Design of a 1.0mm multiphoton microscopy microendoscope

Early indicators of cancer manifest as cellular abnormalities that can be imaged via high resolution imaging modalities such as label-free Multiphoton Microscopy (MPM). Implementing MPM endoscopically can aid in the early diagnosis of cancer. We are developing a minimally invasive microendoscope system capable of simultaneous co-registered multiphoton imaging (two- and three-photon excited fluorescence, second and third harmonic generation) of the epithelial layer in small diameter ductal tissues via helical scanning of a 1.0mm diameter endoscope distal end with a fixed focus. The endoscope working length is comprised of a stationary outer sheath housing a proximally driven endoscope distal optical system. The lenses are 0.5mm in diameter and side viewing, requiring a novel optical design with power on the exit surface of the fold prism. Additive manufacturing (three-dimensional [3D] printing) opens significantly more possibilities for distal end microendoscope optical design. We present the design of the distal end outer sheath, housing, and optics, as well as an evaluation of the feasibility of 3D printed optics for a high numerical aperture (HNA) MPM microendoscope system. The selected distal end outer sheath meets flexibility, size, and optical requirements suitable for a first iteration lab prototype. The distal end housing was custom designed to be easily attached and removed from the proximal system and to ensure stable and consistent helical motion of the inner probe distal end when it is flexed and bent in manners needed for use in curved tissue lumens. We have also designed and manufactured (via two photon polymerization) multiple configurations of a 0.5mm monolithic multi-element lens system containing an aspheric surface on the exit face of the prism and evaluated its optical performance.