*1.2. Shadowgraphic Optical Probe and Online Microscope*

The in situ data of the experimental investigations in this study were recorded with two measurement systems: a commercial QICPIC online microscope (Sympatec, Germany) installed in a bypass and a shadowgraphic inline probe. The online microscope was using the transmitted light technique, where a pulsed light source is vis-à-vis of a camera. The measurement volume was formed by a flow-through cuvette that was placed between the optics and the light source. The parts were adjusted, so that the focus plane was in the middle of the cuvette. Thus, particles that were transported through the cell were captured sharply, with constant image quality.

A peristaltic pump fed the suspension via a temperature-controlled bypass to the cuvette and back to the crystallizer. The measurement volume had a fixed width of 2 mm given by the cuvette geometry. The camera and lens provided a square field of view of 5 mm in height and width at a resolution of 1024 pixel × 1024 pixel. The microscope software supports an autofocus function to adjust the focus plane of the camera in the middle of the flow cell, alternatively it could be adjusted manually.

The shadowgraphic probe is a further development of the so-called optical multimode online probe (OMOP) [48,49]. The primary design of the probe is based on a transmitted light technique and consists of two opposite protection tubes in a measurement flange.

One tube contains the illumination unit and the other one the camera and a telecentric lens. The light source consists of a LED placed in the focus point of a plano-convex lens, which emits a parallel light beam. The light beam is passed through the measurement volume between the two tubes, which are sealed with inspection windows in the front. Through the parallel light, high contrast images of the particles within the measurement volume can be acquired, even if the particles are nearly transparent.

In contrast, commercial image-based probes apply an incident light technique with an endocentric optics. In comparison, these probes have lower contrast ratios and natural image distortion is easily caused by the illumination and the optics [50,51]. Therefore, image analysis is quite challenging and requires significant effort to achieve quantitative results [52]. Furthermore, the depicted particles captured by the camera appear smaller, the larger the distance from the entocentric lens, and need sophisticated correction. Due to a comparably small focus areas, only a limited number of particles can be evaluated.

Alternatively, telecentric lenses provide a distant independent image of the particles when using parallel light. An aperture in the image-sided focus point of the lens filters out non-parallel light beams and, thus, shadowgraphic pictures are generated by parallel light only. Hence, no prior calibration is necessary. In addition, these lenses have higher depth of field compared to entocentric lenses, therefore having a large measurement volume instead of a focus plane. Hence, various versions of the OMOP for different applications, like capturing droplets [53,54], bubbles [55–57], or sprays [58,59] were developed.

In order to achieve easier access to an apparatus and to promote industrial applications, two probes have been designed recently; first, a robust DN 80 variant for industrial applications, with the full functionality of the two-sided OMOP principle [60]. Second, as a further development, a single sided endoscopic probe in DN 50 version was designed for laboratory scale [56,61], and was used for the experiments of this article. The probe has an adjustment mechanism where the position inside the apparatus and width of the measurement volume can be changed, even during the crystallization process, to adapt it to the increasing particle concentration (see Figure 1).

**Figure 1.** One-sided DN 50 telecentric shadowgraphic probe for laboratory scale published in [56,61].
