Assistant Professor, Department of Chemical and Life Science Engineering | Chemical and Life Science Engineering
Richmond, VA, UNITED STATES, Biotech 8, 419A
Advance material manufacturing for health and energy applications
Ph.D., Chemical Engineering
M.S., Chemical Engineering
Virginia Business online
“Our goal is to improve the batteries so that they can last longer, be more durable and safer,” Gupta said in a statement. He will work with Mo Jiang, a VCU assistant professor, and Parans Paranthaman, a corporate fellow at Oak Ridge National Laboratory.view more
With expanding demand of lithium-ion batteries in portable electronic devices, such as smartphones and iPads and environmental-friendly vehicles (e.g., electric and hybrid vehicles), it is important to further improve safety, extend battery life, increase charge capacity, and reduce cost. A key missing component is effective and efficient manufacturing of complex active cathode materials, such as nickel-cobalt-manganese oxide micron-sized particles, at needed production scales. Cathode microparticle quality and uniformity are difficult to control with current reactor technologies, requiring post-synthesis procedures such as milling and sieving to narrow the particle size distribution. This risks product quality and reduces production efficiency. An innovative slug-flow reactor manufacturing process is developed to directly produce well-controlled microparticles for advanced battery performance and accelerated scale-up. The availability of controllable cathode materials makes electronic devices using lithium-ion batteries safer and of better quality at a lower cost. One impact of this research is reduced environmental impact due to efficient materials use and increased battery life.view more
In the pharmaceutical and chemical industries, the continuous generation of crystals of target size distribution has the potential to improve efficiency for post-crystallization operations. The control of crystallization processes can be challenging when undesirable phenomena such as particle attrition and breakage occur. Segmented/slug flow crystallization is one of the effective continuous processes demonstrated to allow enhanced control of organic crystal properties such as size and shape. The slurry flow is combined with an air flow and fed to a tube to induce a multiphase hydrodynamic instability that spontaneously generates well-mixed slugs where the crystals continue to grow. The slug flow continuous crystallization platform is developed and process designed for important pharmaceuticals.
Department of Energy $2.5M (PI: Gupta, co-PIs: Jiang, Paranthaman)
Advanced Slug-flow Manufacturing of Uniform and Tunable Battery Cathode Particlesview more
National Science Foundation $529K (PI: Jiang, co-PI: Gupta)
This research is to develop a new process for the manufacture of uniform nickel-cobalt-manganese (NCM) oxide microparticles to serve as cathodes in lithium-ion batteries. It explores a continuous slug-flow manufacturing technology. Microscopically, in a slug-flow reactor, each particle experiences the same environment with spatially uniform reaction kinetics and hydrodynamics conditions throughout the nucleation and growth process, leading to uniform particles with controlled compositions, microstructures and properties. Macroscopically, the manufacturing setup and conditions can remain the same while allowing convenient tuning of the production rate, i.e., scaling up or scaling down. The slug flow process is also equipped with in-line bright-field imaging for microparticle monitoring and quality control. The research advances the fundamental understanding of microparticle nucleation, growth, and reaction engineering. It also studies the link between microparticles with high uniformity and controlled spatial composition and battery performance, which sheds light on a rational way to produce next-generation battery materials.view more
Boehringer-Ingelheim Pharmaceuticals Inc. $140K (PI: Jiang)
This project includes: (1) the process design and strategies for continuous slug-flow crystallization that controls the crystallization phenomena; (2) the tuning of crystal properties without changing the equipment set-up. Process intensification strategy is also developed and applied which makes the whole process more robust. Experimental validation confirms that the proposed crystallizer designs reduce production time and equipment cost evidently while suppressing secondary nucleation, attrition, and aggregation—dominant but undesired phenomena that worsen the ability to control the crystal properties.
Bill and Melinda Gates Foundation $25M (PI: Gupton, co-PIs: Jiang and others)
Help increase access to lifesaving medications for HIV/AIDS, malaria, tuberculosis and other diseases around the worldview more
The goals of this core course are to train undergraduate students to develop mathematical models that involve material and energy balance equations for dynamic single and multi-unit reactive and non-reactive chemical processes with recycle and bypass streams. Students will also learn to define transfer functions that relate the input and output variables in the system and understand the dynamics of first-, second-, and higher-order systems by quantitatively describing the system response to inputs, such as step changes. Finally, students will apply a variety of techniques that enhance feedback control that include designing a simple feedback control loop, performing stability analysis on feedback and cascade systems and tuning control loops and address safety.
This graduate-level core course builds upon foundations of chemical reaction engineering with a goal of educating students to apply contemporary tools for the analysis and design of modern chemical reactor systems. The course will provide a review of chemical reaction engineering principles before progressing to advanced topics. Advanced material in this course will include the development of mathematical models and computational implementation to simulate reacting systems and experimental approaches to determine reaction parameters and mechanisms. Additional materials will cover current approaches of industrial crystallization for production, purification, and formulation of solid chemicals.
The goals of this core course for pharmaceutical engineering are to help students to understand the principles, know state-of-the-arts, and gain practical experience of important process analytical technology. Specifically, the operation and techniques of analytical instrumentation commonly used, for in-line monitoring/control, on-line or off-line analysis. Also, students will get better understanding and preventing common mistakes on data collection (e.g., sampling), data comprehension, and data analysis (e.g., chemometrics).
M. Mou, M. Jiang
Glycine has been widely used as pharmaceutical excipients and synthesis reagents, and commercial glycine has a significant amount of aggregation and wide particle size distribution. A simple but reproducible process for generating uniform glycine crystals is always desired for both product quality and process efficiency purposes. Glycine crystals of α-form and narrow size distribution can be continuously generated within 10 min from cooling crystallization in millimeter-sized slug flow, without using external seeds nor adding solvent/additives. And, the operational boundaries of crash cooling time (at proper starting concentrations) for pure α-form non-aggregating product crystals are identified.view more
M. Jiang, R. D. Braatz
Crystallization is an effective, low-cost purification & formulation process widely applied to pharmaceuticals and fine chemicals. This review describes recent advances in research on lab-scale solution-based continuous crystallization, including (1) a 5-step general design procedure; (2) key design/operational parameters; (3) process intensification strategies; and (4) a case study. The continuous crystallizers reviewed include mixed-suspension mixed-product removal, fluidized beds, oscillatory baffled flow, and tubular laminar/segmented/slug-flow crystallizers. Their corresponding design and operational considerations are summarized in terms of general parameters (e.g., residence time), and crystallizer-specific parameters and strategies (e.g., mixing strategies). In-line nucleation and crystal modification methods are categorized, including use of micromixers, wet milling, ultrasonication, temperature cycling, and recycling selection (filtration, sedimentation). Throughout the article, links are drawn with extensive existing knowledge of batch crystallizers, to facilitate the understanding and design of continuous crystallizers.view more
M. S. Hong, K. Severson, M. Jiang, A. E. Lu, J. C. Love, R. D. Braatz
This article provides a perspective on control and operations for biopharmaceutical manufacturing. Challenges and opportunities are described for (1) microscale technologies for high-speed continuous processing, (2) plug-and-play modular unit operations with integrated monitoring and control systems, (3) dynamic modeling of unit operations and entire biopharmaceutical manufacturing plants to support process development and plant-wide control, and (4) model-based control technologies for optimizing startup, changeover, and shutdown. A challenge is the ability to simultaneously address the uncertainties, nonlinearities, time delays, non-minimum phase behavior, constraints, spatial distributions, and mixed continuous-discrete operations that arise in biopharmaceutical operations. The design of adaptive and hybrid control strategies is discussed. Process data analytics and grey-box modeling methods are needed to deal with the heterogeneity and tensorial dimensionality of biopharmaceutical data. Novel bioseparations as discussed as a potential cost-effective unit operation, with a discussion of challenges for the widespread application of crystallization to therapeutic proteins.view more
M. Jiang, K. A. Severson, J. C. Love, H. Madden, P. Swann, L. Zang, and R. D. Braatz
Real‐time release testing (RTRT) is defined as “the ability to evaluate and ensure the quality of in‐process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls” (ICH Q8). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small‐molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality—with improved productivity including faster release and potentially decreased costs—all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on‐line and in‐line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT.view more
M. L. Rasche, M. Jiang, and R. D. Braatz
Inspired from experimental progress in continuous crystallizer designs based on air/liquid slug flow that generate crystals of target sizes at high production rates and low capital costs, a mathematical model and procedure are derived for the design of slug-flow crystallizers with spatially varying temperature profiles. The method of moments is applied to a population balance model for the crystals, to track the spatial variation of characteristics of the crystal size distribution along the crystallizer length. Design variables for the cooling slug-flow crystallizer such as tubing lengths and types and numbers of heat exchangers are analyzed and optimized for product crystal quality (e.g., minimized secondary nucleation and impurity incorporation) and experimental equipment costs, while ensuring high yield. This study provides guidance to engineers in the design of slug-flow crystallizers including their associated heat exchanger systems.view more
M. Jiang, C. Gu, and R. D. Braatz
The discovery that crystal nuclei can be generated by combining hot and cold saturated solutions in a dual-impinging-jet (DIJ) mixer motivates the theoretical analysis in this article. Nucleation is shown to be facilitated in solute–solvent systems that have much higher energy transfer than mass transfer rates near the impingement plane between the two jets. One- and two-dimensional spatial distributions of velocity, temperature, concentration, and supersaturation provide an improved understanding of primary nucleation in cooling DIJ mixers. In the most important spatial region for characterization of nucleation, the two-dimensional fields are shown to be very close to analytical solutions derived from a one-dimensional approximation of the energy and molar balances. This simplification enables the derivation of design criteria that facilitates assessment of whether any particular solute–solvent combination will nucleate crystals in a cooling DIJ mixer, based on the physicochemical properties of the system. These criteria could save time and material by avoiding or reducing trial-and-error experiments, which is helpful at the early stage of pharmaceutical process development.view more
M. Jiang, C. D. Papageorgiou, J. Waetzig, A. Hardy, M. Langston, and R. D. Braatz
Continuous-flow solution crystallization is an approach to manufacture pharmaceutical crystals with improved control of product characteristics, simplified postcrystallization operations, higher production rate flexibility, and reduced capital costs and footprint. An indirect ultrasonication-assisted nucleation process is designed to vary the seed generation rate during operation independent of mass flow rate, by varying the ultrasonication power. The ultrasonication probe is pressed against a tube to generate a spatially localized zone within the tube inside of a temperature bath for the generation of crystal nuclei without heating or contaminating the supersaturated solution. This nucleation design is integrated into a continuous slug-flow crystallization process to generate uniform-sized product crystals within each slug at a high supersaturation level and a short residence time of ∼8.5 min, without inducing significant secondary nucleation. By increasing size uniformity, the indirect ultrasonication-assisted slug-flow crystallizer has potential as a final crystallization step to produce crystals for direct compression tableting without having any possibility of metal contamination.view more
M. Jiang, X. Zhu, M. C. Molaro, M. L. Rasche, H. Zhang, K. Chadwick, D. M. Rainmondo, K.-K. K. Kim, L. Zhou, Z. Zhu, M. H. Wong, D. O'Grady, D. Hebrault, J. Tedesco, and R. D. Braatz
The evolution of particle shape is an important consideration in many industrial crystallizations. This article describes the design of temperature-cycling experiments (between alternating positive and negative supersaturations) to substantially change crystal shape with only a small number of cycles. The growth and dissolution of monosodium glutamate crystals of varying shapes were monitored using in-process attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), focused beam reflectance measurement (FBRM), particle vision and measurement (PVM), and off-line optical microscopy. The growth and dissolution kinetics were estimated in a multidimensional population balance model based on solute concentration and crystal dimension measurements. This model fitted the experimental data with a limited number of parameters of small uncertainty. In addition, with the estimated kinetic parameters, the model predicted the crystal size and shape distribution in a different temperature-cycling experiment reasonably well. In contrast to previous studies that have estimated kinetics along multiple crystal axes in mixed-tank crystallizers, this study implements dissolution terms in the multidimensional population balance model along multiple axes.view more
M. Jiang, Z. Zhu, E. Jimenez, J. Xu, C. Papageorgiou, J. Waetzig, A. Hardy, and R. D. Braatz
A novel continuous crystallizer design is described with the potential to provide improved control of crystal properties, improved process reproducibility, and reduced scale-up risk. Liquid and gas are introduced into one end of the tube at flow rates selected to spontaneously generate alternating slugs of liquid and gas that remain stable while cooling crystallization occurs in each liquid slug. Mixing within each stable self-circulating slug is maximized by controlling the slug aspect ratio through specification of liquid and gas flow rates. The crystallizer is designed so that nucleation and growth processes are decoupled to enhance the individual control of each phenomenon. Coaxial or radial mixers combine liquid streams to generate seed crystals immediately upstream of the growth zone where nucleation is minimized, and crystal growth is controlled by the varying temperature profile along the length of the tube. The slug-flow crystallizer design is experimentally demonstrated to generate large uniform crystals of l-asparagine monohydrate in less than 5 min.view more
M. Jiang, M. H. Wong, Z. Zhu, J. Zhang, L. Zhou, K. Wang, A. N. Ford, T. Si, L. M. Hasenberg, Y.-N. Li, and R. D. Braatz
A semi-continuous crystallizer configuration that combines continuous seeding using a dual impinging jet with growth rate control in a stirred tank was experimentally demonstrated for the manufacture of l-asparagine monohydrate (LAM) crystals with the objective of obtaining a target flattop size distribution. The dual impinging jets combined hot and cold saturated solutions to generate highly uniform 20-μm crystals that were further grown to a desired size in the stirred tank with suppressed nucleation that was instrumented with attenuated total reflection–Fourier transform infrared (ATR–FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The construction of calibration models and the measurement of solubility and metastable limit were obtained by an automated system that followed preset supersaturation profiles using feedback control. The experiments confirm that greatly enhanced control of the crystal size distribution can be achieved using continuous seeding.view more