rounded corners.  
      Thus with reference to  FIGS. 1-3 , the system of the present invention has samples to be tested which are impregnated in designated areas on a filter card  13 . The system has first and second inert layers  11 ,  12  juxtaposing opposite surfaces of filter card  13  for protecting the filter card. Apertures  14 ,  15  in the inert layers  11 ,  12  are positioned to substantially overlay the designated areas when the inert layers  11 ,  12  and the filter card  13  juxtapose as seen in  FIGS. 2 and 3 . As described above and subsequently in more detail, a sampling assembly removes a portion of the sample impregnated in the designated areas on the filter card  13 .  
      As seen in  FIG. 1 , the apertures  14  are substantially square with the corners of the substantially square apertures being rounded. The designated areas on the filter card  13  are substantially circular and the length of the side of the square  14  substantially corresponds with the diameter of the substantially circular designated areas.  
      The sampling assembly includes a punch and die assembly  17 ,  18  (as in  FIG. 3 ) and locating means position the punch and die assembly relative to the designated area on filter card  13 . Punch  17  is positioned adjacent inert layer  11  and die  18  is positioned adjacent the other inert layer  12 , the locating means being the apertures  14 ,  15  in the respective inert layers  11 ,  12 .  
      Punch  17  is adapted to remove a portion of the sample which is substantially smaller than the designated area, such that a plurality of samples can be removed from a designated area.  
      Die  18  may have a single recess  20  for cooperating with punch  17  to receive the removed portion, the die  18  and the punch  17  both moving relative to the filter card  13  and being positioned prior to punching by the respective apertures  14 ,  15  in both inert layers  11 ,  12 .  
      Alternatively as seen in  FIG. 3 , die  18  can have a plurality of recesses  20  for cooperating with punch  17  to receive the removed portion. Punch  17  is positioned prior to punching by an aperture  14  in inert layer  11 , die  18  having been positioned in an aperture  15  in the other inert layer  12 .  
      The apertures  15  in inert layer  12  which locate die  18  are substantially frustro-conical and the portion  19  of die  18  adapted to engage these apertures  15  is correspondingly frustro-conical.  
      Alternatively in an embodiment not illustrated, the apertures  15  in inert layer  12  which locate die  18  are slightly larger than apertures  14  in inert layer  11  which locate punch  17 . Suitably the side of apertures  15  are 8 mm and the side of apertures  14  are 7 mm.  
      The filter card assembly for analysing laboratory samples in accordance with a further aspect of this invention is thus seen to include a filter card  13  whereon samples to be tested can be impregnated in designated areas. First and second inert layers  11 ,  12  juxtapose opposite surfaces of the filter card  13  for the protection thereof. Apertures  14 ,  15  in the inert layers  11 ,  12  substantially overlay the designated areas when the inert layers and the filter card juxtapose. Apertures  14 ,  15  are substantially square and are adapted to locate a punch  17  positioned adjacent inert layer  11  and a die  18  positioned adjacent the other inert layer  12 .  
      In use, the method of another aspect of the present invention provides for the analysis of laboratory samples which have been impregnated in designated areas on a filter card  13 . First and second inert layers  11 ,  12  are juxtaposed adjacent opposite surfaces of the filter card  13  to protect the card. Apertures  14 ,  15  are formed in the inert layers  11 ,  12  and positioned to substantially overlay the designated areas when the inert layers  11 ,  12  and the filter card  13  juxtapose. A portion of the sample impregnated in the designated areas on the filter card is removed by positioning a punch  17  adjacent inert layer  11  and positioning a die  18  adjacent the other inert layer  12 . Punch  17  and die  18  are located in the apertures  14 ,  15  in the respective inert layers  11 ,  12  and the portion of the sample is removed by punching the portion into die  18 .  
      Alternatively, as seen in  FIG. 6 , in another preferred embodiment of the invention, the method of this other aspect of the invention provides for the analysis of laboratory samples which have been impregnated in designated areas on a filter card  13 . First and second inert layers  11 ,  12  are juxtaposed adjacent opposite surfaces of the filter card  13  to protect the card. Apertures  14  are formed in the inert layers  11  and positioned to substantially overlay the designated areas when the inert layers  11 ,  12  and the filter card  13  juxtapose. Inert layer  23  is relatively stiff and constitutes a backing. A portion of the sample impregnated in the designated areas on the filter card is removed by positioning a corer  22  adjacent inert layer  11  and then in the apertures  14  in inert layers  11 . The portion of the sample is then removed by operating the corer  22  in either rotating or reciprocating fashion.  
      A further embodiment of the system of the invention is depicted in FIGS.  7  to  9 , which system includes a sampling apparatus  30  configured for operation with a frame  39  supporting a sheet medium  37  including a filter card. Indicative dimensions are included on the drawings (which are not to scale) to provide an appreciation of relative sizes. For example, the frame  39  is approximately 50 mm square, having a central window of about 34 mm wide by 23 mm long wherein the medium  37  carrying a sample  40  is exposed. This frame is similar in size to frames otherwise employed to hold photographic slides, and thus are widely available.  
      The sampling apparatus  30  provides a common support assembly for a punch  32 , which travels in a bore provided in a guide member  31 , and a die member  33 , which includes a die hole  34  arranged co-axially with the punch bore. The support assembly has a generally C-shaped configuration wherein the mouth of the C is constituted by a slot  36  arranged to receive the frame  39 , whilst the arms of the C are constituted by the guide member  31  and the opposing die member  33 .  
      The guide member  31  guides the direction of the punch  32 , which in this example has a 3 mm diameter cylindrical configuration, and moves from one side of the medium  37  to the other side, by extending out of the bore and into the die hole  34  in the opposing die member  33 , thereby punching out a disk  38  retaining a portion of a designated area of the sample  40 . The die member  33  includes a raised section  35  arranged to directly support the medium  37  adjacent the portion to be punched and removed from the sample  40 . The medium  37  would otherwise be suspended in the frame  39 , by virtue of the frame resting on an upper surface of the die member  33 , as evident from  FIG. 7 .  
      An enlarged view of the raised section  35  of the die member  33  is shown in  FIG. 9 . The raised section  35  of the embodiment includes an annular portion  42  disposed circumferentially with respect to the die hole  34  and an inclined portion  41  extending from the annular portion down to the upper face  43  of the die member  33 . The annular portion has a height of 1 mm above the upper face  43 . The angle of the inclined portion is desirably about 10°, such that the frame  39  carrying the filter card  37  can be easily introduced into the 4 mm high slot  36 , either manually or by machine.  
      Whilst the guide member and the die member are integrally formed in the support assembly of embodiment, it will be appreciated that separate guide and die members may be fixed together in other embodiments. The guide and die members are desirably integral or fixed relative to one another to achieve the accuracies and clearances required as part of the operation of punching a fine gauged medium. In order for such punching apparatus to operate effectively, the punch and die mechanism is desirably manufactured so that the bore of the guide  31  and the hole  34  in the die  33  are desirably created at the same time and in the same process, often by machining.  
      A further embodiment of the system of the invention, which employs a physically larger frame, is shown in  FIG. 10 . In this embodiment, the sampling apparatus  50  is adapted for use with a medium  46  supported in a frame  45  that is approximately 8 mm in height, thereby suspending the medium some 4 mm to 5 mm above a lowermost surface of the frame.  
      The sampling apparatus  50  here includes an upper guide member  51  having a bore  52  for guiding a punch  53 . The support assembly further includes a lower die member  54  defining a mouth or slot  55 , which slot is approximately 16 mm high and 90 mm deep to accommodate a medium  46  having a greater length dimension. The medium may suitably be up to about 75 mm long.  
      In this example, and in other examples where disks (not shown) are to be punched from the medium in close proximity to the edge of a supporting frame, it is less than practical to provide the die member with a raised portion having a gentle incline to the raised section, as has been done in the embodiment of FIGS.  7  to  9 . Instead, in  FIG. 10 , the raised section  56  has substantially upright sides  57  which may be vertical or near to vertical. In this case, the frame  45  may be lifted in the card slot  55  (either manually or mechanically) so that the lowermost surface  47  of the frame  45  is clear of the raised section  56 , allowing insertion of the frame  45  and medium  46  into the card slot  55 .  
      Once the lower surface  47  of the frame moves past the raised section  56 , the frame can be lowered onto the die plate or die member  54 . The raised section  56  of the die member will then support the medium  46  suspended in the frame  45  adjacent to the area to be removed from the medium by the punch  53 . A plan view of the raised section  56 , which has a square shape with radiused corners to facilitate access to corners of the medium  47  in proximity to the frame  45 , is depicted in  FIG. 11   
      The frame can then be moved to various positions within the card slot  55 , suitably by a mechanical locating means such as a pneumatic actuator (not shown), to allow for punching out portions or disks of the medium  46  from different places in a designated area of the sample. Alternatively, it will be appreciated that the sampling apparatus  50  may be moved relative to the frame  45 .  
      The direct support of the medium by the die, suitably a raised section of the die dimensioned in accordance with a frame supporting a filter paper or like medium, reduces the chance of tearing of the medium and thus promotes clean punching of disks retaining a portion of the sample. It will be appreciated that the medium may further comprise inert layers applied to either or both faces of the filter card, as required.  
      It will of course be realised that whilst the above has been given by way of an illustrative example of this invention, all such and other modifications and variations hereto, as would be apparent to persons skilled in the art, are deemed to fall within the broad scope and ambit of this invention as is set forth herein and defined in the claims which follow.