We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63).

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We present a bang-bang phase-locked loop (PLL) generator that encapsulates design methodologies for its circuit blocks and the complete PLL system. The generator is fully automated and parameterized, producing the layout and schematic based on process characterization and top-level specifications. Three 14GHz PLLs are instantiated in TSMC 16nm, GF 14nm and Intel 22nm technologies, demonstrating the process portability. The rapid generation time of less than four days enables fast PLL design and technology porting. The PLL design fabricated in TSMC 16nm shows RMS jitter of 565.4fs and power of 6.64mW from a 0.9V supply.@en