Integrated Real-Time CMOS Luminescence Sensing and Impedance Spectroscopy in Droplet Microfluidics.

High-throughput biosensor screening and optimization are critical for health and environmental monitoring applications to ensure rapid and accurate detection of biological and chemical targets. Traditional biosensor design and optimization methods involve labor-intensive processes, such as manual pipetting of large sample volumes, making them low throughput and inefficient for large-scale library screenings under various environmental and chemical conditions. We address these challenges by introducing a modular droplet microfluidic system embedded with custom CMOS integrated circuits (ICs) for impedance spectroscopy and bioluminescence detection. Fabricated in a 65 nm process, our CMOS ICs enable efficient droplet detection and analysis. We demonstrate successful sensing of luciferase enzyme-substrate reactions in nL-volume droplets. The impedance spectroscopy chip detects 4 nL droplets at 67 mm/s with a 45 pA resolution, while the luminescence detector senses optical signals from 38 nL droplets with a 6.7 nA/count resolution. We show real-time concurrent use of both detection methods within our hybrid platform for cross-validation. This system greatly advances conventional biosensor testing by increasing flexibility, scalability, and cost-efficiency.