ISS: Collaborative Research: Interfacial bioprocessing of pharmaceuticals via the Ring-Sheared Drop (RSD) module aboard ISS

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This project will support experiments using a device called the Ring-Sheared Drop module aboard the International Space Station (ISS) to study the dynamics of proteins at the surfaces of liquid drops. In the microgravity environment on the ISS, the drop can be held in place with only minimal contact with solid walls. This configuration allows flows at the surface of the drop and inside the drop to be examined without effects from surrounding walls, which is impossible to do on Earth. In the Ring-Sheard Drop module, flows at the surface of a drop can be measured without complications from chemical, sorption, and electrostatic interactions with solid walls. The project will focus on flows of concentrated protein solutions, both in the Ring-Sheared Drop module and in supporting experiments on Earth. The goal of the project is to understand and control protein aggregation at free surfaces, especially when the concentration of protein is high. Protein aggregation at free surfaces is an Achilles' heel in pharmaceutical manufacturing that degrades product quality and process yield. Thus, the experimental results and accompanying numerical simulations will enable the development and testing of predictive models that will be useful for improving pharmaceutical manufacturing.The development of mechanistic models to predict flow behavior of concentrated protein solutions under conditions of practical interest requires accurate non-Newtonian constitutive equations for both the interfacial and bulk flows and coupling the interfacial and bulk stresses. The coupled problem is intrinsically nonlinear, requiring robust and accurate numerical techniques to interrogate dynamics and accurate experimental data for validating model predictions. The project will support experiments to measure interfacial and bulk fluid velocities for concentrated protein systems. Data from experiments on the ISS using the RSD and experiments on Earth using a knife-edge surface viscometer will examine the rheological response of an adsorbed interfacial protein layer when the bulk phase remains Newtonian and the rheological response of the interface and bulk fluid when both phases are non-Newtonian. The role of protein aggregation and fibril formation on interfacial and bulk rheology will be determined.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.