crystallization; monitoring; morphology; control; particle size distribution
Bötschi Stefan, Rajagopalan Ashwin Kumar, Rombaut Igor, Morari Manfred, Mazzotti Marco (2019), From needle-like toward equant particles: A controlled crystal shape engineering pathway, in Computers & Chemical Engineering
, 131, 106581-106581.
Bötschi Stefan, Rajagopalan Ashwin Kumar, Morari Manfred, Mazzotti Marco (2019), Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. IV. Modeling and Control of Dissolution, in Crystal Growth & Design
, 19(7), 4029-4043.
Rajagopalan Ashwin Kumar, Bötschi Stefan, Morari Manfred, Mazzotti Marco (2019), Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. III. Wet Milling, in Crystal Growth & Design
, 19(5), 2845-2861.
Rajagopalan Ashwin Kumar, Bötschi Stefan, Morari Manfred, Mazzotti Marco (2018), Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. II. Cooling Crystallization Experiments, in Crystal Growth & Design
, 18(10), 6185-6196.
Bötschi Stefan, Rajagopalan Ashwin Kumar, Morari Manfred, Mazzotti Marco (2018), An Alternative Approach to Estimate Solute Concentration: Exploiting the Information Embedded in the Solid Phase, in The Journal of Physical Chemistry Letters
, 9, 4210-4214.
Bötschi Stefan, Rajagopalan Ashwin Kumar, Morari Manfred, Mazzotti Marco (2018), Feedback Control for the Size and Shape Evolution of Needle-like Crystals in Suspension. I. Concepts and Simulation Studies, in Crystal Growth & Design
, 18(8), 4470-4483.
Rajagopalan Ashwin Kumar, Schneeberger Janik, Salvatori Fabio, Bötschi Stefan, Ochsenbein David R., Oswald Martin R., Pollefeys Marc, Mazzotti Marco (2017), A comprehensive shape analysis pipeline for stereoscopic measurements of particulate populations in suspension, in Powder Technology
, 321, 479-493.
Bötschi Stefan, Ochsenbein David R., Morari Manfred, Mazzotti Marco (2017), Multi-Objective Path Planning for Single Crystal Size and Shape Modification, in Crystal Growth & Design
, 17(9), 4873-4886.
Ochsenbein David R., Vetter Thomas, Morari Manfred, Mazzotti Marco (2015), Agglomeration of Needle-like Crystals in Suspension. II. Modeling, in Crystal Growth & Design
, 15(9), 4296-4310.
CrystOCAM 2.0 is a proposed follow-up project for a currently ongoing undertaking of the same name (SNF project number 200021-135218). CrystOCAM 2.0 aims at the design and further refinement of a new generation of process analytical technology (PAT) tools and software that allow for an unprecedented capability to measure, model and control the size and shape of crystals during crystallization from solution. The importance of crystallization in the pharmaceutical, food and fine chemical industries stems from its ability to yield highly pure solid products. Beside the final chemical purity, however, the solid state form, the size and the shape of the resulting particles are of paramount importance for the product quality, because they determine characteristics such as filterability, tabletability, flowability and even bioavailability. Practitioners in these industries are well aware of the fact that crystals can take on a variety of shapes, even for the same chemical substance. Any form of control over particle size and especially shape should allow for the design of improved processes. Until recently, however, the optimization of crystallization processes in terms of particle morphology has been hindered by a major obstacle: The lack of reliable, fast and quantitative measurement devices, which prohibited the online monitoring and hence modeling and optimization. The measurement setup and the analysis protocols developed in CrystOCAM are reliable, sensitive as well as accurate and therefore recognized by the scientific community as valuable contributions. Using these newly developed techniques, concepts and phenomena have been uncovered that could not have been monitored in a quantitative fashion prior to the CrystOCAM project. Given these developments, additional opportunities to ask and answer more complex questions have emerged, which are not only of interest from a purely scientific point of view, but also possess the potential to impact industrial applications. These considerations can be categorized into two major research directions which we would like to pursue within the scope of a follow-up project (CrystOCAM 2.0), namely: the study of single crystals and the evaluation of advanced shape manipulation concepts by unconventional processing techniques. The first point, initially motivated by an unexpected discovery during the monitoring of crystal growth of particle ensembles (a significant broadening of the shape distribution; see below), will permit a focused, separate investigation of crystal growth under idealized and highly controlled conditions. The resulting information in turn may be used to shed light on the mechanistic details affecting entire distributions. The second subject aims at expanding the list of decision variables that allow tuning particle shape, e.g., through the introduction of inline milling or temperature cycling.Both subjects would profit from the knowledge and tools that have been developed during the fruitful cooperation of the previous venture and would further advance the field of particle shape measurement, modeling, and control. With the tackling of more complex processes and an additional, heightened focus on the behavior of single crystals, CrystOCAM 2.0 will continue to improve the understanding of fundamental aspects of crystal shape evolution in crystallization processes as a whole.The work is to be carried out by two doctoral students at two groups at ETH Zurich, the Separation Processes Laboratory (SPL) headed by Prof. Marco Mazzotti and the Automatic Control Laboratory (IfA) headed by Prof. Manfred Morari.The following deliverables are expected:- Design of a novel apparatus capable of measuring the exact morphology of single crystals in suspension in real time, allowing the determination of growth and dissolution kinetics of individual facets and helping to acquire data useful for determining the influence of surface defects in seed particles.- A set of verified dynamic models for additional, more complex dynamic processes, such as growth and dissolution cycles, agglomeration and needle breakage.- Development of novel controller structures that are based on the knowledge obtained from both simulations and experiments of the above mentioned complex processes. - Experimental investigations into the practical feasibility and efficacy of the proposed schemes.