Taehong Kwon - Past research at MIT

Micro/nanofluidic Platforms for Continuous Bioprocessing

At MIT, I developed micro/nanofluidic technologies for continuous bioprocessing, including membrane-less cell retention, continuous removal of nonviable cells, and online protein quality monitoring. This work demonstrated the potential of these approaches to address limitations of conventional filtration and offline analytics and to support more reliable and efficient continuous biomanufacturing.

Membrane-less cell retention for perfusion bioreactors

We developed a novel cell retention device for perfusion culture based on inertial sorting [1, 5, 6]. This membrane-less microfiltration utilizes size-dependent hydrodynamic forces to separate suspended mammalian cells. The device has been extensively evaluated for cell retention efficiency, long-term biocompatibility, and scalability, demonstrating its effectiveness in retaining cells and its compatibility for long-term use. Moreover, we have successfully demonstrated its applicability in long-term and small-scale perfusion cultures, showcasing clog-free cell retention and high product recovery. Our findings suggest a promising approach for improving perfusion culture performance while avoiding some of the limitations of traditional membrane-based filtration methods.

Continuous removal of small nonviable CHO cells from bioreactors

Next, we implemented a high-throughput size-based cell separation technique using inertial sorting to remove small dead cells from bioreactor cultivation [2]. Through the optimization of device parameters, we achieved efficient removal of dead cells, even at high throughputs and concentrations. Our work demonstrated the capability of this approach to effectively remove small dead cells from bioreactor cultures, suggesting a useful strategy for improving the overall health and viability of cell-based processes.

Continuous online protein quality monitoring during perfusion culture

Finally, we demonstrated continuous online monitoring of protein purity in the cell culture supernatant during perfusion culture using a novel nanofluidic filter array [3, 4]. This innovative device, integrated with the microfluidic cell retention system, enabled real-time sample preparation and automated monitoring of protein purity for over a week. By providing a robust online sensing technology, the nanofluidic filter array has the potential to complement or partially replace conventional offline analytical methods and improve the efficiency and reliability of protein purity monitoring in continuous biomanufacturing processes.

In summary, this work introduced a novel micro/nanofluidic system for the separation and monitoring of cells and proteins in continuous biomanufacturing [4]. This approach demonstrated potential for improving the long-term reliability and efficiency of biomanufacturing processes. By addressing challenges in cell and protein separation and monitoring, it contributed to the broader development of continuous biomanufacturing technologies.

This work laid the foundation for my subsequent interests in small-scale bioprocessing, process analytical technology, and platform development for biomanufacturing.

References:

[1] T. Kwon, H. Prentice, J. D. Oliveira, N. Madziva, M. E. Warkiani, J.-F. P. Hamel, and J. Han, “Microfluidic Cell Retention Device for Perfusion of Mammalian Suspension Culture,” Scientific Reports. 7, 6703 (2017). link

[2] T. Kwon, R. Yao, J.-F. P. Hamel, and J. Han, “Continuous Removal of Small Nonviable Suspended Mammalian Cells and Debris from Bioreactors Using Inertial Microfluidics,” Lab on a Chip, 18, 2826 – 2837 (2018). link

[3] S. H. Ko, D. C., W. Ouyang, T. Kwon, P. Karande, and J. Han, “Nanoﬂuidic device for continuous multiparameter quality assurance of biologics,” Nature Nanotechnology, 12, 804 – 812 (2017). link

[4] T. Kwon, S. H. Ko, J.-F. P. Hamel, and J. Han, “Continuous online protein quality monitoring during perfusion culture production using an integrated micro/nanofluidic system,” Analytical Chemistry, 92, 5267 - 5275 (2020). link

[5] L. Yin, W. Y. Au, C. C. Yu, T. Kwon, Z. Lai, M. Shang, M. E. Warkiani, R. Rosche, C. T. Lim, and J. Han, “Miniature auto‐perfusion bioreactor system with spiral microfluidic cell retention device,” Biotechnology and Bioengineering, 118, 1951 - 1961 (2021). link

[6] T. Kwon, K. Choi, and J. Han, “Separation of Ultra-high-density Cell Suspension via Elasto-inertial Microfluidics,” Small, 17, 2101880 (2021). link

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