Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery

preprint OA: closed
Full text JSON View at publisher

Abstract

Abstract Implantable silicon neural probes with integrated optical emitters and electrodes are emerging tools for simultaneous optogenetic stimulation and electrophysiological recording in deep brain regions. In parallel, neural probes with microfluidic channels have been developed for localized drug delivery and neurochemical sampling. However, thus far, such fluidic probes have lacked optical and electrical functionalities or been limited to a low number of optical emitters and/or electrodes, constraining their utility in multimodal investigations of neural circuits. Here, we introduce foundry-fabricated silicon nanophotonic neural probes with monolithically integrated microfluidics. Each probe has 16 silicon nitride grating coupler emitters, 18 titanium nitride microelectrodes, and one embedded microfluidic channel. We evaluate the photonic, electrophysiological, and microfluidic functionalities in vivo in optogenetic, blue-light-sensitive mice. With our multifunctional neural probes, we demonstrate local suppression of epileptic seizure activity (induced by microfluidic injection of 4-aminopyridine) using photostimulation. Through foundry-compatible microfluidics integration, this work advances the versatility of nanophotonic neural probes and presents new possibilities for multimodal neuroscience experiments leveraging this scalable neurotechnology.
Full text 18,998 characters · extracted from preprint-html · click to expand
Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery Xin Mu, Homeira Chameh, Mandana Movahed, Fu Der Chen, John Straguzzi, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7464471/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Microsystems & Nanoengineering → Version 1 posted 11 You are reading this latest preprint version Abstract Implantable silicon neural probes with integrated optical emitters and electrodes are emerging tools for simultaneous optogenetic stimulation and electrophysiological recording in deep brain regions. In parallel, neural probes with microfluidic channels have been developed for localized drug delivery and neurochemical sampling. However, thus far, such fluidic probes have lacked optical and electrical functionalities or been limited to a low number of optical emitters and/or electrodes, constraining their utility in multimodal investigations of neural circuits. Here, we introduce foundry-fabricated silicon nanophotonic neural probes with monolithically integrated microfluidics. Each probe has 16 silicon nitride grating coupler emitters, 18 titanium nitride microelectrodes, and one embedded microfluidic channel. We evaluate the photonic, electrophysiological, and microfluidic functionalities in vivo in optogenetic, blue-light-sensitive mice. With our multifunctional neural probes, we demonstrate local suppression of epileptic seizure activity (induced by microfluidic injection of 4-aminopyridine) using photostimulation. Through foundry-compatible microfluidics integration, this work advances the versatility of nanophotonic neural probes and presents new possibilities for multimodal neuroscience experiments leveraging this scalable neurotechnology. Physical sciences/Nanoscience and technology/Nanobiotechnology/Nanofabrication and nanopatterning Physical sciences/Nanoscience and technology/Nanobiotechnology/Microfluidics Physical sciences/Optics and photonics Full Text Additional Declarations There is no conflict of interest Supplementary Files supplementary.pdf Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery Cite Share Download PDF Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Microsystems & Nanoengineering → Version 1 posted Editorial decision: revise 22 Oct, 2025 Review # 3 received at journal 17 Oct, 2025 Reviewer # 3 agreed at journal 05 Oct, 2025 Review # 2 received at journal 01 Oct, 2025 Review # 1 received at journal 30 Sep, 2025 Reviewer # 2 agreed at journal 17 Sep, 2025 Reviewer # 1 agreed at journal 17 Sep, 2025 Reviewers invited by journal 17 Sep, 2025 Submission checks completed at journal 27 Aug, 2025 Editor assigned by journal 26 Aug, 2025 First submitted to journal 26 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7464471","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":516321588,"identity":"39022a22-45e7-4e81-9105-8a934eafd6ea","order_by":0,"name":"Xin Mu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIie3PMQrCMBSA4SeFurzUtS56AiEgBAfxLBFBFxHBpYNDQaiHsHgJwdki1qWgY6UOde/g6KSmpeIU7SiYfwgh5CN5ACrVL6aliwWgAwLE4/wUv5IgJ5wWIWklJ79WiNA92a3Icj0ygHhXTtvQWMyPkFhyUp0Z/Yiso4kORs/ktA/sHIxLbiAnFQ1ZSrpOPaGCbIGFQ64RR070jLiCADZvnD5ycv/2ip0RJl7ZCDLYaMT+NAuyk+unsyBrcdpDMQt4ri8n9BCwMJlGo7qNzfBqdWosml/iZConr/hrg2Ci+F6B+HtrluMiQqVSqf6nJ3TNTLWXHFAUAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-6188-7969","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":true,"prefix":"","firstName":"Xin","middleName":"","lastName":"Mu","suffix":""},{"id":516321589,"identity":"8eb5e0bf-9d7f-4e9a-b798-93918a9cf611","order_by":1,"name":"Homeira Chameh","email":"","orcid":"","institution":"Krembil Brain Institute","correspondingAuthor":false,"prefix":"","firstName":"Homeira","middleName":"","lastName":"Chameh","suffix":""},{"id":516321590,"identity":"02dbde55-43ca-46ad-9b7f-85f7576bb4c6","order_by":2,"name":"Mandana Movahed","email":"","orcid":"","institution":"Krembil Brain Institute","correspondingAuthor":false,"prefix":"","firstName":"Mandana","middleName":"","lastName":"Movahed","suffix":""},{"id":516321591,"identity":"e4cf6bbc-dc8a-4087-9724-1b0305b74cf4","order_by":3,"name":"Fu Der Chen","email":"","orcid":"","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"Fu","middleName":"Der","lastName":"Chen","suffix":""},{"id":516321592,"identity":"edefdbc0-bd2e-4fec-b148-20e065df422c","order_by":4,"name":"John Straguzzi","email":"","orcid":"","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Straguzzi","suffix":""},{"id":516321593,"identity":"96f9cd6a-45e0-47a6-9905-78708df848d3","order_by":5,"name":"Piyush Kumar","email":"","orcid":"https://orcid.org/0000-0002-9965-8691","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"Piyush","middleName":"","lastName":"Kumar","suffix":""},{"id":516321594,"identity":"262ac657-67e1-4928-8fd9-357594e21175","order_by":6,"name":"Andrei Stalmashonak","email":"","orcid":"","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"Andrei","middleName":"","lastName":"Stalmashonak","suffix":""},{"id":516321595,"identity":"5f81605c-c661-41f7-a994-de7a29906a72","order_by":7,"name":"Hannes Wahn","email":"","orcid":"","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"Hannes","middleName":"","lastName":"Wahn","suffix":""},{"id":516321596,"identity":"660cbecf-c449-439b-8a57-69ddf289806a","order_by":8,"name":"Hongyao Chua","email":"","orcid":"","institution":"Advanced Micro Foundry Pte. Ltd.","correspondingAuthor":false,"prefix":"","firstName":"Hongyao","middleName":"","lastName":"Chua","suffix":""},{"id":516321597,"identity":"d0b10b1f-e147-48ef-85c8-a7149bed3b5e","order_by":9,"name":"Xianshu Luo","email":"","orcid":"","institution":"Advanced Micro Foundry Pte. Ltd.","correspondingAuthor":false,"prefix":"","firstName":"Xianshu","middleName":"","lastName":"Luo","suffix":""},{"id":516321598,"identity":"49280dde-2331-41ae-83a2-508f0d8650d0","order_by":10,"name":"Guo-Qiang Lo","email":"","orcid":"","institution":"Advanced Micro Foundry Pte. Ltd.","correspondingAuthor":false,"prefix":"","firstName":"Guo-Qiang","middleName":"","lastName":"Lo","suffix":""},{"id":516321599,"identity":"d5c03fd9-8084-4998-bb0a-fff61458c56b","order_by":11,"name":"Joyce Poon","email":"","orcid":"https://orcid.org/0000-0002-3691-4344","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"Joyce","middleName":"","lastName":"Poon","suffix":""},{"id":516321600,"identity":"d00dfba3-7f1d-4873-bac4-a71dde7a798c","order_by":12,"name":"Taufik Valiante","email":"","orcid":"","institution":"Krembil Brain Institute","correspondingAuthor":false,"prefix":"","firstName":"Taufik","middleName":"","lastName":"Valiante","suffix":""},{"id":516321601,"identity":"42b2ce84-3856-442f-858c-5bbf4512317c","order_by":13,"name":"Wesley Sacher","email":"","orcid":"","institution":"Max Planck Institute of Microstructure Physics","correspondingAuthor":false,"prefix":"","firstName":"Wesley","middleName":"","lastName":"Sacher","suffix":""}],"badges":[],"createdAt":"2025-08-26 15:30:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7464471/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7464471/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41378-026-01192-6","type":"published","date":"2026-03-20T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92221423,"identity":"8406eeec-bb2e-4ce1-9b69-1b23eee8043b","added_by":"auto","created_at":"2025-09-26 03:24:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3353328,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7464471/v1/003d1a73fda67727279f45bb.pdf"},{"id":92221420,"identity":"5a4c7309-1df8-41e5-a77e-f534dd43447d","added_by":"auto","created_at":"2025-09-26 03:24:36","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":13505,"visible":true,"origin":"","legend":"","description":"","filename":"MICRONANO04837.json","url":"https://assets-eu.researchsquare.com/files/rs-7464471/v1/c1e3f9713bf077b261524daa.json"},{"id":92221422,"identity":"da572646-c13f-4511-9c3a-7ad5f8333b16","added_by":"auto","created_at":"2025-09-26 03:24:36","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":642469,"visible":true,"origin":"","legend":"","description":"","filename":"supplementary.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7464471/v1/7c95a56e8c9b0fdf906347bc.pdf"},{"id":105038448,"identity":"6eb45b4a-9196-462c-afc4-be6a015652ef","added_by":"auto","created_at":"2026-03-20 07:43:36","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3381961,"visible":true,"origin":"","legend":"Article File","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7464471/v1_covered_7da5c41a-1fbb-4ac2-877a-a8a4d5faec6e.pdf"},{"id":92221421,"identity":"ee539fe8-843e-4191-9e61-1b4c94f470e2","added_by":"auto","created_at":"2025-09-26 03:24:36","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":642469,"visible":true,"origin":"","legend":"Nanophotonic neural probes for \u003ci\u003ein vivo\u003c/i\u003e photostimulation, electrophysiology, and microfluidic delivery","description":"","filename":"supplementary.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7464471/v1/ee7923522451e1f231e819f4.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Nanophotonic neural probes for \u003ci\u003ein vivo\u003c/i\u003e photostimulation, electrophysiology, and microfluidic delivery","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"microsystems-and-nanoengineering","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"micronano","sideBox":"Learn more about [Microsystems \u0026 Nanoengineering](http://www.nature.com/micronano/)","snPcode":"41378","submissionUrl":"https://mts-micronano.nature.com/","title":"Microsystems \u0026 Nanoengineering","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7464471/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7464471/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Implantable silicon neural probes with integrated optical emitters and electrodes are emerging tools for simultaneous optogenetic stimulation and electrophysiological recording in deep brain regions. In parallel, neural probes with microfluidic channels have been developed for localized drug delivery and neurochemical sampling. However, thus far, such fluidic probes have lacked optical and electrical functionalities or been limited to a low number of optical emitters and/or electrodes, constraining their utility in multimodal investigations of neural circuits. Here, we introduce foundry-fabricated silicon nanophotonic neural probes with monolithically integrated microfluidics. Each probe has 16 silicon nitride grating coupler emitters, 18 titanium nitride microelectrodes, and one embedded microfluidic channel. We evaluate the photonic, electrophysiological, and microfluidic functionalities \u003ci\u003ein vivo\u003c/i\u003e in optogenetic, blue-light-sensitive mice. With our multifunctional neural probes, we demonstrate local suppression of epileptic seizure activity (induced by microfluidic injection of 4-aminopyridine) using photostimulation. Through foundry-compatible microfluidics integration, this work advances the versatility of nanophotonic neural probes and presents new possibilities for multimodal neuroscience experiments leveraging this scalable neurotechnology.","manuscriptTitle":"Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 03:24:31","doi":"10.21203/rs.3.rs-7464471/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-10-22T07:07:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-17T06:43:53+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-10-05T12:05:27+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-02T02:40:00+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-01T03:26:37+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-17T16:44:48+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-17T07:13:40+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-09-17T06:53:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-28T02:53:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-26T15:25:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Microsystems \u0026 Nanoengineering","date":"2025-08-26T15:25:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"microsystems-and-nanoengineering","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"micronano","sideBox":"Learn more about [Microsystems \u0026 Nanoengineering](http://www.nature.com/micronano/)","snPcode":"41378","submissionUrl":"https://mts-micronano.nature.com/","title":"Microsystems \u0026 Nanoengineering","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e4f1735b-1244-4f39-8f5e-73151a958043","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":54854359,"name":"Physical sciences/Nanoscience and technology/Nanobiotechnology/Nanofabrication and nanopatterning"},{"id":54854360,"name":"Physical sciences/Nanoscience and technology/Nanobiotechnology/Microfluidics"},{"id":54854361,"name":"Physical sciences/Optics and photonics"}],"tags":[],"updatedAt":"2026-03-20T07:36:11+00:00","versionOfRecord":{"articleIdentity":"rs-7464471","link":"https://doi.org/10.1038/s41378-026-01192-6","journal":{"identity":"microsystems-and-nanoengineering","isVorOnly":false,"title":"Microsystems \u0026 Nanoengineering"},"publishedOn":"2026-03-20 04:00:00","publishedOnDateReadable":"March 20th, 2026"},"versionCreatedAt":"2025-09-26 03:24:31","video":"","vorDoi":"10.1038/s41378-026-01192-6","vorDoiUrl":"https://doi.org/10.1038/s41378-026-01192-6","workflowStages":[]},"version":"v1","identity":"rs-7464471","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7464471","identity":"rs-7464471","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00