Ingenious integration of synthetic biology and droplet microfluidics

Abstract

As an interdisciplinary subject integrating biology, engineering and computer science, synthetic biology is committed to designing functional biological systems through engineering means to meet challenges in biomanufacturing, medicine and energy. However, traditional gene modification technology faces bottlenecks such as low efficiency of high-throughput screening, high reagent consumption and detection complexity. Droplet microfluidics constructs independent reaction units by precisely manipulating micron-sized droplets. With the advantages of compartmentalization, high throughput and low cost, it provides an innovative technology platform for synthetic biology. This article systematically reviews three major applications of this technology in synthetic biology: in green biomanufacturing, high-throughput detection of enzymes and other metabolites along with efficient strain selection can be achieved by encapsulating mutation libraries; in the field of biomedicine, combining single-cell sequencing and digital PCR technology can realize cell heterogeneity analysis and precise quantification of trace nucleic acids, and promote the development of organoids drug screening and microbial community analysis; in in vitro cell-free systems, key biological processes such as DNA synthesis, plasmid transformation and protein expression can be reconstructed through modular design within droplets. In addition, this review also discusses current technical challenges in chip design standardization, real-time detection with multi-parameters and large-scale production, as well as envisioning its potential directions in platform construction and industrial transformation for synthetic biology. The deep integration of droplet microfluidics will accelerate the transition of synthetic biology from basic research to practical application.