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.
Highlights
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
Fluorescence imaging modalities proved to be especially useful in this scope of application due to their ability to observe neuronal spikings in real time after a viral transduction of genetically encoded calcium indicators [23,24,25] or synthetic dyes [26,27,28], and represent the method of choice for respective endomicroscopes
We demonstrate a stand alone, versatile applicable, very flexible one-photonepifluorescence endomicroscope which enables for less invasive in-vivo probing of biological tissue
Summary
Using fluorescence endoscopy to visualize regions inside a living organism which are too deep to reach with traditional, table-top microscopes has drawn great interest in recent years, especially in biomedical research [1,2,3,4,5,6,7,8,9,10,11] and medical fields [12,13,14,15,16,17,18,19,20]. Attention originates from the neuroscience community which aims to achieve deeper insights of how the brain works by correlating cellular activity in neuronal subpopulations with animal behavior [21,22,23] In this context, tiny and highly flexible devices are required which can be attached to the head of the animal to image behaviorally evoked brain zone activities over long time periods [3,4,5]. The probe convinces due to a reduced size of the rigid tip of only 6.7 mm length and 1.6 mm diameter, a low weight of 60 mg, a high robustness and flexibility, an improved optical performance comparable to what is achieved by commercially available table-top microscopes as well as an easy plug-and-play usability
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