Device for incubating and monitoring multiwell assays

Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing

Reexamination Certificate

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Details

C435S288700, C422S065000, C422S082050, C356S388000, C356S395000, C382S128000, C382S133000

Reexamination Certificate

active

06271022

ABSTRACT:

FIELD OF THE INVENTION
The present invention provides easy-to-use, adaptable, and convenient solutions to a heretofore unmet need for an instrument that can incubate and kinetically monitor assays, especially multiwell assays. In particular, the present invention finds use in monitoring assays contained within various test formats, including, but not limited to microtiter plates, miniaturized test panels (e.g., MICROCARDS™), and petri plates.
BACKGROUND OF THE INVENTION
Various methods are available to analyze biological samples using optical analyses, including reflective and transmitted light, fluorescence, and luminescence. The purpose of the analysis is often to assay the response of cells, for example, to the presence of a chemical (e.g., a nutrient, hormone, antibiotic, pharmaceutical, toxic chemical, etc.).
However, methods and devices in use to date are generally limited in terms of their mechanical reliability, easy of use, capacity, speed, expense, and format flexibility. For example, devices currently in use are only capable of monitoring certain, specific formats, and are not capable of being adapted for use with multiple formats such as various microtiter plates (e.g., 96-, 384-, and 1536-well plates) or petri plates. All existing readers read one multiwell assay plate at a time. In addition, most or all available readers have an optical system which reads one row of a multiwell test panel at a time. Some examples of instruments that incubate and read a large number of multiwell plates are the Vitek (See e.g., 5,762,873, 5,853,667, 5,853,666, 5,798,085, 5,798,084, 5,670,375, 5,843,380, 5,766,553, D382,647, 5,697,409), MicroScan, and Sensititre instruments. The Vitek and MicroScan instruments have complex mechanisms for sliding out each plate, one at a time, for reading, and then sliding it back onto its shelf, while Sensititre has a single reading station, with an elevator transport system that moves each plate, one at a time, first onto the elevator, then to the reading station, and then back to its shelf. While these features allow for the analysis of multiple plates, the mechanisms are inefficient and are not capable of use with multiple formats. Thus, a need exists for improved instruments that increase mechanical reliability, easy of use, capacity, speed, affordability, and flexibility with multiple formats.
SUMMARY OF THE INVENTION
The present invention provides easy-to-use, adaptable, and convenient solutions to a heretofore unmet need for an instrument that can incubate and kinetically monitor assays, especially multiwell assays. In particular, the present invention finds use in monitoring assays contained within various test formats, including, but not limited to microtiter plates, miniaturized test panels (e.g., MICROCARDS™), and petri plates.
The present invention provides an instrument comprising: 1) an enclosure cabinet; 2) a plurality of sliding shelves mounted in said cabinet, wherein said shelves are capable of holding one or more assay plates; 3) an imaging device mounted in said cabinet for simultaneously capturing within a field of view one or more images of two or more of said assay plates located on one or more of said shelves; and 4) a means for moving said imaging device, whereby said imaging device can be selectively positioned, without moving said assay plates on said shelves, to simultaneously capture images of all wells in said field of view of said assay plates located on any of said shelves.
In some preferred embodiments the shelves have a dimension of approximately eight by eight inches, to facilitate use on laboratory benches, although the present invention is not limited to any particular size of shelves. In other preferred embodiments, the plurality of sliding shelves consists of at least twenty sliding shelves, although a greater or fewer number of shelves is contemplated by the present invention. In particularly preferred embodiments, the shelves are capable of holding at least two assay plates. For example, the assay plates can be multiwell assay plates or petri plates, although the present invention is not limited by type of assay plate used. In other embodiments, the shelves contain one or more openings for viewing at least one multiwell assay plate from the bottom of the shelves. The shelves may also contain one or more thumbholes to facilitate loading and unloading of the sample plates.
In some embodiments, the imaging device comprises a camera. In preferred embodiments, the camera is selected from the group consisting of a CCD camera and a CMOS camera. In other embodiments the imaging device comprises a scanner, although it is not intended that the present invention be limited by the type of imaging device used. In some embodiments, the means for moving the imaging device comprises a motor. For example, the present invention contemplates motors including, but not limited to, a stepper motor.
In some embodiments of the present invention, the cabinet is a temperature controlled incubator. In preferred embodiments, the cabinet is gas-tight and can maintain a controlled level of a gas. In yet other embodiments, the cabinet comprises an access door, and in particular embodiments, the shelves are accessible from the door.
In some embodiments of the present invention, the instrument further comprises a means for controlling the instrument. For example, in some embodiments, the means for controlling the instrument controls elements of the instrument selected from the group consisting of: internal temperature of the cabinet, internal lighting of the cabinet, internal gas composition of the cabinet, positions of the plurality of sliding shelves, position of the imaging device, activity of the means for moving the imaging device, imaging by the imaging device, door closing, door opening, and combinations thereof. In preferred embodiments, the means for controlling the instrument comprises a computer. In some embodiments, the computer is connected to the instrument by a standard RS-232 interface. In particularly preferred embodiments, the computer comprises electronics for receiving digital image information from said imaging device. In yet other preferred embodiments, the computer monitors, records data on, and/or controls elements of the instrument selected from the group consisting of: internal temperature of the cabinet, internal lighting of the cabinet, internal gas composition of the cabinet, positions of the plurality of sliding shelves, position of the imaging device, activity of the means for moving the imaging device, imaging by the imaging device, door closing, door opening, and combinations thereof. In other embodiments, the computer records data on the images of the assay plates.
The present invention further provides an instrument comprising: 1) an enclosure cabinet; 2) a plurality of sliding shelves mounted in the cabinet, wherein the shelves are capable of holding two or more assay plates; and 3) an imaging device mounted in the cabinet for capturing one or more images of the two or more assay plates located on each of said shelves, wherein each of the images captures all of the assay plates on any one or more of the shelves.
The present invention also provides a system comprising: 1) an enclosure cabinet; 2) a plurality of sliding shelves mounted in the cabinet; 3) two or more assay plates located on at least one of the sliding shelves; and 4) an imaging device mounted in the cabinet for simultaneously capturing within a field of view one or more images of the two or more assay plates. In some embodiments, the system further comprises 5) a means for moving the imaging device, whereby the imaging device can be selectively positioned, without moving the assay plates on the shelves, to simultaneously capture images of all wells in the field of view of the assay plates located on any of the shelves.
The systems and devices of the present invention find use in methods for kinetically monitoring assay plates. For example, the present invention provides a method comprising: providing a system comprising: 1) an enclosure cabi

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