Advancing Discovery and Growth of Crystalline Materials using Continuous-Flow, Well-Mixed Microfluidic Devices

Significance 

Crystallization is an important step in various industrial applications. However, due to the various factors involved, developing effective and controlled crystallization processes have remained a long-time challenge. This has recently attracted research attention owing to its considerable effects on the physical properties of the resulting crystals. Presently, prediction of the crystallization taking into consideration the polymorphs, morphology and crystal sizes depend mainly on the estimated model parameters. Unfortunately, the prediction accuracy is limited to the range of crystallization within the model parameters.

To facilitate the design of crystallization processes in the early stages of materials discovery, the focus has shifted to the development of experimental screening techniques that can screen several factors to obtain specific crystal polymorphs and morphology. Based on the size scales, these techniques include mL-1 L batch crystallizers, mini-batch crystallizers, microfluidic device, and microtiter plates.

Recent advancement of screening techniques includes miniaturizing the compartments to accommodate several experiments in a single device. Whereas the external conditions i.e. temperature and solvent composition can be kept constant, the decrease in the internal conditions i.e. supersaturation greatly influence the formation of the polymorphs and morphology. Additionally, supersaturation has considerable effects on the crystallization kinetics, morphology and crystal sizes which may also lead to the gravitation of the produced polymorphs into different undesirable forms. Therefore, the development of a more controlled screening technique permitting nucleation and growth of crystals in a controlled supersaturation crystallization manner is highly desirable.

To this note, University of Illinois at Chicago researchers: Paria Coliaie (PhD candidate) and Dr. Meenesh Singh together with Dr. Manish Kelkar and Dr. Nandkishor Nere at the Center of Excellence for Isolation & Separation Technologies (CoExIST), Process R&D, AbbVie Inc. have developed an innovative continuous-flow, well-mixed microfluidic device for effective screening of polymorphs and morphology in a controlled supersaturated environment. Generally, the device depends on the continuous flow of solvents and antisolvents to create a vortex in the micromixer to allow the continuous crystallization of the solute at constant supersaturation. The scientists developed and validated their continuous-flow microfluidic device for the screening of crystal polymorphs at controlled supersaturation environments. The work was published and was featured on the cover of the research journal, Lab on a Chip.

Briefly, the research team cross-examined different types of microfluidic devices: T-junction, cell sorter, cross-flow, H-shaped and cyclone mixture. These devices typically entail three critical sections i.e. thermalizer used for cooling or heating the entering solution, mixer for mixing the antisolvent and solution and a diffuser to isolate the crystal from the flowing solution. Particularly, the H-shaped and cyclone mixer designs were used to validate the crystallization at constant supersaturation.

The developed device allowed for continuous crystallization of the solute through cooling the saturated solution or mixing the antisolvent. This was attributed to the fact that the H-shaped design was effective for screening crystals with slower kinetics while the cyclone mixer was used for crystals with faster kinetics. To actualize the study, it was necessary to analyze the polymorphs and morphology of o-aminobenzoic acid at different supersaturations and the results compared to that of the microtiter design. Interestingly, the design was observed to constantly screen stable polymorphs unlike in the microtiter plate where the polymorphs were affected by the depleting supersaturation. Altogether, the study by Dr. Meenesh Singh and the research team provides an excellent solution that will advance continuous manufacturing operations in pharmaceuticals industry and other materials manufacturing industries.

Advancing Discovery and Growth of Crystalline Materials using Continuous-Flow, Well-Mixed Microfluidic Devices - Advances in Engineering

About the author

Paria Coliaie is currently a PhD student in the department of chemical engineering at the University of Illinois at Chicago (UIC), where she is supervised by Prof. Meenesh Singh. She received her BS in Chemical Engineering from Sharif university of Technology in 2016. She joined UIC in 2016 as graduate research assistant.

Her research is focused on development of microfluidic Lab-on-a-Chip platforms for pharmaceuticals, and high-throughput screening of crystal growth, nucleation and polymorph.”

About the author

Manish S Kelkar received his B.E. degree in Chemical Engineering from ICT, Mumbai in 2002, and his Ph.D. in Chemical Engineering from the University of Notre Dame in 2007 under the guidance of Prof Ed Maginn. After doing 2 years of postdoctoral research at DuPont and University of Delaware (Prof Norman Wagner), he joined DuPont CR&D at the Experimental Station in Wilmington DE. About 2.5 years ago he moved to Abbvie where he focuses on developing separation processes-especially crystallization, filtration, and drying. He is an avid football follower- both college and the NFL.

About the author

Nandkishor Nere completed his Ph.D. with Professor J. B. Joshi at the Institute of Chemical Technology, Mumbai in the area of ‘Transport Phenomena in Multiphase Reactors’ with an emphasis on the CFD modeling of turbulence and mixing in stirred tanks. He joined Abbott Laboratories in 2008 after working with Professor Ramkrishna at Purdue University on post-doctoral assignments related to the application of population balance modeling, CFD and applied mathematics for liquid-liquid dispersions, crystallization and milling. He rejoined AbbVie in 2013 after a brief stint as a General Manager in Aditya Birla Science and Technology Company in India where he led a group on Advanced Engineering and Process Scale-up.

He founded a cross-functional modeling forum comprising of 45+ scientist and engineers at AbbVie and is leading a Center of Excellence for Particle Design and PAT. Amongst various awards, he also received AbbVie R&D President’s award for innovative contributions to the process development of a leading late stage API. He is author/co-author of 21 research publications and a book chapter on ‘Mathematics in Chemical Engineering’ in Albright’s Chemical Engineering, edited by Albright, L. CRC Press, 2008. He has delivered 23 conference presentations and seminars He was a guest editor of the special issue on Advances in Computational Fluid Dynamics in International Journal of Chemical Engineering, 2012.

About the author

Meenesh R. Singh: Meenesh Singh is an assistant professor in the Department of Chemical Engineering, and the director of Materials and Systems Engineering Lab (MaSEL) at UIC, where his research group is developing state-of-the-art computational and experimental tools to solve grand challenges of the 21st century – i) develop carbon sequestration methods, ii) manage nitrogen cycle, iii) provide access to clean water and iv) engineer better medicines. Dr. Singh obtained his B. E. degree in chemical engineering from Sardar Patel University in 2005, M. Tech. degree in chemical engineering from Indian Institute of Technology Bombay in 2008 and Ph. D. in chemical engineering from Purdue University in 2013. His doctoral research at Purdue University was under the guidance of Prof. D. Ramkrishna, where he developed novel computational and experimental tools to study shape evolution of crystals. After his Ph.D., he joined UC Berkeley as a Postdoctoral Fellow to work with Prof. Rachel A. Segalman (2013-14) and Prof. Alexis T. Bell (2014-16) on artificial photosynthesis.

He has developed various artificial photosynthetic systems for water-splitting and CO2 reduction. His research resulted in > 29 publications in high impact journals including PNAS and Energy & Environmental Science, >60 presentations at international conferences, and >9 invited talks. He a reviewer for >20 leading journals.

Reference

Coliaie, P., Kelkar, M., Nere, N., & Singh, M. (2019). Continuous-flow, well-mixed, microfluidic crystallization device for screening of polymorphs, morphology, and crystallization kinetics at controlled supersaturation. Lab on a Chip, 19(14), 2373-2382.

Go To Lab on a Chip

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