Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Department of Chemical and Biomolecular Engineering, Lehigh University, 111 Research Dr., Iacocca Hall, Bethlehem, PA, 18015, USA.
Pharm Res. 2021 Oct;38(10):1765-1775. doi: 10.1007/s11095-021-03106-9. Epub 2021 Oct 18.
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.
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).
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.
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.
测量浓缩蛋白质溶液的黏度对于蛋白质治疗药物的制造和输送至关重要。传统的黏度测量方法需要大量的溶液体积，这在蛋白质开发的早期阶段造成了严重的限制。这项工作的目的是开发一种需要最小样本量的强大技术。
在这项工作中，开发了一种基于液滴的微流控装置，用于在微米级液滴中浓缩的同时量化蛋白质溶液的黏度。该技术仅需要几微升的样品。相应的黏度通过多颗粒跟踪微流变学（MPT）进行表征。
我们表明，微流控装置中量化的黏度与通过传统流变仪测量的聚乙二醇（PEG）溶液的宏观结果一致。该技术进一步用于量化已研究充分的溶菌酶和牛血清白蛋白（BSA）溶液的黏度。与宏观测量和模型（Krieger-Dougherty 模型）的比较证明了该方法的有效性。
基于液滴的微流控装置提供了蛋白质溶液在小样本量（约 μL）和高组成分辨率下的黏度的准确定量值，范围广泛。该装置将扩展到研究不同赋形剂和其他添加剂对蛋白质溶液黏度的影响。
