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)上名为环剪切液滴模块的设备进行的实验，以研究液滴表面蛋白质的动力学。在国际空间站的微重力环境中，水滴可以固定在适当的位置，只需最小限度地接触固体墙壁。这种配置允许检查液滴表面和内部的流动，而不受周围墙壁的影响，这在地球上是不可能做到的。在环形剪切液滴模块中，可以测量液滴表面的流量，而不会出现与固体壁发生化学、吸附和静电相互作用的复杂情况。该项目将专注于浓缩蛋白质溶液的流动，无论是在环形剪切下降模块中，还是在支持地球上的实验中。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较高时。蛋白质在自由表面的聚集是制药生产中的一个致命弱点，它会降低产品质量和工艺产量。因此，实验结果和随之而来的数值模拟将使预测模型的开发和测试成为可能，这些预测模型将有助于改进制药生产。要开发预测实际感兴趣的条件下浓缩蛋白质溶液流动行为的机理模型，需要针对界面和本体流动以及耦合界面和本体应力的准确的非牛顿本构方程。耦合问题本质上是非线性的，需要稳健和准确的数值技术来询问动力学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整体流体速度的实验。国际空间站上使用RSD的实验数据和地球上使用刀口表面粘度计的实验数据将检查当主体相保持牛顿状态时被吸附的界面蛋白质层的流变性响应，以及当两相都是非牛顿状态时界面和主体流体的流变性响应。将确定蛋白质聚集和纤维形成对界面和整体流变学的作用。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.