Microfluidics for Control of Synthetic Biology

Microfluidic systems with integrated analysis and control of environmental parameters can enable precise control of metabolic activity and protein expression. Here, we couple microfluidic controls in a polycarbonate-PDMS microbioreactor (Fig. 1) with closed-loop control of temperature, pH, dissolved oxygen, and cell density [1,2] to the biochemical control of synthetic gene circuits [3,4]. In situ measurements of optical density were used to calibrate flow rates and peristaltic mixing times in the microbioreactor growth chamber. Long-term culture requires precise injection and extraction of fluid from the 1 mL growth chamber. In this case, 831.3 nL injections were used for fluid addition/extraction via peristaltic metering valves [2]. This precision comes at the cost of slow change-over times for the chemical concentration (here glucose and galactose) in the growth chamber – the measured change-over time was around 6 hours for flow rate typical for yeast culture. However, a control algorithm can be used to dynamically alter the concentration of the injected glucose/galactose to rapidly reduce the change-over time to <1 hour achieving control of the chemical environment faster than the doubling time (Fig. 2).