Planar objective design for multiphoton brain imaging

Achieving sub-cellular imaging of the full mouse brain is a pivotal challenge in modern neuroscience, with the potential to transform our understanding of neural circuits and their spatiotemporal activity patterns. Multiphoton microscopy (MPM), particularly two-photon microscopy (2PM) and three-photon microscopy (3PM), offers powerful tools for deep-tissue, high-resolution imaging. While 2PM excels in imaging superficial brain layers, 3PM demonstrates superior performance at greater depths due to its longer excitation wavelength. In this paper we propose a groundbreaking approach by integrating an entire multiphoton objective into a unified imaging system using a novel metalens plate as a cranial window. The metalens plate incorporates two metasurfaces optimized for aberration correction and supports high numerical aperture (NA). The implementation of the metalens plate as a planar cranial window simplifies its integration into in-vivo mouse brain studies. This technique promises to unravel neural mechanisms across extensive brain volumes, offering profound insights and catalyzing advancements in neuroscience.