Solid phase peptide synthesis reactor (Grindeks, JSC)

Used controller: Siemens Simatic S7-313 DP with explosion-proof "touch screen" 6" display TP270.

Used visualization program: Excel based program with specially created Visual Basic scripts, and connected with OPC server (Matrikon).

This system of dosage provides a definite level of medical injection liquid in the reactor during the filling of ampules. The system works in the way, that controller having got the information about the level of the liquid from capacity l sensor, is giving controlling signals to switch on/off the peristaltic pump. It is possible to determine the set point of level and extra safety criteria from operator's control panel.

This peptide synthesis reactor is intended for carrying out synthesis of peptides and other products being obtained in the similar way. It is used for both research and developing a synthesis reactions, as well as industrial production. The synthesis reactor design provides for development and optimisation of processes starting from 3 litres reaction vessel, but this particular solution can be further scaled-up for even up to 50 litres reaction vessel, and also for larger volumes depending upon a customer's needs. Where the scale is increased, a reaction vessel with a larger volume should be mounted inside the synthesis reactor, but the synthesis process control program and the most part of essential parameters remain unchanged. This makes possible rapid optimisation of peptides or other substances synthesis in small scale, and then, without any substantial changes in the program, to transit rapidly to manufacture of products in a larger scale.

The main elements of this system are interconnected according to the following block-diagram:

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The peptide synthesis reaction vessel(with 3 litres volume) is placed on aplatform scales. In such the way, information is being acquired on changes in weight within the volume of reaction vessel. Nitrogen connection and regulation cabinet provides the atmosphere of nitrogen, its overpressure during filtration, and operation of pneumatic valves. The pneumatic control pumps, when the corresponding feeding valves open, provide feeding of the corresponding solvent into the reaction vessel (proportioning till 6 solvents is provided for).

The power control cabinet is located in an adjacent room, where explosion hazard conditions do not exist. In the said room, the following elements are placed: the controller Siemens Simatic S7-313 DP, indicator/transmitter of platform scales, commutation elements, pilot valves of pneumatic control, and manual control switches.

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Information from the platform scales is being input to the controller input through serial port of indicator/transmitter. The controller is interconnected with operator's panel and computer via the Profibus DP data transmission line.

The solvents tanks are placed in an adjacent room, where the proper conditions for placement of volatile solvents are ensured. From the leak-proof tanks, solvents through the pneumatic control pumps are fed into the reaction vessel. Both the pressurized gas and solvents supply pipes are led into the room through a wall.

To make programming of the synthesis process and registration of different parameters moreconvenientthe program is created in such the way, so that the commonly known Excel formatis used. Such spreadsheets provide wide opportunities for creation of synthesis programs by copying uniform operation blocks, as well as using different programs for archives. In Excel spreadsheets, different process parameters, such as weight of a proportioned solution, duration of stirring, regime, and temperature inside the reaction vessel, are being registered automatically. It is essential, that in the same spreadsheets the data of analytical control of a corresponding stage of synthesis, such as the results of polymer inter-stage analyses, obtained by either operator or analytical laboratory from the samples taken from the reaction vessel, are being registered, too. Thus all the available information on the synthesis process can be found gathered together, so it can be conveniently used for both the process optimisation tasks, and at some later time also for meeting the requirements of large-scale GMP production.

    1. Within the computer software, a pre-programmed sequence of the synthesis processes is formed.
    2. Prior to commencement of the synthesis process in the computer, the prepared program is input to the process controller.
 
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  1. Upon entering the "Start the system's process" command from the computer, the synthesis process is commenced according to the assigned program of synthesis.
  2. Each operation within the framework of the synthesis process, as well as the results, are accounted and pre-fixed with the help of computer software.

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    1. It is possible to suspend the synthesis process and then resume it from the same point.
    2. It is possible to stop the synthesis process either entirely or in any its line.
    3. During the synthesis process, it is possible to switch to manual control mode. It should be noted, that manually controlled operations are not fixed in the computer. Therefore, the manual control mode is recommended for performing a preparation operation prior to commencement of the synthesis, or in some especial cases of necessity, which may occur during the synthesis.
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The program for forming, editing and managing/controlling performance of the synthesis process is created on the basis of Excel software, complemented with our developed Visual Basic scripts. The idea of the program is given through the main window image with necessary explanations:

 

 

The synthesis process includes the following sub-processes:

  1. Proportioning of solvents;
  2. Mixing;
  3. Adding operator's reactant 1 (ie., prior to filtration);
  4. Taking analytical sample and/or inter-stage ones 1 (ie., prior to filtration);
  5. Express-analysis and test 1 (ie., prior to filtration);
  6. Filtration or discharge;
  7. Adding operator's reactant 2 (ie., after filtration);
  8. Taking analytical sample 2 (ie., after filtration);
  9. Express-analysis and test 2 (ie., after filtration).

Each individual process of synthesis may include 1-9 of the above-specified sub-processes. Transition to any succeeding sub-process takes place upon completion of the preceding one. Upon completion of the last sub-process in a line, a new process of synthesis begins from a new line. If the succeeding process of synthesis is performed in automated control mode, then it begins in operators' absence. Otherwise, if it is programmed for being performed in either manual control mode or dialogue mode, then it begins upon receipt of operator's confirmation.

 

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