Patent Publication Number: US-2015087078-A1

Title: Well seals in pipette workstations

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application claims priority from provisional application Ser. No. 61/881,840, filed Sep. 24, 2013. 
    
    
     TECHNICAL FIELD 
     The invention relates generally to analytical chemistry processing clinical and research laboratory equipment and, more particularly, to well seals for microtiter plates that can be manipulated by a pipette or a pipette array. 
     BACKGROUND ART 
     Covers for well plates are known. For example, in U.S. Pat. No. 5,604,130 to Warner et al. disclose a cover effective to releasably seal a multiwell container, such as a microtitration plate. Multiwell plates may also be referred to as multiwell plates, microwell plates, microtiter plates, among other names. Such plates commonly have 96 wells, although 12, 24, 48, 384, and 1536 well plates. The cover contains a pad, fashioned from a flexible polymer sheet, and a plurality of resiliently compressible ridges formed on the sheet. The ridges are deformable, such that application of pressure applied to the cover is effective to form a fluid-tight seal between the pad and the well openings. The ridges extend from the pad sufficiently to break the seal upon release of the pressure. 
     In U.S. Pat. No. 6,500,390 to Boulton et al. disclose a microplate assembly having a multi-well microplate, a plurality of vent caps and a porous vent film. The microplate includes a frame that houses a plurality of open wells in a rectangular array. Vent caps mount on the microplate to seal and vent the wells. When the vent caps are coupled to the wells, an interior volume is formed in each well. The wells function as a vessel for liquid samples that occupy predetermined spaces within the interior volumes. Each liquid sample remains within its predetermined space for all orientations of the microplate assembly. The vent cap has an array of well inserts. Each well insert has a sealing plus and a vent tube. A flexible perforated web interconnects the well inserts to each other. The vent tubes are fixed to the sealing plugs and terminate in a vent. A barrier formed from a plurality of nested flaps resiliently mounts on the vent tube to partially cover the vent. 
     In a U.S. Pat. No. 7,968,061 to Goodwin discloses a microplate having a plate body with at least one well formed therein, the well having a first open end, a second end, an aperture being formed in the second end, and a side wall extending between the first end and the second end. A membrane extends across the aperture formed in the second end. 
     An object of the invention was to devise a workstation that seals and covers wells in microtiter plates. 
     SUMMARY OF THE INVENTION 
     The above objective has been met with a apparatus for sealing microtiter plates with well closure structures in a multi-function workstation. Multiwell plates may also be referred to as multiwell plates, microwell plates, microtiter plates, among other names. Such plates commonly have 96 wells, although 12, 24, 48, 384, and 1536 well plates. The workstation has a table for supporting microtiter plates and other fluid receptacles, an arm, and a multi-function head affixed for reciprocal movement along the arm. The workstation combines into a single programmable system the capabilities for automation of a wide range of bioanalytical procedures including, not only sample pipetting, serial dilution, reagent additions, mixing, reaction timing, washing of reaction vessels, and incubation that requires sealing of the reaction vessel with thimble-shaped, ribbed, closure structures of the invention. 
     The well closure structures are thimble-shaped ridged members or strips of identical members made of yieldable material, such as rubber or soft inert polymer. Each closure structure or seal has spaced apart peripheral ridges that serve to seal wells into which the structure are pushed by a pipette tip. At the downhole closed end of a closure structure a beveled edge nose allows self-centering entry into a well. A lower peripheral ridge terminates the nose and has a diameter that yieldably contacts walls of the well. 
     An upper peripheral ridge at the top of the closure structure, spaced from the lower ridge, has a yieldable wedge fit into the well and stops entry of the structure after a short distance. An intermediate ridge, spaced between the lower and upper ridges has an intermediate diameter that is less than the upper ridge diameter and not less than the lower ridge diameter. When the closure structures are made in strips, the upper ridges may have an upper joinder strip so that a plurality of structures can be manipulated at the same time. For example, an 8-channel pipette could pick and insert a strip of 8 closure structures joined together. 
     The workstation can be adapted to transfer, dispense, and aspirate liquid from one location to another automatically and optionally robotically in accordance with user programmed instructions. Fluid is dispensed and aspirated using the multi-function head having one or a selected plurality of nozzles associated with pipettes. Affixed to the nozzles are disposable pipettor tips, which are automatically picked up by the nozzles and ejected by a tip ejector mechanism that include a separate set of tips used to flush and wash the reaction vessels at the control of the user. The same nozzles used to dispense are used to transport novel ridged structures for microtiter plate well closures that seal the reaction vessels. A motor coupled to an actuator may be used to control the multiple functions including tip coupling fluid aspiration, fluid dispensing, tip ejection, and cover placement, sealing, and closure structure placement and removal. The workstation is designed for interactive connection with a remote computer. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an isometric view of the well closure structures of the invention used with a multi-channel pipette and a multi-well plate. 
         FIG. 2  is an isometric view of the multi-channel pipette of  FIG. 1  with well closure structures engaged. 
         FIG. 3  is a close up view of well closure structures attached to a multi-channel pipette. 
         FIG. 3   a  is a magnification of well closure structures attached to a lower portion of the multi-channel pipette of  FIG. 3  at the circle E of  FIG. 3 . 
         FIG. 3   b  is a section of the well closure structures of  FIG. 3   a  taken along lines G-G of  FIG. 3   a.    
         FIG. 4  is a close up side view of pipette well closure structures in wells of a multi-well plate. 
         FIG. 4   a  is a sectional view of the well closure structures of  FIG. 4  taken along lines A-A in  FIG. 4 . 
         FIG. 5  is a front plan view of a well closure structures shown in  FIG. 4   a.    
         FIG. 5   a  is a perspective view of the well closure structures of  FIG. 5 . 
         FIG. 6  is a cross sectional view of the well closure structures of  FIG. 5 . 
         FIGS. 7 ,  8 , and  9  are perspective view of successive steps for joinder of a strip of well closure structures to a multi-channel pipette and insertion into a multi-well plate. 
         FIG. 10  is a front plan view of a strip of well closure structures. 
         FIG. 11  is a cross sectional view of the strip of wells closure structures shown in  FIG. 10 . 
     
    
    
     DETAILED DESCRIPTION 
     With reference to  FIG. 1  a multi-channel pipette  200  engages a strip of well closure structures (“seals”)  100  that are designed to be transferred by the multi-channel pipette  200  from a storage container to a multi-well plate  300 . The multi-channel pipette  200  picks up seals  100  by applying even force to the seals in the storage container as shown in  FIG. 2 . The pipette needs only to go halfway down the well to keep the seals secured. As an example, tips are placed firmly in 8 wells of a 96-well plate  300  as shown in  FIGS. 3 and 4 . Note the ridge seals  102  and  103  in  FIG. 4   a  that will be described below. 
     With reference to  FIGS. 5 ,  5   a , and  6  the function of the seal ridges  101  and  102  is to prevent evaporation and leakage of materials in the well. The ridges  101  and  102  on the thimble-shaped seal  100  firmly wedge the seal into the well. The seal ridge  103  being slightly wider than the well into which the seal is inserted stops the well seals from being pushed too far into the well. The ejection mechanism of the 8-channel pipette  200  of  FIG. 1  can then be used to press against the seal ridge  103  to push the seal off the pipette while it remains in the well. The seals are made of firm rubber that provides a universal seal around the edge of the well. To extract the well seals vacuum produced by the 8-channel pipette  200  of  FIG. 1  can be used to contact the seal ridge  103  to make removal possible. The vacuum from the 8-channel pipette  200  also improves the grip of the well seals  100  by the pipette. 
     The well seals completely seal off the well with the ridges  101 ,  102 , and  103 . Ridge  103  stops the well seal from penetrating too far into the well, but may allow slight penetration into the well since the ridge  13  has a very slightly larger diameter than the well to form a wedge fit, and provides a platform on which the ejection mechanism of the pipette  200  can apply force. The large ridge  103  acts as the upper seal and an ejection platform. Seals  101  and  102  provide additional seal security and ensure the well seal will stay in place. The bottom of the seal  104  will remain above any materials in the well. Ridge  101  has a beveled nose for self-centering insertion into a well taper outwardly to a diameter slightly small than the well diameter. The intermediate ridge  102  has about the same diameter as the well diameter. 
     In the cross section of  FIG. 6  the inside of the well seal  100  is seen to have a hollow inside that is stopped or closed by the end of the seal  104 . The top is open to allow access for the pipette to place and remove the seals. The seal is made of a yieldable, generally inert material such as rubber or a deformable polymer such as Neoprene. The structure should be self-supporting but not rigid, similar to washers used in plumbing. 
     An alternative design consists of the well seals connected by a continuous strip of rubber  104  to form a well seal strip. This strip can be picked up and transferred with an 8-channel pipette to wells in the same manner as the well seals as shown in  FIGS. 7-9 . The strip prevents loss of well seals and promotes easy transfer and removal of seals.