WO2001003838A1

WO2001003838A1 - Temperature control in multi-station reaction apparatus

Info

Publication number: WO2001003838A1
Application number: PCT/GB2000/002627
Authority: WO
Inventors: Christopher John Orlopp
Original assignee: Electrothermal Engineering Limited
Priority date: 1999-07-07
Filing date: 2000-07-07
Publication date: 2001-01-18
Also published as: GB9915953D0; GB0016802D0; GB2351925A

Abstract

A multi-station reaction apparatus (1), each station (2-6) of which defines a location adapted to receive a reaction vessel (7-11), and thermal insulation being provided to impede thermal coupling between stations. Each station is provided with respective and individually energisable heating means (14), and cooling means (12) are provided to achieve a desired reaction temperature within a prescribed operating range.

Description

TEMPERATURE CONTROL IN MULTI-STATION REACTION APPARATUS

This invention relates to multi-station reaction apparatus, and it relates particularly to such apparatus as may be employed to create and maintain differing thermal environments for a plurality of reaction vessels.

In such apparatus, particularly where there is a requirement for relatively compact overall dimensions, considerable difficulty is encountered in ensuring adequate thermal independence as between neighbouring stations. This is especially the case in circumstances where the prescribed thermal environments of neighbouring reaction vessels can vary significantly, and in effect randomly, from one another. Multi-station reaction apparatus of the general kind described above requires both heating and cooling facilities at each station, as a reaction at any station might need to be carried out at any temperature within the. range handled by the apparatus, typically -30 to +150 degrees C, since it is the practice for test tubes, or other glass reaction vessels, containing reactants to be presented at any free station, of which a typical compact apparatus contains ten. In known equipment, all of the stations share a common heating device, so the required temperature variations from station to station cannot be achieved. This known arrangement is also wasteful of energy and tends to create an environment in which significant amounts of heat are absorbed by and transmitted around within the apparatus, tending to exert unwanted influence on station temperatures and thus to disturb carefully balanced thermal parameters.

This invention aims to reduce unnecessary thermal wastage and/or to reduce thermal interdependence between stations, particularly neighbouring ones.

According to the invention there is provided a multi-station reaction apparatus; each station defining a location adapted to receive a reaction vessel, and thermal insulation being provided to impede thermal coupling between stations, wherein each station is provided with respective and individually energisable heating means, and cooling means are provided to achieve a desired reaction temperature within a prescribed operating range. Respective temperature sensing means may be provided at each station, each individually capable of sensing departure, at its station, from a desired reaction temperature in said range, and providing control signals for said heating and/or cooling means as required to re-establish the desired reaction temperature at that station.

Preferably, the cooling means comprises respective coolant-fed coils, a hollow cylinder or a thermoelectric cooler module at each station, disposed so as to thermally couple with reaction vessels supported thereat. This arrangement assists in the reduction of temperature differentials within the apparatus, and also functions as a thermal sink for media within the reactor vessels . Preferably also, each station is provided with drive means for a magnetically coupled stirring device locatable in a reaction vessel; the drive means being configured to resist thermal transfer thereto and/or to position active components thereof in a thermally protected environment. This permits stirring of the reactant materials to be achieved whilst protecting the driver from the effects of temperatures at the extremes of the range; particularly from the effects of extreme cold which can cause drive motors to seize and fail. It is further preferred that an individually temperature controlled reflux means be provided at each station t^'ό cool the top section of a reactor vessel, thus providing condensing or refluxing of evaporated reactants. Conveniently, the reflux means comprises a hollow cylinder or a tubular coil through which flows cooled refrigerant fluid. In addition, an inert gas may be passed around the cooled cylinder or coil to further improve thermal contact with the reaction vessel.

It is also preferred that the individual heating means at each station comprise infra-red heaters below, sleeve heaters surrounding, or heater elements adjacent to, the reaction vessel locations.

The invention is primarily concerned with the multiple synthesis of compounds in an apparatus of compact dimensions which is preferably usable in conjunction with laboratory auto-samplers and robots. Typically the stations are arranged in two parallel banks of five to accommodate respective reaction vessels within which simultaneous automatic or manually programmed reactions are conducted. Preferably, as mentioned, a respective magnetic stirrer is provided at each station, and conveniently each stirrer is driven, via a magnetic clutch system, from an hermetically sealed driver. Reference will now be made, by way of example, to the accompanying drawings, of which:

Figure 1 shows a schematic and partially cut-away side view of apparatus in accordance with an exemplary embodiment of the invention; Figure 2 shows in detail a drive system for a magnetic stirring device for use with the embodiment of Figure 1 ; and

Figures 3 and 4 show respective cross-sectional views of part of an alternative embodiment of the invention.

Referring now to Figure 1, a multi-station reaction apparatus 1 defines ten reaction stations, of which only five, referenced 2-6, are visible in the drawing. The other five stations are disposed in a bank parallel to stations 2-6 and in precise alignment therewith, though the two banks can be staggered or otherwise offset relative to one another if desired. Each of the reaction stations such as 2-6 defines a location for a respective reaction vessel such as 7-11 in each of which an individual reaction is run at a respective, selected temperature within an overall operative temperature range which, in this example, is from -30 to +150 degrees C.

In order that the temperatures at the various reaction stations may be individually controlled, each station is provided respectively with a cooling means and a heating means. The heating and cooling means are similar for all stations, so only those associated with station 2 will be described.

Station 2 is provided with a cooling device which, in this example, comprises a cooling coil 12 having a top inlet fed, through an inlet manifold (not shown) common to the coils associated with the other reaction stations, with coolant fluid. The coolant fluid exits through a lower outlet of the cooling coil 12 and passes through a common outlet manifold (not shown) to a large bore outlet tube 13. The coolant fluid is thus delivered from a refrigerant unit of suitable capacity, through a small bore capillary tube to the inlet manifold, and thence through the coils such as 12 to the outlet manifold and via the large bore "exhaust" tube 13 back to the refrigerant unit. This arrangement ensures that the coolant fluid is fed evenly to each coil such as 12.

It will be appreciated that, instead of coils such as 12, other forms of coolant guide, such as hollow cylinders, could be used if desired. Alternatively, as shown in Figure 3 which illustrates a single station 2 by way of example, each station 2-6 may be provided with a cooling means comprising respective thermoelectric cooler modules 112, also called Peltier devices. Each Peltier device 112 is arranged such that one face of the Peltier device 112 is thermally coupled to the reaction vessel at that station, and the other face is thermally coupled to a heat sink 113, which is in turn cooled by cold water flow through rails 115. The cooling action of each Peltier device 112 is individually controlled by means of an electric current applied to it which is regulated by the temperature monitoring electronic system. Figure 3 also shows, in addition to the magnetic stirring device 17, motor 18 and magnet carrier 20: a PTFE-coated aluminium block 116 with a through drilling 117 for a reaction vessel 7-11; O-rings 118, 199 at the top and bottom of the block 116; and a metal cover 120. A section through a corner of the block 116 is shown in Figure 4 to illustrate the heating means of this embodiment. Stations 2-6 have respective DC- powered electrical heater elements 114 individually controlled through wires 121 by the temperature monitoring electronic system. Each heater element 114 is provided within the block 116 and comprises a cartridge heater which is resistive.

Returning to the embodiment of Figure 2, however, station 2^" is also provided with an individual infra-red heating element 14; similar elements being provided for all other stations, and all of the elements being individually energisable. Other forms of heater, such as a cylindrical sleeve-like heater or the heater element of Figure 3, can be used instead of, or as well as, the infra-red element 14.

In this example of the invention, each reaction vessel such as 7 is fitted with a sealing cap such as 15, and is surrounded near its top by a reflux cooling coil such as 16. As before, the coil can be replaced by a hollow cylinder if desired.

Beneath each reaction station such as 2 there is further provided a respective magnetic stirring driver device such as 17; this comprises a multi-stage drive designed to ensure that a prime mover device 18 is protected, as far as is possible, from the extremes of temperature to which the reaction vessel 7 may be subjected. This arrangement is shown in more detail in

Figure 2, to which specific reference will now be made.

The device 17 is intended to enable stirring of the reactant media to be effected under all thermal conditions without overheating, freezing or the formation of excessive condensation, all of which can adversely affect the prime mover 18 which, in this example, is an electrically driven motor. Device 17 comprises a three-zone device with the first zone 19 (that nearest the reaction station 2) being hermetically sealed and either gas-filled or under vacuum. A mild steel keeper bar 20 can rotate within the sealed first zone 19; the bar 20 supporting, in known manner, a first (upper) pair 21 of cylindrical bar magnets of opposed polarity, disposed with their respective axes parallel to the axis of rotation of the bar 20 and equally spaced to either side of the rotational axis on a common diameter. The upper magnet pair 21 provides magnetic coupling to a stirrer magnet (not shown) , typically a PTFE or glass- coated rod magnet, located within the reaction vessel and capable, either by itself or by means of an attached vane or other device, of stirring the contents of the reaction vessel 7.

The bar 20 also supports a second (lower) magnet pair 22, similar to the pair 21 but with polarities reversed, which is magnetically coupled to a second stage magnetic system, located in a second zone 23 outside the sealed first zone 19. The second stage system comprises a second keeper bar 24 supporting an upper magnet pair 25 identical to the magnet pair 21; the bar 24 and magnet pair 25 being disposed in an outer case 26 made of thermally resistant material which acts as a thermal shunt.

Bar 24 is directly driven by the motor 18 which is located in a third zone 27. Thus, motor 18 drives bar 24 directly, whereas bar 20 is driven by magnetic coupling between magnets 25 and 22, and the stirrer magnet (not shown) in the reaction vessel 7 is driven via magnetic coupling from magnets 21, thereby providing a two-stage magnetic clutch system. The operation of drive motor 18 is electronically controlled so as to maintain the rotation of the stirrer magnet in the reaction vessel 7 at a given speed; the voltage and current necessary to achieve this being monitored to permit indications to be derived of significant events, such as crystallisation points, which materially affect the viscosity of the reactant media and thus the power needed to drive the motor 18. Reverting to Figure 1, the apparatus as a whole is operated under electronic control; selection and/or controlling inputs and measured outputs being conveyed to an electronic control pad 28. In order that the thermal environments of all stations such as 2-6 can be individually controlled, each station is provided with an electronic temperature sensor, such as that shown at 29, which feeds control data into the electronic control system. Each sensor such as 29 is placed within its respective reaction vessel such as 7, to enable each station to be kept at its individually selected operating temperature as appropriate to the reaction being run therein. These sensors such as 29 are typically PT100 platinum resistance sensors, though sensors based on other technologies, such as thermistors, can be used instead, or in addition, if preferred. Conveniently each sensor such as 29 is sealed into a small diameter, corrosion-resistant tube which in turn is fixed to the cap of the relevant reaction vessel, and contains a suitable connector by means of which it can be coupled into the temperature monitoring electronic system.

In addition, in order to monitor the overall thermal environment of the apparatus 1, it is preferred to provide a solid state electronic temperature sensor 30, monitoring the coolant system, and respective thermocouples such as 31 associated with the individual infra-red heaters at each reaction station.

The sensor 30 is preferably mounted in excellent thermal contact with the outlet tube 13, and is intended to detect whether the system is operating correctly and, if so, when its steady state has been reached. Sensors such as 30 typically generate digital output signals which, beneficially, reduces their susceptibility to interference.

Claims

CLAIMS :

1. A multi-station reaction apparatus (1); each station (2 to 6) defining a location adapted to receive a reaction vessel (7 to 11) , and thermal insulation being provided to impede thermal coupling between stations (2 to 6) , characterised in that each station (2 to 6) is provided with respective and individually energisable heating means (14) , and cooling means (12) are provided to achieve a desired reaction temperature within a prescribed operating range.

2. Apparatus according to claim 1 further comprising respective temperature sensing means (29) at each station (2 to 6) , each individually capable of sensing departure, at its station (2 to 6) , from a desired reaction temperature in said range, and providing control signals for said heating and/or cooling means (14/12) as required to re-establish the desired reaction temperature at that station (2 to 6) .

3. Apparatus according to claim 1 or claim 2 wherein the cooling means (12) comprises respective, coolant- fed coils at each station (2 to 6) , disposed so as to thermally couple with reaction vessels (7 to 11) supported thereat .

4. Apparatus according to claim 1 or claim 2 wherein the cooling means comprises a respective hollow cylinder at each station (2 to 6) , disposed so as to thermally couple with reaction vessels (7 to 11) supported thereat .

5. Apparatus according to claim 1 or 2 wherein the cooling means comprises respective thermoelectric cooler modules (112) at each station (2 to 6) , disposed so as to thermally couple with reaction vessels (7 to 11) supported thereat.

6. Apparatus according to any preceding claim, wherein each station (2 to 6) is provided with drive means (17) for a magnetically coupled stirring device locatable in a reaction vessel (7 to 11) .

7. Apparatus according to claim 6 wherein the drive means (17) is configured to resist thermal transfer thereto.

8. Apparatus according to claim 6 or claim 7 wherein the drive means (17) is configured to position active components thereof in a thermally protected environment .

9. Apparatus according to any preceding claim including individually temperature controlled reflux means (16) provided at each station (2 to 6) to cool the top section of a reactor vessel (7 to 11) , thus providing condensing or refluxing of evaporated reactants.

10. Apparatus according to claim 9 wherein the reflux means (16) comprises a hollow cylinder through which flows cooled refrigerant fluid.

11. Apparatus according to claim 9 wherein the reflux means comprises a tubular coil through which flows cooled refrigerant fluid.

12. Apparatus according to any of claims 9, 10 or 11 further including means for passing an inert gas around the reflux means to further improve thermal contact with the reaction vessel. -ills . Apparatus according to any preceding claim wherein the individual heating means (14) at each station (2 to 6) comprise infra-red heaters below the reaction vessel locations .

14. Apparatus according to any of claims 1 to 12 wherein the individual heating means at each station (2 to 6) comprise sleeve heaters surrounding the reaction vessel locations.

15. Apparatus according to any of claims 1 to 12 wherein the individual heating means at each station (2 to 6) comprise respective heater elements (114) adjacent to the reaction vessel locations.

16. Apparatus according to any preceding claim wherein the stations (2 to 6) comprise ten stations, arranged in two parallel banks of five to accommodate respective reaction vessels within which simultaneous automatic or manually programmed reactions are to be conducted.