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However, the resulting large and complex PSF spatial footprints reduce biological throughput and applicability by requiring lower labeling densities to avoid overlapping fluorescent signals. We quantitatively compare the density dependence of single-molecule light field microscopy (SMLFM) to other 3D PSFs (astigmatism, double helix and tetrapod) showing that SMLFM enables an order-of-magnitude speed improvement compared to the double helix PSF by resolving overlapping emitters through parallax. We demonstrate this optical robustness experimentally with high accuracy (\u2009&gt;\u200999.2\u2009\u00b1\u20090.1%,\u20090.1\u2009locs\u2009\u03bcm\n                    <jats:sup>\u22122<\/jats:sup>\n                    ) and sensitivity (\u2009&gt;\u200986.6\u2009\u00b1\u20090.9%,\u20090.1\u2009locs\u2009\u03bcm\n                    <jats:sup>\u22122<\/jats:sup>\n                    ) through whole-cell (scan-free) imaging and tracking of single membrane proteins in live primary B cells. We also exemplify high-density volumetric imaging (0.15\u2009locs\u2009\u03bcm\n                    <jats:sup>\u22122<\/jats:sup>\n                    ) in dense cytosolic tubulin datasets.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-45828-5","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T08:01:33Z","timestamp":1709366493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["High-density volumetric super-resolution microscopy"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8559-3161","authenticated-orcid":false,"given":"Sam","family":"Daly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-6709","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Ferreira Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-1443","authenticated-orcid":false,"given":"Ezra","family":"Bruggeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoushka","family":"Handa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Benaissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4726-230X","authenticated-orcid":false,"given":"Joseph S.","family":"Beckwith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-7702","authenticated-orcid":false,"given":"Edward W.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-6405","authenticated-orcid":false,"given":"Ruth R.","family":"Sims","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-6954","authenticated-orcid":false,"given":"David","family":"Klenerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"O\u2019Holleran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-5139","authenticated-orcid":false,"given":"Steven F.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"45828_CR1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nmeth929","volume":"3","author":"MJ Rust","year":"2006","unstructured":"Rust, M. 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