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

Fatemeh Aghimand, Chelsea Hu, Saransh Sharma, Krishna K. Pochana, Richard M. Murray, Azita Emami

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 [1], [3]. However, detecting the weak FL signal requires complex optical setups, especially narrowband optical filters to block the strong excitation (EX) light. Prior efforts [1] 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 in [1] is not compatible with most of the commonly used fluorescent proteins that work with living cells [4]. Luminescence is another mechanism for detecting biomarkers that does not require an EX source and optical filtering [2]. However, there are 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 [5].