A Highly Integrated Lab-on-a-CMOS Platform for Real-Time Monitoring of E. Coli Growth Kinetics

Abstract

Existing miniaturized and cost-effective solutions for bacterial growth monitoring usually require offline incubators with constant temperature to culture the bio-samples prior to measurement. Such a separated sample preparation and detection scheme requires extensive human intervention, risks contamination, and suffers from poor temporal resolution. To achieve integrated sample preparation and real-time bacterial growth monitoring, this article presents a lab-on-a-CMOS platform incorporates an optical sensor array, temperature sensor array, micro-heaters, and readout circuits. Escherichia coli's (E. coli) optimum growth temperature of 37 ^°C is achieved through a heat regulation system consisting of two micro-heaters and an on-chip temperature sensor array. A photodiode array with an in-pixel capacitive trans-impedance amplifier to reduce inter-pixel cross-coupling is designed to extract the optical information during bacterial growth. To balance the footprint, power consumption, and quantization speed, a 10 b column successive-approximation register (SAR)/single-slope (SS) dual-mode analog-to-digital converter (ADC) is designed to digitize the temperature and optical signals. Fabricated in a standard 0.18 um CMOS process, the proposed platform can regulate the sample temperature to 37 +/- 0.2/0.3 ^°C within 32 mins. Enabled by an on-chip heat regulation system and photodetectors, the prototype demonstrates a real-time monitoring of bacterial growth kinetics and antibiotic responses. Minute-level temporal resolution is achieved as this proposed platform is free of extensive and time-consuming human intervention. The proposed platform can be viably used in contamination sensitive applications such as antibiotic tests, stem cell cultures, and organ-on-chips.