{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:36:06Z","timestamp":1785404166499,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,13]]},"group-title":"Biophysics","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["5R00AG056636"],"award-info":[{"award-number":["5R00AG056636"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R34NS127103"],"award-info":[{"award-number":["1R34NS127103"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01NS126076"],"award-info":[{"award-number":["R01NS126076"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2045120"],"award-info":[{"award-number":["2045120"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2217582"],"award-info":[{"award-number":["2217582"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0515k5w36","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04qjbd269","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/02hkvad16","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001082","name":"Camille and Henry Dreyfus Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001082","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000181","name":"United States Air Force Office of Scientific Research","doi-asserted-by":"crossref","award":["FA9550-21-1-0312"],"award-info":[{"award-number":["FA9550-21-1-0312"]}],"id":[{"id":"10.13039\/100000181","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tissue-clearing techniques have transformed optical imaging of fixed specimens, yet their application to living systems remains limited by toxicity and removal of key tissue components. We recently demonstrated that absorbing molecules such as tartrazine can reversibly render live mouse skin transparent. Subsequently, it was reported that isotonic protein solutions can achieve\n                  <jats:italic>ex vivo<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  cellular clearing. However, discrepancies remain regarding the optimal refractive index (RI) for live-cell clearing and the impact of elevated osmolality on cell viability. Here, using cultured mammalian cells, we systematically examine the dependence of optical contrast on medium RI and the effects of hyperosmolality. We find that, contrary to the recent report of an optimal RI of 1.36\u223c1.37 for suspended cells, densely-packed adherent cells exhibit a monotonic decrease in phase contrast up to an RI of 1.41 with tartrazine. Moreover, even under highly hyperosmotic conditions (\u223c1200 mOsm\/kg), cultured cells exhibit minimal deformation and negligible loss of viability for up to 30 min in the clearing solution. These results demonstrate that tartrazine enables effective live-cell clearing at RI up to 1.41 while preserving viability under elevated osmolality, and motivate future studies to define optimal conditions for\n                  <jats:italic>in vivo<\/jats:italic>\n                  optical clearing.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"717314v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.09.717314","type":"posted-content","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:00:22Z","timestamp":1776110422000},"source":"Crossref","is-referenced-by-count":0,"title":["Tartrazine clears live cells while preserving viability at high refractive indices and osmolality"],"prefix":"10.64898","author":[{"given":"Xuandi","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Baghdasaryan","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Crunkleton","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark L.","family":"Brongersma","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Geballe Laboratory for Advanced Materials, Stanford University, Stanford, CA, USA"},{"name":"Department of Applied Physics, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041701150440000_2026.04.09.717314v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-016-0008"},{"issue":"9","key":"2026041701150440000_2026.04.09.717314v1.2","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/acs.accounts.6b00239","article-title":"Tissue-Specific near-Infrared Fluorescence Imaging","volume":"49","year":"2016","journal-title":"Acc. 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