Biotechnology and Bioprocess Engineering 2024; 29(1): 25-33  
Microfluidics‑driven high‑throughput phenotyping and screening in synthetic biology: from single cells to cell‑free systems
Taeok Kim1,2 · Minji Ko1,3 · Eugene Rha1 · Haseong Kim1,3,4 · Hyewon Lee1,3
1 Synthetic Biology Research Center and the K‑Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea
2 Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Korea
3 Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon 34113, Korea
4 Graduate School of Engineering Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
Correspondence to: Hyewon Lee
hlee@kribb.re.kr
Received: September 6, 2023; Revised: October 27, 2023; Accepted: October 30, 2023; Published online: February 16, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The interdisciplinary nature of synthetic biology merges engineering principles with biology and provides innovative solutions for issues in the biomanufacturing industry. To develop industrially applicable biocatalysts and/or microbial cell factories, a design-build-test-learn cycle-based iterative process is necessary, which is often time-consuming and labor-intensive. The integration of microfluidic technologies into synthetic biology can accelerate these processes, particularly for achieving high-throughput phenotyping and screening. In this review, we examine the potential of microfluidic technologies to revolutionize synthetic biology. Although commercial microfluidics demonstrate superior throughput for single-cell assays, their application can be limited, for example, in cases where products are retained inside the cells. Droplet microfluidics, on the other hand, is a rather flexible platform and shows high diversity in single-cell, cell-to-cell interaction-based, and cell-free reaction-based analyses. By examining previous studies, we have summarized the potential of microfluidic technologies to foster sustainable biomanufacturing and advanced biological engineering.
Keywords: Microfluidics · Synthetic biology · High-throughput screening · Biofoundry

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