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Leveraging a high-resolution 3D printing technology based on 2-photon polymerization and scalable microfabrication processes, we fabricated arrays of 6,600 microelectrodes 10-130 \u00b5m tall and at 35-\u03bcm pitch onto a planar silicon-based microelectrode array. The process enables customizable electrode shape, height and positioning for precise targeting of neuron populations distributed in 3D. As a proof of concept, we addressed the challenge of specifically targeting retinal ganglion cell (RGC) somas when interfacing with the retina. The array was customized for insertion into the retina and recording from somas while avoiding the axon layer. We verified locations of the microelectrodes with confocal microscopy and recorded high-resolution spontaneous RGC activity at cellular resolution. This revealed strong somatic and dendritic components with little axon contribution, unlike recordings with planar microelectrode arrays. The technology could be a versatile solution for interfacing silicon microelectronics with neural structures and modulating neural activity at large scale with single-cell resolution.<\/jats:p>","DOI":"10.1101\/2023.05.30.542925","type":"posted-content","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:18Z","timestamp":1685750418000},"source":"Crossref","is-referenced-by-count":3,"title":["Direct-print three-dimensional electrodes for large-scale, high-density, and customizable neural interfaces"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9249-6642","authenticated-orcid":false,"given":"Pingyu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Ulu\u015fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.J.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline Rose","family":"Hays","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidhar","family":"Madugula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2104-4921","authenticated-orcid":false,"given":"Ramandeep S.","family":"Vilkhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praful Krishna","family":"Vasireddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hierlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5613-0248","authenticated-orcid":false,"given":"E.J.","family":"Chichilnisky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Melosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023060609300594000_2023.05.30.542925v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.032"},{"key":"2023060609300594000_2023.05.30.542925v1.2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.neuron.2020.10.011","article-title":"Recent Advances in Electrical Neural Interface Engineering: Minimal Invasiveness, Longevity, and Scalability","volume":"108","year":"2020","journal-title":"Neuron"},{"key":"2023060609300594000_2023.05.30.542925v1.3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1601649"},{"key":"2023060609300594000_2023.05.30.542925v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.03.037"},{"key":"2023060609300594000_2023.05.30.542925v1.5","doi-asserted-by":"crossref","unstructured":"Go, G.-T. , Lee, Y. , Seo, D.-G. & Lee, T.-W. 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