How to quickly change from batch to continuous processing
Adopting a new technology may sound daunting but it doesn’t have to be complicated. If you have been thinking about moving to continuous processing for a while but don’t know where to start, employing experimental design is a systematic way to quickly determine the optimum operating conditions for a flow process.
First, determine which is more appropriate for your process, batch or flow? In a typical batch process the solid reagents are loaded into a reactor, liquid reagents are added and the reaction occurs within the vessel. Following this, the product solution is typically discharged and undergoes a work up. While this may be easy to set up, there are a number of drawbacks associated with batch chemistry which include: batch-to-batch variation; bottlenecks; restrictions in dealing with hazardous chemicals or processes; maintaining control (e.g. temperature, exotherms etc). In flow chemistry, the reactants are typically pumped through tubing or microreactors where they meet, mix and react, then the product is continuously collected. With a flow process in the right equipment, mixing can be exceptional and this leads to a number of benefits including rapid mass and heat transfer (heating or cooling) which delivers improved reaction control and can improve the safety and efficiency of your process; fewer impurities and faster reactions.
The scale up of a batch process can be problematic with additional complications surrounding mixing and mass transfer. Chemical selectivities can even change depending on the equipment used and the scale of the reaction; large effects can be seen when changing from research lab to process lab or on scale up. In theory, the scale up of a continuous process is much more straightforward and can be achieved in a number of ways: maintaining the equipment used on a small scale but increasing the run time; maintaining the equipment used e.g. a microreactor, but increasing the number in use; increasing the capacity of the reactor. In the first two cases the experimental parameters remain the same. When increasing the capacity of the reactor some settings, such as the flow rate, may need to be modified but the difference in the heat and mass transfer when increasing, for example, the diameter of the tubing is a much smaller difference than when increasing the volume of a batch reactor. Furthermore, there are options for easily implementing solvent recycling options when operating in flow, which will improve the sustainability factor of the process especially on scale.
If your process goals and needs align with continuous processing, it’s time to think about the experimental protocol. If you have read our DoE demystified series you will be familiar with factor selection. This involves thinking of all the potential factors which may affect your process, then choosing whether to investigate or control all these factors. When developing a new flow process, you may wish to consider the following factors: length of tubing, diameter of tubing, flow rate, concentration, solvent, stoichiometry, temperature, pressure, mixing (in tube, t-piece, static mixers etc), residence time… there may be many more that you can think of relating to your process and we strongly recommend carrying out the factor selection with a diverse team of chemists and engineers.
DoE is the perfect tool to enable the rapid development of your flow process whether you are starting from scratch with parameter screening or are looking to optimise an existing process. While it is already an efficient way to screen reaction space it can be even faster with flow chemistry especially in combination with automation.
At PMCC we apply DoE to a wide range of chemical and engineering challenges and can provide support in all aspects of experimental design including factor selection, the setting up of design and analysis.