Patent Publication Number: US-7900525-B2

Title: Cathode handler system

Description:
FIELD OF THE INVENTION 
     The present disclosure is directed to a pre-assembled, disposable cathode handler assembly structured to facilitate the efficient loading of a cathode with a sample analyte, which is subsequently utilized in spectrometric analysis. The cathode handler assembly is structured to be utilized with any one of a plurality of different cathodes. 
     DESCRIPTION OF THE RELATED ART 
     Mass spectrometry has been a useful chemical analytical tool since its inception in the late 1800&#39;s. This technology utilizes the charge-to-mass ratio of charged particles to separate charged particles from within a molecule or sample, thus identifying the isotopic composition of the sample analyte. With the advent of electrostatic accelerators, accelerator mass spectrometry (AMS) allows for the detection and identification of even trace amounts of atomic isotopic ratios. This highly sensitive technique has gained appreciation and is enabling rapid changes to take place in biosciences and pharmaceutical development. For instance, the ultrahigh sensitivity of AMS allows for the detection of  14 C a very rare and unstable isotope of carbon, in parts per trillion (attomole) levels within molecular structures. The ability to use and measure “microdose” levels of  14 C has lead to revolutionary applications within Absorption, Distribution, Metabolism, Excretion studies (ADME). Appreciation for this is evidenced by the U.S. Food and Drug Administrations January 2006 publication  Guidance for Industry, Investigators, and Reviewers Exploratory IND Studies  outlining the use of microdosing in association with its Critical Path Initiative for new drug development. 
     In order to take advantage of this AMS technology, a sample analyte must first be loaded into a cathode, which in turn becomes part of the ion source used in the AMS instrument. Since a cathode holds only a very minute amount of analyte, the cathode itself may measure fractions of a centimeter in length. The small size of the cathode, combined with the even smaller diameter of the hole through which to load the analyte, makes the handling of a cathode, for loading purposes, difficult and cumbersome. An instrument for handling and manipulating the cathode which allows for easier analyte loading is therefore needed to increase the efficiency of AMS technology and growth. 
     In addition to the above, AMS microdosing studies utilized in pharmacokinetic studies require many, many measurements to be made under strictly time constrained conditions to obtain accurate results. Thus, study throughput and new drug development is “bottle-necked” by the steps required to load graphite synthesized from carbon dioxide evolved from the study compound into the cathode. Alternative ion sources utilizing the carbon dioxide rather than graphite are under study thereby eliminating the need for graphite preparation and cathode loading. However, carbon dioxide analysis is inhibited by technological limitations associated with gas manipulation, memory effects within the AMS, lower counting efficiencies than graphite and the high cost of carbon dioxide ion sources. Accordingly, a preferred and proposed cathode handler system and assembly solves the “bottleneck” associated with the loading of the graphite into cathode and as such improves the efficiency and efficacy of AMS microdosing utilizing the existing AMS technologies. 
     SUMMARY OF THE INVENTION 
     The cathode handler assembly of the present invention is to be used in conjunction with a separate cathode to facilitate the loading of the cathode with an analyte, which is subsequently used in spectrometric analysis. The cathode handler assembly is comprised of a plurality of component parts which work cooperatively together to form a total self contained, preferably pre-assembled assembly that increases the manageability of handling a cathode. 
     Specifically, the assembled cathode handler system comprises a single use self-contained disposable unit which is discarded after each use. The ultra high sensitivity of AMS requires non-disposable cathode holder systems to be cleaned to a very high level between uses in order to avoid cross contamination between analytes. The cleaning process is time consuming, labor intensive and requires very special care. Accordingly, a preferred and proposed cathode handler assembly would comprise a single unit, different units to be used for different cathode loadings, which would thereby eliminate the need for reuse of cleaned, non-disposable cathode holders. A source of potential error would thereby be eliminated. Such a preferred and proposed cathode handling assembly would also simplify the loading process and reduce the loading labor overhead. It may further provide a potential for higher sample throughput over non-disposable units since this system can be provided pre-assembled, ready to load with analyte. It can be loaded without preparation and inventory of units may not be limited to the number of non-disposable units available between cleaning. 
     In addition, a channeling unit is located above the cathode or otherwise in direct communication therewith so as to direct and/or introduce analyte into the supported cathode. A liner may be used in conjunction with the channeling unit to further assist in the efficient loading of analyte into the cathode. The channeling unit also may contain an analyte cap holder, which retains analyte cap material until after analyte is loaded. The integration of an analyte cap holder into the assembly further eases the problem of “bottlenecking” by maintaining the analyte cap material, which forms a backing for the analyte and prevents ion sputtering, nearby. A stopper is located beneath or is otherwise positioned in connection with the cathode and in at least partially sealing engagement therewith. Moreover, the stopper is disposed and structured to retain analyte within the cathode. As such, the analyte which is introduced into the cathode is prevented from escape or inadvertent passage there from. This stopper is connected to and/or supported by a housing, which also interacts with the channeling unit to assist in the stabilization of the cathode, especially, but not exclusively, during introduction of the analyte into the cathode. 
     The present cathode handler assembly is contemplated for both automated and manual loading of a cathode. In the case of manual loading, a support and loading stand may be integrated into the cathode handler assembly which stabilizes the assembly in a position conducive to loading and facilitates efficient loading of analyte. 
     These and other features and advantages of the present invention will become clearer when the drawings as well as the detailed description are taken into consideration. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       For a fuller understanding of the nature of the present invention, reference should be had to the following detailed description taken in connection with the accompanying drawings in which: 
         FIG. 1  is a cross-sectional view in partial cutaway of the cathode handling assembly of this invention. 
         FIG. 2A  is a cross-sectional view of a cathode of the embodiment of  FIG. 1 . 
         FIG. 2B  is a perspective view of the cathode of  FIG. 2A . 
         FIG. 3A  is a cross-sectional view in partial phantom of the channeling unit and cathode of the embodiment of  FIG. 1 . 
         FIG. 3B  is a cross-sectional view of the channeling unit of one embodiment. 
         FIG. 3C  is a top plan view of the channeling unit of  FIG. 3B . 
         FIG. 4A  is a cross-sectional plan view of the liner of the embodiment of  FIG. 1 . 
         FIG. 4B  is a perspective view of the liner of  FIG. 4A . 
         FIG. 5A  is a cross-sectional view of the stopper of the embodiment of  FIG. 1 . 
         FIG. 5B  is a perspective view of the stopper of  FIG. 5A . 
         FIG. 6A  is a cross-sectional view of the housing of the embodiment of  FIG. 1 . 
         FIG. 6B  is a perspective view of the housing of  FIG. 6A . 
         FIG. 7  is an exploded cross-sectional view of the cathode handler assembly and integrated manual loading stand. 
         FIG. 8  is a cross-sectional view of the cathode handler assembly and integrated manual loading stand showing exemplar stem collars. 
         FIG. 9  is a cross-sectional view of yet another preferred embodiment of the present invention. 
     
    
    
     Like reference numerals refer to like parts throughout the several views of the drawings. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     As shown in the accompanying figures, and with particular reference to  FIG. 1 , the present invention is directed to a cathode handler assembly, generally indicated as  10 . This cathode handler assembly  10  works interactively with a separate cathode  12  to facilitate a more efficient and expedient loading of sample analyte into the cathode  12 . 
     The cathode handler assembly  10  comprises a single self-contained unit that is pre-assembled with a select cathode. As such, the cathode can be loaded with analyte without further preparation, therefore simplifying the loading process and reducing the labor overhead. Since it is available in pre-assembled form, the cathode handler assembly  10  provides the potential for a higher sample throughput compared to standard cathode assemblies in the field as it can be loaded faster and easier than conventional cathode assemblies. Moreover, the cathode handler assembly  10  is manufactured of such a material that it is disposable after a single use. Examples of such material include, but are not limited to, plastic, nylon, aluminum, etc. Since each cathode handler assembly  10  is used only once, there is no need to clean and reuse hardware associated with handling the cathode  12 . Thus, the cathode handler assembly  10  of the present invention removes the lengthy and arduous cleaning process currently in place, decreasing labor overhead as a result. Also the disposable feature eliminates a source of potential error in spectrometric result output, since the possibility of cross contamination is eliminated. 
     The cathode handler assembly  10  is comprised of a plurality of components, which are preferably pre-assembled and disposable after use. Each of the plurality of components works interactively to collectively form the complete assembly. As seen in a preferred embodiment represented in  FIG. 1 , the cathode handler assembly  10  comprises at least a channeling unit  18  and a stopper  28  disposed in connected, supporting relation to the cathode  12 . As seen in  FIGS. 1 ,  2 A and  2 B, the cathode  12  is structured to include an interior chamber  14  which is correspondingly disposed, dimensioned and configured to receive the analyte therein. Moreover, the receipt and maintenance of the analyte in the interior chamber  14  as the stopper and channeling unit are connected to maintain the cathode in a vertical or other appropriate orientation within the cathode handler assembly  10  to facilitate the loading of the cathode with sample analyte. 
     The channeling unit  18  of  FIG. 1  connects to and/or engages the cathode  12  in a location which is preferably opposite the stopper  28  such that the cathode is effectively clamped in a “sandwiched” relation between the channeling unit  18  and the stopper  28 . Further, the cooperative connection of the cathode  12  between the stopper  28  and the channeling unit  18  is sufficient to exert a “displacement resisting” force of the cathode  12 . In turn, the cathode  12  is maintained in a stable position and/or orientation so as to allow the packing or forced placement of the analyte within the interior chamber  14 . In addition,  FIG. 3B  shows the channeling unit  18  includes an open distal end  20  and an opposite open proximal end  22 . The open proximal end  22  of the channeling unit  18  is disposed in direct communicating relation with the cathode  12  at an open end of the interior chamber  14 , as represented. The open proximal end  22  of the channeling unit  18  abuts or is otherwise cooperatively and adjacently or contiguously disposed relative to the correspondingly positioned or topmost edge of the interior chamber  14  of the cathode  12 . As such, the analyte introduced into the cathode  12  through the channeling unit  18  is directed substantially entirely into the interior chamber  14  of the cathode  12 . 
     Thus, when a cathode  12  is placed in the cathode handler assembly  10  for loading, substantially all analyte introduced in to the channeling unit  18  is consequently directed into the stably supported cathode  12 . Thus, the channeling unit  18  of the present invention allows for more efficient loading of sample analyte and eliminates or significantly reduces the possibility of analyte spillage that would occur if direct cathode loading was attempted without the benefit of the structural and operative features of the present invention. Moreover, in at least one preferred embodiment of the present invention it is contemplated that the channeling unit  18  may be, but is not necessarily, of a substantially conical or funnel-like shape to better direct introduced sample analyte into the interior chamber  14  of the supported cathode  12 . 
     The channeling unit  18  also contains an analyte cap holder  19 , as seen in.  FIGS. 3B and 3C , which is designed to retain analyte cap material during loading of an analyte and subsequently allow the passage of this analyte cap material through an aperture therein once the analyte is properly loaded and packed within the cathode. The analyte cap holder  19  protrudes from the channeling unit  18  such that analyte cap material forced there through follows the same path as the analyte, and indeed, covers the top of the analyte and may be forced into sealing relation over the top of the cathode  12 , thus encasing the loaded analyte within the cathode  12  and providing a terminal point for sputtered ion pathway through chamber  14 . 
     Further, the channeling unit  18  may contain at least one exterior groove  24  which matingly fits a corresponding groove  16  in the cathode  12 , as displayed in  FIG. 3B . These grooves  24  and  16  connect and lock the channeling unit  18  in substantially sealing relation to the cathode  12 , thus stabilizing this portion of the cathode handler assembly  10 . Similarly, the channeling unit  18  may also contain at least one other exterior groove  27  which matingly fits a corresponding groove  38  in the housing  34  for the increased stabilization of the cathode holder assembly  10 , discussed in more detail below. 
     At least one preferred embodiment of the present invention contemplates a liner  26  to be disposed within the channeling unit  18  to further facilitate the transfer of sample analyte into the cathode  12 , as in  FIGS. 1 ,  4 A and  4 B. This liner  26  is disposed in overlying relation to an interior surface of the channeling unit  18 , and is structured to be in substantially continuous confronting engagement with the interior surface of the channeling unit  18 . Moreover, in at least one embodiment of the present invention, the liner  26  is disposed and dimensioned to extend between the open proximal end  22  and open distal end  20  of the channeling unit  18 . Further, the open proximal end  22  is contiguously or adjacently disposed relative to the corresponding opening edge of the interior edge  14  of the cathode  12  to facilitate the transfer of analyte into the interior chamber, as set forth above. Thus, the liner  26  is disposed to at least partially seal the engagement between the channeling unit  18  and the cathode  12  at the opening of the interior chamber  14 . The spillage of analyte is thereby eliminated or significantly reduced within the housing  34  of the cathode handler assembly  10  while it is loaded into the cathode  12 . 
     The stopper  28  as represented in  FIGS. 1 ,  5 A and  5 B is structured within the cathode handler assembly  10  such that it interacts with the cathode  12  to retain the analyte within the interior chamber  14  of the cathode  12 . More specifically, the stopper  28  is dimensioned to at least partially correspond to at least a portion of the cathode  12  at least to the extent of forming an at least partially sealing engagement with the cathode  12 . In at least one preferred embodiment, the sealing or retaining function of the stopper  28  is accomplished by a protruding portion or segment  30  of the stopper  28 , which is structured to protrude, penetrate or otherwise fit in a mated relation, at least partially, within the interior chamber  14  of the cathode  12 , in a manner clearly represented in the above noted Figures. 
     Such protruding segment  30  extends into interior chamber  14  of the cathode  12  and abuts the bottom or correspondingly disposed portion of the cathode  12  supported therein. Thus, the stopper  28  facilitates the retention of analyte within the cathode as well as supporting the cathode  12  in a stable, displacement resisting disposition within the housing  34 . The stopper  28  also possesses at least one exterior groove  32  to interact with the housing  34 , described in detail below to further connection with the cathode in a preferred stable manner. 
     The interconnection and support of the housing  34  with the channeling unit  18  and stopper  28  further serves to stabilize the cathode  12  as seen in  FIGS. 1 ,  6 A and  6 B. More specifically, the housing  34  contains at least one interior groove  36  which is structured to matingly correspond to an exterior groove  32  of the stopper  28 , thereby locking the housing  34  and stopper  28  together and stabilizing the position of the stopper  28  as well as the cathode  12 . The housing  34  also contains an exterior groove  38  which matingly fits and locks with a corresponding groove  27  in the channeling unit  18  such that the housing  34  matingly engages the corresponding portion of the channeling unit  18 , further increasing the stability of the entire cathode handler assembly  10 . Moreover, the groove  38  of the housing  34  and the groove  27  of the channeling unit  18  are disposed such that the channeling unit  18  may be outwardly removed or detached from the housing  34 . Otherwise, unless forcibly detached, the channeling unit  18  is in locking engagement with the housing  34 , and the cathode handler assembly  10  is intact. One embodiment contemplates the removal of the channeling unit  18  from the housing  34  in a vertical direction, but other outward directions are possible and acknowledged. 
     Further, as set forth herein, the cathode  12  is interconnected to and supported by the channeling unit  18  and the stopper  28  in a sufficiently stable manner to facilitate and allow pressure to be directed onto the cathode  12  without it being displaced while loading the analyte into the interior chamber  14 . Such directed pressure serves to augment the packing of sample analyte in to the cathode  12 . 
     It is contemplated that the cathode handler assembly  10  may be used for both automated and manual loading of analyte. Accordingly the cathode holder assembly is adaptable for manual loading utilizing a manual loading stand  40 , as represented in  FIG. 7 , which stabilizes the cathode  12  independently so that a technician may have both hands free to load the cathode  12 . The integrated manual loading stand  40  of comprises a base  42  and a stem  44  which together stably support the cathode handler assembly  10  in position. Specifically, the stem  44  extends from the base  42  to a portion of the cathode handler assembly  10 . In one embodiment of the integrated manual loading base  40 , the stem  44  extends from the base  42  to the stopper  28  of the cathode handler assembly  10 . 
     The base  42  comprises a cavity  46  which is structured and dimensioned to receive the stem  44  and support it therein.  FIG. 8  shows one such embodiment. The interior walls of the cavity  46  are in spaced relation to the exterior of the stem  44  received therein. As such, there is a gap or space between the sides of the stem  44  and the interior walls of the cavity  46 . This allows for at least some movement of the stem  44  within the cavity  46  and the transfer of “vibrations” to the cathode through the stem  44 , as will be explained in greater detail hereinafter. More specifically, the bottom of the stem  44  and the bottom of the cavity  46  are cooperatively dimensioned to enhance vibrations produced by tapping or applying other appropriate forces to the stem  44 . These vibrations travel up the stem  44  to the cathode  12  and further assist in the efficient packing of the analyte therein. By way of example, in one embodiment the bottom of the cavity  46  and the bottom of the stem  44  are substantially curved in order to facilitate the production and perpetuation of vibrations along the stem  44 . 
     Furthermore, a stem collar  48  at least partially surrounds the stem  44  at the base  42  to permit the stem  44  to vibrate without disrupting the integrity of the manual loading stand  40  or the cathode handler assembly  10 . Many variations of the stem collar  48  are contemplated, and are understood to be included herein. Two sample embodiments are illustrated in  FIG. 8 . In one embodiment, the stem collar  48  is a sleeve disposed at least partially surrounding the stem  44  and between the stem  44  and the inner walls of the cavity  46 , as seen in  FIG. 8 . The material of this example stem collar  48  is permissive of stem  44  movement, such as foam. In another embodiment, also shown in  FIG. 8 , the stem collar  48  at least partially encircles the stem  44  and comprises a plurality of angled arms which may extend into the cavity  46  and are fastened to the base  42 . The angles of the arms allow the stem collar  48  of this embodiment to act as a spring and allow movement of the stem  44 . 
     With primary references to  FIG. 9 , yet another preferred embodiment of the cathode handler assembly is represented and generally indicated as  10 ′. This embodiment includes equivalent structural components with certain structural modifications to be set forth in greater detail hereinafter. More specifically, the cathode handler assembly  10 ′ comprises the structural components, preferably preassembled and disposable after use, similar to the embodiment of  FIG. 1 . As such, the cathode handler assembly  10 ′ comprises a channeling unit  18 ′ and a stopper  28  disposed in connected, supporting relation to the cathode  12 ′. Further, the stopper  28  includes the protruding portion  30  extending within the interior chamber  14  of the cathode  12 ′. The channeling unit  18 ′ connects to and/or engages the cathode  12 ′ at a location which is opposite to the position of the stopper  28 , such that the cathode  12 ′ is effectively sandwiched there between. As with the above noted embodiment of  FIG. 1 , the channeling unit  18 ′ includes an open distal end  20  and an opposite, open proximal end disposed in direct communicating relation with the corresponding open end of the interior chamber  14  of the cathode  12 ′. 
     The additional preferred embodiment of  FIG. 9  further includes a liner  26 ′ to be disposed within the channeling unit  18 ′ to further facilitate the transfer of sample analyte into the cathode  12 ′ as described with reference to the above-noted embodiments of  FIGS. 1 ,  4 A and  4 B. The liner  26 ′ is disposed in overlying relation to an interior surface of the channeling unit  18 ′ and is structured to be in substantially continuous confronting engagement with the interior surface of the channeling unit  18 ′. Further, with regard to the preferred embodiment of  FIG. 9 , structural and/or dimensional differences exists specifically, but not exclusively, with the liner  26 ′ for purposes of facilitating flow of the analyte sample into the cathode  12 ′. More specifically, the height, schematically represented as  52 , of the liner  26 ′ has been reduced from that of the liner  26  of the embodiment of  FIG. 1 . As such, the open upper end  27  of the liner  26 ′ is not in corresponding or substantially contiguous relation to the open distal end  20  of the channeling unit  18 ′ but is inwardly spaced at least a minimal distal therefrom. In addition, the interior diameter, schematically indicated as  52 ′, has been increased thereby further facilitating accurate and reliable flow of the analyte sample into the interior chamber  14  of the cathode  12 ′. Accordingly, the interior dimensions collectively indicated as  50  of the liner  26 ′ are altered or modified from the corresponding dimensions of the embodiment of  FIG. 1 , wherein the operative features of the channeling unit  18 ′ and the liner  26 ′ are believed to be enhanced. 
     Additional structural modifications of the embodiment of  FIG. 9  includes the absence of any snap-ring type of construction between the upper end  35  of the housing  34  and the interior surface of a depending flange  54  of the channeling unit  18 ′. In order to further facilitate a smooth interconnection and placement of the channeling unit  18 ′ relative to the upper end  35  of the housing  34 , the innermost peripheral edge  56  has been beveled or chamfered. In addition, the upper wall portions  34 ′ and  35  each have an increased and substantially equivalent thickness as compared to the embodiment of  FIG. 1 . In contrast the wall portion  34 ″, disposed below the location of the cathode  12 ′ is proportionally the same as the embodiment of  FIG. 1  and substantially less than the wall portions  34 ′ and  35 . Interconnection and support of the channeling unit  18 ′ relative to the housing  34  is thereby further facilitated. 
     Other structural modifications included in the additional preferred embodiment of  FIG. 9  include the peripheral dimensions of the channeling unit  18 ′ being such as to be at least minimally spaced from the interior, correspondingly disposed surface of the housing  34 , particularly at the wall portions  34 ′ and the upper end  35  thereof. As such, at least a minimal spacing may exist there between as clearly represented. Also, in order to accommodate a smooth and easily accomplished fitting and supported interaction between the channeling unit  18 ′ and the housing  34 , the interior peripheral portion as at  57  has a predetermined radius formed thereon such that there will be no hard contacting engagement between the outer surface of the channeling unit  18 ′ and the inner surface of the upper end of the housing as at  34 ′,  35 . 
     Finally, the relative dimensioning between the interior groove  16  and the exterior ring-type flange  24 ′ is also reduced to allow easier separation or “breakaway”. Similarly reduced dimensioning maybe occurred between the interior ring  24  and the upper peripheral portion of the cathode  12 ′. 
     Since many modifications, variations and changes in detail can be made to the described preferred embodiment of the invention, it is intended that all matters in the foregoing description and shown in the accompanying drawings be interpreted as illustrative and not in a limiting sense. Thus, the scope of the invention should be determined by the appended claims and their legal equivalents. 
     Now that the invention has been described,