Abstract:
A method and apparatus for automatically removing used magazines with used pipette tips from a pipetting head in an automated pipettor, and for automatically inserting an unused or cleaned magazine with unused or cleaned pipette tips in their place. The apparatus includes a gripping mechanism having two separate and independently operated gripping heads, one gripping head being associated exclusively with unused or cleaned magazines and pipetting tips, and the other gripping head being associated exclusively with used magazines and pipette tips. A transporting mechanism is provided for moving the gripping heads between the pipetting head, a disposal mechanism, and a supply of unused or cleaned magazines and pipetting tips. The supply preferably includes a carousel with a multiplicity of locations for storing unused or cleaned magazines and tips in a vertical alignment. The carousel is rotated so that a compartment containing unused or cleaned magazines and tips is in alignment with an opening in the carousel. The gripping head automatically scans the carousel looking for the next available unused or cleaned magazine and tips for transport to the pipetting head. Another scanning mechanism locates the used magazine in the pipetting head for removal. The method includes the steps of withdrawing a used magazine and tips from a pipetting head, inserting unused or cleaned magazine and tips in the pipetting head, and transporting the used magazine and tips to a disposal location. The method also includes the step of automatically retrieving unused or cleaned magazines and tips from a storage location for transport to the pipetting head.

Description:
FIELD OF THE INVENTION  
         [0001]    This invention relates generally to liquid transfer and dispensing devices for liquid reagents and samples, and more particularly to an automated apparatus and method for handling magazines containing pipetting tips.  
         BACKGROUND OF THE INVENTION  
         [0002]    Pipetting systems are well known, and typically are used in laboratories and hospitals for the aspiration and dispensing of relatively small, predetermined quantities of liquids into the wells of plates such as microplates, deep-well blocks and the like. Examples of liquids being dispensed include blood, other biological samples, solvents, reagents, and the like. Some or all of the liquid is normally drawn by suction through pipette tips from one set of plates or a reservoir of liquid and is subsequently released through the pipette tips into the wells of other plates.  
           [0003]    Not all plates have the same well spacings, and not all plates have the same number of wells. Therefore, it is desirable to vary the number of pipette tips, or the spacings between tips in such automated systems to accommodate plates with different well numbers and spacings. Moreover, it is desirable to be able to replace used pipette tips with unused ones. Such flexibility is essential in most laboratories and hospitals. It is also desirable to be able to perform such operations rapidly, and to be able to perform a high volume of operations in a very short period of time.  
           [0004]    In existing high volume, automated, multichannel pipetting systems, typically trays or magazines of disposable pipette tips are positioned in the dispensing head of the pipettor. Such magazines are configured to support a predetermined number of tips of a certain size and with a defined spacing. Each pipette tip has an enlarged upper end which is configured to be engaged in sealing relation to with an apparatus for aspirating liquid into the tip and expelling it therefrom. The lower end of each tip is tapered and has an opening through which liquid in a well of a microplate or a supply reservoir is withdrawn and expelled. Typically, these magazines are removable from the dispensing head of the pipetting apparatus to allow replacement of one magazine of pipette tips with another to prevent contamination of liquid from one pipetting operation with that of another pipetting operation. These tips may either be disposed of or washed for future pipetting operations. In some existing, automated pipetting apparatus, the magazines containing tips are manually replaced, while in others, the insertion and removal of magazines is accomplished in an automatic or semi-automatic fashion. These exchanges should be performed rapidly and automatically to maintain a high throughput, and to minimize needed operator time. Automated systems performing such exchanges must be able to interface with existing automated pipetting systems.  
           [0005]    An example of an automated pipetting system which uses magazines containing pipette tips is disclosed in co-pending U.S. application Ser. No. 09/865,404, filed May 25, 2001, and assigned to the Assignee of the present application. Other automated, high volume systems include those shown in U.S. Pat. Nos. 4,830,832; 6,148,878; and 5,988,236. An example of an existing automated pipette tip changer is sold by Cybio AG of Jena, Germany.  
         SUMMARY OF THE INVENTION  
         [0006]    The present invention relates to a method and apparatus for handling magazines containing pipette tips and is used in conjunction with high volume, automated pipetting systems. In particular, the present invention is used with automated pipetting systems which have a dispensing head configured to receive a magazine of pipette tips in which one magazine of used or inappropriately sized tips can be replaced with another magazine of unused or appropriately sized tips.  
           [0007]    One aspect of the invention relates to a magazine handling apparatus having one or more gripper heads for gripping a magazine. These gripper heads are associated with a transfer apparatus which moves the gripper heads from a dispensing head of a pipettor to a location for disposal of used magazines containing pipette tips, and from a source of unused magazines containing unused pipette tips to the dispensing head of the automated pipettor. In one embodiment of this aspect, two gripper heads are disclosed, and one gripper head is configured to grip only a used magazine with used pipette tips and convey the used magazine from the pipettor to a disposal location. The other gripper head is configured to grip only an unused magazine with unused tips and convey the unused magazine from a source of unused magazines to the dispensing head of the pipettor. In another embodiment of this invention, the two gripper heads are disposed vertically, one above the other, with the upper gripper head being the gripper configured only to grip unused magazines, while the lower gripper head is configured to only grip used magazines with used pipette tips.  
           [0008]    In another embodiment of this aspect of the invention, each gripper head includes a sensor which senses a particular location on a tip magazine to align the gripper head with the magazine. In particular, in a preferred embodiment, the location sensed is a tab or handle on the magazine which is to be grasped by the gripper head. Preferably, the sensor is a converging, diffuse, reflective sensor which has a controlled depth of field.  
           [0009]    In another aspect of the invention, the source of unused tips and magazines is a carousel accessible by a gripper head. In one embodiment, the carousel includes a plurality of stacker assemblies each of which is configured to contain a plurality of magazines and associated pipette tips. Each stacker assembly is removable from the carousel for filling thereof with magazines and tips, and each stacker assembly is replaceable into the carousel when filled with magazines and tips. Each stacker assembly has an open side which may be aligned with an opening in the carousel which is accessible by a gripper head. In another embodiment, the carousel is automatically rotated until a source of unused magazines and tips is disposed adjacent the opening accessible by the gripper head. In yet another embodiment of this aspect, the carousel is disposed vertically below the dispensing head on the automated pipetting system.  
           [0010]    In another aspect of the invention, a method is provided for automatically removing used or dirty magazines and pipette tips from the dispensing head of an automated pipetting system, and replacing the used magazine with an unused magazine with unused tips. In one embodiment of this aspect, the method includes the steps of removing the used magazine from the dispensing head using an automated gripper, inserting an unused magazine in the dispensing head in place of the used magazine, and conveying the used magazine to a disposal location. In one embodiment of this method, two gripper heads are used, and one gripper head carries only unused magazines and the other gripper head carries only used magazines. In a further embodiment, the one gripper head carries an unused magazine ready for insertion into the dispensing head prior to the removal of the used magazine by the other gripper head, so that the unused magazine is inserted upon removal of the used magazine. Preferably, in this embodiment, the gripper head holding the unused magazine is disposed above the gripper head holding the used magazine, so that the unused magazine is not contaminated by the used magazine.  
           [0011]    In a further embodiment of the method of this invention, clean, unused magazines are stored in a carousel in a stacked array. The gripper head searches for the next available magazine, retrieves it from an opening in the carousel, and returns to the dispensing head to await completion of the pipetting operation, and removal of the used magazine. In this embodiment of the method, the magazines may be stored in a stacker which can be retrieved from the carousel and replaced after being filled with new, unused magazines and tips. The carousel may be automatically rotated to a position such that a stacker containing unused magazines is presented to an opening which can be accessed by the gripper head. In another embodiment of the method, the carousel is disposed vertically below the dispensing head in the automated pipettor.  
           [0012]    The foregoing method and apparatus permit rapid, accurate and automated replacement of pipette tip magazines in the dispensing head of an automated pipettor. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0013]    The objects, advantages and features of this invention will be more clearly appreciated from the following detailed description, when taken in conjunction with the accompanying drawings in which:  
         [0014]    [0014]FIG. 1 is a perspective view illustrating the apparatus of this invention for handling pipette tip magazines in conjunction with an automated pipettor;  
         [0015]    [0015]FIG. 2 is a top plan view of the apparatus of FIG. 1;  
         [0016]    [0016]FIG. 3 is a cross-sectional side view taken along the line  3 - 3  of FIG. 2;  
         [0017]    [0017]FIG. 4 is a cross-sectional top, plan view taken along the line  4 - 4  of FIG. 3;  
         [0018]    [0018]FIG. 5 is a cross-sectional, side view of the upper and lower gripper heads taken along the line  5 - 5  of FIG. 4;  
         [0019]    [0019]FIG. 6 is a front elevational view of a gripper head as seen along line  6 - 6  of FIG. 5;  
         [0020]    [0020]FIG. 7 is a cross-sectional side view of the gripper head taken along line  7 - 7  of FIG. 6;  
         [0021]    [0021]FIG. 7A is a cross-sectional side view of the gripper head of FIG. 7 showing one step in the operation thereof;  
         [0022]    [0022]FIG. 7B is a cross-sectional side view of the gripper head of FIG. 7 showing another step in the operation thereof;  
         [0023]    [0023]FIG. 7C is a cross-sectional side view of the gripper head of FIG. 7 showing another step in the operation thereof;  
         [0024]    [0024]FIG. 8 is a partial, perspective view of the apparatus of FIG. 1 showing the carousel and transport mechanism of this invention;  
         [0025]    [0025]FIG. 9A is a schematic side view of the apparatus of FIG. 1 showing a step in the method of this invention;  
         [0026]    [0026]FIG. 9B is a schematic side view of the apparatus of FIG. 1, showing another step in the method of this invention;  
         [0027]    [0027]FIG. 9C is a schematic side view of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0028]    [0028]FIG. 9D is a schematic side view of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0029]    [0029]FIG. 9E is a schematic side view of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0030]    [0030]FIG. 9F is a partial, schematic view of a portion of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0031]    [0031]FIG. 9G is a schematic side view of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0032]    [0032]FIG. 9H is a schematic side view of the apparatus of FIG. 1 showing another step in the method of this invention;  
         [0033]    [0033]FIG. 9I is a schematic, side view of the apparatus of FIG. 1 showing another step in the method of this invention; and  
         [0034]    [0034]FIG. 9J is a schematic, side view of the apparatus of FIG. 1 showing another step in the method of this invention. 
     
    
     DETAILED DESCRIPTION  
       [0035]    With reference now to the drawings, and more particularly to FIGS. 1 and 2 thereof, the pipette tip magazine handling apparatus  10  of this invention will now be described. In a preferred embodiment, apparatus  10  includes a gripper assembly  20 , a gripper transport mechanism  100  and a magazine supply  200 . Gripper assembly  20  is configured to interact with an automated pipetting system  400  having a pipette dispensing head  410 . Dispensing head  410  includes a clamp  420  (see FIG. 3) or other like device for holding a pipette tip magazine  300  in head  410  during the pipetting operation. A sensor  440  indicates the position of clamp  420  and is electrically coupled to apparatus  10  (See FIG. 3).  
         [0036]    Each pipette tip magazine  300  typically includes a body  304  and a handle or tab  302 . Body  304  includes a plurality of sleeves  308 , each of which supports or is configured to support a pipette tip  310  within it (See FIG. 5). Typically, body  304  of magazine  300  is formed of a molded plastic material. However, body  304  may also be formed of metal or any other material which provides sufficient strength, is not breakable, and can withstand high temperatures. In a preferred embodiment, body  304  is formed of a material which is sufficiently inexpensive that magazines  300  can be disposed of after one use. Tips  310  may be any conventional pipette tips which are tapered from an upper end  314  having an enlarged opening to a lower, distal end  316  having a smaller opening (See FIG. 5). Typically, upper end  314  is placed in airtight, fluid communication with a seal  450  surrounding an opening of a piston chamber or the like which withdraws air from tip  310  to aspirate liquid through the lower end  316  of tip  310  and forces air into tip  310  to expel liquid from tip  310  through lower end  316 . Seal  450  provides an air tight seal between the upper end  314  of tips  310  and the dispensing head, to provide accurate, error-free pipetting. In one embodiment, seal  450  is a silicone or other like sealing layer. In an alternative embodiment, upper ends  314  of tip  310  could be urged into tight, sealing engagement with nozzle ends (not shown) protruding downwardly from dispensing head  410  for providing the necessary air- and liquid-tight seal with the dispensing head. Lower end  316  typically is placed into a well in a microplate or into a supply reservoir for aspirating liquid therefrom and later transferring that aspirated liquid to another well in a different microplate (not shown). These latter features are all conventional and well known in the art, and will not be described further.  
         [0037]    Tab  302  extends outwardly from one edge of body  304  of magazine  300 . Tab  302  contains relatively flat upper and lower surfaces  318  and  320  respectively. Disposed in lower surface  320  of tab  302  are one and preferably two holes  306  (See FIG. 7), the purpose of which will be described hereinafter.  
         [0038]    Typically, pipetting system  400  rests on a table  430  or other like support surface to place system  400  at a level convenient for operation of apparatus  10  and for observation of the pipetting operation. However, system  400  need not be disposed on a table  430 , and it may be disposed at some much more elevated position.  
         [0039]    For accurate operation of apparatus  10  of this invention, automated pipetting system  400  must be precisely and fixedly disposed with respect to apparatus  10 . Preferably, system  400  is bolted or in some other way fixedly attached to table  430  to prevent movement of system  400  with respect to apparatus  10  during operation. In one embodiment, mounts  432  are fixedly positioned on table  430  such as by bolts or screws  433 , and system  400  is removably attached to mounts  432  such as by screws  435 , so that system  400  can be removed from table  430 , to allow system  400  to be exchanged with another system  400  or to be removed for maintenance or repair. Mounts  432  allow system  400  to be returned to table  430  in the precise position desired. In this way, system  400  need not be repositioned every time it is replaced, repaired or maintained.  
         [0040]    In this application, for purposes of illustration only, the pipette tip magazine handling apparatus  10  of this invention will be described in conjunction with an automated pipetting system described in U.S. copending application Ser. No. 09/865,404 filed on May 25, 2001, entitled AUTOMATED PIPETTING SYSTEM, and assigned to the Assignee of the present application. U.S. application Ser. No. 09/865,404 is hereby specifically incorporated herein by reference. However, it is to be understood, that the pipette tip magazine handling apparatus  10  of this invention is not limited to use with the automated pipetting system disclosed in U.S. application Ser. No. 09/865,404 but may be used in conjunction with other types of automated pipetting systems. The automated pipetting system of U.S. application Ser. No. 09/865,404 forms no part of this invention.  
         [0041]    As shown in FIGS. 3, 4,  7  and  8 , gripper assembly  20  is mounted on slideways  102  on gripper transport mechanism  100 . Gripper transport mechanism  100  moves gripper assembly  20  on a path extending from magazine supply  200  to a position adjacent dispensing head  410 . The operation of gripper assembly  20 , gripper transport mechanism  100  and magazine supply  200  is controlled by a personal computer or programmable processor  14 .  
         [0042]    Gripper assembly  20  will now be described with particular reference to FIGS.  3 - 7 . Gripper assembly  20  includes a housing  22 . Disposed within housing  22  are one, and preferably two gripper heads  24  and  26 . Each gripper head  24  and  26  rides on an associated set of slides  28  which move along rails  31  and which allow gripper heads  24  and  26  to move in a generally horizontal direction in and out of housing  22  toward dispensing head  410  or toward magazine supply  200 . Gripper heads  24  and  26  are each independently moved along associated slides  28  and rails  31  by associated motors  32  and  34  respectively. Heads  24  and  26  are coupled to associated chains  36  and  38  respectively by a belt clamp  35 . Chains  36  and  38  ride over associated respective pairs of sprocket wheels  40  and  42 . Motor  32  is coupled to one of sprocket wheels  40  for moving chain  36  and thus head  24 , and motor  34  is coupled to one of sprocket wheels  42  for moving chain  38  and thus head  26 .  
         [0043]    In a preferred embodiment, gripper heads  24  and  26  are vertically disposed one above the other to provide a more compact arrangement. However, it is to be understood, that gripper heads  24  and  26  could be aligned in a side-by-side relationship, or, only a single gripper head could be used. An advantage of gripper heads  24  and  26  being aligned one above the other is that transport mechanism  100  need not be moved horizontally or in the X-direction as shown in FIG. 1, with respect to pipetting system  400  when two heads are used. The only movement required of gripper assembly  20  is vertically or in the Z-direction as shown in FIG. 1, along transport mechanism  100 .  
         [0044]    Each gripper head  24  and  26  has an associated pair of spaced jaws  44 ,  46  and  48 ,  50 . Preferably, each lowerjaw  44  and  48  is moveable with respect to associated stationary upper jaw  46  and  50 . Jaws  44  and  48  ride on respective guide shafts  52  and  54 . Preferably, although not necessarily, each lower jaw  44  and  48  includes a pair of upstanding pins  56  which are configured to engage corresponding holes  306  in tabs  302  of magazines  300 . When lower jaws  44  and  48  are raised against respective upper jaws  46  and  50 , tab  302  is captured by jaws  44  and  48  within a cutout  45  disposed within respective jaws  46  and  50 .  
         [0045]    Lower jaws  44  and  48  may be raised and lowered along respective guide shafts  52  and  54  in ways that are well-known to those of ordinary skill in the art. For example, jaws  44  and  48  may be raised and lowered using an electric solenoid, or a pneumatic actuator (not shown), or jaws  44  and  48  may be raised and lowered mechanically using a motor and a camming mechanism.  
         [0046]    In one embodiment of this invention, lower jaws  44  and  48  are raised and lowered mechanically. This embodiment will now be described with particular reference to FIGS. 6 and 7. Each jaw  44  and  48  includes a motor  68  that rotates a cam  70  eccentrically mounted with respect to a motor shaft  72 . Bearing  74  on cam  70  rotates about pin  76  and is positioned within a correspondingly formed slide  73  in jaws  44  and  48 . Thus, as motor  68  rotates shaft  72 , cam  70  raises and lowers jaws  44  or  48  as it moves along slide  73 . This configuration causes jaws  44  and  48  to rise rapidly at first and more slowly thereafter.  
         [0047]    Each gripper head  24  and  26  includes an associated perspective sensor  60  for locating the front edge of a tab  302  of a magazine  300  when associated gripper  24  or  26  is in a partially retracted position with respect to housing  22 . Transport mechanism  100  has been positioned with respect to system  400 , and processor  14  has been programmed such that processor  14  knows precisely the distance from gripper head  24  to tab  302  when magazine  300  is disposed within dispensing head  410  and from gripper head  26  to tab  302  for a magazine disposed in supply  200 . Sensor  60  preferably has a controlled depth of field so that the presence of tab  302  is only detected when tab  302  is at that known distance from gripper head  24  or  26 . Since there are no other objects which are spaced that known distance from gripper heads  24  and  26  when in a predetermined, partially extended position, only detection of a tab  302  at that distance will activate gripper heads  24  and  26 . Sensor  60  is preferably a converging diffuse reflective sensor and includes one light emitting diode (LED)  64  which emits a light beam and one photosensor  66 . LED  64  and photosensor  66  are each angled or converged toward one another and each includes a focusing lens, so that photosensor  66  only detects light from LED  64  reflected from a surface at a predetermined, known distance from gripper heads  24  and  26  in a defined area of sensitivity. Such converging diffuse reflective sensors are well-known, and are commercially available under product designation EX14A from SunX, Ltd. of Japan. Typically, LED  64  and photosensor  66  are spaced one above the other, to allow location of tab  302  with respect to a vertical or a Z-direction (FIG. 1) to allow proper alignment of gripper heads  24  and  26 .  
         [0048]    In a preferred embodiment, gripper assembly  20  positions itself above where a gripper head  24  or  26  would expect to detect a tab  302  on a magazine  300  and then begins moving downwardly until the desired sensor  60  detects a tab  302  on a magazine  300 , as will be described. Typically, sensor  60  on gripper head  24  is used to position assembly  20  with respect to dispensing head  410 . Typically sensor  60  on gripper head  26  is utilized to position assembly  20  with respect to magazine supply  200 , as will be described.  
         [0049]    Gripper transport mechanism  100  will now be described with particular reference to FIGS. 3, 4 and  6 . Transport mechanism  100  includes a vertical support  104  which is fixedly mounted to table  430  by a bracket  106 . Bracket  106  secures transport mechanism  100  such that gripper assembly  20  is aligned with dispensing head  410  in a horizontal or X-direction, and has a known spacing form head  410  in the Y-direction when aligned therewith in the vertical or Z-direction (See FIG. 1). Similarly, bracket  106  assures that gripper assembly  20  has a known spacing in a horizontal or Y-direction from tabs  302  of magazine  300  disposed in magazine supply  200  when gripper assembly  20  is aligned with magazine supply  200  in a vertical or Z-direction. These known locations and distances are programmed into processor  14  to allow proper operation and control of magazine handling apparatus  10 .  
         [0050]    While gripper transport mechanism  100  may comprise any apparatus suitable for providing the desired vertical motion of gripper assembly  20 , in a preferred embodiment, transport mechanism  100  includes a carrier plate  108  which includes or is mounted onto vertical slideways  102  which ride on rails  109 . Rails  109  are mounted on or are formed integrally with vertical stiffener  113 . Stiffener  113  extends substantially along all of the vertical or Z-direction height of mechanism  100 . Gripper assembly  20  is mounted onto plate  108  through plate  111 . Supports  130  couple plate  111  to plate  132  on assembly  20 . Plate  108  is sufficiently large and of sufficient mass that gripper assembly  20  may be mounted to it at multiple locations to provide precise movement and control of gripper assembly  20 . Vertical movement of plate  108  and thus of gripper assembly  20  is provided along rails  109  by a motor  112 . Motor  112  drives a grooved or toothed roller  114  which in turn drives a grooved belt  116  which is mounted to carrier plate  108 . Belt  116  passes over idler roller  118 , and passes on both sides of stiffener  113 . Preferably, but not necessarily, opening  110  is covered by belt  116  which moves with plate  108  about rollers  114  and  118 . Belt  116  covers the internal operation of transport mechanism  100 , and prevents the operator from becoming entangled. Belt  116  may be provided with a V-projection  122  in its center for maintaining alignment of belt  116 . A corresponding V-groove  121  is provided in rollers  114  and  118 .  
         [0051]    In a preferred embodiment, control buttons  126  are provided in a housing  128  on support  104 . Buttons  126  may include an emergency stop, a setup selector, a stop button, a reset button and a start button.  
         [0052]    Magazine supply  200  will now be described with particular reference to FIGS. 14 and 8. It is to be understood that supply  200  may comprise any mechanism capable of supplying clean or unused tip magazines  300  loaded with clean or unused tips  310  for use in dispensing head  410 . The following is one embodiment of a suitable supply that may be used in conjunction with the gripper assembly  20  and gripper transport mechanism  100  of this invention.  
         [0053]    In this embodiment, magazine supply  200  comprises a carousel  202  which is rotatably mounted within housing  204  (See FIG. 4). Housing  204  includes an opening  206  which permits access to magazines  300  within carousel  202 . Preferably, although not necessarily, housing  204  is mounted on a post  208  by connectors  209 . Post  208  is rotatably mounted on bearings  211  which permit post  208  to be rotated and which allow housing  204  to be pivoted from a position beneath table  430  to an exposed position, as shown in FIG. 4, to allow insertion of magazines  300  into carousel  202  through an opening  210  in the top of housing  204 . Opening  210  may also be accessed through a door  212  in table  430 , typically behind system  400 .  
         [0054]    Carousel  202  is rotated within housing  204  about a central axle  218  by a motor  214  which is coupled to carousel  202  by a clutch mechanism  216 . Axle  218  is mounted on bearings  219  which permit rotation of axle  218 .  
         [0055]    Arrayed about axle  218  are a plurality of compartments  220 . Typically, although not necessarily, ten compartments  220  are provided. In one embodiment, each compartment is configured to receive a stacker  222 . Stackers  222  are configured to contain magazines  300  in a stacked configuration and are removable from associated compartments  220 . Each compartment includes a frame  250  that includes rear bracket  240  having a vertically extending, central support  242 .  
         [0056]    Each stacker  222  typically includes three vertical walls including rear wall  224  and opposed, parallel side walls  228 . One side of the stacker has a vertically extending opening  226 . Magazines  300  are inserted and withdrawn through opening  226 . Disposed on opposed side walls  228  are a series of pairs of aligned rails  230  which are configured to support a magazine body  304  within stacker  222 . Each aligned opposed pair of rails  230  disposed on opposed side walls  228  is vertically spaced or spaced in the Z-direction from other opposed pairs of rails  230  a distance sufficient to support a magazine  300  and associated tips  310  depending therefrom without interference with other magazines  300  and associated depending tips  310  disposed above and below. In one embodiment, each stacker  222  is configured to receive five vertically stacked magazines  300 . Disposed on an end of each lip facing opening  226  is a detent  232  which prevents magazine  300  from inadvertently sliding out of stackers  222 . Stackers  222  may contain one or more horizontal support walls or struts  251  that provide strength and rigidity to stackers  222 .  
         [0057]    Preferably, each stacker  222  includes a top handle  234  mounted on side walls  228  which allows manual removal of stacker  222  from it&#39;s associated compartment  220 . Each compartment contains a plurality of upstanding pegs  236  disposed on vertically extending frame members  238 . Walls  228  of each stacker  222  include sleeves  244  which correspond to and are aligned with upstanding pegs  236  in compartments  220 . Sleeves  244  ride over pegs  236  when stacker  222  is inserted into a compartment  220  through opening  210  to align and hold each stacker  222  in its associated compartment  220 . This configuration of pegs  236  and sleeves  244  allows easy and quick insertion, removal and alignment of stackers  222  in associated compartments  220  through opening  210 . Each stacker  222  is manually supplied with magazines  300  either while in its compartments  220  or at a location remote from apparatus  10 . Stackers  222  are then inserted into carousel  202  as described.  
         [0058]    Disposed on carousel  202  are at least two sensors  246  and  248 . Sensor  246  determines whether a stacker  222  is disposed in any one compartment  220 . If there is no stacker  222  in a compartment  220 , motor  214  continues to rotate carousel  202  so that that compartment  220  passes by opening  206  and is not aligned therewith. Motor  214  continues to rotate carousel  202  until sensor  246  detects a stacker  222  in a particular compartment  220 . The speed of rotation of carousel  202  is reduced until sensor  248  detects the location of vertical support  242  of the compartment  220  which has already been indicated by sensor  246  to contain a stacker  222 . Sensor  248  sends a signal to controller  14  which causes motor  214  to rotate carousel  202  a predetermined, preprogrammed distance, which is the distance from the point where vertical support  242  is sensed by sensor  248  to the point where vertical support  242  is centered within opening  206 . At this point, rotation of carousel  202  is stopped, and compartment  220  is aligned with opening  206  such that magazines  300  disposed within associated stacker  222  may be accessed and removed by gripper assembly  20 .  
         [0059]    When it is desired to withdraw a magazine  300  from carousel  202 , gripper assembly  20  is lowered on gripper transport mechanism  100  until gripper assembly  20  is disposed in alignment with the top of opening  206 . In a preferred embodiment, sensor  62  on upper gripper head  26  scans opening  206  from the top moving downwardly in a Z-direction (FIG. 1) until it detects a tab  302  on a magazine body  304 . At this point, it moves downwardly an additional, predetermined distance to align jaws  48  and  50  of gripper head  26  with tab  302 . Gripper head  26  then extends outwardly toward opening  206  along slides  30  a predetermined distance until upper jaw  50  of gripper head  26  is aligned with the top surface  318  of tab  302 . At this point, lower jaw  48  is raised so that pins  58  enter into holes  306  and tab  302  is clamped between jaws  48  and  50 . At this point, gripper assembly  20  rises up slightly to raise magazine  300  off detents  232 , and then magazine  300  thereafter is withdrawn by gripper assembly  20 . This process is repeated until all magazines  300  in any one stacker  222  have been removed. When gripper head  26  is positioned to remove the lowermost magazine from a stacker  222 , a signal is sent by processor  14  to motor  214  to rotate carousel  202  until the next compartment  220  containing a stacker  222  is aligned with opening  206 .  
         [0060]    Disposal mechanism  350  will now be described with particular reference to FIGS. 1, 2 and  8 . Disposal mechanism  350  includes a tray  352  having a bottom wall  354 , and three side walls  358  which have upper edges  356 . An opening  368  is provided at one end of tray  352 . A track  362  is provided along table  430 . Track  362  extends from about vertical support  104  toward the left side of table  430  as shown in FIG. 1. Block  374  rides on track  362  and is coupled to tray  352  by a pivot coupling  370  which permits tray  352  to ride along track  362 . Movement of tray  352  along track  362  is produced by a motor  360  and associated screw drive  372 . Disposed along track  362  and adjacent an end thereof on the left side of table  430 , as shown in FIG. 9, is a tilt block  366 . As tray  352  encounters block  366 , tilting of tray  352  about coupling  370  is produced, as drive  372  continues to move tray  352  away from support  104 , pivoting tray  352  in a counterclockwise direction about coupling  370  as shown in FIGS. 1 and 8. In this way, magazines  300  with their associated tips  310  are permitted to slide out of tray  352  and into a bin  376  disposed therebelow. Bin  376  may then be removed for disposal of used magazine  300  and tips  310 .  
         [0061]    With reference now to FIGS.  7 - 7 C and  9 A- 9 J, typical methods of operation of the pipette tip magazine handling apparatus  10  of this invention will now be described. While operation of this apparatus  10  will be described with particular reference to the automated pipetting system of U.S. application Ser. No. 09/865,404, it is to be understood that the apparatus  10  of this invention may be operated with other automated pipetting systems. Moreover, the particular method described with respect to FIGS.  9 A- 9 J represents only an exemplary method of operation of the apparatus  10  of this invention and that this apparatus may be operated in other ways in accordance with this invention by appropriately programming processor  14  as will be apparent to one of ordinary skill in the art.  
         [0062]    Typically, although not necessarily, apparatus  10  commences the cycle by having a clean, unused pipette tip magazine  300  with clean, unused tips  310  being held by gripper head  26 , ready for insertion into dispensing head  410 , as shown in FIG. 9A. Gripper assembly  20  is positioned on transport mechanism  100  at a location generally even with dispensing head  410  in the Z-direction, as shown in FIG. 9A. Gripper head  26  is retracted into housing  22  awaiting the next step while holding tab  302  on magazine  300  in readiness for inserting magazine  300  into dispensing head  410 . This position is considered the “remove scan position”. In this position, lower gripper head  24  is disposed generally above clamp  420  and above tab  302  of magazine  300  disposed in dispensing head  410 . Lower gripper head  24  is extended a short distance from housing  22  into a scan position in which it looks for a tab  302  on a magazine  300  disposed in dispensing head  410 . (See FIG. 7) Gripper head  24  is approximately 10 inches from housing  22  and 2 inches from dispensing head  410 , in a preferred embodiment. In this position, if there is a magazine  300  in dispensing head  410 , tab  302  is within the sensing range or depth of field of the sensor  60  on gripper head  24  and will be sensed by sensor  60  as gripper assembly  20  begins its preprogrammed scan movement downwardly in the Z-direction along gripper transport mechanism  100 . If there is a magazine  300  in dispensing head  410 , tab  302  will be sensed. Once tab  302  has been detected, the gripper assembly  20  lowers a preprogrammed amount so that the gripper head  24  is exactly aligned with tab  302 . The processor  14  knows the exact distance between the sensor  60  and jaws  44  and  46 . At this point, if the pipetting operation is still in progress and clamp  420  is closed, gripper assembly  20  remains stationary and waits until the pipetting operation has been completed.  
         [0063]    Once sensor  440  sends a signal to processor  14  that clamp  420  is in its open position, indicating completion of the pipetting operation, gripper head  24  is extended from housing  22  toward magazine  300  in dispensing head  410 , as shown in FIG. 9B. At the same time, jaw  44  is lowered with respect to jaw  46 , so that jaws  44  and  46  are able to accept tab  302  (See FIG. 7A). Once tab  302  resides between jaws  44  and  46 , jaw  44  is raised with respect to jaw  46  to extend pins  56  through holes  306  in tab  302  to clamp tab  302 .  
         [0064]    In one embodiment, magazine  300  is simply withdrawn horizontally in the Y-direction from dispensing head  410 . However, in an alternative embodiment of the method of this invention, motor  112  is first activated to lower assembly  20  a small amount to move magazine  300  downwardly in the Z-direction with respect to dispensing head  410 , as shown in FIG. 7B. This downward movement is performed to withdraw the pipette tips  310  out of sealing engagement with a seal  450  or nozzles (not shown) that may be present in dispensing head  410 . Should the downward movement be insufficient to break the seal between the upper end  314  of tips  310  and the dispensing head, whether it be a silicone seal  450  or nozzle ends (not shown), motor  32  is activated to produce oscillating horizontal movement of gripper head  24  and thus magazine  300  in a Y-direction into and out of dispensing head  410 , as shown in FIG. 7C. This horizontal oscillating movement further serves to break any seal that may exist between upper end  314  of tip  310  and seal  450  or nozzle ends in the dispensing head  410 . Thereafter, the used magazine  300  and associated tips  310  are withdrawn from dispensing head  410  toward housing  22 , as shown in FIG. 9C. However, preferably, magazine  300  is only withdrawn part of the way toward housing  22 , and remains in a position such that gripper head  24  grasps magazine  300  at a location somewhat spaced in the Y-direction from housing  22 .  
         [0065]    If sensor  60  does not detect a tab  302  of a magazine  300  within dispensing head  410 , apparatus  10  skips the withdrawal step described above and goes directly to the insertion step described below in which gripper head  26  inserts an unused magazine into dispensing head  410 .  
         [0066]    Processor  14  has been preprogrammed, so that once the used magazine  300  has been withdrawn, stepper motor  112  is activated to lower assembly  20  to a precise position so that the new magazine  300  containing unused tips  310  in gripper head  26  is now aligned with dispensing head  410 . Motor  34  is then activated to extend gripper head  26  to insert the unused magazine  300  into clamp  420  of dispensing head  410 , as shown in FIG. 9D. Once automated pipetting system  400  detects that an unused magazine  300  is disposed within clamp  420 , clamp  420  is automatically closed by system  400  to grasp unused magazine  300 . Sensor  440  then provides a signal to processor  14  indicating that clamp  420  is in a closed position. Thereafter, jaws  44  and  46  are opened and processor  14  sends a signal to motor  34  to retract gripper head  26  within housing  22 .  
         [0067]    After a used magazine  300  with used tips  310  has been withdrawn from dispensing head  410 , gripper assembly lowers automatically to disposal mechanism  350 . Processor  14  has been preprogrammed to know the distance that gripper assembly  20  must be lowered in the Z-direction so that used magazine  300  is aligned with dump tray  352 , as shown in FIG. 9E. Dump tray  352  already has been moved by processor  14  to a receiving location  378  so that tray  352  is aligned with gripper head  24  in a Y-direction. As assembly  20  is lowered by transport mechanism  100 , used tips  310  and magazine  300  drop directly onto tray  352 . The lower ends  316  of tips  310  rest on bottom wall  354  of tray  352 , while magazine  300  sits on upper edge  356  of sidewalls  358 . Jaw  44  then lowers with respect to jaw  46  to release tab  302 , and gripper head  24  is retracted back into housing  22 , leaving magazine housing  300  and tips  310  sitting in tray  352 . Thereafter, motor  360  is activated to move tray  352  to the left, as shown in FIG. 1, or in a direction away from transport mechanism  100  along tracks  362  to a dump position  364 . In dump position  364 , tray  352  strikes a tilt block  366 , causing tray  352  to tilt downwardly to the left, or in a counterclockwise direction, as shown in FIG. 9F, or into a dump position  364  where tilt block  366  is positioned. Once tray  352  strikes tilt block  366 , tray  352  tilts so that open end  368  faces downwardly. Used magazine  300  and associated tips  310  slide out of tray  352  through open end  368  under the influence of gravity and into bin  376 . Thereafter, tray  352  remains in this position, until another used magazine  300  is withdrawn from dispensing head  410 . It will be apparent, that this step is skipped if no used magazine  300  is withdrawn from head  410 .  
         [0068]    In the next step of this method, assembly  20  is lowered to retrieve a new, unused magazine  300  from magazine supply  200 , as shown in FIG. 9H. In this step, assembly  20  is lowered a preprogrammed amount so that gripper head  26  is positioned at the top edge of carousel  202  and in alignment with opening  206 . Motor  112  then moves assembly  20  downwardly past opening  206  in a scan mode in which sensor  62  looks for a tab  302  on an unused magazine  300  in compartment  220 . In this position, gripper head  26  is spaced a predetermined distance from carousel  202 , so that a tab  302 , on any magazine  300  within compartment  220 , is within the depth of field of sensor  62 . Assembly  20  continues to move downwardly, until a tab  302  is sensed. Assembly  20  then drops a predetermined amount so that jaws  48  and  50  are is aligned with the sensed tab  302 . Gripper head  26  is then extended by motor  34 , and jaw  48  is lowered with respect to jaw  50 , as shown in FIG. 9H. Tab  302  is then grasped by raising jaw  48  with respect to jaw  50 . Assembly  20  is raised slightly to lift magazine  300  over detents  232 . Thereafter, gripper head  26  and magazine  300  are withdrawn from carousel  202 , as shown in FIG. 9I. Assembly  20  is then raised into its initial position in which assembly  20  is aligned with dispensing head  410  as previously discussed, as shown in FIG. 9J.  
         [0069]    The next time gripper head  26  is lowered to select an unused magazine  300  from carousel  202 , it will select the next lower magazine  300  within the particular stacker  222  removed when gripper head  26  is lowered to the lowest level of carousel  202  for selection of the lowest magazine  300 . When gripper  26  is detected as having selected a magazine  300  at this level, a processor  14  sends a signal to motor  214  which indexes carousel  202  to the next compartment containing a stacker  222 . Typically, carousel  202  is rotated in a counterclockwise direction, although it could be rotated in a clockwise direction. If the next adjacent compartment  220  in a clockwise direction contains no stacker  222 , carousel  202  continues to rotate. The presence or absence of a stacker is detected by sensor  246 . Carousel  202  will continue to rotate until a stacker  222  is detected. Thereafter, rotation is slowed, and the carousel is automatically rotated a predetermined amount once spine  242  has been detected by sensor  248  to align opening  226  in the stacker  222  with opening  206  in housing  204 . Thereafter, the process is repeated for withdrawing an unused magazine  300  from carousel  202 . If no compartments  220  contain stackers  222 , a signal will be sent to the operator that additional magazines are required.  
         [0070]    When power is on, clutch  216  is engaged, to prevent unwanted rotation of carousel  202 . Once power is turned off, carousel  202  is free-wheeling to allow easy positioning of carousel  202  to allow manual insertion or withdrawal of stackers  222  from compartments  220 . As indicated, stackers  222  may be inserted and withdrawn from compartments  220  either by pivoting housing  204  into the position shown in FIG. 4, or by inserting or withdrawing the stackers  222  through door  212 . Typically, stackers  222  are manually loaded with unused magazines  300  at another location.  
         [0071]    All of the motors and chain drives described in this application are conventional and are well known to those of ordinary skill in the art. In one embodiment, some or all of the motors described herein are closed loop stepper motors.  
         [0072]    It will be appreciated that, instead of a table  430 , a laboratory bench or other like support may be used for pipetting system  400 . All that is required is precise positioning of system  400  with respect to magazine handling apparatus  10  and magazine supply  200 .  
         [0073]    While preferably, a separate processor  14  is utilized for magazine handling apparatus  10  and a separate processor (not shown) is used for automated pipetting system  400 , it will be appreciated, that a single processor or personal computer could be used for both systems. In the embodiment described above, the only electrical connection between system  400  and apparatus  10  is sensor  440  which is disposed on clamp  420  and which has an electrical connection with processor  14 . However, sensor  440  could be coupled to a processor for a system  400 , which in turn could communicate with processor  14 . In this way, system  400  could be integrated with system  10 , as opposed to the two separate, stand alone systems described herein.  
         [0074]    Modifications and improvements within the scope of this invention will occur to those skilled in the art. The above description is intended to be exemplary only. The scope of this invention is defined only by the following claims and their equivalents.