(187g) A Workflow for the Fabrication of Innovative Crystallizers Using 3D-Printing

3D printing offers the unique possibility to fabricate customized process equipment at reduced cost and without compromising on the fabrication time. The high potential of 3D printing as a manufacturing technology can especially be exploited for the fabrication of process equipment with a complex geometry and no moving components. These advantages of 3D printing have been exploited for the fabrication of micro and meso-scale reactors.^1,2In particular, all of the four major 3D printing techniques (i.e., stereolithography³, selective laser sintering⁴, polyjet printing⁵and fused deposition molding⁶) have been used in the fabrication of reactors. Despite the wide utilization in reaction engineering, 3D printing has found limited applications in the fabrication of equipment for separation processes, including crystallization. Crystallization is an important separation and purification technology in various industries such as the fine chemical and pharmaceutical industry. Recently, we have developed a 3D-printed airlift crystallizer for batch protein crystallization⁷. 3D printing proved to be useful due to the need for customization of the complex geometry and the absence of moving parts in such crystallizer. Furthermore, crystallization processes often operate under mild conditions, which allows for different types of materials to be used. Other types of crystallizers may also be fabricated efficiently with 3D printing. For example, tubular crystallizers with mixing internals^8,9would be another class of innovative crystallizers that could utilize the advantages offered by 3D printing. Different types of crystallizers may require different 3D printing techniques. Furthermore, in general, a workflow that guides decision making when using 3D printing to fabricate prototype crystallizers can facilitate faster adoption by industry. However, such workflows or advisory documents are currently lacking.

The objective of this work is to present a workflow that will guide a user through the different steps and decisions that are needed to use 3D printing for the physical realization of a crystallizer. The major steps in the development of the crystallizer include, selection of crystallizer type, sizing of the equipment based on the process requirements, an optional step for computational analysis (e.g., CFD simulations), selection of an appropriate 3D printing technique, detailed 3D drawing of the equipment, selection of a 3D printer and the material, fabrication of the equipment and finally testing. An important step in the development of a crystallizer is the selection of an appropriate 3D printing technique. The key considerations involved in the selection of the 3D printing technique include the required accuracy, build resolution, ease of the removal of the unused material and support structures, if any, and the ability to print stable leak-proof parts. An additional advantage is that the fabrication speed and lower fabrication cost with 3D printing makes it possible to have multiple iterations of the above-mentioned workflow in a relatively short duration, which is difficult to achieve with traditional manufacturing methods. A workflow detailing the above-mentioned steps will be presented. Finally, the application of the workflow will be demonstrated for the case of an airlift crystallizer. The possibility to fabricate innovative process equipment rapidly and at a lower cost makes 3D printing an attractive manufacturing technology in situations where early learning of the process is important but time to market has to be as fast as possible or when the attrition rate of new product concepts is high, such as in the pharmaceutical industry.

Acknowledgement: The work described in this abstract was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China, Project No. 16242916.

References

(1) Kitson, P. J.; Rosnes, M. H.; Sans, V.; Dragone, V.; Cronin, L. Configurable 3D-Printed Millifluidic and Microfluidic “lab on a Chip” Reactionware Devices. Lab Chip2012, 12(18), 3267–3271.

(2) Lin, C. G.; Zhou, W.; Xiong, X. T.; Xuan, W.; Kitson, P. J.; Long, D. L.; Chen, W.; Song, Y. F.; Cronin, L. Digital Control of Multistep Hydrothermal Synthesis by Using 3D Printed Reactionware for the Synthesis of Metal–Organic Frameworks. Angew. Chemie - Int. Ed.2018, 57(51), 16958–16962.

(3) Okafor, O.; Weilhard, A.; Fernandes, J. A.; Karjalainen, E.; Goodridge, R.; Sans, V. Advanced Reactor Engineering with 3D Printing for the Continuous-Flow Synthesis of Silver Nanoparticles. React. Chem. Eng.2017, 2(2), 129–136.

(4) Maier, M. C.; Lebl, R.; Sulzer, P.; Lechner, J.; Mayr, T.; Zadravec, M.; Slama, E.; Pfanner, S.; Schmölzer, C.; Pöchlauer, P.; et al. Development of Customized 3D Printed Stainless Steel Reactors with Inline Oxygen Sensors for Aerobic Oxidation of Grignard Reagents in Continuous Flow. React. Chem. Eng.2019,4(2), 393–401.

(5) Lee, K. G.; Park, K. J.; Seok, S.; Shin, S.; Kim, D. H.; Park, J. Y.; Heo, Y. S.; Lee, S.-J.; Lee, T. J. 3D Printed Modules for Integrated Microfluidic Devices. RSC Adv.2014, 4, 32876–32880.

(6) Rossi, S.; Porta, R.; Brenna, D.; Puglisi, A.; Benaglia, M. Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D-Printed Mesoreactors. Angew. Chemie - Int. Ed.2017, 56(15), 4290–4294.

(7) Mathew Thomas, K.; Lakerveld, R. A 3D-Printed Airlift Crystallizer for Protein Crystallization. Submited2019.

(8) Alvarez, A. J.; Myerson, A. S. Continuous Plug Flow Crystallization of Pharmaceutical Compounds. Cryst. Growth Des.2010, 10(5), 2219–2228.

(9) Yang, H.; Peczulis, P.; Inguva, P.; Li, X.; Heng, J. Y. Y. Continuous Protein Crystallisation Platform and Process: Case of Lysozyme. Chem. Eng. Res. Des.2018, 136, 529–535.