Patent Publication Number: US-6669911-B1

Title: Frame for multiwell tray

Description:
FIELD OF THE INVENTION 
     This invention relates to multiwell trays or titre plates used as containers for chemical or biochemical reactions, such as for polymerase chain reaction (PCR) and more particularly, to a rigid frame for holding a plastic PCR plate planar. 
     BACKGROUND OF THE INVENTION 
     Molecular biological reactions are often carried out in trays, or titre plates, containing an array of wells. The polymerase chain reaction (PCR) is one such reaction. In it, tiny quantities of materials are processed through a long sequence of steps, including being heated with a heater block. Multiwell trays increase throughput by allowing many reactions to be performed at one time. 
     PCR has become such a routine procedure that cutting the cost of the apparatus by even small increments is important. Wells can be machined out of a rigid slab of material to form a multiwell plate, but injection molding has been found to produce a somewhat acceptable, and cheaper, plate. U.S. Des. Pat. No. D420,743 (Monks) is exemplary of plastic injection-molded trays. 
     The various liquid reactants can be individually inserted into each well by a hand-operated micropipettor. Typically, though, an automated dispenser performs this repetitive operation. Salomon et al. disclose (U.S. Pat. No. 4,478,094) such a dispenser. The Salomon apparatus has a row of dispensing tips that fill an entire row of wells on a tray. Other liquid dispensers have tips arranged in a matrix, which may be large enough to fill all the wells on a tray with one dispense cycle. 
     Ganged dispensers require that the trays have consistent dimensions and be planar. The longitudinal axes of the wells must be paraller to the direction of travel of the dispenser head, otherwise the dispensing tips may miss one or more of the wells, or jam against the walls of some of the wells such that the tray is picked up by the tips as the dispensing head retracts. This causes a “crash” of the dispenser, which must be reset by the operator and may result in loss of the samples contained in a tray. 
     Although multiwell trays molded from polyethylene or polypropylene are superior in some ways, they are likely to have residual internal stresses from the molding operation. These stresses often cause warping of the tray immediately after ejection from the mold, or may cause delayed warping or dimensional change after thermal cycling of the tray. As a result of warping of the trays, the trays&#39; handling features for automated handling have large variations in their positions. This causes problems for automated handling equipment. In some applications, trays are stacked such that the positioning variations are compounded and the problems are greater. 
     Therefore, there is a need for a means for causing multiwell trays, injection molded from flexible plastic, to have the desirable qualities of rigid trays. Such a means preferably would hold the top surface of the tray planar, reduce dimensional variation of the tray, and not interfere with use of the tray. 
     SUMMARY OF THE INVENTION 
     The present invention is a rigid frame for holding a multiwell tray planar on top. By holding the tray top planar, the wells are kept parallel to each other so that a gang dispenser can be used without crashes. 
     In an exemplary embodiment, the multiwell tray has a rectangular tray top with wells suspended from it, a side wall projecting downward, and a flange around the base of the side wall forming a base that the tray stands on. There are apertures spaced around the side wall. The frame for holding this tray is a rectangular frame of a rigid material with low thermal expansion. 
     The frame has barbs spaced around its interior. When the frame is placed over the tray and pressed downward relative to the tray, the barbs snap into the apertures to retain the tray securely in the frame. Because the frame is attached at points around the perimeter of the tray, it holds the tray top planar, causing the long axes of the wells to be parallel, and perpendicular to the plane of the tray top. The frame adds weight to the tray, thus keeping it from being tipped or knocked over. 
     The frame remains on the tray throughout whatever processing the materials in the wells are undergoing. In the case of PCR, particularly, the process may include several thermal excursions. The frame constrains the tray from warping and keeps the outside dimensions of the tray/frame combination fairly constant. The frame includes features, such as machined indentations, that allow the frame to be manipulated by automated handlers. One aspect of the invention is that the tray can be installed in the frame in only one orientation. Index marks on the exterior of the frame indicate the orientation and can be used to allow automated handling in only one orientation, making it easier to keep track of well contents. 
    
    
     The invention will now be described in more particular detail with respect to the accompanying drawings in which like reference numerals refer to like parts throughout. 
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a perspective view, partly exploded, of an exemplary frame and multiwell tray. 
     FIG. 2 is a top plan view of the tray and frame of FIG. 1, with the tray installed in the frame of the present invention. 
     FIG. 3 is a cross-sectional view taken on line  3 — 3  of FIG. 2, through the tray top, wells, and retaining means. 
     FIG. 4 is an enlarged perspective view of a barb  41  from upper right of FIG.  1 . 
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a perspective view, partly exploded, of an exemplary frame  10  and multiwell tray  80 . Frame  10  generally comprises frame wall  20 , having outward-facing exterior surface  30 , inward-facing interior surface  40 , and retaining means  25  for retaining tray  80  inside frame  10 . 
     FIG. 2 is a top plan view of tray  80  and frame  10  of FIG.  1 . FIG. 3 is a cross-sectional view taken on line  3 — 3  of FIG. 2, through tray top  82  and wells  91  of tray  80 , and through frame  10  at retaining means  25 . 
     Multiwell tray  80  generally comprises a plurality of wells  91  for containing chemical reactants connected by tray top  82 . Tray top  82  comprises perimeter  82 P, peripheral wall  85  connected to perimeter  82 P and enclosing it, and retaining features  98  for engaging frame retaining means  25 . In the exemplary embodiment, peripheral wall  85  extends downward from tray top  82 . Wells  91 , best seen in FIG. 3, include an opening surrounded by rim  92 , downwardly converging walls  94 , and a closed bottom  93 . Each well  91  has a longitudinal axis  99 . 
     Tray  80  is typically an injection molded one piece tray  81 , made from a nonreactive, flexible plastic, such as unfilled polypropylene or polyethylene. Tray top  82  of injection-molded tray  81  is thin, flexible, and substantially planar. Peripheral wall  85  of tray  81  may be vertical, or, more typically, have a slight draft angle to allow easier removal from the mold. If there is a draft angle, the length and width of peripheral wall  85  are greater at bottom part  87 B than at top part  87 T. 
     Peripheral wall  85  includes retaining features  98 , such as several apertures  86 . Apertures  86  are windows removed from peripheral wall  85 , exposing sections through peripheral wall  85 . In the exemplary embodiment, apertures  86  are located adjacent perimeter  82 P of tray top  82 . Thus, each aperture  86  is not symmetrical about a horizontal axis because the top wall of aperture  86  is the bottom surface of tray top  82 . 
     Frame  10  for holding tray top  82  planar is made of a rigid material, preferably with low thermal expansion and little potential for contaminating the contents of wells  91 . Frame  10  may be machined from aluminum 6061 or similar alloy, or one of the 300 series alloys of stainless steel. Anodizing an aluminum frame  10  after machining results in a more durable, less reactive, and more decorative frame  10 . It is envisioned that frame  10  could also be molded from an engineering plastic with relatively low thermal expansion, such as polycarbonate. 
     Since frame  10  is generally used with automated handling means, a low friction surface is desirable to minimize wear of the handling means. The cost of manufacturing frame  10 , including material and labor, is preferably low, but it is not the major consideration. Because tray  81  is disposable, and frame  10  can be reused indefinitely, it is desirable to build into frame  10  any attributes that allow disposable tray  81  to be lower in cost. 
     Frame  10  includes retaining means  25 , such as a plurality of barbs  41 , which protrude from and are spaced apart on interior surface  40 , for engaging apertures  86 . Referring specifically to FIG. 4, an enlarged perspective view of barb  41 , barb  41  comprises a flat upper ledge  42  and three radiussed sides  43  tapering left, right, and downward from upper ledge  42 . Tapered sides  43  meet at a vertex  44 . 
     Frame  10  is installed on tray  81  by lowering frame  10  over tray  81  as shown in FIG.  1 . Pressure is applied to upper face  21  of frame wall  20  and to the underneath of tray  81 , such as to well bottoms  93  or flange  89 , or foot  90 , best seen in FIG.  3 . In the preferred embodiment shown, sides  43  of barb  41  deform peripheral wall  85 , bowing tray top  82  slightly, allowing barb  41  to snap into aperture  86 . When tray top  82  is no longer bowed, upper ledge  42  of barb  41  protrudes under bottom surface  83  of tray top  82  so as to bear on bottom surface  83  of tray top  82  and cannot be dislodged by forces encountered in normal handling of tray  81 . Exemplary rectangular frame  10  preferably includes at least one barb  41  on each of its sides to ensure that tray top  82  is held rigid and planar. 
     Although not specifically illustrated, barbs  41  can retain tray  81  by becoming embedded in the material of perimeter  82 P of tray top  82  when frame  10  is pressed downward along peripheral wall  85 . 
     In another embodiment (not shown), retaining features  98  of tray  81  comprise a plurality of detente studs protruding upward from the periphery of tray top  82 . Frame wall  20  overlaps the periphery and includes retaining means  25  comprising holes that engage the split studs. 
     In another embodiment (not shown), multiwell tray  81  does not comprise a peripheral wall  85  and retaining feature  98  is perimeter  82 P of tray top  82 . Frame wall  20  has only three sides, forming an open-ended rectangle. Interior surface  40  of frame wall  20  includes an indented channel, the same width as the thickness of tray top  82 . Frame  10  is installed by sliding the channel along the edge of tray top  82 . In yet another embodiment (not shown), frame  10  comprises two frame members, having a channel on interior surface  40 . Each frame member slides onto an opposite end of tray top  82 , then locking means connect the two frame members together. 
     Also, frame  20  and tray  81  are illustrated and described as being generally rectangular, but are not limited thereto. Frame  20  and tray  81  may be of any mating shapes, such as congruent shapes, including circular. Alternative arrangements of retaining means  25  and retaining features  98  are envisioned. 
     Frame wall  20  includes upper face  21  and bottom face  22  opposite upper face  21 . In the preferred embodiment illustrated, bottom  87 B of peripheral wall  85  is surrounded by an outward-projecting flange  89 . Flange  89  is in turn surrounded by downward-projecting foot  90 , on which tray  81  may stand. Frame  10  is adapted to fit around tray  81  such that upper face  21  of frame  10  and top surface  84  of tray top  82  are generally coplanar, and bottom face is disposed just above flange  89 . With this arrangement, opposing forces applied to upper face  21  and flange  89  or foot  90  would not necessarily result in relative movement of frame  10  and tray  81 . To allow relative movement such that barbs  41  and apertures  86  engage, relief slots  23  are relieved from bottom face  22  of frame wall  20  below each barb  41 , best appreciated from FIG.  3 . Preferably, the outside length and width of frame  10  are equal to or less than the outside length and width of flange  89  such that attaching frame  10  to tray  81  does not increase the footprint of tray  181 . 
     It can be seen in FIG. 2 that tray top  82  has identification marks to aid well identification. Referring back to FIG. 1, multiwell tray  81  includes orientation means  96 , such as corners  95 , which include bevelled corner  97 . Bevel  97  is a visual indication of the orientation of tray  81  and can also be used in cooperation with automated handling liquid dispensers (not shown) to maintain unique orientation in the filling process. Frame  10  includes cooperative orientation means  50 , such as bevelled interior corner  52 . If one of the non-bevelled corners  95  of tray  81  is inserted into bevelled corner  52 , the corners will interfere and not allow tray  81  to be installed into frame  10 . 
     Exterior surface  30  of frame wall  20  includes indexing marks  35  to indicate the orientation of tray  81 . Indexing marks  35  also cooperate with the handling means of the automated equipment to allow unidirectional processing. 
     Exterior surface  30  further includes handling features  31 , such as indentations  32 , for cooperating with handling means of automated equipment. Because indentations  32  weaken frame wall  20  by removing material, indentations  32  are disposed opposite barbs  41 , which project from interior surface  40 . This adaptation allows frame wall  20  to not be unduly weakened by indentations  32 . 
     Once tray  81  is installed in frame  10 , tray  81  is processed. Reactants and dilutants are added to wells  91  and wells  91  can be sealed by applying a cover (not shown) over rims  92 . In a typical process, tray  81  is thermal cycled by putting tray  81  and frame  10  on a heater block (not shown). The heater block typically contains an array of wells adapted to receive wells  91  of tray  81 . It is desirable that frame  10  not interfere with operation of the liquid dispenser, sealer, thermal cycler, or other equipment. Frame  10  holds tray  81  throughout processing and maintains consistent outside dimensions, precise indexing, and planarity of tray top  82 . After the reaction process is complete, the wells are emptied for analysis or pooling of reaction products, such as by automated liquid handler. Thus, it is important that tray  81  maintain planarity throughout the entire process, not just through initial filling. 
     As mentioned above, peripheral wall  85  of injection molded tray  81  typically has a draft angle, causing peripheral wall  85  to slant inward toward the top part  87 B. This may result in a gap between interior surface  40  of frame wall  20  and peripheral wall  85 . To compensate for this, interior surface  40  of frame  10 , in a preferred embodiment, includes compression means  46 , such as ridge  47 , for maintaining contact between interior surface  40  and top part  87 T of peripheral wall  85 , resulting in a more secure hold on tray  81 .