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Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time

Moreaux, Laurent C. and Yatsenko, Dimitri and Sacher, Wesley D. and Choi, Jaebin and Lee, Changhyuk and Kubat, Nicole J. and Cotton, R. James and Boyden, Edward S. and Lin, Michael Z. and Tian, Lin and Tolias, Andreas S. and Poon, Joyce K. S. and Shepard, Kenneth L. and Roukes, Michael L. (2020) Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time. Neuron, 108 (1). pp. 66-92. ISSN 0896-6273.

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We propose a new paradigm for dense functional imaging of brain activity to surmount the limitations of present methodologies. We term this approach “integrated neurophotonics”; it combines recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics. This approach has the potential to enable lens-less functional imaging from within the brain itself to achieve dense, large-scale stimulation and recording of brain activity with cellular resolution at arbitrary depths. We perform a computational study of several prototype 3D architectures for implantable probe-array modules that are designed to provide fast and dense single-cell resolution (e.g., within a 1-mm³ volume of mouse cortex comprising ∼100,000 neurons). We describe progress toward realizing integrated neurophotonic imaging modules, which can be produced en masse with current semiconductor foundry protocols for chip manufacturing. Implantation of multiple modules can cover extended brain regions.

Item Type:Article
Related URLs:
URLURL TypeDescription
Moreaux, Laurent C.0000-0003-1276-5062
Yatsenko, Dimitri0000-0002-1844-641X
Sacher, Wesley D.0000-0003-3306-4556
Choi, Jaebin0000-0002-8348-7701
Lee, Changhyuk0000-0002-1108-6327
Cotton, R. James0000-0001-5714-1400
Lin, Michael Z.0000-0002-0492-1961
Tian, Lin0000-0001-7012-6926
Tolias, Andreas S.0000-0002-4305-6376
Shepard, Kenneth L.0000-0003-0665-6775
Roukes, Michael L.0000-0002-2916-6026
Additional Information:© 2020 Elsevier. Available online 14 October 2020. M.L.R., A.S.T., and K.L.S. gratefully acknowledge funding from the NIH (grant Nos. NS090596 and NS009717), NSF (grant Nos. 1265055 and 1403817), DARPA (grant Nos. N66001-17-C-4002 and N66001-17-C-4012), IARPA (grant No. DP1EY023176), and the Kavli Foundation through Caltech’s Kavli Nanoscience Institute’s “Fill the gap” award program. J.K.S.P. acknowledges the Natural Sciences and Engineering Research Canada, Canadian Institutes of Health Research, and Canada Research Chair program. We thank the following individuals for their participation in various phases of this work: Joe Redford (initial numerical simulations); Eran Segev, Derrick Chi, Trevor Fowler, Xinyu Liu, Kukjoo Kim, Warren Fon (nanofabrication); Fu-Der Chen, John Straguzzi, Thomas Lordello, and Ilan Felts Almog (photonic probe characterization); and Andres Lozano, Anton Fomenko, Taufik Valiante, Homeira Moradi-Chameh, Prajay Shah, Zach Blumenfeld (in vitro and in vivo experiments). We thank François Berger, Miyoung Chun, Andrei Faraon, Leslie Greengard, Gilles Laurent, Konrad Kording, and Liam Paninski for helpful discussions. We especially thank our reviewers for their insightful comments. We are grateful for the participation of our foundry partners, including scientists and engineers at: CEA-Leti (Grenoble, France): Laurent Duraffourg, Bruno Paing, Salim Boutami, Jean-Marc Fedeli, Benoit Giffard Pierre Labeye, Hughes Metras, Eric Rouchouze, Denis Renaud, and Alexei Tchelnokov; at Advanced Micro Foundry (AMF, Singapore): Patrick Lo and Xianshu Luo; and at TSMC (Taiwan). Declaration of Interests. Three patents owned by the California Institute of Technology have been pursued in connection with this work: (1) Roukes (2011). Brain-machine interface based on photonic neural probe arrays. U.S.P.T.O. Patent No. 10,638,933, Issued May 5, 2020, Priority Date: December 8, 2011. (2) Segev, E., Moreaux, L.C., Fowler, T.M. Faraon, A., Roukes, M.L. Implantable, highly collimated light-emitters for biological applications. U.S.P.T.O. Patent No. 10,471,273, Issue date: 12 November 2019; Priority date: 16 October 2015. (3) Roukes et al. (2016). One-photon integrated neurophotonic systems. U.S.P.T.O. Patent Application 20160150963, Filing date: November 5, 2014; Publication date: June 2, 2016.
Group:Kavli Nanoscience Institute
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)N66001-17-C-4002
Defense Advanced Research Projects Agency (DARPA)N66001-17-C-4012
Intelligence Advanced Research Projects Activity (IARPA)DP1EY023176
Kavli FoundationUNSPECIFIED
Kavli Nanoscience InstituteUNSPECIFIED
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Canada Research Chairs ProgramUNSPECIFIED
Canadian Institutes of Health Research (CIHR)UNSPECIFIED
Issue or Number:1
Record Number:CaltechAUTHORS:20201014-111855866
Persistent URL:
Official Citation:Laurent C. Moreaux, Dimitri Yatsenko, Wesley D. Sacher, Jaebin Choi, Changhyuk Lee, Nicole J. Kubat, R. James Cotton, Edward S. Boyden, Michael Z. Lin, Lin Tian, Andreas S. Tolias, Joyce K.S. Poon, Kenneth L. Shepard, Michael L. Roukes, Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time, Neuron, Volume 108, Issue 1, 2020, Pages 66-92, ISSN 0896-6273,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106057
Deposited By: George Porter
Deposited On:14 Oct 2020 19:52
Last Modified:14 Oct 2020 19:52

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