A Threshold-Based Bioluminescence Detector With a CMOS-Integrated Photodiode Array in 65 nm for a Multi-Diagnostic Ingestible Capsule
Qijun Liu, Miguel Jiménez, María Eugenia Inda, Arslan Riaz, Timur Zirtiloglu, Anantha P. Chandrakasan, Timothy K. Lu, Giovanni Traverso, Phillip Nadeau, Rabia Tugce Yazicigil
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.