Rigid and high NA multiphoton fluorescence GRIN-endoscopes

Multiphoton autofluorescence imaging offers minimal-invasive examination of cells without the need of staining and complicated confocal detection systems. Therefore, it is especially interesting for non-invasive clinical diagnostics. To extend this sophisticated technique from superficial regions to deep lying cell layers, internal body parts and specimens difficult of access, the bulky optics need to be reduced in diameter. This is done by tiny GRIN-optics, based on a radial gradient in the reflective index. Of especial interest for multi-photon applications is the newly developed GRIN-lens assembly with increased numerical aperture. High resolution images of plant tissue, hair and cells show the improved image quality,compared to classical GRIN-lenses. The rigid GRIN-endoscopes are already applied in wound healing studies. Here, the GRIN-lenses with diameters smaller than 3 mm enter small skin depressions. They reproduce the focus of a conventional laser scanning tomograph tens of mm apart in the specimen under study. We present first clinical measurements of elastin and SHG of collagen of in-vivo human skin of venous ulcers (ulcer curis).