Patent Publication Number: US-2006018799-A1

Title: Universal tissue homogenizer device and methods

Description:
BACKGROUND  
      1. Technical Field  
      The present disclosure relates to tissue homogenizing devices and methods of use thereof.  
      2. Discussion of Related Art  
      Biological samples, such at tissue samples (i.e. brain, lung, kidney etc . . . ) and fluid samples (i.e. blood, plasma, urine, milk etc . . . ) are well known sources of information regarding the condition or health of the host. For many assays involving such samples, particularly tissue samples, it is advantageous to break up or otherwise homogenize the sample to gain proper access to constituents contained therein.  
      Accordingly, a continuing need exists for an improved device for collection, separating and distributing tissue and blood samples for examination.  
      A need also exists for a method of using the improved device for collecting, and easily homogenizing tissue samples.  
     SUMMARY  
      The present disclosure relates to a tissue homogenizer device for testing a sample of blood and/or tissue. The device includes an outer cylinder including an open distal end, an open proximal end, and defining a lumen therethrough; an inner cylinder slidably disposed within the lumen of the outer cylinder, the inner cylinder including an open distal end, a closed proximal end, and defining a chamber therewithin; and a seal extending across the open distal end of the inner cylinder. The device further includes a piston having a piston rod extending proximally from the closed proximal end of the inner cylinder and through the open proximal end of the outer cylinder. Axial displacement of the piston axially displaces the inner cylinder relative to the outer cylinder, the device including a first position in which the distal end of the inner cylinder is in close proximity to the open distal end of the outer cylinder, and a second position in which the distal end of the inner cylinder is spaced a distance from the open distal end of the outer cylinder.  
      Desirably, when the device is in the first position the proximal end of the inner cylinder is spaced a distance from the proximal end of the outer cylinder, and when the device is in the second position the proximal end of the inner cylinder is in close proximity with the proximal end of the outer cylinder.  
      The device further includes particulate in the chamber of the inner cylinder. The particulate may include pellets, granules, shots, BBs and/or aggregate. The piston rod desirably includes a region of reduced strength formed along the length thereof.  
      The device further includes a cap removably connectable to the open distal end of the outer cylinder. The cap includes at least one rod extending therefrom for penetrating the seal of the inner cylinder when the cap is secured to the distal end of the outer cylinder. The cap desirably includes an engagement element for securing the cap to a complementary engagement element provided at the distal end of the outer cylinder.  
      The device further includes a dispensing cap removably connectable to the open distal end of the outer cylinder. The dispensing cap includes a lumen extending therethrough. The dispensing cap further includes an engagement element for securing the cap to a complementary engagement element provided at the distal end of the outer cylinder. The dispensing cap may further include a filter extending across the lumen thereof.  
      The device may further include a septum cap removably connectable to the open distal end of the outer cylinder. The septum cap includes an annular outer wall, an annular inner wall defining a passage and a septum seal extending across the passage. The septum seal is desirably made from rubber. The device may further include a filter slidably disposed in the chamber of the inner cylinder.  
      In one aspect of the present disclosure, the proximal end of the outer cylinder may include a hub operatively associated therewith through which the piston rod extends. Additionally, the proximal end of the inner cylinder may include a hub operatively associated therewith to which the piston rod is secured.  
      The piston rod desirably slidably extends through an opening formed in the closed proximal end of the inner cylinder. The piston includes a head operatively connected to a distal end of the piston rod. The head desirably includes at least one aperture formed therethrough.  
      The piston rod includes a region of reduced strength formed along the length thereof enabling the piston rod to be separated from the head. The piston rod reciprocatingly drives the head axially through the chamber of the inner cylinder. A filter may be provided which extends across the opening formed in the proximal end of the inner cylinder.  
      The open proximal end of the outer cylinder may include a flange formed therearound. Desirably, the piston rod includes a series of indicia along the length thereof, wherein the indicia indicates a quantity of a sample drawn into the chamber and/or indicates a quantity of a sample expressed from the chamber.  
      According to another embodiment, the tissue homogenizer device may include a cylinder including an open distal end, a closed proximal end, and defining a chamber therewithin; a seal extending across the chamber to define a closed proximal reservoir and an open distal reservoir; particulate disposed in the proximal reservoir; and a cap operatively securable to the distal end of the cylinder. The cap desirably includes an end wall defining an opening therein; a seal extending across the opening formed in the end wall of the cap; and at least one puncturing element extending from an inner surface of the end wall of the cap, wherein the puncturing element is configured to penetrate the seal when the cap is secured to the distal end of the cylinder.  
      The distal end of the cylinder may include a cutting edge, wherein the cutting edge is desirably serrated. The cap may include an engagement element for engaging a complementary engagement element provided on the cylinder.  
      According to another aspect of the present disclosure, a method of examining a tissue or blood sample is provided. The method includes the steps of providing a tissue homogenizing device. The device includes an outer cylinder having an open distal end, an open proximal end, and defining a lumen therethrough; an inner cylinder slidably disposed within the outer cylinder, the inner cylinder having an open distal end, a closed proximal end, and defining a chamber therewithin; a seal extending across the chamber of the inner cylinder; particulate disposed within the chamber of the inner cylinder; a piston having a piston rod extending through the open proximal end of the outer cylinder and operatively associated with the closed proximal end of the inner cylinder; and a cap securable to the distal end of the outer cylinder. The device has a first position in which the proximal end of the inner cylinder is spaced a distance from the proximal end of the outer cylinder, wherein the distal end of the inner cylinder does not extend beyond the distal end of the outer cylinder, and at least one second position in which the proximal end of the inner cylinder is in close proximity to the proximal end of the outer cylinder.  
      The method further includes the steps of inserting the distal ends of the outer cylinder and the inner cylinder into a quantity of a sample; at least one of withdrawing the piston to proximally displace the inner cylinder relative to the outer cylinder to evacuate the lumen of the outer cylinder and draw in a test sample of the quantity of sample, and urging at least the distal end of the outer cylinder into the quantity of the sample; and securing the cap onto the distal end of the outer cylinder.  
      The cap desirably includes a piercing element extending therefrom such that when the cap is secured to the distal end of the outer cylinder the piercing element penetrates the seal. The method further includes the step of separating the piston rod from the inner cylinder. The piston rod desirably includes a series of indicia along the length thereof indicating a volume of test sample acquired in the lumen of the outer cylinder.  
      The method further includes the step of agitating the device following separation of the piston from the inner cylinder. The method further includes the step of replacing the cap with a dispensing cap following agitation of the device. The dispensing cap desirably defines a lumen extending therethrough and includes a filter extending across the lumen thereof. The method further includes the step of urging the inner cylinder in a distal direction relative to the outer cylinder to force the test sample through the filter and out through the lumen of the dispensing cap.  
      Desirably, the piston rod slidably extends through an opening formed in the proximal end of the inner cylinder. The piston includes a head provided on the distal end of the piston rod and disposed within the chamber of the inner cylinder. The piston rod has a first position in which the head is in close proximity to the proximal end of the inner cylinder and at least one second position in which the head is spaced a distance from the proximal end of the inner cylinder. Desirably, the piston rod is separable from the head.  
      The device may further include a septum seal extending across the opening formed in the proximal end of the outer cylinder. The method further includes the step of urging the head from the first position to at least one second position, inserting a pipette into the chamber of the outer cylinder through the opening in the proximal end of the cylinder, and withdrawing the test sample from the device. Desirably, the head includes at least one aperture formed therethrough.  
      According to another aspect, the method further includes the step of replacing the cap with a septum cap. The septum cap desirably defines a passage therethrough and which includes a seal extending across the passage. The device may further include a filter slidably disposed within the chamber of the inner cylinder.  
      Further features of the above embodiments and methods will become more readily apparent to those skilled in the art from the following detailed description of the apparatus taken in conjunction with the drawings.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      By way of example only, preferred embodiments of the disclosure will be described with reference to the accompanying drawings, in which:  
       FIG. 1  is a side cross sectional elevational view of a universal tissue homogenizing device, in accordance with one illustrative embodiment of the present disclosure, illustrating a stage of use thereof;  
       FIG. 2  is a side elevational view of the tissue homogenizing device of  FIG. 1  illustrating another stage of use thereof;  
       FIG. 3  is a side elevational view of the tissue homogenizing device of  FIGS. 1 and 2  illustrating yet another stage of use thereof;  
       FIG. 4  is a side elevational view of the tissue homogenizing device of  FIGS. 1-3  as configured for manual use in still another stage of use thereof;  
       FIG. 4   a  is a side elevational view of the tissue homogenizing device of  FIGS. 1-4  following partial distal advancement of the inner tube relative to the outer tube;  
       FIG. 5  is a side elevational view of the tissue homogenizing device of  FIGS. 1-3  as configured for automated use in still a further stage of use thereof;  
       FIG. 6  is a side cross sectional elevational view of a universal tissue homogenizing device, in accordance with another illustrative embodiment of the present disclosure, illustrating a stage of use thereof;  
       FIG. 7  is a side elevational view of the tissue homogenizing device of  FIG. 6  illustrating another stage of use thereof;  
       FIG. 8  is a side cross-sectional elevational view of the tissue homogenizing device of  FIGS. 6 and 7  illustrating yet another stage of use thereof;  
       FIG. 9  is a side cross-sectional elevational view of the tissue homogenizing device of  FIGS. 6-8  as configured for manual use in still another stage of use thereof;  
       FIG. 10A  is a cross-sectional side elevational view of the tissue homogenizing device of  FIGS. 6-9 , further including a piston having a tip configured and adapted for filtering;  
       FIG. 10B  is a plan view of the tip of the piston of  FIG. 10A ;  
       FIG. 11  is a side elevational view of the tissue homogenizing device of  FIG. 10A  as configured for automated use in still a further stage of use thereof;  
       FIG. 12  is a side cross sectional elevational view of a universal tissue homogenizing device, in accordance with still another illustrative embodiment of the present disclosure, illustrating a stage of use thereof;  
       FIG. 13  is a side elevational view of the tissue homogenizing device of  FIG. 12  illustrating another stage of use thereof; and  
       FIG. 14  is a perspective view of a distal end of the tissue homogenizing device of  FIGS. 12 and 13 . 
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS  
      Preferred embodiments of the presently disclosed tissue homogenizer will now be described more fully hereinafter with reference to the accompanying drawings. Referring to  FIGS. 1-5 , a universal tissue homogenizing device, in accordance with one illustrative embodiment of the present disclosure, is generally designated as  100 . Although the presently disclosed tissue homogenizing device  100  will be described and illustrated hereinafter in connection with specific embodiments and uses, such as, for example, use in the medical field, it will be readily appreciated and understood by one skilled in the art that the presently disclosed tissue homogenizing device  100  may be adapted for usage in other applications and fields of use as well.  
      In the drawings and in the description that follows, the term “proximal”, as is traditional, will refer to the end of the instrument, device and/or apparatus which is closest to the operator while the term “distal” will refer to the end of the instrument, device and/or apparatus which is furthest away from the operator.  
      As seen in  FIGS. 1-5 , tissue homogenizing device  100  includes a pair of concentric cylinders, namely an outer cylinder  102  and an inner cylinder  104 , wherein outer and inner cylinders  102  and  104  are longitudinally displaceable relative to one another. Outer cylinder  102  includes an open distal end  106  and an open proximal end  108  defining a lumen  110  therebetween. Preferably, at least one engaging member  112  (e.g., in the form of helical threads, bayonet-type structure, etc.) is provided on the outer surface of outer cylinder  102  at or near distal end  106 . Outer cylinder  102  includes a hub  114  operatively connected to and/or integrally formed with proximal end  108 . Hub  114  defines an opening  116  axially aligned with the central axis of outer cylinder  102 .  
      Inner cylinder  104  defines a chamber  124  including an open distal end  120  and a closed proximal end  122  defined by a proximal end wall  123 . Inner cylinder  104  further includes a hub  126  operatively connected to and/or integrally formed on an outer surface of proximal end wall  123 . Hub  126  of inner cylinder  104  is preferably axially aligned with hub  114  of outer cylinder  102 . A seal  118  is preferably disposed across distal end  120  to effectively cap and/or close distal end  120  of inner cylinder  104 . In this manner, chamber  124  of inner cylinder  104  can be hermetically sealed against contamination from the outside environment until device  100  is used. Preferably, inner cylinder  104  has an overall length that is less than the overall length of outer cylinder  102 .  
      Tissue homogenizing device  100  further includes an amount of particulate matter “P” including and not limited to pellets, granules, shots, “BBs”, aggregate and the like contained in chamber  124  of inner cylinder  104 . Chamber  124  can also contain various reagents that facilitate assaying of a sample, such as, for example, buffers, preservatives, solvents, specific binding proteins (e.g. antibodies, antigens, peptides) and marking reagents.  
      Tissue homogenizing device  100  further includes a plunger and/or piston  130  having a piston rod  132  configured and dimensioned to extend through opening  116  of hub  114  provided in outer cylinder  102  and configured and dimensioned to operatively engage hub  126  of inner cylinder  104 . Accordingly, as will be described in greater detail below, in use, as piston  130  is displaced in an axially proximal and/or distal direction relative to outer cylinder  102 , inner cylinder  104  is also displaced in a corresponding axially proximal and/or distal direction.  
      Preferably, piston rod  132  of piston  130  includes at least one, and more preferably, a plurality of marks  134  (e.g., grooves, ticks, marks, indicia or the like) formed thereon at a distal end  136  thereof which indicate to the operator the distance piston  130  has been displaced relative to outer cylinder  102 . In addition, as will be described in greater detail below, each mark  134  indicates to the operator the amount of sample “S” drawn into distal end  106  of outer cylinder  102 .  
      Piston rod  132  of piston  130  further includes a region of reduced strength  138  (i.e., a break-away area) wherein a portion of piston  130 , proximal of region  138 , can be broken away from the portion of piston  130  distal of region  138 . Alternatively, a distal end of piston rod  132  can include an inter-engaging structure (not shown), e.g., helical threads, for engaging hub  126  of inner cylinder  104  such that piston rod  132  can be removably attached to hub  126  of inner cylinder  104 .  
      With continued reference to  FIGS. 1-3 , a method of use of tissue homogenizing device  100  will now be described. In use, with piston  130  in a distal position such that distal end  106  of inner cylinder  104  is substantially flush with distal end  106  of outer cylinder portion  102 , distal end of outer cylinder  102  is inserted into a quantity of sample “S”. Preferably, distal end  106  of inner cylinder  104  is flush with distal end  106  of outer cylinder  102 . As seen in  FIG. 2 , with distal end  106  disposed in the quantity of sample “S”, piston  130  is withdrawn in a proximal direction (as indicated by arrow “A”) relative to outer cylinder  102  thereby displacing inner cylinder  104  in a proximal direction relative to outer cylinder  102 . Accordingly, a vacuum is formed at the distal end thereof and a test sample “T” of the quantity of sample “S” is drawn into distal end  106  of outer cylinder  102 .  
      Preferably, piston  130  is displaced, in a proximal direction (as indicated by arrow “A”), a distance sufficient to draw in a desired amount of the quantity of sample “S” into distal end  106  of outer cylinder  102 . As mentioned above, the quantity of sample “S” drawn into distal end  106  of outer cylinder  102  directly corresponds to the number of marks  134  of piston  130  exposed from outer cylinder  102  when piston  130  is displaced in the proximal direction. For example, marks  134  can be spaced from one another and outer cylinder  102  can be dimensioned such that each mark  134  represents a fixed volume, such as, for example,  100 l of the quantity of sample “S” being drawn into distal end  106  of outer cylinder  102 . In this exemplary embodiment, outer cylinder  102 , inner cylinder  104  and markings  134  of piston  130  are configured and dimensioned such that when piston  130  is displaced a maximum amount in the proximal direction hub  126  of inner cylinder  104  contacts hub  114  of outer cylinder  102 , three marks  134  are exposed and 300 μL of the quantity of sample “S” is drawn into distal end  106  of outer cylinder  102 . Sample acquisition can be facilitated by rotation or other manipulation by the user. For example, when the sample is disposed adjacent a relatively rigid surface, device  100  can be manipulated in a manner similar to operating a “cookie-cutter”.  
      As seen in  FIG. 3 , with test sample “T” drawn into distal end  106  of outer cylinder  102 , a closure cap  140 , configured and dimensioned to removably engage distal end  106  of outer cylinder  102 , is coupled to distal end  106  of outer cylinder  102 . Cap  140  includes at least one, preferably a plurality of, penetrating members such as rods  142  extending longitudinally from an inner surface thereof. Each rod  142  preferably includes a tip  144  (e.g., in the form of a sharpened point, taper, cone and the like) configured and dimensioned to penetrate seal  118 . Accordingly, when cap  140  is coupled to distal end  106  of cylinder  102 , rods  142  penetrate seal  118  thereby allowing test sample “T” to enter chamber  124  of inner cylinder  104  and combine and/or mix with particulate matter “P” and any reagents contained therein. Preferably, cap  140  includes at least one engaging member  146  configured and adapted to inter-engage with engaging member  112  provided on the outer surface of outer cylinder  102 . In this manner, cap  140  is prevented from inadvertently becoming separated and/or otherwise disassociated from outer cylinder  102 .  
      With cap  140  secured on distal end  106  of outer cylinder  102 , the portion of piston  130  proximal of region  138  is broken-off and/or otherwise separated from the portion of piston  130  distal of region  138 , preferably along region  138 .  
      With test sample “T” now contained in chamber  124 , tissue homogenizing device  100  can be placed in an agitating apparatus, a homogenizer and/or the like, such as a ribolyser (e.g. a FastPrep® ribolyser available from Bio  101 , Inc., or a Magnalyser™ available from Roche) whereby particulate matter “P” acts to agitate, grind or otherwise break-up test sample “T”.  
      Following homogenization of test sample “T”, tissue homogenizing device  100  can be configured for either manual and/or robotic use. As seen in  FIG. 4 , tissue homogenizing device  100  is configured for manual use by removing cap  140  and attaching a dispensing cap  150  to distal end  106  of outer cylinder  102 . Dispensing cap  150  is funnel-like including a frusto-conical tip  152  defining a lumen  154  therethrough. Preferably, a filter  157  is disposed between dispensing cap  150  and distal end  106  of outer cylinder  102 . Filter  160  functions to strain out particulate matter “P” from test sample “T”. Dispensing cap  150  can include at least one engaging member  156  configured and adapted to inter-engage with engaging member  112  provided on the outer surface of outer cylinder  102 . In this manner, dispensing cap  150  is prevented from inadvertently becoming separated and/or otherwise disassociated from outer cylinder  102 .  
      Dispensing cap  150  further includes a stem  158  extending proximally of tip  152 . Stem  158  is configured and dimensioned to be received within the distal end of inner cylinder  104 . Preferably, stem  158  forms a fluid tight seal with the inner surface of inner cylinder  104 . Stem  158  includes a lumen  159  formed therein which is in fluid communication with lumen  154  of tip  152 . Lumen  159  is separated from lumen  154  by filter  157 . Stem  158  provides volume displacement of air (i.e., stem  158  replaces the dead volume created by cap  140  that tears the seal at the distal end of chamber  124 ). Stem  158  is useful in that there is a limited amount of stroke available to inner cylinder  104  relative to outer cylinder  102  and thus the air would interfere with and/or otherwise inhibit the user&#39;s ability to discharge a desired volume of sample “S”.  
      With dispensing cap  150  connected to distal end  106  of outer cylinder  102 , the distal end of piston rod  132  is re-introduced into hub  114  of outer cylinder  102  to operatively engage hub  126  of inner cylinder  104 . As such, piston  130  may be advanced in a distal direction to push sample “S” out through lumen  154  of dispensing cap  150 . As seen in  FIG. 4   a,  inner cylinder  104  has been displaced in a distal direction relative to outer cylinder  102  and sample “S” has been forced through lumen  159  of stem  158  and not along the outer surface of stem  158 .  
      Alternatively, as seen in  FIG. 5 , tissue homogenizing device  100  can be configured for robotic use by attaching a septum cap  160  to distal end  106  of outer cylinder  102 . Septum cap  160  includes an annular wall  162  having a substantially U-shaped cross-sectional profile defined by an outer wall  162   a  and an inner wall  162   b.  Septum cap  160  includes a septum seal  164 , preferably rubber, supported on inner wall  162   b.  Prior to attaching septum cap  160  to outer cylinder  102 , a filter  166  is desirably slidingly positioned within chamber  124  of inner cylinder  104 . In this manner, filter  166  can be moved axially along chamber  124  as needed and/or desired. In use, a tip of a septum piercing pipette  168  penetrates septum seal  164  and it used to withdraw a quantity of test sample “T” from chamber  124 . Since filter  166  is slidingly positioned in chamber  124 , filter  166  can be repositioned as needed to avoid being penetrated by the tip of pipette  168 , as seen in  FIG. 5 .  
      Turning now to  FIGS. 6-11 , a tissue homogenizing device, in accordance with yet another illustrative embodiment of the present disclosure, is shown generally as  200 . As seen in  FIGS. 6-8 , tissue homogenizing device  200  includes a pair of concentric cylinders, namely an outer cylinder  202  and an inner cylinder  204 , wherein outer and inner cylinders  202  and  204  are longitudinally displaceable relative to one another. Outer cylinder  202  includes an open distal end  206  and an open proximal end  208  defining a lumen  210  therebetween. Preferably, at least one engaging member  212  is provided on the outer surface of outer cylinder  202 . Proximal end  208  of outer cylinder  202  includes a radially inward extending annular flange and/or rim  214 .  
      Inner cylinder  204  defines a chamber  224  including an open distal end  220  and a closed proximal end  222  defined by a proximal end wall  223 . Inner cylinder  204  further includes an opening  226  formed in proximal end wall  223 . A seal  218  is preferably disposed across distal end  220  to effectively cap and/or close distal end  220  of inner cylinder  204 . In this manner, chamber  224  of inner cylinder  204  can be hermetically sealed against contamination from the outside environment until device  200 . Preferably, inner cylinder  204  has an overall length which is less than the overall length of outer cylinder  202 .  
      As described above with respect to tissue homogenizing device  100 , tissue homogenizing device  200  further includes an amount of particulate matter “P” contained in chamber  224  of inner cylinder  204 .  
      Tissue homogenizing device  200  further includes a plunger and/or piston  230  having piston rod  232  slidably extending through proximal end  208  of outer cylinder  202  and through opening  226  formed in proximal end wall  223  of inner cylinder  204 . Piston  230  includes a head  234  operatively coupled to and/or integrally formed with a distal end of piston rod  232 . Preferably, head  234  is sized and dimensioned to contact the inner surface of inner cylinder  204  along the entire periphery thereof. Piston rod  232  includes at least one, and more preferably, a plurality of marks  236  (see  FIG. 9 ) formed thereon which indicate to the operator the distance piston  230  has been displaced relative to outer cylinder  202 .  
      Piston rod  232  further includes a region of reduced strength  238  wherein a portion of piston  230 , proximal of head  234 , can be broken away therefrom, preferably along region  238 . Alternatively, a distal end of piston rod  232  can include an inter-engaging structure (not shown), e.g., helical threads, while a proximal surface of head  234  can include a complementary inter-engaging structure (not shown), e.g., a helically threaded bore, such that piston rod  232  can be removably attached to head  234 .  
      With continued reference to  FIGS. 6-8 , a method of use of tissue homogenizing device  200  will now be described. In use, with distal end  206  of outer cylinder  202  substantially flush with distal end  220  of inner cylinder  204  and with piston  230  positioned such that head  234  rests against and/or is in contact with proximal end wall  223  of inner cylinder  204 , distal end of outer cylinder  202  is inserted into a quantity of sample “S”. As seen in  FIG. 7 , with distal end  206  of outer cylinder  202  disposed in the quantity of sample “S”, piston  230  is withdrawn in a proximal direction (as indicated by arrow “A”) relative to outer cylinder  202  thereby displacing inner cylinder  204  in a proximal direction relative to outer cylinder  202 . Accordingly, a vacuum is formed at the distal end thereof and a test sample “T” of the quantity of sample “S” is drawn into distal end  206  of outer cylinder  202 .  
      Preferably, piston  230  is displaced, in a proximal direction, a distance sufficient to draw in a desired amount of the quantity of sample “S” into distal end  206  of outer cylinder  202 . Marks  236  of piston  230  function in the same manner as marks  134  of piston  130  described above. The maximum distance inner cylinder  204  can be proximally displaced relative to outer cylinder  202  is defined by annular flange  214  which acts as a stop to the displacement of inner cylinder  204  relative to outer cylinder  202 .  
      As seen in  FIG. 8 , with test sample “T” drawn into distal end  206  of outer cylinder  202 , a closure cap  240 , similar to closure cap  140  described above, is coupled to distal end  206  of outer cylinder  202 . Closure cap  240  includes a plurality of rods  242  configured and dimensioned to penetrate seal  218 . Accordingly, when closure cap  240  is coupled to distal end  206  of outer cylinder  202 , rods  242  penetrate seal  218  thereby allowing test sample “T” to enter chamber  224  of inner cylinder  204  and combine and/or mix with particulate matter “P” contained therein.  
      With closure cap  240  secured on distal end  206  of outer cylinder  202 , the portion of piston  230  proximal of head  234  is broken-off and/or otherwise separated therefrom, preferably along region  236 .  
      As with tissue homogenizing device  100 , with test sample “T” now contained in chamber  224  and combined with particulate matter “P”, tissue homogenizing device  200  can be placed in an agitating apparatus, a homogenizer, ribolyser, or the like whereby particulate matter “P” acts to agitate and/or break-up test sample “T”.  
      Following separation and/or homogenization of test sample “T” tissue homogenizing device  200  can be configured for either manual and/or robotic use. As seen in  FIG. 9 , tissue homogenizing device  200  is configured for manual use by removing closure cap  240  and attaching a dispensing cap  250 , similar to dispensing cap  150  described above, to distal end  206  of outer cylinder  202 . Preferably, a filter  260  is disposed between dispensing cap  250  and distal end  206  of outer cylinder  202 .  
      With dispensing cap  250  and filter  260  operatively associated with distal end  206  of outer cylinder  202 , inserting a distal end of piston rod  232  into opening  226  formed in proximal end wall  223  of inner cylinder  204  such that the distal end of piston rod  232  engages head  234 . With piston rod  232  engaged with head  234 , piston  230  is displaced in a distal direction (as indicated by arrow “B”) an amount sufficient to expel and/or otherwise eject test sample “T” from tissue homogenizing device  200 .  
      Alternatively, as seen in  FIGS. 10A, 10B  and  11 , tissue homogenizing device  200  can be configured for robotic use. As so configured, prior to use, head  234  of piston  230  is replaced with a filter head  234   a  including a plurality of apertures  234   b  formed therethrough which act to filter out particulate and the like. Preferably, apertures  234   b  are arranged in an annular array therearound. A septum seal  260  is preferably disposed between filter head  234   a  and proximal end wall  223  of inner cylinder  204  and includes an opening  262  formed therein.  
      Accordingly, following separation and/or homogenization of test sample “T”, piston rod  232  is inserted through opening  226  formed in proximal end wall  223 , through opening  262  formed in septum seal  260 , and attached to and/or otherwise engaged with filter head  234   a  and displaced in a distal direction (as indicated by arrow “B”) to thereby displace filter cap  234   a  in a distal direction through chamber  224  and separate particulate matter “P” from test sample “T”. With test sample “T” filtered and filter cap  234   a  repositioned, a tip of a pipette  268  is inserted into chamber  224  through opening  262  of septum seal  260 . Pipette  268  is then used to withdraw a quantity of test sample “T” from chamber  224 .  
      Turning now to  FIGS. 12 and 13 , a tissue homogenizing device, in accordance with yet another illustrative embodiment of the present disclosure, is shown generally as  300 . As seen in  FIGS. 12 and 13 , tissue homogenizing device  300  includes a cylindrical container  302  having an open distal end  306  and a closed proximal end  308  defined by a proximal end wall  309 . Container  302  defines a chamber  304  therein. Container  302  preferably includes at least one engaging member  312  (e.g., in the form of helical threads, bayonet-type structure, etc.) provided on the outer surface thereof at or near distal end  306 .  
      Preferably, container  302  includes at least one aperture and/or vent hole  310  formed at or near distal end  306 , preferably at a location distal of engaging member  312 . A seal  318  is disposed across chamber  304  to thereby divide chamber  304  into a distal reservoir  304   a  and a proximal reservoir  304   b.  Preferably, seal  318  is disposed at a location proximal of vent hole(s)  310 . In this manner, as will be described in greater detail below, vent hole(s)  310  allow displacement of air from distal reservoir  304   a  when a quantity of sample “S” is introduced into distal reservoir  304   a.  Preferably, seal  318  is positioned within chamber  304  at a location which fixes and/or defines the volume of distal reservoir  304   a  to a predetermined amount.  
      As with the previously described embodiments, tissue homogenizing device  300  also further includes an amount of particulate matter “P” contained in proximal reservoir  304   b  of chamber  304 .  
      Tissue homogenizing device  300  further includes a closure cap  340 , configured and dimensioned to removably engage distal end  306  of container  302 . Cap  340  includes an annular side wall  342  supporting an end wall  344  on a distal surface thereof. End wall  344  includes an opening  346  formed therethrough and a septum seal  348  (e.g., a rubber septum seal) extending across opening  346 . Side wall  342  preferably has a length sufficient to cover and/or otherwise block vent hole(s)  310  and thereby prevent the escape of sample “S” from container  302 .  
      Cap  340  further includes at least one, preferably a plurality of, penetrating members such as rods  350  extending longitudinally from an inner surface of end wall  344 . Each rod  350  preferably includes a tip  352  (e.g., in the form of a sharpened point, taper, cone and the like) configured and dimensioned to penetrate seal  318  when cap  340  is coupled to distal end  306  of container  302 . Cap  340  further includes at least one engaging member  354  extending from an inner surface of side wall  342 . Engaging member(s)  354  is/are configured and dimensioned to inter-engage with engaging member  312 . As such, cap  340  is prevented from inadvertently becoming separated and/or otherwise disassociated from container  302 .  
      Preferably, as seen in  FIG. 14 , distal end  306  of container  302  is provided with a cutting edge  360 . Preferably, cutting edge  360  is serrated. Cutting edge  360  acts like and can be used by the user of tissue homogenizing device  300  as a knife or similar cutting instrument/device, to facilitate in the cutting and/or acquisition of tissue.  
      With continued reference to  FIGS. 12 and 13 , a method of use of tissue homogenizing device  300  will now be described. In use, a user (e.g., surgeon, nurse, technician or the like) places a quantity of sample “S” into distal reservoir  304   a  by scooping, pressing and/or otherwise transferring sample “S” to distal reservoir  304   a.  Vent hole(s)  310 , as described above, allow for the escape of air from distal reservoir  304   a  and thus enable greater quantities of sample “S” to be transferred to distal reservoir  304   a.  Preferably, vent hole(s)  310  allow the entire volume of distal reservoir  304   a  to be filled with sample “S”. By filling distal reservoir  304   a  to capacity, a uniform amount of sample “S” can be consistently gathered and thereafter processed.  
      With a quantity of sample “S” placed in distal reservoir  304   a  or, preferably, with distal reservoir  304   a  filled with sample “S”, closure cap  340  is coupled to distal end  306  of container  302 . In so doing, rods  350  penetrate seal  318  thereby allowing test sample “T” to enter proximal reservoir  304   b  and combine and/or interact with particulate matter “P” contained therein.  
      With test sample “T” contained within chamber  304  and with cap  350  secured on distal end  306  of container  302 , tissue homogenizing device  300  can be placed in an agitating apparatus, a homogenizer and/or the like whereby particulate matter “P” acts to agitate and/or break-up test sample “T”.  
      Following separation and/or homogenization of test sample “T”, a tip of a septum piercing pipette  168  (see  FIG. 5 ) can be used to penetrate septum seal  348  of cap  340  and is used to withdraw a quantity of test sample “T” from chamber  304 .  
      It is envisioned that a hypodermic needle assembly (not shown) can be removably attached to the distal end of the outer cylinder of any of the above-described devices to facilitate collection of test sample “T” into the distal end of the outer cylinder.  
      It is envisioned that tissue homogenizing devices  100 ,  200 , and  300  can be used in connection with sample acquisition and/or distribution procedures wherein homogenization of the sample is desires and/or required, such as, for example, in the testing for Bovine Spongiform Encephalopathy, otherwise known as “Mad Cow” disease.  
      Although the present disclosure has been described with respect to preferred embodiments, it will be readily apparent to those having ordinary skill in the art to which it appertains that changes and modifications may be made thereto without departing from the spirit or scope of the disclosure.