A Threshold-Based Bioluminescence Detector With a CMOS-Integrated Photodiode Array in 65 nm for a Multi-Diagnostic Ingestible Capsule

Abstract

This article presents a highly miniaturized ingestible electronic capsule for biochemical detection via onboard genetically engineered biosensor bacteria. The core integrated circuit (IC) is a threshold-based bioluminescence detector with a CMOS-integrated photodiode array in a 65-nm technology that utilizes a dual-duty-cycling front end to achieve low power consumption. The implemented IC achieved 59-nW active power consumption, 25-fA/count resolution, and a 59-fA minimum detectable signal (MDS) using a calibrated optical source. The IC was then integrated with other system components into a battery-powered wireless ingestible capsule measuring just 6.5 mm thick <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times $ </tex-math></inline-formula> 12 mm diameter. We demonstrated successful detection of low-intensity bioluminescent signals from bioengineered bacterial sensors when exposed to the intestinal inflammation biomarker tetrathionate in vitro. Together, the IC and mm-scale smart pill systems demonstrate high sensitivity with low-power multiplexed measurement capability suitable for noninvasive disease diagnosis and monitoring in the gastrointestinal (GI) tract.