Deyu Yang1, Maryam Daviran2, Kelly M Schultz2, Lynn M Walker3. 1. Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA. 2. Department of Chemical and Biomolecular Engineering, Lehigh University, 111 Research Dr., Iacocca Hall, Bethlehem, PA, 18015, USA. 3. Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA. lwalker@andrew.cmu.edu.
Abstract
PURPOSE: Measurement of the viscosity of concentrated protein solutions is vital for the manufacture and delivery of protein therapeutics. Conventional methods for viscosity measurements require large solution volumes, creating a severe limitation during the early stage of protein development. The goal of this work is to develop a robust technique that requires minimal sample. METHODS: In this work, a droplet-based microfluidic device is developed to quantify the viscosity of protein solutions while concentrating in micrometer-scale droplets. The technique requires only microliters of sample. The corresponding viscosity is characterized by multiple particle tracking microrheology (MPT). RESULTS: We show that the viscosities quantified in the microfluidic device are consistent with macroscopic results measured by a conventional rheometer for poly(ethylene) glycol (PEG) solutions. The technique was further applied to quantify viscosities of well-studied lysozyme and bovine serum albumin (BSA) solutions. Comparison to both macroscopic measurements and models (Krieger-Dougherty model) demonstrate the validity of the approach. CONCLUSION: The droplet-based microfluidic device provides accurate quantitative values of viscosity over a range of concentrations for protein solutions with small sample volumes (~ μL) and high compositional resolution. This device will be extended to study the effect of different excipients and other additives on the viscosity of protein solutions.
PURPOSE: Measurement of the viscosity of concentrated protein solutions is vital for the manufacture and delivery of protein therapeutics. Conventional methods for viscosity measurements require large solution volumes, creating a severe limitation during the early stage of protein development. The goal of this work is to develop a robust technique that requires minimal sample. METHODS: In this work, a droplet-based microfluidic device is developed to quantify the viscosity of protein solutions while concentrating in micrometer-scale droplets. The technique requires only microliters of sample. The corresponding viscosity is characterized by multiple particle tracking microrheology (MPT). RESULTS: We show that the viscosities quantified in the microfluidic device are consistent with macroscopic results measured by a conventional rheometer for poly(ethylene) glycol (PEG) solutions. The technique was further applied to quantify viscosities of well-studied lysozyme and bovine serum albumin (BSA) solutions. Comparison to both macroscopic measurements and models (Krieger-Dougherty model) demonstrate the validity of the approach. CONCLUSION: The droplet-based microfluidic device provides accurate quantitative values of viscosity over a range of concentrations for protein solutions with small sample volumes (~ μL) and high compositional resolution. This device will be extended to study the effect of different excipients and other additives on the viscosity of protein solutions.
Authors: Feng He; Christopher E Woods; Jennifer R Litowski; Lauren A Roschen; Himanshu S Gadgil; Vladimir I Razinkov; Bruce A Kerwin Journal: Pharm Res Date: 2011-05-15 Impact factor: 4.200