CMOS SINGLE PHOTON AVALANCHE DIODES AND TIME-TO-DIGITAL CONVERTERS FOR TIME-RESOLVED FLUORESCENCE ANALYSIS

Abstract

Fluorescence lifetime imaging (FLIM) has the potential to provide rapid screening and detection of diseases. However, time-resolved fluorescence measurements require high-performance detectors with single-photon sensitivity and sub-nanosecond time resolution. These systems should also be compact, reliable, inexpensive, and easily deployable for laboratory and clinical applications. It is with these applications in mind that the development of single photon avalanche diodes (SPAD) and time-to-digital converter (TDC) prototype integrated circuits (IC) in standard digital CMOS have been pursued in this thesis. SPAD and TDC ICs were designed and fabricated in 130 nm IBM CMOS technology and then intensively studied. Several different SPAD pixels were modeled and designed, and the electro-optical performance was characterized and comparatively studied. By repurposing existing design layers of a standard CMOS process, the fabricated SPAD pixel test structures achieved up to 20× improvement of dark count rate (DCR) compared to previous designs. Optical measurements also showed up to 10× improvement in the detection limits for low-level light. Detailed dark noise characterization was performed at various temperatures using free-running and time-gated modes of operation. Optimal operating conditions were found for minimal afterpulsing effects. The SPAD’s capability to accurately measure fast fluorescence decays was also demonstrated in a practical setting with the lifetime measurements of two fluorophores, Rhodamine 6G and Ruby crystal, which have fluorescence lifetimes of approximately 4 ns and 3 ms, respectively. A fast and accurate TDC prototype circuit for time-correlated single-photon counting (TCSPC) applications was designed, fabricated and characterized. With a coarse-fine delay line architecture, the TDC size was reduced without compromising its linearity and jitter performance. Extensive characterization of the fabricated SPAD and TDC ICs shows that the measured performance met the stated design goals.