Abstract:
A multi-well plate cover and assembly comprises a lid and a gasket. The lid is formed of a resilient material and configured to apply a compressive spring force to the surface of the gasket to seal the wells in a multi-well plate when the cover is secured to the multi-well plate. The lid has members for mechanical manipulation and for attachment to the multi-well plate.

Description:
This application claims domestic priority from Provisional Patent Application No. 60/236,391, Filed: Sep. 29, 2000. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to an improved multi-well plate cover of the type typically used in the laboratory science fields of biology, chemistry and pharmaceutical research to cover multi-well plates. More specifically, the improved cover and assembly is adapted for improved sealing function and for mechanical manipulation by robotic or other mechanical means. 
     2. Description of the Related Art 
     In the areas of biological, chemical and pharmaceutical research, it is a common practice to utilize multi-well plates for storage and analytical purposes. Generally these plates, normally constructed of plastic materials, have a 3″×5″ footprint and contain from 12 to 1536 wells organized in rows. The individual well geometry of a multi-well plate can vary between round and square, with contained volumes from 1 microliter to 200 microliters. The plates are particularly suited to the use of laboratory automation for the handling, storage and assay of chemical and biological entities. 
     The multi-well plates, being liquid-filled and subject to storage, have a number of lidding options available to the user. The simplest form of cover is a molded plastic lid that loosely fits over the multi-well plate. For some researchers this may provide an adequate seal, but other researchers may require a more robust cover that provides for protection from both the ingress and egress of materials into the individual wells. The nature of ingression can include the absorbence of material such as water in the presence of DMSO (dimethyl sulfoxide), a preferred storage solvent with a hygroscopic nature, and transfer of materials between wells. Egression can include the loss of volume due to evaporation or sublimation. 
     Another form of lidding is that of an adhesive seal type cover such as Costar® Thermowell™ sealers (Catalog No. 6570). An adhesive seal is approximately 3″×5″ and consists of a substrate material such as a thin foil or plastic film to which an adhesive has been applied. These seals can be applied by mechanical or manual means. The adhesive seal is removed by hand as there is no mechanical device for removal. The adhesive seal provides superior sealing properties in contrast to the plastic lid but has a number of deficiencies: (1) it can only be used once; (2) its adhesive can come in contact with the stored entity; and (3) during removal if any of the stored entity is on the inner surface of the seal, it may be problematic for worker safety. Additionally, if repeated seals are applied to the same multi-well plate the adhesive tends to build up, compromising the seals of successive applications. 
     Yet another form of lidding is the use of a heat-sealed cover such as the Abgene Easy Peel Polypropylene Sealing Film (Catalog No. AB-0745). A heat-sealed cover is 3″×5″ and consists of a substrate material such as polypropylene film. Most of the multi-well plates used for storage are polypropylene. With the application of heat and pressure by means of an Abgene Combi Thermal Sealer, the heat-sealed cover can be bonded to the polypropylene multi-well plate on the plate&#39;s upper surface. This seal is in essence a molecular bond caused by the melting of the polypropylene of the respective entities. As such, the heat seal cover sets the standard for multi-well plate sealing in terms of protection from both the ingress and egress of materials into the individual wells. It can be applied by manual and mechanical means such as the Abgene 1000, a semi-automatic applicator that uses roll stock of the Abgene Easy Peel Sealing Film. However, there is no mechanical device for the removal of heat-sealed covers. Heat-sealed covers cannot be reused. Each time a heat-sealed cover is attached to the plate there can be distortion on the standoffs of the individual wells, plus polypropylene remnants, affecting the quality of future seals on the same plate. 
     Examples of mechanical coverage of multi-well plates are disclosed in U.S. Pat. No. 5,342,581 entitled “Apparatus for Preventing Cross Contamination of Multi-Well Test Plates”, issued Aug. 30, 1994, in the name of Sanadi; U.S. Pat. No. 5,516,490 entitled “Apparatus for Preventing Cross Contamination of Multi-Well Test Plates”, issued May 14, 1996, in the name of Sanadi; and U.S. Pat. No. 5,741,463 entitled “Apparatus for Preventing Cross Contamination of Multi-Well Test Plates”, issued Apr. 21, 1998, in the name of Sanadi; the disclosures of which are incorporated herein by reference. 
     Another example of mechanical coverage of multi-well plates is disclosed in a brochure entitled “SealTite Microplate Cover” from TekCel Corporation, Martinsville, N.J. Additional information on the “SealTite Microplate Cover” can be found on the WWW site “www.tekcel.com/sealtite.htm”, Copyright ©1998 TekCel Corporation. 
     SUMMARY OF THE INVENTION 
     The subject invention is directed toward the repeated effective sealing and unsealing of multi-well plates utilizing mechanical manipulation. As noted above, there are a number of approaches to sealing multi-well plates. In the adhesive and thermal bonding approaches, a sealing mechanism is used to bond (either thermally or with an adhesive) a film over the wells of a multi-well plate to create an air and fluid barrier. While adequate for a single bonding instance, film approaches do not lend themselves to the requirement to access the multi-well plate multiple times in automation-based plate handling systems. 
     In the mechanically-based lid systems referenced above, the art describes the use of resilient materials which are pressed against the upper surface of the multi-well plate. These approaches also employ lids with clamps to secure the resilient material against the upper surface of the multi-well plate. An important requirement for this type of sealing is the ability to apply a normal force to the resilient material in a uniform manner. 
     In the invention described herein, the source of the compressive force is the lid itself by means of a curvilinear section of the lid which can provide a spring force when deformed, thereby applying a normal force more or less equally to the planar surface of a gasket which in turn seals the individual wells of a multi-well plate. Perpendicular side walls of the lid, which can be displaced laterally, are used to attach the lid to the multi-well plate. In this manner, a multi-well plate can be accessed multiple times by displacing the side walls and removing the cover. 
     The invention described herein is particularly adapted to work with robotic systems, which can use mechanical devices to secure the cover, apply it to a multi-well plate and remove the cover if desired. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view of a preferred embodiment of the invention showing a multi-well plate cover designated  1 , a lid  3 , side walls  7  of said lid  3 , notched tabs  12  with locator holes  11  of lid  3 , stacking locators (slots)  13  of lid  3 , and stacking lugs  17  of lid  3 . 
         FIG. 2  is an end view of a portion of multi-well plate cover  1  of  FIG. 1  designated by Roman numeral II in  FIG. 1 , showing lid  3  of multi-well plate cover  1  and an uncompressed gasket  23  disposed on the underside of lid  3 . 
         FIG. 3  is a perspective view of multi-well plate cover  1  of  FIG. 1  positioned over a multi-well plate  5  (shown in dashed line), with side walls  7  extended in preparation for attachment to multi-well plate  5 . 
         FIG. 4  is a perspective view of multi-well plate cover  1  of  FIG. 1  attached to a multi-well plate  5 . 
         FIG. 5  is an end view of multi-well plate cover  1 , showing a curvilinear spring section  19  of lid  3 , side walls  7  of lid  3 , stacking lugs  17  of said lid  3 , notched tabs  12  with locator holes  11  of lid, multi-well plate holders  15  of lid  3  and uncompressed gasket  23 . 
         FIG. 6  is a view similar to  FIG. 5  in which side walls  7  are laterally displaced outward. 
         FIG. 7  is a view similar to  FIG. 6 , in which multi-well plate cover  1  is pressed against a multi-well plate  5  to compress gasket  23  while side walls  7  remain laterally displaced. 
         FIG. 8  is a view similar to  FIG. 7 , in which multi-well plate cover  1  abuts and extends over multi-well plate  5  to compress gasket  23 . Side walls  7  secure multi-well plate cover  1  to multi-well plate  5  by means of multi-well plate holders  15 . 
         FIG. 9  is a perspective view showing means which could be used to perform the mechanical actions in attaching multi-well plate cover  1  to a multi-well plate  5 . Means  31  is shown for holding multi-well plate  5  during covering and uncovering; means  29  is shown for vertical movement of multi-well plate cover  1  and compression of multi-well plate cover  1 ; means  21  is shown for laterally displacing side walls  7 ; and means  27  is shown for gripping multi-well plate cover  1 . 
         FIG. 10  is a view similar to  FIG. 9  showing means  21  laterally displacing side walls  7  of lid  3  of multi-well plate cover  1 . 
         FIG. 11  is a view similar to  FIG. 10  showing means  29  vertically placing multi-well plate cover  1  on multi-well plate  5  held by means  31 , while means  21  maintains side walls  7  in a laterally displaced position. 
         FIG. 12  is a view similar to  FIG. 11  showing means  21  releasing side walls  7  of lid  3  of multi-well plate cover  1 , thereby securing multi-well plate cover  1  to multi-well plate  5 . 
         FIG. 13  is a view similar to  FIG. 12  showing means  29  vertically moving multi-well plate cover  1  attached to multi-well plate  5 . 
         FIG. 14  is a perspective view of several multi-well plate covers  1  in a stacked orientation utilizing stacking lugs  17  and stacking locators  13 . 
         FIG. 15  is a perspective view of several multi-well plate covers  1  and multi-well plates  5  in a stacked orientation utilizing stacking lugs  17  and stacking locators  13 . 
     
    
    
     DETAILED DESCRIPTION 
     Referring now more particularly to the drawings, a multi-well plate cover generally designated  1  in  FIG. 1  comprises a one-piece metal lid  3  which is fabricated by conventional metal fabrication techniques employing the cutting, stamping and/or bending of sheet metal. Suitable metals include steel, spring steel, stainless steel and stainless spring steel, preferably having a thickness between about 0.015″ and 0.024″. The metallic design provides a high degree of chemical resistance, especially to dimethyl sulfoxide, the solvent most commonly used in multi-well plate storage. Included as part of the lid  3  are the side walls  7 , integral to and formed at approximately 90 degrees to the top surface of lid  3 ; the notched tabs  12  with locator holes  11  integral with and extending from lid  3 ; stacking locators (slots)  13 ; and stacking locator lugs  17 . The slots  13  configured to accent corresponding lugs  17  of a second cover  1  stacked over a first cover  1  (see  FIG. 14 ) and thus align the covers laterally and longitudinally.  FIG. 2  shows a planar, uncompressed gasket  23  disposed on the convex side of a curvilinear section  19  of lid  3 , covering the surface thereof in sufficient area to fully engage the upper surface of a multi-well plate. Gasket  23  is preferably made from a low-durometer (Shore ISA or less) thermoplastic polymer or elastomer with a thickness of approximately 3/32″ or 0.100″. Gasket  23  is manufactured using standard injection molding or extrusion technology, and is preferable affixed by an adhesive to the bottom surface of the lid  3 . A preferred gasket material is SYNPRENE 5A manufactured by Polyone.  FIG. 1  also shows a longitudinal axis “L” of the cover  1  parallel to the side walls  7 . 
       FIG. 3  shows multi-well plate cover  1 , with side wall  7  laterally displaced in preparation for attachment to a multi-well plate  5 . The lateral displacement of side walls  7  is accomplished by mechanical means which is not shown in  FIG. 3  for illustrative purposes, but is shown in  FIGS. 10-12 . Similarly, the means for gripping multi-well plate cover  1  and for placing multi-well plate cover  1  on multi-well plate  5  are not shown in  FIG. 3  but are shown in  FIGS. 9-13 .  FIG. 4  shows multi-well plate cover  1  attached to a multi-well plate  5  (shown in dashed line) in the normal storage mode. 
       FIG. 5  is an end view of multi-well plate cover  1  and serves to illustrate the spring nature of multi-well plate cover  1 .  FIG. 6  is also an end view of multi-well plate cover  1  and depicts the displacement of side walls  7  of multi-well plate cover  1  in preparation for attachment to a multi-well plate (not shown in FIG.  6 ).  FIG. 7  shows a continuation of the process of attaching multi-well plate cover  1  to a multi-well plate  5  (in phantom) in which multi-well plate cover  1  is vertically pressed in the direction shown by arrows  18  onto multi-well plate  5 , causing the compression of uncompressed gasket  23  onto the upper surface of multi-well plate  5  while side walls  7  are outwardly extended.  FIG. 8  shows a continuation of the process of attaching the multi-well plate cover  1  to multi-well plate  5  in which multi-well plate cover  1  having been placed in contact with the upper surface of multi-well plate  5  has side walls  7  released into their normal position in which multi-well plate holders or clamps  15  engage a skirt  20  of multi-well plate  5  by moving in the direction of arrows  22 . The engagement of multi-well plate holders  15  with skirt  20  exerts a downward force on the ends of curvilinear section  19  to exert a compressive force on gasket  23 . In the embodiment of  FIG. 5  the multi-well plate holders or clamps  15  project (extend) inwardly from respective side walls  7  and each have a first portion  15 A proximal to the side wall from which the respective multi-well plate holder or clamp  15  extends and a second relatively distal portion  15 B having a convex transverse (lateral) cross-section (transverse relative to the longitudinal axis “L” of the cover  1 ) such that a distal end  15 C of the respective multi-well plate holder or clamp  15  is directed generally downwardly.  FIG. 5  also shows the stacking locator lugs  17  project downwardly from the side walls  7  a distance lower than the multi-well plate holders or clamps  15 .  FIG. 8  shows the pair of side walls  7  extend downwardly from the cover  1  a sufficient length for the multi-well plate holders or clamps  15  to contact the multi-well plate  5  from underneath by contacting a lower surface of the multi-well plate  5  in a grasping position. The multi-well plate holders or clamps  15  being located a sufficient distance from the upper edge of their respective side wall  7  to downwardly urge peripheral sides, of the cover  1 , integral with the sidewalls  7 . 
     FIG.  9  through  FIG. 13  show how a mechanical system such as an automated plate server would function with multi-well plate cover  1 . In  FIG. 9 , a multi-well plate  5  is shown held by means  31  in preparation for attachment of multi-well plate cover  1 . Means  21  is shown for laterally displacing side walls  7  in the direction shown by arrow  24 , and means  27  is shown for gripping multi-well plate cover  1 . Means  29  provides for the positioning of multi-well plate cover  1  in the direction shown by arrow  26 .  FIG. 10  shows means  21  laterally displacing side walls  7  in the direction shown by arrow  28  in preparation for attachment of multi-well plate cover  1 . Continuing with the sequence,  FIG. 11  shows multi-well plate cover  1  placed on the upper surface of multi-well plate  5 . This action also serves to compress the uncompressed gasket  23  shown in  FIG. 6  to produce the compressed gasket  23  shown in FIG.  7 . In  FIG. 12 , means  21  is shown releasing side walls  7  so the multi-well plate holders  15 , as  FIG. 8 , can engage and secure skirt  20  of multi-well plate  5 .  FIG. 13 , completing the sequence, shows multi-well plate cover  1  attached to multi-well plate  5  being moved by means  29 . In  FIG. 14 , a stack of multi-well plate covers  1  is shown arranged vertically. The interaction of the stacking locators  13  and stacking lugs  17  of adjacent multi-well plate cover  1  provides stability and geometric alignment of the stack. Because multi-well plate covers  1  are normally used in automation based systems, a geometrically constrained stack is important to the pick and place robotic manipulation. 
       FIG. 15 , a stack of multi-well plate covers  1  attached to multi-well plates  5  is shown arranged vertically. The interaction of stacking locators  13  and stacking lugs  17  of adjacent multi-well plate covers  1  provides stability and geometric alignment of the stack. The covered multi-well plate  5  is normally stored in storage units that are robotic material handling systems. Geometrically constrained stacks are important to the pick and place robotic manipulation.