Abstract:
A punching apparatus ( 10 ) and method for delivering disk samples ( 20 ) from media containing a dried bio-sample into a receptacle for use in an assay. In one aspect, the shape of the disk is altered, such as by folding, so that a disk of larger cross sectional size may fit into a receptacle having a cross sectional size less than the disk punched from the media.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to improvements in devices designed to remove a portion from a bio-sample for use in an analysis. 
       BACKGROUND OF THE INVENTION 
       [0002]    Dried sample on media is becoming increasingly popular as the primary source of bio-sample used in assays in a range of applications. 
         [0003]    High throughput situations call for automated solutions. This usually involves the use of standardised formats for sample receptacles, (e.g. standard sized test tubes) and the use of standardised formats for the racks to hold those tubes, or for the laboratory plates incorporating the receptacles (e.g. SBS footprint for plates/tube racks). Receptacles are almost always round in shape. 
         [0004]    Typically, once a disk has been punched into a receptacle, liquid is then added to the receptacle as part of the processing. Often, after that processing, the liquid has to be drawn out of the receptacle, through devices such as pipettes, either manually or automatically. Sometimes as part of the flow of the liquid into the pipette tip, the punched disk becomes lodged on, or in the end of the tip, stopping the liquid flow. This is a common problem for laboratories using dried sample on media. 
         [0005]    Furthermore, occasionally in some applications, the reaction with the liquid requires more sample material to be provided than can be found in a disk that is the same diameter as the receptacle. While it is possible using some instruments to punch multiple samples into the one receptacle, sometimes these multiple disks may come to rest in the bottom of the receptacle on top of each other, thus limiting the extent of contact between the liquid and the surface area of the punched disk (where the dried bio-sample is present). The present invention seeks to lessen these problems and/or provide more reliable, repeatable performance. 
       SUMMARY 
       [0006]    The invention in one preferred aspect involves punching a disk with a diameter larger than the diameter of the receptacle, folding that disk into a curved shape so that one of the resulting “gross” dimensions of the shape is less than the diameter of the receptacle, and then manipulating the travel of the folded disk when it is free of the punch at the end of its travel so that the long dimension is moved to a vertical orientation, and allows the folded disk to then fall via a special chute into the receptacle. 
         [0007]    When the disk falls into the receptacle, it will often lodge itself against one part of the wall of the (round) receptacle, (i.e. so that the curve of the disk matches the curve of the receptacle wall) allowing for pipette tips to be inserted into the receptacle without interference from the punched disk. Often the curved disk will have a memory and move into a shape that further matches the curvature of the wall of the receptacle. 
         [0008]    A further example would involve punching a rectangular disk to get greater sample material, but this does not offer the advantages that come as a result of the folded disk aligning itself against the wall of the receptacle and allowing access for pipettes of similar devices. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]    In order that this invention may be more readily understood and put into practical effect, reference will now be made to the accompanying drawings that illustrate preferred embodiments of the invention, and wherein: 
           [0010]      FIG. 1  is a front view of a punching apparatus in accordance with a preferred embodiment of the present invention; 
           [0011]      FIG. 2  is a partial cross sectional side view of the punching apparatus of  FIG. 1  taken along line C-C of  FIG. 1 ; 
           [0012]      FIG. 3  is a partial cross sectional front view of the punching apparatus of  FIG. 1  taken along line D-D of  FIG. 2 ; 
           [0013]      FIG. 4  is a sectional perspective view of a punching apparatus of another preferred embodiment of the present invention; 
           [0014]      FIG. 5  is a front view of a punch for the punching apparatus of the other embodiment; 
           [0015]      FIG. 6  is an enlarged sectional perspective view of a manifold for the other embodiment; and 
           [0016]      FIG. 7  is an enlarged sectional perspective view of a chute for the other embodiment. 
       
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0017]    Alternative embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the claims which follow. 
         [0018]      FIGS. 1 to 3  show a preferred embodiment of a punching apparatus  10  having a punch  100 , a manifold assembly  102  and a chute  104 . The preferred elements of and their interrelationship are described below. 
         [0019]    Referring to  FIG. 2 , punch  100  includes a passage  106  for passage of an ejector pin  110  therethrough. Punch  100  has a central longitudinal axis CLA. Passage  106  is preferably offset from the CIA of punch  100 . Ejector pin  110  is adapted to encourage the disk of media removed by punch  100  to free itself from bottom  108  of punch  100  with one end of the long dimension of the folded disk moving downwards first. Ejector pin  110  is preferably associated with a spring mounted in the top part of passage  106 . 
         [0020]    Manifold assembly  102  is connected to punch  100  preferably immediately below the die plate of the punch. Manifold assembly  102  preferably includes an air inlet  112  for the inflow of air (using a small pump) on a side of the manifold opposite to where the vacuum is applied (direction 1) and an air outlet  114  to which a vacuum pump is connected, to extract dust from the manifold (in direction 2) as the punch and punched disk pass through manifold  102 . Manifold assembly  102  further preferably includes an inlet cavity  116  in communication with bottom  108  of punch  100  and an outlet  118  for connection with chute  104 . 
         [0021]    As shown in  FIG. 2 , chute  104  preferably includes an inlet  120  for connection to outlet  118  of manifold assembly  102 , a curved section  122  configured at an angle relative to the CLA of punch  100 , and an outlet  124 . Chute  104  further preferably includes a projection such as a pin  126  proximate inlet  120 . 
         [0022]    Having described the preferred components of the punch apparatus, a preferred method of use will now be described with reference to  FIGS. 2 and 3 . 
         [0023]    Punch  100  is used to remove a portion  20  of the media containing the dried bio-sample. At least one ejector pin  110 , (see  4  and  8  in  FIGS. 2 and 3 ) in passage  106  (see  5 ) is preferably offset from CLA of punch  100  so as to encourage the disk  20  to free itself from bottom  108  of punch  100 , with one end of the long dimension of the folded disk  20  moving downwards first. Air is introduced into the top of passage  106  (preferably to push down the leading edge of folded disk  20 , but also to create positive air pressure in passage  106  to prevent paper dust from entering into that passage, which could potentially cause cross contamination between samples. Air may also be introduced laterally through manifold assembly  102  in the direction 2 ( FIG. 2 ) to extract dust from the manifold as punch  100  and punched disk  20  pass through manifold assembly  102 . 
         [0024]    Punch  100  and disk  20  travel into a portion of chute  104 , where the chute is essentially of a diameter slightly bigger than the small dimension of folded disk  20 . The centre of chute  104  is preferably offset relative to the centre of punch  100 . Pin  124  of chute  104  is preferably in contact with the trailing edge of folded disk  20  so as to briefly delay the fall of disk  20  as it becomes free of the punch (see  7  and  8  of  FIGS. 2 and 3 ). The act of holding up the trailing edge of the folded disk, while positively ejecting the leading edge, causes folded disk  20  to adopt the preferred orientation in chute  104 . Chute  104  is preferably controlled so that it is allowed to fall onto the top of the receiving receptacle immediately prior to the disk falling through the chute into the receptacle. The gap between outlet  124  of the chute and the receptacle might typically be in the range of approximately 1-3 mm. 
         [0025]    Preferably chute  104  incorporates one or more detectors to confirm that disk  20  has passed successfully through the chute. Once this has been detected, then chute  104  is raised. In the event that the detectors do not detect that the disk has passed through chute  104 , the system may be programmed to operate in such a way that chute  104  is moved up and down as necessary to dislodge the disk. The system preferably includes a computer-controlled means for bringing the appropriate receiving receptacle under the end of the chute. 
         [0026]    It will be appreciated that certain of the steps described above may be performed in a different order, varied, or omitted entirely without departing from the scope of the present invention. 
         [0027]    Another embodiment of the invention, which employs a straight (rather than curved) chute will be described with reference to a punching apparatus  200  depicted in  FIGS. 4 to 7 . The punching apparatus  200  shown in  FIG. 4  includes a punch  201  and a punch cap  202 , which cap incorporates an air intake  203 . The punch  201  is operatively associated with two ejector pins  204  which are biased by respective ejector springs  205 . The punch  201  has a cutting profile portion  206 , as depicted in  FIG. 5 . 
         [0028]    Turning to  FIG. 6 , there is shown a punch manifold including a punch guide  207  and a punch die  208  having an annulus  209 . The manifold further includes a port  210  which is suitably used for application of a vacuum to extract unwanted particulate matter, such as dust particles created when a disk is punched from sample media, and other contaminants. A straight chute  211  for receiving punched disks from the cutting apparatus  200  is shown in  FIG. 7 . The chute  211  includes a deflector  212  at a first normally upper end and spot detectors  213  at a lower end thereof. 
         [0029]    The springs  205  for the ejector pins  204  provide a downward force to assist release of a punched disk from the cutting profile  206  in the bottom portion of the punch  201 . An ejector pin located at the front of the punch  201 , where an edge of the disk is to be oriented downwards into the chute  211 , is longer or the spring has a stronger bias or both. 
         [0030]    The straight chute, which is suitably disposed vertically in  FIG. 6 , is designed to reduce the likelihood that punched disks will become lodged in the curved chute ( FIG. 2 ), as may sometimes occur with the curved chute. 
         [0031]    The air system into the punch depicted in  FIG. 4  may be configured to either allow air pressure to be added into the ejector system to prevent the build-up of paper dust and/or lint around the holes in the bottom of the punch where the ejectors protrude, or alternatively, to have vacuum applied to remove that dust. In some applications, the positive pressure configuration has been found to be superior to the vacuum arrangement. 
         [0032]    In some applications where the invention may be used, the sensitivity of the assay being undertaken on the sample may be such that even a very small amount of particle carry-over in the punching system from one sample to the next may be sufficient to throw the conclusions of the assay with respect to a second or subsequent sample into doubt. This is particularly the case where the assay in question is intended to diagnose whether the subject providing the sample has, or does not have a particular disease or disorder. Typically, the assays involve assessment processes such as those which amplify a specific DNA type such as a disease type. 
         [0033]    It is known that the application of particular levels of Ultra Violet radiation, in the C range, typically with wavelengths in the range 230-280 nm, but especially around 254 nm, will damage DNA whether in hydrated or dehydrated states. Damaged DNA will not be amplified in the assessment process, and is therefore not recognised in an assay. 
         [0034]    To substantially eliminate the potential for any particle carryover between one sample and the next to confuse the outcomes of the second assay, the device can been fitted, in one embodiment, with a UVC emitter which will be exposed to the appropriate surfaces of the device for a sufficient period to damage any remaining particles which may be a source of cross-contamination. This exposure occurs between the punching of each new sample. Any DNA on remaining particles is, as a result of the UV application, not recognised as being of the disease type being examined, and therefore does not confuse the results of the assay. 
         [0035]    The appropriate surfaces of the device are those which either come into direct contact with the sample or those that come into contact with particles from the sample media that become loose from the sample during the handling, such as those, for example, that become airborne. 
         [0036]    The foregoing description is by way of example only, and may be varied considerably without departing from the scope of the present invention. For example only, the floor of the concave section in the punch could be at an angle other than 90 degrees to the central longitudinal axis of the punch to assist in getting the disk to free itself from the end of the punch in such a way as to assist in its preferred orientation in the chute. Air could be used instead of the ejector pin in the punch. There could be two ejector pins in the punch, either of different lengths and with the same method of driving the disk off the punch, (e.g. two springs of the same size) or two ejectors of the same length, but with different means of driving the disk off the punch, i.e. providing more force of the leading edge of the disk than the trailing edge. 
         [0037]    Examples of systems or elements of systems that may be adapted in conformity with the present invention include those described in U.S. Application No. 10/982,539, entitled “System and Method for Analysing Laboratory Samples,” (Publication No. 2005/0129579); U.S. Application No. 11/148,094, entitled “Method and Apparatus for Inspecting Biological Samples,” (Publication No. 2005/0287678); International Application No. PCT/AU2007/000171, entitled “Biological Sample Collection Device;” and International Application No. PCT/AU99/00485, entitled “a Punching Apparatus,” the disclosure of each being incorporated herein by reference. 
         [0038]    The features described with respect to one embodiment may be applied to other embodiments, or combined with or interchanged with the features other embodiments, as appropriate, without departing from the scope of the present invention. 
         [0039]    It will of course be realised that the above has been given only by way of illustrative example of the invention and that all such modifications and variations thereto as would be apparent to persons skilled in the art are deemed to fall within the broad scope and ambit of the invention as herein set forth.