Parallel reactor for sampling and conducting in situ...

Chemical apparatus and process disinfecting – deodorizing – preser – Chemical reactor – Including internal mixing or stirring means

Reexamination Certificate

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C422S164000, C422S131000, C422S236000, C422S062000, C422S105000, C422S110000, C422S116000, C422S129000, C422S130000, C422S050000, C422S081000, C422S297000, C436S034000, C436S037000, C436S093000

Reexamination Certificate

active

06692708

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to an apparatus and method for carrying out and in situ monitoring of the progress and properties of multiple parallel reactions.
BACKGROUND OF THE INVENTION
In combinatorial chemistry, a large number of candidate materials are created from a relatively small set of precursors and subsequently evaluated for suitability for a particular application. As currently practiced, combinatorial chemistry permits scientists to systematically explore the influence of structural variations in candidates by dramatically accelerating the rates at which they are created and evaluated. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each candidate.
Combinatorial chemistry has revolutionized the process of drug discovery. One can view drug discovery as a two-step process: acquiring candidate compounds through laboratory synthesis or through natural products collection, followed by evaluation or screening for efficacy. Pharmaceutical researchers have long used high-throughput screening (HTS) protocols to rapidly evaluate the therapeutic value of natural products and libraries of compounds synthesized and cataloged over many years. However, compared to HTS protocols, chemical synthesis has historically been a slow, arduous process. With the advent of combinatorial methods, scientists can now create large libraries of organic molecules at a pace on par with HTS protocols.
Recently, combinatorial approaches have been used for discovery programs unrelated to drugs. For example, some researchers have recognized that combinatorial strategies also offer promise for the discovery of inorganic compounds such as high-temperature superconductors, magnetoresistive materials, luminescent materials, and catalytic materials. See, for example, co-pending U.S. patent application Ser. No. 08/327,513 “The Combinatorial Synthesis of Novel Materials” (published as WO 96/11878) and co-pending U.S. patent application Ser. No. 08/898,715 “Combinatorial Synthesis and Analysis of Organometallic Compounds and Catalysts” (published, in part, as WO 98/03251), which are all herein incorporated by reference.
Because of the success of the combinatorial approach in eliminating the synthesis bottleneck in drug discovery, many researchers have come to narrowly view combinatorial methods as tools for creating structural diversity. Few researchers have emphasized that, during synthesis, variations in temperature, pressure, ionic strength, and other process conditions can strongly influence the properties of library members. For instance, reaction conditions are particularly important in formulation chemistry, where one combines a set of components under different reaction conditions or concentrations to determine their influence on product properties.
In recent years, researchers have begun to design apparatus to be used in combinatorial experiments that allow parallel processing of multiple reactions, particularly where it is desirable to vary one or more parameters of the reactions. For instance, commonly assigned pending U.S. application Ser. No. 09/548,848 filed on Apr. 13, 2000, discloses a parallel reactor including vessels for containing a plurality of reaction mixtures, a stirring system, and a temperature control system adapted to maintain the individual vessels or groups of vessels at different temperatures. The Ser. No. 09/548,848 application is a continuation-in-part of pending U.S. application Ser. Nos. 09/239,223 and 09/211,982 filed Jan. 29, 1999 and Dec. 14, 1998, respectively, wherein the Ser. No. 09/211,982 application is a continuation-in-part of pending U.S. Ser. No. 09/177,170 filed on Oct. 22, 1998, which is itself a continuation-in-part of Provisional Application No. 60/096,603 filed Aug. 13, 1998, now abandoned, all of which are incorporated herein by reference.
Commonly assigned pending Provisional Application Ser. No. 60/255,716 filed on Dec. 14, 2000, incorporated herein by reference, also describes a related apparatus. In particular Application No. 60/255,716 discloses parallel semi-continuous or continuous reactors for synthesizing combinatorial libraries of materials and screening combinatorial libraries of materials such as catalysts.
Given the growing interest in combinatorial research, it may be desirable to have a parallel reactor adapted to create various flow paths through the reactor block while allowing in situ monitoring and control over the progress and properties of multiple parallel reactions, as well as permit the removal of a portion of the reaction mixtures during the experiment or the performance of flow-through experiments, wherein both sampling and flow-through can occur without depressurizing or reducing the pressure in the respective reaction chambers.
SUMMARY OF THE INVENTION
The present invention relates to an apparatus and method for carrying out and in situ monitoring multiple parallel reactions. Specifically, the apparatus can be used for making, characterizing and sampling reaction mixtures, and can include a reactor block, reaction chambers, a stirring system, interchangeable manifolds and a sampling manifold assembly.
The reactor block can include reaction chambers for containing reaction mixtures under pressure. The reactor block can further include a first sidewall, a second sidewall, and a first plurality of fluid flow paths providing fluid communication with the first sidewall and respective reaction chambers and the second sidewall and respective reaction chambers.
In a preferred embodiment the, first and second plurality of flow paths are channels formed through the reactor block and the base plate of the stirring system, respectively, and a group of four fluid flow paths from the first plurality of fluid flow paths are in fluid communication with a single reaction chamber. More specifically, two of the four fluid flow paths are defined by the first sidewall and two of the four fluid flow paths are defined by the second sidewall. And even more specifically, one of the two fluid flow paths defined by the first sidewall is in fluid communication with a respective reaction chamber reaction chamber via a respective flow path from the second plurality of flow paths, and one of the two fluid flow paths defined by the second sidewall is in fluid communication with a respective reaction chamber via one flow path of the second plurality of flow paths.
The stirring system can include a base plate defining a second plurality of flow paths. At least one flow path of the second plurality of flow paths is in fluid communication with respective reaction chambers, at least one fluid flow path of the first plurality of flow paths. The base plate supporting a plurality of stirring blade assemblies for mixing the reaction mixtures, wherein one stirring blade assembly of the plurality of stirring blade assemblies is received in the respective reaction chambers.
The interchangeable manifolds can be supported by the first sidewall and the second sidewall, and can define a plurality of manifold inlet/outlet ports. Each respective inlet/outlet port of the plurality of inlet/outlet ports is in communication with respective fluid flow paths of the first plurality of fluid flow paths and permits fluid to be introduced into or vented from the respective reaction chambers.
The interchangeable manifolds allow the first and second plurality of flow paths to be coupled in a variety of configurations. For instance, the plurality of inlet/outlet ports of the interchangeable manifold bars can define separate flow paths through the respective interchangeable manifold bars which align with respective flow paths through the reactor block or the base plate, respectively. For instance, a first group of inlet/outlet ports of the plurality of inlet/outlet ports can include inlet/outlet ports placed in fluid communication with respective flow paths of the first plurality of flow paths and respective flow paths of the second plurality of flow paths, wherein each inlet/outlet po

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