WO2003003135A1

WO2003003135A1 - A device in performing a process in a process medium

Info

Publication number: WO2003003135A1
Application number: PCT/SE2002/001261
Authority: WO
Inventors: Christer Ljung; Dario Kriz
Original assignee: Implementa Hebe AB
Current assignee: Implementa Hebe AB
Priority date: 2001-06-27
Filing date: 2002-06-26
Publication date: 2003-01-09
Anticipated expiration: 2003-12-27
Also published as: EP1421455A1

Abstract

The present invention relates to a device in performing a process in a process medium by varying the parameters of said process medium over time in a laboratory scale, according to a predetermined scheme. The device comprises at least one reaction receptacle, cooling/-heating means (A) comprising at least one peltiere element (B), parameter sensing means, stirring means and a data processing unit (J). The data processing unit is adapted to send out signals to said peltiere element in response to incoming signals from said parameter sensing means. The invention further relates to a computer program product comprising a computer program for controlling a data processing unit (J).

Description

A DEVICE IN PERFORMING A PROCESS IN A PROCESS MEDIUM

Technical field of the invention

The present invention relates to a device in performing a process in a process medium by varying the parameters of said process medium. The invention further relates to a computer program product comprising a computer program for controlling a data processing unit for varying the parameters of said process medium. Background Art

Chemists working in a laboratory scale within dif- ferent areas need means to control and accurately follow reactions in a process medium, for example a solution. Ordinary means of decreasing the temperature in for example a solution has been to place the beaker containing the solution, wherein reactions are taking place, in an ice-bath for example causing the temperature to be lowered. This does lead to a temperature decrease but it is not possible to follow the reactions, for example a crystallisation of the solution, accurately and precisely. It is also difficult in these cases in a laboratory scale to obtain results which can be reproduced. In certain research areas considerable advantages would be obtained where the chemist could follow a reaction over time accurately and precisely.

In the patent SE 9203388-5 a device for keeping the temperature constant in a solution in a laboratory scale is described, said device being characterised by that a cooling unit comprising a peltiere element has been combined with a magnetic stirrer.

Within the art there is a considerable need of a de- vice for controlling processes accurately in a laboratory scale.

Summary of the invention

The present invention relates in one aspect to a device in performing a process in a process medium by vary- ing the parameters of said process medium over time in a laboratory scale, according to a predetermined scheme, said device comprising at least one reaction receptacle, cooling/heating means (A) comprising at least one peltiere element (B) , parameter sensing means, stirring means and a data processing unit (J) , said data processing unit being adapted to send out signals to said peltiere element in response to incoming signals from said parameter sensing means.

The invention in another aspect relates to a com- puter program product comprising a computer program for controlling a data processing unit (J) , said computer program, when processed, performing the steps: i) from a parameter sensing means receiving an input signal having information on the parameters of a process medium; ii) processing the input signal by comparing said signal with a predetermined scheme value; iii) and, if a difference compared to the predetermined scheme value is registered, sending a first output signal to a peltiere element (B) . Description of embodiments of the invention In one embodiment of the invention said data processing unit has means for storing information as to the appropriate variation of the parameters over time, such as the predetermined scheme .

In another embodiment of the invention the parameter is the temperature and in another the parameter is the pH of the process medium.

In a further embodiment of the invention said parameter sensing means is an internal digital temperature sensor or an external temperature sensor immersed in said process medium. The internal digital temperature sensing means may be a part of the plate (A) .

In another embodiment of the invention said peltiere element (B) in response to the output signal from the data processing unit is adapted to heat or cool a metal plate (A), with which it is in contact. In another embodiment one side of said peltiere element (B) is in con- tact with the cooling/heating means (A) and the other side is in contact with a cooling flange (C) .

In one embodiment of the invention a motor is situated at the cooling flange, at the axis of which a magnet is located.

In a further embodiment of the invention said computer program, when processed, further performing the step of sending a second output signal to a fan (D) .

In still a further embodiment of the invention said computer program, when processed, further performing the step of sending a third output signal to a motor controlling the number of revolutions of a stirring means.

In a further embodiment of the invention said parameter to be controlled by the computer program product comprising the computer program is the temperature.

In another embodiment of the invention the data processing unit (J) further comprises units such as a program memory, a working memory and a processor.

In a further embodiment of the invention said proc- ess medium is a solution.

The predetermined scheme according to which the parameters, preferably the temperature, of the solution are to follow is set by the user. The predetermined scheme usually contains a start value and a stop value. The rate at which the parameters of the solution, preferably the temperature, are to increase or decrease from said start value and stop value, respectively, over time is also determined by the user and depending naturally on the conditions of the chemical process. The parameters of the solution, preferably the temperature, will follow the predetermined scheme in response to the output signals from the data processing unit in turn responsing to the input signals from the temperature sensing means . The user desiring to follow and observe the accuracy of a chemical process will set both a start set value, a stop set value and a rate (°C/min) at which the chemical process is to follow from said start set value to said stop set value. The rate (°C/min) may be rising or falling from the start value to the stop set value and depends on the conditions of the chemical process. Thus, the predetermined scheme can be regarded as the temperature as a function of time.

In the present disclosure the expression "real value" is meant the actual value obtained in the process, ie the real temperature of the process medium measured with temperature sensing means. The variation of the temperature over time may be in the interval from 0, 001°C/minute to 10°C/minute depending naturally on the process the user wants to follow.

In the present disclosure the expression reaction receptacle is meant to include any kind of vessel suited for the desirable heating or cooling transfer from the peltiere element via the heating/cooling means to the receptacle containing the solution.

By the expression "heating/cooling means" used in the present disclosure is meant a plate capable of trans- ferring heat or cold, preferably a metal plate, more preferably a brass plate.

The polarity of the current flowing through the peltiere element used in the device according to the invention may be changed, causing both heat and cold to be generated.

In order to vary the temperature of the solution a method is also provided according to the invention. Said method comprises measuring the temperature of a solution by a temperature sensing means and sending an input sig- nal, real value, to a data processing unit (J) , comparing the input signal with the predetermined scheme, set value, and if there is a difference between real value and set value, sending an output signal to a peltiere element (B) from the data processing unit (J) , whereby said peltiere element (B) in response to the output signal heats or cools a metal plate (A) , with which it is in contact. The plate (A) being heated or cooled in the last step above is directly or indirectly in contact with the reaction reciptacle containing the solution. A fan (D) may also be activated by an output signal from the data processing unit (J) in order to conduct away heat or cold generated. Stirring means may also be regulated in response to an output signal from the data processing unit in order to either increase or decrease the number of revolutions of the stirring means .

In one embodiment of the invention one side of said peltiere element (B) is in contact with the plate (A) and the other side is in contact with a cooling flange (C) , whereby said cooling flange (C) is in contact with a fan (D) . The fan (D) is intended to be used for passing away generated heat or cold from the peltiere element and cooling flange, respectively.

In some sensitive chemical reactions the temperature variation needs to be controlled very accurately whereby the stirring of the solution is important and is effected with a magnetic stirrer. The stirrer secures that said solution has a homogeneous temperature.

The variation of the temperature over time in the solution can be an increase or decrease of the temperature within the range of 0 , 001-10°C/min. The chosen variation over time depends on the chemical reaction and on the different conditions.

Different applications of the device according to the present invention include, but are not necessarily limited to, crystallisation and precipitation of inorganic materials, organic polymers and biochemical sub- stances, enantiomeric selective precipitation of a D-form or L-form of an enantiomer of a substance, selective dissolution at different temperatures of components in a substance in order to remove undesirable agents, controlled and delicate dissolution of temperature sensitive substances in need of heating in connection with dissolution, controlled and delicate melting of inorganic, organic and biochemical substances. Other applications within the field of biotechnology include, but are not necessarily limited to, controlled temperature cycling of enzymatic reactions, controlled temperature cycling of DNA or RNA hybridisation reactions, kinetic studies of the effect of the temperature on chemical reactions, enzymatic reactions, complex formation reactions and DNA/RNA hybridisation reactions, temperature regulation of chemical and enzymatic reactions by reactants or products may be activated or deactivated by a controlled tem- perature change of the reaction mixture. The device according to the invention may be used in any other application, wherein a control of the temperature is needed and is of substantial value.

The computer program stored in the memory media con- trols the following functions of the device: the size of the variation of the temperature over time, start and stop temperature set value, regulation of the starting of the electrical fan, over heating control of the peltiere element and control of the rpm of the magnetic stirrer. Further, the computer program follows the actual temperature of the process medium measured by said temperature sensing means as a function of time and controls the starting of and polarity of the peltiere element. Said control occurs so that the process medium is cooled or heated depending on if its temperature differs from the predetermined temperature scheme which is to be maintained from the start temperature set value to the stop set temperature value .

The device according to the invention has many ad- vantages in a laboratory scale. By varying the temperature over time accurately in a process medium containing different chemical species it is possible to obtain a selective dissolution of each species present. This is an important tool for example when impurities are to be re- moved.

Another important advantage obtained is in connection with chemical, biological or enzymatic reactions where reactants or products may be activated or deactivated by a controlled temperature change of the reaction mixture used on the device according to the present invention. By using the device according to the present invention to accurately follow chemical reactions one very important advantage of the invention obtained is the ability to reproduce the same results over and over again due to the precise control of the parameters of the process medium.

A further advantage is the increased yield of a substance such as crystals that may be obtained by the precise control of the parameters by the device of the invention. Brief description of drawings

Fig. 1 illustrates a drawing of a device according to the present invention. The device contains a gilded brass plate (A) containing an internal digital temperature sensor (DS1820, Dallas Inc., USA). The upper side of said plate is intended to be in contact with the bottom of a beaker containing a sample solution, the lower side being in contact with a peltiere element (B) , in turn being in contact with a cooling flange (C) containing a centrally provided motor, on the axis of which a magnetic stirrer is fixed. Below the cooling flange (C) a fan (D) is located. By the data processing unit (J) (Basic Stamp 2, Parallax Inc., USA) the following functions are regulated: By the effect step G the peltiere element (B) generating cold or heat in plate (A) is activated, thereby tempering the solution within the beaker; by the effect step E the fan (D) is activated passing away the cold or heat generated by the cooling flange and the peltiere element; by the effect step F the number of revolutions (rpm) of the motor is regulated and thereby also the rpm of said magnet causing the rpm of the magnetic stirrer located in said beaker to be adjusted. The support unit (H) (PIC12C671, Microchip Inc., USA) collects data from an external digital temperature sensor (I) (DS1820, Dallas Inc., USA) providing a better illustration of the actual temperature of the solution compared to if only said internal digital temperature sensor is used. The support unit (H) mediates only temperature data from the temperature sensor (I) if it is connected, otherwise the temperature data of the internal digital temperature sensor is mediated to the data processing unit (J) . If the support unit (H) registers that the temperature of the plate (A) is greater than the maximum allowed values according to the manufacturer of the peltiere element, this is signalled to the data processing unit J. The data processing unit (J) presents the actual settings and values on the display (K) . Parameters such as start and stop tempera- ture value, size of the temperature variation over time, and stirring rate are entered on the keyboard and then a computer program in the data processing unit is responsible for that the device achieves adjusted values. The data processing unit (J) can collect or send information to a network or other computer by way of a serial interface M.

Fig. 2 illustrates an example where a beaker containing 80 ml water, under stirring (250 rpm) , has been placed on a device according to the present invention. From the graph it can be concluded that the temperature of said solution has been lowered from 25,0°C to 15,0°C with a decrease of the temperature over time of 0,43 °C/minute, thereafter kept constant at the latter temperature. Fig. 3 illustrates a purification process by re- crystallisation of a substance with a device according to the present invention. The start set value has been set at 40°C, the stop set value at 5°C and the decrease of the temperature over time set at l°C/minute. Example

This example describes a purification process by re- crystallisation of a substance, viz aspartic acid, being contaminated with 5% NaCl . Firstly, said contaminated substance (0,33 g) and water (50 ml) is added to a flat bottom beaker (100 ml) and is placed on a device according to the present invention. Thereafter the temperature of the solution is raised to 40,0 °C and the substance is dissolved under stirring (rpm = 250) during 1 hour. Thereafter a controlled temperature decrease is started with 1 °C/minute according to figure 3. When the solution has reached the temperature of 5,0 °C, see indication A in figure 3, small crystals become visible. The temperature of the solution is allowed to stabilise at 4,0 °C and the solution is allowed to stand over night while stirring (rpm=10) . Finally, the solution containing a white precipitate is filtered, the result being a white powder consisting of pure crystals of aspartic acid.

Claims

1. A device in performing a process in a process me- dium by varying the parameters of said process medium over time in a laboratory scale, according to a predetermined scheme, said device comprising at least one reaction receptacle, cooling/heating means (A) comprising at least one peltiere element (B) , parameter sensing means, stirring means and a data processing unit (J) , said data processing unit being adapted to send out signals to said peltiere element in response to incoming signals from said parameter sensing means .

2. A device according to claim 1, wherein said data processing unit has means for storing information as to the appropriate variation of the parameters over time.

3. A device according to claim 1 or 2 , wherein said parameter is the temperature.

4. A device according to any one of claims 1-3, wherein said parameter sensing means is an internal digital temperature sensor.

5. A device according to any one of claims 1-3, wherein said parameter sensing means is an external temperature sensor immersed in said solution.

6. A device according to any one of claims 1-5, wherein said peltiere element (B) in response to the output signal from the data processing unit (J) is adapted to heat or cool a metal plate (A) , with which it is in contact .

7. A device according to any one of claims 1-6, wherein one side of said peltiere element (B) is in contact with the cooling/heating means (A) and one side is in contact with a cooling flange (C) .

8. A computer program product comprising a computer program for controlling a data processing unit (J) , said computer program, when processed, performing the steps: i) from a parameter sensing means receiving an input signal having information on the parameters of a process medium; ii) processing the input signal by comparing said signal with a predetermined scheme value; iii) and, if a difference compared to the predetermined scheme value is registered, sending a first output signal to a peltiere element (B) .

9. A computer program product according to claim 8 , said computer program, when processed, further performing the step of sending a second output signal to a fan (D) .

10. A computer program product according to claim 8 or 9, said computer program, when processed, further performing the step of sending a third output signal to a motor controlling the number of revolutions of a stirring means .

11. A computer program product according to any one of claims 8-10, wherein said parameter is the temperature .