FLUODIAMON · Ultra-high resolution and ultra-sensitive fluorescence methods for objective sub-cellular diagnosis of early disease and disease progression in breast and prostate cancer

The overall objective of this proposal is to develop and validate a quantitative, minimally invasive diagnostic tool for early and conclusive detection, diagnosis and monitoring of disease and disease progression of breast and prostate cancer. A methodology will be developed making use of a combination of the probably most exciting recent advances in the field of light microscopy, for fluorescence-based optical imaging of individual sample cells. It includes advances which will take the spatial resolution far beyond the fundamental limits of optical resolution, the sensitivity down to an ultimate single-molecule level, and multi-parameter detection schemes significantly increasing the fluorescence information by which these cellular images can be analysed. Apart from detecting and identifying tumour markers in the samples, tumour-specific spatio-temporal molecular distributions within the intact sample cells will be exploited. This is to date an almost unexploited dimension of diagnostic information. By combining and supporting these novel optical methods with state-of-the-art affinity molecule biotechnology, , tumor biomarkers, fluorophore chemistry, and bioinformatic validation tools, all possible means will be exploited to extract a maximum amount of information out of very small amounts of sample material. We thereby expect that an improved, early and reliable diagnosis of breast and prostate cancer will be possible, from amounts of sample material small enough that a minimally invasive procedure such as Fine-needle aspiration (FNA) can be used. In addition, by the minimally invasive FNA-based sampling, serious sampling-related side-effects, such as seeding and spread of cancer cells can be completely avoided. Given the high incidence of breast and prostate cancer, and the utmost importance of an early and conclusive diagnosis for the prognosis of these diseases, the relevance of this project can not be overestimated.