FemtoSCOPE — a highly resolving
two-photon system for diagnosis of cancer

The “FemtoSCOPE” project aims to develop an innovative diagnostic system for use in patients suspicious for cancer. It consists of a flexible high-resolution two-photon endoscope based on two-photon-microscopy in combination with in-vivo suitable adopted contrast agents (Fig. D.1.6). Using this endoscope, diseases in hollow organs directly in the human body down to the single cell-level could be diagnosed. Since laboratory preparation and analyses of histological samples constitute a large portion of the workload at the moment, this system will significantly improve the pathological classification of diseases without the need to take biopsy samples.

For this project, it is intended to focus on superficial bladder cancer. Till now, only very few clinically applicable fluorochromes that might provide a good morphological or functional contrast on a cellular level have been identified and characterised. LFL (Laser-Forschungslabor, LMU) has experience in fluorescence microscopy and endoscopy and can perform both in-vitro cell and tissue examination and clinical evaluation.

The main technical challenges in transferring two-photon microscopy into flexible endoscopes are the linear and nonlinear effects arising during propagation of highly intense pulses in glass fibre, which change the pulse characteristics. The group-velocity dispersion must be compensated and at the same time the self-phase modulation must be reduced. For generation of the necessary short laser pulses (lower fs regime) a compact high-performance femtosecond laser source is necessary, delivering a high repetition rate and thus less radiation exposure. Furthermore, it has to be tunable over the relevant wavelength range for exciting the fluorophores.