Abstract:
A method for assembling a multiwell plate assembly, and a multiwell plate assembly prepared thereby, are provided. The method includes providing a lid for a multiwell plate body having at least one channel being formed therethrough; positioning the lid in proximity to a gasket member; applying sufficient negative pressure to the channel to draw the gasket member towards the lid; positioning the lid above a multiwell plate body, while continuing to apply negative pressure to the channel; emplacing the lid on the multiwell plate body; and, releasing the negative pressure from the channel. Advantageously, as will be recognized by those skilled in the art, various gasket members can be used in conjunction with the subject method, without altering the method. In this manner, gaskets can be selected based on their suitability for use with various biological and/or chemical samples which may be used in the bioassays.

Description:
CROSS REFERENCE TO RELATED APPLICATION  
       [0001]    This application claims priority of U.S. Provisional Patent Application No. 60/332,735, filed Nov. 19, 2001. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    This invention relates to multiwell plate assemblies and methods for assembling multiwell assemblies and, more particularly, to methods of sealing multiwell plate assemblies.  
         BACKGROUND OF THE INVENTION  
         [0003]    Multiwell plate assemblies are known in the prior art which are commonly used for bioassays. Each multiwell plate assembly includes a multiwell plate body having an array of wells formed therein, typically having 96, 384, or 1,536 wells. Because of the commonplace use of multiwell plate bodies, standard dimensions of the plates have been developed to facilitate use with pick-and-place machines. Each well is cup-shaped and accommodates various chemical and/or biological fluids and matters in conducting parallel bioassays, such as with parallel drug screening.  
           [0004]    In certain instances, it is desired to minimize, if not prevent, contamination of the bioassays from external sources, as well as, intermixing of the fluids/matters of the various wells. To this end, various techniques have been developed to seal the wells, including providing an emplaceable lid atop the multiwell plate body, and/or adhering a thin film across the open ends of the wells. These prior art techniques, however, suffer from several drawbacks, including having an excessively-loose seal provided by the emplaceable lid, and/or requiring adhesion of a film.  
         SUMMARY OF THE INVENTION  
         [0005]    To overcome deficiencies of the prior art, a method for assembling a multiwell plate assembly, and a multiwell plate assembly prepared thereby, are provided. The method includes providing a lid for a multiwell plate body having at least one channel being formed therethrough; positioning the lid in proximity to a gasket member; applying sufficient negative pressure to the channel to draw the gasket member towards the lid; positioning the lid above a multiwell plate body, while continuing to apply negative pressure to the channel; emplacing the lid on the multiwell plate body; and, releasing the negative pressure from the channel. Advantageously, as will be recognized by those skilled in the art, various gasket members can be used in conjunction with the subject method, without altering the method. In this manner, gaskets can be selected based on their suitability for use with various biological and/or chemical samples which may be used in the bioassays.  
           [0006]    In addition, the multiwell plate body may be formed with latchable members which may be formed to engage the multiwell plate body. As such, the lid may be formed to tightly latch onto the multiwell plate body and provide a compressive force against the gasket, thereby causing the gasket to form a tight seal with the multiwell plate body, without being adhered thereto. Preferably, the gasket is resilient, and may be formed of one or more layers, depending on the necessary sealing characteristics. The lid may be moved using any technique known to those skilled in the art.  
           [0007]    In another aspect of the invention, a vacuum may also be applied to the lid to allow the lid to be lifted and maneuvered separately, or together with, the gasket.  
           [0008]    These and other features of the invention will be better understood through a study of the following detailed description and accompanying drawings. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]    [0009]FIG. 1 is an exploded perspective view of a multiwell plate assembly having a lid formed in accordance with a first embodiment of the subject invention;  
         [0010]    [0010]FIG. 2 is an exploded side view of the assembly of FIG. 1;  
         [0011]    [0011]FIG. 3 is a bottom view of the lid shown in FIG. 1;  
         [0012]    [0012]FIG. 4 is a cross-sectional view taken along line  4 - 4  of FIG. 3;  
         [0013]    [0013]FIG. 5 shows the lid of FIG. 1 being connected to a source of negative pressure with the lid being positioned in proximity to a plurality of gasket members;  
         [0014]    [0014]FIG. 6 shows a gasket member being maintained on the lid due to negative pressure, with the lid being positioned in proximity to a multiwell plate body;  
         [0015]    [0015]FIG. 7 is a side view of an assembled multiwell plate assembly with the components shown in FIG. 1;  
         [0016]    [0016]FIG. 8 shows a second embodiment of a lid utilizable with the subject invention;  
         [0017]    [0017]FIG. 9 is an exploded perspective view showing a carrier for maneuvering the lid of FIG. 8;  
         [0018]    [0018]FIGS. 10A and 10B, respectively, show schematically actuation of the carrier;  
         [0019]    [0019]FIG. 11 is a lower perspective view of a vacuum pick apparatus for use with the embodiment of the lid shown in FIG. 8;  
         [0020]    [0020]FIG. 12 is a bottom plan view of the vacuum pick apparatus;  
         [0021]    [0021]FIG. 13 is a cross-sectional view of the vacuum pick apparatus taken along line  13 - 13  of FIG. 12;  
         [0022]    [0022]FIG. 14 is an exploded perspective view showing a gasket member together with the lid of the second embodiment and the vacuum pick apparatus; and,  
         [0023]    [0023]FIG. 15 is an exploded perspective view showing a third embodiment of a lid utilizable with the subject invention having a top portion shaped convexly inwardly. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0024]    With reference to FIGS.  1 - 7 , a first embodiment of the subject invention is depicted wherein a multiwell plate assembly  10  is prepared. The multiwell plate assembly  10  includes a lid  12 , a gasket member  14 , and a multiwell plate body  16 . The multiwell plate body  16  is formed in accordance with conventional principles, wherein an array of wells  18  are defined therein. The dimensions of the multiwell plate body  16  are such so that the multiwell plate body  16  is usable with known pick-and-place machines.  
         [0025]    The gasket member  14  is preferably resilient and may be formed of one or more layers. The selection of the constituent material(s) for the layer(s) of the gasket member  14  may be selected based on the material&#39;s suitability for use with the biological and/or chemical substances which may be disposed within the wells  18  of the multiwell plate body  16 . With reference to FIG. 2, by way of non-limiting example, the gasket member  14  may have three layers  20 ,  22 ,  24 , with one or more of the layers  20 - 24  being resilient, and/or having good sealing and/or barrier (e.g., moisture; gas) properties. Any gasket material known to those skilled in the art which is suitable for use with bioassays may be utilized in the gasket member  14 .  
         [0026]    As described below, the lid  12  may be formed in various manners. FIGS.  1 - 7  depict a first embodiment of the lid  12 , wherein a boss  26  extends upwardly from a top surface  27  of a top  28  of the lid  12 . As best shown in FIGS. 3 and 4, a channel  30  extends from an opening  32  formed at an end of the boss  26 , with the channel  30  coming into communication with a plurality of secondary channels  34  that extend through the top  28  and terminate at openings  36  formed in a lower surface  38  of the top  28 .  
         [0027]    In a preferred embodiment, latchable members  40  extend from the lower surface  38  which are formed to engage, and latch onto, the multiwell plate body  16 . Each of the latchable members  40  includes a deflectable, downwardly-extending arm  42  which terminates at an inwardly-extending tab  44 , with this configuration generally defining a L-shape. Preferably, the latchable members  40  are integrally formed with the lid  12  and formed of a resilient material, preferably a thermoplastic. A sufficient number of the latchable members  40  is provided to facilitate tight latching of the lid  12  onto the multiwell plate body  16 . In a preferred arrangement, each of the corners of the lid  12  is provided with one of the latchable members  40  to generate a perimetric holding force.  
         [0028]    With reference to FIGS.  5 - 7 , the method of preparing the multiwell plate assembly  10  is depicted therein. As shown in FIG. 5, in a first step, a source of negative pressure (such as a hose)  46  is connected to the boss  26 , and the lid  12  is positioned in proximity to a supply of the gasket members  14 . It is preferred that inner dimensions defined by the latchable members  40  be selected so as to permit passage therethrough of the gasket members  14 . Sufficient negative pressure is applied such that one of the gasket members  14  is drawn towards the lower surface  38  of the lid  12 , and preferably drawn into abutting contact therewith. The negative pressure is applied through the channel  30  and the secondary channels  34  to preferably engage the gasket member  14  at multiple locations via the openings  36 . The openings  36  are positioned to facilitate a generally even application of the negative pressure.  
         [0029]    With the application of negative pressure being maintained, the lid  12  is positioned above the multiwell plate body  16  (FIG. 6), and relative movement therebetween is generated such that the latchable members  40  latch onto the bottom of the multiwell plate body  16 , as shown in FIG. 7. The movement of the lid  12  may be achieved through any technique known to those skilled in the art, including a pick-and-place apparatus. To allow for mounting of the lid  12  onto the multiwell plate body  16 , the latchable members  40  may be caused to deflect outwardly (as shown in dashed lines in FIG. 6) through contact with the multiwell plate body  16 , or be deflected outwardly by a guide or tool (not shown).  
         [0030]    In an assembled state, the lid  12  and the multiwell plate body  16  encompass a volume therebetween in which the gasket member  14  resides. Preferably, the gasket member  14  is maintained in at least a partially compressed state to provide a tight seal for the multiwell plate assembly  10 . As is readily apparent, the subject invention can be used in an automated technique for assembling multiwell plate assemblies, where the specific type of gasket may be readily changed during the assembly procedure.  
         [0031]    With reference to FIG. 8, a second embodiment of the lid utilizable with the subject invention is depicted therein and generally designated with the reference numeral  100 . The lid  100  includes a top portion  102  and downwardly extending sides  104 . Channels  106  are defined through the top  102  at various locations thereabout. Preferably, the channels  106  are straight holes formed through the top portion  102 .  
         [0032]    The sides  104  are outwardly deflectable in the same manner as the deflectable members  40  described above, so as to allow for latching onto a multiwell plate body. Relief apertures  108  may be provided to enhance the deflectability of the sides  104 . Lower lips  110  extend from the bottom edges of the sides  104  inwardly and are shaped and configured to latch onto the bottom of a multiwell plate body. Depending on the method used to handle the lid  100 , one or more tabs  112  may be provided which extend from the top portion  102 .  
         [0033]    With reference to FIGS. 9, 10 a  and  10   b , an apparatus  114  is shown for maneuvering the lid  100  in preparing a multiwell plate assembly. The apparatus  114  includes a plate  116  from which extends a boss  118 . A channel  120  is formed to extend through the boss  118  and through the plate  116 . L-shaped members  122  are pivotally mounted to support blocks  124  affixed to the plate  116 . The L-shaped members are positioned and shaped to slip under the tabs  112  of the lid  100  in providing support thereof in movement. Linkages  126  are rigidly connected to each of the L-shaped members  122  and to a control link  128  pivotally mounted to a control block  130 . As shown in FIGS. 10 a  and  10   b , upon rotation of the control link  128 , the linkages  126  are displaced, thereby causing the L-shaped members  122  to pivot and be radially displaced outwardly. As such, the L-shaped members  122  can be manipulated to be positioned below the tabs  112 . Preferably, the tabs  112  have inner edges  132  which limit excessive inward movement of the L-shaped members  122 , with outward movement thereof being unobstructed.  
         [0034]    Again, with reference to FIG. 9, the apparatus  114  may be positioned above the lid  100  and caused to lift the lid  100  with selective placement of the L-shaped members  122  below the tabs  112 . Thereafter, negative pressure may be introduced through the channel  120 , and through the channels  106  in the lid  100 , to draw a gasket member  14  towards the lid  100 , and preferably into contact therewith. Thereafter, the lid  100  may be positioned above a multiwell plate body  16  with the lid  100  having its sides  104  latched thereonto. The application of the negative pressure through the channel  120  is then discontinued, and the L-shaped members  122  are caused to displace radially to allow for the apparatus  114  to separate from the lid  100 .  
         [0035]    With reference to FIGS.  11 - 14 , a vacuum pick apparatus  200  is shown which may be used to maneuver the lid  100  along with a gasket  14 . Referring to FIGS.  11 - 13 , the apparatus  200  includes a plate portion  202  from which extend a first boss  204  and a second boss  206  having channels  208  and  210 , respectively, extending therethrough and through the plate  202 . A separating member  212 , preferably resilient, is mounted to a lower surface  214  of the plate  202  so as to bound the channel  208 . The area bounded within the separating member  212  constitutes a first zone  216 , whereas, the area beyond the separating member  212  constitutes a second zone  218 . A sealing member  220 , preferably resilient, may be provided that bounds the outer perimeter of the second zone  218 . As best shown in FIG. 13, the first zone  216  is in communication with the channel  208 , and the second zone  218  is in communication with the channel  210 . By connecting separate sources of negative pressure to the bosses  204  and  206 , negative pressure within the first zone  216  can be controlled independently from the second zone  218 . As shown in FIG. 11, the two sources can be connected through a common conduit  222  which passes through a hood  224  with separate lines being fixed to the bosses  204  and  206 .  
         [0036]    Referring to FIG. 14, the apparatus  200  may be used to maneuver the lid  100  of the second embodiment of the subject invention. For optimum performance with the apparatus  200 , it is preferred that the channels  106  be formed in the lid  100  so as to define an intact engaging surface  226  dimensioned larger than the first zone  216 . Accordingly, in use, the apparatus  200  may be positioned above the lid  100  and negative pressure may be applied to the first zone  216  which can act on the engaging surface  226  and cause the lid  100  to be drawn to the apparatus  200 . Separately, negative pressure may be applied to the second zone  218  which passes through the channels  106  to draw any gasket member  14  towards the lid  100 . The gasket  14  and the lid  100  can be selectively lifted in this manner by the apparatus  200 . As can be seen in FIG. 14, the tabs  112  need not be provided on the lid  100 , such as, for example, when used with the apparatus  200 .  
         [0037]    A third embodiment of a lid utilizable with the subject invention is depicted in FIG. 15 and designated with the reference numeral  300 . The lid  300  may be formed as the lid  12  or the lid  100  described above, but with a top portion  302  which is shaped convexly downwardly in a natural state. The top portion  302  may be shaped convexly downwardly along its longitudinal axis  304 , in a direction transverse to the longitudinal axis  304 , or a combination thereof. Accordingly, upon latching the lid  300  onto a multiwell plate body, the top portion  302  becomes stressed, thereby providing additional holding force for pressing against a gasket member in generating a better seal with a multiwell plate body.  
         [0038]    Various changes and modifications can be made in the present invention. It is intended that all such changes and modifications come within the scope of the invention as set forth in the following claims.