Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
1995-05-16
2001-07-10
Soderquist, Arlen (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C422S051000, C422S105000, C436S177000, C436S178000
Reexamination Certificate
active
06258325
ABSTRACT:
This invention relates generally to multi-well plates and tube arrays in which samples (biological, chemical, etc.) are analyzed or processed. More specifically, the present invention solves the problem associated with cross-contamination of samples which may occur in the use of a closely spaced array of wells or tubes. The present invention also relates to a multi-well plate which can be used for analysis or processing in a controlled atmosphere without the possibility of continuation from atmospheric sources. In addition, the present invention describes a new type of multi-well plate which can be clamped together.
BACKGROUND OF THE INVENTION
A number of laboratory and clinical procedures require the use of an array of wells or tubes in which multiple samples are placed for analysis, cell growth, amplification, isolation or other purposes. In general, conventional multi-well plates and tube arrays (non-filtration type) have a single opening at the top through which samples are added or removed.
An important disadvantage in the use of arrays of tubes mounted within a plate, and with multi-well plates (either with or without a filtration feature) is the problem associated with contamination of the samples. Most laboratory protocols must be performed with a high degree of stringency in terms of limiting contamination of the samples. When multiple samples are processed in a confined area, such as an 8×12 or 4×6 format, strip wells (in strips of 8 or 12 wells), or in any format with multiple sample containers in a small area, the risk of cross-contamination of samples is significant, giving rise to erroneous results. If a single unitary plate (as currently available) is used as a collective lid to cover the tops of all the wells or tubes, the lack of a seal could allow the migration of samples between wells or tubes during handling, or simply through condensation and capillary processes. Tapes which are used currently to seal the tops of the wells are not very reliable. Adhesive tapes limit the number of conditions that the plate can be subjected to (efficient boiling, freeze-thawing and vortexing the plate are difficult without causing cross-contamination) and heat sealing tape requires specialized heat-sealing equipment. Incorporation of a tape sealing process in automated systems would be difficult. In addition, multi-well or tube arrays which utilize individual stoppers are unwieldy and allow the introduction of contaminants as the reagents and the like are added to the wells/tubes. This problem of cross-contamination is particularly acute when tight fitting caps and tape are opened, which frequently results in aerosol formation. These aerosols, in addition to being a potential source of cross-contamination, may also be hazardous to the operator.
A problem often encountered with cell culture procedures is the contamination of the cultures by microorganisms from the environment or the atmosphere. This problem has been difficult to overcome, because cell-culture procedures often require the microorganisms to be grown in, a controlled atmosphere (such as 5% carbon dioxide); the conventional plates therefore have a loose fitting lid to reduce evaporation while allowing gas exchange and yet minimizing contamination. Also, it would not be possible to clamp the lid to the multi-well plate without changing the dimensions of the plate, which would make it difficult to use with existing instruments such as plate readers, centrifuges and the like. It is important to appreciate that the use of the membrane in the present invention is very different from prior art involving 96-well filtration devices, where the liquid samples have to come in contact with the membrane for the purpose of filtration. Thus, in the prior art, the membrane provides for flow-through of liquid, with the liquid often in contact with the membrane for prolonged periods of time prior to filtration. In the present invention the membrane prevents flow-through of non-gaseous materials, but allows gas-exchange.
Conventional glass microscope slides having one or more wells are now being used as sample holders for in situ nucleic acid amplification techniques such as PCR. Generally, either glue or cosmetic nail enamel is used to stick the cover directly to the slide, requiring the use of heat or a solvent to remove the cover.
Therefore, it is an object of the present invention to provide a plate/tray assembly having an array of sample containment site, which are designed to reduce the risk of cross-contamination between containment sites.
It is another object of the present invention to provide a multi-well plate or tube array in which cross-contamination of samples is significantly reduced by providing a resilient gasket which isolates each containment site.
It is yet another object of the present invention to have a tube array (or multi-well plate) which can be sealed without the use of a gasket or tight fit caps.
It is a further object of the present invention to provide a method of leaving samples in the sample containment sites in the multi-well plate/tube array open to the atmosphere and yet sealed from microbial, particulate or other contamination from atmospheric sources.
It is still a further object of the present invention to provide a sample containment assembly of multiple samples (such as 96 well plates and cluster plates) which can be hermetically sealed and clamped together without changing the effective dimensions of the assembly so that standardized equipment such as automated well washers, automated scanning instruments and centrifuges can still be used.
Finally, it is still a further object of the present invention to provide a sealing system for glass or plastic slides, which can be used without gluing the cover slip to the slide.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides an apparatus for handling multiple samples having a plurality of containment sites such as wells or tube-like vessels defining wells. The wells or tubes may be discrete elements temporarily attached to a tray or plate or preferably are formed integrally with a plate. Each well has one closed end and one open end. The plate (and thus the closed end) may be formed of a number of fluid impervious materials such as a rigid plastic. The apparatus further includes a lid which covers the principal or top surface of the plate or tray such that the lid simultaneously covers all of the openings of the containment sites or wells. Between the lid and the principal surface of the tray or plate, a layer of resilient material such as a synthetic rubber membrane is provided which serves as a gasket. In one embodiment the gasket is a single unitary sheet which covers all of the openings of the containment sites of the plate or tray. Thus, the gasket serves as a closure for each specimen chamber. The lid is then clamped or otherwise secured to the plate or tray with sufficient force to compress the gasket and provide sealing contact between the gasket and the tray or plate to seal the well openings. The apparatus can then be placed in various orientations without movement or loss of the samples from their respective containment sites.
In another aspect, the gasket feature of the present invention comprises a plurality of discrete gaskets or gasket sections each of which covers one or several openings of the plate. The discrete gaskets extend beyond each individual opening a sufficient distance to provide a seal between the individual containment sites.
In still another aspect, the gasket of the present invention is further provided with openings in register or alignment with each of the openings of the containment sites of the plate or tray such that access to the individual containment sites may be achieved by simply removing the lid.
In another embodiment, a mylar sheet or membrane is disposed on top of the gasket in that embodiment in which the gasket has a plurality of openings.
In yet another embodiment, a new format of multi-well plates or tube arrays is provided which allows the securing of the lid to the
Dykema Gossett PLLC
Soderquist Arlen
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