Chip-on-the-tip compact flexible endoscopic epifluorescence video-microscope for in-vivo imaging in medicine and biomedical research

Abstract

Abstract:We demonstrate a 60 mg light video-endomicroscope with a cylindrical shape of the rigid tip of only 1.6 mm diameter and 6.7 mm length. A novel implementation method of the illumination unit in the endomicroscope is presented. It allows for the illumination of the biological sample with fiber-coupled LED light at 455 nm and the imaging of the red-shifted fluorescence light above 500 nm in epi-direction. A large numerical aperture of 0.7 leads to a sub-cellular resolution and yields to high-contrast images within a field of view of 160 µm. A miniaturized chip-on-the-tip CMOS image sensor with more than 150,000 pixels captures the multicolor images at 30 fps. Considering size, plug-and-play capability, optical performance, flexibility and weight, we hence present a probe which sets a new benchmark in the field of epifluorescence endomicroscopes. Several ex-vivo and in-vivo experiments in rodents and humans suggest future application in biomedical fields, especially in the neuroscience community, as well as in medical applications targeting optical biopsies or the detection of cellular anomalies.

Vibrating dichroic MEMS scanner based line scan multiphoton endomicroscope

“…Therefore, no beam expander required in this case. Different from other kinds of micro-objective lenses designed for conventional endoscopes [33][34][35][36][37][38][39], the micro-objective lens described in this article has been infinite-corrected, mid-high NA (~0.66), large angle of view (totally 20 degrees) and its back focal plane out of the lens body. Usually the back focal plane of a microscopic objective lens in middle to high NA always locates within the lens body due to its short focal length.…”

Design of a real-time fiber-optic infrared imaging system with wide-angle and large depth of field

“…With the development of minimally invasive surgery and optical imaging techniques, endoscopic imaging is widely used in the interior of the human body, enabling disease diagnosis and surgical image guidance [5][6][7][8][9] . For example, nonlinear optical endoscopy was developed for three-dimensional (3D) optical imaging [10] , and fluorescent endoscopy can provide realtime cellular imaging [11,12] . Optical coherence tomography (OCT)-based endoscopy can be applied in elastic scattering imaging [13] .…”

Design, fabrication, and preclinical testing of a miniaturized, multispectral, chip-on-tip, imaging probe for intraluminal fluorescence imaging of the gastrointestinal tract

“…Flexibility and higher resolution, delivered in a compact size, fuel advancement in miniature chip-on-tip endoscopes over existing fiber-based systems for white light and fluorescence modalities. [13,14] While chip-on-tip endoscopes have seen growth, there remains a significant opportunity for improved imaging modalities to increase the sensitivity and specificity of GI cancer diagnosis. Multimodal imaging in chip-on-tip endoscopic screenings for GI cancers may improve contrast between cancerous and noncancerous tissues.…”

“…[7] Flexibility, higher resolution, and affordability, all delivered in a compact size, fuel advancement in miniature chip-on-tip endoscopes over existing fiber-based systems for white light and fluorescence modalities. [8,9] While chip-on-tip endoscopes have seen growth, there remains a significant opportunity for advancing imaging techniques to increase the sensitivity and specificity within GI cancer diagnosis.…”