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Implantable photonic neural probes for light-sheet fluorescence brain imaging

Sacher, Wesley D. and Chen, Fu-Der and Moradi-Chameh, Homeira and Luo, Xianshu and Fomenko, Anton and Shah, Prajay T. and Lordello, Thomas and Liu, Xinyu and Almog, Ilan Felts and Straguzzi, John N. and Fowler, Trevor M. and Jung, Youngho and Hu, Ting and Jeong, Junho and Lozano, Andres M. and Lo, Patrick Guo-Qiang and Valiante, Taufik A. and Moreaux, Laurent C. and Poon, Joyce K. S. and Roukes, Michael L. (2021) Implantable photonic neural probes for light-sheet fluorescence brain imaging. Neurophotonics, 8 (2). Art. No. 025003. ISSN 2329-423X. PMCID PMC8059764. doi:10.1117/1.NPh.8.2.025003.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription Paper CentralArticle
Sacher, Wesley D.0000-0003-3306-4556
Luo, Xianshu0000-0002-5531-5689
Fomenko, Anton0000-0003-4131-6784
Shah, Prajay T.0000-0002-6668-9301
Lozano, Andres M.0000-0001-8257-3694
Valiante, Taufik A.0000-0002-3443-3790
Poon, Joyce K. S.0000-0002-3691-4344
Roukes, Michael L.0000-0002-2916-6026
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.
Group:Kavli Nanoscience Institute
Funding AgencyGrant Number
Canadian Institutes of Health Research (CIHR)FRN151949
Natural Sciences and Engineering Research Council of Canada (NSERC)CHRPJ 508406
Canada Foundation for InnovationUNSPECIFIED
Ontario Research FundUNSPECIFIED
Kavli Nanoscience InstituteUNSPECIFIED
University of ManitobaUNSPECIFIED
Subject Keywords:neurophotonics; integrated optics; functional imaging; microscopy; biophotonics; light-sheet fluorescence microscopy
Issue or Number:2
PubMed Central ID:PMC8059764
Record Number:CaltechAUTHORS:20201001-102536035
Persistent URL:
Official Citation:Wesley D. Sacher, Fu-Der Chen, Homeira Moradi-Chameh, Xianshu Luo, Anton Fomenko, Prajay Shah, Thomas Lordello, Xinyu Liu, Ilan Felts Almog, John N. Straguzzi, Trevor M. Fowler, Youngho Jung, Ting Hu, Junho Jeong, Andres M. Lozano, Patrick Guo-Qiang Lo, Taufik A. Valiante, Laurent C. Moreaux, Joyce K. S. Poon, and Michael L. Roukes "Implantable photonic neural probes for light-sheet fluorescence brain imaging," Neurophotonics 8(2), 025003 (19 April 2021).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105719
Deposited By: Tony Diaz
Deposited On:01 Oct 2020 18:59
Last Modified:05 May 2021 19:31

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