Optical neural recording is recognized among all neural recording methods for its high resolution, large field of view (FOV) and low invasiveness. An ideal neural recording device would enable a resolution sufficiently high to identify the activity of each individual neuron, a FOV sufficiently large to cover all neurons within the cortex region of interest for a certain study, and a form factor sufficiently small to allow the studied animal to freely behave.

Realizing that the trade-off between size and weight, resolution, and FOV of lens-based microscopes prevents the possibility to simultaneously achieve cellular resolution and large FOV with a small and lightweight lens-based microscope, our lab developed a lens-less microscope, “Bio-FlatScope”. By replacing lenses with a phase-shifting mask and image reconstruction algorithms, we demonstrated large FOV, cellular-resolution fluorescence imaging of fixed biological samples, as well as in vivo imaging of stimulus-evoked calcium activity from neuron clusters in the cortex of head-fixed mice.

In this thesis, we show an upgraded version of Bio-FlatScope, termed “MiniFlatScope”, with an integrated illumination module, further decreased form factor, and a finer reconstruction algorithm. We demonstrate near-cellular resolution and large FOV in a resolution test target and fixed biological samples, and show the ability of this prototype to be carried by a mouse, enabling the future in vivo behavioral study in freely-behaving mice.