Parallel reaction devices

Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition

Reexamination Certificate

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Details

C422S091000, C422S105000, C422S129000, C422S130000, C422S131000, C435S288400, C435S305200, C435S305300, C435S305400

Reexamination Certificate

active

06682703

ABSTRACT:

COPYRIGHT NOTIFICATION
Pursuant to 37 C.F.R. §1.71(e), Applicants note that a portion of this disclosure contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
CROSS-REFERENCES TO RELATED APPLICATIONS
Not Applicable.
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
Not Applicable.
BACKGROUND OF THE INVENTION
Modern techniques for identifying compounds with desired chemical or physical properties typically involve assembling complex libraries of compounds that are systematically screened to isolate members having the desired properties. One general approach to library construction involves creating compounds using combinatorial, parallel, or other synthetic processes in which sets of compounds are prepared from sets of building blocks, e.g., via multi-step solution- or solid-phase synthesis. For example, split/pool combinatorial synthetic techniques can be used to produce all possible combinations of a set of building blocks. In particular, the methods typically include splitting an initial pool of solid supports with attached chemical moieties into a selected number of individual pools. Each pool is subjected to a first randomization reaction that generates a different modification to the solid supports in each separate pool. Following this first set of reactions, the individual pools of solid supports are typically combined, mixed, and split once again into separate pools. Each split pool is then subjected to a second randomization, which again is different for each pool. This process is repeated until the desired library of target compounds is produced. Additional details relating to library synthesis using combinatorial and parallel approaches are described in, e.g., Houghten (2000) “Parallel array and mixture-based synthetic combinatorial chemistry: Tools for the next millennium,”
Annu. Rev. Pharmacol. Toxicol.
40:273-282, Thompson (2000) “Recent applications of polymer-supported reagents and scavengers in combinatorial, parallel, or multistep synthesis,”
Curr. Opin. Chem. Biol.
4:324-337, Bunin et al. (1999) “Application of combinatorial and parallel synthesis to medicinal chemistry,”
Annu. Rep. Med. Chem.
34:267-286, and Brooking et al. (1999) “Split-split. A multiple synthesiser approach to efficient automated parallel synthesis,
Tetrahedron Lett.
40(7):1405-1408.
A standard tool for parallel chemistry, including randomization steps in combinatorial protocols, such as split/pool synthesis, is the multiple well reaction vessel that typically includes a collection of tubes or a reaction block bored out with a designated number of reaction wells or holes. These reaction wells are generally fitted with a filter at one end, which allows the individual wells to be employed for solid-liquid separations or other purification processes. The footprint of such reaction blocks typically corresponds to an array of wells in a standard micro-well assay plate. A series of individually addressable open reactors is generally formed within a reaction block by contacting a gasket to the bottom or outlets of the reaction wells. In addition, a series of enclosed reactors is typically made by sealing the top or inlets to the reaction wells with another gasket. Sealed reaction wells provide for aggressive agitation of well contents and for the use of extreme reaction conditions.
Sub-optimal sealing and clamping mechanisms inhibit throughput in multiple well reaction vessels of the prior art. Specifically, preexisting technologies typically require users to operate a series of latches, screws, and/or other fasteners, which hinders safe and efficient access to reaction chambers. Further, the clamping mechanisms of these devices generally do not provide secure reaction well seals such that leakage of materials from the reaction wells commonly results. Sample leakage typically causes reaction failure for the reaction within the particular well from which the leakage occurred and/or cross-contamination among multiple reaction wells. One source of leakage in preexisting devices is uneven clamp load over the reaction wells. In addition, the inferior designs that characterize the prior art also suffer from general losses of clamp load over time, which further contributes to the aforementioned leakage-related problems.
From the above, it is apparent that there is a substantial need for new parallel reaction devices that permit efficient and rapid access to reaction wells. It would also be desirable to have reaction blocks that remain securely sealed under diverse reaction conditions, including varied extremes of temperature and agitation. These and a variety of additional features of the present invention will become evident upon complete review of the following.
SUMMARY OF THE INVENTION
The present invention relates to devices for performing multiple reactions, such as combinatorial synthesis reactions, or other processes in parallel. More specifically, the invention provides parallel reaction devices that include secure and efficient sealing or clamping mechanisms, which significantly improve throughput relative to existing devices. The devices of the invention incorporate reaction blocks that include arrays of reaction wells. Reaction blocks are sometimes disposable or at least not intended for indefinite use. In addition to reaction blocks, the devices of the present invention include lids and gaskets for sealing reaction wells within the reaction blocks and attachment components for attaching the lids to the reaction blocks. In preferred embodiments, lids include arrays of protrusions that axially align with reaction wells in assembled devices to further enhance reaction well seals. The lids of the devices of the invention are also typically removably attached to reaction blocks and produce substantially even clamp loads across inlet or outlet portions of reaction blocks. Reaction block containers, systems, and kits that include these devices or device components are additionally provided.
In one aspect, the invention provides a parallel reaction device that includes (a) a reaction block that includes an array of reaction wells in which at least one reaction well in the array is disposed through the reaction block, which reaction well includes an inlet portion and an outlet portion, (b) a top lid attached to the reaction block by at least one top attachment component, which top lid includes at least one protrusion disposed on a surface that engages the reaction block, which protrusion presses a top gasket into contact with the inlet portion of the reaction well to seal the inlet portion, and (c) a bottom lid attached to the reaction block by at least one bottom attachment component, which bottom lid presses a bottom gasket into contact with the outlet portion of the reaction well to seal the outlet portion.
In another aspect, the invention relates to a parallel reaction device that includes (a) a reaction block that includes an array of reaction wells, wherein at least one reaction well in the array is disposed through the reaction block, which reaction well includes an inlet portion and an outlet portion, (b) a top lid attached to the reaction block by at least one top hinge component and at least one top latch component, which top lid presses a top gasket into contact with the inlet portion to the reaction well to seal the inlet portion, and (c) a bottom lid attached to the reaction block by at least one bottom hinge component and at least one bottom latch component, which bottom lid presses a bottom gasket into contact with the outlet portion of the reaction well to seal the outlet portion.
In yet another aspect, the invention provides a parallel reaction device that includes (a) a reaction block that includes an array of reaction wells in which at least one reaction well in the array is dis

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