Abstract:
The pipetting method is directed to mounting and ejecting a disposable pipette tip. The pipetting system has one or more tip mounting shafts with an upper locking section and a lower sealing section. The upper locking section has outwardly extending lobes spaced around the mounting shaft and located above a stop member. The lower sealing section on the tip mounting shaft is located below the stop. As the mounting shaft is inserted into the collar of the disposable pipette, the collar distorts out of round and engages the lobes on the upper locking section of the tip mounting shaft. Contemporaneously, the lower sealing section of the mounting shaft seals against the barrel of the disposable pipette tip.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application is a continuation of U.S. patent application Ser. No. 13/952,731, now U.S. Pat. No. 8,877,513, filed Jul. 29, 2013, entitled “Method of Using a Disposable Pipette Tip”, by Gregory Mathus, Terrence Kelly and Richard Cote, which is a continuation of U.S. patent application Ser. No. 12/578,714, now U.S. Pat. No. 8,501,118, filed Oct. 14, 2009, entitled “Disposable Pipette Tip”, by Gregory Mathus, Terrence Kelly and Richard Cote; which is a continuation of U.S. patent application Ser. No. 11/934,381, filed Nov. 2, 2007, now U.S. Pat. No. 7,662,344, issued Feb. 16, 2010 entitled “Locking Pipette Tip and Mounting Shaft, by Gregory Mathus, Terrence Kelly and Richard Cote, which is a Continuation-In-Part of U.S. patent application Ser. No. 11/552,384, which is entitled “Locking Pipette Tip And Mounting Shaft”, by Gregory Mathus, Terrence Kelly and Richard Cote filed on Oct. 24, 2006, now U.S. Pat. No. 7,662,343, issued Feb. 16, 2010, all assigned to the assignee of the present application. 
    
    
     FIELD OF THE INVENTION 
     The invention relates to improvements in pipettes and automated liquid handling systems. More specifically, the invention relates to a configuration for pipette tip mounting shafts and disposable pipette tips that provides robust sealing engagement with low insertion and ejection forces as well as enhanced resistance to unintentional removal, and maintains the mounted ftp in optimum position and orientation when the tip is mounted on the pipette tip mounting shaft. 
     BACKGROUND OF THE INVENTION 
     The use of disposable pipette tips with hand-held pipettes and automated liquid handling systems is well known. Disposable pipette tips enable repeated use of such pipetting systems to transfer different fluids or different fluid samples without carryover contamination. Disposable pipette tips are normally formed of a plastic material, such as polypropylene, and have a hollow, elongated, generally conical shape. The upper end of the pipette tip typically includes a collar that is mounted to the tip mounting shaft on the pipette device. The mounting shaft includes an internal bore through which an is displaced in order to aspirate liquid sample into and dispense liquid sample from the pipette tip. The far end of the pipette tip has a small opening through which liquid sample is received into and dispensed from the barrel of the pipette tip. 
     Disposable pipette tips have historically relied on tapered fits between the mounting shaft and the pipette tip collar, as well as sealing rings on the inside circumference of the pipette tip collar, to secure and seal the pipette tips to the mounting shaft. In most cases, the fit between the mounting shaft and the disposable tip is achieved by pushing the tapered mounting shaft into the tapered pipette tip collar until it wedges into the tip. At this point, a seal is achieved between the tip collar and the mounting shaft as a result of crushing the sealing ring and/or stretching the diameter of the collar. In addition to achieving a proper seal, it is also important that position and orientation of the mounted tip also be stable in the face of lateral momentum or slight knocking forces that are typical during normal use such as during touch-off on the sidewall of a vessel. In order to assure tip stability, users tend to jam the pipette mourning shaft into the tip with excessive force. 
     Various systems have been devised to provide proper sealing and stability without requiring excessive mounting and ejection forces. For example, the use of cylindrical mounting shafts and cylindrical tip collars lessens mounting and ejection forces. Also, it is well known to use a step within the pipette tip collar as a depth limiting means for the pipette mounting shaft. Even so, such systems typically require the force of an interference fit or stretching of the pipette tip collar to maintain stable engagement of the pipette tip and ensure a reliable seal of the collar against the mounting shaft. 
     A further approach is described in U.S. Patent Application Publication No. US 2005/0175511 A1 which the pipette up collar has inwardly projecting, cantilevered fingers that latch over a circumferential rim on the mounting, shaft. In this approach, sealing is achieved by an O-ring on the mounting shaft that is located below the location of the latching engagement. Ejection of the tip is achieved by modifying the ejection mechanism on the pipette so that it can release the inwardly projecting fingers on the pipette tip before asserting pressure to eject the tip from the mounting shaft. 
     SUMMARY OF THE INVENTION 
     In one aspect, the invention relates to a pipette tip mounting shaft configuration and a disposable pipette tip having a matching configuration. In its preferred form, the pipette tip mounting shaft includes a locking section located above a lower sealing section. The locking section includes a lower stop member and two or more outwardly extending locking lobes located above the stop member. The pipette tip collar locks onto the mounting shaft when mounting shaft is fully inserted into the collar of a mating pipette tip. The bore of the pipette tip includes a circumferential shelf or shoulder separating its upper collar from the sealing area of the tip located in the upper region of the tip barrel. The collar preferably includes a locking ring located at or near the upper opening of the collar. The dimensions of the collar, and in particular the distance between the circumferential shelf and the locking ring, are selected to match the dimensions on the mounting shaft between the stop member and the upper end of the locking lobes. The locking lobes preferably include a ramp portion that gently flexes and distorts the pipette tip collar out of round as the mounting shaft is inserted into the pipette tip collar. Due to relieved portions of the mounting shaft between the lobes, the tip collar flexes to distort out of round rather than stretch in order to accommodate the interference fit over the locking lobes. This configuration results in an ergonomic, over-center locking engagement. The feel of the engagement provides tactile feedback to the user of a hand-held pipette, in part, as a result of the flexing of the upper collar as the locking ring passes over the lobes on the mounting shaft into locking engagement. At the same time, the stop member on the mounting shaft limits penetration of the mounting shaft into the tip as the stop member engages the shelf in the tip, thus providing a clear indication that the tip is fully mounted 
     The lower sealing area on the mourning shaft extends below the stop member. The lower sealing section is preferably tapered in a frustoconical shape, but can be cylindrical, depending on the geometry of the matching pipette tip. Similarly, the pipette tip preferably includes a sealing ring in a sealing area located below the circumferential shelf at the upper end of the pipette tip barrel. The shape of the tip sealing area should match the shape of the lower sealing section of the mounting shaft. The circumferential shelf on a pipette tip isolates the distortion of the collar from the sealing area when the tip is mounted on the mounting shaft, thus maintaining the roundness of the sealing area (i.e. a circular circumference for the inside surface of the pipette tip barrel) in which the sealing ring is located. This is important in order to facilitate reliable engagement of the sealing ring around the lower sealing section of the mounting shaft. 
     As the mounting shaft is pushed into the tip collar, the first point of contact is where the leading edge of the mounting shaft, i.e., the lower sealing section, enters through the circumferential shelf in the pipette tip and contacts the sealing ring. As the mounting shaft is further depressed into the pipette tip bore, sealing ring interference increases simultaneously as the ramp area of the lobes of the mounting shaft engages the locking ring on the tip collar to distort the upper portion of the collar our of round. As mentioned, while the overall insertion force is relatively light and ergonomic, the force increases noticeably and provides tactile feedback to the user that the tip is almost fully mounted. This increase in insertion force continues until the stop member on the mounting shaft engages the circumferential shelf on the pipette tip to abruptly stop further movement of the mounting shaft into the tip, at which point the lobes also snap engage under the locking ring in the collar bore. Thus alerting the user not to use additional, excessive force to mount the tip. These interrelated mounting conditions result in a secure stable mount with consistent sealing at the sealing ring. Alternatively, the initial engagement of the sealing, ring can be staggered with respect to the engagement of the locking ring in order to lessen insertion force. 
     Moreover, the tip requires relatively low ejection force. When the pipette stripper sleeve pushes against the upper end of the tip collar, a relatively small ejection force is required to release the locking ring on the collar from the locking lobes on the mounting shaft. The flexing of the collar in its distorted shape when it is locked, over the mounting shaft lobes stores energy. When the tip is released from the lobes, the combination of the pressure from the stripper and the release of the stored energy throw the tip from the mounting shaft, thereby facilitating convenient ejection of the tips from the mounting shaft after use. 
     In some circumstances, it may be desirable to further lessen tip insertion and injection forces, such as is particularly desirable with hand-held multi-channel pipettors. In order to achieve this objective, it may be desirable to lessen the amount of interference between the pipette tip and the mounting shaft prior to full insertion of the mounting shaft into the pipette tip. In one embodiment of the invention, this is achieved by reducing the diameter of the mounting shaft below the sealing area on the mounting shaft so that there is little or no interference with the circumferential sealing ring on the pipette tip, and by further providing the sealing area on the mounting shaft with a frustoconical shape to facilitate effective sealing engagement of the circumferential sealing ring on the pipette tip with the mounting shaft. This embodiment is particularly useful for small volume pipette tips, such as 12.5μ liter or 125μ liter pipette tips. The purpose of the frustoconical sealing zone is to accommodate a preselected vertical range of travel, such as 0.025 to 0.030 inches of vertical travel, for which the circumferential sealing ring on the pipette tip can effectively engage the frustoconical sealing area on the mounting shaft. The preferred amount of taper in the frustoconical sealing area on the mounting shaft is between 4° and 7° included angle, and is preferably calculated to accommodate for normal manufacturing tolerances for molded pipette tips. In other words, pipette tips in which the diameter of the circumferential sealing ring is relatively small within normal manufacturing tolerances will typically engage the lower edge of the frustoconical sealing area on the mounting shaft, whereas pipette tips with larger circumferential sealing rings within normal manufacturing tolerances will engage slightly higher in the frustoconical sealing area on the mounting shaft. 
     In another embodiment that is particularly well suited to reduce insertion and ejection forces, the diameter of substantially all of the lower portion of the mounting shaft is reduced such that there is little or no interference between the circumferential sealing ring, on the pipette tip and the mounting shaft, thereby rendering the circumferential sealing ring a stabilization ring rather than a sealing ring. In this embodiment, the mounting shaft has an annular groove containing a sealing ring, preferably an O-ring made of flouroelastomeric material to effectuate a reliable seal with the pipette tip. This embodiment has been found to be particularly effective for pipettors having relatively large pipette tips, such as 300μ liters or 1250μ liters. The sealing O-ring is on the mounting shaft, preferably located so that it seals against the upper end of the barrel of the pipette tip. Preferably, in order to lessen long term wear on the O-ring as well as insertion and ejection forces, the center line of the O-ring will reside no more than about 0.03 inches into the barrel of the pipette tip below the circumferential shelf on the pipette tip. 
     In another aspect, the invention relates to the configuration of a disposable pipette tip in which a sealing, area with a sealing ring is located below a circumferential shelf that separates and isolates the sealing area from the upper mounting collar. By moving the sealing function away from the collar or shelf area into the upper area of the barrel, the design limitations for the mounting configuration of the pipette tip collar is less restrictive. For example, in the cases of the preferred embodiment of the invention, the collar is flexed and distorted out of round when mounted on the mounting shaft. Locating the sealing area on the pipette tip below the circumferential shelf to isolate the sealing area from distortion facilitates this mounting arrangement. 
     These and other aspects, features and advantages of the invention are now described in greater detail with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a hand-held, electronic air displacement pipette incorporating the concepts of the present invention. 
         FIG. 2  is a perspective view showing a disposable pipette tip and a pipette tip mounting shaft in accordance with a preferred embodiment of the invention. 
         FIG. 3  is a side elevational view of the mounting shaft and pipette tip shown in  FIG. 2 . 
         FIG. 4  is a longitudinal cross-section taken along, line  4 - 4  in  FIG. 3 . 
         FIG. 5  is a detailed view of the area encircled by line  5 - 5  in  FIG. 4  showing an upper locking collar, sealing area and circumferential shelf of the disposable pipette tip illustrated in  FIG. 2 . 
         FIG. 6  is a detailed view of the area encircled by line  6 - 6  in  FIG. 4  showing a locking section, sealing section and stop member of the mounting shaft shown in  FIG. 2 . 
         FIG. 7  is a side elevational view showing the mounting shaft being inserted into the disposable pipette tip. 
         FIG. 8  is a longitudinal cross-section taken along line  8 - 8  in  FIG. 7 . 
         FIG. 9  is a detailed view over the area encircled by line  9 - 9  in  FIG. 8  showing insertion of the mounting shaft into the pipette tip just prior to final engagement. 
         FIG. 10  is a detailed view similar to  FIG. 9  showing full insertion of the mounting shaft into the pipette tip. 
         FIG. 11  is a view taken along line  11 - 11  in  FIG. 10  illustrating the pipette tip collar and locking, ring being distorted out of round when the pipette tip is fully mounted onto the mounting shaft. 
         FIG. 12  is a view similar to  FIG. 10  illustrating the pipette tip being stripped off the mounting shaft. 
         FIG. 13  is a detailed view similar to  FIG. 10  showing full insertion of a mounting shaft into the pipette tip, wherein the mounting shaft has been modified to include an annular groove and an O-ring seal in accordance with another embodiment of the invention. 
         FIG. 14  is a detailed view showing the full insertion of a mounting shaft into the pipette tip, wherein the mounting shaft has been modified in accordance with another embodiment of the invention to incorporate a frustoconical sealing area which accounts for normal manufacturing tolerances. 
         FIGS. 15 and 16  are schematic views of the area depicted by line  15 - 15  in  FIG. 14 , illustrating the interaction between the circumferential sealing, ring on the pipette tip and the frustoconical sealing area on the pipette mounting shaft. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       FIG. 1  illustrates a hand-held, electronic air displacement pipette  10  that incorporates a pipette mounting shaft  12  and a disposable pipette tip  14  constructed in accordance with the preferred embodiment of invention. The pipette  10  includes a housing  16  designed to be held in the palm of the user. Internal components of the pipette (not shown) drive a piston that extends through a seal assembly to displace air within an aspiration and dispensing cylinder. The pipette mounting shaft  12  is threaded or otherwise attached to the lower end of the pipette such that it is in fluid communication with the aspiration and dispensing chamber. The attachment of the mounting shaft to the pipette is not particularly relevant to the concepts of the invention, and is well known in the art. Button  18  is provided for the user to instruct the electronic pipette to aspirate and dispense. The pipette  10  also includes a lever  20  that is actuated in the direction of arrow  22  to move an ejection mechanism sleeve  24  downward in order to eject the disposable pipette tip  14  from the mounting shaft  12 . 
     While the invention is shown and described with respect to its use on a hand-held, electronic air displacement pipette  10 , the invention is also useful in connection with other types of hand-held pipettes, as well as automated liquid handling machines using dispensable pipette tips. For example, the ergonomic features provided by the invention are particularly useful for hand-held manual pipettes as well as electronic pipettes. In addition, features of the invention that relate to the security and stability of the engagement of the pipette tip to the mounting shaft are quite useful for automated liquid handling systems as well as band-held pipettes. 
     As shown in  FIG. 2 , the mounting shaft  12  preferably has threads  26  for attaching the mounting shaft  12  to the lower end of the aspiration and dispensing cylinder (not shown). As discussed herein, the dimensions of the mounting shaft  12  match the dimensions of the pipette tip  14  so that only pipette tips  14  with the proper dimensions can fit onto the mounting shaft  12 . In order to use pipette tips with different bore dimensions in the collar and sealing region, it is necessary to replace the mounting shaft  12  and/or the tubular stripper shaft  24  with one having appropriate dimensions. 
     Referring now to  FIGS. 2-6 , the mounting shaft  12  contains a central bore  28  that provides for air passage between the aspiration and dispensing cylinder in the pipette  10  and the pipette tip  14 , as is well known in the art. The mounting shaft  12  includes an upper locking section  30 , a lower sealing section  32 , and a stop member  34  located between the locking section  30  and the lower sealing section  32 . The pipette tip  14  generally consists of a collar  36 , a barrel  38  and a circumferential shelf  40  that extends around the inside bore of the tip  14  and connects the lower end of the collar  36  to the upper end of the barrel  38 . The upper end of the collar  36  has an opening  42  to receive the pipette mounting shaft  12 . The lower end of the barrel  38  has a small opening  44  through which liquid is aspirated into the tip barrel  38  and dispensed from the tip barrel  38  during normal operation of the pipette  10 . Support ribs  46  extend downward on the outside surface of the pipette tip  14  from the collar  36 . The support ribs  46  function to hold the tip  14  or an array of tips  14  in a tray or the like for subsequent use, as is known in the art. 
     The internal surface of the pipette tip  14  is now described in more detail, referring in particular to  FIG. 5 . The inside surface of the collar  36  preferably includes a circumferential locking ring  48 , although aspects of the invention can be accomplished without the locking ring  48 . The locking ring  48  is preferably located at or slightly below the opening  42  for the collar  36 . The locking ring  48  extends inward from the inside wall of the collar  36  a slight amount, preferably in the range of 0.001 inches to 0.010 inches, in order to provide a locking fit over the lobes  50  on the mounting shaft  12 . It is important, however, that the locking ring  48  not extend so far inward to interfere with efficient and effective ejection of the disposable tip  14  from the mounting shaft  12  after use. The locking ring  48  can optionally include one or more air bleeds  52 . The air bleed can optionally be incorporated on the mounting shaft  12  instead of, or in addition to), the locking ring  48  of the pipette tip. The primary purpose of such air bleeds is to prevent aspiration of liquid in the case that an improperly sized pipette tip is mounted onto the mounting shaft. This is important in order to reduce the chance of contamination of the pipette cylinder, for example, when a large volume of liquid is accidentally aspirated into a tip designed for a small volume of liquid. 
     The inside surface of the collar  36  is preferably tapered or slightly frustoconical, but can also be cylindrical in accordance with the invention. Preferably, the taper is between 0° and 10°. In any event, horizontal cross-sections through the main section of the collar  36  are preferably circular. 
     The upper portion  39  of the barrel  38  is the sealing area for the pipette tip  14 . A circumferential sealing ring  54  preferably extends inward from the inner surface of the upper portion  39  of the barrel  38  in the sealing area. Alternatively, sealing can be accomplished without sealing ring  54 . The sealing, area  39  in the barrel  38  is preferably frustoconical, but can also be substantially cylindrical, in accordance with the invention. The preferred taper is between ½° and 4°. Preferably, the sealing ring  54  extends 0.003 inches inward from the surface of the barrel  38 , and its longitudinal thickness is 0.010 inches. 
     The circumferential shelf  40  of the pipette tip  14  connects the lower portion of the collar  36  to the upper portion  39  of the barrel  38 . The shelf  40 , as shown in the Figures, is angular and continuous around the inside circumference of the tip  14 . The shelf  40  need not be angular, however, and can for example be horizontal. The shelf  40  serves to separate the locking region or collar  36  of the pipette tip  14  from the sealing area  39  of the pipette  14  in the upper portion of the barrel  38 . As best illustrated in  FIG. 11 , the collar  36  is distorted out of round when the mounting shaft  12  is fully inserted into the pipette tip  14 . The shelf  40  serves to isolate the sealing area in the upper portion of the barrel  38  from this distortion, thereby facilitating an effective seal of the sealing ring  54  against the sealing section  32  of the mounting shaft  12 . It also serves to accurately locate the tip on the mounting shaft. With multiple channel devices, the tip shelf insures the same vertical mounting distance from tip to tip. This allows precise and consistent tip position during pipetting. 
     It is contemplated that pipette tips  14  manufactured in accordance with the invention will be typically made of molded plastic, normally polyethylene or polypropylene with or without various additives, as is known in the art. This design embodies a locking ring  48  and sealing ring  54  that help the injection molding process. They serve as a way to keep the molded tip on the core of the mold instead of using a puller ring for this process. 
     Referring now in particular to  FIGS. 2, 3, 4 and 6 , the sealing section  32  of the mounting shaft  12  is tapered in an amount corresponding to the sealing area  39  of the pipette tip in the upper portion of the pipette tip barrel  38 . The outer surface of the sealing, section  32  of the mounting shaft  12  forms an interference fit with the sealing ring  54  on the pipette tip  14  to provide an air-tight seal in order to effectuate accurate aspiration and dispense of liquid into and from the pipette tip barrel  38 . The locking section  30  of the mounting shaft preferably includes a central cylindrical stabilizing section  56 , which is located immediately above and adjacent the stop member  34 . When the pipette tip  14  is mounted on the mounting shaft  12  the central cylindrical stabilizing section  56  on the mounting shaft  12  helps to support the tip  14  in a stable straight orientation. One of the advantages of the invention is that the mating locking mechanism allows the tips  14  to be securely mounted in a consistently straight orientation. This allows the use of longer pipette tips  14 , which can be particularly desirable in certain applications. The diameter of the mounting shaft  12  decreases at the stop member  34  between the central stabilizing section  56  and the upper portion of the sealing section  32  commensurate with the reduction in diameter of the matching pipette tip  14  at its circumferential shelf  40 . As mentioned, this reduction is preferably in the range of about 0.004 to 0.040 inches. Note that it is not necessary that the cylindrical stabilizing section  56  and the stop member  34  be continuous around the circumference of the mounting shaft  12  inasmuch as the purpose of these components is to provide secure, stable locking engagement of the pipette tip  14  on the mounting shaft  12  and not to provide a seal. Above the cylindrical stabilizing section  56 , the diameter of the mounting shaft  12  may or may not reduce slightly in order to provide clearance between the mounting shaft  12  and the collar  36  of the pipette tip  14 . The top of the locking section  30  of the mounting shaft  12  preferably includes two or more locking lobes  50  spaced equally around the mounting shall  12 , as well as corresponding recessed areas  58  spanning between the locking lobes  50 . The lobes  50  include relatively gently sloping inclined ramps  60 . The preferred slope of the ramp  60  incline with respect to the vertical axis of the mounting shaft  12  is between 10° and 20°. The lobes  50  extend outward along the ramp  60  towards the top of the locking section  30  until the lobes  50  turn abruptly inward to form catch surfaces  62 . The intersection between the ramp surface  60  and the catch surface  62  at the peak of each lobe  50  is preferably slightly rounded. At its peak, the lobes  50  preferably extend outward beyond the outer surface of the cylindrical stabilizing section  56 , although the exact preferred dimensions will depend on the amount of taper of the collar  36  in the corresponding matching pipette tip  14  as well as the tip wall thickness. 
     The mounting shaft  12  is preferably made from machined steel or machined or molded from chemically resistant plastic such as PEEK or polypropylene, and the specific dimensions are selected to correspond to the dimensions of the matching pipette tip  14 . For example, the distance between the stop member  34  and the catch surfaces  62  of the lobes  50  of the mounting shaft  12  is selected, to correspond to the distance between the circumferential shelf  40  and the locking ring  48  on the collar  36  of the pipette tip  14 . 
     Referring now to  FIGS. 7-9 , as the mounting shaft  12  is pushed into the tip  14 , the first point of contact is when the leading edge of the sealing section  32  on the mounting shaft  12  enters through the circumferential shelf  40  on the pipette tip  14  and contacts the sealing ring  54 . As the mounting shaft  12  is further inserted into the tip  14 , the sealing ring  54  interference force against the sealing section  32  of the mounting shaft  12  increases. At the same time, the ramp area  60  of the lobes  50  begins to engage the upper portion of the tip collar  36 . Alternatively, as mentioned above, the initial engagement of the sealing ring  54  can be staggered with respect to the engagement of the upper portion of the tip collar  36  in order to lessen insertion force. As the mounting shaft  12  is further inserted into the tip  14 , the ramps  60  on the lobes  50  push against the locking ring  48  on the collar  36  of the tip  14  and gently flex the collar  36  and distort it out of round. The recessed areas  58  on the mounting shaft  12  provide ample clearance for the straightening of the collar  30  that occurs between the lobes  50 . The intent is for the lobes  50  to flex the collar  36  out of round rather than stretch the collar  36 . 
     Referring now to  FIGS. 10 and 11 , as the mounting shaft  12  is fully inserted into the pipette tip collar  36 , the stop member  34  on the mounting shaft engages the circumferential shelf  40  on the pipette tip  14  thus preventing further movement of the shaft  12  into the tip  14 . At the point of engagement, the locking ring  48  on the inside surface of the tip collar  36  more or less simultaneously snaps over the lobes  50  on the mounting shaft  12 . Thus, the pipette tip  14  is securely locked into place onto the mounting shaft  12  with there being a positive engagement between the stop members  34  on the mounting shaft  12  and the circumferential shelf  40  on the pipette tip  14  on the one hand, and the catch surface  62  of the lobes  50  on the mounting shaft  12  and the underside of the locking ring  48  of the tip collar  36  on the other hand.  FIG. 11  shows a cross-sectional view looking down on the tip collar  36  being locked onto the mounting shaft  12  over the lobes  50 . The collar  36  is flexed and distorted to an out of round condition. Note that phantom line  70  indicates the outside surface of the collar  36  opening in its preferred round state before being mounted on the mounting shaft  12 . Phantom line  72  indicates the position of the inside surface of the locking ring  48  of the collar  36  in its preferred round state before being mounted over the lobes  50  on the mounting shaft  12 . While the mounted collar  36  is flexed and distorted out of round, the circumferential shelf  40  below the collar  36  remains circular due to its structural integrity. 
     By flexing and distorting the tip collar  36  rather than stretching the collar  36  in order to mount the tip  14 , the required insertion force is relatively small as compared to other designs which require tight interference fits or stretching of the tip collar. The user senses that full engagement is near as the mounting shaft  12  is inserted into the tip  14  because of the slightly increasing resistance of the interference with the sealing ring  54  on the tip and the increasing diameter of the ramp lobes  50 . Definite feedback of full engagement occurs when the stop member  34  engages the circumferential shelf  40  and the locking ring  48  snaps over the lobes  50 . The locking engagement is robust and reduces unintentional dismounting of the tip when a side force is applied to the tip, such as during touching-off procedures. 
     In addition, the system enables low ejection forces, which is particularly advantageous for hand-held pipettes. As mentioned, the out of round distortion of the collar  36  storing energy in the mounted collar  36  is useful for throwing off the tips  14  after use. Conventional ejection or stripping mechanisms can be used to push on the top of the collar  36  and push the locking ring  48  over the lobes  50  in order to eject the tips  14 .  FIG. 12  shows a stripper tube  24  moving downward (arrow  22   a ) to push on the top of the collar  36  to eject the tip  14 . When the locking ring  48  clears the peaks of the lobes  50 , the energy stored in the distorted collar  36  is released and facilitates efficient ejection of the tip  14  from the mounting shaft  12 . 
     A preferred embodiment of the invention has been described in connection with the drawings, however, various aspects and features of the invention can be implemented in other forms. For example, it is not necessary that the mounting shaft  12  have more than two lobes. Moreover, as previously mentioned, while the preferred embodiment of the invention provides for low insertion and ejection forces as well as tactile feedback when the mounting shaft is inserted into the pipette tip, the invention is also quite useful in automated liquid handling systems where these attributes may not be as important. 
     Also, although not preferred, it may be desirable to move the sealing area on the pipette tip from below the shelf to above the shelf, configure the mounting shaft so that it accommodates sealing above the stop, rather than below. Even though this is not a preferred design, such a design preferably, in accordance with the invention, includes a mounting shaft with locking lobes as described above. The sealing area on the tip, however, still has to be sufficiently isolated from distortion. This normally requires that the sealing area be located adjacent the shelf and relatively fir from the upper portion of the collar that becomes distorted by the mounting shaft lobes. 
     Another embodiment of the invention designed to further reduce insertion and injection forces is illustrated in  FIG. 13 . In  FIG. 13 , the pipette tip  14  has the same or similar configuration to that described in the above Figures, for example  FIGS. 3-5 . In this regard, the same reference numbers are used in  FIG. 13  as in the earlier Figures to describe the components of the pipette tip  14 . For example, the pipette tip  14  shown in  FIG. 13  generally consists of a collar  36 , a barrel  38 , and a circumferential shelf  40  that extends around the inside bore of the tip  14  and connects the lower end of the collar to the upper end  39  of the barrel  38 . The pipette tip also includes a circumferential ring  54  on the inside surface of the barrel  38 , which in the earlier embodiment served as a circumferential sealing ring but in this embodiment does not serve as a sealing ring because of modifications made to the mounting shaft  112 . The pipette tip  14  also preferably includes a circumferential locking ring  48  along the inside surface of the collar  36  at or slightly below the opening of the collar  36 , as described previously. 
     In  FIG. 13 , the mounting shaft  112  is modified so that the diameter of the lower sealing section  132  is reduced in comparison to the earlier embodiment. The configuration of the locking section  130  of the modified mounting shaft  112  is quite similar to that described in the earlier embodiments, especially with respect to the lobes  50  and the step  34  and the interaction of the lobes  50  and the step  34  with the pipette tip  14 , with a caveat being that it has been found that the diameter of the central stabilizing section  156  may be reduced slightly to provide less interference between the pipette tip  14  and the mounting shaft  112  when the mounting shaft  112  is inserted into the pipette tip  14 . 
     The lower sealing section  132  of the mounting shaft  112  in  FIG. 13  is modified to reduce the diameter of the lower sealing section at the tip  133  of the mounting shaft  112  so that there is little or no interference between the circumferential ring  54  of the pipette tip  14  and the lower portion  132  of the mounting shaft  112 . An annular groove  135  containing a sealing ring  137  is located at the upper end of the lower sealing section  132  of the mounting shaft  112 . The sealing ring  137 , as mentioned, is preferably an O-ring made of flouroelastomeric material. For a 300μ liter pipettor, the preferred O-ring has a 0.030 inches cross-section, and a 0.130 inside diameter which is stretched to a 0.147 groove diameter, which provides a 0.006 inch interference fit between the O-ring  137  and the upper portion  39  of the barrel  38  of the pipette tip  14 . For a 1250μ liter pipettor, the preferred O-ring has a 0.037 inch cross-section, and a 0.172 inside diameter, which is stretched over a groove diameter of 0.189 inches again to produce an interference of about 0.006 inches between the O-ring  137  and the upper portion  39  of the barrel  38  of the pipette tip  14 . Preferably, the upper edge of the groove  139  is no more than about 0.015 inches, e.g. about 0.008 inches, below the top  41  of the inside surface of the barrel  38  of the pipette tip  14 . In this manner, the sealing O-ring  137  does not travel a substantial distance after it is in contact with the pipette tip  14  barrel  38 . Preferably, the lower section  132  of the mounting shaft  112  includes a tapered section  141  located proximate the groove  139  above the location where the circumferential ring  54  on the pipette tip  14  would be located after the mounting shaft  112  is fully inserted into the tip  14 . The tapered portion  141  tapers outward as it approaches the groove  139  in order to protect the O-ring seal  137  from damage that might otherwise be caused by contact with the pipette tip shelf  40  as the mounting shaft  112  is inserted into the pipette tip  14 . 
     While not generally preferred, it may be desirable in some circumstances to locate the groove  137  and O-ring seal  139  within the upper locking portion  130  of the mounting shaft, so that the O-ring seal  137  engages the collar  36  of the pipette tip  14 . 
     Another embodiment of the invention designed to further reduce the insertion and ejection forces is disclosed in  FIGS. 14-16 . The embodiment of the invention illustrated in  FIGS. 14-16  is particularly useful when it is not desirable or practical to use an O-ring seal, yet it is desirable to further reduce insertion and ejection forces, such as in hand-held multi-channel pipettor applications. In  FIGS. 14-16 , the configuration of the pipette tip mounting shaft  212  is modified, yet as with the embodiment disclosed in  FIG. 13 , it is preferred that the configuration of the pipette tip  14  remain similar to the earlier embodiments. For example, it has been found that the embodiment shown in  FIGS. 14-16  is particularly well suited for use on multi-channel pipettors having pipette volumes of 12.5μ liter and 125μ liter. Referring, to  FIGS. 14-16 , the lower section  232  of the mounting shaft  212  is modified to reduce the diameter of the lowermost portion  233 . The diameter of the lowermost portion  233  of the mounting shaft is reduced so that there is little or no interference between the circumferential sealing ring  56  on the pipette tip  14  and the lowermost portion  233  of the mounting shaft. The lower section  232  of the mounting shaft  212  contains a frustoconical sealing area  200  located in the vicinity that the circumferential sealing ring  56  is expected to reside when the mounting shaft  212  is fully inserted into the tip  14 . With respect to the upper locking portion  230  on the mounting shaft  212 , it is preferred as in the embodiment shown in  FIG. 13  to slightly reduce the diameter of the central stabilizing section  256  to reduce interference drag between the mounting shaft  212  and the collar  36  of the pipette tip  14 . 
       FIGS. 15 and 16  are schematic views illustrating the operation of the frustoconical sealing area  200  on the mounting shaft  212 . It should be understood that the dimensions of the frustoconical sealing area  200  are exaggerated in  FIGS. 15 and 16  in order to illustrate the concept of this aspect of the invention. Referring in particular to  FIGS. 15 and 16 , sealing of the pipette tip  14  to the mounting shaft  212  is due to the interference between the circumferential sealing ring  56  on the pipette tip  14  and the frustoconical sealing area  200  on the mounting shaft  212 . The specific dimensions of the frustoconical sealing area  200  are determined to account for normal manufacturing tolerances for molded pipette tips. In general, molded pipette tips having relatively small dimensions within normal manufacturing tolerances, will form an interference fit at the lower portion of the frustoconical section  200  as the mounting shaft  212  is inserted into the pipette tip, as shown in  FIG. 15 . On the other hand, molded pipette tips having a relatively large dimension, within normal manufacturing tolerances, will engage towards the upper portion of the frustoconical sealing area  200  as shown in  FIG. 16 . Below the frustoconical sealing area  200 , it is desirable that the mounting shaft  212  does not interfere with the sealing ring  56  as the mounting shaft is inserted into the pipette tip  14 . Note that in  FIG. 15 , there is a slight amount of clearance between the step  34  on the mounting, shaft  212  and the circumferential shelf  40  between the collar  36  and the barrel  38  of the pipette tip  14 . On the other hand, in  FIG. 16 , there is no such clearance  201  as shown in  FIG. 15 , but the step  34  on the mounting shaft  212  engages the circumferential shelf  40  on the barrel  38  of the pipette tip  14 , as illustrated by reference number  202 . For the preferred dimensions of the frustoconical sealing area  200 , and the associated vertical range of travel  203  for effective sealing, it has been found that the use of a frustoconical sealing area  200  as described has little or no effect on the ability of the upper locking section  230  to lock into place within the collar  36  of the pipette tip  14 . 
     Using quality control statistical analysis, it has been determined that the preferred range of vertical travel  203  for the frustoconical sealing area  200  be 0.025 inches for 12.5μ liter pipette tips and that the frustoconical area have an included angle of 5°; whereas, for 125μ liter pipette tips, the preferred range of vertical travel is 0.03 inches with an included taper angle of 4°. These dimensions were selected to provide a nominal interference of 0.002 inches to ensure an effective seal, and were selected so that the range would include the mean pipette tip dimension at the sealing ring  56  plus or minus three times the standard deviation.