Single-shot 3D widefield fluorescence imaging with a computational miniature mesoscope
Xue, Yujia; Davison, Ian G.; Boas, David A.; Tian, Lei
Fluorescence imaging is indispensable to biology and neuroscience. The need for largescale
imaging in freely behaving animals has further driven the development in miniaturized
microscopes (miniscopes). However, conventional microscopes / miniscopes are inherently
constrained by their limited space-bandwidth-product, shallow depth-of-field, and inability
to resolve 3D distributed emitters. Here, we present a Computational Miniature Mesoscope
(CM2) that overcomes these bottlenecks and enables single-shot 3D imaging across an 8 ×
7-mm2 field-of-view and 2.5-mm depth-of-field, achieving 7-μm lateral resolution and
better than 200-μm axial resolution. Notably, the CM2 has a compact lightweight design
that integrates a microlens array for imaging and an LED array for excitation in a single
platform. Its expanded imaging capability is enabled by computational imaging that
augments the optics by algorithms. We experimentally validate the mesoscopic 3D imaging
capability on volumetrically distributed fluorescent beads and fibers. We further quantify
the effects of bulk scattering and background fluorescence on phantom experiments.
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