Single-photon detector arrays for time-resolved fluorescence imaging

Time-correlated single photon counting techniques have recently established themselves in numerous fields of research. In particular, for fluorescence lifetime imaging, time-correlated single photon counting is often considered the absolute reference in terms of accuracy and image quality. However, the lack of significant detector arrays capable of single photon sensitivity and precise photon timing with sub-nanosecond resolution has imposed the use of optical scanning to acquire fluorescence lifetime images. As a consequence, the acquisition times are often prohibitively long and the image acquisition of fast phenomena or the rendering of live and moving objects very difficult to achieve. This thesis presents a new type of detector array capable of single photon sensitivity, low noise and accurate photon timing. The core detector technology is based on single photon avalanche diode structures. Given both the complexity of achieving sub-nanosecond time resolution on many parallel pixels and the large amount of data time-resolved imagers produce, the use of advanced electronic fabrication process is inevitable. Thus the design of high performance single photon detectors in deep-submicron (130 nm) CMOS is investigated, leading to excellent photon detection probability (up to 15 – 35 %, depending on bias and wavelength), low noise (a few tens of Hertz) and a photon timing jitter of 125 ps. The fabrication of these detectors has opened the way to the integration of complex electronics on pixel level. A time discriminator implemented as a compact time-to-digital converter was designed relying on a two-level interpolator approach. A global clock provides a stable, coarse resolution while an in-pixel delay line allows for a finer time resolution of 119 ps. The combination of single photon detector and time discriminator, with the addition of some read-out and glue electronics, enabled the fabricating of a small (50 × 50 µm), scalable pixel for integration in a larger array. An array consisting of 32 × 32 pixels was implemented and thoroughly characterized. With a timing mismatch of only a few tens of picoseconds across the entire array, a low noise count and good sensitivity, the array is well suited for various time-correlated applications, and FLIM in particular. The large data rate (up to 10.24 Gb/s) of the 1024 parallel acquisition channels is handled by a motherboard with significant computing power in the form of two FPGA's. An on-board data compression scheme is implemented by creating a histogram of photon arrival times for each individual pixel within the array, allowing for an efficient data transfer out of the motherboard. Finally, the suitability and efficiency of the proposed detector array for fluorescence lifetime imaging is shown with a wide variety of measurements, from high time-resolution single detector measurements to wide-field fluorescence lifetime image acquisition. Fluorescence lifetimes were resolved with high accuracy for very short acquisition times, down to a few hundreds of milliseconds for the parallel acquisition on all pixels.