Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
2001-08-24
2004-01-27
Warden, Jill (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C422S067000, C422S068100, C422S091000, C436S037000, C436S174000, C436S177000, C436S178000
Reexamination Certificate
active
06682702
ABSTRACT:
TECHNICAL FIELD
This invention relates to simultaneously reacting multiple chemical samples using arrays. In particular, the invention relates to an apparatus for and a method of conducting multiple chemical reactions or assays simultaneously using microarray technology for diagnostic, therapeutic and analytical applications.
BACKGROUND ART
Devices for processing multiple biological assays are known (U.S. Pat. Nos. 5,545,531 and 6,083,763, for example). The devices typically comprise reaction vessels having a plurality of reaction wells, each well has sidewalls and a closed end or bottom and an array of chemical samples fixed to the closed end. The end opposite to the closed end is open to access the reaction well for performing the assays with the array. Conventional microtiter plates are examples of conventional reaction vessels.
One conventional reaction vessel is made from a biochip wafer having a plurality of biological arrays fixed to the wafer surface and a microtiter-type plate attached to the wafer surface. The microtiter-type plate has a plurality of through holes formed completely through the thickness of the plate instead of closed-end wells as described above. The through holes in the microtiter-type plate are aligned with the plurality of arrays on the wafer. Reaction wells are formed by the attachment, wherein the wafer becomes the closed end and the through hole walls are the sidewalls of each reaction well. The arrays on the wafer are accessible via the open ends. Biological test samples are added to the open end to perform multiple assays at one time.
Another conventional reaction vessel is a conventional type of microtiter plate having a plurality of wells, wherein each well has sidewalls and a closed end. Individual biochips are attached inside each well. The individual biochips are obtained by dicing up the biochip wafer mentioned above. The individual biochips comprise an array of chemical samples fixed to a chip surface. The chip is adhered to the closed end of the well, such that the array surface of the chip is accessible from the open end of the well. Again, biological test samples are added to the open end to perform multiple assays at one time.
U.S. Pat. No. 5,324,633 discloses still another conventional reaction vessel that utilizes a flow cell having reservoirs that align with arrays of reactants on a substrate when the substrate is placed on the flow cell. Channels extending between the reservoir and the outside of the flow cell are used to inject the test sample into the reservoirs after the reaction vessel is assembled. O-rings are used to seal the substrate to the flow cell around each reservoir. Alternatively, the reaction vessel is a channel block having multiple channels therein. The channel block is mated with a substrate supporting arrays of biological material. The channels of the channel block are then filled with different reaction solutions that react with the arrays of biological materials similar to the flow cell.
The conventional reaction vessels are not self-contained (e.g., gas tight or fluid tight). Therefore, special handling and processing equipment must be used to perform assays using these conventional reaction vessels in order to provide stable handling and to control assay conditions, such as atmosphere, temperature, contamination, and prevent loss of sample or reagents, and the like. The special handling and processing equipment is expensive and not conducive to increased throughput, without added expense. Moreover, additional materials and assembly steps are needed if one skilled in the art wanted to seal the conventional reaction vessels to render them gas or fluid tight. For example, an additional cover plate or film must be placed over the open ends of the plurality of wells of the conventional reaction vessel to close or seal the open ends after the assay ingredients are added to the array therein. In the flow cell embodiments, the channels must be blocked with a cap or plug, for example, to seal the reservoirs.
Thus, it would be advantageous to have a method of simultaneously conducting multiple chemical reactions and a reaction vessel that is fully enclosed and gas, liquid and/or fluid tight without the need for cover plates and/or caps and the associated additional assembly steps. Such an apparatus and a method could decrease cost and increase throughput in the art of performing multiple assays.
SUMMARY OF THE INVENTION
The present invention provides a novel method of simultaneously conducting multiple chemical reactions and a reaction assembly apparatus that are low cost because the present invention can use pre-existing equipment, materials and well-known techniques to provide a self-contained, gas, liquid and/or fluid tight reaction vessel. In particular, the present invention is an apparatus for and a method of simultaneously conducting assays of multiple biological samples, such as assays of proteins, nucleic acids, specific binding pairs, and the like, advantageously that can use conventional microarrays and microtiter plates in a low cost manner for diagnostic, therapeutic and analytical applications, for example. The method and apparatus of the present invention can be subjected to handling and reaction conditions that are not available to the conventional reaction vessels described above. The handling and reaction conditions promote or accelerate the chemical reactions within the apparatus.
In one aspect of the invention, a method of simultaneously conducting multiple chemical reactions in a reaction assembly that comprises a microtiter plate of wells containing test samples and a microarray of sets of chemical reactants is provided. The method comprises the step of assembling the microarray of sets of chemical reactants to the microtiter plate of test samples such that the microarray covers open ends in the test sample wells of the microtiter plate to form a plurality of closed cells. Each closed cell comprises a set of chemical reactants and a respective test sample. The method further comprises the steps of sealing the microtiter plate to the microarray to create one or more of a gas, a liquid and a fluid tight seal; and mechanically agitating the sealed reaction assembly to contact test samples with the chemical reactants in each closed cell simultaneously.
In another aspect of the invention, a method of simultaneously conducting multiple chemical reactions between a first chemical sample and a second chemical sample is provided. The method comprises the step of providing a plate, having a plurality of spatially arranged wells in a well array pattern. Each well has a side wall adjacent to a closed end that enclose the well except for an open end opposite the closed end. The open end is adjacent to the plate surface for receiving a volume of the first chemical sample. The method further comprises the step of providing the second chemical sample bound to a surface of a substrate in an array pattern of features. The array of second chemical samples is spatially arranged in sets of features on the substrate surface similar in layout to the arrangement of the wells in the plate.
The method yet still further comprises the step of assembling the array and the plate into a reaction assembly and sealing the assembly. The array and plate are assembled such that the array substrate encloses the open ends of the plurality of wells in the plate. The features of the second chemical samples on the array are aligned with the open ends of the wells in the plate. Such aligned features and wells become multiple separate closed cells or reaction chambers in the reaction assembly. The reaction assembly is sealed to have one or more of a gas, liquid and fluid tight seal between the plate and the array, such that each closed cell is sealed.
The method yet still further comprises the step of simultaneously contacting the first chemical sample with the second chemical sample for a period of time in the plurality of closed cells to facilitate reactions therebetween. A variety of reaction parameters may be used for accomplishi
Amorese Douglas A.
Barth Phillip W.
Schembri Carol T.
Agilent Technologie,s Inc.
Handy Dwayne K
Warden Jill
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