(16a) Advanced Crystallization Technologies for (Bio)Manufacturing

Research Interests:  To create novel crystallization strategies and processes for the purification and separation of proteins and other biologically derived molecules.

Teaching Interests: All core courses of chemical engineering. My goal is to help students build a strong background in chemical engineering, sharpen their analytical skills, and apply their knowledge and skills creatively.

Crystallization from solution is a key unit operation for purification, separation, and manufacturing in the environmental, food, pharmaceuticals, chemicals, and materials industries. Challenges that can arise during crystallization include (1) high sensitivities of crystal nucleation and growth kinetics to small variations in the concentrations of contaminating chemicals, (2) high sensitivities of aggregation and agglomeration kinetics to flow fields and particle size, (3) spatial inhomogeneity, (4) sensor limitations, and (5) many orders of magnitude variation in length scales (0.1 nm to 100s of microns) and time scales (20 ps to many hours).

New process designs are described that employ process intensification strategies to greatly enhance the control of the crystal size distribution. These strategies include using noncontact focused ultrasonication, exploiting differences in molecular and thermal diffusion rates at fluid-fluid interfaces to induce nucleation, and selecting crystallizer designs and operations to spontaneously induce multiphase flows that decouple nucleation and growth to enable their individual control. My experiments are supported by mathematical modeling and theoretical analysis, which collectively are also relevant to other chemical process systems.

The growth in demand for new therapeutics and fine chemicals manufactured in bioreactors motivates the invention of technologies to reduce purification and storage costs by at least an order of magnitude compared to existing technologies. A research program is proposed that employs fundamental understanding, mathematical models, and cleverly designed experiments to create novel crystallization strategies and processes for the purification and separation of proteins and other biologically derived molecules.

Keywords: Process intensification, kinetics, separation, biomanufacturing, process design and control, crystallization, purification, protein