Abstract:
A well plate assembly includes a well plate with a base wall, a peripheral wall extending up from the base wall and spaced inwardly from the outer periphery of the base wall. A well array is formed on the base wall at locations inwardly from the peripheral wall. A lid is mounted on the peripheral wall of the well plate. The lid and the peripheral wall have areas that are indented from the outer periphery of the base wall to facilitate manipulation by robotic stacking equipment. The well plate and the lid further include substantially registered robotic gripper plates aligned with the outer periphery of the base wall to facilitate manipulation of the assembled well plate and lid by robotic grippers.

Description:
RELATED APPLICATIONS  
       [0001]     This application claims the benefit of U.S. Provisional Application No. 60,557,977 filed on Mar. 31, 2004 which is hereby incorporated by reference in its entirety. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     1. Field of the Invention  
         [0003]     The invention relates to an assembly of a micro-plate and a lid that can be manipulated by robotic stackers and/or by robotic arms.  
         [0004]     2. Description of the Related Art  
         [0005]     Many laboratory procedures require analysis to be performed on chemicals or biological specimens, such as tissue cultured cells, proteins and enzymes. The specimen may be deposited in a liquid growth medium or buffer. An analysis then is performed after a specified time which will vary depending upon the nature of the biological specimen and the type of analysis that is to be performed.  
         [0006]     The chemical or biological specimen often is deposited in a micro-plate. The plate may be moved from a first location where the specimen is deposited to a second location where the specimen is permitted to grow or otherwise develop over a specified time. The specimen then will be moved to another location for analysis.  
         [0007]     The typical micro-plate for performing the above-described laboratory analysis is rectangular with a bottom wall, upstanding sidewalls and an open top. A lid may be mounted to the open top of the sidewalls to control evaporation. The footprint defined by the bottom wall of the plate generally is one of several standard sizes dimensioned to accommodate robotic handling equipment in a laboratory. Other characteristics of the plates, however, vary considerably from one manufacturer to another and from one type of analysis to another. One significant difference relates to the number of biological specimens that can be accommodated in the plate. For example, some plates define a single large reservoir in which tissue cultures may grow. Other laboratory analysis can be carried out with low volume assays. Thus, a single plate can accommodate a plurality of wells into which liquid and/or tissue cultures can be deposited. The plurality of wells typically are arranged in a rectangular matrix with formats that conform to standard formats for pipettes. For example, some standardized micro-plates include 2, 4, 8, 24, 96, 384, 1,536, 3456, or 4,080 wells.  
         [0008]     A micro-plate with an appropriate number of wells can be molded unitarily in a dedicated mold for the particular number of wells. However, some micro-plates are formed from plural parts that are assembled together. For example, the micro-plate may include a unitary frame and a separate unitary well array with a pattern of wells. The well array with an appropriate number of wells is assembled to the standard frame.  
         [0009]     Micro-plates often are stored in stacked arrays in the laboratory while the tissue or other biological material in the wells is permitted to grow. The micro-plates then are moved from the stacked array robotically and are transferred to appropriate work stations for analysis. There are two different approaches for robotically transferring the micro-plates from the stacked array to the work station for analysis. One option employs robotic gripping devices with grippers or fingers that grab opposite sides of the plates for transfer to a work station. Robotic grippers generally function to grab the top plate in a stacked array. The robotic grippers then lift the plate from the top of the stack and transfer the plate to the appropriate work station. Other laboratory devices stack the micro-plates in a magazine that permits the plates to be removed sequentially from the bottom of the stacked array. More particularly, the stack of plates may rest on two sets of solenoid controlled pins or levers that can retract and extend. Retraction of the pins releases the bottom plate in the array. The pins then extend to catch beneath the next plate, while the remaining stack of plates indexes down one position. The bottom plate is released onto an elevator lift that rises up from a location beneath the stacked array to engage the plate and to keep the plate aligned horizontally, thereby avoiding spills. The plate then is lowered by the elevator lift onto a shuttle that moves the plate to the appropriate work station.  
         [0010]     Robotic grippers must have specialized features for contacting the plate. These features may include gripper pads, gripper points, gripper fingers or a serrated edge. These gripping features typically require smooth uninterrupted flat surfaces on the plate and/or the lid for proper engagement. Many plates can be handled efficiently by robotic grippers when the plate is stored independently of a lid. However, robotic grippers are likely to encounter gripping difficulties when the plate is being manipulated with the lid in place. More particularly, the known plate/lid assemblies are not configured for simultaneously gripping the lid and the plate in a manner that will hold the plate and lid in their assembled condition. There is the potential that the robotic gripper will grip only the lid or that the robotic gripper will grip portions of the lid below the top-most plate in a stacked array. Thus, many plates are stacked without lids to facilitate manipulation by robotic grippers. However, the absence of a lid significantly increases evaporation rates.  
         [0011]     Robotic stackers that remove plates sequentially from a stacked array also encounter problems with lids. More specifically, the stacker is not well suited to distinguishing between a plate and a lid. Thus, the stacker may drop just the plate from the magazine, while retaining the lid for the dropped plate. The next cycle, then will drop the retained lid.  
         [0012]     In view of the above, it is an object of the subject invention to provide a plate and lid assembly that is well suited to robotic handling by both robotic grippers and stackers.  
         [0013]     It is another object of the subject invention to provide a micro-plate molding method for efficiently producing plates with a plurality of different well arrays.  
         [0014]     A further object of the subject invention is to provide a plate and lid assembly that resists evaporation and facilitates robotic manipulation.  
       SUMMARY OF THE INVENTION  
       [0015]     The invention is a well plate assembly that is suited for automated handling by robotic equipment. The assembly includes a well plate and a lid. The well plate includes a substantially rectangular base wall with opposite end edges and opposite side edges extending between the end edges. The end edges and the side edges of the base wall define a footprint conforming to a standard specified footprint for the laboratory equipment with which the assembly is to be used. The well plate further includes a well array that may be formed unitarily with the base wall. The well array includes at least one open-topped well for receiving liquid that will be subject to analysis in the laboratory. In many embodiments, the well array will include a rectangular matrix of open-topped wells, with the particular pattern of wells in the matrix conforming to the laboratory equipment with which the plate assembly is used. The well plate preferably includes a peripheral wall with opposite end walls spaced inwardly from the end edges of the base wall and opposite sidewalls spaced inwardly from the side edges of the base wall. The sidewalls meet the respective end walls at four corners. The end walls and/or the sidewalls preferably are formed with indentations for stacker compatibility. More particularly, the indentations are disposed to align with the solenoid indexing pins of the stacker.  
         [0016]     The well plate may further include robotic gripper pads that project up from the side edges and/or the end edges of the bottom wall. The robotic gripper pads define relatively large outer peripheral areas that can be engaged by robotic grippers for lifting the well plate assembly from the top of a stacked array of well plate assemblies.  
         [0017]     The lid of the well plate assembly includes a top wall and a peripheral frame. The top wall may include a substantially planar center panel that is recessed with respect to at least portions of the peripheral frame. The center panel may be dimensioned and configured for support on the top of the well array so that the center panel of the top wall of the lid closes the open tops of the wells. The peripheral frame of the top wall is configured to rest on top edges of the peripheral wall of the well plate. The lid further includes a peripheral skirt configured to nest with the peripheral wall of the well plate. Thus, the peripheral skirt of the lid is formed with indentations that will nest with the indentations on the peripheral wall of the well plate. Accordingly, the indentations in the peripheral skirt of the lid will align with the solenoid indexing pins of the stacker.  
         [0018]     The lid of the well plate assembly may also include robotic gripper pads that register with the robotic gripper pads that project up from the bottom wall of the well plate. Thus, the outer surfaces of the robotic gripper pads on the lid cooperate with outer surfaces of the robotic gripper pads of the well plate to define regions that may be engaged by robotic grippers.  
         [0019]     The subject invention also relates to a method for forming a well plate. The method includes injection molding the well plate with a first mold plate corresponding to the base wall of the well plate and a plurality of second mold plates corresponding to a plurality of different well arrays. Each of the plurality of second mold plates is configured to form one of the specified matrices of wells compatible with laboratory equipment. The method comprises selecting an appropriate second mold plate for use with the first mold plate to achieve the appropriate matrix of wells. The first and second mold plates then are secured in opposed relationship to one another and a resin is injected into the cavity defined between the first mold plate and the selected second mold plate. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0020]      FIG. 1  is an exploded perspective view of a well plate and lid in accordance with the subject invention.  
         [0021]      FIG. 2  is a perspective view of the well plate.  
         [0022]      FIG. 3  is a top plan view of the well plate.  
         [0023]      FIG. 4  is a prospective view of the well plate and lid in their assembled condition.  
         [0024]      FIG. 5  is a cross-sectional view taken along line  5 - 5  in  FIG. 4 .  
         [0025]      FIG. 6  is a cross-sectional view taken along line  6 - 6  in  FIG. 4 . 
     
    
     DETAILED DESCRIPTION  
       [0026]     A plate assembly in accordance with the invention is identified generally by the numeral  10  in  FIGS. 1 and 4 - 6 . The plate assembly  10  includes a well plate  12  and a lid  14 .  
         [0027]     The well plate  12  is molded unitarily from a resin material such as polypropylene, polystyrene cyclic olfin, or polycarbonate. Well plate  12  includes a substantially planar base wall  16  and a downwardly depending skirt  20 . Skirt  20  includes first and second substantially parallel ends  22  and  24  and first and second substantially parallel sides  26  and  28 . Ends  22  and  24  are of substantially equal length and are substantially linear. Sides  26  and  28  also are of substantially equal length and are substantially linear. However, sides  26  and  28  are longer than ends  22  and  24 . Thus, skirt  20  defines a substantially rectangular footprint for well plate  12 . The dimensions of the footprint defined by skirt  20  of well plate  12  are selected in accordance with standardized dimensions for multi-wall plates and the laboratory equipment with which such plates are used.  
         [0028]     Well plate  12  is characterized further by a well array  30  formed unitarily with base wall  16 . Well array  30  is generally rectangular and is spaced inwardly from first and second ends  22  and  24  and first and second sides  26  and  28  of skirt  20 . Well array  30  includes a substantially planar top surface  32  aligned substantially parallel to base wall  16 . Top surface  32  of well array  30  is characterized by a plurality of upwardly open wells  34  that extend down toward base wall  16 . Wells  34  are arranged in well array  30  to define a substantially rectangular matrix. The number of wells  34  may vary depending upon the types of tests that will be carried out with plate assembly  10  and the types of laboratory equipment that will be employed to carry out such tests. However, the matrix of wells  34  typically will conform to a pattern of pipettes or other sample accommodating equipment. Thus, well array  30  may have 1; 2; 4; 8; 24; 96; 384; 1,536; 3,456; 4,080 or some other standardized number of wells  34 .  
         [0029]     Well plate  12  further includes an outer peripheral sidewall  40  that extends perpendicularly up from base wall  16  at locations spaced outwardly from well array  30 . Peripheral sidewall  40  includes a top edge  41  that defines a plane aligned substantially parallel to top surface  32  of well array  30 . Top surface  32  of well array  30  is recessed relative to top edge  41  of peripheral sidewall  40  as shown most clearly in  FIGS. 1, 2 ,  5  and  6 . Peripheral sidewall  40  includes first and second end sections  42  and  44  respectively and first and second sidewall sections  46  and  48  respectively. End wall sections  42  and  44  and sidewall sections  46  and  48  are not linear. Rather, first end wall section  42  includes an indentation  43  disposed symmetrically thereon. Portions of first end wall section  42  defined by indentation  43  are spaced from first end  22  of peripheral skirt  20  by distance “a”. In contrast, portions of end wall section  42  closer to sidewall sections  46  and  48  are spaced a distance “b” from first end edge  22 . Distance “a” exceeds distance “b”.  
         [0030]     Second end wall section  44  of peripheral side wall  40  is substantially symmetrical with first end wall section  42 . More particularly, second end wall section  44  includes a symmetrically disposed indentation  45 . First and second sidewall sections  46  and  48  also are characterized by symmetrically disposed indentations  47  and  49  respectively.  
         [0031]     First end wall section  42  meets first and second sidewall sections  46  and  48  at well defined right angle corners. However, second end wall section  44  meets sidewall sections  46  and  48  at truncated corners to provide a rotational orientation for well plate  12 .  
         [0032]     Multi-well tray  12  further includes first and second robotic gripper pads  56  and  58  that extend perpendicularly up from base wall  18  at locations aligned with first and second sides  26  and  28  of skirt  20 . Robotic gripper pads  56  and  58  have top edges that lie in a plane parallel to the plane defined by top edge  41  of outer peripheral sidewall  40  of well plate  12 , but disposed closer to base wall  16 . Robotic gripper pads  56  and  58  also have outer surfaces  57  and  59  respectively that are parallel to one another.  
         [0033]     Lid  14  is formed unitarily from a resin material, and preferably the same material as well plate  12 . Lid  14  includes substantially planar central panel  60  and a peripheral frame  62 . Peripheral frame  62  has a top wall  64  that is parallel to central panel  60  but offset upwardly from central panel  60 . Peripheral frame  62  also includes a skirt  66  that depends down from top wall  64  for telescoping over peripheral sidewall  40  of well plate  12 . Frame  62  is configured so that top wall  64  can rest on and closely engage top edge  41  of peripheral sidewall  40  of well plate  12  to control evaporation of liquid from well array  30 . Additionally, skirt  66  extends from top wall  64  of frame  62  a distance less than the height of peripheral sidewall  40  of well plate  12 . Thus, skirt  66  will not touch base wall  16  of well plate  12 , and top wall  64  is assured of sealing against top edge  41  of peripheral side wall  40 . In this embodiment, central panel  60  does not rest on top surface  32  of well array  30  to seal individual wells  34 . However, other embodiments may have a lid configured to close each well  34 . Skirt  66  includes first and second end walls  72  and  74  and first and second sidewalls  76  and  78 . First and second end walls  72  and  74  are formed respectively with indentations  73  and  75  that nest with indentations  43  and  45  of peripheral sidewall  40  of well plate  12 . Similarly, first and second sidewalls  76  and  78  are formed with indentations that nest respectively with indentations  47  and  49  of peripheral sidewall  40  of well plate  12 . Indentations  73 ,  75 ,  77  and  79  are disposed at locations that will align with the solenoid pins of a robotic stacker so that plate assembly  10  can be dropped efficiently from the bottom of a stacked array without separating lid  14  from well plate  12 .  
         [0034]     Lid  14  further includes robotic gripper pads  86  and  88  that project from frame  62 . More particularly, robotic gripper pads  86  and  88  extend down from the plane defined by top wall  64  of frame  62 . Robotic gripper pads  86  and  88  have outer surfaces  87  and  89  that align respectively that with outer surfaces  57  and  59  of robotic gripper pads  56  and  58  on well plate  12 . Additionally, robotic gripper pads  86  and  88  are dimensioned to be spaced slightly from the top edges of robotic gripper pads  52  and  54  when lid  14  rests on well plate  12 . Outer surfaces  87  and  89  of robotic gripper pads  86  and  88  can be gripped by robotic grippers substantially simultaneously with outer surfaces  57  and  59  of robotic gripper pads  56  and  58  for lifting plate assembly  10  from the top of a stack of such plate assemblies.  
         [0035]     The number of wells required for a well plate vary substantially based on the volume of liquid required for a particular laboratory test and in accordance with the specifications of the laboratory equipment. As noted above, the number of wells employed on well plates vary from 1 to 4,080 in accordance with certain established standards. Some well plates are manufactured by molding an appropriate well array and then mounting the molded well array to a base that has a uniform footprint. The mounting can be by purely mechanical means, such as a snap fit or by application of adhesive or ultrasonic welding. Other well plates are manufactured by dedicated mold pairs that unitarily mold a well plate of appropriate dimensions. The well plate  12  of the subject invention preferably is molded with a first mold defining a standard base wall  16  and a mating second mold defining a standard periphery wall  40  of the well plate  12 . Additionally, the mold assembly includes a plurality of mold inserts, any one of which can be mounted in the mating second mold for forming a well array  30  with an appropriate number of wells  34 . Thus, post-molding assembly steps can be avoided and molding equipment can be adapted at low cost for producing plate assemblies  10  with a specified number of wells  34  with a substantially reduced cost, as compared to costs associated with dedicated molds.  
         [0036]     Plate assembly  10  is employed by depositing liquid specimens into wells  34  of well array  30  by robotic equipment that employs an array of pipettes corresponding in number and location to wells  34 . Lid  14  then is telescoped onto well plate  14 . In this mounted condition, top wall  64  of frame  62  will rest on top edge  41  of peripheral end wall  40  of well plate  12  to substantially seal wells  34  to prevent or minimize evaporation. Indentations  73 ,  75 ,  77  and  79  of lid  14  will nest with indentation  43 ,  45 ,  47  and  49  of well array  30  and will be spaced inwardly from edges  22 ,  24 ,  26  and  28  of skirt  20  of well plate  12 . Additionally, robotic gripper pads  86  and  88  of lid  14  will align with robotic gripper pads  56  and  58  of well plate  12 . Outer surfaces  87  and  89  of robotic gripper pads  86  and  88  will align with outer surfaces  57  and  59  of robotic gripper pads  56  and  58  on well plate  12 .  
         [0037]     Plate assemblies  10  may be stacked in a laboratory for a selected time while biological samples in the respective wells  34  are permitted to grow or react. Plate assemblies  10  then can be removed sequentially from the bottom of a stacked array by actuation of solenoid pins of a robotic stacker. More particularly, the pins will align with the indentations  73 ,  75 ,  77  and/or  79 . The pins will retract sufficiently to allow well plate assembly  10  to drop onto the elevator lift of the robotic stacker. The pins then will quickly extend to engage the next lowest well plate assembly  10 . The indentations  73 ,  75 ,  77  and  79  ensure that the pins will engage the next sequential plate assembly  10  without separating lid  14  from its respective well plate  12 . The ability to stack and process well plates  12  with lids  14  in position substantially reduces evaporation. Assemblies  10  also can be used with robotic grippers that function to engage robotic gripper pads  56 ,  58 ,  86  and  88  from opposed sides of assembly  10  for lifting and transporting assembly  10  to a location for analysis.