A 65nm CMOS Living-Cell Dynamic Fluorescence Sensor with 1.05fA Sensitivity at 600/700nm Wavelengths

Abstract

Integrated, low-cost and miniaturized devices that can detect clinically relevant biomarkers are crucial for the growing field of precision medicine, as they can enable point-of-care diagnosis, continuous health monitoring and closed-loop drug delivery. Fluorescence (FL) sensing is known to be one of the most reliable, sensitive, and widely adopted sensing modality for many biomarkers. However, detecting the weak FL signal requires complex optical setups, especially narrowband optical filters to block the strong excitation (EX) light. Prior efforts to miniaturize and implement FL sensing in CMOS technologies have been limited to on-chip high-pass filters using dense vertical waveguide arrays. More importantly, the reported wavelength range of 800nm is not compatible with most of the commonly used fluorescent proteins that work with living cells. Luminescence is another mechanism for detecting biomarkers that do not require an EX source and optical filtering. However, there are a limited number of luminescence proteins, and it is not feasible to use them in a closed-loop system since they can interfere with optogenetic control integration.