Published April 2021 | Published + Supplemental Material + Submitted
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Implantable photonic neural probes for light-sheet fluorescence brain imaging

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Abstract

Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for highspeed 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. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass 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. Approach: We 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, in vitro, and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses <16 μm for propagation distances up to 300 μm in free space. Imaging areas were as large as ≈240 μm × 490 μm in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals.

Additional Information

© 2021 The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. Paper 20060R received Aug. 12, 2020; accepted for publication Mar. 4, 2021; published online Apr. 19, 2021. This work was supported by the National Institutes of Health, Awards NS090596 and NS099726; Canadian Institute of Health Research, Award FRN151949; and the Natural Sciences and Engineering Research Council of Canada, Award CHRPJ 508406. Funding support from the Canadian Foundation for Innovation and Ontario Research Fund is also gratefully acknowledged. W.D.S. was supported by the Kavli Nanoscience Institute Prize Postdoctoral Fellowship in Applied Physics and Materials Science. A.F. was supported by the Clinician Investigator Program, University of Manitoba. The authors thank Michael Chang and Azadeh Naderian at the Krembil Research Institute for their assistance with the animal colonies and genotyping. The authors also thank Alex Jacob in the group of Professor Sheena Josselyn at SickKids Research Institute (Toronto, Canada) for his advice on GCaMP6 functional imaging. Code, Data, and Materials Availability: The data are available from the corresponding authors upon reasonable request. The authors declare no competing interests.

Attached Files

Published - 025003_1.pdf

Submitted - 2020.09.30.317214v1.full.pdf

Supplemental Material - NPh_8_2_025003_ds004.mp4

Supplemental Material - NPh_8_2_025003_ds005.mp4

Supplemental Material - NPh_8_2_025003_ds006.mp4

Supplemental Material - NPh_8_2_025003_ds007.mp4

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Created:
August 22, 2023
Modified:
December 22, 2023