Implantable photonic neural probes for light-sheet fluorescence brain imaging

Sacher, W. D.; Chen, F.-D.; Moradi-Chameh, H.; Luo, X.; Fomenko, A.; Shah, P.; Lordello, T.; Liu, X.; Felts Almog, I.; Straguzzi, J. N.; Fowler, T. M.; Jung, Y.; Hu, T.; Jeong, J.; Lozano, A. M.; Guo-Qiang Lo, P.; Valiante, T. A.; Moreaux, L. C.; Poon, J. K. S.; Roukes, M. L.

doi:10.1101/2020.09.30.317214

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bioRxiv · 10.1101/2020.09.30.317214

Implantable photonic neural probes for light-sheet fluorescence brain imaging

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Abstract

SignificanceLight-sheet fluorescence microscopy is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. Here, we demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. AimMass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. ApproachWe develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200 mm diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed and in vitro mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. ResultsThe probes had 5 to 10 addressable sheets and average sheet thicknesses < 16 m for propagation distances up to 300 m in free space. Imaging areas were as large as {approx} 240 m x 490 m in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. ConclusionsThe neural probes can lead to new variants of light-sheet fluorescence microscopy for deep brain imaging and experiments in freely-moving animals.

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Sacher, W. D., Chen, F.-D., Moradi-Chameh, H., Luo, X., Fomenko, A., Shah, P., Lordello, T., Liu, X., Felts Almog, I., Straguzzi, J. N., Fowler, T. M., Jung, Y., Hu, T., Jeong, J., Lozano, A. M., Guo-Qiang Lo, P., Valiante, T. A., Moreaux, L. C., Poon, J. K. S., Roukes, M. L.. 2020-09-30. Implantable photonic neural probes for light-sheet fluorescence brain imaging. https://doi.org/10.1101/2020.09.30.317214

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