**4. Conclusions**

A novel inline shadowgraphic probe was utilized to determine the transient crystal size distribution in different crystallization processes, based on acquired greyscale images. For validation, three experiments in a well-known seeded KH2PO4/H2O cooling crystallization were carried out, and the crystal size distributions between the new shadowgraphic probe were compared with an established bypass online microscope and sieve analysis. The measured number and mass distributions showed a good agreement for both image-based techniques in all three experiments. The percentiles support the results, as they exhibit similar trends and values with an average deviation of 10–20 μm. Classifying effects, such as shifts in the crystal size distributions could not be observed up to a characteristic crystal size of 600 μm. This is confirmed by sieve analyses of suspension samples that were compared to the final mass-based distributions of the optical techniques. The experiments were performed for different seed loadings, and hence, different suspension densities up to 8%, and an optical density up to 11%, without any influence with respect to the measured distributions.

In addition, a fourth experiment, with the same substances at a higher starting saturation, temperature was executed. It was shown that the probe can be applied to these elevated temperatures and conditions, while a measurement with the bypass variant failed due to a blockage within the bypass tubes.

Needle-like thiamine hydrochloride monohydrate was crystallized from a clear thiamine/water solution when adding ethanol as an anti-solvent. The process was only investigated using the shadowgraphic probe, since measurements with the bypass online microscope failed due to blocking. In addition, the images captured by the online microscope had poor image quality, due to blurry edges of the imaged objects. The needle-like crystals could be measured in length and width up to a suspension density of three percent, until the image algorithm based on binarization failed, due to missing segmentation methods and massive particle overlapping. It was shown that the shadowgraphic probe can be applied to systems that form fragile crystals, where other techniques fail. It was found that the needle-like crystals align with the flow direction in the measurement gap, which offers a great potential for different image processing routines at a higher solid content.

A suspension density limit for the applied techniques cannot be generally determined. The measured optical density on pixel ratios does not necessarily match with the mass-based suspension density, but it can identify trends. The optical suspension density is mutually connected to the particulate state, such as size, distribution, and particle shape, and it must be evaluated for each system individually.

It was shown that the shadowgraphic probe is capable of monitoring the transient evolution of the PSD in a crystallization processes, with an extended range of operation conditions, and was compared to an established online bypass variant and sieve analysis. While bypass variants mainly suffer from blockage at high temperatures and supersaturations, the shadowgraphic probe can be applied under these conditions. In view of industrial application, it is desirable to extend the range of operation up to industrial conditions, i.e., suspension density, temperature, pressure, and chemical resistance. It is well known that image analysis fails at a high solid content, but mathematical algorithms (e.g., neuronal networks) have significantly developed in the recent years to overcome this gap. Hence, it is desirable to enhance the analysis range to industrially relevant conditions (e.g., larger suspension densities). With endoscopic probes, in combination with appropriate image analysis software, processes can be designed and scaled to industrially relevant size, as the development is less based on experience than on intrinsic data, including the particulate state.

In the state-of-the-art crystallization processes, the particulate phase is mostly not monitored and therefore largely unknown, which is one of the key problems in developing continuous crystallization processes.

**Author Contributions:** Conceptualization, E.T. and D.W.; methodology, E.T. and D.W.; investigation, formal analysis, validation, data curation and visualization, E.T. and D.W.; experiments, E.T., M.H. and D.W. writing—original draft preparation, E.T., D.W., M.H., H.L., A.S.-M., and H.-J.B.; writing—review and editing, D.W. and E.T., H.L., H.-J.B. and A.S.-M.; supervision, H.L., H.-J.B. and A.S.-M.; project administration and funding acquisition, H.-J.B. and A.S.-M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** The support of Holger Eisenschmidt is gratefully acknowledged.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
