US20030190755A1 - Parallel reactor with internal sensing and method of using same - Google Patents

Abstract

Devices and methods for controlling and monitoring the progress and properties of multiple reactions are disclosed. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial libraries, but also offer significant advantages over conventional experimental reactors as well. The apparatus generally includes multiple vessels for containing reaction mixtures, and systems for controlling the stirring rate and temperature of individual reaction mixtures or groups of reaction mixtures. In addition, the apparatus may include provisions for independently controlling pressure in each vessel, and a system for injecting liquids into the vessels at a pressure different than ambient pressure. In situ monitoring of individual reaction mixtures provides feedback for process controllers, and also provides data for determining reaction rates, product yields, and various properties of the reaction products, including viscosity and molecular weight. Computer-based methods are disclosed for process monitoring and control, and for data display and analysis.

Description

CROSS REFERENCE TO RELATED APPLICATIONS
• This application is a continuation-in-part of U.S. application Ser. No. 09/239,223, filed Jan. 29, 1999, and a continuation-in-part of U.S. application Ser. No. 09/211,982, filed Dec. 14, 1998, which is a continuation in part of U.S. application Ser. No. 09/177,170, filed Oct. 22, 1998, which claims the benefit of U.S. Provisional Application No. 60/096,603, filed Aug. 13, 1998. All four of the foregoing applications are incorporated herein by reference in their entirety.[0001]
BACKGROUND OF THE INVENTION
• 1. Technical Field[0002]
• The present invention relates to methods, devices, and computer programs for rapidly making, screening, and characterizing an array of materials in which process conditions are controlled and monitored.[0003]
• 2. Discussion[0004]
• 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.[0005]
• 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.[0006]
• 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.[0007]
• Because of its success 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.[0008]
• Moreover, because the performance criteria in materials science is often different than in pharmaceutical research, many workers have failed to realize that process variables often can be used to distinguish among library members both during and after synthesis. For example, the viscosity of reaction mixtures can be used to distinguish library members based on their ability to catalyze a solution-phase polymerization—at constant polymer concentration, the higher the viscosity of the solution, the greater the molecular weight of the polymer formed. Furthermore, total heat liberated and/or peak temperature observed during an exothermic reaction can be used to rank catalysts.[0009]
• Therefore, a need exists for an apparatus to prepare and screen combinatorial libraries in which one can monitor and control process conditions during synthesis and screening.[0010]
SUMMARY OF THE INVENTION
• The present invention generally provides an apparatus for parallel processing of reaction mixtures. The apparatus includes vessels for containing the reaction mixtures, a stirring system, and a temperature control system that is adapted to maintain individual vessels or groups of vessels at different temperatures. The apparatus may consist of a monolithic reactor block, which contains the vessels, or an assemblage of reactor block modules. A robotic material handling system can be used to automatically load the vessels with starting materials. In addition to heating or cooling individual vessels, the entire reactor block can be maintained at a nearly uniform temperature by circulating a temperature-controlled thermal fluid through channels formed in the reactor block. The stirring system generally includes stirring members—blades, bars, and the like—placed in each of the vessels, and a mechanical or magnetic drive mechanism. Torque and rotation rate can be controlled and monitored through strain gages, phase lag measurements, and speed sensors.[0011]
• The apparatus may optionally include a system for evaluating material properties of the reaction mixtures. The system includes mechanical oscillators located within the vessels. When stimulated with a variable-frequency signal, the mechanical oscillators generate response signals that depend on properties of the reaction mixture. Through calibration, mechanical oscillators can be used to monitor molecular weight, specific gravity, elasticity, dielectric constant, conductivity, and other material properties of the reaction mixtures.[0012]
• The present invention also provides an apparatus for monitoring rates of production or consumption of a gas-phase component of a reaction mixture. The apparatus generally comprises a closed vessel for containing the reaction mixture, a stirring system, a temperature control system and a pressure control system. The pressure control system includes a pressure sensor that communicates with the vessel, as well as a valve that provides venting of a gaseous product from the vessel. In addition, in cases where a gas-phase reactant is consumed during reaction, the valve provides access to a source of the reactant. Pressure monitoring of the vessel, coupled with venting of product or filling with reactant allows the investigator to determine rates of production or consumption, respectively.[0013]
• One aspect of the present invention provides an apparatus for monitoring rates of consumption of a gas-phase reactant. The apparatus generally comprises a closed vessel for containing the reaction mixture, a stirring system, a temperature control system and a pressure control system. The pressure control system includes a pressure sensor that communicates with the vessel, as well as a flow sensor that monitors the flow rate of reactant entering the vessel. Rates of consumption of the reactant can be determined from the reactant flow rate and filling time.[0014]
• The present invention also provides a method of making and characterizing a plurality of materials. The method includes the steps of providing vessels with starting materials to form reaction mixtures, confining the reaction mixtures in the vessels to allow the reaction to occur, and stirring the reaction mixtures for at least a portion of the confining step. The method further includes the step of evaluating the reaction mixtures by tracking at least one characteristic of the reaction mixtures for at least a portion of the confining step. Various characteristics or properties can be monitored during the evaluating step, including temperature, rate of heat transfer, conversion of starting materials, rate of conversion, torque at a given stirring rate, stall frequency, viscosity, molecular weight, specific gravity, elasticity, dielectric constant, and conductivity.[0015]
• One aspect of the present invention provides a method of monitoring the rate of consumption of a gas-phase reactant. The method comprises the steps of providing a vessel with starting materials to form the reaction mixture, confining the reaction mixtures in the vessel to allow reaction to occur, and stirring the reaction mixture for at least a portion of the confining step. The method further includes filling the vessel with the gas-phase reactant until gas pressure in the vessel exceeds an upper-pressure limit, P[0016]_H, and allowing gas pressure in the vessel to decay below a lower-pressure limit, P_L. Gas pressure in the vessel is monitored and recorded during the addition and consumption of the reactant. This process is repeated at least once, and rates of consumption of the gas-phase reactant in the reaction mixture are determined from the pressure versus time record.
• Another aspect of the present invention provides a method of monitoring the rate of production of a gas-phase product. The method comprises the steps of providing a vessel with starting materials to form the reaction mixture, confining the reaction mixtures in the vessel to allow reaction to occur, and stirring the reaction mixture for at least a portion of the confining step. The method also comprises the steps of allowing gas pressure in the vessel to rise above an upper-pressure limit, P[0017]_H, and venting the vessel until gas pressure in the vessel falls below a lower-pressure limit, P_L. The gas pressure in the vessel is monitored and recorded during the production of the gas-phase component and subsequent venting of the vessel. The process is repeated at least once, so rates of production of the gas-phase product can be calculated from the pressure versus time record.
• The present invention provides an apparatus for parallel processing of reaction mixtures comprising vessels for containing the reaction mixtures, a stirring system for agitating the reaction mixtures, a temperature control system for regulating the temperature of the reaction mixtures, and a fluid injection system. The vessels are sealed to minimize unintentional gas flow into or out of the vessels, and the fluid injection system allows introduction of a liquid into the vessels at a pressure different than ambient pressure. The fluid injection system includes fill ports that are adapted to receive a liquid delivery probe, such as a syringe or pipette, and also includes conduits, valves, and tubular injectors. The conduits provide fluid communication between the fill ports and the valves and between the valves and the injectors. The injectors are located in the vessels, and can have varying lengths, depending on whether fluid injection is to occur in the reaction mixtures or in the vessel headspace above the reaction mixtures. Generally, a robotic material handling system manipulates the fluid delivery probe and controls the valves. The injection system can be used to deliver gases, liquids, and slurries, e.g., catalysts on solid supports.[0018]
• One aspect of the present invention provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels, a temperature control system, and a stirring system having a magnetic feed through device for coupling an external drive mechanism with a spindle that is completely contained within one of the vessels. The magnetic feed through device includes a rigid pressure barrier having a cylindrical interior surface that is open along the base of the pressure barrier. The base of the pressure barrier is attached to the vessel so that the interior surface of the pressure barrier and the vessel define a closed chamber. The magnetic feed through device further includes a magnetic driver that is rotatably mounted on the rigid pressure barrier and a magnetic follower that is rotatably mounted within the pressure barrier. The drive mechanism is mechanically coupled to the magnetic driver, and one end of the spindle is attached to a leg portion of the magnetic follower that extends into the vessel headspace. Since the magnetic driver and follower are magnetically coupled, rotation of the magnetic driver induces rotation of the magnetic follower and spindle.[0019]
• Another aspect of the present invention provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels, a temperature control system, and a stirring system that includes multi-piece spindles that are partially contained in the vessels. Each of the spindles includes an upper spindle portion that is mechanically coupled to a drive mechanism, a removable stirrer contained in one of the vessels, and a coupler for reversibly attaching the removable stirrer to the upper spindle portion. The removable stirrer is made of a chemically resistant plastic material, such as polyethylethylketone or polytetrafluoroethylene, and is typically discarded after use.[0020]
• The exact combination of parallel processing features depends on the embodiment of the invention being practiced. In some aspects, the present invention provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels and an injection system. The present invention also provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels, an injection system and a stirring system. The present invention also provides an apparatus for parallel processing of reaction mixtures comprising vessels having a temperature control system and a stirring system. The present invention also provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels and a pressure control system. The present invention also provides an apparatus for parallel processing of reaction mixtures comprising sealed vessels, an injection system and a system for property or characteristic monitoring.[0021]
• The present invention also provides computer programs and computer-implemented methods for monitoring the progress and properties of parallel chemical reactions. In one aspect, the invention features a method of monitoring a combinatorial chemical reaction. The method includes (a) receiving a measured value associated with the contents of each of a plurality of reactor vessels; (b) displaying the measured values; and (c) repeating steps (a) and (b) multiple times over the course of the combinatorial chemical reaction.[0022]
• Implementations of the invention can include one or more of the following advantageous features. The measured values include a set of values for a number of reaction conditions associated with each of the reactor vessels. Step (c) is performed at a predetermined sampling rate. The method also includes changing a reaction parameter associated with one of the reactor vessels in response to the measured value to maintain the reactor vessel at a predetermined set point. Reaction parameters include temperature, pressure, and motor (stirring) speed. The method also includes quenching a reaction in one of the reactor vessels in response to the measured value associated with the contents of the reactor vessel. The method also includes using the measured value to calculate an experimental variable or value for one of the reactor vessels. Examples of experimental variables include rates of change of temperature or pressure, percent conversion of a starting material, and viscosity. The method also includes displaying the experimental variable.[0023]
• In general, in another aspect, the invention features a method for controlling a combinatorial chemical reactor including multiple reactor vessels, each containing a reaction environment. The method includes receiving a set point for a property associated with each vessel's reaction environment; measuring a set of experimental values for the property for each vessel; displaying the set of experimental values; and changing the reaction environment in one or more of the plurality of reactor vessels in response to the set point and a change in one or more of the set of experimental values. For example, the method may terminate a reaction (change the reaction environment) in response to reactant conversion (experimental value) indicating that a target conversion (set point) has been reached. During reaction, a graphical representation of the set of experimental values is displayed, often as a histogram.[0024]
• In general, in another aspect, the invention features a computer program on a computer-readable medium for monitoring a combinatorial chemical reaction. The program includes instructions to (a) receive a measured value associated with the contents of each of a plurality of reactor vessels, instructions to (b) display the measured values, and instructions to (c) repeat steps (a) and (b) multiple times during the course of the combinatorial chemical reaction. The computer program includes instructions to change a reaction parameter associated with one of the reactor vessels in response to the measured value to maintain the reactor vessel at a predetermined set point.[0025]
• In general, in another aspect, the invention features a reactor control system for monitoring and controlling parallel chemical reactions. The reactor system includes a system control module for providing control signals to a parallel chemical reactor including multiple reactor vessels, a mixing monitoring and control system, a temperature monitoring and control system, and a pressure monitoring and control system. The reactor system also includes a data analysis module for receiving a set of measured values from the parallel chemical reactor and for calculating one or more calculated values for each of the reactor vessels. In addition, the reactor control system includes a user interface module for receiving reaction parameters and for displaying the set of measured values and calculated values.[0026]
• Advantages that can be seen in implementations of the invention include one or more of the following. Process variables can be monitored and controlled for multiple elements in a combinatorial library as a chemical reaction progresses. Data can be extracted for each library element repeatedly and in parallel over the course of the reaction, instead of extracting only a limited number of data points for selected library elements. Calculations and corrections can be applied automatically to every available data point for every library element over the course of the reaction. A single experimental value can be calculated from the entire data set for each library element.[0027]
• A further understanding of the nature and advantages of the present invention may be realized by reference to the remaining portions of the specification, drawings, and claims.[0028]
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 illustrates a parallel reactor system in accordance with the present invention.[0029]
• FIG. 2 shows a perspective view of a modular reactor block with a robotic liquid handling system.[0030]
• FIG. 3 shows a temperature monitoring system.[0031]
• FIG. 4 shows a cross-sectional view of an integral temperature sensor-vessel assembly.[0032]
• FIG. 5 shows a side view of an infrared temperature measurement system.[0033]
• FIG. 6 shows a temperature monitoring and control system for a reactor vessel.[0034]
• FIG. 7 illustrates another temperature control system, which includes liquid cooling and heating of the reactor block.[0035]
• FIG. 8 is a cross-sectional view of thermoelectric devices sandwiched between a reactor block and heat transfer plate.[0036]
• FIG. 9 is a cross-sectional view of a portion of a reactor block useful for obtaining calorimetric data.[0037]
• FIG. 10 is an exploded perspective view of a stirring system for a single module of a modular reactor block of the type shown in FIG. 2.[0038]
• FIG. 11 is a schematic representation of an electromagnetic stirring system.[0039]
• FIGS.[0040]12-13 are schematic representations of portions of electromagnet stirring arrays in which the ratios of electromagnets to vessel sites approach 1:1 and 2:1, respectively, as the number of vessel sites becomes large.
• FIG. 14 is a schematic representation of an electromagnet stirring array in which the ratio of electromagnets to vessel sites is 4:1.[0041]
• FIG. 15 shows additional elements of an electromagnetic stirring system, including drive circuit and processor.[0042]
• FIG. 16 illustrates the magnetic field direction of a 2×2 electromagnet array at four different times during one rotation of a magnetic stirring bar.[0043]
• FIG. 17 illustrates the magnetic field direction of a 4×4 electromagnet array at five different times during one full rotation of a 3×3 array of magnetic stirring bars.[0044]
• FIG. 18 illustrates the rotation direction of the 3×3 array of magnetic stirring bars shown in FIG. 17.[0045]
• FIG. 19 shows a wiring configuration for an electromagnetic stirring system.[0046]
• FIG. 20 shows an alternate wiring configuration for an electromagnetic stirring system.[0047]
• FIG. 21 shows the phase relationship between sinusoidal source currents, I[0048]_A(t) and I_B(t), which drive two series of electromagnets shown in FIGS. 19 and 20.
• FIG. 22 is a block diagram of a power supply for an electromagnetic stirring system.[0049]
• FIG. 23 illustrates an apparatus for directly measuring the applied torque of a stirring system.[0050]
• FIG. 24 shows placement of a strain gauge in a portion of a base plate that is similar to the lower plate of the reactor module shown in FIG. 10.[0051]
• FIG. 25 shows an inductive sensing coil system for detecting rotation and measuring phase angle of a magnetic stirring blade or bar.[0052]
• FIG. 26 shows typical outputs from inductive sensing coils, which illustrate phase lag associated with magnetic stirring for low and high viscosity solutions, respectively.[0053]
• FIG. 27 illustrates how amplitude and phase angle will vary during a reaction as the viscosity increases from a low value to a value sufficient to stall the stirring bar.[0054]
• FIGS.[0055]28-29 show bending modes of tuning forks and bimorph/unimorph resonators, respectively.
• FIG. 30 schematically shows a system for measuring the properties of reaction mixtures using mechanical oscillators.[0056]
• FIG. 31 shows an apparatus for assessing reaction kinetics based on monitoring pressure changes due to production or consumption various gases during reaction.[0057]
• FIG. 32 shows results of calibration runs for polystyrene-toluene solutions using mechanical oscillators.[0058]
• FIG. 33 shows a calibration curve obtained by correlating M of the polystyrene standards with the distance between the frequency response curve for toluene and each of the polystyrene solutions of FIG. 32.[0059]
• FIG. 34 depicts the pressure recorded during solution polymerization of ethylene to polyethylene.[0060]
• FIGS.[0061]35-36 show ethylene consumption rate as a function of time, and the mass of polyethylene formed as a function of ethylene consumed, respectively.
• FIG. 37 shows a perspective view of an eight-vessel reactor module, of the type shown in FIG. 10, which is fitted with an optional liquid injection system.[0062]
• FIG. 38 shows a cross sectional view of a first embodiment of a fill port having an o-ring seal to minimize liquid leaks.[0063]
• FIG. 39 shows a second embodiment of a fill port.[0064]
• FIG. 40 shows a phantom front view of an injector manifold.[0065]
• FIG. 40A shows a perspective view of an[0066]injector manifold1006.
• FIG. 40B shows a cross sectional view of the injector manifold shown in FIG. 40A.[0067]
• FIGS.[0068]41-42 show a cross sectional view of an injector manifold along first and second section lines shown in FIG. 40, respectively.
• FIG. 43 shows a phantom top view of an injector adapter plate, which serves as an interface between an injector manifold and a block of a reactor module shown in FIG. 37.[0069]
• FIG. 44 shows a cross sectional side view of an injector adapter plate along a section line shown in FIG. 43.[0070]
• FIG. 45 shows an embodiment of a well injector.[0071]
• FIG. 46 shows a top view of a reactor module.[0072]
• FIG. 47 shows a “closed” state of an injector system valve prior to fluid injection.[0073]
• FIG. 48 shows an “open” state of an injector system valve prior during fluid injection, and shows a stirring mechanism and associated seals for maintaining above-ambient pressure in reactor vessels.[0074]
• FIG. 49 shows a cross sectional view of a magnetic feed through stirring mechanism that helps minimize gas leaks associated with dynamic seals.[0075]
• FIG. 50 shows a perspective view of a stirring mechanism shown in FIG. 48, and provides details of a multi-piece spindle.[0076]
• FIG. 50A shows an alternative design for a multi-piece spindle.[0077]
• FIG. 50B shows details of the alternative design for a multi-piece spindle shown in FIG. 50B.[0078]
• FIG. 51 shows details of a coupler portion of a multi-piece spindle.[0079]
• FIG. 52 shows a cross sectional view of the coupler shown in FIG. 51.[0080]
• FIG. 53 is a block diagram of a data processing system showing an implementation of the invention.[0081]
• FIGS.[0082]54-57 are schematic diagrams of a parallel reactor suitable for use with the invention.
• FIG. 58 is a flow diagram of a method of controlling and analyzing a parallel chemical reaction.[0083]
• FIG. 59 is an illustration of a dialog window for user input of system configuration information.[0084]
• FIG. 60 is an illustration of a dialog window for user input of data display information.[0085]
• FIG. 61 is an illustration of a dialog window for user input of parallel reactor parameters.[0086]
• FIG. 62 is an illustration of a dialog window for user input of a temperature gradient for reactor blocks in a parallel reactor.[0087]
• FIGS.[0088]63-64 are illustrations of windows displaying system status and experimental results for a parallel reactor.
• FIG. 65 is an illustration of a window displaying experimental results for a single reactor vessel.[0089]
• FIG. 66 is an illustration of a dialog window for user input of color scaling parameters.[0090]
• FIG. 67 is a schematic diagram of a computer platform suitable for implementing the data processing system of the invention.[0091]
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
• The present invention provides an apparatus, methods, and computer programs for carrying out and monitoring the progress and properties of multiple reactions in situ. It is especially useful for synthesizing, screening, and characterizing combinatorial libraries, but offers significant advantages over conventional experimental reactors as well. For example, in situ monitoring of individual reaction mixtures not only provides feedback for process controllers, but also provides data for determining reaction rates, product yields, and various properties of the reaction products, including viscosity and molecular weight during an experiment. Moreover, in situ monitoring coupled with tight process control can improve product selectivity, provide opportunities for process and product optimization, allow processing of temperature-sensitive materials, and decrease experimental variability.[0092]
• Other advantages result from using small mixture volumes. In addition to conserving valuable reactants, decreasing sample size increases surface area relative to volume within individual reactor vessels. This improves the uniformity of reaction mixtures, aids gas-liquid exchange in multiphase reactions, and increases heat transfer between the samples and the reactor vessels. Because large samples respond much slower to changes in system conditions, the use of small samples, along with in situ monitoring and process control, also allows for time-dependent processing and characterization.[0093]
• The parallel reactor of this invention is useful for the research and development of chemical reactions, catalysts and processes. The same type of reaction may be preformed in each vessel or different reactions may be performed in each vessel. Thus, each reaction vessel may vary with regard to its contents during an experiment. Each reaction vessel can vary by a process condition, including catalyst amounts (volume, moles or mass), ratios of starting components, time for reaction, reaction temperature, reaction pressure, rate of reactant addition to the reaction, reaction atmosphere, reaction stir rate, injection of a catalyst or reactant or other component (e.g., a reaction quencher) and other conditions that those of skill in the art will recognize. Each reaction vessel can also vary by the chemicals present, such as by using different reactants or catalysts in two or more vessels.[0094]
• For example, the parallel reactor of this invention may have reaction vessels that are of different volume. The reactor vessel volume may vary from about 0.1 milliliter (ml) to about 500 ml, more particularly from about 1 ml to about 100 ml and even more particularly from about 5 ml to about 20 ml. These reactor vessel sizes allow for reactant volumes in a range that functionally allow for proper stirring (e.g., a 15 ml reactor vessel allows for reactant volumes of between about 2-10 ml). Also, the parallel reactor of this invention allows the reactor pressure to vary from vessel to vessel or module to module or cell to cell, with each vessel being at a pressure in the range of from about atmospheric pressure to about 500 psi and more particularly in the range of from atmospheric to about 300 psi. In still other embodiments, the reactor temperature may vary from vessel to vessel or module to module or cell to cell, with each vessel being at a temperature in the range of from about 150° C. to about 250° C. and more particularly in the range of from −100° C. to about 200° C. The stirring rates may also vary from vessel to vessel or module to module or cell to cell, with each vessel being stirred by mechanical stirring at a rate of from about 0 to about 3000 revolutions per minute (rpm) and more particularly at a rate of from about 10 to about 2000 rpm and even more particularly at a rate of from about 100 to about 1000 rpm. In other embodiments, the parallel reactor of this invention allows for the injection of reactants or other components (such as catalysts) while a reactor vessel is at reaction pressure (as discussed in detail below). Generally, the injection of reactants or components allows for the reaction conditions to be varied from vessel to vessel, such as by adding a reaction quencher at a timed frequency or a conversion frequency. Reaction times can vary depending on the experiment being performed, but may be in the range from less than one minute to about 48 hours, more particularly in the range of from about one minute to about 24 hours and even more particularly in the range of from about 5 minutes to about 12 hours.[0095]
• Overview of Parallel Reactor[0096]
• The parallel reactor system of the present invention is an integrated platform for effecting combinatorial research in chemistry and materials science applications. An integrated parallel reactor system comprises a plurality of reactors that can be operated in parallel on a scale suitable for research applications—typically bench scale or smaller scale (e.g., mini-reactors and micro-reactors). The reactors of such an integrated system can typically, but not necessarily, be formed in, be integral with or be linked by a common substrate, be arranged in a common plane, preferably with spatial uniformity, and/or can share a common support structure or housing. The integrated parallel reactor system can also include one or more control and monitoring systems that are fully or partially integral therewith.[0097]
• FIG. 1 shows one embodiment of a[0098]parallel reactor system100. Thereactor system100 includesremovable vessels102 for receiving reactants.Wells104 formed into areactor block106 contain thevessels102. Although thewells104 can serve as reactor vessels,removable vessels102 or liners provide several advantages. For example, following reaction and preliminary testing (screening), one can remove a subset ofvessels102 from thereactor block106 for further in-depth characterization. When usingremovable vessels102, one can also selectvessels102 made of material appropriate for a given set of reactants, products, and reaction conditions. Unlike thereactor block106, which represents a significant investment, thevessels102 can be discarded if damaged after use. Finally, one canlower system100 costs and ensure compatibility with standardized sample preparation and testing equipment by designing thereactor block106 to accommodate commercially available vessels.
• As shown in FIG. 1, each of the[0099]vessels102 contains astirring blade108. In one embodiment, eachstirring blade108 rotates at about the same speed, so that each of the reaction mixtures within thevessels102 experience similar mixing. Because reaction products can be influenced by mixing intensity, a uniform rotation rate ensures that any differences in products does not result from mixing variations. In another embodiment, the rotation rate of eachstirring blade108 can be varied independently, which as discussed below, can be used to characterize the viscosity and molecular weight of the reaction products or can be used to study the influence of mixing speed on reaction.
• Depending on the nature of the starting materials, the types of reactions, and the method used to characterize reaction products and rates of reaction, it may be desirable to enclose the[0100]reactor block106 in achamber110. Thechamber110 may be evacuated or filled with a suitable gas. In some cases, thechamber110 may be used only during the loading of starting materials into thevessels102 to minimize contamination during sample preparation, for example, to prevent poisoning of oxygen sensitive catalysts. In other cases, thechamber110 may be used during the reaction process or the characterization phase, providing a convenient method of supplying one or more gases to all of thevessels102 simultaneously. In this way, a gaseous reactant can be added to all of thevessels102 at one time. Note, however, it is often necessary to monitor the rate of disappearance of a gaseous reactant—for example, when determining rates of conversion—and in such cases thevessels102 are each sealed and individually connected to a gas source, as discussed below.
• FIG. 2 shows a perspective view of a[0101]parallel reactor system130 comprised of amodular reactor block132. Themodular reactor block132 shown in FIG. 2 consists of sixmodules134, and eachmodule134 contains eight vessels (not shown). Note, however, the number ofmodules134 and the number of vessels within each of themodules134 can vary. In some embodiments, amodule134 may be broken down into component cells (not shown), for example with each cell containing one well104 holding areaction vessel102. Thus, if a module is to contain eight reaction vessels, there may be eight cells, which facilitates lower cost manufacturing as well as replacement of damaged or worn cells. There may any number of cells per module, such as cell that contains two reaction vessels per cell, etc.
• The use of[0102]modules134 offers several advantages over a monolithic reactor block. For example, the size of thereactor block132 can be easily adjusted depending on the number of reactants or the size of the combinatorial library. Also, relativelysmall modules134 are easier to handle, transport, and fabricate than a single, large reactor block. A damaged module can be quickly replaced by a spare module, which minimizes repair costs and downtime. Finally, the use ofmodules134 improves control over reaction parameters. For instance, stirring speed, temperature, and pressure of each of the vessels can be varied between modules.
• In the embodiment shown in FIG. 2, each of the[0103]modules134 is mounted on abase plate136 having a front138 and a rear140. Themodules134 are coupled to thebase plate136 using guides (not shown) that mate withchannels142 located on the surface of thebase plate136. The guides prevent lateral movement of themodules134, but allow linear travel along thechannels142 that extend from the front138 toward the rear140 of thebase plate136.Stops144 located in thechannels142 near thefront138 of thebase plate136 limit the travel of themodules134. Thus, one or more of themodules134 can be moved towards thefront138 of thebase plate136 to gain access to individual vessels while theother modules134 undergo robotic filling. In another embodiment, themodules134 are rigidly mounted to thebase plate136 using bolts, clips, or other fasteners.
• As illustrated in FIG. 2, a conventional robotic[0104]material handling system146 is ordinarily used to load vessels with starting materials. Therobotic system146 includes a pipette or probe148 that dispenses measured amounts of liquids into each of the vessels. Therobotic system146 manipulates theprobe148 using a 3-axis translation system150. Theprobe148 is connected tosources152 of liquid reagents throughflexible tubing154.Pumps156, which are located along theflexible tubing154, are used to transfer liquid reagents from thesources152 to theprobe148.Suitable pumps156 include peristaltic pumps and syringe pumps. Amulti-port valve158 located downstream of thepumps156 selects which liquid reagent from thesources152 is sent to theprobe148 for dispensing in the vessels.
• The robotic[0105]fluid handling system146 is controlled by aprocessor160. In the embodiment shown in FIG. 2, the user first supplies theprocessor160 with operating parameters using a software interface. Typical operating parameters include the coordinates of each of the vessels and the initial compositions of the reaction mixtures in individual vessels. The initial compositions can be specified as lists of liquid reagents from each of thesources152, or as incremental additions of various liquid reagents relative to particular vessels.
• Temperature Control and Monitoring[0106]
• The ability to monitor and control the temperature of individual reactor vessels is an important aspect of the present invention. During synthesis, temperature can have a profound effect on structure and properties of reaction products. For example, in the synthesis of organic molecules, yield and selectivity often depend strongly on temperature. Similarly, in polymerization reactions, polymer structure and properties—molecular weight, particle size, monomer conversion, microstructure—can be influenced by reaction temperature. During screening or characterization of combinatorial libraries, temperature control and monitoring of library members is often essential to making meaningful comparisons among members. Finally, temperature can be used as a screening criteria or can be used to calculate useful process and product variables. For instance, catalysts of exothermic reactions can be ranked based on peak reaction temperature and/or total heat released over the course of reaction, and temperature measurements can be used to compute rates of reaction and conversion.[0107]
• FIG. 3 illustrates one embodiment of a[0108]temperature monitoring system180, which includestemperature sensors182 that are in thermal contact withindividual vessels102. For clarity, we describe thetemperature monitoring system180 with reference to themonolithic reactor block106 of FIG. 1, but this disclosure applies equally well to themodular reactor block132 of FIG. 2.Suitable temperature sensors182 include jacketed or non-jacketed thermocouples (TC), resistance thermometric devices (RTD), and thermistors. Thetemperature sensors182 communicate with atemperature monitor184, which converts signals received from thetemperature sensors182 to a standard temperature scale. Anoptional processor186 receives temperature data from thetemperature monitor184. Theprocessor186 performs calculations on the data, which may include wall corrections and simple comparisons betweendifferent vessels102, as well as more involved processing such as calorimetry calculations discussed below. During an experimental run, temperature data is typically sent tostorage188 so that it can be retrieved at a later time for analysis.
• FIG. 4 shows a cross-sectional view of an integral temperature sensor-[0109]vessel assembly200. Thetemperature sensor202 is embedded in thewall204 of areactor vessel206. Thesurface208 of thetemperature sensor202 is located adjacent to theinner wall210 of the vessel to ensure good thermal contact between the contents of thevessel206 and thetemperature sensor202. The sensor arrangement shown in FIG. 3 is useful when it is necessary to keep the contents of thereactor vessel206 free of obstructions. Such a need might arise, for example, when using a freestanding mixing device, such as a magnetic stirring bar. Note, however, that fabricating an integral temperature sensor such as the one shown in FIG. 4 can be expensive and time consuming, especially when using glass reactor vessels.
• Thus, in another embodiment, the temperature sensor is immersed in the reaction mixture. Because the reaction environment within the vessel may rapidly damage the temperature sensor, it is usually jacketed with an inert material, such as a fluorinated thermoplastic. In addition to low cost, direct immersion offers other advantages, including rapid response and improved accuracy. In still another embodiment, the temperature sensor is placed on the[0110]outer surface212 of the reactor vessel of FIG. 4. As long as the thermal conductivity of the reactor vessel is known, relatively accurate and rapid temperature measurements can be made.
• One can also remotely monitor temperature using an infrared system illustrated in FIG. 5. The[0111]infrared monitoring system230 comprises anoptional isolation chamber232, which contains thereactor block234 andvessels236. The top238 of thechamber232 is fitted with awindow240 that is transparent to infrared radiation. An infrared-sensitive camera242 positioned outside theisolation chamber232, detects and records the intensity of infrared radiation passing through thewindow240. Since infrared emission intensity depends on source temperature, it can be used to distinguish high temperature vessels from low temperature vessels. With suitable calibration, infrared intensity can be converted to temperature, so that at any given time, thecamera242 provides “snapshots” of temperature along thesurface244 of thereactor block234. In the embodiment shown in FIG. 5, thetops246 of thevessels236 are open. In an alternate embodiment, thetops246 of thevessels236 are fitted with infrared transparent caps (not shown). Note that, with stirring, the temperature is uniform within a particular vessel, and therefore the surface temperature of the vessel measured by infrared emission will agree with the bulk temperature measured by a TC or RTD immersed in the vessel.
• The temperature of the reactor vessels and block can be controlled as well as monitored. Depending on the application, each of the vessels can be maintained at the same temperature or at different temperatures during an experiment. For example, one may screen compounds for catalytic activity by first combining, in separate vessels, each of the compounds with common starting materials; these mixtures are then allowed to react at uniform temperature. One may then further characterize a promising catalyst by combining it in numerous vessels with the same starting materials used in the screening step. The mixtures then react at different temperatures to gauge the influence of temperature on catalyst performance (speed, selectivity). In many instances, it may be necessary to change the temperature of the vessels during processing. For example, one may decrease the temperature of a mixture undergoing a reversible exothermic reaction to maximize conversion. Or, during a characterization step, one may ramp the temperature of a reaction product to detect phase transitions (melting range, glass transition temperature). Finally, one may maintain the reactor block at a constant temperature, while monitoring temperature changes in the vessels during reaction to obtain calorimetric data as described below.[0112]
• FIG. 6 shows a useful[0113]temperature control system260, which comprisesseparate heating262 andtemperature sensing264 elements. Theheating element262 shown in FIG. 6 is a conventional thin filament resistance heater whose heat output is proportional to the product of the filament resistance and the square of the current passing through the filament. Theheating element262 is shown coiled around areactor vessel266 to ensure uniform radial and axial heating of thevessel266 contents. Thetemperature sensing element264 can be a TC, RTD, and the like. Theheating element262 communicates with aprocessor268, which based on information received from thetemperature sensor264 through atemperature monitoring system270, increases or decreases heat output of theheating element262. Aheater control system272, located in the communication path between theheating element262 and theprocessor268, converts aprocessor268 signal for an increase (decrease) in heating into an increase (decrease) in electrical current through theheating element262. Generally, each of thevessels104 of theparallel reactor system100 shown in FIG. 1 or FIG. 3 are equipped with aheating element262 and one ormore temperature sensors264, which communicate with a centralheater control system272,temperature monitoring system270, andprocessor268, so that the temperature of thevessels104 can be controlled independently.
• Other embodiments include placing the[0114]heating element262 andtemperature sensor264 within thevessel266, which results in more accurate temperature monitoring and control of thevessel266 contents, and combining the temperature sensor and heating element in a single package. A thermistor is an example of a combined temperature sensor and heater, which can be used for both temperature monitoring and control because its resistance depends on temperature.
• FIG. 7 illustrates another temperature control system, which includes liquid cooling and heating of the[0115]reactor block106. Regulating the temperature of thereactor block106 provides many advantages. For example, it is a simple way of maintaining nearly uniform temperature in all of thereactor vessels102. Because of the large surface area of thevessels102 relative to the volume of the reaction mixture, cooling thereactor block106 also allows one to carryout highly exothermic reactions. When accompanied by temperature control ofindividual vessels102, active cooling of thereactor block106 allows for processing at sub-ambient temperatures. Moreover, active heating or cooling of thereactor block106 combined with temperature control ofindividual vessels102 or groups ofvessels102 also decreases response time of the temperature control feedback. One may control the temperature ofindividual vessels102 or groups ofvessels102 using compact heat transfer devices, which include electric resistance heating elements or thermoelectric devices, as shown in FIG. 6 and FIG. 8, respectively. Although we describe reactor block cooling with reference to themonolithic reactor block106, one may, in a like manner, independently heat or coolindividual modules134 of themodular reactor block132 shown in FIG. 2.
• Returning to FIG. 7, a[0116]thermal fluid290, such as water, steam, a silicone fluid, a fluorocarbon, and the like, is transported from auniform temperature reservoir292 to thereactor block106 using a constant orvariable speed pump294. Thethermal fluid290 enters thereactor block106 from apump outlet conduit296 through aninlet port298. From theinlet port298, thethermal fluid290 flows through apassageway300 formed in thereactor block106. The passageway may comprise single or multiple channels. Thepassageway300 shown in FIG. 7, consists of a single channel that winds its way between rows ofvessels102, eventually exiting thereactor block106 at anoutlet port302. Thethermal fluid290 returns to thereservoir292 through a reactorblock outlet conduit304. Aheat pump306 regulates the temperature of thethermal fluid290 in thereservoir292 by adding or removing heat through aheat transfer coil308. In response to signals from temperature sensors (not shown) located in thereactor block106 and thereservoir292, aprocessor310 adjusts the amount of heat added to or removed from thethermal fluid290 through thecoil308. To adjust the flow rate ofthermal fluid290 through thepassageway300, theprocessor310 communicates with avalve312 located in areservoir outlet conduit314. Thereactor block106,reservoir292, pump294, andconduits296,304,314 can be insulated to improve temperature control in thereactor block106.
• Because the[0117]reactor block106 is typically made of a metal or other material possessing high thermal conductivity, thesingle channel passageway300 is usually sufficient for maintaining the temperature of the block106 a few degrees above or below room temperature. To improve temperature uniformity within thereactor block106, the passageway can be split into parallel channels (not shown) immediately downstream of theinlet port298. In contrast to thesingle channel passageway300 depicted in FIG. 7, each of the parallel channels passes between a single row ofvessels102 before exiting thereactor block106. This parallel flow arrangement decreases the temperature gradient between theinlet298 andoutlet302 ports. To further improve temperature uniformity and heat exchange between thevessels102 and theblock106, thepassageway300 can be enlarged so that thewells104 essentially project into a cavity containing thethermal fluid290. Additionally, one may eliminate thereactor block106 entirely, and suspend or immerse thevessels102 in a bath containing thethermal fluid290.
• FIG. 8 illustrates the use of thermoelectric devices for heating and cooling individual vessels. Thermoelectric devices can function as both heaters and coolers by reversing the current flow through the device. Unlike resistive heaters, which convert electric power to heat, thermoelectric devices are heat pumps that exploit the Peltier effect to transfer heat from one face of the device to the other. A typical thermoelectric assembly has the appearance of a sandwich, in which the front face of the thermoelectric device is in thermal contact with the object to be cooled (heated), and the back face of the device is in thermal contact with a heat sink (source). When the heat sink or source is ambient air, the back face of the device typically has an array of thermally conductive fins to increase the heat transfer area. Preferably, the heat sink or source is a liquid. Compared to air, liquids have higher thermal conductivity and heat capacity, and therefore should provide better heat transfer through the back face of the device. But, because thermoelectric devices are usually made with bare metal connections, they often must be physically isolated from the liquid heat sink or source.[0118]
• For example, FIG. 8 illustrates one way of using[0119]thermoelectric devices330 to heat andcool reactor vessels338 using a liquid heat sink or source. In the configuration shown in FIG. 8,thermoelectric devices330 are sandwiched between areactor block334 and aheat transfer plate336.Reactor vessels338 sit withinwells340 formed in thereactor block334.Thin walls342 at the bottom of thewells340, separate thevessels338 from thethermoelectric devices330, ensuring good thermal contact. As shown in FIG. 8, each of thevessels338 thermally contacts a singlethermoelectric device330, although in general, a thermoelectric device can heat or cool more than one of thevessels338. Thethermoelectric devices330 either obtain heat from, or dump heat into, a thermal fluid that circulates through aninterior cavity344 of theheat transfer plate336. The thermal fluid enters and leaves theheat transfer plate336 throughinlet346 andoutlet348 ports, and its temperature is controlled in a manner similar to that shown in FIG. 7. During an experiment, the temperature of the thermal fluid is typically held constant, while the temperature of thevessels338 is controlled by adjusting the electrical current, and hence, the heat transport through thethermoelectric devices330. Though not shown in FIG. 8, the temperature of thevessels338 are controlled in a manner similar to the scheme depicted in FIG. 6. Temperature sensors located adjacent to thevessels338 and within the heattransfer plate cavity344 communicate with a processor via a temperature monitor. In response to temperature data from the temperature monitor, the processor increases or decrease heat flow to or from thethermoelectric devices330. A thermoelectric device control system, located in the communication path between thethermoelectric devices330 and the processor, adjusts the magnitude and direction of the flow of electrical current through each of thethermoelectric devices330 in response to signals from the processor.
• Calorimetric Data Measurement and Use[0120]
• Temperature measurements often provide a qualitative picture of reaction kinetics and conversion and therefore can be used to screen library members. For example, rates of change of temperature with respect to time, as well as peak temperatures reached within each of the vessels can be used to rank catalysts. Typically, the best catalysts of an exothermic reaction are those that, when combined with a set of reactants, result in the greatest heat production in the shortest amount of time.[0121]
• In addition to its use as a screening tool, temperature measurement—combined with proper thermal management and design of the reactor system—can also be used to obtain quantitative calorimetric data. From such data, scientists can, for example, compute instantaneous conversion and reaction rate, locate phase transitions (melting point, glass transition temperature) of reaction products, or measure latent heats to deduce structural information of polymeric materials, including degree of crystallinity and branching.[0122]
• FIG. 9 shows a cross-sectional view of a portion of a[0123]reactor block360 that can be used to obtain accurate calorimetric data. Each of thevessels362 contain stirringblades364 to ensure that thecontents366 of thevessels362 are well mixed and that the temperature within any one of thevessels362, T_j, is uniform. Each of thevessels362 contains athermistor368, which measures T_jand heats thevessel contents366. Thewalls370 of thevessels362 are made of glass, although one may use any material having relatively low thermal conductivity, and similar mechanical strength and chemical resistance. Thevessels362 are held withinwells372 formed in thereactor block360, and each of thewells372 is lined with an insulatingmaterial374 to further decrease heat transfer to or from thevessels362. Useful insulatingmaterials374 include glass wool, silicone rubber, and the like. The insulatingmaterial374 can be eliminated or replaced by a thermal paste when better thermal contact between thatreactor block360 and thevessels362 is desired—good thermal contact is needed, for example, when investigating exothermic reactions under isothermal conditions. Thereactor block360 is made of a material having high thermal conductivity, such as aluminum, stainless steel, brass, and so on. High thermal conductivity, accompanied by active heating or cooling using any of the methods described above, help maintain uniform temperature, T_o, throughout thereactor block360. One can account for non-uniform temperatures within thereactor block360 by measuring T_oj, the temperature of theblock360 in the vicinity of each of thevessels362, usingblock temperature sensors376. In such cases, T_oj, instead of T_o, is used in the calorimetric calculations described next.
• An energy balance around the[0124]contents366 of one of the vessels362 (jth vessel) yields an expression for fractional conversion, X_j, of a key reactant at any time, t, assuming that the heat of reaction, ΔH_rjand the specific heat of thevessel contents366, C_Pj, are known and are constant over the temperature range of interest:$\begin{array}{cc}{M}_jc_{P,j}\frac{T_j}{t}=m_{o,j}\Delta H_{r,j}\frac{X_j}{t}+Q_{in,j}-Q_{\mathrm{out},j}.& I\end{array}$

  
• In expression I, M[0125]_jis the mass of thecontents366 of the jth vessel; m_ojis the initial mass of the key reactant; Q_injis the rate of heat transfer into the jth vessel by processes other than reaction, as for example, by resistance heating of thethermistor368. Q_outjis the rate of heat transfer out of the jth vessel, which can be determined from the expression:
• Q_out,j=U_jA_j(T_j−T_o)=U_jA_jΔT_j  II
• where A[0126]_jis the heat transfer area—the surface area of the jth vessel—and U_jis the heat transfer coefficient, which depends on the properties of thevessel362 and itscontents366, as well as the stirring rate. U_jcan be determined by measuring the temperature rise, ΔT_j, in response to a known heat input.
• Equations I and II can be used to determine conversion from calorimetric data in at least two ways. In a first method, the temperature of the[0127]reactor block360 is held constant, and sufficient heat is added to each of thevessels362 through thethermistor368 to maintain a constant value of ΔT_j. Under such conditions, and after combining equations I and II, the conversion can be calculated from the expression$\begin{array}{cc}{X}_j=\frac{1}{m_{o,j}\Delta H_{r,j}}\left(U_jA_jt_f\Delta T_j-{\int }_0^{t_f}Q_{in,j}t\right),& \mathrm{III}\end{array}$

  
• where the integral can be determined by numerically integrating the power consumption of the[0128]thermistor368 over the length of the experiment, t_f. This method can be used to measure the heat output of a reaction under isothermal conditions.
• In a second method, the temperature of the[0129]reactor block360 is again held constant, but T_jincreases or decreases in response to heat produced or consumed in the reaction. Equation I and II become under such circumstances$\begin{array}{cc}{X}_j=\frac{1}{m_{o,j}\Delta H_{r,j}}\left(M_jc_{P,j}\left(T_{f,j}-T_{i,j}\right)+U_jA_j{\int }_0^{t_f}\Delta T_{j}t\right).& \mathrm{IV}\end{array}$

  
• In equation IV, the integral can be determined numerically, and T[0130]_fjand T_ijare temperatures of the reaction mixture within the jth vessel at the beginning and end of reaction, respectively. Thus, if T_fjequals T_ij, the total heat liberated is proportional to${\int }_0^{t_f}\Delta T_{j}t.$

  
• This method is simpler to implement than the isothermal method since it does not require temperature control of individual vessels. But, it can be used only when the temperature change in each of the[0131]reaction vessels362 due to reaction does not significantly influence the reaction under study.
• One may also calculate the instantaneous rate of disappearance of the key reactant in the jth vessel, −r[0132]_j, using equation I, III or IV since −r, is related to conversion through the relationship$\begin{array}{cc}-r_j=C_{o,j}\frac{X_j}{t},& V\end{array}$

  
• which is valid for constant volume reactions. The constant C[0133]_ojis the initial concentration of the key reactant.
• Stirring Systems[0134]
• Mixing variables such as stirring blade torque, rotation rate, and geometry, may influence the course of a reaction and therefore affect the properties of the reaction products. For example, the overall heat transfer coefficient and the rate of viscous dissipation within the reaction mixture may depend on the stirring blade rate of rotation. Thus, in many instances it is important that one monitor and control the rate of stirring of each reaction mixture to ensure uniform mixing. Alternatively, the applied torque may be monitored in order to measure the viscosity of the reaction mixture. As described in the next section, measurements of solution viscosity can be used to calculate the average molecular weight of polymeric reaction products.[0135]
• FIG. 10 shows an exploded, perspective view of a stirring system for a[0136]single module390 of a modular reactor block of the type shown in FIG. 2. Themodule390 comprises ablock392 having eightwells394 for containingremovable reaction vessels396. The number ofwells394 andreaction vessels396 can vary. Thetop surface398 of a removablelower plate400 serves as the base for each of thewells394 and permits removal of thereaction vessels396 through thebottom402 of theblock392.Screws404 secure thelower plate400 to thebottom402 of theblock392. Anupper plate406, which rests on the top408 of theblock392, supports and directs elongatedstirrers410 into the interior of thevessels396. Each of thestirrers410 comprises aspindle412 and a rotatable stirring member or stirringblade414 which is attached to the lower end of eachspindle412. Agear416 is attached to t h e upper end of each of eachspindle412. When assembled, eachgear416 meshes with anadjacent gear416 forming a gear train (not shown) so that eachstirrer410 rotates at the same speed. ADC stepper motor418 provides torque for rotating thestirrers410, although an air-driven motor, a constant-speed AC motor, or a variable-speed AC motor can be used instead. A pair of driver gears420 couple themotor418 to the gear train. Aremovable cover422 provides access to the gear train, which is secured to theblock392 using threadedfasteners424. In addition to the gear train, one may employ belts, chains and sprockets, or other drive mechanisms. In alternate embodiments, each of thestirrers410 are coupled to separate motors so that the speed or torque of each of thestirrers410 can be independently varied and monitored. Furthermore, the drive mechanism—whether employing a single motor and gear train or individual motors—can be mounted below thevessels362. In such cases, magnetic stirring blades placed in thevessels362 are coupled to the drive mechanism using permanent magnets attached to gear train spindles or motor shafts.
• In addition to the stirring system, other elements shown in FIG. 10 merit discussion. For example, the[0137]upper plate406 may contain vessel seals426 that allow processing at pressures different than atmospheric pressure. Moreover, theseals426 permit one to monitor pressure in thevessels396 over time. As discussed below, such information can be used to calculate conversion of a gaseous reactant to a condensed species. Note that eachspindle412 may penetrate theseals426, or may be magnetically coupled to an upper spindle member (not shown) attached to thegear416. FIG. 10 also showstemperature sensors428 embedded in theblock392 adjacent to each of thewells394. Thesensors428 are part of the temperature monitoring and control system described previously.
• In another embodiment, an array of electromagnets rotate freestanding stirring members or magnetic stirring bars, which obviates the need for the mechanical drive system shown in FIG. 10. Electromagnets are electrical conductors that produce a magnetic field when an electric current passes through them. Typically, the electrical conductor is a wire coil wrapped around a solid core made of material having relatively high permeability, such as soft iron or mild steel.[0138]
• FIG. 11 is a schematic representation of one embodiment of an[0139]electromagnet stirring array440. Theelectromagnets442 or coils belonging to thearray440 are mounted in thelower plate400 of thereactor module390 of FIG. 10 so that their axes are about parallel to the centerlines of thevessels396. Although greater magnetic field strength can be achieved by mounting the electromagnets with their axes perpendicular to the centerlines of thevessels396, such a design is more difficult to implement since it requires placing electromagnets between thevessels396. The eight crosses orvessel sites444 in FIG. 11 mark the approximate locations of the respective centers of each of thevessels396 of FIG. 10 and denote the approximate position of the rotation axes of the magnetic stirring bars (not shown). In thearray440 shown in FIG. 11, fourelectromagnets442 surround eachvessel site444, though one may use fewer or greater numbers ofelectromagnets442. The minimum number of electromagnets per vessel site is two, but in such a system it is difficult to initiate stirring, and it is common to stall the stirring bar. Electromagnet size and available packing density primarily limit the maximum number of electromagnets.
• As illustrated in FIG. 11, each[0140]vessel site444, except those at theends446 of thearray440, shares its fourelectromagnets442 with two adjacent vessel sites. Because of this sharing, magnetic stirring bars at adjacent vessel sites rotate in opposite directions, as indicated by thecurved arrows448 in FIG. 11, which may lead to stalling. Other array configurations are possible. For example, FIG. 12 shows a portion of anarray460 in which the ratio ofelectromagnets462 tovessel sites464 approaches 1:1 as the number ofvessel sites464 becomes large. Because each of thevessel sites464 shares itselectromagnets462 with its neighbors, magnetic stirring bars at adjacent vessel sites rotate in opposite directions, as shown bycurved arrows466. In contrast, FIG. 13 shows a portion of anarray470 in which the ratio ofelectromagnets472 tovessel sites474 approaches 2:1 as the number of vessel sites becomes large. Because of the comparatively large number ofelectromagnets472 tovessel sites474, all of the magnetic stirring bars can be made to rotate in thesame direction476, which minimizes stalling. Similarly, FIG. 14 shows an array480 in which the number ofelectromagnets482 tovessel sites484 is 4:1. Each magnetic stirring bar rotates in thesame direction486.
• FIG. 15 illustrates additional elements of an[0141]electromagnetic stirring system500. For clarity, FIG. 15 shows asquare electromagnet array502 comprised of fourelectromagnets504, although larger arrays, such as those shown in FIGS.12-14, can be used. Each of theelectromagnets504 comprises awire506 wrapped around a high permeabilitysolid core508. The pairs ofelectromagnets504 located on the two diagonals of thesquare array502 are connected in series to form afirst circuit510 and asecond circuit512. The first510 and second512 circuits are connected to adrive circuit514, which is controlled by aprocessor516. Electrical current, whether pulsed or sinusoidal, can be varied independently in the twocircuits510,512 by thedrive circuit514 andprocessor516. Note that within eachcircuit510,512, the current flows in opposite directions in thewire506 around thecore508. In this way, each of theelectromagnets504 within aparticular circuit510,512 have opposite magnetic polarities. Theaxes518 of theelectromagnets504 are about parallel to thecenterline520 of thereactor vessel522. Amagnetic stirring bar524 rests on the bottom of thevessel522 prior to operation. Although theelectromagnets504 can also be oriented with theiraxes518 perpendicular to thevessel centerline520, the parallel alignment provides higher packing density.
• FIG. 16 shows the magnetic field direction of a 2×2 electromagnet array at four different times during one full rotation of the magnetic stirring[0142]bar524 of FIG. 15, which is rotating at a steady frequency of ω radians s⁻¹. In FIG. 16, a circle with aplus sign532 indicates that the electromagnet produces a magnetic field in a first direction; a circle with aminus sign534 indicates that the electromagnet produces a magnetic field in a direction opposite to the first direction; and a circle with nosign536 indicates that the electromagnet produces no magnetic field. At time t=0, theelectromagnets530 produce an overall magnetic field with a direction represented by afirst arrow538 at the vessel site. At time$t=\frac{\mathrm{<figure-callout\; label="\pi "\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00015.png"\; state="\{\{state\}\}">\pi </figure-callout>}}{2\omega },$

  
• the[0143]electromagnets540 produce an overall magnetic field with a direction represented by asecond arrow542. Since the magnetic stirring bar524 (FIG. 15) attempts to align itself with the direction of the overall magnetic field, it rotates clockwise ninety degrees from thefirst direction538 to thesecond direction542. At time$t=\frac{\pi }{\omega },$

  
• the[0144]electromagnets544 produce an overall magnetic field with a direction represented by athird arrow546. Again, the magnetic stirringbar524 aligns itself with the direction of the overall magnetic field, and rotates clockwise an additional ninety degrees. At time$t=\frac{3\mathrm{<figure-callout\; label="\pi "\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00015.png"\; state="\{\{state\}\}">\pi </figure-callout>}}{2\omega },$

  
• the[0145]electromagnets548 produce an overall magnetic field with a direction represented by afourth arrow550, which rotates the magnetic stirringbar524 clockwise another ninety degrees. Finally, at time$t=\frac{2\pi }{\omega },$

  
• the[0146]electromagnets530 produce an overall magnetic field with direction represented by thefirst arrow538, which rotates the magnetic stirringbar524 back to its position at time t=0.
• FIG. 17 illustrates magnetic field direction of a 4×4 electromagnetic array at five different times during one full rotation of a 3×3 array of magnetic stirring bars. As in FIG. 15, a circle with a[0147]plus sign570, aminus sign572, or nosign574 represents the magnetic field direction of an individual electromagnet, while anarrow576 represents the direction of the overall magnetic field at a vessel site. As shown, sixteen electromagnets are needed to rotate nine magnetic stirring bars. But, as indicated in FIG. 18, due to sharing of electromagnets by multiple magnetic stirring bars, the rotational direction of the magnetic fields is non-uniform. Thus, five of the fields rotate in aclockwise direction590 while the remaining four fields rotate in acounter-clockwise direction592.
• FIG. 19 and FIG. 20 illustrate wiring configurations for electromagnet arrays in which each vessel site is located between four electromagnets defining four corners of a quadrilateral sub-array. For each vessel site, both wiring configurations result in an electrical connection between electromagnets located on the diagonals of a given sub-array. In the[0148]wiring configuration610 shown in FIG. 19,electromagnets612 in alternating diagonal rows are wired together to form two series ofelectromagnets612. Dashed and solid lines represent electrical connections betweenelectromagnets612 in afirst series614 and asecond series616, respectively.Plus signs618 andminus signs620 indicate polarity (magnetic field direction) ofindividual electromagnets612 at any time, t, when current in thefirst series614 and thesecond series616 ofelectromagnets612 are in phase. FIG. 20 illustrates analternate wiring configuration630 ofelectromagnets632, where again, dashed and solid lines represent electrical connections between the first634 andsecond series636 ofelectromagnets632, andplus signs638 andminus signs640 indicate magnetic polarity.
• Note that for both[0149]wiring configurations610,630, the polarities of theelectromagnets612,632 of thefirst series614,634 are not the same, though amplitudes of the current passing through the connections between theelectromagnets612,632 of thefirst series614,634 are equivalent. The same is true for thesecond series616,636 ofelectromagnets612,632. One can achieve opposite polarities within thefirst series614,634 orsecond series616,636 ofelectromagnets612,632 by reversing the direction of electrical current around the core of theelectromagnet612,632. See, for example, FIG. 15. In the twowiring configurations610,630 of FIGS. 19 and 20, every quadrilateral array of fouradjacent electromagnets612,632 defines a site for rotating a magnetic stirring bar, and the diagonal members of each of the fouradjacent electromagnets612,632 belong to thefirst series614,634 and the second616,636 series ofelectromagnets612,632. Moreover, within any set of fouradjacent electromagnets612,632, each pair ofelectromagnets612,632 belonging to the same series have opposite polarities. The twowiring configurations610,630 of FIGS. 19 and 20 can be used with any of thearrays460,470,480 shown in FIGS.12-14.
• The[0150]complex wiring configurations610,630 of FIGS. 19 and 20 can be placed on a printed circuit board, which serves as both a mechanical support and alignment fixture for theelectromagnets612,632. The use of a printed circuit board allows for rapid interconnection of theelectromagnets612,632, greatly reducing assembly time and cost, and eliminating wiring errors associated with manual soldering of hundreds of individual connections. Switches can be used to turn stirring on and off for individual rows of vessels. A separate drive circuit may be used for each row of vessels, which allows stirring speed to be used as a variable during an experiment.
• FIG. 21 is a[0151]plot650 of current versus time and shows the phase relationship between sinusoidal source currents, I_A(t)652 and I_B(t)654, which drive, respectively, thefirst series614,634 and thesecond series616,636 ofelectromagnets612,632 shown in FIGS. 19 and 20. The twosource currents652,654 have equivalent peak amplitude and frequency, ω_D, though I_A(t)652 lags I_B(t)654 by$\frac{\mathrm{<figure-callout\; label="\pi "\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00015.png"\; state="\{\{state\}\}">\pi </figure-callout>}}{2}$

  
• radians. Because of this phase relationship, magnetic stirring bars placed at rotation sites defined by any four[0152]adjacent electromagnets612,632 of FIGS. 19 and 20 will each rotate at an angular frequency of ω_ij, though adjacent stirring bars will rotate in opposite directions when theelectromagnet array460 depicted in FIG. 12 is used. If, however, thearrays470,480 shown in FIGS. 13 and 14 are used, adjacent stirring bars will rotate in the same direction. In an alternate embodiment, a digital approximation to a sine wave can be used.
• FIG. 22 is a block diagram of a[0153]power supply670 for anelectromagnet array672.Individual electromagnets674 are wired together in a first and second series as, for example, shown in FIG. 19 or20. The first and second series ofelectromagnets674 are connected to apower source676, which provides the two series with sinusoidal driving currents that are$\frac{\mathrm{<figure-callout\; label="\pi "\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00015.png"\; state="\{\{state\}\}">\pi </figure-callout>}}{2}$

  
• radians out of phase. Normally, the amplitudes of the two driving currents are the same and do not depend on frequency. A[0154]processor678 controls both the amplitude and the frequency of the driving currents.
• Viscosity and Related Measurements[0155]
• The present invention provides for in situ measurement of viscosity and related properties. As discussed below, such data can be used, for example, to monitor reactant conversion, and to rank or characterize materials based on molecular weight or particle size.[0156]
• The viscosity of a polymer solution depends on the molecular weight of the polymer and its concentration in solution. For polymer concentrations well below the “semidilute limit”—the concentration at which the solvated polymers begin to overlap one another—the solution viscosity, η, is related to the polymer concentration, C, in the limit as C approaches zero by the expression[0157]
• η=(1+C[η])η_s  VI
• where η[0158]_sis the viscosity of the solvent. Essentially, adding polymer to a solvent increases the solvent's viscosity by an amount proportional to the polymer concentration. The proportionality constant [η], is known as the intrinsic viscosity, and is related to the polymer molecular weight, M, through the expression
• [η]=[η₀]M^α,   VII
• where [η[0159]₀] and α are empirical constants. Equation VII is known as the Mark-Houwink-Sakurda (MHS) relation, and it, along with equation VI, can be used to determine molecular weight from viscosity measurements.
• Equation VI requires concentration data from another source; with polymerization reactions, polymer concentration is directly related to monomer conversion. In the present invention, such data can be obtained by measuring heat evolved during reaction (see equation III and IV) or, as described below, by measuring the amount of a gaseous reactant consumed during reaction. The constants in the MHS relation are functions of temperature, polymer composition, polymer conformation, and the quality of the polymer-solvent interaction. The empirical constants, [η[0160]₀] and α, have been measured for a variety of polymer-solvent pairs, and are tabulated in the literature.
• Although equations VI and VII can be used to approximate molecular weight, in situ measurements of viscosity in the present invention are used mainly to rank reaction products as a function of molecular weight. Under most circumstances, the amount of solvent necessary to satisfy the concentration requirement of equation VI would slow the rate of reaction to an unacceptable level. Therefore, most polymerizations are carried out at polymer concentrations above the semidilute limit, where the use of equations VI and VII to calculate molecular weight would lead to large error. Nevertheless, viscosity can be used to rank reaction products even at concentrations above the semidilute limit since a rise in viscosity during reaction generally reflects an increase in polymer concentration, molecular weight or both. If necessary, one can accurately determine molecular weight from viscosity measurements at relatively high polymer concentration by first preparing temperature-dependent calibration curves that relate viscosity to molecular weight. But the curves would have to be obtained for every polymer-solvent pair produced, which weighs against their use for screening new polymeric materials.[0161]
• In addition to ranking reactions, viscosity measurements can also be used to screen or characterize dilute suspensions of insoluble particles—polymer emulsions or porous supports for heterogeneous catalysts—in which viscosity increases with particle size at a fixed number concentration. In the case of polymer emulsions, viscosity can serve as a measure of emulsion quality. For example, solution viscosity that is constant over long periods of time may indicate superior emulsion stability, or viscosity within a particular range may correlate with a desired emulsion particle size. With porous supports, viscosity measurements can be used to identify active catalysts: in many cases, the catalyst support will swell during reaction due to the formation of insoluble products within the porous support.[0162]
• In accordance with the present invention, viscosity or related properties of the reactant mixtures are monitored by measuring the effect of viscous forces on stirring blade rotation. Viscosity is a measure of a fluid's resistance to a shear force. This shear force is equal to the applied torque, Γ, needed to maintain a constant angular velocity of the stirring blade. The relationship between the viscosity of the reaction mixture and the applied torque can be expressed as[0163]
• Γ=K_ω(ω,T)η,   VIII
• where K[0164]_ω is a proportionality constant that depends on the angular frequency, ω, of the stirring bar, the temperature of the reaction mixture, and the geometries of the reaction vessel and the stirring blade. K_ω can be obtained through calibration with solutions of known viscosity.
• During a polymerization, the viscosity of the reaction mixture increases over time due to the increase in molecular weight of the reaction product or polymer concentration or both. This change in viscosity can be monitored by measuring the applied torque and using equation VIII to convert the measured data to viscosity. In many instances, actual values for the viscosity are unnecessary, and one can dispense with the conversion step. For example, in situ measurements of applied torque can be used to rank reaction products based on molecular weight or conversion, as long as stirring rate, temperature, vessel geometry and stirring blade geometry are about the same for each reaction mixture.[0165]
• FIG. 23 illustrates an[0166]apparatus700 for directly measuring the applied torque. Theapparatus700 comprises astirring blade702 coupled to adrive motor704 via arigid drive spindle706. Thestirring blade702 is immersed in areaction mixture708 contained within areactor vessel710.Upper712 and lower714 supports prevent thedrive motor704 andvessel710 from rotating during operation of thestirring blade702. For simplicity, thelower support714 can be a permanent magnet. A torque orstrain gauge716 shown mounted between theupper support712 and thedrive motor704 measures the average torque exerted by themotor704 on thestirring blade702. In alternate embodiments, thestrain gauge716 is inserted within thedrive spindle706 or is placed between thevessel710 and thelower support714. If located within thedrive spindle706, a system of brushes or commutators (not shown) are provided to allow communication with the rotating strain gauge. Often, placement of thestrain gauge716 between thevessel710 and thelower support714 is the best option since many stirring systems, such as the one shown in FIG. 10, use a single motor to drive multiple stirring blades.
• FIG. 24 shows placement of a[0167]strain gauge730 in a portion of abase plate732 that is similar to thelower plate400 of thereactor module390 shown in FIG. 10. Thelower end734 of thestrain gauge730 is rigidly attached to thebase plate732. A firstpermanent magnet736 is mounted on thetop end738 of thestrain gauge730, and a secondpermanent magnet740 is attached to thebottom742 of areactor vessel744. When thevessel744 is inserted in thebase plate732, the magnetic coupling between thefirst magnet736 and thesecond magnet740 prevents thevessel744 from rotating and transmits torque to thestrain gauge730.
• Besides using a strain gauge, one can also monitor drive motor power consumption, which is related to the applied torque. Referring again to FIG. 23, the method requires monitoring and control of the[0168]stirring blade702 rotational speed, which can be accomplished by mounting asensor718 adjacent to thedrive spindle706.Suitable sensors718 include optical detectors, which register the passage of a spot on thedrive spindle706 by a reflectance measurement, or which note the interruption of a light beam by an obstruction mounted on thedrive spindle706, or which discern the passage of a light beam through a slot on thedrive spindle706 or on a co-rotating obstruction. Othersuitable sensors718 include magnetic field detectors that sense the rotation of a permanent magnet affixed to thespindle706. Operational details of magnetic field sensors are described below in the discussion of phase lag detection. Sensors such as encoders, resolvers, Hall effect sensors, and the like, are commonly integrated into themotor704. Anexternal processor720 adjusts the power supplied to thedrive motor704 to maintain aconstant spindle706 rotational speed. By calibrating the required power against a series of liquids of known viscosity, the viscosity of an unknown reaction mixture can be determined.
• In addition to direct measurement, torque can be determined indirectly by measuring the phase angle or phase lag between the stirring blade and the driving force or torque. Indirect measurement requires that the coupling between the driving torque and the stirring blade is “soft,” so that significant and measurable phase lag occurs.[0169]
• With magnetic stirring, “soft” coupling occurs automatically. The torque on the stirring bar is related to the magnetic moment of the stirring bar, μ, and the amplitude of the magnetic field that drives the rotation of the stirring bar, H, through the expression[0170]
• Γ=μHsin θ,   IX
• where θ is the angle between the axis of the stirring bar (magnetic moment) and the direction of the magnetic field. At a given angular frequency, and for known μ and H, the phase angle, θ, will automatically adjust itself to the value necessary to provide the amount of torque needed at that frequency. If the torque required to stir at frequency ω is proportional to the solution viscosity and the stirring frequency—an approximation useful for discussion—then the viscosity can be calculated from measurements of the phase angle using the equation[0171]
• Γ=μH sin θ=αηω  X
• where α is a proportionality constant that depends on temperature, and the geometry of the vessel and the stirring blade. In practice, one may use equation VIII or a similar empirical expression for the right hand side of equation X if the torque does not depend linearly on the viscosity-frequency product.[0172]
• FIG. 25 shows an inductive[0173]sensing coil system760 for measuring phase angle or phase lag, θ. Thesystem760 comprises fourelectromagnets762, which drive the magnetic stirringbar764, and a phase-sensitive detector, such as a standard lock-in amplifier (not shown). Agradient coil766 configuration is used to sense motion of the stirringbar764, though many other well known inductive sensing coil configurations can be used. Thegradient coil766 is comprised of afirst sensing coil768 and asecond sensing coil770 that are connected in series and are wrapped in opposite directions around afirst electromagnet772. Because of their opposite polarities, any difference in voltages induced in the twosensing coils768,770 will appear as a voltage difference across theterminals774, which is detected by the lock-in amplifier. If no stirringbar764 is present, then the alternating magnetic field of thefirst electromagnet772 will induce approximately equal voltages in each of the twocoils768,770—assuming they are mounted symmetrically with respect to thefirst electromagnet772—and the net voltage across theterminals774 will be about zero. When amagnetic stirring bar764 is present, the motion of therotating magnet764 will induce a voltage in each of the twosensing coils768,770. But, the voltage induced in thefirst coil768, which is closer to the stirringbar764, will be much larger than the voltage induced in thesecond coil770, so that the voltage across theterminals774 will be nonzero. A periodic signal will thus be induced in the sensing coils768,770, which is measured by the lock-in amplifier.
• FIG. 26 and FIG. 27 show[0174]typical outputs790,810 from the inductivesensing coil system760 of FIG. 25, which illustrate phase lag associated with magnetic stirring for low and high viscosity solutions, respectively.Periodic signals792,812 from the sensing coils768,770 are plotted with sinusoidal reference signals794,814 used to drive the electromagnets. Time delay,Δt796,816, between theperiodic signals792,812 and the reference signals794,814 is related to the phase angle by θ=ω·Δt. Visually comparing the twooutputs790,810 indicates that the phase angle associated with the high viscosity solution is larger than the phase angle associated with the low viscosity solution.
• FIG. 27 illustrates how amplitude and phase angle will vary during a reaction as the viscosity increases from a low value to a value sufficient to stall the stirring bar. A waveform or signal[0175]820 from the sensing coils is input to a lock-inamplifier822, using the drive circuit sinusoidal current as a phase andfrequency reference signal824. The lock-inamplifier822 outputs theamplitude826 of thesensing coil signal820, andphase angle828 or phase lag relative to thereference signal824. The maximum phase angle is$\frac{\mathrm{<figure-callout\; label="\pi "\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00015.png"\; state="\{\{state\}\}">\pi </figure-callout>}}{2}$

  
• radians, since, as shown by equation X, torque decreases with further increases in θ leading to slip of the stirring[0176]bar764 of FIG. 25. Thus, as viscosity increases during reaction, thephase angle828 or phase lag also increases until the stirring bar stalls, and theamplitude826 abruptly drops to zero. This can be seen graphically in FIG. 27, which shows plots of {overscore (A)}830 and {overscore (θ)}832, the amplitude of the reference signal and phase angle, respectively, averaged over many stirring bar rotations. One can optimize the sensitivity of thephase angle828 measurement by proper choice of the magnetic field amplitude and frequency.
• To minimize interference from neighboring stirring bars—ideally, each set of gradient coils should sense the motion of a single stirring bar—each vessel should be provided with electromagnets that are not shared with adjacent vessels. For example, a 4:1 magnet array shown in FIG. 14 should be used instead of the 2:1 or the 1:1 magnet arrays shown in FIGS. 13 and 12, respectively. In order to take readings from all of the vessels in an array, a multiplexer can be used to sequentially route signals from each vessel to the lock-in amplifier. Normally, an accurate measurement of the phase angle can be obtained after several tens of rotations of the stirring bars. For rotation frequencies of 10-20 Hz, this time will be on the order of a few seconds per vessel. Thus, phase angle measurements for an entire array of vessels can be typically made once every few minutes, depending on the number of vessels, the stirring bar frequency, and the desired accuracy. In order to speed up the measurement process, one may employ multiple-channel signal detection to measure the phase angle of stirring bars in more than one vessel at a time. Alternate detection methods include direct digitization of the coil output waveforms using a high-speed multiplexer and/or an analog-to-digital converter, followed by analysis of stored waveforms to determine amplitude and phase angle.[0177]
• Phase angle measurements can also be made with non-magnetic, mechanical stirring drives, using the[0178]inductive coil system760 of FIG. 25. For example, one may achieve sufficient phase lag between the stirring blade and the drive motor by joining them with a torsionally soft, flexible connector. Alternatively, the drive mechanism may use a resilient belt drive rather than a rigid gear drive to produce measurable phase lag. The stirring blade must include a permanent magnet oriented such that its magnetic moment is not parallel to the axis of rotation. For maximum sensitivity, the magnetic moment of the stirring blade should lie in the plane of rotation. Note that one advantage to using a non-magnetic stirring drive is that there is no upper limit on the phase angle.
• In addition to directly or indirectly measuring torque, one may sense viscosity by increasing the driving frequency, ω[0179]_D, or decreasing the magnetic field strength until, in either case, the stirring bar stalls because of insufficient torque. The point at which the stirring bar stops rotating can be detected using the same setup depicted in FIG. 25 for measuring phase angle. During a ramp up (down) of the driving frequency (field strength), the magnitude of the lock-in amplifier output will abruptly fall by a large amount when the stirring bar stalls. The frequency or field strength at which the stirring bar stalls can be correlated with viscosity: the lower the frequency or the higher the field strength at which stalling occurs, the greater the viscosity of the reaction mixture.
• With appropriate calibration, the method can yield absolute viscosity data, but generally the method is used to rank reactions. For example, when screening multiple reaction mixtures, one may subject all of the vessels to a series of step changes in either frequency or field strength, while noting which stirring bars stall after each of the step changes. The order in which the stirring bars stall indicates the relative viscosity of the reaction mixtures since stirring bars immersed in mixtures having higher viscosity will stall early. Note that, in addition to providing data on torque and stall frequency, the inductive[0180]sensing coil system760 of FIG. 25 and similar devices can be used as diagnostic tools to indicate whether a magnetic stirring bar has stopped rotating during a reaction.
• Mechanical Oscillators[0181]
• Piezoelectric quartz resonators or mechanical oscillators can be used to evaluate the viscosity of reaction mixtures, as well as a host of other material properties, including molecular weight, specific gravity, elasticity, dielectric constant, and conductivity. In a typical application, the mechanical oscillator, which can be as small as a few mm in length, is immersed in the reaction mixture. The response of the oscillator to an excitation signal is obtained for a range of input signal frequencies, and depends on the composition and properties of the reaction mixture. By calibrating the resonator with a set of well characterized liquid standards, the properties of the reaction mixture can be determined from the response of the mechanical oscillator. Further details on the use of piezoelectric quartz oscillators to measure material properties are described in co-pending U.S. patent application Ser. No. 09/133,171 “Method and Apparatus for Characterizing Materials by Using a Mechanical Resonator,” filed Aug. 12, 1998, which is herein incorporated by reference.[0182]
• Although many different kinds of mechanical oscillators currently exist, some are less useful for measuring properties of liquid solutions. For example, ultrasonic transducers or oscillators cannot be used in all liquids due to diffraction effects and steady acoustic (compressive) waves generated within the reactor vessel. These effects usually occur when the size of the oscillator and the vessel are not much greater than the characteristic wavelength of the acoustic waves. Thus, for reactor vessel diameters on the order of a few centimeters, the frequency of the mechanical oscillator should be above 1 MHz. Unfortunately, complex liquids and mixtures, including polymer solutions, often behave like elastic gels at these high frequencies, which results in inaccurate resonator response.[0183]
• Often, shear-mode transducers as well as various surface-wave transducers can be used to avoid some of the problems associated with typical ultrasonic transducers. Because of the manner in which they vibrate, shear mode transducers generate viscous shear waves instead of acoustic waves. Since viscous shear waves decay exponentially with distance from the sensor surface, such sensors tend to be insensitive to the geometry of the measurement volume, thus eliminating most diffraction and reflection problems. Unfortunately, the operating frequency of these sensors is also high, which, as mentioned above, restricts their use to simple fluids. Moreover, at high vibration frequencies, most of the interaction between the sensor and the fluid is confined to a thin layer of liquid near the sensor surface. Any modification of the sensor surface through adsorption of solution components will often result in dramatic changes in the resonator response.[0184]
• [0185]Tuning forks840 and bimorph/unimorph resonators850 shown in FIG. 28 and FIG. 29, respectively, overcome many of the drawbacks associated with ultrasonic transducers. Because of their small size,tuning forks840 and bimorph/unimorph resonators850 have difficulty exciting acoustic waves, which typically have wavelengths many times their size. Furthermore, though one might conclude otherwise based on the vibration mode shown in FIG. 28,tuning forks840 generate virtually no acoustic waves: when excited, each of thetines832 of thetuning fork840 acts as a separate acoustic wave generator, but because thetines832 oscillate in opposite directions and phases, the waves generated by each of thetines832 cancel one another. Like the shear mode transducers described above, the bimorph/unimorph850 resonators produce predominantly viscous waves and therefore tend to be insensitive to the geometry of the measurement volume. But unlike the shear mode transducers, bimorph/unimorph850 resonators operate at much lower frequencies, and therefore can be used to measure properties of polymeric solutions.
• FIG. 30 schematically shows a[0186]system870 for measuring the properties of reaction mixtures usingmechanical oscillators872. An important advantage of thesystem870 is that it can be used to monitor the progress of a reaction. Theoscillators872 are mounted on theinterior walls874 of thereaction vessels876. Alternatively, theoscillators872 can be mounted along thebottom878 of thevessels876 or can be freestanding within thereaction mixtures880. Eachoscillator872 communicates with a network analyzer882 (for example, an HP8751A analyzer), which generates a variable frequency excitation signal. Each of theoscillators872 also serve as receivers, transmitting their response signals back to thenetwork analyzer882 for processing. Thenetwork analyzer882 records the responses of theoscillators872 as functions of frequency, and sends the data tostorage884. The output signals of theoscillators872 pass through a highimpedance buffer amplifier886 prior to measurement by thewide band receiver888 of thenetwork analyzer882.
• Other resonator designs may be used. For example, to improve the suppression of acoustic waves, a tuning fork resonator with four tines can be used. It is also possible to excite resonator oscillations through the use of voltage spikes instead of a frequency sweeping AC source. With voltage spike excitation, decaying free oscillations of the resonator are recorded instead of the frequency response. A variety of signal processing techniques well known to those of skill in the art can be used to distinguish resonator responses.[0187]
• Alternate embodiments can be described with reference to the[0188]parallel reactor system130 shown in FIG. 2. A single resonator (not shown) is attached to the 3-axis translation system150. Thetranslation system150, at the direction of theprocessor160, places the resonator within a reactor vessel of interest. A reading of resonator response is taken and compared to calibration curves, which relate the response to viscosity, molecular weight, specific gravity, or other properties. In another embodiment, a portion of the reaction mixture is withdrawn from a reactor vessel, using, for example, theliquid handling system146, and is placed in a separate vessel containing a resonator. The response of the resonator is measured and compared to calibration data. Although thesystem870 shown in FIG. 30 is better suited to monitor solution properties in situ, the two alternate embodiments can be used as post-characterization tools and are much simpler to implement.
• In addition to mechanical oscillators, other types of sensors can be used to evaluate material properties. For example, interdigitated electrodes can be used to measure dielectric properties of the reaction mixtures.[0189]
• Pressure Control System[0190]
• Another technique for assessing reaction kinetics is to monitor pressure changes due to production or consumption of various gases during reaction. One embodiment of this technique is shown in FIG. 31. A[0191]parallel reactor910 comprises a group ofreactor vessels912. A gas-tight cap914 seals each of thevessels912 and prevents unintentional gas flow to or from thevessels912. Prior to placement of thecap914, each of thevessels912 is loaded with liquid reactants, solvents, catalysts, and other condensed-phase reaction components using theliquid handling system146 shown in FIG. 2. Gaseous reactants fromsource916 are introduced into each of thevessels912 through agas inlet918.Valves920, which communicate with acontroller922, are used to fill thereaction vessels912 with the requisite amount of gaseous reactants prior to reaction. Apressure sensor924 communicates with the vessel head space—the volume within each of thevessels912 that separates thecap914 from the liquid components—through aport926 located in thecap914. Thepressure sensors924 are coupled to aprocessor928, which manipulates and stores data. During reaction, any changes in the head space pressure, at constant temperature, reflect changes in the amount of gas present in the head space. This pressure data can be used to determine the molar production or consumption rate, r_i, of a gaseous component since, for an ideal gas at constant temperature,$\begin{array}{cc}{r}_i=\frac{1}{\mathrm{RT}}\frac{p_i}{t}& \mathrm{XI}\end{array}$

  
• where R is the universal gas constant and p, is the partial pressure of the ith gaseous component.[0192]Temperature sensors930, which communicate with theprocessor928 throughmonitor932, provide data that can be used to account for changes in pressure resulting from variations in head space temperature. The ideal gas law or similar equation of state can be used to calculate the pressure correction.
• In an alternate embodiment, the[0193]valves920 are used to compensate for the consumption of a gaseous reactant, in a reaction where there is a net loss in moles of gas-phase components. Thevalves920 are regulated by thevalve controller922, which communicates with theprocessor928. At the beginning of the reaction, thevalves920 open to allow gas from thehigh pressure source916 to enter each of thevessels912. Once the pressure within each of thevessels912, as read by thesensor924, reaches a predetermined value, P_H, theprocessor928 closes thevalves920. As the reaction consumes thesource916 gas, the total pressure within each of thevessels912 decreases. Once the pressure in aparticular vessel912 falls below a predetermined value, P_L, theprocessor928 opens thevalve920 associated with theparticular vessel912, repressurizing it to P_H. This process—filling each of thevessels912 withsource916 gas to P_H, allowing the head space pressure to drop below P_L, and then refilling thevessels912 withsource916 gas to P_H—is usually repeated many times during the course of the reaction. Furthermore, the total pressure in the head space of each of thevessels912 is continuously monitored and recorded during the gas fill-pressure decay cycle.
• An analogous method can be used to investigate reactions where there is a net gain of gas-phase components. At the beginning of a reaction, all reaction materials are introduced into the[0194]vessels912 and thevalves920 are closed. As the reaction proceeds, gas production results in a rise in head space pressure, whichsensors924 andprocessor928 monitor and record. Once the pressure within aparticular vessel912 reaches P_H, theprocessor928 directs thecontroller922 to open theappropriate valve920 to depressurize thevessel912. Thevalve920, which is a multi-port valve, vents the gas from the head space through anexhaust line934. Once the head space pressure falls below P_L, theprocessor928 instructs thecontroller922 to close thevalve920. The total pressure is continuously monitored and recorded during the gas rise-vent cycle.
• The gas consumption (production) rates can be estimated from the total pressure data by a variety of methods. For simplicity, these methods are described in terms of a[0195]single reactor vessel912 andvalve920, but they apply equally well to aparallel reactor910 comprisingmultiple vessels912 andvalves920. One estimate of gas consumption (production) can be made from the slope of the pressure decay (growth) curves obtained when the valve is closed. These data, after converting total pressure to partial pressure based on reaction stoichiometry, can be inserted into equation XI to calculate r_i, the molar consumption (production) rate. A second estimate can be made by assuming that a fixed quantity of gas enters (exits) the vessel during each valve cycle. The frequency at which the reactor is repressurized (depressurized) is therefore proportional to the gas consumption (production) rate. A third, more accurate estimate can be obtained by assuming a known gas flow rate through the valve. Multiplying this value by the time during which the valve remains open yields an estimate for the quantity of gas that enters or leaves the vessel during a particular cycle. Dividing this product by the time between the next valve cycle—that is, the time it takes for the pressure in the vessel head space to fall from P_Hto P_L—yields an average value for the volumetric gas consumption (production) rate for the particular valve cycle. Summing the quantity of gas added during all of the cycles equals the total volume of gas consumed (produced) during the reaction.
• The most accurate results are obtained by directly measuring the quantity of gas that flows through the valve. This can be done by noting the change in pressure that occurs during the time the valve is open—the ideal gas law can be used to convert this change to the volume of gas that enters or leaves the vessel. Dividing this quantity by the time between a particular valve cycle yields an average volumetric gas consumption (production) rate for that cycle. Summing the volume changes for each cycle yields the total volume of gas consumed (produced) in the reaction.[0196]
• In an alternate embodiment shown in FIG. 31, the gas consumption rate is directly measured by inserting[0197]flow sensors936 downstream of thevalves920 or by replacing thevalves920 withflow sensors936. Theflow sensors936 allow continuous monitoring of the mass flow rate of gas entering each of thevessels912 through thegas inlet918. To ensure meaningful comparisons between experiments, the pressure of thesource916 gas should remain about constant during an experiment. Although theflow sensors936 eliminate the need for cycling thevalves920, the minimum detectable flow rates of this embodiment are less than those employing pressure cycling. But, the use offlow sensors936 is generally preferred for fast reactions where the reactant flow rates into thevessels912 are greater than the threshold sensitivity of theflow sensors936.
• Illustrative Example of Calibration of Mechanical Oscillators for Measuring Molecular Weight[0198]
• Mechanical oscillators were used to characterize reaction mixtures comprising polystyrene and toluene. To relate resonator response to the molecular weight of polystyrene, the[0199]system870 illustrated in FIG. 30 was calibrated using polystyrene standards of known molecular weight dissolved in toluene. Each of the standard polystyrene-toluene solutions had the same concentration, and were run in separate (identical) vessels using tuning fork piezoelectric quartz resonators similar to the one shown in FIG. 28. Frequency response curves for each resonator were recorded at intervals between about 10 and 30 seconds.
• The calibration runs produced a set of resonator responses that could be used to relate the output from the[0200]oscillators872 immersed in reaction mixtures to polystyrene molecular weight. FIG. 32 shows results of calibration runs970 for the polystyrene-toluene solutions. The curves are plots of oscillator response for polystyrene-toluene solutions comprising nopolystyrene952, and polystyrene standards having weight average molecular weights (M_w) of 2.36×10³954, 13.7×10³956, 114.2×10³958, and 1.88×10⁶960.
• FIG. 33 shows a[0201]calibration curve970 obtained by correlating M_wof the polystyrene standards with the distance between the frequency response curve fortoluene952 and each of thepolystyrene solutions954,956,958,960 of FIG. 32. This distance was calculated using the expression:$\begin{array}{cc}{d}_i=\sqrt{\frac{1}{f_1-{\mathrm{<figure-callout\; label="f"\; filenames="US20030190755A1-20031009-D00008.png,US20030190755A1-20031009-D00010.png"\; state="\{\{state\}\}">f</figure-callout>}}_0}{\int }_{f_0}^{{\mathrm{<figure-callout\; label="f"\; filenames="US20030190755A1-20031009-D00010.png,US20030190755A1-20031009-D00020.png"\; state="\{\{state\}\}">f</figure-callout>}}_1}{\left(R_o-R_i\right)}^2f},& \mathrm{XII}\end{array}$

  
• where f[0202]₀and f₁are the lower and upper frequencies of the response curve, respectively; R₀is the frequency response of the resonator in toluene, and R_iis the resonator response in a particular polystyrene-toluene solution. Given response curves for an unknown polystyrene-toluene mixture and pure toluene952 (FIG. 32), the distance between the two curves can be determined from equation XII. The resulting d, can be located along thecalibration curve970 of FIG. 33 to determine M_wfor the unknown polystyrene-toluene solution.
• Illustrative Example of Measurement of Gas-Phase Reactant Consumption by Pressure Monitoring and Control[0203]
• FIG. 34 depicts the pressure recorded during solution polymerization of ethylene to polyethylene. The reaction was carried out in an apparatus similar to that shown in FIG. 31. An ethylene gas source was used to compensate for ethylene consumed in the reaction. A valve, under control of a processor, admitted ethylene gas into the reaction vessel when the vessel head space pressure dropped below P[0204]_L≈16.1 psig due to consumption of ethylene. During the gas filling portion of the cycle, the valve remained open until the head space pressure exceeded P_H≈20.3 psig.
• FIG. 35 and FIG. 36 show ethylene consumption rate as a function of time, and the mass of polyethylene formed as a function of ethylene consumed, respectively. The average ethylene consumption rate, −r[0205]_C2,k(atm min⁻¹), was determined from the expression$\begin{array}{cc}-r_{\mathrm{C2},k}=\frac{{\left(P_H-P_L\right)}_k}{\Delta t_k}& \mathrm{XIII}\end{array}$

  
• where subscript k refers to a particular valve cycle, and Δt[0206]_kis the time interval between the valve closing during the present cycle and the valve opening at the beginning of the next cycle. As shown in FIG. 35, the constant ethylene consumption rate at later times results from catalyzed polymerization of ethylene. The high ethylene consumption rate early in the process results primarily from transport of ethylene into the catalyst solution prior to establishing an equilibrium ethylene concentration in the liquid phase. FIG. 36 shows the amount of polyethylene produced as a function of the amount of ethylene consumed by reaction. The amount of polyethylene produced was determined by weighing the reaction products, and the amount of ethylene consumed by reaction was estimated by multiplying the constant average consumption rate by the total reaction time. A linear least-squares fit to these data yields a slope which matches the value predicted from the ideal gas law and from knowledge of the reaction temperature and the total volume occupied by the gas (the product of vessel head space and number of valve cycles during the reaction).
• Automated, High Pressure Injection System[0207]
• FIG. 37 shows a perspective view of an eight-[0208]vessel reactor module1000, of the type shown in FIG. 10, which is fitted with an optionalliquid injection system1002. Theliquid injection system1002 allows addition of liquids to pressurized vessels, which, as described below, alleviates problems associated with pre-loading vessels with catalysts. In addition, theliquid injection system1002 improves concurrent analysis of catalysts by permitting screening reactions to be selectively quenched through the addition of a liquid-phase catalyst poison.
• The[0209]liquid injection system1002 helps solve problems concerning liquid-phase catalytic polymerization of a gaseous monomer. When using thereactor module390 shown in FIG. 10 to screen or characterize polymerization catalysts, each vessel is normally loaded with a catalyst and a solvent prior to reaction. After sealing, gaseous monomer is introduced into each vessel at a specified pressure to initiate polymerization. As discussed in Example 1, during the early stages of reaction, the monomer concentration in the solvent increases as gaseous monomer dissolves in the solvent. Although the monomer eventually reaches an equilibrium concentration in the solvent, catalyst activity may be affected by the changing monomer concentration prior to equilibrium. Moreover, as the monomer dissolves in the solvent early in the reaction, additional gaseous monomer is added to maintain the pressure in the vessel headspace. This makes it difficult to distinguish between pressure changes in the vessels due to polymerization in the liquid phase and pressure changes due to monomer transport into the solvent to establish an equilibrium concentration. These analytical difficulties can be avoided using theliquid injection system1002, since the catalyst can be introduced into the vessels after the monomer has attained an equilibrium concentration in the liquid phase.
• The[0210]liquid injection system1002 of FIG. 37 also helps solve problems that arise when using thereactor module390 shown in FIG. 10 to investigate catalytic co-polymerization of gaseous and liquid co-monomers. Prior to reaction, each vessel is loaded with a catalyst and the liquid co-monomer. After sealing the vessels, gaseous co-monomer is introduced into each vessel to initiate co-polymerization. However, because appreciable time may elapse between loading of liquid components and contact with the gaseous co-monomer, the catalyst may homo-polymerize a significant fraction of the liquid co-monomer. In addition, the relative concentration of the co-monomers in the liquid-phase changes during the early stages of reaction as the gaseous co-monomer dissolves in the liquid phase. Both effects lead to analytical difficulties that can be avoided using theliquid injection system1002, since catalysts can be introduced into the vessels after establishing an equilibrium concentration of the gaseous and liquid co-monomers in the vessels. In this way, the catalyst contacts the two co-monomers simultaneously.
• The[0211]liquid injector system1002 shown in FIG. 37 also allows users to quench reactions at different times by adding a liquid phase catalyst poison, which improves screening of materials exhibiting a broad range of catalytic activity. When using thereactor module390 of FIG. 10 to concurrently evaluate library members for catalytic performance, the user may have little information about the relative activity of library members. If every reaction is allowed to proceed for the same amount of time, the most active catalysts may generate an excessive amount of product, which can hinder post reaction analysis and reactor clean up. Conversely, the least active catalysts may generate an amount of product insufficient for characterization. By monitoring the amount of product in each of the vessels—through the use of mechanical oscillators or phase lag measurements, for instance—the user can stop a particular reaction by injecting the catalyst poison into the vessels once a predetermined conversion is achieved. Thus, within the same reactor and in the same experiment, low and high activity catalysts may undergo reaction for relatively long and short time periods, respectively, with both sets of catalysts generating about the same amount of product.
• Referring again to FIG. 37, the[0212]liquid injection system1002 comprises fillports1004 attached to aninjector manifold1006. Aninjector adapter plate1008, sandwiched between anupper plate1010 and block1012 of thereactor module1000, provides conduits for liquid flow between theinjector manifold1006 and each of the wells or vessels (not shown) within theblock1012. Chemicallyinert valves1014 attached to theinjector manifold1006 and located along flow paths connecting thefill ports104 and the conduits within theadapter plate1008, are used to establish or prevent fluid communication between thefill ports1004 and the vessels or wells. Normally, theliquid injection system1002 is accessed through thefill ports1004 using aprobe1016, which is part of an automated liquid delivery system such as the roboticmaterial handling system146 shown in FIG. 2. However, liquids can be manually injected into the vessels through thefill ports1004 using a pipette, syringe, or similar liquid delivery device. Conventional high-pressure liquid chromatography loop injectors can be used as fillports1004. Otheruseful fill ports1004 are shown in FIG. 38 and FIG. 39.
• FIG. 38 shows a cross sectional view of a first embodiment of a[0213]fill port1004′ having an o-ring seal to minimize liquid leaks. Thefill port1004′ comprises a generally cylindricalfill port body1040 having afirst end1042 and asecond end1044. Anaxial bore1046 runs the length of thefill port body1040. An elastomeric o-ring1048 is seated within theaxial bore1046 at a point where there is anabrupt narrowing1050, and is held in place with asleeve1052 that is threaded into thefirst end1042 of thefill port body1040. Thesleeve1052 has acenter hole1054 that is sized to accommodate the widest part of theprobe1016. Thesleeve1052 is typically made from a chemically resistant plastic, such as polyethylethylketone (PEEK), polytetrafluoroethylene (PTFE), and the like, which minimizes damage to theprobe1016 and fillport1004′ during liquid injection. To aid in installation and removal, thefill port1004′ has a knurled firstouter surface1056 located adjacent to thefirst end1042 of thefill port1004′, and a threaded secondouter surface1058, located adjacent to thesecond end1044 of thefill port1004′.
• FIG. 38 also shows the position of the[0214]probe1016 during liquid injection. Like a conventional pipette, theprobe1016 is a cylindrical tube having an outer diameter (OD) at the point of liquid delivery that is smaller than the OD over the majority of theprobe1016 length. As a result, near theprobe tip1060, there is atransition zone1062 where theprobe1016 OD narrows. Because the inner diameter (ID) of the o-ring1048 is about the same as the OD of theprobe tip1060, a liquid-tight seal is formed along theprobe transition zone1060 during liquid injection.
• FIG. 39 shows a second embodiment of a[0215]fill port1004″. Like thefirst embodiment1004′ shown in FIG. 38, thesecond embodiment1004″ comprises a generally cylindricalfill port body1040′ having afirst end1042′ and asecond end1044′. But instead of an o-ring, thefill port1004″ shown in FIG. 39 employs aninsert1080 having a taperedaxial hole1082 that results an interference fit, and hence a seal, between theprobe tip1060 and the ID of the taperedaxial hole1082 during liquid injection. Theinsert1080 can be threaded into thefirst end1042′ of thefill port1004″. Typically, theinsert1080 is made from a chemically resistant plastic, such as PEEK, PTFE, and the like, which minimizes damage to theprobe1016 and fillport1004″ during liquid injection. To aid in removal and installation, the fill port' has a knurled firstouter surface1056′ located adjacent to thefirst end1042′ of thefill port1004″, and a threaded secondouter surface1058′ located adjacent to thesecond end1044′ of thefill port1004″.
• FIG. 40 shows a phantom front view of the[0216]injector manifold1006. Theinjector manifold1006 includes a series offill port seats1100 located along atop surface1102 of theinjector manifold1006. Thefill port seats1100 are dimensioned to receive the second ends1044,1044′ of thefill ports1004′,1004″ shown in FIG. 38 and FIG. 39. Locatingholes1104, which extend through theinjector manifold1006, locate thevalves1014 of FIG. 37 along the front of theinjector manifold1006.
• An alternative design for the[0217]valve1014, which is used with the injection ports is shown is FIG. 40A and FIG. 40B. FIG. 40A shows theinjector manifold1006, which is shown in a cross sectional view in FIG. 40B. The alternative valve design is essentially a check valve that has aspring2005 under apoppet2006. When not injecting, thespring2005 assisted by the pressure of the reaction vessel pushes thepoppet2006 against aseal2007 to seal the reaction vessel. The seal may be of a type known to those of skill in the art, such as an o-ring seal. When injecting, a pump associated with theprobe1016 forces the material to be injected against thepoppet2006 overcoming the pressure in the chamber and thespring2005 force to allow the material being injected to flow past the poppet into the reaction vessel via the channel in the module.
• FIG. 41 shows a cross sectional view of the[0218]injector manifold1006 along afirst section line1106 of FIG. 40. The cross section illustrates one of a group offirst flow paths1130. Thefirst flow paths1130 extend from thefill port seats1100, through theinjector manifold1006, to valve inlet seats1132. Each of thevalve inlet seats1132 is dimensioned to receive an inlet port (not shown) of one of thevalves1014 depicted in FIG. 37. Thefirst flow paths1130 thus provide fluid communication between thefill ports1004 and thevalves1014 of FIG. 37.
• FIG. 42 shows a cross sectional view of the[0219]injector manifold1006 along asecond section line1108 of FIG. 40. The cross section illustrates one of a group ofsecond flow paths1150. Thesecond flow paths1150 extend fromvalve outlet seats1152, through theinjector manifold1006, tomanifold outlets1154 located along aback surface1156 of theinjector manifold1006. Each of thevalve outlet seats1152 is dimensioned to receive an outlet port (not shown) of one of thevalves1014 depicted in FIG. 37. Themanifold outlets1154 mate with fluid conduits on theinjector adapter plate1008.Annular grooves1158, which surround themanifold outlets1154, are sized to receive o-rings (not shown) that seal the fluid connection between themanifold outlets1154 and the fluid conduits on theinjector adapter plate1008. Thesecond flow paths1150 thus provide fluid communication between thevalves1014 and theinjector adapter plate1008.
• FIG. 43 shows a phantom top view of the[0220]injector adapter plate1008, which serves as an interface between theinjector manifold1006 and theblock1012 of thereactor module1000 shown in FIG. 37. Theinjector adapter plate1008 comprisesholes1180 that provide access to the vessels and wells within theblock1012. Theinjector adapter plate1008 also comprisesconduits1182 extending from afront edge1184 to the bottom surface of theadapter plate1008. When theadapter plate1008 is assembled in thereactor module1000,inlets1186 of theconduits1182 make fluid connection with themanifold outlets1154 shown in FIG. 42.
• As shown in FIG. 44, which is a cross sectional side view of the[0221]injector adapter plate1008 along asection line1188 of FIG. 43, theconduits1182 terminate on abottom surface1210 of theinjector plate1008 atconduit outlets1212. Thebottom surface1210 of theadapter plate1008 forms an upper surface of each of the wells in thereactor module1000block1012 of FIG. 37. To ensure that liquid is properly delivered into the reaction vessels, elongated well injectors, as shown in FIG. 45 and FIG. 48 below, are connected to theconduit outlets1212.
• FIG. 45 shows an embodiment of a[0222]well injector1230. Thewell injector1230 is a generally cylindrical tube having afirst end1232 and asecond end1234. Thewell injector1230 has a threadedouter surface1236 near thefirst end1232 so that it can be attached to threadedconduit outlets1212 shown in FIG. 44.Flats1238 located adjacent to the threadedouter surface1236 assist in twisting thefirst end1232 of thewell injector1230 into theconduit outlets1212. The length of thewell injector1230 can be varied. For example, thesecond end1234 of thewell injector1230 may extend into the liquid mixture; alternatively, thesecond end1234 of theinjector1230 may extend a portion of the way into the vessel headspace. Typically, thewell injector1230 is made from a chemically resistant plastic, such PEEK, PTFE, and the like.
• Liquid injection can be understood by referring to FIGS.[0223]46-48. FIG. 46 shows a top view of thereactor module1000, and FIG. 47 and FIG. 48 show, respectively, cross sectional side views of thereactor module1000 along first andsecond section lines1260,1262 shown in FIG. 46. Prior to injection of a catalyst or other liquid reagent, theprobe1016, which initially contains a first solvent, withdraws a predetermined amount of the liquid reagent from a reagent source. Next, theprobe1016 withdraws a predetermined amount of a second solvent from a second solvent source, resulting in a slug of liquid reagent suspended between the first and second solvents within theprobe1016. Generally, probe manipulations are carried out using a robotic material handling system of the type shown in FIG. 2, and the second solvent is the same as the first solvent.
• FIGS. 47 and 48 show the inlet and outlet paths of the[0224]valve1014 prior to, and during, liquid injection, respectively. Once theprobe1016 contains the requisite amount of liquid reagent and solvents, theprobe tip1058 is inserted in thefill port1004, creating a seal as shown, for example, in FIG. 38 and FIG. 39. Thevalve1014 is then opened, and the second solvent, liquid reagent, and a portion of the first solvent are injected into thereactor module1000 under pressure. From thefill port1004, the liquid flows into theinjector manifold1006 through one of thefirst flow paths1130 that extend from thefill port seats1100 to the valve inlet seats1132. The liquid enters thevalve1014 through aninlet port1280, flows through avalve flow path1282, and exits thevalve1014 through an outlet port1284. After leaving thevalve1014, the liquid flows through one of thesecond flow paths1150 to amanifold outlet1154. From themanifold outlet1154, the liquid flows through theinjector adapter plate1008 within one of thefluid conduits1182, and is injected into areactor vessel1286 or well1288 through thewell injector1230. In the embodiment shown in FIG. 48, thesecond end1234 of thewell injector1230 extends only a fraction of the way into thevessel headspace1290. In other cases, thesecond end1234 may extend into thereaction mixture1292.
• Liquid injection continues until the slug of liquid reagent is injected into the[0225]reactor vessel1286 and the flow path from thefill port1004 to thesecond end1234 of thewell injector1230 is filled with the first solvent. At that point, thevalve1014 is closed, and theprobe1016 is withdrawn from thefill port1004.
• Reactor Vessel Pressure Seal and Magnetic Feed-Through Stirring Mechanism[0226]
• FIG. 48 shows a stirring mechanism and associated seals for maintaining above-ambient pressure in the[0227]reactor vessels1286. The direct-drive stirring mechanism1310 is similar to the one shown in FIG. 10, and comprises agear1312 attached to aspindle1314 that rotates a blade orpaddle1316. Adynamic lip seal1318, which is secured to theupper plate1010 prevents gas leaks between therotating spindle1314 and theupper plate1010. When newly installed, the lip seal is capable of maintaining pressures of about 100 psig. However, with use, thelip seal1318, like o-rings and other dynamic seals, will leak due to frictional wear. High service temperatures, pressures, and stirring speeds hasten dynamic seal wear.
• FIG. 49 shows a cross sectional view of a magnetic feed through[0228]1340 stirring mechanism that helps minimize gas leaks associated with dynamic seals. The magnetic feed-through1340 comprises agear1342 that is attached to amagnetic driver assembly1344 usingcap screws1346 or similar fasteners. Themagnetic driver assembly1344 has a cylindricalinner wall1348 and is rotatably mounted on a rigidcylindrical pressure barrier1350 using one ormore bearings1352. Thebearings1352 are located within anannular gap1354 between anarrow head portion1356 of thepressure barrier1350 and theinner wall1348 of themagnetic driver assembly1344. Abase portion1358 of thepressure barrier1350 is affixed to theupper plate1010 of thereactor module1000 shown in FIG. 48 so that the axis of thepressure barrier1350 is about coincident with the centerline of thereactor vessel1286 or well1288. Thepressure barrier1350 has a cylindricalinterior surface1360 that is open only along thebase portion1358 of thepressure barrier1350. Thus, theinterior surface1360 of thepressure barrier1350 and thereactor vessel1286 or well1288 define a closed chamber.
• As can be seen in FIG. 49, the magnetic feed through[0229]1340 further comprises a cylindricalmagnetic follower1362 rotatably mounted within thepressure barrier1350 using first1364 and second1366 flanged bearings. The first1364 and second1366 flanged bearings are located in first1368 and second1370annular regions1368 delimited by theinterior surface1360 of thepressure barrier1350 and relativelynarrow head1372 andleg1374 portions of themagnetic follower1362, respectively. Akeeper1376 and retainingclip1378 located within the secondannular region1370 adjacent to the second flanged bearing1366 help minimize axial motion of themagnetic follower1362. A spindle (not shown) attached to thefree end1380 of theleg1374 of themagnetic follower1362, transmits torque to thepaddle1316 immersed in thereaction mixture1292 shown in FIG. 48.
• During operation, the[0230]rotating gear1342 andmagnetic driver assembly1344 transmit torque through therigid pressure barrier1350 to the cylindricalmagnetic follower1362. Permanent magnets (not shown) embedded in themagnetic driver assembly1344 have force vectors lying in planes about perpendicular to the axis of rotation1382 of themagnetic driver assembly1344 andfollower1362. These magnets are coupled to permanent magnets (not shown) that are similarly aligned and embedded in themagnetic follower1362. Because of the magnetic coupling, rotation of thedriver assembly1344 induces rotation of thefollower1362 and stirring blade orpaddle1316 of FIG. 48. Thefollower1362 andpaddle1316 rotate at the same frequency as the magnetic driver assembly, though, perhaps, with a measurable phase lag.
• Removable and Disposable Stirrer[0231]
• The[0232]stirring mechanism1310 shown in FIG. 48 includes amulti-piece spindle1314 comprising anupper spindle portion1400, acoupler1402, and aremovable stirrer1404. Themulti-piece spindle1314 offers certain advantages over a one-piece spindle. Typically, only theupper drive shaft1400 and thecoupler1402 are made of a high modulus material such as stainless steel: theremovable stirrer1404 is made of a chemically resistant and inexpensive plastic, such as PEEK, PTFE, and the like. In contrast, one-piece spindles, though perhaps coated with PTFE, are generally made entirely of a relatively expensive high modulus material, and are therefore normally reused. However, one-piece spindles are often difficult to clean after use, especially following a polymerization reaction. Furthermore, reaction product may be lost during cleaning, which leads to errors in calculating reaction yield. With themulti-piece spindle1314, one discards theremovable stirrer1404 after a single use, eliminating the cleaning step. Because theremovable stirrer1404 is less bulky than the one-piece spindle, it can be included in certain post-reaction characterizations, including product weighing to determine reaction yield.
• FIG. 50 shows a perspective view of the[0233]stirring mechanism1310 of FIG. 48, and provides details of themulti-piece spindle1314. Agear1312 is attached to theupper spindle portion1400 of themulti-piece spindle1314. Theupper spindle1400 passes through apressure seal assembly1420 containing a dynamic lip seal, and is attached to theremovable stirrer1404 using thecoupler1402. Note that theremovable stirrer1404 can also be used with the magnetic feed throughstirring mechanism1340 illustrated in FIG. 49. In such cases, theupper spindle1400 is eliminated and theleg1374 of the cylindricalmagnetic follower1362 or thecoupler1402 or both are modified to attach themagnetic follower1362 to theremovable stirrer1404.
• FIG. 51 shows details of the[0234]coupler1402, which comprises a cylindrical body having first1440 and second1442 holes centered along an axis ofrotation1444 of thecoupler1402. Thefirst hole1440 is dimensioned to receive acylindrical end1446 of theupper spindle1400. Ashoulder1448 formed along the periphery of theupper spindle1400 rests against anannular seat1450 located within thefirst hole1440. A set screw (not shown) threaded into alocating hole1452 prevents relative axial and rotational motion of theupper spindle1400 and thecoupler1402.
• Referring to FIGS. 50 and 51, the[0235]second hole1442 of thecoupler1402 is dimensioned to receive afirst end1454 of theremovable stirrer1404. Apin1456, which is embedded in thefirst end1454 of the removable stirrer, cooperates with alocking mechanism1458 located on thecoupler1402, to prevent relative rotation of thecoupler1402 and theremovable stirrer1404. Thelocking mechanism1458 comprises anaxial groove1460 formed in aninner surface1462 of the coupler. Thegroove1460 extends from anentrance1464 of thesecond hole1442 to alateral portion1466 of aslot1468 cut through awall1470 of thecoupler1402.
• As shown in FIG. 52, which is a cross sectional view of the[0236]coupler1402 along asection line1472, thelateral portion1466 of theslot1468 extends about 60 degrees around the circumference of thecoupler1402 to anaxial portion1474 of theslot1468. To connect theremovable stirrer1404 to thecoupler1402, thefirst end1454 of theremovable stirrer1404 is inserted into thesecond hole1442 and then rotated so that thepin1456 travels in theaxial groove1460 andlateral portion1466 of theslot1468. Aspring1476, mounted between thecoupler1402 and ashoulder1478 formed on the periphery of theremovable stirrer1404, forces thepin1456 into theaxial portion1474 of theslot1468.
• An alternative design for the[0237]multi-piece spindle1314 is shown in FIG. 50A, which has anupper spindle portion1400, acoupler1402 and aremovable stirrer1404. The details of this alternative design are shown in FIG. 50B. This alternative design is essentially a spring lock mechanism that allows for quick removal of theremovable stirrer1404. Theremovable stirrer1404 is locked in to the coupling mechanism by a series ofballs2001 that are held into a groove in theremovable stirrer1404 by acollar2002, which is part of thecoupler1402. Theremovable stirrer1404 is released by pulling thecollar2002 back against aspring2003 and allowing theballs2001 to fall into a pocket in thecollar2002 and releasing the removable stirrer.
• Parallel Pressure Reactor Control and Analysis[0238]
• FIG. 53 shows one implementation of a computer-based system for monitoring the progress and properties of multiple reactions in situ.[0239]Reactor control system1500 sendscontrol data1502 to and receivesexperimental data1504 fromreactor1506. As will be described in more detail below, in oneembodiment reactor1506 is a parallel polymerization reactor and the control andexperimental data1502 and1504 include set point values for temperature, pressure, time and stirring speed as well as measured experimental values for temperature and pressure. Alternatively, inother embodiments reactor1506 can be any other type of parallel reactor or conventional reactor, anddata1502,1504 can include other control or experimental data.System control module1508 providesreactor1506 withcontrol data1502 based on system parameters obtained from the user through user I/O devices1510, such as a display monitor, keyboard or mouse. Alternatively,system control module1508 can retrievecontrol data1502 fromstorage1512.
• [0240]Reactor control system1500 acquiresexperimental data1504 fromreactor1506 and processes the experimental data insystem control module1508 anddata analysis module1514 under user control throughuser interface module1516.Reactor control system1500 displays the processed data both numerically and graphically throughuser interface module1516 and user I/O devices1510, and optionally throughprinter1518.
• FIG. 54 illustrates an embodiment of[0241]reactor1506 in which pressure, temperature, and mixing intensity are automatically controlled and monitored.Reactor1506 includesreactor block1540, which contains sealedreactor vessels1542 for receiving reagents. In one embodiment,reactor block1540 is a single unit containing each ofreactor vessels1542. Alternatively,reactor block1540 can include a number of reactor block modules, each of which contains a number ofreactor vessels1542.Reactor1506 includes a mixing control andmonitoring system1544, a temperature control andmonitoring system1546 and a pressure control andmonitoring system1548. These systems communicate withreactor control system1500.
• The details of mixing control and[0242]monitoring system1544 are illustrated in FIG. 55. Each ofreactor vessels1542 contains astirrer1570 for mixing the vessel contents. In one embodiment,stirrers1570 are stirring blades mounted onspindles1572 and driven bymotors1574. Separate motors.1574 can control eachindividual stirrer1570; alternatively,motors1574 can control groups ofstirrers1570 associated withreactor vessels1542 in separate reactor blocks. In another embodiment, magnetic stirring bars or other known stirring mechanisms can be used.System control module1508 provides mixing control signals tostirrers1570 throughinterface1576,1578, and one ormore motor cards1580.Interface1576,1578 can include acommercial motor driver1576 andmotor interface software1578 that provides additional high level motor control, such as the ability to initializemotor cards1580, to control specific motors or motor axes (where each motor1580 controls a separate reactor block), to set motor speed and acceleration, and to change or stop a specified motor or motor axis.
• Mixing control and[0243]monitoring system1544 can also includetorque monitors1582, which monitor the applied torque in each ofreactor vessels1542. Suitable torque monitors1582 can include optical sensors and magnetic field sensors mounted onspindles1572, or strain gauges (not shown), which directly measure the applied torque and transmit torque data tosystem control module1508 anddata analysis module1514.Monitors1582 can also include encoders, resolvers, Hall effect sensors and the like, which may be integrated intomotors1574. These monitors measure the power required to maintain aconstant spindle1572 rotational speed, which is related to applied torque.
• Referring to FIG. 56, temperature control and[0244]monitoring system1546 includes atemperature sensor1600 and aheating element1602 associated with eachreactor vessel1542 and controlled bytemperature controller1604.Suitable heating elements1602 can include thin filament resistance heaters, thermoelectric devices, thermistors, or other devices for regulating vessel temperature. Heating elements can include devices for cooling, as well as heating,reactor vessels1542.System control unit1508 transmits temperature control signals toheating elements1602 throughinterface1606,1608 andtemperature controller1604.Interface1606,1608 can include a commercialtemperature device driver1606 implemented to use hardware such as an RS232 interface, andtemperature interface software1608 that provides additional high level communication withtemperature controller1604, such as the ability to control the appropriate communication port, to send temperature set points totemperature controller1604, and to receive temperature data fromtemperature controller1604.
• [0245]Suitable temperature sensors1600 can include thermocouples, resistance thermoelectric devices, thermistors, or other temperature sensing devices.Temperature controller1604 receives signals fromtemperature sensors1600 and transmits temperature data toreactor control system1500. Upon determining that an increase or decrease in reactor vessel temperature is appropriate,system control module1508 transmits temperature control signals toheating elements1602 throughheater controller1604. This determination can be based on temperature parameters entered by the user throughuser interface module1516, or on parameters retrieved bysystem control module1508 from storage.System control module1508 can also use information received fromtemperature sensors1600 to determine whether an increase or decrease in reactor vessel temperature is necessary.
• As shown in FIG. 57, pressure control and[0246]monitoring system1548 includes apressure sensor1630 associated with eachreactor vessel1542. Eachreactor vessel1542 is furnished with a gas inlet/outlet1632 that is controlled byvalves1634.System control module1508 controls reactor vessel pressure throughpressure interface1636,1638 andpressure controller1640.Pressure interface1636,1638 can be implemented in hardware, software or a combination of both.Pressure controller1640 transmits pressure control signals tovalves1634 allowing gases to enter or exitreactor vessels1542 through inlet/outlet1632 as required to maintain reactor vessel pressure at a level set by the user throughuser interface1516.
• [0247]Pressure sensors1630 obtain pressure readings fromreactor vessels1542 and transmit pressure data tosystem control module1508 anddata analysis module1514 throughpressure controller1640 andinterface1636,1638.Data analysis module1514 uses the pressure data in calculations such as the determination of the rate of production of gaseous reaction products or the rate of consumption of gaseous reactants, discussed in more detail below.System control module1508 uses the pressure data to determine when adjustments to reactor vessel pressure are required, as discussed above.
• FIG. 58 is a flow diagram illustrating the operation of a[0248]reactor control system1500. The user initializesreactor control system1500 by setting the initial reaction parameters, such as set points for temperature, pressure and stirring speed and the duration of the experiment, as well as selecting the appropriate hardware configuration for the experiment (step1660). The user can also set other reaction parameters that can include, for example, a time at which additional reagents, such as a liquid co-monomer in a co-polymerization experiment, should be added toreaction vessels1542, or a target conversion percentage at which a quenching agent should be added to terminate a catalytic polymerization experiment. Alternatively,reactor control system1500 can load initial parameters fromstorage1512. The user starts the experiment (step1662).Reactor control system1500 sends control signals toreactor110, causing motor, temperature andpressure control systems1544,1546 and1548 to bringreactor vessels1542 to set point levels (step1664).
• [0249]Reactor control system1500 samples data through mixingmonitoring system1544,temperature monitoring system1546 andpressure monitoring system1548 at sampling rates, which may be entered by the user (step1666).Reactor control system1500 can provide process control by testing the experimental data, including sampled temperature, pressure or torque values as well as elapsed time, against initial parameters (step1668). Based on these inputs,reactor control system1500 sends new control signals to the mixing, temperature and/or pressure control and monitoring systems of reactor1506 (steps1670,1664). These control signals can also include instructions to a material handling robot to add material, such as a reagent or a catalyst quenching agent, to one or more reactor vessels based upon experimental data such as elapsed time or percent conversion calculated as discussed below. The user can also enter new parameters during the course of the experiment, such as changes in motor speed, set points for temperature or pressure, or termination controlling parameters such as experiment time or percent conversion target (step1672), which may also causereactor control system1500 to send new control signals to reactor1506 (steps1672,1670,1664).
• [0250]Data analysis module1514 performs appropriate calculations on the sampled data (step1674), as will be discussed below, and the results are displayed on monitor1510 (step1676). Calculated results and/or sampled data can be stored indata storage1512 for later display and analysis.Reactor control system1500 determines whether the experiment is complete—for example, by determining whether the time for the experiment has elapsed (step1678).Reactor control system1500 can also determine whether the reaction occurring in one or more ofreactor vessels1542 has reached a specified conversion target based on results calculated instep1674; in that case,reactor control system1500 causes the addition of a quenching agent to the relevant reactor vessel or vessels as discussed above, terminating the reaction in that vessel. For any remaining reactor vessels,reactor control system1500 samples additional data (step1666) and the cycle begins anew. When allreactor vessels1542 inreactor block1540 have reached a specified termination condition, the experiment is complete (step1680). The user can also cause the reaction to terminate by aborting the experiment at any time. It should be recognized that the steps illustrated in FIG. 58 are not necessarily performed in the order shown; instead, the operation ofreactor control system1500 can be event driven, responding, for example, to user events, such as changes in reaction parameters, or system generated periodic events.
• Analysis of Experimental Data[0251]
• The type of calculation performed by data analysis module[0252]1514 (step1674) depends on the nature of the experiment. As discussed above, while an experiment is in progress,reactor control system1500 periodically receives temperature, pressure and/or torque data fromreactor1506 at sampling rates set by the user (step1666).System control module1508 anddata analysis module1514 process the data for use in screening materials or for performing quantitative calculations and for display byuser interface module1516 in formats such as those shown in FIGS.63-64 and65.
• [0253]Reactor control system1500 uses temperature measurements fromtemperature sensors1600 as a screening criteria or to calculate useful process and product variables. For instance, in one implementation, catalysts of exothermic reactions are ranked based on peak reaction temperature reached within each reactor vessel, rates of change of temperature with respect to time, or total heat released over the course of reaction. Typically, the best catalysts of an exothermic reaction are those that, when combined with a set of reactants, result in the greatest heat production in the shortest amount of time. In other implementations,reactor control system1500 uses temperature measurements to compute rates of reaction and conversion.
• In addition to processing temperature data as a screening tool, in another implementation,[0254]reactor control system1500 uses temperature measurement—combined with proper thermal management and design of the reactor system—to obtain quantitative calorimetric data. From such data,reactor control system1500 can, for example, compute instantaneous conversion and reaction rate, locate phase transitions (e.g., melting point, glass transition temperature) of reaction products, or measure latent heats to deduce structural information of polymeric materials, including degree of crystallinity and branching. For details of calorimetric data measurement and use, see description accompanying FIG. 9 and equations I-V.
• [0255]Reactor control system1500 can also monitor mixing variables such as applied stirring blade torque in order to determine the viscosity of the reaction mixture and related properties.Reactor control system1500 can use such data to monitor reactant conversion and to rank or characterize materials based on molecular weight or particle size. See, for example, the description of equations VI-VIII above.
• [0256]Reactor control system1500 can also assess reaction kinetics by monitoring pressure changes due to production or consumption of various gases during reaction.Reactor control system1500 usespressure sensors1630 to measure changes in pressure in each reactor vessel headspace—the volume within each vessel that separates the liquid reagents from the vessel's sealed cap. During reaction, any changes in the head space pressure, at constant temperature, reflect changes in the amount of gas present in the head space. As described above (equation XI),reactor system1500 uses this pressure data to determine the molar production or consumption rate, r_i, of a gaseous component.
• Operation of a Reactor Control System[0257]
• Referring to FIG. 59,[0258]reactor control system1500 receives system configuration information from the user throughsystem configuration window1700, displayed onmonitor1510.System configuration window1700 allows the user to specify the appropriate hardware components for an experiment. For example, the user can choose the number ofmotor cards1580 and the set a number of motor axes per card inmotor pane1702.Temperature controller pane1704 allows the user to select the number ofseparate temperature controllers1604 and the number of reactor vessels (the number of feedback control loops) per controller. Inpressure sensor pane1706, the user can set the number of pressure channels corresponding to the number of reactor vessels inreactor1506. The user can also view the preset safety limits for motor speed, temperature and pressure throughsystem configuration window1700.
• As shown in FIG. 60,[0259]reactor control system1500 receives data display information from the user throughsystem option window1730.Display interval dialog1732 lets the user set the refresh interval for data display. The user can set the number of temperature and pressure data points kept in memory indata point pane1734.
• At any time before or during an experiment, the user can enter or modify reaction parameters for each[0260]reactor vessel1542 inreactor block1540 usingreactor setup window1760, shown in FIG. 61. Inmotor setup pane1762, the user can set a motor speed (subject to any preset safety limits), and can also select single or dual direction motor operation. The user can specify temperature parameters intemperature setup pane1764. These parameters include temperature set point1766, turn offtemperature1768,sampling rate1770, as well as the units for temperature measurement and temperature controller operation modes. By selectinggradient button1772, the user can also set a temperature gradient, as will be discussed below. Pressure parameters, including a pressure set point and sampling rate, can be set inpressure setup pane1774.Panes1762,1764 and1774 can also display safety limits for motor speed, temperature and pressure, respectively. The values illustrated in FIG. 61 are not intended to limit this invention and are illustrative only.Reactor setup window1760 also lets the user set a time for the duration of the experiment.Reactor setup window1760 lets the user save any settings as defaults for future use, and load previously saved settings.
• FIG. 62 illustrates the setting of a temperature gradient initiated by selecting[0261]gradient button1772. Ingradient setup window1800, the user can set a temperature gradient acrossreactor1506 by entering differenttemperature set points1802 for each reactor block module of amulti-block reactor1506. As with other setup parameters, such temperature gradients can be saved inreactor setup window1760.
• Referring to FIG. 63, the user can monitor an experiment in[0262]reaction window1830.System status pane1832 displays the current system status, as well as the status of the hardware components selected insystem configuration window1700.Setting pane1834 andtime pane1836 display the current parameter settings and time selected inreactor setup window1760, as well as the elapsed time in the experiment. Experimental results are displayed indata display pane1838, which includes twodimensional array1840 for numerical display of data points corresponding to eachreactor vessel1542 inreactor1506, andgraphical display1842 for color display of the data points displayed inarray1840.Color display1842 can take the form of a two dimensional array of reactor vessels or threedimensional color histogram1870, shown in FIG. 64. The color range forgraphical display1842 andhistogram1870 is displayed inlegends1872 and1874, respectively.Data display pane1838 can display either temperature data or conversion data calculated from pressure measurements as described above. In either case, the displayed data is refreshed at the rate set in thesystem options window1730.
• By selecting an[0263]individual reactor vessel1542 indata display pane1838, the user can view adetailed data window1900 for that vessel, as shown in FIG. 65.Data window1900 provides a graphical display of experimental results, including, for example, temperature, pressure, conversion and molecular weight data for that vessel for the duration of the experiment.
• Referring again to FIG. 64,[0264]toolbar1876 lets the user set reactor parameters (by entering reactor setup window1760) and color scaling forcolor displays1842 and1870. The user can also begin or end an experiment, save results andexit system1500 usingtoolbar1876. The user can enter any observations or comments incomment box1878. User comments and observations can be saved with experimental results.
• Referring to FIG. 66, the user can set the color scaling for[0265]color displays1842 and1870 throughcolor scaling window1920.Color scaling window1920 lets the user select a color range corresponding to temperature or conversion incolor range pane1922. The user can also set a color gradient, either linear or exponential, throughcolor gradient pane1924.Color scaling window1920 displays the selected scale incolor legend1926.
• The invention can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them. Apparatus of the invention can be implemented in a computer program product tangibly embodied in a machine-readable storage device for execution by a programmable processor; and method steps of the invention can be performed by a programmable processor executing a program of instructions to perform functions of the invention by operating on input data and generating output. The invention can be implemented advantageously in one or more computer programs that are executable on a programmable system including at least one programmable processor coupled to receive data and instructions from, and to transmit data and instructions to, a data storage system, at least one input device, and at least one output device. Each computer program can be implemented in a high-level procedural or object-oriented programming language, or in assembly or machine language if desired; and in any case, the language can be a compiled or interpreted language.[0266]
• Suitable computer programs in[0267]modules1508 and1514 can be implemented in classes as set forth in the following tables. (The prefix “o” in a name indicates that the corresponding property is a user-defined object; the prefix “c” in a name indicates that the corresponding property is a collection.)
• 1. Application Class[0268]
• Property Table:[0269]

  Category	Name	Access	Description/Comments
  General	ClsName	Get	Class name
  	AppName	Get	Application name
  	sRootDir	Get/Let	Root directory of all
  			system files
  	bDebugMode	Get/Let	System running mode.
  			If TRUE, display
  			message boxes for errors
  			in addition to error
  			logging. If FALSE, log
  			the error to the log file
  	DBIsConnected	Get/Let	Whether database is
  			connected
  System	SectionGeneral	Get	General section
  Registry	SectionSystemLimits	Get	Section for System Limit
  			Values
  	SectionDefaultParam	Get	Section for system
  			default parameters
  ColorScaling	oTempScale	Get	Color Scale object for
  			temperature data
  	oViscosityScale	Get	Color Scale object for
  			viscosity data
  	oConversionScale	Get	Color Scale object for
  			conversion data
  	oMWScale	Get	Color Scale object for
  			molecule weight data

• Method Table:[0270]

  	Argument
  Name	List	Return Type	Description/Comments
  SaveCnfg		Boolean	Save application configurations to
  			the system registry

• 2. ColorScale Class[0271]
• Parent Class: Application[0272]
• Property Table:[0273]

  Name	Access	Description/Comments
  ClsName	Get	Class name
  Highest	Get/Let	Highest value
  GradientType	Get/Let	Type of the gradient between the lowest
  		and highest to the log file
  LegendValues	Get	A collection of legend values

• Method Table:[0274]

  	Argument	Return
  Name	List	Type	Description/Comments
  SetLegendValues			Recalculate the legend values
  			according to the current property
  			values
  GetLegendColor	fValue	long	Get color of the specified data
  			value

• 3. ColorLegend Class[0275]
• Parent Class: ColorScale[0276]
• Property Table:[0277]

  	Name	Access	Description/Comments
  	ClsName	Get	Class Name
  	ColorCount	Get	Number of colors used in the legend

• Method Table:[0278]

  	Argument	Return
  Name	List	Type	Description/Comments
  GetColorValue	fValue	long	Get color for the specified data
  			value

• 4. System Class[0279]
• Property Table:[0280]

  Category	Name	Access	Description/Comments
  General	ClsName	Get
  	ExpID
  System Status	Status	Get/Let	Status variable
  	STATUS_OFF	Get	constant
  	STATUS_RUN	Get	constant
  	STATUS_IDLE	Get	constant
  	STATUS_ERROR	Get	constant
  System Timing	oExpTiming	Get	Control and record the
  			experiment time
  	oDisplayTiming	Get	Control the data
  			display updating rate
  System Alarming	oAlarm	Get	Provide alarm when
  			system error occurs
  System	oMotors	Get
  Components	oHeaters	Get
  	oPressures	Get

• Method Table:[0281]

  Name	Argument List	Return Type	Description/Comments
  Run
  StopRunning
  Archive

• 5. ExpTiming Class[0282]
• Parent Class: System[0283]
• Property Table:[0284]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  TimingByTime	Get/Let	Boolean type
  TimingByPressure	Get/Let	Boolean type
  TimingByTemperature	Get/Let	Boolean type
  TargetTime	Get/Let	System will stop if specified target
  		value is achieved
  TargetPressure	Get/Let	System will stop if specified target
  		value is achieved
  TargetTemperature	Get/Let	System will stop if specified target
  		value if achieved
  ExpDate	Get/Let	Date when experiment starts to run
  ExpStartTime	Get/Let	Time when experiment starts to fun
  ExpEndTime	Get/Let	Time when experiment stop running
  ExpElapsedTime	Get/Set	The time passed during the experiment
  TimerInterval	Let	Timer used to update the elapsed time

• Method Table:[0285]

  Name	Argument List	Return Type	Description
  LoadDefaultExpTiming		Boolean
  SaveDefaultExpTiming		Boolean

• 6. DisplayTiming Class[0286]
• Parent Class: System[0287]
• Property Table:[0288]

  	Name	Access	Description/Comments
  	ClsName	Get	Class Name
  	DisplayTimer	Get/Set	Timer used to update the data
  	TimerIntercal	Get/Let

• Method Table:[0289]

  Name	Argument List	Return Type	Description

  SaveDefaultParam		Boolean

• 7. Alarm Class[0290]
• Parent Class: System[0291]
• Property Table:[0292]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  BeepTimer	Set	Timer used to control beep
  PauseTimer	Set	Timer used to pause the beep
  BeepStatus	Get	A boolean value: FALSE if paused,
  		otherwise TRUE
  BeepPauseTime	Let	Time duration for beep to pause

• Method Table:[0293]

  	Name	Argument List	Return Type	Description
  	TurnOnBeep			Start to beep
  	TurnOffBeep			Stop beeping
  	BeepPause			Disable beep
  	BeepResume			Enable beep

• 8. Motors Class[0294]
• Parent Class: System[0295]
• Property Table:[0296]

  	Name	Access	Description/Comments
  	ClsName	Get	Class Name
  	SpeedLimit	Get/Let	Safety Limit
  	MotorIsOn	Get/Let	Status variable
  	Card1AxesCount	Get/Let	Axes count in card1
  	Card2AxesCount	Get/Let	Axes count in card2
  	oMotorCard1	Get	Motor card object
  	oMotorCard2	Get	Motor card object
  	oSpinTimer	Get/Set	Timer for dual spin
  	FoundDLL	Get	Motion DLL
  	ErrCode	Get	Error code

• Method Table:[0297]

  		Argument	Return
  Category	Name	List	Type	Description
  To/From	LoadDefaultParam		Boolean
  system	SaveDefaultParam		Boolean
  Registry	SaveCardAxesCount		Boolean
  	SaveSystemLimit		Boolean
  Create/	CreateCard1	iAxesCount
  Delete	CreateCard2	iAxesCount
  Card	DeleteCard1
  Objects	DeleteCard2
  Motor	Init		Boolean	For all axes
  Control	Spin	iAxis,	Boolean
  		dSpeed
  	run		Boolean	For all axes
  	StopRunning		Boolean	For all axes
  Archive	ArchiveParam	iFileNo	Boolean

• 9. MotorAxis Class[0298]
• Parent Class: Motors[0299]
• Property Table:[0300]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  Parent	Set	Reference to the parent object
  MotorID	Get/Let	Motor Axis ID
  oCurParam	Get	Reference to current parameter setting

• Method Table:[0301]

  	Argument
  Name	List	Return Type	Description
  GetParamSetting	[index]	MotorParam	Return the last in the
  			parameter collection
  Run		Boolean	Add oCurParam to the
  			Param collection, and run
  			this motor axis

• 10. MotorParam Class[0302]
• Parent Class: Motors[0303]
• Property Table:[0304]

  Name	Access	Description/Comments
  clsName	Get	Class Name
  Parent	Set	Reference to the parent object
  MotionType	Get/Let	Dual or single direction spin
  DeltaT	Get/Let	Time duration before changing spin direction
  SpinRate	Get/Let	Spin rate in RPM
  EffectiveTime	Get/Let	Time the parameters take effect

• Method Table:[0305]

  Name	Argument List	Return Type	Description
  PrintParam	iFileNo	Boolean	Print the parameters to file

• 11. Heaters Class[0306]
• Parent Class: System[0307]
• Property Table:[0308]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  oParent	Get	Reference to the parent object
  TempLimit	Get/Let	Temperature Safety Limit
  SplRateLimit	Get/Let	Sample Rate Limit
  CtlrLoopCount	Get/Let	Loop count in controller1
  CtlrLoopCount	Get/Let	Loop count in controller2
  HeaterIsOn	Get/Let	Status variable
  oHeaterCtlr1	Get	Heater controller object as clsHeaterCtlr
  oHeaterCtlr2	Get	Heater controller object as clsHeaterCtlr
  oData	Get	Data object as clsHeaterData
  1DataPointsInMem	Get/Let	Number of data points kept in
  		memory
  FoundDLL	Get	RS232 DLL. If found, 1, otherwise −1
  ErrCode	Get	Error Code

• Method Table:[0309]

  		Argument	Return
  Category	Name	List	Type	Descriptions
  To/From	LoadDefaultParam		Boolean
  system	SaveDefaultParam		Boolean
  Registry	SaveCtlrLoopCount		Boolean
  	SaveSystemLimit		Boolean
  Create/	Create Ctlr 1	iLoopCount
  Delete	Create Ctlr 2	iLoopCount
  Ctlr	Delete Ctlr 1
  Objects	DeleteCtlr 2
  Heater	Init		Boolean	Open
  Control				COM1,COM2
  	OutputHeat		Boolean	For all loops
  	TurnOff		Boolean	For all loops
  	GetTemp		Boolean	For all loops
  	SafetyMonitor	Icount,vData		Check
  				Temperature
  	SafetyHandler
  Archive	ArchiveParam	iFileNo	Boolean

• 12. HeaterCtlr Class[0310]
• Parent Class: Heaters[0311]
• Property Table:[0312]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  Parent	Set	Reference to the parent object
  oCurParam	Get	Reference to current parameter setting

• Method Table:[0313]

  	Argument	Return
  Name	List	Type	Description
  AddParamSetting	oParam	Boolean	Add the parameter object to
  			the parameter collection
  GetParamSetting	[index]	HeaterParam	Return the last in the
  			parameter collection

• 13. HeaterParam Class[0314]
• Parent Class: HeaterCtlr[0315]
• Property Table:[0316]

  	Name	Access	Description/Comments
  	clsName	Get	Class Name
  	Parent	Set	Reference to the parent object
  	Setpoint	Get/Let	Setpoint for temperature
  	SplRate	Get/Let	Sampling Rate (Hz)
  	EffectiveTime	Get/Let	Time the parameters take effect

• Method Table:[0317]

  Name	Argument List	Return Type	Description
  PrintParam	iFileNo	Boolean	Print the parameters to file

• 14. HeaterData Class[0318]
• Parent Class: Heaters[0319]
• Property Table:[0320]

  	Name	Access	Description/Comments
  	clsName	Get	Class Name
  	Parent	Set	Reference to the parent object
  	DataPointsInMem	Let
  	LoopCount	Let	Total loop count
  	DataCount	Get	Data point count
  	cTime	Get	Get time data collection
  	cTemp	Get	Get temperature data collection

• Method Table:[0321]

  	Argument	Return
  Name	List	Type	Description
  GetData	ByRef fTime,	Boolean	Get current data set, or the data
  	ByRef vTemp		set with specified index
  	[,index]
  AddData	fTime, vTemp		Add the data set to the data
  			collections
  ClearData			Clear the data collection
  WriteToDisk			Write the current data to disk
  			file

• 15. Pressures Class[0322]
• Parent Class: System[0323]
• Property Table:[0324]

  Name	Access	Description/Comments
  ClsName	Get	Class Name
  oParent	Get	Reference to the parent object
  PressureLimit	Get/Let	Pressure Safety Limit
  SplRateLimit	Get/Let	Sample Rate Limit
  ChannelCount	Get/Let	Analog Input channel count
  PressureIsOn	Get/Let	Status variable
  oData	Get	Data object as clsPressureData
  1DataPointsInMem	Get/Let	Number of data points kept in memory
  oCWAOP	Get	Object of analog output ActiveX control
  oCWAIP	Get	Object of analog input ActiveX control
  ErrCode	Get	Error code

• Method Table:[0325]

  		Argument	Return
  Category	Name	List	Type	Description
  To/From	LoadDefaultParam		Boolean
  System	SaveDefaultParam		Boolean
  Registry	SaveChannelCount		Boolean
  	SaveDataPointsInMem
  	SaveSystemLimit		Boolean
  Pressure	AnalogOutput		Boolean	Output Pset
  System	GetAIData		Boolean	Analog Input
  Control
  Archive	ArchiveParam	iFileNo	Boolean

• 16. PressureParam Class[0326]
• Parent Class: Pressures[0327]
• Property Table:[0328]

  	Name	Access	Description/Comments
  	clsName	Get	Class Name
  	Parent	Set	Reference to the parent object
  	Setpoint	Get/Let	Setpoint for pressure (psi)
  	SplRate	Get/Let	Sampling Rate (Hz)
  	EffectiveTime	Get/Let	Time the parameters take effect

• Method Table:[0329]

  	Argument
  Name	List	Return Type	Description
  PrintParam	iFileNo	Boolean	Print the parameters to the file

• 17. PressureData Class[0330]
• Parent Class: Pressures[0331]
• Property Table:[0332]

  Name	Argument	Access	Description/Comments
  clsName		Get	Class Name
  Parent		Set	Reference to the parent object
  DataPointsInMem		Let
  ChannelCount		Let	Total AI channel count
  PresCount		Get	Pressure data point count
  ConvCount		Get	Conversion data point count
  cPresTime		Get	Get time collection for
  			pressure data
  cPressure		Get	Get pressure data collection
  cConvTime	iChannelNo	Get	Get time collection for
  			conversion data
  cConversion	iChannelNo	Get	Get conversion data collection

• Method Table:[0333]

  	Argument	Return
  Name	List	Type	Description
  GetCurPres	ByRef vPres	Boolean	Get current pressure data
  			set
  GetCurConv	ByRef	Boolean	Get current conversion data
  	vConv		set
  AddPres	fTime, vPres		Add the pressure data set to
  			the pressure data
  			collections, then calculate
  			conversions
  ClearData			Clear all the data
  			collections
  WritePresToDisk		Boolean	Write the current pressure
  			data to disk file
  WriteConvToDisk		Boolean	Write the current
  			conversion data to disk file

• 18. ErrorHandler Class[0334]
• Property Table:[0335]

  	Name	Access	Description/Comments
  	ClsName	Get	Class Name
  	LogFile	Get/Let	Log file for error messages

• Method Table:[0336]

  		Return
  Name	Argument List	Type	Description
  SaveConfg		Boolean
  OpenLogFile	iFileNo	Boolean	Open log file with specified
  			file number for APPEND,
  			lock WRITE
  OpenLogfile	iFileNo	Boolean	Open log file with specified
  			file number for APPEND,
  			lock WRITE
  CloseLogFile
  LogError	sModName,		Write error messages to the
  	sFuncName,		log file, also call DisplayError
  	iErrNo,		in debug mode
  	sErrText
  DisplayError	sModName,		Show message Box to display
  	sFuncName,		the error
  	iErrNo,
  	sErrText

• Suitable processors include, by way of example, both general and special purpose microprocessors. Generally, a processor will receive instructions and data from a read-only memory and/or a random access memory. Storage devices suitable for tangibly embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices, such as EPROM, EEPROM, and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM disks. Any of the foregoing can be supplemented by, or incorporated in, ASICs (application-specific integrated circuits).[0337]
• To provide for interaction with a user, the invention can be implemented on a computer system having a display device such as a monitor or LCD screen for displaying information to the user and a keyboard and a pointing device such as a mouse or a trackball by which the user can provide input to the computer system. The computer system can be programmed to provide a graphical user interface through which computer programs interact with users.[0338]
• An example of one such type of computer is shown in FIG. 67, which shows a block diagram of a[0339]programmable processing system1950 suitable for implementing or performing the apparatus or methods of the invention. Thesystem1950 includes aprocessor1952, a random access memory (RAM)1954, a program memory1956 (for example, a writable read-only memory (ROM) such as a flash ROM), ahard drive controller1958, and an input/output (I/O)controller1960 coupled by a processor (CPU)bus1962. Thesystem1950 can be preprogrammed, in ROM, for example, or it can be programmed (and reprogrammed) by loading a program from another source (for example, from a floppy disk, a CD-ROM, or another computer).
• The[0340]hard drive controller1958 is coupled to ahard disk1964 suitable for storing executable computer programs, including programs embodying the present invention, and data including the images, masks, reduced data values and calculated results used in and generated by the invention. The I/O controller1960 is coupled by means of an I/O bus1966 to an I/O interface1968. The I/O interface1968 receives and transmits data in analog or digital form over communication links such as a serial link, local area network, wireless link, and parallel link. Also coupled to the I/O bus1966 is adisplay1970 and akeyboard1972. Alternatively, separate connections (separate buses) can be used for the I/O interface1966,display1970 andkeyboard1972.
• The invention has been described in terms of particular embodiments. Other embodiments are within the scope of the following claims. Although elements of the invention are described in terms of a software implementation, the invention may be implemented in software or hardware or firmware, or any combination of the three. In addition, the steps of the invention can be performed in a different order and still achieve desirable results.[0341]
• Moreover, the above description is intended to be illustrative and not restrictive. Many embodiments and many applications besides the examples provided will be apparent to those of skill in the art upon reading the above description. The scope of the invention should therefore be determined, not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. The disclosures of all articles and references, including patent applications and publications, are incorporated by reference for all purposes.[0342]

Claims (162)

What is claimed is:

1. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures;

a stirring system for agitating the reaction mixtures; and

a temperature control system that is adapted to maintain a first group of the vessels at a different temperature than a second group of the vessels.

2. The apparatus ofclaim 1, further comprising a reactor block;

wherein the vessels comprise wells formed in the reactor block.

3. The apparatus ofclaim 2, wherein the vessels further comprise removable liners, each of the liners having an interior surface defining a cavity for containing one of the reaction mixtures and an exterior surface dimensioned so that the liners fit within the wells formed in the reactor block.

4. The apparatus ofclaim 3, wherein the removable liners are glass vials.

5. The apparatus ofclaim 3, further comprising an insulating material filling gaps between the removable liners and the wells.

6. The apparatus ofclaim 5, wherein the insulating material is glass wool or silicone rubber.

7. The apparatus ofclaim 3, further comprising a conductive material filling gaps between the removable liners and the wells.

8. The apparatus ofclaim 7, wherein the conductive material is a thermal paste.

9. The apparatus ofclaim 2, wherein the wells comprise holes extending from a top surface of the reactor block to a bottom surface of the reactor block, the apparatus further comprising:

a removable lower plate disposed on the bottom surface of the reactor block, the removable lower plate defining a base of each of the wells; and

a removable upper plate disposed on the top surface of the reactor block, the removable upper plate defining an upper end of each of the wells.

10. The apparatus ofclaim 9, wherein the removable upper plate further comprises vessel seals in substantial alignment with the wells, the vessel seals allowing processing of the reaction mixtures at pressures different than atmospheric pressure.

11. The apparatus ofclaim 2, further comprising a passageway formed in the reactor block adapted to provide a flow path for a thermal fluid and adapted to provide heat exchange between the vessels and the thermal fluid.

12. The apparatus ofclaim 2, further comprising:

a passageway formed in the reactor block adapted to provide a flow path for a thermal fluid and to provide heat exchange between the thermal fluid and the vessels.

13. The apparatus ofclaim 2, further comprising:

thermoelectric devices and a heat transfer plate, the thermoelectric devices disposed between the reactor block and the heat transfer plate such that the thermoelectric devices transfer heat from the vessels to the heat transfer plate or from the heat transfer plate to the vessels.

14. The apparatus ofclaim 13, wherein each of the thermoelectric devices transfers heat predominantly to or from a single vessel.

15. The apparatus ofclaim 13, wherein the heat transfer plate further comprises a passageway formed in the heat transfer plate adapted to provide a flow path for a thermal fluid.

16. The apparatus ofclaim 1, further comprising a chamber enclosing the vessels, the chamber being substantially gas impermeable.

17. The apparatus ofclaim 1, further comprising a plurality of modules, each of the modules containing a portion of the vessels.

18. The apparatus ofclaim 17, wherein each of the modules comprises a block and wherein vessels comprise wells formed in the block.

19. The apparatus ofclaim 1, further comprising a robotic material handling system for loading the vessels with starting materials.

20. The apparatus ofclaim 1, wherein the temperature control system includes a temperature monitoring system comprising:

temperature sensors in thermal contact with the vessels; and

a temperature monitor that communicates with the temperature sensors and converts signals received from the temperature sensors to a standard temperature scale.

21. The apparatus ofclaim 20, wherein the temperature sensors are thermocouples, resistance thermometric devices, or thermistors, alone or in combination.

22. The apparatus ofclaim 20, further comprising a processor that communicates with the temperature monitor, the processor adapted to perform calculations on data received from the temperature monitor.

23. The apparatus ofclaim 1, wherein the temperature control system includes a remote temperature monitoring system comprising an infrared-sensitive camera positioned to detect infrared radiation emanating from each of the vessels.

24. The apparatus ofclaim 23, wherein each of the vessels are fitted with a cap that transmits infrared radiation.

25. The apparatus ofclaim 23, further comprising an isolation chamber enclosing the vessels.

26. The apparatus ofclaim 1, wherein the temperature control system further comprises temperature sensors and heat transfer devices, the temperature sensors and the heat transfer devices in thermal contact with the vessels, and the heat transfer devices adapted to transfer heat to or from the vessels in response to signals received from the temperature sensors.

27. The apparatus ofclaim 26, wherein the temperature control system further comprises:

a processor that communicates with the temperature sensors and the heat transfer devices, the processor and the heat transfer devices adapted to adjust heat flow to or from the heat transfer devices in response to signals received by the processor from the temperature sensors.

28. The apparatus ofclaim 26, wherein the heat transfer devices are electric resistance heaters.

29. The apparatus ofclaim 28, wherein the temperature sensors and the electric resistance heaters are the same.

30. The apparatus ofclaim 29, wherein the temperature sensors and the electric resistance heaters are thermistors.

31. The apparatus ofclaim 26, wherein the heat transfer devices are thermoelectric devices.

32. The apparatus ofclaim 26, wherein the temperature control system further comprises a uniform temperature reservoir in thermal contact with the vessels.

33 The apparatus ofclaim 32, wherein the uniform temperature reservoir is adapted to contain a thermal fluid.

34. The apparatus ofclaim 33, wherein the vessels are suspended in the uniform temperature reservoir.

35. The apparatus ofclaim 32, wherein the temperature control system further comprises a heat pump in thermal contact with the uniform temperature reservoir, the heat pump adapted to maintain the uniform temperature reservoir at a selected temperature.

36. The apparatus ofclaim 1, wherein the stirring system comprises:

stirring members at least partially contained in the vessels; and

a drive mechanism coupled to the stirring members, the drive mechanism adapted to rotate the stirring members.

37. The apparatus ofclaim 36, wherein the drive mechanism comprises motors coupled to the stirring members so that the speed, torque, or speed and torque of the stirring members can be independently varied.

38. The apparatus ofclaim 37, further comprising strain gauges for measuring torque exerted by the motors on the reaction mixtures, wherein the motors are rigidly attached to a motor support, and the strain gauges are mounted between the motor support and the motors.

39. The apparatus ofclaim 37, further comprising speed sensors integral to the motors for monitoring rotational speed of the stirring members.

40. The apparatus ofclaim 39, further comprising a processor in communication with the speed sensors, the processor adjusting power supplied to each of the motors in response to signals received from the speed sensors to maintain the rotational speed of the stirring members at selected values.

41. The apparatus ofclaim 36, further comprising strain gauges for measuring torque exerted by the drive mechanism on the reaction mixtures, each of the strain gauges having a first end and a second end, the first end of each of the strain gauges rigidly attached to the vessel support, and the second end of each of the strain gauges rigidly attached to the vessels such that each of the vessels is attached to one of the strain gauges.

42. The apparatus ofclaim 41, further comprising:

first permanent magnets attached to the second end of each of the strain gauges; and

second permanent magnets attached to the vessels so that magnetic coupling between the first permanent magnets and the second permanent magnets prevents the vessels from rotating.

43. The apparatus ofclaim 36, wherein the drive mechanism comprises:

a motor; and

a drive train coupling the motor to the stirring members.

44. The apparatus ofclaim 43, wherein the drive train comprises:

gears attached to the motor and to portions of the stirring members located external to the vessels, each of the gears dimensioned and arranged to mesh with at least one adjacent gear so that rotational energy is transmitted along the drive train from the motor to the stirring members.

45. The apparatus ofclaim 36, wherein each of the stirring members comprises:

a spindle, each spindle having a first end and a second end; and

a stirring blade attached to the first end of the spindle.

46. The apparatus ofclaim 45, wherein the second end of the spindle is mechanically coupled to the drive mechanism.

47. The apparatus ofclaim 45, wherein the second end of the spindle is magnetically coupled to the drive mechanism.

48. The apparatus ofclaim 45, further comprising a strain gauge located within the spindle.

49. The apparatus ofclaim 45, further comprising an optical speed sensor mounted adjacent to the spindle for monitoring rotational speed of the spindle.

50. The apparatus ofclaim 36, wherein the stirring members are magnetic stirring bars, and the drive mechanism comprises an array of electromagnets that produce rotating magnetic fields in the vessels.

51. The apparatus ofclaim 50, wherein the array of electromagnets is arranged so that each of the vessels is located between four electromagnets, the four electromagnets defining four corners of a quadrilateral sub-array.

52. The apparatus ofclaim 50, wherein the array of electromagnets comprises:

a first group of electromagnets, and a second group of electromagnets, the first group of electromagnets electrically connected in series so that pairs of successive electromagnets define two opposite corners of each quadrilateral sub-array, and the second group of electromagnets electrically connected in series such that pairs of successive electromagnets define two opposite corners of each quadrilateral sub-array.

53. The apparatus ofclaim 52, further comprising a drive circuit and a processor, the drive circuit controlled by the processor and adapted to independently and temporally vary electrical current in the first group of electromagnets and in the second group of electromagnets.

54. The apparatus ofclaim 53, wherein the drive circuit further comprises a power source that is adapted to provide sinusoidal electrical currents.

55. The apparatus ofclaim 53, wherein the drive circuit further comprises a power source that is adapted to provide pulsed electrical currents.

56. The apparatus ofclaim 50, wherein the array of electromagnets is mounted on a printed circuit board.

57. The apparatus ofclaim 36, wherein the stirring system further comprises a system for measuring phase lag between the stirring members and the drive mechanism.

58. The apparatus ofclaim 57, wherein the system for measuring phase lag comprises inductive sensing coils located adjacent to the vessels and displaced laterally from the axes of rotation of the stirring members, and a phase-sensitive detector adapted to monitor phase differences among signals generated by the inductive sensing coils and a reference signal having the same phase behavior as the drive mechanism.

59. The apparatus ofclaim 1, further including a system for evaluating reaction mixtures comprising at least one mechanical oscillator in contact with the reaction mixtures, the at least one mechanical oscillator adapted to receive a variable frequency excitation signal and to transmit a response signal that depends on one or more material properties of the reaction mixtures.

60. The apparatus ofclaim 59, further comprising a plurality of mechanical oscillators, each of the mechanical oscillators located in the vessels.

61. The apparatus ofclaim 59, wherein the at least one mechanical oscillator is a tuning fork resonator or bimorph/unimorph resonator.

62. The apparatus ofclaim 59, further comprising a three-axis translation system for placing the at least one mechanical oscillator in the vessels.

63. The apparatus ofclaim 59, further comprising:

a probe adapted to withdraw and dispense the reaction mixtures; and

a three-axis translation system coupled to the probe for manipulating the probe position;

wherein the at least one mechanical oscillator is located in a separate vessel and the three-axis translation system is adapted to withdraw a portion of one of the reaction mixtures from one of the vessels and to dispense the portion of one of the reaction mixtures in the separate vessel.

64. The apparatus ofclaim 1, further comprising a pressure control system.

65. The apparatus ofclaim 64, wherein each of the vessels has a gas inlet for introducing a vapor-phase component of the reaction mixtures into the vessels.

66. The apparatus ofclaim 65, further comprising a flow sensor located between the gas inlet and a source of the vapor-phase component of the reaction mixture.

67. The apparatus ofclaim 64, wherein the vessels have a removable seal for loading the vessels with condensed-phase components of the reaction mixtures.

68. The apparatus ofclaim 64, further comprising temperature sensors in thermal contact with the vessels, the temperature sensors providing data for determining pressure corrections based on temperature changes of the reaction mixtures.

69. An apparatus for monitoring rates of production or consumption of a gas-phase component of a reaction mixture comprising:

a vessel for containing the reaction mixture, the vessel having a gas inlet for introducing a gas-phase component of the reaction mixture into the vessel and a removable seal for loading the vessel with one or more condensed-phase components of the reaction mixture;

a temperature control system for regulating the temperature of the reaction mixture; and

a pressure control system comprising:

a pressure sensor in fluid communication with the vessel;

a conduit providing fluid communication between a source of the gas-phase component and the gas inlet of the vessel;

a valve located along the conduit between the source of the gas-phase component and the gas inlet of the vessel;

a valve controller communicating with the valve, the valve controller regulating the amount of the gas-phase component entering the vessel by selectively opening or closing the valve; and

a processor communicating with the valve controller and the pressure sensor, the processor directing the valve controller to selectively open or close the valve in response to a signal received from the pressure sensor.

70. The apparatus ofclaim 69, further comprising a temperature sensor in thermal contact with the vessel, the temperature sensor communicating with the processor and providing the processor with data for determining pressure corrections based on temperature changes of the reaction mixture.

71. The apparatus ofclaim 69, further comprising a flow sensor located along the conduit between the valve and the gas inlet of the vessel, the flow sensor communicating with the processor and providing the processor with data for determining an amount of the gas-phase component entering the vessel.

72 An apparatus for monitoring rates of consumption of a gas-phase reactant of a reaction mixture comprising:

a vessel for containing the reaction mixture, the vessel having a gas inlet for introducing the gas-phase reactant into the vessels and a removable seal for loading the vessel with one or more condensed-phase components of the reaction mixture;

a temperature control system for regulating the temperature of the reaction mixture; and

a pressure control system comprising:

a pressure sensor in fluid communication with the vessel;

a conduit providing fluid communication between a source of the gas-phase reactant and the gas inlet of each of the vessels;

a flow sensor located along the conduit between the source of the gas-phase component and the gas inlet of the vessel; and

a processor communicating with the flow sensor, the flow sensor providing the processor with data for determining an amount of the gas-phase reactant entering the vessel during processing.

73. A method of making and characterizing materials comprising the steps of:

providing vessels with starting materials to form reaction mixtures;

allowing the reaction mixtures in the vessels to react;

stirring the reaction mixtures during at least a portion of the reaction; and

evaluating the reaction mixtures by measuring at least one characteristic of the reaction mixtures during at least a portion of the reaction;

wherein the reaction is carried out at about the same time for each of the reaction mixtures.

74. The method ofclaim 73, wherein the vessels are provided with starting materials using a robotic material.

75. The method ofclaim 73, further comprising blanketing the vessels in an inert gas atmosphere while providing vessels with starting materials.

76. The method ofclaim 73, wherein the reaction mixtures are evaluated by monitoring temperatures of each of the reaction mixtures.

77. The method ofclaim 76, wherein monitoring temperatures comprises detecting infrared emissions from the reaction mixtures.

78. The method ofclaim 73, wherein the reaction mixtures are evaluated by monitoring heat transfer rates into or out of the vessels.

79. The method ofclaim 78, wherein monitoring heat transfer rates comprises:

measuring temperature differences between each of the reaction mixtures and a thermal reservoir surrounding the vessels; and

determining heat transfer rates from a calibration relating the temperature differences to heat transfer rates.

80. The method ofclaim 78, further comprising computing conversion of the starting materials based on the heat transfer rates of the monitoring step.

81. The method ofclaim 80, further comprising determining rates of reaction based on conversion of the starting materials.

82. The method ofclaim 73, wherein stirring comprises:

supplying the reaction mixtures with stirring members; and

rotating each of the stirring members.

83. The method ofclaim 82, wherein the stirring members rotate at the same rate.

84. The method ofclaim 82, wherein the reaction mixtures are evaluated by monitoring the torque needed to rotate the stirring members.

85. The method ofclaim 84, wherein the torque is monitored by measuring phase lag between the torque and the stirring members.

86. The method ofclaim 84, wherein the reaction mixtures are evaluated by determining viscosity of each of the reaction mixtures from a calibration relating the torque and viscosity.

87. The method ofclaim 86, wherein the reaction mixtures are evaluated by:

measuring heat transfer rates into or out of the vessels;

computing conversion of the starting materials based on heat transfer rates into or out of the vessels; and

calculating molecular weight of a component of the reaction mixtures based on conversion of the starting materials and on viscosity of each of the reaction mixtures.

88. The method ofclaim 82, wherein the evaluating step further comprises the step of monitoring the power needed to rotate each of the stirring members in the rotating step.

89. The method ofclaim 88, wherein the reaction mixtures are evaluated by determining viscosity of each of the reaction mixtures from a calibration relating power and viscosity.

90. The method ofclaim 89, wherein the reaction mixtures are evaluated by:

measuring heat transfer rates into or out of the vessels;

computing conversion of the starting materials based on heat transfer into or out of the vessels; and

calculating molecular weight of a component of the reaction mixtures based on conversion of the starting materials and on viscosity of each of the reaction mixtures.

91. The method ofclaim 82, wherein the reaction mixtures are evaluated by monitoring stall frequencies of the stirring members in the rotating step.

92. The method ofclaim 91, wherein the reaction mixtures are evaluated by determining viscosity of each of the reaction mixtures from a calibration relating stall frequencies and viscosity.

93. The method ofclaim 92, wherein the reaction mixtures are evaluated by:

measuring rates of heat transfer into or out of the vessels;

computing conversion of the starting materials based on rates of heat transfer into or out of the vessels; and

calculating molecular weight of a component of the reaction mixtures based on conversion of the starting materials and on viscosity of each of the reaction mixtures.

94. The method ofclaim 73, wherein the reaction mixtures are evaluated by:

stimulating mechanical oscillators in contact with the reaction mixtures with a variable frequency excitation signal;

monitoring response signals from the mechanical oscillators;

determining a property of each of the reaction mixtures from a calibration relating response signals and the property.

95. The method ofclaim 94, wherein the property is molecular weight, specific gravity, elasticity, dielectric constant or conductivity.

96. The method ofclaim 73, wherein the reaction mixtures are evaluated by:

supplying a separate vessel with a mechanical oscillator;

placing a portion of a particular reaction mixture in the separate vessel;

stimulating the oscillator with a variable frequency excitation signal;

monitoring a response signal from the mechanical oscillator; and

determining a property of the particular reaction mixture from a calibration relating response signals and the property.

97. The method ofclaim 73, wherein there is a net loss of moles of gas-phase components of each of the reaction mixtures due to reaction, and the reaction mixtures are evaluated by:

filling the vessels with a gas-phase reactant until gas pressure in each of the vessels exceeds an upper-pressure limit, P_H;

allowing gas pressure in each of the vessels to decay below a lower-pressure limit, P_L;

monitoring the gas pressure in each of the vessels to generate a record of pressure versus time for each of the vessels;

repeating filling, allowing, and monitoring at least once; and

determining rates of consumption of the gas-phase reactant in each of the reaction mixtures from the record of pressure versus time for each of the vessels.

98. The method ofclaim 97, wherein the rates of consumption are determined by:

converting the record of pressure versus time for each of the vessels to partial pressure of the gas-phase reactant versus time for each of the vessels; and

calculating rates of consumption of the gas-phase reactant in each of the reaction mixtures from time rates of change of the partial pressure of the gas-phase reactant versus time during the gas pressure decays.

99. The method ofclaim 97, wherein the rates of consumption are determined from frequencies of the filling steps over particular time intervals.

100. The method ofclaim 97, wherein the rates of consumption are determined by:

estimating a volumetric flow rate of the gas-phase reactant entering a given vessel during a particular filling operation;

multiplying the volumetric flow rate of the gas-phase reactant entering the given vessel during the particular filling operation by an amount of time elapsed during the particular filling operation to obtain an estimate of an amount of the gas-phase reactant entering the given vessel during the particular filling operation;

dividing the estimate of the amount of the gas-phase reactant entering the given vessel during the particular filling step by an amount of time elapsed during a subsequent gas pressure decay to obtain an average rate of consumption of the gas-phase reactant in the given vessel for the particular filling operation and the subsequent gas pressure decay.

101. The method ofclaim 97, wherein the rates of consumption are determined by:

measuring an amount of the gas-phase reactant entering a given vessel during a particular filling operation;

dividing the amount of the gas-phase reactant entering the given vessel during the particular filling operation by an amount of time elapsed during a subsequent gas pressure decay to obtain an average rate of consumption of the gas-phase reactant in the given vessel for the particular filling operation and the subsequent gas pressure decay.

102. The method ofclaim 73, wherein there is a net gain of moles of gas-phase components of each of the reaction mixtures due to reaction, and the reaction mixtures are evaluated by:

allowing gas pressure in each of the vessels to rise above an upper-pressure limit, P_H;

venting the vessels until gas pressure in each of the vessels falls below a lower-pressure limit, P_L;

monitoring the gas pressure in each of the vessels during the gas pressure rise and venting to generate a record of pressure versus time for each of the vessels;

repeating allowing, venting, and monitoring at least once; and

determining rates of production of a gas-phase product in each of the reaction mixtures from the record of pressure versus time for each of the vessels.

103. The method ofclaim 102, wherein the rates of production are determined by:

converting the record of pressure versus time for each of the vessels to partial pressure of the gas-phase product versus time for each of the vessels;

calculating rates of production of the gas-phase product in each of the reaction mixtures from time rates of change of the partial pressure of the gas-phase product versus time during the gas pressure rises.

104. The method ofclaim 102, wherein the rates of production are determined from frequencies of venting over particular time intervals.

105. The method ofclaim 102, wherein the rates of production are determined by:

estimating a volumetric flow rate of the gas-phase product leaving a given vessel during a particular venting operation;

multiplying the volumetric flow rate of the gas-phase product leaving the given vessel during the particular venting operation by an amount of time elapsed during the particular venting operation to obtain an estimate of an amount of the gas-phase product leaving the given vessel during the particular venting operation;

dividing the estimate of the amount of the gas-phase product leaving the given vessel during the particular venting operation by an amount of time elapsed during a subsequent gas pressure rise to obtain an average rate of production of the gas-phase product in the given vessel for the particular venting operation and the subsequent gas pressure rise.

106. The method ofclaim 102, wherein the rates of production are determined by:

measuring an amount of the gas-phase product leaving a given vessel during a particular venting operation;

dividing the amount of the gas-phase product leaving the given vessel during the particular venting operation by an amount of time elapsed during a subsequent gas pressure rise to obtain an average rate of production of the gas-phase product in the given vessel for the particular venting operation and the subsequent gas pressure rise.

107. The method ofclaim 73, further comprising controlling temperatures of each of the reaction mixtures.

108. The method ofclaim 107, wherein temperatures of each of the reaction mixtures are controlled independently.

109. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures;

a stirring system for agitating the reaction mixtures;

a temperature control system for regulating the temperature of the reaction mixtures; and

an injection system for introducing a fluid into the vessels at a pressure different than ambient pressure.

110. The apparatus ofclaim 109, wherein the injection system comprises:

fill ports adapted to receive a fluid delivery probe;

first conduits and valves, the first conduits providing fluid communication between the fill ports and the valves; and

second conduits and injectors, the second conduits providing fluid communication between the valves and the injectors;

wherein the injectors are located in the vessels.

111. The apparatus ofclaim 110, further comprising a robotic fluid handling system, wherein the robotic fluid handling system is adapted to manipulate the fluid delivery probe.

112. The apparatus ofclaim 111, further comprising a computer to control both the robotic fluid handling system and the valves.

113. The apparatus ofclaim 110, wherein the fill port comprises:

an elongated body having a longitudinal axis and a bore centered on the longitudinal axis, the bore extending the length of the elongated body and characterized by first, second, and third diameters, wherein the first diameter is greater than the second diameter, and the second diameter is greater than the third diameter;

an elastomeric o-ring seated within the bore of the elongated body on a first ledge defined by the second diameter and the third diameter; and

a cylindrical sleeve having a hole centered on its axis of rotation, the hole extending the length of the cylindrical sleeve;

wherein the cylindrical sleeve is seated within the bore of the elongated body on a second ledge defined by the first diameter and the second diameter and the cylindrical sleeve abuts the elastomeric o-ring.

114. The apparatus ofclaim 113, wherein the cylindrical sleeve is made of a chemically resistant plastic material.

115. The apparatus ofclaim 114, wherein the chemically resistant plastic material is a perfluoro-elastomer or polyethylethylketone or polytetrafluoroethylene.

116. The apparatus ofclaim 110, wherein the fill port comprises:

an elongated body having a longitudinal axis and a bore centered on the longitudinal axis, the bore extending the length of the elongated body and characterized by a first diameter and a second diameter, wherein the first diameter is greater than the second diameter; and

a cylindrical insert having a tapered hole centered on its axis of rotation, the tapered hole extending the length of the cylindrical insert;

wherein the cylindrical insert is seated within the bore of the elongated body on a ledge defined by the first diameter and the second diameter.

117. The apparatus ofclaim 116, wherein the cylindrical insert is made of a chemically resistant plastic material.

118. The apparatus ofclaim 117, wherein the chemically resistant plastic material is a perfluoro-elastomer or polyethylethylketone or polytetrafluoroethylene.

119. The apparatus ofclaim 110, further comprising a reactor block;

wherein the vessels comprise wells formed in the reactor block.

120. The apparatus ofclaim 119, further comprising an injector manifold associated with the reactor block;

wherein the fill ports and valves are in fluid communication with the injector manifold.

121. The apparatus ofclaim 120, wherein the injector manifold is attached to the reactor block, and the first conduits and the second conduits are passageways formed in the injector manifold.

122. The apparatus ofclaim 120, wherein the wells comprise holes extending from a top surface of the reactor block to a bottom surface of the reactor block, the apparatus further comprising:

a lower plate disposed on the bottom surface of the reactor block, the lower plate defining a base of each of the wells;

an injector adapter plate disposed on the top surface of the reactor block, the injector adapter plate having holes substantially aligned with the wells and having channels extending from a front edge of the injector adapter plate to a bottom surface of the injector adapter plate, wherein the injectors are attached to the bottom surface of the injector adapter plate and are in fluid communication with the channels, and the injector manifold is attached to the front edge of the injector adapter plate so that the second conduits are in fluid communication with the channels of the injector adapter plate; and

an upper plate disposed on the injector adapter plate, the upper plate defining an upper end of each of the well.

123. The apparatus ofclaim 122, wherein the injectors extend into the reaction mixtures.

124. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures, the vessels sealed to minimize unintentional gas flow into or out of the vessels;

a temperature control system for regulating the temperature of the reaction mixtures; and

a stirring system for agitating the reaction mixtures, the stirring system comprising:

spindles contained in the vessels, each of the spindles having a first end and a second end;

a stirring blade attached to the first end of each of the spindles;

a drive mechanism located external to the vessels that is adapted to rotate the spindles; and

magnetic feed through devices for magnetically coupling the drive mechanism to the second end of each of the spindles.

125. The apparatus ofclaim 124, wherein each of the magnetic feed through devices comprises:

a rigid cylindrical pressure barrier having an interior surface that together with one of the vessels defines a closed chamber;

a magnetic driver rotatably mounted concentrically with the pressure barrier and external to the closed chamber; and

a magnetic follower rotatably mounted within the closed chamber;

wherein the drive mechanism is mechanically coupled to the magnetic driver and the magnetic follower follows the magnetic driver, and the second end of one of the spindles is attached to the magnetic follower so that the spindles rotate as driven by the drive mechanism.

126. The apparatus ofclaim 125, wherein the drive mechanism further comprises:

a motor; and

a drive train coupling the motor to the magnetic driver of the magnetic feed through devices.

127. The apparatus ofclaim 125, wherein the drive train comprises:

gears attached to the motor and to the magnetic driver of the magnetic feed through devices, each of the gears dimensioned and arranged so as to mesh with at least one adjacent gear so that rotational energy is transmitted along the drive train from the motor to the spindles through the magnetic feed through devices.

128. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures;

a temperature control system for regulating the temperature of the reaction mixtures; and

a stirring system for agitating the reaction mixtures, the stirring system comprising multi-piece spindles partially contained in the vessels, and a drive mechanism coupled to the spindles, the drive mechanism adapted to rotate the spindles;

wherein each of the spindles includes an upper spindle portion mechanically coupled to the drive mechanism, and a removable stirrer contained in one of the vessels.

129. The apparatus ofclaim 128, wherein the removable stirrer is made of a chemically resistant plastic material.

130. The apparatus ofclaim 129, wherein the chemically resistant plastic material is a perfluoro-elastomer or polyethylethylketone or polytetrafluoroethylene or glass.

131. The apparatus ofclaim 129, further comprising a coupler for reversibly attaching the removable stirrer to the upper spindle portion, the coupler comprising:

a cylindrical body having first and second holes centered along an axis of rotation of the coupler, the first hole dimensioned to receive an end of the upper spindle portion, and the second hole of the coupler dimensioned to receive an end of the removable stirrer.

132. The apparatus ofclaim 131, further comprising a locking mechanism for preventing relative rotation of the coupler and the removable stirrer, the locking mechanism including:

a pin embedded in the end of the removable stirrer;

a spring mounted between the coupler and a shoulder formed on the removable stirrer periphery; and

an axial groove extending from an entrance of the second hole to a lateral slot cut through a wall of the coupler, the lateral slot extending partway around the coupler circumference to an axial slot cut through the wall of the coupler;

wherein the axial groove, the lateral slot, and the axial slot are sized to accommodate the pin when the end of the removable stirrer is inserted into the second hole and rotated, and the pin is held in the axial slot by a force exerted by the spring.

133. The apparatus ofclaim 128, wherein the removable stirrer is snapped into the upper spindle portion.

134. A method of making and characterizing materials comprising:

providing vessels with starting materials to form reaction mixtures;

injecting a fluid into at least one of the vessels;

stirring the reaction mixtures; and

evaluating the reaction mixtures by measuring at least one characteristic of the reaction mixtures.

135. The method ofclaim 134, wherein the fluid comprises a catalyst.

136. The method ofclaim 134, wherein the fluid comprises a catalyst poison.

137. The method ofclaim 134, wherein the fluid comprises a comonomer.

138. A method for monitoring parallel, combinatorial chemical reactions, the method comprising:

(a) communicating a plurality of measured values to a microprocessor, the plurality of measured values being associated, respectively, with the contents of a plurality of reactors during simultaneous reaction of two or more reactants in the plurality of reactors, the reactants or reaction environments varying between the plurality of reactors,

(b) displaying the measured values, and

(c) repeating steps (a) and (b) at least once during the reactions.

139. The method ofclaim 138 wherein the plurality of measured values are associated, respectively, with the reaction environments for the plurality of reactors.

140. The method ofclaim 138, wherein step (c) is performed at a predetermined sampling rate.

141. The method ofclaim 138, further comprising:

changing a reaction parameter associated with one of the plurality of reactor vessels in response to the measured value to maintain the reactor vessel at a predetermined set point.

142. The method ofclaim 141, wherein the reaction parameter comprises a reactor vessel temperature.

143. The method ofclaim 141, wherein the reaction parameter comprises a reactor vessel pressure.

144. The method ofclaim 141, wherein the reaction parameter comprises a reactor vessel motor speed.

145. The method ofclaim 138, further comprising:

quenching a catalyst in one of the plurality of reactor vessels in response to the measured value associated with the contents of the reactor vessel.

146. The method ofclaim 138 further comprising:

calculating an experimental value for one or more of the plurality of reactors based on one or more measured values for that one or more reactors.

147. The method ofclaim 146, wherein the experimental value comprises temperature change.

148. The method ofclaim 146, wherein the experimental value comprises pressure change.

149. The method ofclaim 146, wherein the experimental value comprises percent conversion of starting material.

150. The method ofclaim 146, wherein the experimental value comprises viscosity.

151. The method ofclaim 146, further comprising displaying the experimental value.

152. A method for controlling parallel, combinatorial chemical reactions, the method comprising

communicating a plurality of experimental values to a microprocessor, the plurality of experimental values being associated, respectively, with a property of reaction environments for a plurality of reactors during simultaneous reaction of two or more reactants in the plurality of reactors, the reactants or reaction environments varying between the plurality of reactors,

comparing the plurality of experimental values, respectively, to a plurality of setpoints for the property, and

changing the reaction environment in one or more of the reactors in response to a difference between the experimental value and the setpoint associated with that one or more reactors.

153. The method ofclaim 152, wherein changing the reaction environment in one or more of the plurality of vessels comprises terminating a reaction occurring in one or more vessels, the set point comprises a conversion target, and the change in one or more of the set of experimental values comprises a change in percent conversion of starting material.

154. The method ofclaim 152 wherein displaying the set of experimental values comprises displaying a graphical representation of the set of experimental values.

155. The method ofclaim 154 wherein the graphical representation comprises a histogram.

156. A computer program on a computer-readable medium for monitoring parallel, combinatorial chemical reactions, the computer program comprising instructions to:

(a) receive a plurality of measured values, the plurality of measured values being associated, respectively, with the contents of a plurality of reactors during simultaneous reactions of two or more reactants, the reactants or reaction environments varying between the plurality of reactors,

(b) display the measured values, and

(c) repeating steps (a) and (b) at least once during the reactions.

157. The computer program ofclaim 156, further comprising instructions to:

change a reaction parameter associated with one of the plurality of reactor vessels in response to the measured value.

158. A reactor control system for monitoring and controlling parallel, combinatorial chemical reactions, the reactor control system comprising:

a system control module for providing control signals to an integrated parallel reactor system, the control signals being based on a set of reaction parameters, the integrated parallel control system comprising a plurality of reactors and a monitoring and control system selected from the group consisting of a mixing monitoring and control system, a temperature monitoring and control system and a pressure monitoring and control system,

a data analysis module for receiving a plurality of measured values from the integrated parallel reactor system, directly or indirectly via the system control module, and for calculating a plurality of calculated values from the respective measured values, and

a user interface module for receiving the set of reaction parameters, and for displaying the plurality of measured values and the plurality of calculated values.

159. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures;

a stirring system for agitating the reaction mixtures; and

a pressure control system that is adapted to maintain a first group of the vessels at a different pressure than a second group of the vessels during processing.

160. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures;

a pressure control system that is adapted to maintain the vessels at a pressure greater than about 10 psig; and

a temperature control system that is adapted to maintain a first group of the vessels at a different temperature than a second group of the vessels.

161. An apparatus for parallel processing of reaction mixtures comprising:

vessels for containing the reaction mixtures; and

an injection system for introducing a fluid into the vessels at a pressure that is greater than about 10 psig.

162. A method of making and characterizing materials comprising:

providing vessels with starting materials to form reaction mixtures;

allowing the reaction mixtures in the vessels to react while stirring each of the reaction mixtures;

evaluating the reaction mixtures by measuring at least one characteristic of the reaction mixtures during at least a portion of the reaction;

wherein the reaction is carried out at about the same time for each of the reaction mixtures.

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