{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:13:11Z","timestamp":1788545591446,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52205312"],"award-info":[{"award-number":["52205312"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52275200"],"award-info":[{"award-number":["52275200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["52205312"],"award-info":[{"award-number":["52205312"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["52275200"],"award-info":[{"award-number":["52275200"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Nanoneedle arrays provide a promising interface for intracellular delivery, yet scalable control of array geometry and membrane penetration mechanics remains insufficiently understood. Here, we developed a rapid and scalable strategy for fabricating geometry-tunable silicon nanoneedle arrays. One-step SF6\/O2 etching produced ordered arrays with center-to-center spacing of 1\u20135 \u03bcm, whereas pseudo-Bosch etching produced high-aspect-ratio (HAR) nanoneedles. Using a microwell-assisted cell-on-probe atomic force microscopy platform, we quantified the first penetration force, penetration probability, and number of penetration events at the single-cell level. For one-step-etching arrays, increasing spacing from 1 to 5 \u03bcm reduced the first penetration force from 34.87 \u00b1 2.90 to 4.05 \u00b1 0.30 nN and increased the penetration probability from 0.21 \u00b1 0.03 to 0.87 \u00b1 0.04. A phenomenological inverse-square model captured the force\u2013spacing relationship, supporting an array-level load-sharing mechanism. Under identical vibration-assisted microfluidic conditions, the FITC-dextran-positive fraction increased from 22.8% for 1 \u03bcm arrays to 77.1% for 5 \u03bcm arrays, whereas 1 \u03bcm HAR arrays achieved 28.8%. These results identify array spacing as a key factor governing single-cell penetration and delivery and provide a mechanistic basis for nanoneedle-based biosensor and cell-interface design.<\/jats:p>","DOI":"10.3390\/bios16090495","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:25:56Z","timestamp":1788542756000},"page":"495","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Geometry-Tunable Nanoneedle Arrays Reveal Membrane Penetration Mechanics for Intracellular Delivery"],"prefix":"10.3390","volume":"16","author":[{"given":"Xuanhe","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Micro\/Nano Optoelectronic Devices of Ministry of Education & Hunan Provincial Key Laboratory of Low-Dimensional Structural Physics and Devices, School of Physics and Electronics, Hunan University, Changsha 410082, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Yiqing","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Lele","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-2450","authenticated-orcid":false,"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Jiadao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nature19764","article-title":"In vitro and ex vivo strategies for intracellular delivery","volume":"538","author":"Stewart","year":"2016","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7409","DOI":"10.1021\/acs.chemrev.7b00678","article-title":"Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts","volume":"118","author":"Stewart","year":"2018","journal-title":"Chem. 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