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Droplet-Based Microfluidic Tool to Quantify Viscosity of Concentrating Protein Solutions

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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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

MPT:

Multiple particle tracking microrheology

PEG:

Poly(ethylene) glycol

BSA:

Bovine Serum Albumin

MSD:

Mean-squared displacement

PDMS:

Polydimethylsiloxane

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Acknowledgements

The authors would like to acknowledge Dr. Junchi Ma for bulk rheology measurements of 100 kg/mol PEG solutions. Funding for this work is provided by department of Chemical Engineering, Carnegie Mellon University. The authors report no conflicts of interest in this work.

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Authors and Affiliations

  1. Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA

    Deyu Yang & Lynn M. Walker

  2. Department of Chemical and Biomolecular Engineering, Lehigh University, 111 Research Dr., Iacocca Hall, Bethlehem, PA, 18015, USA

    Maryam Daviran & Kelly M. Schultz

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  1. Deyu Yang
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  2. Maryam Daviran
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Correspondence to Lynn M. Walker.

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Yang, D., Daviran, M., Schultz, K.M. et al. Droplet-Based Microfluidic Tool to Quantify Viscosity of Concentrating Protein Solutions. Pharm Res 38, 1765–1775 (2021). https://doi.org/10.1007/s11095-021-03106-9

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