Continuous Biomanufacturing Using Micro/Nanofluidics

Continuous biomanufacturing is a growing trend in the biopharmaceutical industry because it can reduce manufacturing cost and increase product quality. Ideas from micro/nanofluidics can be employed in all aspects of continuous biomanufacturing to enhance the over-all productivity as well as the efficacy and safety of the final products.

First, we introduce a novel cell retention device based on inertial sorting for perfusion culture. The cell retention device maintains cells in the bioreactor and removes biologics and metabolites. Hollow fiber membrane is commonly used in the biopharmaceutical industry. However, it has challenges, such as membrane clogging/fouling, low product recovery, and inability to remove dead cells. In this context, we developed a membrane-less microfluidic cell retention device and demonstrated perfusion culture of high-concentration mammalian cells producing monoclonal antibodies for >3 weeks with high product recovery (>99%).

Second, we present a nanofluidic system for continuous-flow, multi-variate (purity, bioactivity, and protein folding) protein analysis for real-time critical quality assessments. This size-based nanofluidic system can complement the existing bench-type conventional analytical tools, such size exclusion chromatography and gel electrophoresis, to meet quality assurance requirements of current and future biomanufacturing systems. We demonstrated rapid purity and bioactivity monitoring of protein drugs, such as hGH, IFN-alfa-2b, and G-CSF, using the nanofluidic system.