The goals of this project are to improve measurements of fluid structure and mechanical properties under a variety of flow conditions. We focus on fluids and conditions that are industrially and biologically relevant such as polymers, surfactant solutions, protein solutions, suspensions and soft materials and measure quantities such as viscosity at high shear rate, aggregation of biomolecules, and viscoelastic flow instabilities.
This work is motivated significantly by applications such as biomanufacturing of protein therapeutics, for which critical concerns are aggregation and excessive viscosity at high protein concentration.
We are developing rheological tools that use minimal fluid volume and measure local fluid dynamics and structure at high shear.
The goals of this project are to improve measurements of fluid structure and mechanical properties under a variety of flow conditions. We aim therefore to develop rheological tools that use minimal fluid volume and measure local properties and the dynamics of flow and structure, especially at high shear rate. We focus on fluids and conditions that are industrially and biologically relevant such as polymers, surfactant solutions, protein solutions (link to protein rheology project page), suspensions and soft materials and measure quantities such as viscosity at high shear rate, aggregation of biomolecules, and viscoelastic flow instabilities.
Microcapillary rheometers that use only 10 µL of solution developed
Tiny volume is a key requirement for the biopharmaceutical industry during drug formulation development, because they must test hundreds of different combinations and concentrations and the amount of protein available for such tests at that stage is limited. MedImmune (now Astra-Zeneca) thus set up a CRADA with us to develop a rheometer that needed less than 100 µL of solution.
As a result, a versatile and accurate microcapillary rheometer has been developed. This instrument uses less than 10 µL of fluid, is accurate and precise to a few percent, can measure a two-decade span of shear rate in approx. 10 minutes, and is temperature controlled ((0 – 80)°C). (Journal of Pharmaceutical Science 2015) Using this instrument, we demonstrate that various protein antibody solutions may exhibit Newtonian or non-Newtonian rheology, emphasizing the need to measure at a range of shear rate, temperature and other solution conditions.
The dynamics of concentrated self-associating protein solution was measured (Biomicrofluidics
Improvements to this technology, including smaller form factor, continue through the NIST on a Chip initiative’s flow metrology development.
High-resolution particle-tracking flow metrology, turbulent structures and other flow instabilities characterized
Particle tracking is another essential aspect of our flow metrology research. Most importantly, this analysis determines when flow is suitable for measurement of fluid viscosity and steady-state structure, or when conversely flow instabilities occur at high shear rates encountered during manufacturing and use. Among the particle tracking methods used, holographic microscopy has exceptional temporal and spatial dynamic range. Our microscope can resolve particle position to 10s of nm over a depth of field of 200 um, and flow velocities (from 0.001 to 50) mm/s. fig: fse_sdh_holog_scheme
Using these features, we have compared with flow calibration (Experiments in Fluids 2017) and tested viscoelastic flow. When fluids are viscoelastic (such as polymer solutions), normal stress differences can cause flow instability, and even turbulent flow, at negligible Reynolds number, especially when the flow has curved streamlines. We have reported studies of:
New high shear RheoSANS approached validated
Particle tracking and pressure gradient measurements demonstrated that some shear banding fluids surprisingly are slow to develop a rheometric flow for rheological measurements. (Journal of Rheology 2020) When rheometric flow is achieved, a depth sectioning technique, first demonstrated by Fernandez-Ballester, enables high shear rate rheoSANS measurements on a beamline. fse_sdh_urheoSANS_depth_section (Rheologica Acta 2018)
Protein adsorption and aggregation correlated
Globular proteins in solution adsorb to solid, liquid and air surfaces. These surfaces are sometimes a pathway to aggregation, and this instability must be prevented. Reversible and irreversible adsorption of NIST mAb and other proteins to various surfaces (stainless steel, alumina, and monolayer with different surface charge) has been measured by quartz crystal microbalance and neutron reflectometry and correlated to the amount of aggregated particles formed during flow. When high solution concentrations are in contact with stainless steel, for example, the molecules adjacent to the surface are conformationally altered, and in this condition most particle aggregates form. We are developing approaches to determine transport mechanisms leading to this surfaced-induced protein aggregation.
Rheological effects of particle shape and friction determined https://www.nist.gov/news-events/news/2016/05/crack-mystery-oobleck-friction-thickens-fluids
Measuring fluid properties and structure establishes the mechanisms that give rise to non-Newtonian rheology. One striking phenomenon is shear thickening, when the fluid viscosity rises sharply at high stress. To test interactions between particles, whether frictional or lubricating, we measured other stress components such as the first normal stress difference. Exploiting the strong temperature dependence of the viscosity of our glycerol based suspending fluid, we could readily access the stresses needed to initiate shear thickening while avoiding the flow instabilities that accompany high shear rates. This allowed us to explore shear thickening over an exceptionally wide range of volume fraction, and to measure normal forces too. Frictional force chain interactions between particles span across the fluid only at high stress. (Physical Review Letters 2016) Research elsewhere continues to test how frictional interactions arise and can be controlled.
Particle shape or directional interactions also affect fluid properties dramatically. Proteins and even mainly commercial particles are anisotropic. To help take colloidal rheology understanding beyond uniformly charged spheres, we have prepared and studied solutions of model cubelike particles. fse_sdh_cubic_colloid (Soft Matter 2015)