Crystallization process instrumentation

Breitschuh and Windhab (1996) described a novel use of DSC for directly investigating or monitoring crystallization processes such as those used in the fractionation of milk fat. In their technique, called DSC direct, a small sample of fat is taken from the process line, placed immediately in the sample pan of the DSC instrument, and within seconds, subjected to a heating scan. In this way, the melting characteristics of the fat at that particular stage of the process, as determined by processing conditions up to that stage, can be determined directly. 

In recent years robots and other automated instruments, and entire integrated systems, have been developed to accelerate the crystallization process (Luft et al., 2003 DeLucas et al., 2003 Hosfield et al., 2003 Bard et al., 2004). They have the capacity to screen thousands of crystallization conditions, and they do so precisely and reliably, with fewer errors and better record keeping than most humans. In many large laboratories these have become essential pieces of equipment. Using standard, usually commercially available screening kits, sometimes supplemented by local favorites, they can often arrive at acceptable crystals in the most expeditious possible manner. 

It should be noted that development of the crystallization processes in most of the examples presented in later chapters occurred before the availability of many of the online measurement and control methods that are now available. Utilization of these methods would have aided both the process development and the manufacturing operations. The literature that describes these methods—for example, feedback control of supersaturation for crystallization (Nonoyama et al. 2006 Zhou et al. 2006)—is now extensive, and the instrumentation to carry out the measurements and control continues to be improved. 

Determination of the solution concentration, either at supersaturated or saturated states, can be done offline by taking slurry samples from the process, similar to the measurement of solubility in Section 2.1.6. This method involves complications due to temperature variation and solvent evaporation. In addition, sampling is generally time and labor intensive. As mentioned earlier, in-situ analytical instrument such as FTIR or UV-visible spectrophotometry can measure the solution concentration and calculate the supersaturation given the solubility information. Accurate determination of supersaturation can greatly increase the understanding of crystallization kinetics and the development of the crystallization process. 

Direct geometry instruments use choppers or crystal monochromators to fix the incident energy and they are found on both continuous and pulsed sources. To compensate for the low incident flux resulting from the monochromation process, direct geometry instruments have a large detector area. This makes the instruments expensive, they are generally twice the price of a crystal analyser instrument. At present, they are used infrequently for the study of hydrogenous materials, so we will limit our discussion to a chopper spectrometer at a pulsed source and a crystal monochromator at a continuous source. 

The CEF instrument is similar to an HPLC or TREF apparatus, as shown in the schematic diagram of Fig. 27 the main CEF characteristic is the ability to provide a small controlled flow during the crystallization process. 

However, both soft ionization of analytes and tandem MS are difficult to achieve with typical SIMS technique (8). In contrast, spatial resolution of MALDI-IMS is lower than that of SIMS. The spatial resolution depends on the experimental conditions and the instrument used but is typically 20-100 jim. Limitations of the spatial resolution of MALDI-IMS include the size of the organic matrix crystal and the analyte migration during the matrix application process. To overcome these problems, Taira and colleagues reported a nanoparticle (NP)-assisted laser desorption/ionization (nano-PALDI)-based IMS, in which the matrix crystallization process is eliminated (9). The use of nano-PALDI has enabled researchers to image compounds with spatial resolution at the cellular level (15 (xm almost equal to the size of the diameter of a laser spot). 

Process equipment function changes with different steps in process sequence (e.g., same vessel used as feed tank, reactor, crystallizer pump used to pump in/out). Instrumentation and controls not kept in phase with the current process step (e.g., control set points, interlocks etc.). 

The instrument has been evaluated by Luster, Whitman, and Fauth (Ref 20). They selected atomized Al, AP and NGu as materials for study that would be representative of proplnt ingredients. They found that only 2000 particles could be counted in 2 hours, a time arbitrarily chosen as feasible for control work. This number is not considered sufficient, as 18,000 particles are required for a 95% confidence level. Statistical analysis of results obtained for AP was impossible because of discrepancies In the data resulting from crystal growth and particle agglomeration. The sample of NGu could not be handled by the instrument because it consisted of a mixt of needles and chunky particles. They concluded that for dimensionally stable materials such as Al or carborundum, excellent agreement was found with other methods such as the Micromerograph or visual microscopic count. But because of the properties peculiar to AP and NGu, the Flying Spot Particle Resolver was not believed suitable for process control of these materials... 

Figure A2.1 Waters ProMonix On-Line HPLC analyzer. The upper compartment door contains a keypad for programming and operation of the analyzer. The upper window allows viewing of indicator lights and a liquid crystal display that provides the operator with analyzer interface, programmed parameters, and instrument status results. The lower chamber contains the pumps, valves, injector, and detector(s) required for the chromatographic separation. The sample conditioning plate for online process monitoring is to the right of the analyzer. This is a typical process HPLC. (From Cotter, R.L. and Li, J.B., Lab Rob Autom., 1, 251,1989. With permission of VCH Publishers.)...

Before going further, it may be noted that the flipping ratio does not depend either on the Lorentz factor or on absorption in the sample. Certain instrumental parameters such as the polarisation of the neutron beam for the two spin states, the half wavelength contamination of the neutron beam and the dead-time detector can readily be taken into account when analysing the data. On the other hand, the extinction which may occur in the scattering process is not so easy to assess, but must also be included [14]. Sometimes, it is even possible to determine the magnetisation density of twinned crystals [15]. 

---