(4ae) Process Intensification in Chemical Engineering & Crystallization: Improving and Robustifying the Engineered and the Engineer

Research Interests: Crystallization, Process Intensification, Process Control & Design, Active Ingredient Manufacturing, Energetic Materials, Pharmaceuticals, Critical Minerals, Desalination

Process Intensification

Originally defined in the 1990s as the size or footprint reduction of a given process, process intensification in the chemical engineering community is the act of encapsulating a variety of process improvements from optimization to design and control (1). However, not all these process variations represent the mission and call for process intensification originally posed to the community in the 2000s (2).

My lab will address this multifaceted call for process intensification, developing new equipment, and process methods specific to the current industrial crystallization challenges as well as processing chemical processing steps surrounding crystallization.

Strategic Transition of Energetics Manufacturing to Domestic Operations

First manufactured for use in World War II, Research Department/Royal Demolition Explosive (RDX) and High Melting Explosive (HMX), have been applied to military munitions, propellants, and general explosives and continue to be two of the largest manufactured energetic materials among other, new materials (e.g., CL-20). Although the defense community relies on these materials, the amount of manufacturing is reliant on non-domestic sources for processes presents potentially catastrophic supply chain issues. Also, onshore manufacturing processes lack intensification, control, or optimization and are often manufactured with technology dating back over a century. During my Ph.D. I have developed both experimental and computational methods of process intensification of energetic materials manufacturing. Spanning from the application of model-free quality by control direct design approaches and the development of a digital twin which enabled the in-silico design of experiments and design space analysis of multiple industrial energetics manufacturing systems (3-6). My lab will grow from these foundational developments of process intensification techniques by developing novel equipment, unique process pathways, and recycling techniques for strategically redeveloping, and distributing the domestic manufacturing of munitions and their components.

Enhancing Product Quality by Controlling Solid-State Crystal Form

Currently, over 80% of active pharmaceutical ingredients exhibit polymorphism, introducing potential impacts on bioavailability, solubility, morphology, manufacturability, and process behavior (7). This is only predicted to increase with time and with the complexity of new active ingredient molecules. This trend highlights the importance of research that identifies and navigates the crystallization and separation processes required to control polymorphism, the phenomenon when a molecule can exist in multiple crystalline forms. Current standards in crystal form identification heavily rely on the factorial design of experiments and solvent screening which have been improved with high throughput screening equipment (8-9). However, this understanding and approach are generally unguided and require exhaustive searches of the chemical operating space. Recently I have shown the design and control of continuous crystallization processes for the control of polymorphism, metastable and stable at steady-state, through the tuning of key process parameters by leveraging the fundamental driving forces of polymorphism. My lab will research the phenomenological reasons for polymorphism and how a more generic, yet chemistry-specific, approach to the phenomena will open doors for faster and more robust process development for polymorphic crystallization systems. Further understanding of polymorphic form will necessarily increase safety and promote sustainable solids-purification through solvent reduction and green chemistry.

Developing Recycling Pathways Toward Circular Economy for Critical Minerals and Seawater Brine through Crystallization

As defined by the Department of Energy, there exists the “Electric Eighteen”, eighteen critical materials and minerals that are crucial for the production, storage, and conservation of energy (10). The isolation and purification of such materials from wastewater, reactor effluents, and recyclable materials is mostly approached with the combination of membrane distillation and crystallization. However, the current state-of-the-art recovery processes are largely energy and resource-intensive (11). Additionally, the products of membrane distillation (water, and concentrated brine) exacerbate environmental issues by producing a more hazardous stream than the input and contaminating another critical resource (water). This cyclical flaw in sacrificing one critical resource for another can be observed across systems engineering but is frequently amplified during the separation and/or crystallization step of the process. My lab will implement process intensification strategies across mining, desalination, and critical mineral capture by focusing on crystallization and precipitation. We aim to create novel pathways for resource recovery through multifunctional process equipment, green separations, and life cycle analysis to slow and address the consumption of these critical minerals and resources, promoting recycling and a more circular economy to avoid dependence abroad on resource availability.

All sectors of active ingredient and fine chemical processing face crystallization challenges, none of which have a catch-all solution. As the complexity of molecules continues to increase, so does the complexity of their unique challenges and eventual solutions. In my future research group, I will utilize my expertise in developing crystallization design and control strategies, my unique perspective and experience in building a lab safety culture, and my passion for mentorship, teaching, and leadership to answer the growing problems of modern crystallization challenges such as polymorphism phenomena, critical mineral capture, and other unique crystallization process design and control challenges through the implementation of process intensification strategies.

Teaching Interests

I am qualified to teach all core chemical engineering material and have practical experience in Process Dynamics and Controls, and Design and Analysis of Processing Systems at Purdue University. My primary interests and expertise lend way to teaching courses on process systems engineering, crystallization phenomena, and pharmaceutical process development. I have a natural passion for teaching and a desire to pay it forward to the next generation of chemical engineers through mentorship and interactive learning strategies that will not only prepare them for careers as chemical engineers but also stimulate their unique passions and guide them toward the applications and disciplines where they can best serve the chemical engineering community.

AIChE Presentations This Year

• Process Control, Design, and Modeling of the Steady-State Continuous Crystallization of an Industrial Polymorphic Agrochemical
  • Plenary Session: Crystallization and Evaporation - Area 2B (Invited Talks)
  • Monday, October 28, 2024
  • 1:38 PM - 1:58 PM
  • Room 31C (Upper Level, San Diego Convention Center)
• Investigation of Pre-Nucleation Phenomena for Strategic Process Design of an Industrial Agrochemical Antisolvent Crystallization Experiencing Unique Phase Separations
  • Solid Form Characterization and Development: Cocrystals, Salts, Solvates, Polymorphs, and Beyond
  • Thursday, October 31, 2024
  • 1:09 PM - 1:27 PM
  • Room 31C (Upper Level, San Diego Convention Center)

References

1. Ramshaw, C. "The incentive for process intensification." BHR Group Conference Series Publication. Vol. 18. Mechanical Engineering Publications Limited, 1995.
2. Stankiewicz, Andrzej I., and Jacob A. Moulijn. "Process intensification: transforming chemical engineering." Chemical engineering progress 96.1 (2000): 22-34.
3. Smith M, Mackey J, Laky D, Neal M, Doukkali M, Mudryy R, Diallo B, Gauthier E, Nagy ZK. “Digital Design for Batch Cooling Crystallization of Royal Demolition eXplosive (RDX)”. JANNAF Journal (2023), submitted.
4. Smith M, Nagy ZK. JANNAF Journal (2023), submitted.
5. Smith M, Neal M, Mackey J, Gonzalez M, Nagy ZK. JANNAF Journal (2023), submitted.
6. Wu WL, Smith M, Mackey J, Neal M, Nagy ZK. JANNAF Journal (2023), submitted.
7. Hilfiker, R. “Polymorphism in the Pharmaceutical Industry”. John Wiley, 2006.
8. Alvarez, Alejandro J., Aniruddh Singh, and Allan S. Myerson. "Polymorph screening: comparing a semi-automated approach with a high throughput method." Crystal Growth and Design 9.9 (2009): 4181-4188.
9. Simone, Elena, et al. "A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystal morphology for pharmaceutical compounds." Lab on a Chip 18.15 (2018): 2235-2245.
10. “What Are Critical Materials and Critical Minerals?”. Critical Minerals & Materials Program (2023). https://www.energy.gov/cmm/what-are-critical-materials-and-critical-min….
11. Pramanik, Biplob Kumar, et al. "A critical review of membrane crystallization for the purification of water and recovery of minerals." Reviews in Environmental Science and Bio/Technology 15 (2016): 411-439.