Ultra-Compact Microsystems-Based Confocal Endomicroscope

Point-of-care medical diagnosis demands immediate feedback on tissue pathology. Confocal endomicroscopy can provide real-time in vivo images with histology-like features. The working channel in medical endoscopes are becoming smaller in dimension. Microsystems methods can produce tiny mechanical scanners. We demonstrate a flexible fiber instrument for in vivo imaging as an endoscope accessory. The optical path is folded on-axis to reduce length while allowing the beam to expand and achieve a numerical aperture of 0.41. A high-speed parametric resonance mirror produces large deflection angles > 13°, and is mounted on a 2 mm diameter chip designed with clamp structures for reduced space. A compact lens assembly provides diffraction-limited lateral and axial resolution of 1.5 and 12 μm , respectively. A working distance of 50 μm and field-of-view of 350 μm x 350 μm are achieved. Miniature apparatus is fabricated to assemble and align the scanhead components. The optics and scanner are packaged in a distal tip with 2.4 mm diameter and 10 mm rigid length. These dimensions allow the endomicroscope to pass forward easily through the 2.8 mm diameter working channel in medical endoscopes commonly used in clinical practice. Fluorescence images are collected in vivo at 10 frames per second in the colon of genetically-engineered mice that spontaneously develop adenomas. A FITC-labeled peptide heterodimer is administered intravenously to provide specific contrast. Sub-cellular structures are visualized to distinguish pre-malignant from normal mucosa. These results demonstrate use of microsystems methods to produce an ultra-compact instrument with sufficiently small dimensions for broad use.