Abstract:
A method of random-access storage and retrieval of any particular compartmentalized samples from a integral array of storage compartments with an apparatus to wholly excise intact sample-containing compartments and then convey the liberated samples intact in their respective compartments to designated locations of an adapted receiving tray, where they are releaseably locked in place.

Description:
PRIOR APPLICATION INFORMATION 
     This application is a continuation of commonly owned patent application Ser. No. 10/319,159, filed Dec. 13, 2002, now U.S. Pat. No. 7,632,467, which claims benefit from provisional patent application No. 60/340,284, which was filed on Dec. 13, 2001. The entire disclosure of each of the foregoing applications is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to automated chemical, pharmaceutical or biotech compound testing systems using miniature shelf keeping units or test tubes. The shelf keeping units or test tubes are preferably stored in a standing refrigeration unit and are retrieved by a robot. 
     2. Discussion of the Prior Art 
     In prior art systems, shelf keeping unit parts are separately molded to provide, for example, an array of 384 miniature shelf keeping units or test tubes; the tubes are inserted in a matrix of 384 square sockets, thus requiring a very costly assembly. 
     Industry standards promulgated (in draft form) by the Society for Biomolecular Screening (“SBS”) specify standard dimensions and characteristics for microtiter plates (or microplates). The SBS homepage is attached hereto as appendix A; the SBS Microplate Standards Development Committee&#39;web page printout is attached hereto as appendix B. The SBS Microplate Standards Development Committee draft standard SBS-1 (Footprint Dimensions) is attached hereto as appendix C, and the SBS Microplate Standards Development Committee draft standard SBS-4 (Well Positions) is attached hereto as appendix D. Taken together, these serve to enable a person of ordinary skill in the art to understand the specifications of the prior art shelf keeping units. 
     In use, a robotic retrieval system responds to requests wherein individual tubes are taken from a plate and moved in a process called reformatting; the tubes are moved to another plate, e.g., having a different makeup of compound. In executing a reformatting request for a random assortment of tubes in many plates throughout the system, one tube can be taken from each plate and put it in another set-up of plates, ordering the tubes in accordance with the request. 
     The shelf keeping units or tubes are accessed by pipettes having tips dimensioned to fit into the tubes, for withdrawing fluid from the tubes or dispensing fluid into the tubes. Scientific Equipment vendors such as Globe Scientific, Inc. or CCS Packard supply pipette tips adapted for use with robotic or automated laboratory equipment. An excerpt of the “online catalog” taken from the Globe Scientific, Inc. web site describes tips designed to fit pipettors used in automated testing and is attached hereto as appendix E. Additionally, an excerpt of the “Chemicals and Supplies” information taken from the CCS Packard web site describes “Robotic Certified” pipette tips designed for use with 96 or 384 channel pipettors used in automated testing and is attached hereto as appendix F. Taken together, these serve to enable a person of ordinary skill in the art to understand the characteristics of pipettes used in conjunction with industry standard shelf keeping units. 
     The shelf keeping units or tubes of the prior art must be sealed for storage and automated handling and reliably sealing each shelf keeping unit is expensive and difficult, since each shelf keeping unit is small. 
     There is a need, therefore, for an economical and effective automated pharmaceutical or biotech compound testing system using a very small shelf keeping unit. 
     OBJECTS AND SUMMARY OF THE INVENTION 
     Accordingly, it is a primary object of the present invention to overcome the above mentioned difficulties by providing an economical and effective automated pharmaceutical or biotech compound testing system using a very small minitube shelf keeping unit. 
     In accordance with the present invention, an automated pharmaceutical or biotech compound testing system uses a very small molded plastic shelf keeping unit or test tube known as a “minitube”. The minitubes are stored in trays in a standing refrigeration unit and are retrieved by a machine or robot having a die cutting tubular end effector adapted to selectively cut away and remove a minitube from an integrally molded matrix containing hundreds of minitubes (e.g., 384); the matrix is called a minitube well plate. Upon cutting a selected minitube away from the matrix, the end effector is pushed down over the selected minitube, thus forcing the minitube into the cylindrical interior lumen of the end effector, where it is retained by friction fit until such time as the minitube is to be releaseably locked into a plastic receiving tray. 
     Minitubes are stored in the plastic tray which is adapted to receive and releaseably hold or lock the tubes in place. The minitubes themselves are molded plastic tubes having distally projecting spaced apart “rabbit ear” detent lock members which are biased outwardly. The plastic receiving tray has apertures sized to receive the minitubes and each aperture of the tray is terminated at bottom in a hole defined within chamfered shoulders adapted to slidably engage and exert transverse force against the minitube rabbit ears. The two rabbit ears and the hole together comprise a detent lock system, the minitube rabbit ears releaseably engage the shoulder surfaces on the bottom of the hole in each aperture of the tray. The robot end effector can withdraw and replace the tubes as needed to perform automated testing. 
     The minitube receiving tray or plate includes spaces aligned in twenty four columns and rows A through P. That number of minitubes was selected for storage because the standard three hundred and eighty four element well plate from the Society for Biomolecular Screening (SBS) provides exterior dimensions (e.g., as cited above and described in the attached appendices). Conformance with the SBS standard was an important goal of developing the method and apparatus of present invention. 
     The problem presented was to mold the entire 384 well cassette (also referred to as the minitube well plate or matrix) as one unit, in a functional unit that doesn&#39;t need any further assembly. The minitube well plate just one piece, once out of the mold, already in a shape compatible with the format called the SBS Plate or the 384 well plate, so it&#39;s ready to use as-is, coming out of the mold. 
     In use, the individual minitubes are periodically taken out and “reformatted” into another plate, e.g., having a different makeup of compound in the minitubes. A receiving tray may include, for example a random assortment in the 384 well plates throughout the system and a user may need to pick one out of each of these plates and put it in another entire set-up of plates, ordering them for the request. In response to the request, the minitubes are punched out of a minitube well plate with the die end effector and placed in a receiving plate in such a wav that the minitube can be used in the laboratory. The minitube cannot be laid loosely in the plate aperture, instead, each minitube has to be pressed in and releaseably locked in or retained such that it won&#39;t come back out until selectively removed using the robot end effector. 
     The molded matrix structure including the minitubes molded integrally with the holder is referred to as the minitube well plate. The volume of each minitube is about sixty microliters, and the exterior dimensions of each minitube are optimized to conform to the SBS spacing standard for dimensions a 384 tube well plate. The minitube design provides the largest volume that&#39;s functional in that format and size. Within the SBS standard format, the tube structure provides maximum usable volume. Each minitube has a rounded or pointed bottom, so that the pipette can reach close to the bottom, and get almost all of the material out. There are a large number of standard pipettes that are available. A cross-section of pipettes was studied to ensure they could fit down to the bottom easily without hitting the side. Well known pipette companies include Tecan, Becton-Dickenson, and Perkin Elmer. 
     Returning to the minitube well plate, the top surface is substantially planar and all of the minitubes are arranged in an evenly spaced pattern in a two dimensional array, in substantial conformance with the above cited SBS “well positions” draft standard, SBS-4. The minitube well plate shares of the present invention certain characteristics with standard (sBS-4) plate, but differs in the minitube configuration as seen from the bottom and in that the minitubes are integrally molded into the plate structure. 
     The top of the minitube well plate is planar upper surface which permits an operation covering all of the minitubes at once. On that planar top surface, and around each circular hole defining the minitube openings, where the minitube is molded in, there is a small annular ridge around each hole—one can feel the ridge with a fingernail. The annular ridge is raised and is used for heat sealing; a foil sheet with a polymer back is used to seal all the minitubes at once. The polymer layer melts to the polymer on the minitube well plate ridge, this independently sealing each tube at the annular ridge. The first point of contact is that little ridge around each well or minitube interior whereby each tube is completely sealed. Each minitube remains sealed after it&#39;s been cut and released by the die cutter and holder: 
     The preferred “membrane material” for affixing that sealing cover is a commercially available aluminum foil having a polymer coating on the back. The polymer coating may be polypropylene or polyethylene. 
     When attaching the foil to the minitube well plate, even heat and pressure is applied over the entire top surface using a pair of platens. A smooth top platen on the top surface and a platen underneath having holes cut out for each of the (e.g., 384) tubes so that the actual point of contact of the bottom platen is right at the top of the minitube well plate inner wall. Thus, when closed in the heat sealing operation, the two platens are essentially about a sixteenth of an inch apart, a span corresponding to the thickness of the minitube well plate top wall segment. During sealing, the bottom platen comes into intimate contact with the underside of the minitube well plate, and so acts essentially like a female mold, adapted to receive it the underside of the minitube well plate completely, whereas the top platen is just a flat rectangular piece that is slightly larger in area than the minitube well plate planar top surface. 
     During the heat sealing process, the minitube well plates are supported at the very bottom of the plate while the platen on top pushes down, so a very uniform pressure is applied, thereby achieving, among other things, enhanced reliability in the sealing of individual tubes. 
     Returning to the annular sealing ridge, the ridge is substantially triangular in cross section. This ridge shape is suitable for ultrasonic sealing as well as heat sealing and there&#39;s a pretty wide and forgiving range of ridge shape to present on a high spot to take the pressure first and achieve that melt. The melt must bond the sealing membrane completely around the circumference of the minitube and it is important that the bond that is created not be undone when the die cutter reaches in and cuts the minitube out of the well plate. 
     The die cutter shape or dimensions are dictated in part by that goal. Particularly, the die cutter has an angled edge, e.g., 20 degrees to the inside, whereby a knife-like beveled edge is presented. That beveled edge is very sharp, from a design tradeoff perspective, the balance is between having a shallower angle (rendering cleaner cut) or a larger angle (rendering longer wear, for longevity). At present, the priority is functionally making clean cuts, so the individual minitube seals are reliably left intact after the cutting step has taken place. A sharp cutting edge also helps maintain the flatness of that planar surface, over the whole plate, during the removal of all the tubes. The removal process is usually random in that tubes are removed at one point and then another and another. The typical completely random request process for the chemicals in these tubes might have three or four tubes remaining right in the middle after everything else is punched out around them, and a relatively flat well-oriented web must be maintained to hold those tubes. Another advantage of a very sharp cutting beveled edge is that, in use, the minitube well plate remains substantially planar as the tubes are cut out. 
     The minitube itself is tapered from top to bottom, having a gently decreasing diameter from top to bottom and being circular in cross-section. The die cutter has an interior defining a straight cylinder. The cutting edge is on the outside of the cylinder, and the outside is tapered for strength. The die cutter body also has a taper at the top that creates the beveled knife edge. There is a dual taper there; a two degree taper mirroring the minitube sidewall, so the adjacent minitubes allow for a two degree outward taper on the die. The minitube uses every bit of material that will fit within the clearances defined by adjacent placements of the die cutter. The die cutter taper gives enhanced tool strength and the tapered area around each minitube allows for that clearance and allows the die cutter to have that taper outward. 
     The above and still further objects, features and advantages of the present invention will become apparent upon consideration of the following detailed description of a specific embodiment thereof, particularly when taken in conjunction with the accompanying drawings, wherein like reference numerals in the various figures are utilized to designate like components. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a perspective view of the entire automated retrieval system, in accordance with the present invention. 
         FIG. 1B  is an enlarged, perspective view of a minitube well plate used in the automated retrieval system, in accordance with the present invention. 
         FIG. 2  is a cross sectional view of the robot end effector and receiving plate, with a locked-in minitube, in accordance with the present invention. 
         FIG. 3  is a perspective view of the minitube well plate or matrix and the die cutter end effector, in accordance with the present invention. 
         FIG. 4  is a front view, in elevation, of the minitube automated retrieval robot system, in accordance with the present invention. 
         FIG. 5  is a perspective view of the minitube automated retrieval robot system, in accordance with the present invention. 
         FIG. 6  is a perspective view of the minitube automated retrieval robot system, in accordance with the present invention. 
         FIG. 7  is a perspective view of an individual minitube shelf keeping unit, in accordance with the present invention. 
         FIG. 8  is a perspective view of the minitube automated retrieval robot system, in accordance with the present invention. 
         FIG. 9  is a cross sectional perspective view of the robot end effector, minitube and receiving plate, in accordance with the present invention. 
         FIG. 10  is a close-up cross sectional perspective view of the robot end effector, minitube and receiving plate, in accordance with the present invention. 
         FIG. 11  is a cross sectional view of the minitube receiving plate with minitubes locked in place therein, in accordance with the present invention. 
         FIG. 12A  is an end view, in elevation, of an individual minitube shelf keeping unit illustrating the sealing annular ridge, in accordance with the present invention. 
         FIG. 12B  is a side view, in elevation, of an individual minitube shelf keeping unit illustrating the sealing annular ridge and the “rabbit ear” detent lock members, in accordance with the present invention. 
         FIG. 13  is a cross sectional view of a minitube well plate and die cutting end effector in position to cut away a selected sealed individual minitube shelf keeping unit, in accordance with the present invention. 
         FIG. 14  is a cross sectional view of a minitube well plate and die cutting end effector in position to cut away a selected individual minitube shelf keeping unit, in accordance with the present invention. 
         FIG. 15  is an enlarged cross sectional perspective view of the robot end effector, minitube and receiving plate of  FIG. 9 , in accordance with the present invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     Referring to  FIGS. 1-15 , in accordance with the present invention, an automated miniature shelf keeping unit storage and retrieval system  20  uses a very small molded plastic shelf keeping unit or test tube known as a “minitube”  22 . The minitubes  22  are stored in trays in (preferably) a standing refrigeration unit and are retrieved by a machine or robot  24  having a die cutting tubular end effector  26  adapted to selectively cut away and remove a minitube  22  from an integrally molded matrix  28  containing hundreds of minitubes (e.g., 384). The matrix is also called a minitube well plate  28  and preferably includes a sealing membrane or layer covering the upward facing openings of the minitubes. Upon cutting a selected minitube  22  away from the matrix, the end effector  26  is pushed over the selected minitube (as shown in  FIGS. 13 and 14 ), thus forcing the minitube into the cylindrical interior lumen of the end effector  26 , where it is retained by friction fit until such time as the minitube is to be releaseably locked into a plastic minitube receiving tray or plate  30  (as illustrated in  FIGS. 2 ,  9  and  11 ). 
     Referring again to  FIG. 1 , automated miniature shelf keeping unit storage and retrieval system  20  preferably has a capacity of approximately twelve million minitubes  22  and larger capacities are possible. System  20  preferably includes integrated bar code scanners and has a “high priority interrupt” capability as well as a single minitube delivery capability. System  20  preferably includes adept robotics with adept vision guidance and incorporates a user-friendly interface and a Microsoft® SQL server database. System  20  preferably provides automatic plate sealing in an inert environment and cold storage (e.g., at minus twenty decrees Celsius) with redundant refrigeration and fail-safe features to protect against power loss, along with extensive data safeguards. System  20  is adapted for stand-alone use or can be networked to a compound ordering system. 
     Minitubes are stored and moved from place to place in the receiving plate  30  which is adapted to receive and releaseably hold or lock the tubes in place. As best seen in  FIGS. 2 ,  7  and  12 , minitube  22  is a molded plastic tube having distally projecting spaced apart “rabbit ear” detent lock members  32 ,  34  which are biased transversely or outwardly. The plastic receiving tray has apertures sized to receive the minitubes and each aperture of the tray is terminated at bottom in a hole  36  defined within chamfered shoulders adapted to slidably engage and exert transverse force against the minitube rabbit ears  32 ,  34 . The rabbit ears  32 ,  34  and the hole  36  together comprise a detent lock system. The minitube rabbit ears releaseably engage the shoulder surfaces on the bottom of the hole in each aperture of the receiving plate or tray  30 . The robot end effector  26  can withdraw and replace the tubes  22  as needed to perform automated testing. 
     The minitube receiving tray or plate  30  includes spaces aligned in twenty four columns and rows A through P. That number of minitubes  22  was selected for storage because the standard three hundred and eighty four element well plate from the Society for Biomolecular Screening (SBS) provides exterior dimensions (e.g., as cited above and described in the attached appendices). Conformance with the SBS standard was an important goal of developing the method and apparatus of present invention. 
     The problem presented was to mold the entire 384 well cassette (also referred to as the minitube well plate or matrix  28 ) as one unit, in a functional unit that doesn&#39;t need any further assembly. The minitube well plate, once out of the mold, is already in a shape compatible with the format called the SBS Plate or the 384 well plate, so it&#39;s ready to use as-is, coming out of the mold (not shown). 
     In use, the individual minitubes  22  are periodically taken out and “reformatted” into another plate  30 , e.g., having a different makeup of compound in the minitubes. A receiving plate  30  may include, for example a random assortment in the 384 well plates throughout the system and a user may need to pick one out of each of these plates and put it in another entire set-up of plates, ordering them for the request. In response to the request, the minitubes  22  are punched out of a minitube well plate  28  with the die end effector  26  and placed in a receiving plate  30  in such a way that the minitube can be used in the laboratory. The minitube  22  cannot be laid loosely in the plate aperture, instead, each minitube has to be pressed in and releaseably locked in or retained such that it won&#39;t come back out until selectively removed using the robot end effector  26 . 
     Minitube well plate  28  comprises a molded matrix structure including the minitubes  22  molded integrally with the holder. The volume of each minitube  22  is preferably about sixty microliters, and the exterior dimensions of each minitube illustrated in  FIG. 12  and are optimized to conform to the SBS spacing standard for dimensions a 384 tube well plate. The minitube design provides the largest volume that&#39;s functional in that format and size. Within the SBS standard format, the tube structure provides maximum usable volume. Each minitube  22  has a rounded or pointed bottom, so that the pipette can reach close to the bottom, and get almost all of the material out. There are a large number of standard pipettes that are available. A cross-section of pipettes was studied to ensure they could fit down to the bottom easily without hitting the side. Well known pipette companies include Tecan, Becton-Dickenson, and Perkin Elmer. 
     Returning to minitube well plate  28 , the top surface  38  is substantially planar and all of the minitubes  22  are arranged in an evenly spaced pattern in a two dimensional array, in substantial conformance with the above cited SBS “well positions” draft standard, SBS-4. The minitube well plate of the present invention shares certain characteristics with standard (SBS-4) plate, but differs in the minitube configuration as seen from the bottom in that the minitubes are integrally molded into the plate structure. 
     The planar top or upper surface  38  which permits an operation covering all of the minitubes at once. On that planar top surface  38 , and around each circular hole defining the minitube openings, where the minitube is molded in, there is a small annular ridge  40  around each hole—one can feel ridge  40  with a fingernail. Annular ridge  40 , best seen in  FIG. 12 , is raised and is used for heat sealing. A foil sheet with a polymer back is used to seal all the minitubes in the well plate  28  at once. The foil sheet polymer layer melts to the polymer on the minitube well plate ridge  40 , thus independently sealing each tube at the annular ridge. The point of contact is the little ridge around each well or minitube interior and so each tube  22  is completely sealed. Each minitube  22  remains sealed after it&#39;s been cut and released by the die cutter/holder end effector  26 . 
     The preferred “membrane material” for affixing the sealing cover is a commercially available aluminum foil having a polymer coating on the back. The polymer coating may be polypropylene or polyethylene. 
     When attaching the foil to the minitube well plate  28 , even heat and pressure is applied over the entire top surface using a pair of platens (not shown). A smooth top platen on the top surface and a platen underneath having holes cut out for each of the (e.g., 384) tubes  22  so that the actual point of contact of the bottom platen is right at the top of the minitube well plate inner wall. Thus, when closed in the heat sealing operation, the two platens are essentially about a sixteenth of an inch apart, a span corresponding to the thickness of the minitube well plate top wall segment. During sealing, the bottom platen comes into intimate contact with the underside of the minitube well plate  28 , and so acts essentially like a female mold, adapted to receive it the underside of the minitube well plate completely, whereas the top platen is just a flat rectangular piece that is slightly larger in area than the minitube well plate planar top surface  38 . 
     During the heat sealing process, the minitube well plates  28  are supported at the very bottom of the plate while the platen on top pushes down, so a very uniform pressure is applied, thereby achieving, among other things, enhanced reliability in the sealing of individual tubes  22 . 
     Returning to the annular sealing ridge  40 , and referring to  FIG. 12  which shows the ridge (diameter of 0.122″); it is substantially triangular in cross section (and has a height of 0.009″). In fact, there are many useful sealing methods, this ridge shape has been used for ultrasonic sealing as well as heat sealing and there&#39;s a pretty wide and forgiving range of ridge shape to present a high spot to take the pressure first and achieve the desired sealing melt. The melt must bond the sealing membrane completely around the circumference of the minitube and it is important that the bond that is created not be undone when the die cutter reaches in and cuts the minitube out of the well plate. 
     The die cutter shape or dimensions (of end effector  26 ) are dictated in part by the goal or reliable sealing. Particularly, the die cutter has an angled edge, e.g., 20 degrees to the inside, whereby a knife-like beveled edge is presented. Referring to  FIGS. 13-15  and  FIG. 9 , the beveled edge is preferably very sharp; the balance is between having a shallower angle (rendering cleaner cut) or a larger angle (rendering longer wear), for longevity. At present, the priority is functionally making clean cuts, so the seals are reliably intact after the cutting step has taken place. A sharp cutting edge also helps maintain the flatness of planar surface  38 , over the whole plate, during the removal of all the tubes. The removal process is usually random in that tubes  22  are removed at one point and then another and another. The typical completely random request process for the chemicals in these tubes might have three or four tubes remaining right in the middle of matrix  28  after everything else is punched out around them, and a relatively flat well-oriented web must be maintained to hold those few tubes. That&#39;s another reason why a very sharp cutting beveled edge is required, so that the minitube well plate top surface  38  remains substantially planar as the tubes  22  are cut out. 
     As best seen in  FIGS. 7 and 12 , minitube  22  is tapered from top to bottom, having a gently decreasing diameter from top to bottom and being circular in cross-section. The die cutter of end effector  26 , as best seen in  FIGS. 13-15 , has an interior defining a straight cylindrical lumen. The end effector cutting edge is on the outside of the cylinder, and the outside is tapered for strength. The die cutter body also has a taper at the top (best seen in  FIG. 13 ) that creates the beveled knife edge. There is a dual taper there; a two degree taper mirroring the minitube taper, so the adjacent minitubes allow for a two degree outward taper on the end effector cutting die. The minitube  22  uses every bit of material that will fit within the clearances defined by adjacent placements of the die cutter. The die cutter taper gives more tool strength and the tapered area around each minitube allows for that clearance and allows the die cutter to have that taper outward. 
     Turning now to some additional details of the minitube invention, the shape of the rabbit ears and the method of putting a minitube in the holding tray and withdrawing are important novel elements of the invention. The prior art, by comparison, involves much greater cost, because separately molding 384 little tiny tubes and inserting them in a matrix of 384 little square sockets is a very costly assembly. The present invention, by way of contrast, replaces that assembly with something less expensive; the method of the present invention includes molding the entire 384 well cassette as one unit, in a functional unit that doesn&#39;t need any further assembly. It&#39;s just one piece, one out of the mold, already in the format of the SBS Plate, or the 384 well plate, so it&#39;s ready to use as-is, coming out of the mold. Now that&#39;s all well and good but what needs to happen from there is these individual tubes need to be taken out and reformatted into another plate having a different makeup of compound (whatever the compounds are in those little tubes). It might be, a random assortment in the 384 well plates throughout the system and the user may need to pick one out of each of these plates and put it in another entire set-up of plates, such that there&#39;s an order to them now for this request. And so, in the method of the present invention, the molded-in minitubes are punched out and placed in such a way that they can be used in the laboratory. The minitubes can&#39;t just be laid in there, they have to be pressed in, in such a way that the minitubes won&#39;t come back out. And thats why the minitubes have ears which are received in the receiving tray holes. The little ears or detents, when they&#39;re pressed in, they snap into place and then hot or cold, warm or cold, it doesn&#39;t really matter because they&#39;re now retained, and snapped into place. 
     Referring now to the refrigerated storage, the pick and place robotic equipment is novel and more efficient as a result of this minitube structure. The robotic equipment is called an end effector, and is essentially a punching unit that has a punch and a die set up. The punch is a two stroke set-up that, in the first part of the stroke or the first stroke, is used to actually shear the tube out of the molded matrix. The minitube is retained by friction in the die and then the whole unit goes over to the receiving cassette or tray and then the second stroke is all the way through the die, the punch goes all the way through the die down to the bottom and presses the minitube into place in the receiving cassette or tray. Once that minitube is put into the receiving cassette, it can actually be extracted from that receiving cassette and put into another receiving cassette, which allows what is called compression, meaning one can take out the remaining tubes in a well plate—e.g., if one has 384 to start and over a period of, say, six months 350 are taken out, then 34 are left, one can punch those 34 out and place them in a receiving cassette. In addition, the user can extract minitubes out of the receiving tray; instead of punching them out, the system includes a little extractive tool or pin that pushes up from the bottom through the receiver cassette ear-retaining hole and actually replaces that tube inside the die of the punch and die, a feature shown in cross section in the drawings. 
     Having described preferred embodiments of a new and improved method, apparatus and system it is believed that other modifications, variations and changes will be suggested to those skilled in the art in view of the teachings set forth herein. It is therefore to be understood that all such variations, modifications and changes are believed to fall within the scope of the present invention as defined in the claims.