A 65 nm CMOS Digital Phase Imager for Time-Resolved Fluorescence Imaging

This paper presents a CMOS image sensor with direct digital phase output for time-resolved fluorescence imaging applications. A row-level zero-crossing detection is implemented to extract the phase-shift between the intensity modulated excitation signal and the emitted fluorescence, generating a time delay signal proportional to the fluorescence lifetime of the target analyte. A time-interpolated Time-to-Digital Converter (TDC) is subsequently used to quantize the time delay into a digital representation of the phase-shift for post-signal processing and image reconstruction. For proof-of-concept, a prototype chip consisting of a 32×32 P+/N-Well/P-Substrate photodiode array, row-level phase readout circuits, and a global TDC is implemented in a low-power 65 nm CMOS technology. The TDC features a temporal resolution of 110 ps over a 414 μs range, which corresponds to a dynamic range of 132 dB. Extensive characterization results demonstrate a phase readout sensitivity of better than 0.01 degrees at a 1.2 kHz modulation frequency and 0.1 degrees at up to 1 MHz. The complete imager chip is evaluated through a sequence of phase image reconstruction experiments, and the results are presented.