Thin-well microplate and methods of making same

Details Thin-well microplate and methods of making same Thin-well microplate and methods of making same

2002-01-22

2003-03-04

Redding, David A. (Department: 1744)

Chemistry: molecular biology and microbiology

Apparatus

Including measuring or testing

C435S305200, C264S494000, C264S496000, C156S060000, C156S073100

Reexamination Certificate

active

06528302

ABSTRACT:

FIELD OF THE INVENTION
The invention provides a thin-well microplate having an array of sample wells and a combination of specific physical and material properties required for use with automated equipment, such as robotic handling equipment, to withstand conditions of thermal cycling procedures and provide optimal thermal transfer and biological properties. The invention also provides methods of constructing the thin-well microplate as a unitary plate, employing ideal materials of construction to impart and optimize specific physical and material properties of the thin-well microplate.
BACKGROUND OF THE INVENTION
Various biological research and clinical diagnostic procedures and techniques require or are facilitated by an array of wells or tubes in which multiple samples are disposed for qualitative and quantitative assays or for sample storage and retrieval. Prior art devices that provide an array of wells or tubes capable of containing small sample volumes include microtitration plates that are commonly known as multi-well plates.
Multi-well plates have open-top wells, cups or recesses capable of containing small volumes of typically aqueous samples ranging from fractions of a microliter to hundreds of microliters. Multi-well plates also typically include sample well arrays totaling 96 sample wells that are arranged in an array of 8 by 12 sample wells and have center-to-center well spacing of 9 mm, such as the multi-well plate disclosed in U.S. Pat. No. 3,356,462. Sample well arrays also include arrays of 384 wells arranged in 16 by 24 array with a reduced center-to-center well spacing of 4.5 mm. Well arrays are not limited to any particular number of wells nor to any specific array pattern. For example, U.S. Pat. No. 5,910,287 discloses a multi-well plate comprising a well array of more than 864 wells.
Research techniques that use multi-well plates include, but are not limited to, quantitative binding assays, such as radioimmunoassay (RIA) or enzyme-linked immunosorbant assay (ELISA), combinatorial chemistry, cell-based assays, thermal cycle DNA sequencing and polymerase chain reaction (PCR), both of which amplify a specific DNA sequence using a series of thermal cycles. Each of these techniques makes specific demands on the physical and material properties and surface characteristics of the sample wells. For instance, RIA and ELISA require surfaces with high protein binding; combinatorial chemistry requires great chemical and thermal resistance; cell-based assays require surfaces compatible with sterilization and cell attachment, as well as good transparency; and thermal cycling requires low protein and DNA binding, good thermal conductivity, and moderate thermal resistance.
Different uses of multi-well plates make different demands on the overall form and structure of the multi-well plate. The compatibility of plates with automated equipment is perhaps one of the most stringent constraints on the form and structure of plates. Many laboratories automate various steps or phases of procedures, such as depositing and removing small quantities of reaction mixture from sample wells, often 5 &mgr;l or less, using automated dispensing/aspiration systems. Furthermore, plate handling equipment is often used to help facilitate the automation of such procedures. Accordingly, it is desirable to use a multi-well plate that is conducive to use with robotic equipment and can withstand robotic gripping and manipulation.
Efforts to standardize the features which permit successful deployment of multi-well plates in robotic handling and liquid handling instruments have been recommended (Society of Biomolecular Screening Recommended Microplate Specifications http://sbsonline.com/sbs070.htm), and significant effort has been made to achieve a common geometry of key elements of multi-well plate design, including footprint (defined as length and width at the base plane), well location with respect to the exterior of the footprint, and overall flatness as well as rigidity in the robotic gripping area.
Multi-well plates used in thermal cycling procedures form a sub-set of multi-well plates and may be referred to as thin-well microplates. Use in thermal cycling places additional material and structural requirements on the thin-well microplates. Typically, multi-well plates are not exposed to high temperatures or to rapid temperature cycling. Thin-well microplates are designed to accommodate the stringent requirements of thermal cycling. For example, thin-well microplates typically have design adaptations that are intended to improve thermal transfer to samples contained within sample wells. Sample wells of thin-well microplates have thin walls typically on the order of less than or equal to 0.015 inch (0.38 mm). Sample wells typically are conical shaped to allow wells to nest into corresponding conical shapes of heating/cooling blocks of thermal cyclers. The nesting feature of sample wells helps to increase surface area of thin-well microplates while in contact with heating/cooling blocks and, thus, helps to facilitate heating and cooling of samples.
As described above with respect to standard multi-well plate applications, many laboratories utilizing thin-well microplates now automate procedures performed prior to and subsequent to thermal cycling and employ robotic equipment to facilitate such automation. To ensure reliable and accurate use with robotic instruments, the subset of thin-well microplates must also possess general physical and material properties which facilitate robotic handling as well as enable thin-well microplates to retain their dimensional stability and integrity when exposed to high temperatures of thermal cycling.
Thin-well microplates require a specific combination of physical and material properties for optimal robotic manipulation, liquid handling, and thermal cycling. These properties consist of rigidity, strength and straightness required for robotic plate manipulation; flatness of sample well arrays required for accurate and reliable liquid sample handling; physical and dimensional stability and integrity during and following exposure to temperatures approaching 100° C.; and thin-walled sample wells required for optimal thermal transfer to samples. These various properties tend to be contradictory. For instance polymers offering improved rigidity and/or stability typically do not possess the material properties required to be biologically compatible and/or to form thin-walled sample tubes. Existing thin-well microplates are not constructed to impart all of these properties.
The typical manufacturing process for multi-well plates is polymer injection molding due to the economy of such processes. To insure multi-well plates consistently adhere to specifications for rigidity and flatness, manufacturers of prior art multi-well plates employ one or both of two design options, namely incorporating structural features with multi-well plates and using suitable and economical polymers to construct multi-well plates.
The first option of incorporating structural features with multi-well plates includes incorporating ribs with the undersides of multi-well plates to reinforce flatness and rigidity. However, such structural features cannot be incorporated with thin-well microplates used in thermal cycling procedures. Such structural features would not allow samples wells to nest in wells of thermal cycler blocks and, therefore, would prevent effective coupling with block wells resulting in less effective thermal transfer to samples contained within sample wells.
The second option to enhance rigidity and flatness of multi-well plates includes using suitable, economical polymers that impart rigidity and flatness to the plates. Simultaneously the selected polymer must also meet the physical and material property requirements of thin-well microplate sample wells in order for such sample wells to correctly function during thermal cycling. Many prior art multi-well plates are constructed of polystyrene or polycarbonate. Polystyrene and polycarbonate resins exhibit mold-flow properties th

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