Crystallization mechanisms can be studied using three main techniques: visual observation, offline microscopy and real-time microscopy. The benefits and drawbacks of each are described below.
Visual observation. Visual observation can help to determine what is happening in a crystallization mechanism at a basic level. If crystallization is occurring, the solution will become turbid. While the visual observation of crystallization mechanisms is simple, very little is revealed in terms of the actual crystallization mechanism in real time.
Offline particle analysis. Traditional particle size analysis using an offline analyzer is a powerful and widely used technique for the measurement of particle size in quality control (QC) labs. Examples of traditional particle size analysis techniques include sieving, laser diffraction, dynamic light scattering, and electrozone sensing. This approach allows QC laboratories to check the specification of particles at the end of a process against a set specification and identify deviations from the required particle properties.
Offline particle size analysis is a powerful and widely used technique for the measurement of particle size, and for comparison with a set specification in QC. With care, traditional particle size analysis can be used to identify variations in product quality, and can be used to ensure that products meet the specifications required by producers, their customers, and regulators who oversee the quality of products reaching the public.
However, traditional particle size analysis does not lend itself well to characterizing particles continuously as process parameters change, and for this reason they are not especially suited to the task of process optimization. It is extremely difficult to rely on a single offline sample, no matter how reliable the data obtained, in order to completely understand particle behavior from the beginning until the end of a process. In order to develop truly effective process understanding and to translate this into meaningful improvements for the process, continuous measurements are needed that characterize particles in real time as they naturally exist in the process. With this information, particle mechanisms such as growth, breakage, and agglomeration can be directly observed, the influence of process parameters on the system can be determined and an optimized route to the desired particle properties can be identified and implemented quickly.
In-process particle measurement. In-process particle measurement typically relies on inserting a probe-based instrument into a process stream for direct measurement of particles as they naturally exist in the process. This type of measurement occurs at full process concentrations and does not require sampling. Typically, probes can be applied across a range of scales and installation environments, ranging from small scale laboratory reactors to full scale production vessels and pipelines.
In-process measurement of particles is suited particularly well to developing process understanding for complex particle systems and for determining the appropriate parameters needed to deliver particles with the desired properties. In-process particle measurement also complements traditional particle size analysis by supporting quality control efforts through the identification and rectification of process upsets during production. This can help to:
- Avoid errors associated with non-representative sampling
- Avoid physical changes to the particle resulting from sampling, transport, storage, sample preparation, and flow through the offline measurement instrument
- Obtain continuous and real-time information about the particle system as process parameters are changing
- Characterize particles where sampling is challenging due to temperature, pressure, or toxicity
- Directly observe the impact of disturbances and intentional process upsets