Microfluidic-based spatiotemporal control of oxygen concentration in bacteria suspension culture from bulk to the single cells

Abstract

Oxygen plays a crucial role in microbial growth and metabolism. However, the detailed bacterial responses and regulatory mechanisms toward the change of oxygen are still not completely understood partly due to the lack of real-time measurement and control of dissolved oxygen (DO). Here, we present a novel platform for spatiotemporal and real-time controls of oxygen concentrations by a simple microfluidic design in bacteria suspension culture on chip. The DO concentrations are precisely controlled or flexibly tuned in bioreactor arrays in nanoliter scale. Multiple bioreactor groups with diverse DO control strategies are integrated on a single chip. With our platform, adequate oxygen existed in the microfluidic culture channels and may be the critical factor for the fast growth during bacteria suspension culture. Notably, we extend our platform to mimic the DO oscillation environment and monitor the growth of bulk and single bacterium for many generations. This microfluidic platform exhibits the unique capability of spatiotemporal gas control and detection for microbial suspension culture in nanoliter scale, which can be applied for screening, studying, and culturing the industrial or niche-specific environmental microbiome, at bulk, single cell, or consortia level, responding to oxygen or other gas environment, such as carbon dioxide, ammonia, etc.