US20020164275A1 - Combinatorial chemistry reactor system - Google Patents

Abstract

A combinatorial chemistry reactor system for the parallel processing of reaction mixtures. The system comprises a frame, a head mounted in fixed position on the frame, and a reactor block having a plurality of wells therein for containing reaction mixtures. The reactor block is movable with respect to the head between a first position in which the reactor block and head are assembled for conducting reactions in the wells and a second position in which the reactor block is removed from the head for providing access to the vessels. Gaps in the reactor block between the wells serve to thermally isolate the wells from one another. Other features relating to pressure relief, reactor block temperature control, and sensor mounting are also disclosed.

Description

CROSS-REFERENCE TO RELATED APPLICATION
• This application is a continuation-in-part of pending application Ser. No. 09/826,606, filed Apr. 5, 2001, entitled “Parallel Reactor for Sampling and Conducting In Situ Flow-Through Reactions and Method of Using Same”, assigned to Symyx Technologies, Inc., and incorporated herein by reference for all purposes.[0001]
BACKGROUND OF THE INVENTION
• The present invention relates generally to parallel reactors and, in particular, to parallel research reactors suitable for use in a combinatorial (i.e., high-throughput) process for rapidly making, screening and characterizing an array of reaction materials in which process conditions are monitored and controlled.[0002]
• This invention is especially directed to methods and apparatus for conducting combinatorial chemistry in materials science research programs, and is in the same field as the inventions disclosed in U.S. Pat. No. 6,306,658 and International Application No. PCT/US 99/18358, filed Aug. 12, 1999 by Turner et al., entitled Parallel Reactor with Internal Sensing and Method of Using Same, published Feb. 24, 2000 (International Publication No. WO 00/09255), both assigned to Symyx Technologies, Inc. and both of which are incorporated herein by reference. While the apparatus and methods described in these references have proven to be successful, the technology would be further enhanced by providing additional features, including more precise temperature monitoring and control during reactions.[0003]
SUMMARY OF THE INVENTION
• Among the several objectives of this invention is the provision of a system which is useful in the parallel processing of reaction mixtures, particularly liquids, slurries and gels; the provision of such a system which, at least in certain embodiments, provides ready access to the reaction vessels to facilitate loading of reaction materials and cleaning; the provision of such a system which, at least in certain embodiments, permits more precise sensing and control of reaction temperature in each reaction vessel; the provision of such a system which, at least in certain embodiments, is constructed to reduce leakage of pressurized fluids from the reaction vessels; the provision of such a system where, at least in certain embodiments, the reaction vessels are thermally isolated from one another; the provision of such a system which, at least in certain embodiments, has an improved stirrer drive mechanism; and the provision of such a system which has a pressure relief feature for reducing the risk of injury.[0004]
• In one embodiment, a combinatorial chemistry reactor system for the parallel processing of reaction mixtures of this invention comprises a reactor block comprising a monolithic body of thermally conductive material having a plurality of wells therein for containing reaction mixtures. A head is adapted for assembly with the reactor block for conducting reactions in the wells. Passaging in the head is adapted to communicate with the head when the head is assembled with the reactor block and gaps in the monolithic body of the reactor block extend between the wells to thermally isolate the wells from one another.[0005]
• In another embodiment, a combinatorial chemistry reactor system comprises a reactor block comprising a body of thermally conductive material having a first face. A plurality of wells extend from the first face into the body for containing reaction mixtures. A head is adapted for assembly with the reactor block to define reaction chambers. Each reaction chamber being defined at least in part by a respective well and having a bottom end toward the bottom of the well and a head end toward the head. At least one of the reactor block and the head have an area of reduced cross section at a location spaced above the bottom end of at least one reaction chamber to thermally isolate portions of the reaction chamber below the area from portions of the system above the area.[0006]
• In yet another embodiment, a combinatorial chemistry reactor system comprises a reactor block comprising a monolithic body of thermally conductive material essentially devoid of fluid transport passaging and passaging for instrumentation. The body has an upper section, a lower section, and a relatively narrow intermediate section connecting the upper and lower sections for reducing the transfer of heat therebetween. The upper section has an upper face. A plurality of wells in the body are adapted for containing reaction mixtures. Each well extends from the first face down through the upper and intermediate sections into the lower section. Gaps extend between the wells to divide the lower section of the rector body into a plurality of individual well sections thermally isolated from one another by the gaps. Recesses in the body reduce the thickness of the body at locations between opposite ends of each well to reduce the transfer of heat toward the first face of the block. A head is adapted for assembly with the reactor block for conducting reactions in the wells.[0007]
• Other objectives and features of the present invention will be in part apparent and in part pointed out hereinafter.[0008]
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a front perspective of a combinatorial chemistry reactor system of the present invention;[0009]
• FIG. 2 is a front perspective showing the system of FIG. 1 with a carriage lowered away from a head;[0010]
• FIG. 3 is a partial section of the system of FIG. 2 taken in the plane including line[0011]3-3 of FIG. 4, with a reactor block removed from a temperature control unit and portions of the unit removed to show internal construction;
• FIG. 4 is a front elevation of the system of FIG. 1;[0012]
• FIG. 5 is a left side (end) elevation of the system of FIG. 1;[0013]
• FIG. 6 is a top plan view of the system of FIG. 1;[0014]
• FIG. 7 is a partial rear perspective of the system of FIG. 1 with portions of a supporting structure removed to show detail;[0015]
• FIG. 8 is a partial front perspective of the system of FIG. 1;[0016]
• FIG. 9 is a section of a heat transfer plate of the system of FIG. 1 taken in the plane including line[0017]9-9 of FIG. 4;
• FIG. 10 is an elevation of a layer of insulation;[0018]
• FIG. 11 is a partial section of the system of FIG. 1 taken in the plane including line[0019]11-11 of FIG. 5;
• FIG. 12 is a partial section of the system of FIG. 1 taken in the plane including line[0020]12-12 of FIG. 6;
• FIG. 13 is a partial section of the system of FIG. 1, with cooling elements shown, taken in the plane including line[0021]13-13 of FIG. 4;
• FIG. 14 is a partial section of the system of FIG. 1, with cooling elements shown, taken in the plane including line[0022]14-14 of FIG. 4;
• FIG. 15 is a front perspective of the reactor block of FIG. 3;[0023]
• FIG. 16 is a front elevation of the reactor block of FIG. 15;[0024]
• FIG. 17 is a right elevation of the reactor block of FIG. 15;[0025]
• FIG. 18 is a rear perspective of a head of FIG. 2;[0026]
• FIG. 19 is a front perspective of the head of FIG. 18;[0027]
• FIG. 20 is a bottom plan view of the head of FIG. 18;[0028]
• FIG. 21 is a front elevation of the reactor block of FIG. 15 and head of FIG. 18 with portions removed to show internal construction;[0029]
• FIG. 22 is an enlarged partial section of the system of FIG. 12;[0030]
• FIG. 23 is an enlarged partial section of the system of FIG. 12;[0031]
• FIG. 24 is an enlarged partial section of the system of FIG. 12;[0032]
• FIG. 25 is a perspective of a drive shaft and stirrer of the system of FIG. 1;[0033]
• FIG. 26 is a partial section of the system of FIG. 1 taken in the plane including line[0034]26-26 of FIG. 6;
• FIG. 27 is a partial section of the system of FIG. 26;[0035]
• FIG. 27A is a partial section of another system of the present invention;[0036]
• FIG. 28 is a partial section of the system of FIG. 1 taken in the plane including line[0037]28-28 of FIG. 6;
• FIG. 29 is a front perspective of another reactor system of the present invention;[0038]
• FIG. 30 is a bottom perspective of a reactor block of the system of FIG. 29;[0039]
• FIG. 31 is an enlarged partial perspective of FIG. 30;[0040]
• FIG. 32 is a top perspective of the reactor block of FIG. 30; and[0041]
• FIG. 33 is an enlarged partial perspective of FIG. 32.[0042]
• Corresponding parts are designated by corresponding reference numbers throughout the drawings.[0043]
DESCRIPTION OF PREFERRED EMBODIMENT
• Referring now to the drawings, and more particularly to FIGS.[0044]1-3, a combinatorial chemistry system of the present invention for the parallel processing of reaction mixtures is designated in its entirety by thereference numeral1. As shown, thesystem1 comprises a frame, generally designated3, resting on a supportingstructure5, such as a table, a head, generally designated7, mounted in fixed position on the frame, and a carriage, generally indicated at9, mounted on the frame below the head for vertical movement relative to the frame and the head. Thecarriage9 supports a reactor block, generally designated11, cradled by a temperature control unit, generally designated13, for controlling the temperature of the reactor block. Thereactor block11 contains a series ofreaction wells15. As will be described hereinafter, thecarriage9 is movable toward thehead7 so that thereactor block11 and head can be assembled for a reaction process, and down away from the head to separate the reactor block from the head. A locking mechanism, generally indicated at17, is provided for locking thecarriage9 in selected vertical positions relative to theframe3. In general, thesystem1 also includes a stirring assembly, generally designated21 in FIGS.1-3, on thehead7 for stirring reaction materials in thereactor block11, as will be described.
• More specifically, the[0045]frame3 comprises, in one embodiment, a base25 supported by the supportingstructure5, apanel27 extending up from the base, and a pair ofbraces31 supporting the panel in an upright (e.g., generally vertical) position on the base (see FIGS.1-3). A pair of parallel, spaced-apartvertical rails33 are fastened to thepanel27 and constitute tracks for thecarriage9 so that the carriage may be moved toward and away from thehead7. Thecarriage9 itself comprises a pair ofbrackets35 having a sliding fit withrespective rails33, and ahorizontal platform37 which spans the twobrackets35 and is secured thereto by suitable means, the brackets and platform being slidable up and down on the rails to selected positions (compare FIGS. 1 and 2). Thelocking mechanism17 for locking thecarriage9 in selected position comprises a pair of pull-rods41 mounted on the underside of theplatform37 adjacent opposite ends therefor for sliding movement between an extended locking position in which the pull-rods are received in selected openings43 (see FIGS. 3 and 4) of two vertical rows of detent openings in theframe panel27, and a retracted position in which the pull-rods are removed from respective openings to permit vertical movement of the carriage. The pull-rods41 are biased toward the stated extended locking position by springs (not shown). For reasons which will appear, thedetent openings43 are preferably elongate in the vertical direction (e.g., slots) to permit limited vertical movement of thecarriage9 when thelocking mechanism17 is engaged. Other types of locking mechanisms, detent or otherwise, may be used to lock thecarriage9 in selected position.
• As shown in FIGS. 1, 4 and[0046]7, movement of thecarriage9 between raised and lowered positions is effected manually with the assistance of a power assist device comprising a conventional pressurized gas spring unit, generally designated47, which includes acylinder49 having aconnection51 at its lower end with abracket53 on the supporting structure5 (see FIGS. 5 and 7) and arod55 connected at its upper end at57 to the carriage platform37 (see FIG. 7). Thecylinder49 is pressurized with a suitable gas and provides an upward force which counterbalances a substantial portion of the weight of thecarriage9,temperature control unit13 andreaction block11, and thus assists in the lifting and lowering of the carriage. Other types of devices may be used to assist in the manual lowering and raising of the carriage. Alternatively, movement of the carriage can be effected solely by mechanical means, such as by power actuators operated by manual or automatic controls.
• In one embodiment, the[0047]temperature control unit13 comprises a base61 (see FIG. 12) of thermal insulating material (e.g., glass-mica) attached to the top surface of thecarriage platform37, a pair ofparallel end plates65 affixed to the base and extending up from the base at opposite ends of the base, and a heat transfer assembly, generally designated71, above the base between the end plates comprising a plurality of parallelheat transfer plates73 of thermally conductive material (e.g., aluminum). Theseplates73 are thermally separated, or isolated, bylayers75 of thermal insulation (see FIGS. 12 and 14) (e.g., high-temperature millboard having a thermal conductivity of about 0.78 Btu-in/hr./ft²/° F. @ 800° F.). The number ofheat transfer plates73 preferably corresponds to the number ofreaction wells15 in thereactor block11. In the specific embodiment shown in the drawings, thereactor block11 has eightwells15, and there are a corresponding number ofheat transfer plates73, but this number may vary. The two endheat transfer plates73 are wider than the other six heat transfer plates to provide relativelythick closure walls81 toward opposite ends of theunit13. These walls are positioned face-to-face with the twoend plates65.
• Each[0048]heat transfer plate73 has acentral recess85 therein extending down from its upper edge. In one embodiment, thisrecess85 is generally channel shaped (see FIG. 9) and has opposing interior side surfaces indicated at87 and a bottom surface indicated at89. Thelayers75 of thermal insulation have a generally corresponding shape (see FIG. 10). As a result, theheat transfer plates73 and layers75 of insulation define a cavity91 (see FIG. 3) for receiving and cradling thereactor block11. In an embodiment where thetemperature control unit13 operates as a heater to heat thereactor block11, eachheat transfer plate73 has a pair ofbores95 therein (see FIG. 9) located relatively close to respective interior side surfaces of the plate for receiving heating elements97 (e.g., electric cartridge heaters; see FIGS. 13, 26 and27) for heating the plate and the reactor block. Theheating elements97 are connected to suitable controls by wiring99 passing down throughholes101 in thebase61 and thecarriage platform37. The sides of thereactor block11 and the interior side surfaces87 of theheat transfer plates73 are preferably tapered to provide a close fit between the plates and the block for the efficient conductive transfer of heat therebetween. Theheating elements97 are selected to heat thereactor block11 to the desired temperature, such as temperatures in a range from about ambient to about 400° C., more preferably in a range from about ambient to about 250° C., and even more preferably in a range from about ambient to about 200° C.
• The[0049]heat transfer plates73 and layers75 of insulation are supported above thebase61 by a pair ofhorizontal rods105 which extend between the end plates65 (see FIGS. 11 and 12) through aligned holes107 (see FIGS. 9 and 10) in theplates73 and layers75 of insulation. The ends of therods105 are received in holes111 in theend plates65 and can either be free of securement to the end plates or releasably secured in place by set screws or other suitable means (see FIG. 11). Theholes107 in theheat transfer plates65 andinsulation layers75 are somewhat oversize to allow limited vertical movement (e.g., preferably in a range from about {fraction (1/64)} in. to about ¼ in.) of the plates and layers relative to thebase61 and to one another. As shown in FIG. 12, springs115 are provided for urging theplates73 in a generally upward direction into thermal contact with thereactor block11 seated in thecavity91. In one embodiment, eachspring115 comprises a vertically-oriented coil compression spring having its lower end positioned on aboss117 on thebase61 and having its upper end received in arecess121 in a respectiveheat transfer plate73. Other spring or biasing arrangements are contemplated. Theheat transfer plates73 are enclosed by a cover comprising a pair ofside panels125 at opposite sides (e.g., front and back) of thetemperature control unit13, a pair ofend panels127 at opposite ends of the unit, and atop cover panel129 bridging the side panels between the end panels. Thetop cover panel129 has acentral opening131 therein through which thereactor block11 can be placed in thetemperature control unit13 and removed therefrom (see FIG. 27). Thecover panels125,127 and129 are suitably secured to one another and supported by thetemperature control unit13.
• To insure good thermal contact between the[0050]reactor block11 and theheat transfer plates73, a mechanism generally designated135, is provided operable to press the reactor block against the heat transfer plates. This system preferably comprises a pair oflatches137 at opposite ends of thereactor block11 andtemperature control unit13. In the embodiment shown in FIG. 12, eachlatch137 comprises a catch139 (e.g., J-hook) mounted on one end of thereactor block11 and anover-center latching bar141 mounted on a correspondingend cover plate127 of thetemperature control unit13, the latching bar being engageable with the catch and then rotatable to an over-center position in conventional fashion to pull the reactor block down into a fully seated position in thecavity91 defined by the unit. In this seated position, thesprings115 are preferably deflected to bias the individualheat transfer plates73 into good thermal contact with the tapered side surfaces of thereactor block11. Other systems may be used to maintain the reactor block and theheat transfer plates73 in good thermal contact with one another.
• To prevent overheating of the[0051]reactor block11, a temperature sensor147 (e.g., thermocouple device) is provided for sensing the temperature of eachheat transfer plate73, one such sensor being shown in FIGS.5-7 and11, for example. In the event the temperature of one or moreheat transfer plates73 exceeds a predetermined temperature, the appropriate sensor(s)147 will signal for the shut off of power to the plate or plates to prevent overheating of the plate(s) and/orreactor block11.
• FIGS. 13 and 14 show a second embodiment of a temperature control unit, generally designated[0052]151, of the present invention. In this embodiment, theunit151 is constructed for both heating and cooling thereactor block11, which can be useful in conducting reactions at temperatures below ambient temperature (e.g., down to about −45° C.), and also for cooling the reactor block down during or after the heating of reaction mixtures. Theunit151 is essentially the same as thetemperature control unit13 described above (and corresponding parts are given the same reference numbers) except thatunit151 further comprises a plurality ofcooling elements153 for cooling theheat transfer plates73. By way of example, eachheat transfer plate73 may be provided with a cooling element in the form of a conduit, also designated153, carrying a suitable cooling fluid (refrigerant) for cooling the plate. Theconduit153 is preferably formed by tubing installed in passages in theplate73. Alternatively, the conduit can be formed by passaging in theplate73 without tubing, or by passaging in the plate connected by tubing. In any case, theconduit153 is preferably located on opposite sides of the central recess85 (see FIG. 9) in theplate73 to provide for efficient cooling of the respective well section of thereactor block11. Theconduits153 associated with theheat transfer plates73 are connected at their upstream ends to aninlet manifold161 which receives coolant from a conventional refrigeration system (not shown) and at their downstream ends to anoutlet manifold163 for delivery of the coolant back to the refrigeration system (see FIG. 14). Suitable thermal insulation is provided to insulate theconduits153 andmanifolds161,163. In the eventdifferent wells15 are to be cooled to different temperatures, thecooling elements153 can be operated in combination with theheating elements97 to achieve the appropriate temperature control over each heat transfer plate and corresponding well15 independently of the other plates and wells.
• Other types of temperature control units may also be used, such as those disclosed in pending application Ser. No. 09/417,125, filed Nov. 11, 1998 entitled “Multi-Temperature Modular Reactor and Method of Using Same”, assigned to Symyx Technologies, Inc., and incorporated herein by reference. The use of cooling baths and thermoelectric devices is also contemplated. Further, the[0053]temperature control unit151 of the present invention could be formed for cooling thereactor block11 and not for heating it. One embodiment of such aunit151 could be similar to theunit13 shown in FIGS. 13 and 14 but with theheating elements97 omitted.
• The[0054]reactor block11 preferably comprises a monolithic one-piece body of thermally conductive material (e.g., aluminum, stainless steel, ceramic) having properties capable of withstanding the pressure and reaction conditions to which it is subjected (e.g., pressures up to 3000 psi). As shown in FIGS.15-17, theblock11 has anupper face171, alower face173, opposite side faces175 which have a taper generally corresponding to the taper of the interior side walls of thecavity91 in thetemperature control unit13, and opposite end faces179. As viewed in FIG. 17, theblock11 has anupper section181, alower section183, and a relatively narrow intermediate section orneck185 connecting the upper and lower sections. A plurality of theaforementioned wells15 are formed in thereactor block11 by bores, for example, extending down from theupper face171 of the block through the upper andintermediate sections181,185 and into thelower section183 to a level generally adjacent thelower face173 of the reactor block. Thewells15 preferably have rounded bottoms and a generally circular cross sectional shape, although other shapes are contemplated, and each well defines an interior space. Acircular groove187 for receiving an O-ring189 (see FIGS. 22 and 27) is formed in theupper face171 of the block around each well15. The O-ring189 seals against thehead7 when thereactor block11 and head are in assembly to seal the well against leakage.
• A liner[0055]191 (see FIG. 13) comprising, for example, a vial, is preferably (but not necessarily) removably received in each well15. Together, thevial191 and well15 form a reaction vessel for containing reaction mixtures during a chemical process. Alternatively, the reaction vessel may be constituted by the well15 without a vial or other liner. Thus, as used herein, the term “vessel” means a well15 either with or without a liner in it. The term “reaction chamber”, on the other hand, refers to the space defined the walls of the well15 and the removable vial191 (if used) when thereactor block11 andhead7 are assembled for conducting chemical reactions in the wells. In some embodiments (FIGS. 12, 13,22 and27), the reaction chamber may include a recess (further described ascounterbores292 below) in thehead7 communicating with the well15. In other embodiments, thehead7 may have no such recess (see FIG. 27A), in which case the reaction chamber would be defined entirely by the walls of the well15 and thevial191, if one is used. In any event, each reaction chamber has a bottom end toward the bottom of the well and a head end toward thehead7. The portion of the reaction chamber above thefill level193 of the liquid and/or solid material in the reaction chamber is typically referred to as the “head space” of the reaction chamber. The reaction chamber also has a “reaction zone”. The reaction zone refers to the region of the reaction chamber in which the chemical reaction of interest occurs predominantly. Hence, the reaction zone identifies a reactant-containing region having an environment presenting reaction conditions effective for the chemical reaction of interest. The reaction zone may also contain one or more catalysts or other materials in addition to reactants. For liquid-phase reactions, for example, the reaction zone is defined by the volume of the reaction chamber containing the liquid phase reactants. For reactions occurring at a phase interface (e.g., gas-liquid interface, gas-solid interface, liquid-liquid interface, liquid-solid interface) the reaction zone is defined by the volume that includes the interface, together with associated boundary layers. For gas-phase reactions, the reaction zone is defined by the volume of the reaction chamber containing the gas phase reactants. Regardless of the phase state of the reaction, for reactions effected under conditions other than ambient conditions (e.g., reactions effected at non-ambient temperature, or non-ambient pressure), the reaction zone can include a region of the reaction chamber having an environment maintained substantially at the desired reaction conditions (with allowed variations in reaction conditions being acceptable, the extent of such variations depending on the particular reaction of interest, and the nature and/or goals of the experiment).
• The[0056]reaction block11 may contain any practical number of wells15 (e.g., 3, 6, 8, 12) arranged in a row extending from adjacent one end the block to adjacent its opposite end. The volume of each reaction vessel may vary according to application. For example, the volume may vary from about 0.1 ml to about 500 ml, more preferably from about 1 ml to about 100 ml, and even more preferably from about 5 ml to about 20 ml. Further, the side wall of theliner191 may be generally cylindric in shape and have an inside diameter in a range from about 0.5 in. to about 2.5 in., more preferably in a range from about 0.5 in. to about 0.75 in., and most preferably about 0.609 in., and the liner may have an overall height in a range from about 1.0 in. to about 4.0 in., more preferably in a range from about 1.5 in. to about 3.0 in., and most preferably about 2.15 in.
• In one embodiment particularly intended to reduce leakage, the monolithic[0057]reactor block body11 is machined from a single piece of metal and is essentially devoid of any passaging for transporting fluid to or from thewells15, and further essentially devoid of any passaging for instrumentation, such passaging being in thehead7 as will be described. Preferably, there is a complete absence of all such passaging, ports and any other cavities (other than the wells15) in the monolithicreactor block body11 so that the possibility of leakage is minimized. Placement of such passaging in thehead7 and not in thereactor block11 also facilitates assembly and disassembly of thesystem1.
• In accordance with one aspect of this invention, the lower section[0058]183 (i.e., temperature controlled section) of thereactor block11 is formed with gaps195 (see FIG. 16) between thewells15 which function to thermally isolate the wells from one another so that the temperature in each well can be more accurately monitored and controlled. In one embodiment, thesegaps195 are formed by slits (e.g, cuts) in the monolithic body of thereactor block11 extending up from thelower face173 of the body and extending from oneside face175 of the body to theopposite side face175 of the body between adjacent wells, the gaps thus dividing the lower section of the reactor body into a plurality ofwell sections201, each containing at least one well, and preferably only one well, which is thermally isolated from the well(s) in adjacent well sections. When thereactor block11 is seated in thetemperature control unit13, eachwell section201 is adapted for thermal contact with a respectiveheat transfer plate73 of the unit, so that the temperature of each well section can be independently controlled by controlling the temperature of its respective heat transfer plate, independent of the other well sections. Preferably, eachwell section201 has a thickness generally corresponding to the thickness of its respectiveheat transfer plate73, except for the two end plates which comprise somewhatthicker closure walls81. Thegaps195 between thewell sections201 allow chemical reactions indifferent wells15 to be carried out at substantially greater temperature differentials (e.g., differentials in a range from about 1° C. to about 400° C., more preferably in a range from about 5° C. to about 200° C., and even more preferably in a range from about 50° C. to about 50° C.) and within more precise tolerances (e.g., the actual temperature is within about ±20% of the desired temperature, more preferably within about ±10%, and even more preferably within about ±2% or less). The size of thegap195 between adjacentwell sections201 is preferably in a range from about 0.1 in. to about 0.250 in., and more preferably in a range from about 0.125 in. to about 0.156 in. Optionally, thermal insulation layers75 may be placed in thegaps195.
• To reduce the transfer of heat from the lower section[0059]183 (i.e., temperature controlled section) to theupper section181 of theblock11 and to thehead7, the intermediate section orneck185 of the block is of reduced width and thus constitutes an area of reduced cross section. In one embodiment, this reduction is effected by a pair ofnotches205 extending into opposite sides of the block11 (see FIG. 17). The dimensions of thesenotches205 are such as to provide the desired reduction of heat transfer. For example, the vertical height H of eachnotch205 is preferably up to 20% of the overall height (i.e., depth) of the corresponding well15. By way of example, in one embodiment the height H of eachnotch205 is in a range from about 0.1 in. to about 0.5 in., and more preferably in a range from about 0.250 in. to about 0.31 in. The horizontal depths of thenotches205 are such as to reduce the overall horizontal width W of the intermediate section (as viewed in FIG. 17) to a dimension which is preferably in a range from about 0.750 in. to about 1.250 in., and more preferably in a range from 0.875 in. to about 1.0 in. Taking into account the cross sectional dimension (e.g., diameter) of the well15 in a givenwell section201, the thickness T (see FIG. 17) of the wall connecting the upper andlower sections181,183 is relatively small, preferably in a range from about 0.03 in. to about 0.10 in., and more preferably in a range from about 0.05 in. to about 0.07 in., thus substantially reducing the amount of heat transferred from thelower section183 to theupper section181 of thereactor block11. For a design pressure of 1000 psig, a thickness T of about 0.06 in. is preferred.
• In the embodiment described above, the[0060]reactor block body11 is “necked down” (recessed) to form an area of reduced cross section at a location between the ends of each well15 and toward the upper end of the well. However, it is contemplated that the “neck down” (i.e., area of reduced cross section) may be in other regions of thereactor block body11 or even in regions of thehead7 to reduce the transfer of heat through this area so that the lower section183 (i.e., temperature controlled section) of the reactor body which is heated and/or cooled by thetemperature control unit13 is thermally isolated from thehead7 and the various components of the stirringassembly21 carried by the head. For example, the area of reduced cross section (“neck down”) could be at any location above the lower section183 (i.e., temperature controlled section) of thereactor block body11 which is heated and/or cooled. Alternatively, the area of reduced cross section could be at any location above the reaction zones of the reaction chambers to thermally isolate the reaction zones from those portions of thereactor block11 and/orhead7 above the zones. Further, the area of reduced cross section could extend all the way to theupper face171 of theblock11 and even into thehead7. For example, thehead7 depicted in FIGS. 13, 27 and28 contains an area of reduced cross section211 (described in greater detail below) that facilitates in thermally isolating thereactor block body11 and reaction zones from those portions of thesystem1 above the area of reduced cross section. The use of an area (or areas) of reduced cross section to control the amount of heat transfer toward and away from each reaction zone allows the temperature within each reaction zone to be maintained substantially more uniform along the longitudinal (e.g., vertical) axis of the zone than would otherwise be the case without such an area or areas of reduced cross section. In other words, the axial temperature gradient in each such zone is reduced by using an area or areas of reduced cross section to thermally isolate the zone from other parts of the system. This allows the temperature in each reaction zone to be more closely controlled for more accurate results.
• The[0061]head7 andreactor block11 are preferably held in assembly by suitable fasteners215 (e.g., screws) threaded down throughholes216 in the head into tappedopenings217 in theupper face171 of the reactor block (see FIG. 21).
• The[0062]head7 comprises an elongate block of suitable material (e.g., aluminum) mounted in fixed position on theframe3 at the front of theframe panel27 by a bracket, generally designated221, secured to the panel (see FIGS.1-3 and5). The form of thisbracket221 can vary, but in one embodiment it comprises a mountingplate223 fastened to thepanel27 of the frame, and a plurality ofarms225 extending forward from the mounting plate for holding thehead7 in a position spaced forward of thepanel27. Thearms225 are fastened to thehead7 by bolts (not shown) threaded in tapped bores231 (see FIG. 18). Referring to FIG. 19, the head has a generally rectangular bottom section, generally designated241, with alower face243, anupper face245, opposite side faces247, and end faces249, and an upright center section, generally designated251, extending up from the bottom section and having anupper face253, opposite side faces255, and opposite end faces257. Thehead7 has passaging therein adapted for fluid communication with thewells15 when thereactor block11 and head are in assembly. In one embodiment, this passaging comprises a plurality offirst passages261 in thehead7 for the delivery of reagents to thewells15, and a plurality ofsecond passages263 for venting gases from the wells and delivering quenching fluids to the wells to terminate a reaction (see FIGS. 18 and 19). In a preferred embodiment, two suchfirst passages261 are provided for enabling different reactants to be delivered to each well15, for example, and one suchsecond passage263 is provided. The number of such first andsecond passages261,263 may vary without departing from the scope of this invention.Suitable fittings265 may be threaded in these passages for the connection of appropriate fluid transfer lines269 (see FIG. 26).
• The stirring[0063]assembly21 comprises a plurality of stirrers, each generally designated271, positioned in thewells15, and a drive mechanism, generally designated273, sitting atop thehead7 for moving (e.g., rotating or reciprocating) the stirrers to mix the reaction mixtures in thewells15. In one embodiment (see FIG. 22), thedrive mechanism273 comprises a plurality of magnetic feed-through devices, each generally designated281, of the type described in U.S. Pat. No. 6,306,658 incorporated herein by reference. The magnetic feed-throughdevices281 are connected torespective stirrers271 by a series ofdrive shafts283 extending down throughholes285 in thehead7, and bycouplings291 which couple the drive shafts to the stirrers. Theholes285 in thehead7 are coaxial with thewells15 in thereactor block11 and are counterbored at their lower ends, as indicated at292 (see FIG. 27). Thepassages261 and263 for the transfer of fluids to and from thewells15 communicate with thesecounterbores292, as shown in FIG. 28. Furthermore, when thehead7 andreactor block11 are assembled, the aforementioned reaction chambers are formed. In the embodiment shown in FIG. 27, each reaction chamber includes the space defined by the walls of the well15, the removable vial191 (if used), and thecounterbore292 in thehead7. It will be understood, however, that thecounterbore292 could be eliminated in which case the reaction chamber would be defined entirely by the walls of the well15 and thevial191, if one is used.
• As shown in FIGS. 22 and 27, each[0064]stirrer271 comprises astirrer shaft293 having ablade295 at its lower end for mixing particularly viscous materials, but other types of stirrers may be used, including auger stirrers and those disclosed in pending U.S. patent application Ser. No. 09/873,176, filed Jun. 1, 2001, entitled “Parallel Semi-Continuous or Continuous Stirred Reactors”, and pending U.S. patent application Ser. No. 09/961,641, filed Sep. 24, 2001, entitled “Apparatus and Method for Mixing Small Volumes of Reaction Materials”, both of which are owned by Symyx Technologies, Inc. and incorporated by reference herein. Eachstirrer271 may be of any suitable material which is chemically inert and resistant, although a non-metal material such as plastic or glass is preferred. Thecoupling291 is preferably one which allows thestirrer271 to be removed and replaced as needed.
• The[0065]drive mechanism273 also includes adrive train301 connecting the magnetic feed-throughdevices281, amotor305 for drivingdrive elements307 of thedrive train301, and a belt and pulley connection (generally designated309) between the motor and the drive train. In one embodiment (see FIGS. 12 and 23), thedrive train301 and driveelements307 comprise a gear train and gears, respectively, and the belt andpulley connection309 comprises apulley311 mounted on the upper end of avertical idler shaft315 rotatably supported bybearings317 in acylindric housing319. Adrive gear321 is keyed to theidler shaft315 below thepulley311 and meshes with thegear train301. Abelt323 connects thepulley311 and the drive shaft325 of the motor305 (see FIG. 12), so that rotation of the motor drive shaft serves to rotate theidler shaft315 and thegears307 of thegear train301. Themotor305 and belt andpulley connection309 are supported by avertical column335 at one end of thehead7, the lower end of the column being secured by at least onefastener337, for example, threaded into a tappedbore339 in the head7 (see FIGS. 12 and 19). It will be noted that themotor305 and belt andpulley connection309 are spaced a substantial distance from thereactor block11. This arrangement, in combination with the configuration of theblock11 to reduce the amount of heat transfer between the upper andlower sections181,183 of the block, decreases the extent of heat transfer between thewell sections201 of the reactor block and thedrive mechanism273.
• The[0066]drive train301 and driveelements307 could take forms other than a gear train and gears, respectively. For example, the drive train could comprise a series of belt connections between the magnetic feed-throughdevices281, or other types of mechanical connections forming a drive train powered by themotor305.
• The magnetic feed-through[0067]devices281 and drivetrain301 are enclosed by acover327, and the belt andpulley connection309 is enclosed by ahousing329. Thecover327 andhousing329 are removably held in place by acap nut331 threaded on the upper end of theidler shaft315 which extends up through openings in the cover and housing, as shown in FIG. 12.
• In the embodiment of FIG. 24, each magnetic feed-through[0068]device281 comprises acylindric pressure barrier351 co-axially surrounded by a cylindricmagnetic driver361 connected at its upper end to a respective drive element (e.g., gear)307 of thedrive train301 for rotation of the driver on an axis A coincident with the axis of thestirrer271. Thedevice281 also includes amagnetic follower371 inside the pressure barrier. Thefollower371 is magnetically coupled to thedriver361 for rotation of the follower on axis A, as will be apparent to those skilled in this field. Thefollower371 has anaxial bore373 therein for removably receiving thedrive shaft283 coupled to arespective stirrer271. Apin375 or other suitable means secures thedrive shaft283 to thefollower371 so that the two parts rotate in unison. Alternatively, thedrive shaft283 can be formed as an integral part of thefollower371. Thedrive shaft283 extends down through arespective hole285 in the head and into arespective well15. Thedrive shaft283 is rotatably supported by a pair of vertically spaced bearings (see FIG. 22), the upper bearing being designated381 and the lower bearing designated383 (see FIG. 22).
• The[0069]coupling291 between thestirrer shaft293 and thedrive shaft283 can be of any design suitable for removably connecting the two shafts, one such design being shown in FIG. 25. In this embodiment, the lower end of thedrive shaft283 has an axial hollow orrecess387 formed therein for receiving the upper end of thestirrer shaft293. Further, the lower end of thedrive shaft283 surrounding therecess387 is resiliently expansible and contractible in a radial direction due to at least one slit, and preferably two or more slits391 in the drive shaft extending up from its bottom edge. The upper end of thestirrer shaft293 has an outside dimension (e.g., diameter) somewhat larger than the inside dimension (e.g., diameter) of therecess387 when it is vacant so that insertion of the stirrer shaft into the recess causes the recess to expand resiliently and thereby exert a radial gripping force on the stirrer shaft tending to retain it in the recess. A pair ofkeys395 project laterally outwardly from thestirrer shaft293 intokeyways397 in thedrive shaft283 to prevent relative rotation between the two shafts. Other coupling designs can be used, such as those disclosed in U.S. Pat. No. 6,306,658 and International Application No. PCT/US 99/18358, filed Aug. 12, 1999 by Turner et al., entitled Parallel Reactor with Internal Sensing and Method of Using Same, published Feb. 24, 2000 (International Publication No. WO 00/09255), both assigned to Symyx Technologies, Inc.
• Referring again to FIGS. 13, 27 and[0070]28, theupright center section251 of thehead7 extends up from thebottom section241 of the head. Thisupright center section251 includes the area of reducedcross section211 that facilitates thermal isolation of thereactor block body11 or reaction zones from those portions of thesystem1 above the area of reduced cross section. In one embodiment, the area of reducedcross section211 functions to further thermally isolate thedrive mechanism273 from the temperature controlledlower section183 of thereactor block body11 or, more generally, from the reaction zones.
• In accordance with another aspect of this invention, at least one sensing device, generally designated[0071]401, is attached to thehead7 for sensing one or more conditions (e.g., temperature, pH, viscosity, electrical conductivity, optical characteristics, etc.) relating to a chemical reaction taking place in awell15. Preferably, one or more sensing devices, generally indicated401, is provided for each well15. In any event, thesensing device401 is preferably mounted and configured so that when thehead7 andreactor block11 are in assembly, the device actually resides in the reaction materials, thereby allowing in-situ monitoring and control of the reaction mixtures on a real-time basis.
• In one embodiment (see FIG. 27), each[0072]sensing device401 comprises anelongate sensor support403 in the form of a flexible tube of metal or other suitable chemically resistant material extending down through anangled bore407 in thehead7 and down into the well15 when the head andreactor block11 are in assembly. Theangled bore407 communicates at its lower end with arespective counterbore292 in thelower face243 of thehead7. Thesupport403 is preferably spaced radially outwardly from the longitudinal center axis of the well15 away from thestirrer271 to avoid interference with the stirrer during the stirring process. Theelongate support403 is preferably removably secured to thehead7 by a swaged fitting411 or other connector so that it remains attached to the head when thereactor block11 and head are separated. Thesensing device401 also includes asensor415 on thesupport403, typically located toward the lower end of the support in a position which places the sensor in the reaction materials (or closely adjacent such materials) contained in the well15 or theremovable liner191, if a liner is used. Thesensor415 can be attached to thesupport403 in any suitable manner. For example, thesensor415 may be a conventional thermocouple, for example, embedded in the wall of thesupport403. More than onesensing device415 may be used in a well15 to sense different conditions.
• For temperature sensing, the[0073]sensor415 andsensor support403 may be of conventional design. For example, a suitable assembly of such parts is commercially available from Omega, of Stamford Conn. This assembly includes tubular sheath of stainless steel having a diameter in a range from about 0.010 in. to about 0.125 in. (and preferably about 0.06 in.), a thermocouple sensor attached to the wall of the sheath adjacent its lower end, and a glass filled nylon connector (such as shown at421 in FIG. 27) at the opposite end of the tubing for connecting the tubing to suitable electronic equipment.
• As alluded to above, there are advantages to positioning the[0074]sensors415 so that they reside in the reaction mixtures. First, since the sensors are in actual contact with the reaction materials, they are able to more accurately sense the temperatures of the reaction mixtures and to react more quickly to any changes in temperature, in essence providing real-time feedback of the temperatures of the reaction mixtures for more accurate monitoring and control of the reaction. Further, the physical presence of thesensing device401 in the reaction fluids enhances the stirring process in that the device functions as a baffle to increase turbulence in the vessel to obtain a more homogenous distribution of reaction components. Moreover, the fact that thesensing devices401 are affixed to thehead7 and not to thereactor block11 simplifies the construction of the reactor block and facilitates the assembly and disassembly of the reactor block with respect to the head.
• Referring to FIG. 26, the[0075]lower section241 of thehead7 has additional passaging comprising a plurality ofpressure relief passages421 in pressure communication withrespective wells15 in thereactor block11, each such passage extending, for example, from an exterior surface of the head (e.g., side face247) to arespective counterbore292 in thelower face243 of the head. A pressure relief mechanism associated with thepressure relief passages421 is provided to relieve the pressure in thewells15 if the pressure rises to a level above a maximum pressure (e.g., 500 psig). This mechanism preferably comprises a plurality of pressure relief devices, each generally designated425, one for each well15. In one embodiment (see FIG. 26), eachsuch device425 comprises a burst assembly which includes atube431 connected at one end to arespective relief passage421 and at its other end to an open-endedfitting433 containing arupture member435 adapted to rupture at the stated maximum pressure. Therupture member435 may comprise, for example, a rupture disc formed from Iconel Alloy 600 material, such as those discs available from Parr Instrument Company of Moline, Ill., U.S.A. More particularly, therupture member435 may be selected to have a working pressure rating sufficient to withstand the typical operating conditions of thesystem1, and a burst rating appropriate for rupture when the pressure within the system exceeds a designed working pressure. For safety reasons, it is preferred that thefittings433 open away from the front of theapparatus1 so that therelief devices425 are operable to relieve pressure away from any person that might in front of the apparatus. Thus, in one embodiment, thefittings433 extend through thebracket mounting plate223 and are secured in openings in thepanel27 of the frame3 (see FIGS. 5, 6 and26). In another embodiment, not shown, the pressure relief devices (e.g., rupture members) could be mounted in thepressure relief passages421 in thehead7. In yet another embodiment (not shown), a plurality of pressure relief passages in the head, one passage for each well, may connect to a common line or manifold. The manifold, in turn, may communicate with a single pressure relief device which is operable to relieve pressure in all wells in the event the manifold pressure exceeds a predetermined pressure.
• The operation of the system of this invention will now be described. Initially, the[0076]carriage9 is in a lowered position in which thereactor block11 is cradled in thetemperature control unit13 and separated from the head7 (see FIG. 2). In this position, thereactor block11 may conveniently be removed from thetemperature control unit13 by unlatching the twolatches135, lifting thereactor block11 out of thecavity91 defined by the unit, and placing the reactor block in a convenient location for loading of reaction materials either directly into thewells15 of the reactor block or, more preferably, into vials or otherremovable liners191 which are then placed in the wells. Alternatively, reaction preparation can be carried out while thereactor block11 remains latched in place on thecarriage9. Prior to each run of reactions, a clean set ofstirrers271 is coupled to thedrive mechanism273 of the stirringassembly21.
• After the appropriate reaction materials are loaded, the[0077]reactor block11 is replaced in thetemperature control unit13 and latched in position. Thecarriage9 is released from its lowered position by pulling the pull-rods41 out of theirrespective openings43 in theframe panel27, and then raising the carriage to a position in which it is immediately adjacent thehead7 so that thestirrers271 andsensing devices401 are received in respective wells15 (see FIG. 1). Thecarriage9 is locked in this position by releasing the pull-rods41 to extend into another set ofopenings43 in theframe panel27. The threadedfasteners215 are then tightened to raise the reactor block11 (and thecarriage9 and the temperature control unit13) a short distance into sealing engagement with thehead7, as permitted by the vertical slot-openings43 in the frame panel (see FIG. 21). In this position, the O-rings189 inrecesses187 in theupper face171 of the reactor block seal against thelower face243 of thehead7 to seal the wells15 (see FIGS. 15 and 22).
• To initiate a typical run of reactions, a set of purge procedures is followed to purge all inlet lines and[0078]inlet passages261,263 in thehead7, particularly those that will contain reactants. These purge procedures may not be necessary if the previous run left the reactor in a ready or purged state. Generally, the purging is carried out so that all lines and reactor chambers contain a desired atmosphere or gas. In the delivery orinlet lines261, typically, a reactant gas may be used, such as ethylene gas, to ensure that no dead volumes or other gases are in the delivery lines. After the purge procedure is complete, thewells15 are charged with an appropriate gas or gases, which may be inert or reactant gases, to bring the wells to the desired pressure, which is typically greater than about 15 psig, preferably from about 15 psig to about 3500 psig, and more preferably in a range from about 50 psig to about 500 psig, and even more preferably in a range from about 150 psig to about 500 psig delivered to pressurize the wells.
• Using the system controller, the parameters of the run are then set. Such parameters include, for example, the reaction time, the duration and speed of the stirring (if stirring is required), and the temperature(s) at which the reactions are to be carried out. With respect to temperature, for example, a program may be entered in which: (a) the reaction mixtures are allowed to soak for a period of time at ambient temperature; (b) the[0079]heating elements97 are energized to heat the mixtures to an intermediate temperature, as sensed by thesensing devices401; (c) optionally, the reaction mixtures are allowed to soak for a period of time at said intermediate temperature; (d) optionally, theheating elements97 are energized to increase the temperature of the mixtures to a final temperature; and (e) optionally, the reaction mixtures are allowed to soak for a period of time at said final temperature. The program to be carried out will vary, depending on the reactions to be run and the materials involved. Other programs may be followed, including those which involve cooling of theheat transfer plates73 to reduce the temperature of one or morewell sections201 of thereactor block11.
• The run is then carried out under the control of a suitable control system, with the reaction mixtures being heated and/or cooled and/or stirred according to the desired program. During the run, the temperatures or other conditions of the reactions, as sensed by the[0080]sensing devices401, are monitored, recorded and, optionally, controlled. Upon completion of the run, the reactions may be terminated by delivering a quenching gas (e.g., CO₂) to the chambers throughpassages263 in thehead7. Prior to removing samples, appropriate venting procedures may be needed to ensure that there is no loss of product through the vent lines263. Venting procedures may include slow venting (e.g., vent valve cycling) and/or inert gas purging (e.g., argon or nitrogen). After the appropriate venting procedures are complete, thefasteners215 securing thereactor block11 to thehead7 are removed, and thecarriage9 is lowered to separate the reactor block from the head to allow removal of the reaction samples and replacement of theremovable vials191 andstirrers271. If desired, thereactor block11 can be removed from thetemperature control unit13 to facilitate this process. The absence of connections between thereactor block11 and anyfluid transfer lines261,263 or instrumentation-related equipment makes this removal and later replacement much easier and more convenient.
• FIGS.[0081]29-33 show an embodiment of a reactor system described in detail in the aforementioned pending application Ser. No. 09/826,606, filed Apr. 5, 2001, entitled “Parallel Reactor for Sampling and Conducting In Situ Flow-Through Reactions and Method of Using Same”, assigned to Symyx Technologies, Inc., and incorporated herein by reference. This system, generally designated10, which will be briefly described herein using the same reference numbers used in the aforementioned pending application, comprises areactor block12 defining a plurality of reaction chambers in the form ofreactor wells14 for receiving and retaining the reaction mixtures. As shown, thereactor block12 defines eightreactor wells14 formed in thereactor block12 using known machining or metal working techniques. One of a skill in the art will appreciate that thereactor block12 could be designed to include any desired number ofreactor wells14.
• Each[0082]well14 defines a rectangularly shapedbody14athat projects downwardly from thetop surface22a. Eachbody14ais thermally separated, or isolated, from anadjacent body14aby an air gap such that each reactor well14 defines a separate reaction chamber that can be used to perform the same or different experiments in parallel. The air gap also thermally isolates adjacentwell bodies14a, which helps improve the efficiency of theparallel reactor system10. Reference may be made to the aforementioned pending application for further details regarding the construction and operation of the system.
• Thus, the embodiment shown in FIGS.[0083]29-33 and described above is similar to the embodiment first described above in that both embodiments use gaps in the reactor block between the wells to thermally isolate the wells.
• It will be observed from the foregoing that a system of this invention has many advantages. For example, the[0084]reactor block11 is readily removable from thetemperature control unit13 andcarriage9 for convenient cleaning, reaction preparation, etc. The fact that the various ports and passaging for fluid distribution and instrumentation (e.g., sensors) are located entirely in thehead7 and not in thereactor block11 makes removal of the reactor block particularly convenient, since there is no need to disconnect and reconnect fluid lines and/or instrumentation. Further, the absence of such passaging and ports prevents leakage and avoids undesired void space in thereactor block11. Thetemperature control unit13 of this invention is also very efficient and accurate. Theheat transfer plates73 of thetemperature control unit13 are independently spring biased into thermal contact with respectivewell sections201 of the reactor block, so that the temperature of each well section can be controlled independent of other well sections. Also, thegaps195 in thereactor block11 between thewells15 and the reducedintermediate section185 of the reactor block thermally isolate thewell sections201 from one another and from thehead7 and drivemechanism273 of the stirring assembly, thus enabling multiple reactions to be carried out at substantially different temperatures and within closer temperature tolerances. Moreover, thesensing devices401 provide for more efficient sensing and control of reaction conditions in thewells15. In the event the pressure in a particular well or wells becomes excessively high during a reaction, the pressure relief mechanism operates to safely relieve the pressure in a direction away from the front of the apparatus.
• When introducing elements of the present invention or the preferred embodiment(s) thereof, the articles “a”, “an”, “the” and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.[0085]
• In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.[0086]
• As various changes could be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.[0087]

Claims (47)

1. A combinatorial chemistry reactor system for the parallel processing of reaction mixtures, comprising

a reactor block comprising a monolithic body of thermally conductive material having a plurality of wells therein for containing reaction mixtures,

a head adapted for assembly with the reactor block for conducting reactions in the wells,

passaging in the head adapted to communicate with the head when the head is assembled with the reactor block, and

gaps in the monolithic body of the reactor block extending between the wells to thermally isolate the wells from one another.

2. A system as set forth inclaim 1 further comprising a stirring assembly on the head comprising a plurality of stirrers adapted to extend into the wells when the reactor block is assembled with the head, and a drive mechanism for moving said stirrers, said reactor block having a temperature controlled section containing at least portions of said wells, and an area of reduced cross section in at least one of the reactor block and the head at a location between the temperature controlled section of the reactor block and said drive mechanism to thermally isolate the temperature controlled section of the reactor block from said drive mechanism.

3. A system as set forth inclaim 2 wherein said area of reduced cross section is in said reactor block at a location between opposite ends of at least one of said wells.

4. A system as set forth inclaim 2 wherein said area of reduced cross section is in the head.

5. A system as set forth inclaim 1 wherein said head is adapted for assembly with the reactor block to define reaction chambers extending down into the reactor block at locations corresponding to said wells, said reaction chambers having reaction zones in which chemical reactions are conducted, and an area of reduced cross section in at least one of the reactor blocks and the head at a location above at least one reaction zone to thermally isolate the reaction zone from portions of the system above said area of reduced cross section.

6. A system as set forth inclaim 5 wherein said area of reduced cross section is in the reactor block.

7. A system as set forth inclaim 5 wherein said area of reduced cross section is in the head.

8. A system as set forth inclaim 5 wherein the reactor block is recessed to reduce the thickness of the block at locations between opposite ends of each well.

9. A system as set forth inclaim 8 wherein the reactor block has an upper section, a lower section, and a relatively narrow intermediate section connecting the upper and lower sections for reducing the transfer of heat therebetween, the wells extending down through the upper and intermediate sections into the lower sections, and the gaps between the wells dividing the lower section into a plurality of individual well sections thermally isolated from one another by the gaps.

10. A system as set forth inclaim 1 wherein said head is adapted for assembly with the reactor block to define reaction chambers, said head having a section adjacent the reactor block and a remote section away from the reactor block, said reactor block having a temperature controlled section and an area of reduced cross section in at least one of the reactor block and the head at a location between the temperature controlled section of the reactor block and the remote section of the head to thermally isolate the temperature controlled section from the remote section of the head.

11. A system as set forth inclaim 10 wherein said area of reduced cross section is in the reactor block.

12. A system as set forth inclaim 10 wherein said area of reduced cross section is in the head.

13. A system as set forth inclaim 1 wherein the reactor block has an upper section, a lower section, and a relatively narrow intermediate section connecting the upper and lower sections for reducing the transfer of heat therebetween, the wells extending down through the upper and intermediate sections into the lower sections, and the gaps between the wells dividing the lower section into a plurality of individual well sections thermally isolated from one another by the gaps.

14. A system as set forth inclaim 1 wherein said monolithic body is essentially devoid of fluid transport passaging.

15. A system as set forth inclaim 14 wherein said monolithic body is essentially devoid of passaging for instrumentation.

16. A system as set forth inclaim 1 further comprising a temperature control unit defining a cavity for receiving the lower section of the reactor block therein, said temperature control unit being operable to control the temperatures of the reaction mixtures in respective wells independently of one another.

17. A system as set forth inclaim 16 wherein said temperature control unit comprises a plurality of heat transfer plates defining said cavity.

18. A system as set forth inclaim 17 further comprising a mechanism operable to press the reactor block against said heat transfer plates when the reactor block is in said cavity.

19. A system as set forth inclaim 17 further comprising layers of thermal insulation between said heat transfer plates.

20. A system as set forth inclaim 17 wherein said heat transfer plates are spring biased into contact with said reactor body.

21. A system as set forth inclaim 16 wherein said temperature control unit comprises a plurality of heat transfer plates, each being spring biased into contact with said reactor block when the reactor block in received in said cavity.

22. A system as set forth inclaim 21 further comprising layers of thermal insulation between said heat transfer plates.

23. A system as set forth inclaim 16 wherein said temperature control unit is configured for cradling said reactor block therein.

24. A system as set forth inclaim 16 wherein the reactor block and temperature control unit have cooperating tapered surfaces adapted for face to face contact with one another.

25. A system as set forth inclaim 24 further comprising a mechanism operable to press the tapered surfaces of the reactor block against the tapered surfaces of the temperature control unit when the reactor block is in said cavity.

26. A combinatorial chemistry reactor system for the parallel processing of reaction mixtures, comprising

a reactor block comprising a body of thermally conductive material having a first face,

a plurality of wells extending from said first face into the body for containing reaction mixtures,

a head adapted for assembly with the reactor block to define reaction chambers, each reaction chamber being defined at least in part by a respective well and having a bottom end toward the bottom of the well and a head end toward the head, and

at least one of the reactor block and the head having an area of reduced cross section at a location spaced above the bottom end of at least one reaction chamber to thermally isolate portions of the reaction chamber below said area from portions of the system above said area.

27. A system as set forth inclaim 26 further comprising passaging in the head adapted to communicate with the wells when the head is assembled with the reactor block.

28. A system as set forth inclaim 27 wherein said body is a monolithic body essentially devoid of fluid transport passaging.

29. A system as set forth inclaim 28 wherein said monolithic body is essentially devoid of passaging for instrumentation.

30. A system as set forth inclaim 26 wherein the reactor block has gaps between the wells to thermally isolate the wells from one another.

31. A system as set forth inclaim 26 wherein said area of reduced cross section is in said reactor block at a location between opposite ends of at least one of said wells.

32. A system as set forth inclaim 31 wherein the reactor block has an upper section, a lower section constituting a temperature controlled section, and a relatively narrow intermediate section connecting the upper and lower sections and including said area of reduced cross section, the wells extending down through the upper and intermediate sections into the lower sections, and gaps between the wells dividing the lower section into a plurality of individual well sections thermally isolated from one another by the gaps.

33. A system as set forth inclaim 26 wherein said area of reduced cross section is in the head.

34. A system as set forth inclaim 26 wherein said reaction chambers have reaction zones in which chemical reactions are conducted, and wherein said area of reduced cross section is at a location above at least one reaction zone to thermally isolate the reaction zone from said portions of the system above said area of reduced cross section.

35. A system as set forth inclaim 34 wherein said area of reduced cross section is in the reactor block.

36. A system as set forth inclaim 34 wherein said area of reduced cross section is in the head.

37. A system as set forth inclaim 26 wherein said head has a section adjacent the reactor block and a remote section away from the reactor block, said reactor block having a temperature controlled section containing at least portions of said wells, said area of reduced cross section being a location between the temperature controlled section of the reactor block and the remote section of the head to thermally isolate the temperature controlled section from the remote section of the head.

38. A system as set forth inclaim 37 wherein said area of reduced cross section is in the reactor block.

39. A system as set forth inclaim 37 wherein said area of reduced cross section is in the head.

40. A system as set forth inclaim 26 wherein the reactor body has an upper section, a lower section, and a relatively narrow intermediate section connecting the upper and lower sections and corresponding to said area of reduced cross section, the wells extending down through the upper and intermediate sections into the lower sections.

41. A system as set forth inclaim 40 further comprising air gaps extending between the wells and dividing the lower section of the reactor body into a plurality of individual well sections thermally isolated from one another by the gaps.

42. A system as set forth inclaim 40 further comprising a temperature control unit defining a cavity for receiving the reactor block therein, said temperature control unit being operable to control the temperature of said individual well sections.

43. A system as set forth inclaim 42 wherein said temperature control unit comprises a plurality of heat transfer plates defining said cavity.

44. A system as set forth inclaim 43 further comprising a mechanism operable to press the reactor block against said heat transfer plates when the reactor block is in said cavity.

45. A system as set forth inclaim 43 further comprising layers of thermal insulation between said heat transfer plates.

46. A system as set forth inclaim 43 wherein said heat transfer plates are spring biased into contact with said reactor body.

47. A combinatorial chemistry reactor system for the parallel processing of reaction mixtures, comprising

a reactor block comprising a monolithic body of thermally conductive material essentially devoid of fluid transport passaging and passaging for instrumentation, said body having an upper section, a lower section, and a relatively narrow intermediate section connecting the upper and lower sections for reducing the transfer of heat therebetween, said upper section having an upper face,

a plurality of wells in the body for containing reaction mixtures, each well extending from said first face down through the upper and intermediate sections into the lower section,

gaps extending between the wells dividing the lower section of the rector body into a plurality of individual well sections thermally isolated from one another by the gaps,

recesses in the body to reduce the thickness of the body at locations between opposite ends of each well to reduce the transfer of heat toward the first face of the block, and

a head adapted for assembly with said reactor block for conducting reactions in the wells.

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