RT Journal Article SR Electronic T1 In vivo fluorescence imaging with a flat, lensless microscope JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.04.135236 DO 10.1101/2020.06.04.135236 A1 Jesse K. Adams A1 Vivek Boominathan A1 Sibo Gao A1 Alex V. Rodriguez A1 Dong Yan A1 Caleb Kemere A1 Ashok Veeraraghavan A1 Jacob T. Robinson YR 2020 UL http://biorxiv.org/content/early/2020/06/25/2020.06.04.135236.abstract AB Fluorescence imaging over large areas of the brain in freely behaving animals would allow researchers to better understand the relationship between brain activity and behavior; however, traditional microscopes capable of high spatial resolution and large fields of view (FOVs) require large and heavy lenses that restrict animal movement. While lensless imaging has the potential to achieve both high spatial resolution and large FOV with a thin lightweight device, lensless imaging has yet to be achieved in vivo due to two principal challenges: (a) biological tissue typically has lower contrast than resolution targets, and (b) illumination and filtering must be integrated into this non-traditional device architecture. Here, we show that in vivo fluorescence imaging is possible with a thin lensless microscope by optimizing the phase mask and computational reconstruction algorithms, and integrating fiber optic illumination and thin-film color filters. The result is a flat, lensless imager that achieves better than 10 μm spatial resolution and a FOV that is 30× larger than other cellular resolution miniature microscopes.Competing Interest StatementJKA, AV, and JTR are co-founders of Flatcam LLC which is working to commercialize lensless imaging technologies.