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

该项目将支持使用国际空间站（ISS）上的环形剪切液滴模块（Ring-Sheared Drop）设备进行实验，以研究液滴表面的蛋白质动态。 在国际空间站的微重力环境中，液滴可以保持在与固体壁接触最小的位置。 这种结构允许在没有周围墙壁影响的情况下检查液滴表面和液滴内部的流动，这在地球上是不可能做到的。 在环剪切液滴模块中，可以测量液滴表面的流动，而不会因与固体壁的化学、吸附和静电相互作用而产生复杂情况。该项目将侧重于浓缩蛋白质溶液的流动，无论是在环剪落模块和支持地球上的实验。该项目的目标是了解和控制蛋白质在自由表面的聚集，特别是当蛋白质浓度很高时。 蛋白质在自由表面的聚集是药物制造中的阿喀琉斯之踵，其降低了产品质量和工艺产率。 因此，实验结果和伴随的数值模拟将使开发和测试的预测模型，这将是有用的，以提高制药manufacture.The开发的机械模型，以预测浓缩蛋白质溶液的流动行为的条件下，实际利益需要准确的非牛顿本构方程的界面和散装流量和耦合的界面和散装应力。耦合问题本质上是非线性的，需要强大而准确的数值技术来询问动态和准确的实验数据来验证模型预测。 该项目将支持测量浓缩蛋白质系统的界面和本体流体速度的实验。 从国际空间站上使用RSD和实验在地球上使用刀口表面粘度计的实验数据将检查吸附的界面蛋白质层的流变响应时，体相保持牛顿和流变响应的界面和体相流体时，两相都是非牛顿的。 该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.